Regular Action

By O’Connor, Thea

MEDICAL CHECK-UPS CAN BE LIFE-SAVING FOR INDIVIDUALS AND ADD LIFE TO A WORKFORCE, WRITES THEA O’CONNOR As undignified and uncomfortable as they might be, pap smears and prostate checks can add years to your life and that of your workforce. Making an appointment to see a doctor when you’re feeling fine can seem counter-intuitive. But feeling good isn’t a guarantee that all is well. Silent killers, such as diabetes, heart disease, breast and bowel cancer can sneak up on you without any obvious symptoms in the early stages.

“You can have high cholesterol levels, high blood pressure, a lump in your breast or prostate without knowing it,” says Dr John Gullotta, a Sydney GP and chair of the public health committee of the Australian Medical Association. Left untreated these symptoms can be fatal.

That’s why regular medical checkups are vital. “The point of screening and prevention is to pick up disease states early so they can be treated, and ideally to prevent disease occurring in the first place,” says Gullotta.

Convinced of the productivity and personal health benefits, some workplaces are happy to invest in offering on-site health checks. Recent research indicates the investment pays off.

A Wesley Corporate Health study of 4800 employees found that the average Australian worker has heightened risk of heart disease, obesity, diabetes, cancer and depression.

This in turn reduces productivity by up to 7 per cent. The good news is that employees’ health risk factors can be reduced by up to 56 per cent – at a rate of 10 per cent a year – by implementing health screening and health promotion strategies in the workplace, according to the Wesley Corporate Health Study, The Future @Work Health Report, 2006.

Foster’s Australia is one organisation that is encouraging workers to stay on top of their health. “Knowing that half our employees at the Abbotsford site are 40 to 70-year-old men, who are traditionally poorer at preventative health than women, we’ve been really pushing health checks for a number of years now,” says Foster’s occupational health manager, Jo Spencer.

Foster’s employees can attend the on-site centre at any time for a range of health and wellness issues including blood pressure, cholesterol and blood glucose checks.

They also come in response to specific campaigns. “When we ran our drive for prostate cancer checks and provided free, on-site blood tests, we had about 50 per cent of employees come along,” says Spencer. “If we’d written out a referral slip and said, ‘Here, go to the doctor’, it just wouldn’t happen.”

Dreaming up new initiatives to keep workers coming back for health checks is part of Spencer’s job. The healthy weight and lifestyle campaign, “Abby’s Biggest Winner”, which attracted about 170 employees and resulted in a collective loss of more than 360kg, has just been completed.

Scott Davidson, Foster’s operations support manager, has such confidence in the health programs that he’s hiring more staff. “Better general health means less time off for illness, especially among an ageing workforce.”

Minter Ellison Lawyers is another firm that has a long history of offering health checks to its partners. For 20 years it’s been a requirement that partners have a full medical examination at least every two years, with those aged 50 plus encouraged to have an annual assessment. “The firm foots the bill, as there’s obvious merit in having those who are leading the organisation as healthy as possible,” says Neil Hibble, director of partner services.

Using a provider that specialises in health assessments (Good Health Solutions) allows Minter Ellison to ensure a thorough and consistent set of tests, while guaranteeing confidentiality, which Hibble says is vital for participation.

Hibble has undergone the two-to-three-hour full physical examination himself. “You definitely come out at the end knowing what shape you are in,” he says. “No one needs to be frightened of participating -there’s much more to be lost by not getting it done.”

For those workplaces keen to get the best return on any investment in staff health, Gullotta has some advice: “Make sure you match the tests to the age and health of your workforce.” Doing electrocardiogram stress tests on fit and healthy symptom-free 20 to 30-year-olds might not be the best use of money. And if you are using expensive tests, such as a total body scan, make sure you understand how to interpret the results and what benefit they will be to you. For example, if a scan picks up a problem, great. But if it doesn’t, you can’t assume there’s nothing wrong with you since it doesn’t pick up everything. Also make sure that you organise good follow-up, so that when staff get their results, they can talk to a health professional about them, especially if the results have serious implications.”

Health checks: What to have when

N.B. These are guidelines only. Your doctor is best placed to tailor a medical examination that best suits your needs.

All adults

Check-ups for adults of all ages should include a review of smoking, alcohol, diet, exercise, medication, mood checks, blood pressure, cholesterol and skin cancer. Sexual health check-ups are recommended with any change of sexual partner.

Gender-specific tests

Women

* Pap smear two years after first sexual encounter, then every two years until age 70

* Mammogram every two years from age 50 until 70

Men

* Prostate cancer check from age 50 then every two years

Acknowledgements to Dr John Gullotta.

How often do you need a check-up?

Two check-ups per decade for people in their 20s, three check- ups for people in their 30s, four for people in their 40s, then annually for people aged 50 plus.

(American Medical Association)

Thea O’Connor is a health promotion consultant, writer and speaker, www.thea.com.au

Copyright CPA Australia Jul 2008

(c) 2008 Australian CPA. Provided by ProQuest Information and Learning. All rights Reserved.

Grube, Olivia

Grube, Olivia

(Nee Gramoll) Of CEDARBURG. August 6, 2008, age 86 years. Beloved wife of the late Elwood. Dear mother of Harold (Mary Kay), Dennis (Debbie), Wallace and Jim (Sue). Further survived by 7 grandchildren, 3 great-grandchildren, other relatives and friends. Funeral service Monday, August 11, 7 PM at Immanuel Lutheran Church, W61 N498 Washington Ave., Cedarburg. Interment Immanuel Cemetery. In state at the church on Monday from 4 PM until time of service. In lieu of flowers, memorials to the church appreciated. MUELLER FUNERAL HOME W63 N527 HANOVER AVE CEDARBURG (262) 377-0380 www.muellerfuneralhome.com

(c) 2008 Milwaukee Journal Sentinel. Provided by ProQuest Information and Learning. All rights Reserved.

Left Ventricular Myocardial Injury and Syncope Due to Pulmonary Embolism in a Soldier: Normal Coronaries and Novel Pathologic Electrocardiogram Signs

By Nestico, Pasquale F Cassimatis, Dimitri C; Sheikh, Fareed; Huber, Michael; Davison, Jonathan; Modlin, Randolph

ABSTRACT Objective: We present a soldier with a pulmonary embolism presenting with syncope during an ischemic stress test, subsequently found to have normal coronary arteries (CA). case: A 49- year-old soldier had 3 months history of exertional chest pain, shortness of breath, syncope, and malaise. He passed out during a stress echocardiogram and had a positive troponin level. A subsequent cardiac catheterization revealed normal CA but with mild hypokinesis of the distal anterior wall with a left ventricular ejection fraction of 44%. A subsequent nuclear ventilation- perfusion scan was consistent with bilateral pulmonary embolism. Results: A Doppler ultrasound revealed thrombosis in the distal superficial femoral vein of the left leg. Hypercoagulable state markers were normal. Conclusion: This case demonstrates that a pulmonary embolism could express itself as an ST depression myocardial ischemic event perhaps by affecting the coronary flow to the left anterior descending CA. INTRODUCTION

Nondiagnosed pulmonary embolism (PE) carries a high mortality rate.1,2 In the International Cooperative Pulmonary Embolism Registry of 2,554 patients, the overall cumulative mortality due to PE was 17.4% at 3 months.1 Acute PE has been reported in a patient with normal coronary arteries (CA).2

The diagnosis of PE is rendered difficult by a clinical presentation that may be subtle and may mimic other cardiopulmonary illnesses.3 In a study of a total of over 135 million passengers from 145 countries, of whom 56 had confirmed severe PE associated with air travel, suspicion of PE was based on the presence of one or more of the following clinical criteria: malaise, dyspnea, syncope, or chest pain.4 Our patient had all four symptoms and pulmonary hypertension by echocardiography, which is a relatively common serious complication of PE.5 He also had an ischemic exercise electrocardiogram (ECG) (Fig. 1) with elevated troponin level. The troponin probably resulted from a severely compromised coronary perfusion as a result of an acute PE.6 In fact, even before he passed out while on the treadmill, his rhythm strip showed ischemia/ injury (Fig. IB). After he passed out, while supine in the recovery phase, his heart rate (HR) increased from a junctional rhythm of 48 beats per minute (bpm) with ventricular and atrial ectopies to a sinus tachycardia of 138 bpm with global ST segment changes (Fig. 1, C-E). Eventually, the tachycardia and all pathologic ECG signs slowly resolved (Fig. 1, F-H). We believe that all these clinical and electrocardiographic events occurred as a result of an acute embolie event superimposed on chronic PE.

CASE REPORT

A 49-year-old Caucasian male soldier, without previous history of cardiovascular problems, was referred to Landstuhl Regional Medical Center (Germany), for evaluation of possible ischemia. An initial clinical work-up revealed a history of malaise, exertional dyspnea, chest pain, and one episode of syncope. He also described left leg swelling. His risks for CA disease included a 3-year history of smoking and an abnormal untreated lipid profile. He then underwent an exercise treadmill test. The study was terminated when the patient began complaining of dyspnea and dizziness which was shortly followed by syncope while on the treadmill. At that point, the ECG showed junctional bradycardia with ventricular and atrial ectopies, followed, seconds later, by sinus tachycardia (HR = 138 bpm), a 1.1- mm ST segment elevation hi leads augmented vector right (aVR), augmented vector left (aVL), Vl, and V2 and a 2.2-mm downsloping ST segment depression in the other leads (Fig. 1). The patient was transferred to the coronary care unit. Under observation, he remained hemodynamically stable. After his cardiac enzyme determinations demonstrated an elevated troponin I level on the third set, he underwent cardiac catheterization which revealed normal coronary circulation with hypokinesis of the distal anterior wall and a mildly reduced left ventricular (LV) ejection fraction (LVEF) of 44%. At this point, antianginal therapy was discontinued. An admission chest x-ray was normal, A prestress test, technically adequate, echocardiogram/ Doppler revealed a normal LV systolic function (LVEF = 68%), mild LV hypertrophy, mild biatrial enlargement, mild mitral regurgitation, bicuspid regurgitation and aortic insufficiency, mild pulmonary hypertension with a right ventricular (RV) systolic pressure of 45 mm Hg. Pulmonary function test was normal but a ventilation perfusion scintigraphy was consistent with bilateral pulmonary emboli (Fig. 2).

A Doppler venous ultrasound of lower extremities revealed thrombosis in the distal superficial femoral vein of the left leg. He was transferred to Walter Reed Army Medical Center (United States) on 90 mg of enoxaparin subcutaneously twice a day and anticipated systemic anticoagulation for a period of 6 months. At WRAMC, a repeat cardiac catheterization was performed to clarify ostium patency of the right CA. It showed normal coronaries and also a normal LV systolic function.

DISCUSSION

At present, more than 30 years after the experimental studies of Mclntyre and Sasahara,7 RV dysfunction and failure is widely accepted to be the single most important determinant of outcome during acute PE. Since then, several carefully designed cohort studies,8″11 prospective randomized therapeutic trials,12,13 and registries1,14,15 have significantly improved understanding of the clinical course and prognosis of this disease. Currently, the accepted diagnostic algorithm is integrated and includes a methodical history and physical examination supplemented by selective laboratory and radiological testing with chest radiography, ventilation perfusion scanning, helical computed tomography, and pulmonary angiography, the gold standard.6 However, it seems fair to say that physicians need to have a higher index of suspicion for PE when confronted with a patient in the proper clinical setting and that dyspnea, chest pain, and/or syncope may not be due to CA disease. In fact, the majority of preventable deaths associated with pulmonary embolie disease can be ascribed to a missed diagnosis, as was the case for our patient rather than to a failure of existing therapies.6,16 Studies over the years have shown the ECG to be both nonspecific and lacking in sensitivity. Different investigators have reported variable parameters as the most frequent pathologic ECG sign of PE (Table I).17-22 Recently, however, ECG has been described as a useful, inexpensive, and readily available tool for assessing the patient’s prognosis and for guiding further diagnostic work-up.23

Our patient is unique in that the diagnosis of PE was ascertained 3 months after he began to have symptoms (malaise, exertional chest pain, dyspnea, and syncope) and a sign (unilateral leg swelling while in Iraq), as well as an exercise treadmill test consistent with ischemia/injury and subsequent normal coronary angiography. As it can be appreciated, Figure 1, A-H, shows-in a vivid way-the sequence of events. These dramatic serial ECG changes raise, in our opinion, several issues.

First, global significant ST changes with ventricular and atrial arrhythmia and junctional bradycardia together with an elevated troponin I level, LV regional wall motion abnormality, and a depressed LVEF suggest that this ominous clinical picture, never described before, was more a result of LV rather than RV ischemia/ infarction.

Second, it can be speculated that PE (acute superimposed on chronic PE since his symptoms began 3 months before) decreased cardiac output which resulted in diminished LV preload, concomitant hypoxemia, and systemic hypotension (his blood pressure was not measured for 4 minutes and 20 seconds, perhaps because the time was spent to get the patient off the treadmill belt and onto the floor). That, in turn, specifically affected coronary flow to the left anterior descending (LAD) CA and reduced oxygen supply even in a patient with normal CA. Impaired flow throughout the left coronary microcirculation could explain a significant decrease of oxygen delivery to the myocardium supplied by the LAD CA, resulting in LV myocardial ischemia/injury.24 Paradoxical embolization of the LAD CA with a thromboembolus via a patent foramen ovale was echocardiographically excluded. Increased concentration of cardiac troponin I was reported to portend an adverse prognosis for patients with acute PE.25

Third, the present case dramatically confirms that PE must be included in the differential diagnosis of acute coronary syndrome. It shows novel pathologic ECG markers of PE, namely global ST segment changes, ventricular ectopic activities, and junctional bradycardia. It also demonstrates that PE can cause LV injury possibly independent of RV infarction. This phenomenon may, perhaps, be called the “ventricular noninterdependency.”

Finally, the role of suspicion in the diagnosis of PE remains today stronger than ever before.

Landstuhl Regional Army Medical Center, Landstuhl, Germany.

This manuscript was received for review in October 2006. The revised manuscript was accepted for publication in April 2008.

REFERENCES

1. Goldhaber SZ, Visani I, De Rosa M: Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386. 2. Pruszczyk P, Szulc M, Horszczaruk G, Gurba H, Kobylecka M: Right ventricular infarction in a patient with acute pulmonary embolus and normal coronary arteries. Arch Intern Med 2003; 163: 1110-1.

3. Stein PD, Terrin ML, Hales CA, et al: Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no preexisting cardiac or pulmonary disease. Chest 1991; 100: 598-603.

4. Lapostolle F, Surget V, Borron SW, et al: Severe pulmonary embolism associated with ah- travel. N Engl J Med 2001; 345: 779- 83.

5. Pengo V, Leasing AW, Prins MH, et al: Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl S Med 2004; 350: 2257-64.

6. Goldhaber SZ: Pulmonary embolism. N Engl J Med 1998; 339: 93- 104.

7. McIntyre KM, Sasahara AA: Determinants of right ventricular function and hemodynamics after pulmonary embolism. Chest 1974; 65: 534-43.

8. Alpert JS, Smith R, Carlson J, Ockene IS, Dexter L, Dalen JE: Mortality in patients treated for pulmonary embolism. JAMA 1976; 236: 1477-80.

9. Hall RJ, Sutton GC, Kerr IH: Long-term prognosis of treated acute massive pulmonary embolism. Br Heart J 1977; 39: 1128-34.

10. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. Research Committee of the British Thoracic Society. Lancet 1992; 340: 873-6.

11. Carson JL, Kelley MA, Duff A, et al: The clinical course of pulmonary embolism. N Engl J Med 1992; 326: 1240-5.

12. The urokinase pulmonary embolism trial. A national cooperative study. Circulation 1973; 47(suppl 2): II1 -108.

13. Goldhaber SZ, Haire WD, Feldstein ML, et al: Alteplase versus heparin in acute pulmonary embolism: randomized trial assessing right: ventricular function and pulmonary perfusion. Lancet 1993; 341: 507-11.

14. Kasper W, Konstantinides S, Geibel A, et al: Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997; 30: 1165-71.

15. Hamel E, Pacouret G, Vincentelli D, et al: Thrombolysis or heparin therapy in massive pulmonary embolism with right ventricular dilation: results from a 128-patient monocenter registry. Chest 2001; 120: 120-5.

16. Fedullo PF, Tapson VF: The evaluation of suspected pulmonary embolism. N Engl J Med 2003; 349: 1247-56.

17. Cutforth RH, Oram S: The electrocardiogram in pulmonary embolism. Br Heart J 1958; 20: 41-54.

18. Lenegre J, Gerbaux A, Gay J: L’electrocardiogramme dans l’embolie pulmonaire. In: L’embolie Pulmonaire, Vol 8, pp 211-49. Edited by Denolin H. Paris, France, Masson, 1970.

19. Stein PD, Dalen JE, Mclntyre KM, Sasahara AA, Wenger NK, Willis PW 3rd: The electrocardiogram in acute pulmonary embolism. Prog Cardiovasc Dis 1975; 17: 247-57.

20. Ferrari E, Imbert A, Chevalier T, Mihoubi A, Morand P, Baudony M: The ECG in pulmonary embolism: predictive value of negative T waves in precordial leads-80 case reports. Chest 1997; 111: 537-43.

21. Daniel KR, Courtney DM, Kline JA: Assessment of cardiac stress from massive pulmonary embolism with 12-lead ECG. Chest 2001; 120: 474-81.

22. Kucher N, Walpoth N, Wustmann K, Noveanu M, Gertsch M: QR in Vl-an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism. Eur Heart J 2003; 24: 1113- 9.

23. Geibel A, Zehender M, Kasper W, Olschewski M, Klima C, Konstantinides SV: Prognostic value of the ECG on admission in patients with acute major pulmonary embolism. Eur Respir J 2005; 25: 843-8.

24. Gibson CM, Cannon CP, Murphy SA, et al: Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000; 101: 125-30.

25. Kucher N, Goldhaber SZ: Cardiac Biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation 2003; 108: 2191-4.

LTC Pasquale F. Nestico, MC USA; MAJ Dimitri C. Cassimatis, MC USA; Capt Fareed Sheikh, USAF MC; MAJ Michael Huber, MC USA; CPT Jonathan Davison, MC USA; COL Randolph Modlin, MC USA

Copyright Association of Military Surgeons of the United States Jul 2008

(c) 2008 Military Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

Breast Cancer Diagnosis and Prognosis Through Quantitative Measurements of Serum Glycan Profiles

By Kyselova, Zuzana Mechref, Yehia; Kang, Pilsoo; Goetz, John A; Dobrolecki, Lacey E; Sledge, George W; Schnaper, Lauren; Hickey, Robert J; Malkas, Linda H; Novotny, Milos V

BACKGROUND: Glycosylated proteins play important roles in cell- to-cell interactions, immunosurveillance, and a variety of receptor- mediated and specific protein functions through a highly complex repertoire of glycan structures. Aberrant glycosylation has been implicated in cancer for many years. METHODS: We performed specific MALDI mass spectrometry (MS)-based glycomic profile analyses of permethylated glycans in sera from breast cancer patients (12, stage I; 11, stage II; 9, stage III; and 50, stage IV) along with sera from 27 disease-free women. The serum glycoproteins were enzymatically deglycosylated, and the released glycans were purified and quantitatively permethylated before their MALDI-MS analyses. We applied various statistical analysis tools, including ANOVA and principal component analysis, to evaluate the MS profiles.

RESULTS: Two statistical procedures implicated several sialylated and fucosylated N-glycan structures as highly probable biomarkers. Quantitative changes according to a cancer stage resulted when we categorized the glycans according to molecular size, number of oligomer branches, and abundance of sugar residues. Increases in sialylation and fucosylation of glycan structures appeared to be indicative of cancer progression. Different statistical evaluations confirmed independently that changes in the relative intensities of 8 N-glycans are characteristic of breast cancer (P

CONCLUSIONS: MS-based N-glycomic profiling of serum-derived constituents appears promising as a highly sensitive and informative approach for staging the progression of cancer.

(c) 2008 American Association for Clinical Chemistry

Glycosylated proteins play important roles in cell-to-cell interactions, immunosurveillance, and a variety of receptor- mediated and specific protein functions through a highly complex repertoire of glycan structures (1-5). Correspondingly, metabolic dysfunctions and disease states may be reflected in the appearance of abnormal glycans or altered quantitative proportions within the glycome. Such observations provide the rationale for recent developments in the field of functional glycomics (6-10). Differential glycomic measurements between healthy and disease states may even have significant clinical diagnostic potential, as exemplified by the recent utilization of capillary electrophoresis in diagnosing liver cirrhosis (11).

Certain links between cancer diseases and altered protein glycosylation have been noted for several years (12-16) for both N- linked and O-linked glycoconjugates, whereas the most advanced knowledge of abnormal glycosylation in this set of diseases has primarily come from the investigations of tumor tissues and cell cultures. Detecting cancer-related changes in patients’ blood has been a distinct goal of more recent studies but has been less commonly pursued because of methodological difficulties with high- sensitivity measurement of glycans. Coincidentally, some recently identified cancer biomarkers in human serum are glycoproteins (17- 20), usually the mucin-type, large molecules.

In this study, we report that the profiles of N-glycans released from glycoproteins of human serum are highly indicative of the different conditions of breast cancer. Using small (10 [mu]L) serum aliquots, we performed sensitive and quantitative mass spectrometry (MS)5 measurements of the constituent profiles of N-glycans originating from circulating proteins. These profiles could be further evaluated statistically through pattern recognition techniques [principal component analysis (PCA)] in terms of breast cancer disease stage. The N-glycan data cluster remarkably well for different stages, which further differ from a data set recorded from individuals apparently free of the disease. The clusters readily distribute into groups that correlate with the stage of breast disease as determined by pathological assessment. This type of clinically useful information could be obtained from a small volume of blood serum, without biopsy or tumor removal. To implicate certain oligosaccharide structures as biomarkers, we carried out additional statistical evaluations (data mining) through nonparametric ROC and ANOVA analyses for approximately 50 individual N-glycans. Finally, for a comparison, we also examined the glycomic profiles of breast cancer cell lines, both invasive and noninvasive, to determine whether they resemble the glycan patterns derived from patient specimens.

Materials and Methods

MATERIALS

Trypsin (EC: 3.4.21.4) and PNGase F (EC: 3.5.1.52) were obtained from Sigma. We purchased the matrix, 2,5-dihydroxybenzoic acid (DHB), trifluoroethanol, sodium hydroxide, CHAPS, Tris-HCl, sodium pyrophosphate, EDTA, and EGTA from Aldrich; chloroform, iodomethane, and sodium chloride from EM Science; dithiothreitol (DTT) and iodoacetamide (IAA) from Bio-Rad Laboratories; ammonium bicarbonate from Mallinckrodt Chemical Company, and acetonitrile from Fisher Scientific.

BLOOD SERUM SAMPLES AND CLINICAL DIAGNOSIS

Blood serum collections from disease-free female volunteers and women diagnosed with different breast cancer stages were performed by a clinical team according to an institutional review board- approved clinical trial. Venous blood samples were taken during the morning fasting state, with minimal stasis in evacuated tubes. After at least 30 min, but within 2 h, the tubes were centrifuged at 20 [degrees]C for 12 min at 120[degrees]g. Sera were stored frozen in plastic vials at -80 [degrees]C before use in consecutive measurements.

We generated glycomic profiles for samples derived from women in one of two categories: (1) disease-free woman at low risk for developing breast cancer and (2) postmenopausal women with confirmed disease stratified according to their having noninvasive or invasive breast cancer. We divided breast cancer patients into 4 subgroups (I- IV) based on severity of disease (21). We collected samples from 27 healthy individuals and from 12 patients in stage 1,11 in stage II, 9 in stage III, and 50 in stage IV. A detailed characterization of the healthy volunteers and patients with their clinical diagnoses can be found in Tables 1-2 in the Data Supplement that accompanies the online version of this article at http://www.clinchem.org/ content/ vol54/issue7.

CANCER CELL LINES

We lysed cancer cell lines (normal mammary epithelial, MCFlOA; invasive, MDA-MB-231, MDA-MB-435; noninvasive, 578T, ADR-RES, BT549, and T47D) in a CHAPS-based buffer (150 mmol/L NaCl, 0.5% CHAPS, 50 mmol/L Tris (pH 7.5), 10 mmol/L sodium pyrophosphate, 1 mmol/L EDTA, 1 mmol/L EGTA). We then subjected lysates to ultracentrirugation at 16400g, separating the samples into cytosolic and membrane- associated proteins, and 200-[mu]g protein aliquots (determined by Bradford assay) underwent the same procedures described for blood serum.

TRYPSIN DIGESTION

Human serum samples were reduced and alkylated before the addition of trypsin as described (22). Briefly, 10 [mu]L of human serum was dried and then resuspended in 25 [mu]L of 25 mmol/L ammonium bicarbonate, 25 [mu]L trifluoroethanol, and 2.5 [mu]L of 200 mmol/L DTT. We incubated the samples for 45 min at 60 [degrees]C, added 10 [mu]L of 200 mmol/L LAA, and left the samples at room temperature for 1 h in the dark. We added 2.5 [mu]L DIT to remove excess IAA and again left the samples for l h in the dark. Finally, we added 300 [mu]L water to dilute samples and 100 [mu]L ammonium bicarbonate stock solution to adjust pH. Proteolytic digestion was performed using 1 [mu]g/[mu]L [or 1:50 (wt/wt) ratio] proteomics-grade trypsin dissolved in 1 mmol/L HCl and incubated at 37 [degrees]C overnight (at least 18 h). Afterward, enzyme activity was quenched by incubation at 95 [degrees]C for 10 min and allowed to cool at room temperature.

RELEASE OF M-GLYCANS FROM GLYCOPROTEINS AND PURIFICATION

The N-glycans were enzymatically released from human serum samples as previously described (23). Briefly, we added 5 mU PNGase F to the reaction mixture, which was subsequently incubated overnight (18-22 h) at 37 [degrees]C. We removed deglycosylated peptides from the reaction mixture using C18 Sep-Pak(R) cartridges (Waters) that were preconditioned with ethanol and deionized water. We further purified the aqueous eluent containing released N- glycans using activated charcoal microcolumns (Harvard Apparatus). The columns were conditioned with acetonitrile and equilibrated with 0.1% trifluoroacetic acid (TFA). After trapping of the diluted sample, the microcolumns were washed with 0.1% TPA, and the samples were eluted in a minimum volume of 50% acetonitrile containing 0.1% TFA.

CAPILLARY PERMETHYLATION

The N-glycans derived from human blood serum samples, as described above, were finally dried under vacuum and subsequently permethylated using a capillary approach, which involves the use of fused silica capillary reactor (500 [mu]m i.d.; Polymicro Technologies) packed with sodium hydroxide beads (22). We used a Hamilton 100-[mu]L syringe and a syringe pump from KD Scientific to introduce the sample into the reactor. Dried samples were resuspended in 50 [mu]L DMSO to which 0.3 [mu]L water and 22 [mu]L methyl iodide were added before infusion through reactors. This permethylation procedure minimizes oxidative degradation and “peeling” reactions and prevents the need for excessive clean-up (22). Finally, permethylated Nglycans were extracted with chloroform and washed repeatedly with water. MALDI-TOF/TOF MS INSTRUM ENTATION

We resuspended dried permethylated samples in 2 [mu]L methanol:water solution (50:50) containing 1 mmol/L sodium acetate and spotted 0.5-[mu]L sample aliquots directly on the MALDI plate, mixed with an equal volume of 2,5-DHB matrix [prepared by suspending 10 mg of DHB in 1 mL watermethanoi (50:50)], and dried under vacuum.

Mass spectra were acquired in the positive-ion mode on the Applied Biosystems 4700 Proteomic Analyzer. This instrument is equipped with Nd:YAG (355 nm) laser. Argon was used as a collision gas in the tandem MS measurements, and the collision cell pressure was set to 6.5 x 10^sup -6^ torr. The acquired spectra were the average of 1000 laser shots.

DATA EVALUATION

We further processed MS data using DataExplorer 4.0 (Applied Biosystems) and an software tool developed in-house (PeakCalc 2.0). We performed PCA using MarkerView (ABI), allowing the visualization of multivariate information. We used supervised PCA methods with a prior knowledge of the sample groups, such as healthy vs diseased. MS data were weighted using the natural logarithm of the peak intensities. The peak intensities were also scaled using the Pareto option, in which the average value is subtracted from each value and the difference divided by the square root of the standard deviation. This option is suited for MS data, since it prevents intense peaks from completely dominating PCA. Variation within groups was expressed as SE (24).

We also used ROC curve analysis AccuROC 2.5 (Accumetric Corporation) to assess the sensitivity and selectivity of the potential diagnostic variables, and data were statistically analyzed using a single-factor ANOVA test. The difference between the 2 groups of data was considered statistically significant when P values were

Results

SERUM GLYCOMIC PROFILES

In the differential measurements of glycomic data for different patient groups, it was essential to achieve a high degree of methodological precision, so that the individual variations (patient- to-patient), or “profile individuality,” were not overshadowed by the measurement errors. Fortunately, our recently reported glycan mapping procedure (22) yields quantitative reproducibiliry with

We were able to identify and quantify approximately 50 different N-glycan structures, which cover all typical structural types, including high-mannose, hybrid, and complex-type entities. As shown previously (26), the high-energy collision process used in this type of tandem mass spectrometry (MS/MS) yields reliable structural identification of each recorded glycan. MS/MS was employed here to identify the majority of the structures (data not shown). In comparing visually the glycomic profiles of the healthy individuals with those suffering from breast cancer, we were able to note that, within the molecular mass range of 1500-5000 mlz, there was an overall decrease in abundance of smaller N-glycans (m/z: 1500-2700) compensated by an increase in the abundance of larger structures. Representative profiles are illustrated in Fig. 1, A and B, with a healthy profile compared to stage I and IV, respectively. These relative ion intensity changes in a profile (small N-glycans changing into larger structures due to different addition of sugar residues) were enhanced from stage I to stage IV. This general observation is consistent with a published report (13) by Rye and Walker as well as more recent studies on glycosylation in tumor tissues (6, 8, 9). Obviously, the trend of adding fucosyl and sialyl residues to certain glycoprotein structures in tumor tissues, observed in these investigations, was also observed here.

PCA OF N-GLYCAN PROFILES

In assessing more precisely the patterns of N-glycans that could be characteristic for specific cancer conditions, we turned to PCA, which is a chemometric tool designed to reduce the dimensionality in a data set by defining a reduced set of projection axes that allow a maximum amount of the variance information originally in the data set to be retained (27). The acquired profile data, measured for all subjects (healthy and breast cancer patients) were subjected to PCA as described above (Fig. 2) followed by cluster analysis. The numbers of subjects in the early stages of breast cancer (stage 1,12; stage 11,11; stage III, 9) were lower than for stage IV (50) and individuals free of the disease (27). The final clustering of our data indicates that there are significant differences in the glycomic profiles of healthy individuals in comparison to those of individuals in the early stages of breast cancer. This observation supports the notion of the diagnostic potential for recognizing different stages of breast cancer and perhaps even detecting early onset through glycomic analysis of serum specimens. Data clustering was achieved despite the heterogeneity of the sample population studied here. This aspect is believed to be an advantage, since such heterogeneity reflects a true representation of a breast cancer population. However, the presence of such heterogeneity might also prompt challenging data interpretation.

GLYCAN POTENTIAL BIOMARKER IDENTIFICATION THROUGH DATA MINING

We performed a further statistical evaluation of putative biomarkers through nonparametric ROC procedure (28-30). Fig. 3 shows some examples of ROC analysis of N-glycan markers, comparing healthy individuals and stage IV breast cancer patients. Thus, the N-glycan with m/z 3864 had an area under the curve (AUC) value of 0.97, indicating its high diagnostic accuracy (Fig. 3A), whereas another structure (m/z 2111) had an AUC value of only 0.49, similar to random variation (Fig. 3C). An AUC value of 0.88 was calculated for the N-glycan with m/z 1835, making it only a moderately accurate test (Fig. 3B).

In Table 1, we list the AUCs for the N-glycans that were evaluated by ROC analysis and their P values from single-factor ANOVA. We have taken into consideration only the N-glycans for which comparison of nondiseased and diseased experimental groups yielded P values

A further correlation of the favorable AUC values with P values from ANOVA implicates 8 N-glycans whose relative intensity changes profoundly during breast cancer development (Fig. 4A). These particular N-glycans thus represent strong biomarker candidates, as the occurrence of their specific structures has been confirmed by 2 independent statistical approaches, both accepted widely in the biomedical literature.

Whereas data on glycan modifications in cancer cell lines and tumors, including fucosylation and sialylation, are available (31- 35), it seemed prudent to supplement our investigations on serum glycan levels by the parallel analyses of a human mammary epithelium cell (control) and cancer cell lines (invasive and noninvasive) using the same analytical procedure. Examining the 8 N-glycan structures implicated in the blood serum as pertinent to cancer, we found similar trends for 6 of these structures in the extracts prepared from invasive (MDA-MB-231, MDA-MB-435) and noninvasive (578T, ADR-RES, BT549, T47D) breast cancer cells (Fig. 4B). The invasive cell lines, capable of forming tumor metastases distant from their original site of transformation, were found to have a more dramatic change in the glycomic pattern compared with the noninvasive cells. Moreover, N-glycans associated with m/z 3951 and 4226 are not observed in normal cell lines, suggesting their potential role during the tumorigenesis process.

STRUCTURAL CORRELATIONS

Grouping N-glycan profile constituents into categories according to molecular size, number of antennas, and sugar residue abundance (Fig. 5) can be indicative of certain general trends of disease progression. The overall trend in increased N-glycan size due to the addition of sialic acid residues and enhanced fucosylation is clearly evident. A noticeable fact is that all 8 N-glycans selected by AUC values and ANOVA are sialylated to a different degree (mono- , di-, tri-, and tetrasialylated). Moreover, 5 of these structures are fucosylated (2 of them difucosylated), supporting the general notion of fucosylation involvement during progression of cancer in a different organ (33).

Fig. 1. MALDI mirror mass spectra of N-glycans derived from a 10- [mu]L aliquot of the serum of a healthy individual (upper trace) and a stage I breast cancer patient (lower trace) (A) and a healthy individual (upper trace) and a stage IV breast cancer patient (lower trace) (B).

[black square] N-acetylglucosamine; *, mannose; [white circle], galactose; [white triangle up], fucose; *, N-acetylneuraminic acid.

Fig. 2. PCA score plot of MALDI/MS N-glycan profiles derived from the sera of healthy individuals and breast cancer : patients at different stages of the disease. PC1, principal component 1; PC2, principal component 2.

Discussion

Procedural simplicity, combined with sensitivity, information content, and accuracy, has been among the most valued attributes of clinical diagnostic and prognostic methods. Most procedures for breast cancer detection rely on pathology-based criteria such as tumor size and grade, lymph node status, etc. (36) and histological evaluation of hormone receptors and plasminogen activators (37) after biopsy or surgery, which are used to predict patients’ chances for survival. Detection of biomarkers in circulation has been limited to single-protein indicators, such as CA 15-3, MUC1, carcinoembryonic antigen (CEA), BR 27.29, tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS), and the shed form of human epidermal growth factor receptor 2 (HER-2), which all provide (with the possible exception of CA 15-3 (38) and MUC1 (8)) neither the sensitivity nor the specificity needed for early-stage disease (39). Consequently, mammography and histopathology still remain the primary modalities for detecting breast cancer at an early stage of the disease.

Fig. 3. Representative ROC analysis AUC plots for different N- glycan structures reflecting high-accuracy (A), moderate-accuracy (B), and low-accuracy (C) tests.

AUCs are expressed as mean (SE). Symbpis as in Fig. 1.

Additional validation for clinically relevant glycomic mapping from serum samples comes from the correspondence of implicated N- glycan structures with those found in cancer cell lines in association with membrane glycoproteins. As shown in Fig. 4 and Fig. 5, and verified through statistical criteria, a more intense glycosylation is associated with cancerous cells, in agreement with recent observations made elsewhere (6, 8, 9) on glycosylation due to cancer progression. In our measurements, the invasive cell lines capable of forming tumors away from their original site of transformation represented a more extreme change in glycomic pattern compared with the noninvasive cells.

Table 1. Evaluation of diagnostic potential of specific N- glycans according to AUC.

Fig. 4. Relative intensity changes of 8 N-glycans with high- accuracy ROC analysis AUC values (0.9

Symbols as in Fig. 1.

Six N-glycan structures from the cancer cell lines are shared with those implicated as significant in our serum measurements (8 major N-glycans). The corresponding differences in glycomic maps revealed a substantial increase of rucosylation (both within the core component and the branched segments) with malignant transformation. Interestingly, increased rucosylation has also been associated with pancreatic cancer (33), colorectal cancer (40), human leukocyte cancer (34), and renal carcinomas (35 J. At this point in time, measurements of various sialylated structures in serum present a less dear picture. Since various sialylated oligosaccharides were implicated in different malignant cells as both O- and N-linked structures (7-9, 31-35, 40), our future studies will concentrate on these structural types.

Fig. 5. Bar graphs of N-glycan relative intensity changes derived from the blood sera of healthy Individuals vs breast cancer patients according to their structural type.

The lower trace is a zoomed segment of the upper trace.

In conclusion, the MS-based glycomic profiling of serum-derived constituents described here provides a Highly sensitive and informative approach to differential evaluation of cancer conditions. Such an approach can be based on the sound knowledge of aberrant glycobiology of cancerous cells that shed their surface glycoproteins into the surrounding biofluids. Although it is not yet clear which serum glycoproteins are primarily responsible for the diagnostically distinct N-glycans, statistical analyses of selected N-glycans (or their patterns) provide potential for developing diagnostic and prognostic procedures. Whereas MS instrumentation is relatively expensive, the method provides nearly absolute structural information at a moderate level of measurement throughput. PCA, ROC, and ANOVA statistical analyses of the MS data independently confirmed 8 N-glycans (P

Grant/Funding Support: This work was supported in part by grants GM24349 from the National Institutes of Health (NIH) and RR018942 from the National Center for Research Resources, NIH, as a contribution from the National Center for Glycomics and Glycoproteomics at Indiana University to M. Novotny. This work was also supported in part by grant ROl CA83199 to L. Malkas from the National Cancer Institute, NIH, by a Biomedical Research Grant from the Indiana University Medical School to R. Hickey, and a Department of Defense Center of Excellence Grant W81XWH-04-1-0468 to G. Sledge. The initial stages of this investigation were also aided by a grant from the 21st Century Fund of the State of Indiana. This work was also supported in part by a fellowship from Merck Research Laboratories for P. Kang.

Financial Disclosures: None declared.

Acknowledgments: The authors thank Milan Madera for the development of PeakCalc 2.0.

5 Nonstandard abbreviations: MS, mass spectrometry; PCA, principal component analysis; DHB, 2,5-dihydroxybenioic add; DTT, dithiothreitol; IAA, iodoacetamide; TFA, trifluoroacetic acid; AUC, area under the curve.

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19. Shariat SF, Canto El, Kattan MW, Slawin KM. Beyond prostate- specific antigen: new serologic biomarkers for improved diagnosis and management of prostate cancer. Rev Urol 2004;6:58-72.

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36. Elston CW, Ellis IQ, Finder SE. Pathological prognostic factors in breast cancer [Review]. Crit Rev Oncol Hematol 1999;31:209-23.

37. Isaacs C, Stearns V1 Haves DF. New prognostic factors for breast cancer recurrence. Semin Oncol 2001;28;53-67.

38. Duffy MJ. Serum tumor markers in breast cancer: are they of clinical value? Clin Chem 2006;52: 345-51.

39. Cheung KL, Graves CR, Robertson JF. Tumour marker measurements in the diagnosis and monitoring of breast cancer. Cancer Treat Rev 2000; 26:91-102.

40. Izawa M, Kumamoto K, Mitsuoka C, Kanamori C, Kanamori A, Ohmori K, Ishida H, et al. Expression of sialyf 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer. Cancer Res 2000;60: 1410-6.

Zuzana Kyselova,1 Yehia Mechref,1* Pilsoo Kang,1 John A. Goetz,1 Lacey E. Dobrolecki,2 George W. Siedge,2,4 Lauren Schnaper,3 Robert J. Hickey,2,4 Linda H. Malkas,2,4 and Milos V. Novotny1,4*

1 National Center for Glycomics and Glycoproteomics, Department of Chemistry, Indiana University, Bloomincrton, IN; 2 Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; 3 Breast Cancer Center, Greater Baltimore Medical Center, Baltimore, MD; 4 Indiana University Cancer Center, Indianapolis, IN.

* Address correspondence to these authors at: Department of Chemistry, Indiana University, 800 E. Kirkwood Ave., Bloomington, IN 47405- Fax 812-855-8300; e-mail [email protected], [email protected].

Received February 7, 2007; accepted April 8, 2008.

Previously published online at DOI: 10.1373/clinchem.2007.087148

Copyright American Association for Clinical Chemistry Jul 2008

(c) 2008 Clinical Chemistry. Provided by ProQuest Information and Learning. All rights Reserved.

Inhalational Diesel Exhaust Exposure in Submariners: Observational Study

By Duplessis, Christopher A Gumpert, Barton

ABSTRACT Objective: An observational study was performed with a convenience sample of 38 submariners exposed to diesel exhaust for 9 hours, to assess the development of reactive airways dysfunction syndrome (RADS) after prophylactic corticosteroid treatment. Methods: Twenty-four subjects were available for baseline physical examinations, pulmonary function tests, and chest radiographs, and 16 more subjects were available for interviews; 30 subjects were available for 6-month follow-up surveys. Subjects were treated on the basis of presenting symptoms; 19 subjects were treated with a 10- day course of orally administered prednisone, accompanied by 30 days of inhaled fluticasone/ salmeterol therapy. Results: There were no cases of RADS diagnosed at 6-month follow-up evaluations. Conclusion: There were no cases of RADS diagnosed at 6-month follow- up evaluations in submariners with uncontrolled, isolated, heavy diesel exhaust exposure, despite many initial symptoms that portended the diagnosis. To our knowledge, this is the largest reported case study of corticosteroid treatment initiated with an expressed intention to prevent the development of RADS after an isolated diesel exhaust exposure. Although we cannot prove that early intervention with corticosteroids prevented RADS, we think that the implementation of prompt prophylactic treatment expedited symptom resolution and might have prevented RADS development, on the basis of previous historical control data. RADS resulting from diesel exhaust may be an important public health issue, and our hope is to promote increased recognition of the diagnosis, which often is not suspected upon initial presentation but is delayed by up to several years. Increasing awareness may prompt pursuit of more- aggressive interventions with acute and protracted corticosteroid treatment and execution of the necessary controlled trials to establish treatment efficacy in mitigating the severity and/or circumventing the development of RADS. INTRODUCTION

Diesel exhaust exposure is pervasive, given the increased use of diesel power in industrial applications. Concerns have arisen regarding the potential acute and chronic health decrements, notably carcinogenic, neurobehavioral, and cardiorespiratory, resulting from exposure.1-3 Diesel fuels are long-chain hydrocarbons encompassing both aliphatic and aromatic constituents. Exhaust products include oxides of nitrogen and sulfur, volatile organic compounds, alkanes, alkenes, aldehydes (formaldehyde, acetaldehyde, and acrolein), benzene, aliphatic hydrocarbons (polycyclic aromatic hydrocarbons), carbon monoxide (CO), carbon dioxide, dioxins, and carbonaceous particulates.2,3 The particulate matter includes elemental carbon and adsorbed organic compounds, with small amounts of sulfate, nitrates, metals, and trace elements. The fine and ultra-fine particles possess diameters of

Population-based studies suggest that diesel exhaust, as a toxicologie pulmonary irritant, may provoke bronchial hyperresponsiveness, exacerbate preexisting allergies and asthma, and engender new-onset asthma.3-7 There is a paucity of data documenting the duration and severity of exposure (isolated or chronic) that may cause respiratory injury.1-10 Toxic inhalational injuries are often self-limited but may cause severe respiratory injury, bronchiolitis obliterans, pulmonary edema, asphyxia, acute respiratory distress syndrome, and death. Occasionally, irritant- induced pulmonary injury may engender reactive airways dysfunction syndrome (RADS).

RADS manifests as protracted airway disease, encompassing nonimmunologic bronchial hyper-responsiveness and airflow obstruction.10 The development of respiratory symptoms occurs shortly after isolated exposure to elevated concentrations of irritant gases, aerosols, vapors, fumes, smokes, or particles. A prolonged period of airway hyper-responsiveness then ensues, with reversible airway obstruction persisting for at least 3 months, often for years, and sometimes permanently.1,10-13 The acute exposure typically occurs in the setting of workplace accidents or situations involving poor ventilation.10 Allergic sensitization is not a prerequisite in the pathogenesis of RADS, differentiating RADS from occupational asthma (which requires a requisite sensitization period, with symptoms predictably surfacing at work). RADS does not appear to require atopic genetic predisposition for its diagnosis, in contradistinction to occupational asthma.13,14 Risk factors for the development of RADS may include premorbid pulmonary conditions and smoking.15 Finally, many cases may evolve through a conditioning phenomenon, whereby previous subthreshold exposures sensitize or potentiate development.

RADS has been noted after exposure to a myriad of inhalational irritants, including combustion products,3,8 with diesel exhaust being implicated as the seventh most common cause.1,15 Diesel- powered trucks have dominated the industry, and diesel paniculate matter now represents an appreciable proportion of the total burden of environmental airborne particulate pollutants. Diesel exhaust exposure may represent a significant public health hazard, as evidenced by recent articles documenting acute decrements in respiratory function among asthmatic individuals and increased susceptibility to coronary vascular events.4,6 Diesel exhaust injuries have been reported for various Navy diesel engines.16

Empirically administered inhaled and/or oral corticosteroid treatment is commonplace (although perhaps controversial) for initial presentations of presumed chemical pneumonias and/or bronchitis produced by various inhalational irritants. However, there is a dearth of documentation establishing treatment efficacy in ameliorating pulmonary injury. To our knowledge, no documented evidence has established the efficacy of expeditious and/or protracted administration of corticosteroids to circumvent pulmonary remodeling and RADS development.15,17-19 Early parenteral corticosteroid administration after inhalational exposures attenuated the otherwise-anticipated severity of bronchial hyper- responsiveness in animal and human models.15,17,20 One case report documented improvement in pulmonary function and mitigation of bronchial hyper-responsiveness with inhaled steroid treatment after an irritant exposure. The authors documented deterioration in pulmonary performance after cessation of steroid treatment, with improvement upon its reintroduction. That article provides some indirect evidence of the potential efficacy of inhaled steroids in mitigating the severity and/or circumventing the development of RADS.17

Ultimately, we hope to emphasize the importance of considering the diagnosis of RADS, which is often not suspected, upon initial presentation of presumed chemical pneumonitis or bronchitis. Our results, coupled with future dedicated controlled trials, may establish the efficacy of administration of acute and protracted courses of corticosteroids to circumvent the development and to minimize the severity of RADS.

INDEX CASE

A submariner presented to our medical facility ~24 hours after diesel exhaust exposure sustained during drills performed aboard a pier-side submarine (opened to the atmosphere). He complained of a persistent productive cough, wheezing, shortness of breath, chest tightness, and pain with deep inspiration; all symptoms developed several hours after commencement of drills. His physical examination was significant for diffuse end-expiratory wheezing. Laboratory results, including complete blood count, arterial blood gas analysis, and complete metabolic panel, were normal, as were electrocardiographic findings. Chest radiographic findings were normal. Pulmonary function test (PFT) results were significant for a forced expiratory volume in 1 second (FEV^sub 1^) of 2.65 L/min (58% of predicted), a forced vital capacity of 3.27 L/min (62% of predicted), and a decreased diffusion capacity for CO (50% of expected). The laboratory was unable to process a request for a carboxyhemoglobin level because of a machine malfunction. The patient was diagnosed as having chemically induced pneumonitis and was treated with a 10-day course of 40 mg of orally administered prednisone.

Subsequent interrogation regarding the patient’s occupational exposure revealed that the submarine filled with diesel exhaust while pier-side drills were being performed for ~9 hours. The events leading to this exposure involved inadvertent positioning of the air intake manifold in close proximity to the diesel exhaust; this stemmed from a failure of the hydraulic actuator to reposition the manifold.

Realizing that the entire ship’s complement was exposed and vulnerable to experiencing acute pneumonitis, bronchitis, and RADS,1 our pulmonary department communicated to the ship the importance of facilitating medical evaluations of all submariners involved. The submariners almost by consensus described this exposure as the highest concentration of diesel exhaust experienced, admitting that it is not uncommon to experience some low-level exposure during typical pier-side drilling while operating the diesel engine. We elected to prophylactically treat subjects with orally administered and/or inhaled steroids, on the basis of presenting symptoms. Appreciating this unique cohort and exposure history, we performed an observational study cataloging symptoms consistent with fume- induced pneumonitis, assessing for the development of RADS attributable to diesel exhaust after administration of prophylactic steroid treatment. METHODS

Human testing was approved by ethical review boards for the protection of human subjects at Naval Medical Center Portsmouth. Each subject provided written informed consent before participating. The setting was a U.S. fleet ballistic missile submarine performing pier-side maneuvering drills on diesel power. Forty submariners (all male; average age, 29 years; age range, 22-43 years) from the submarine who participated in the pier-side exercise were enrolled. Twentyfour subjects who expressed significant symptoms and desired examinations were available for baseline physical examinations, PFTs, and chest radiographs; 16 additional exposed submariners were interviewed (one of whom exhibited significant pulmonary symptoms warranting treatment but did not feel compelled to be examined), and 30 subjects were available for 6-month follow-up surveys. The 24 subjects examined presented within 4 days after the exposure. Medical histories were acquired in direct interviews, with verification through review of subjects’ medical records. The rest of the submariners who were attached to the submarine and who had participated in the exercise either denied symptoms or were not exposed. Given the delay in the initial interviews, invasive bronchoscopic inspection of the airways and inflammatory biomarker analyses were not undertaken (Table I).

All except four enrolled participants admitted to experiencing the maximum 9-hour exposure. Six subjects donned respiratory protection, via the emergency air breathers (EABs) installed throughout the ship, for variable time periods.

PFTs were conducted in accordance with guidelines for acceptability and reproducibility from the American Thoracic Society.9 A FEV^sub 1^/forced vital capacity ratio of

Subjects were treated on the basis of the severity of presenting symptoms; 19 subjects were treated with a 10-day course of orally administered prednisone with concomitant inhaled steroid therapy (250 [mu]g fluticasone/50 [mu]g salmeterol) for 15 to 30 days, and six subjects received 2 weeks of treatment with inhaled corticosteroid (fluticasone) alone. Severity was based on identification of significant decrements in PFT findings, persistent symptoms at presentation, or significant examination findings, all warranting oral steroid therapy.

RESULTS

Significant medical histories included one subject with a history of pneumonia, one with mitral valve prolapse, and one with reflux disease, two subjects treated for hypertension, and four subjects intermittently treated for allergic rhinitis (with one subject admitting to symptoms before the exposure). Twelve subjects reported current tobacco use. Notably, 10 of the 12 smokers were represented among the initial 24 subjects who presented with appreciable symptoms and were available for baseline PFTs. Physical examinations identified two subjects manifesting acute wheezing.

The symptoms reported within the initial 24 hours after exposure are presented in Table II. Four subjects exhibited obstructive findings in PFTs. With the use of 80% of the reference value as the standard, seven subjects exhibited decrements in diffusion capacity for CO. There were no identifiable abnormalities on chest radiographs (Table III).

Of the four subjects who exhibited reduced FEV^sub 1^, one was a smoker. Five of seven subjects who exhibited decrements in diffusion capacity for CO were smokers. None of the subjects who used EABs manifested decrements on PFTs. In 6-month follow-up evaluations, the 30 interviews retrieved revealed that all symptoms had abated except for two subjects who exhibited continued, intermittent, mild dyspnea, one subject who admitted lightheadedness, and one subject who was experiencing continued nasal congestion. We have no reports of symptoms attributable to the incident among those who did not participate in the study. The two subjects with persistent mild dyspnea exhibited normal methacholine challenge test results. To date, no subjects have developed RADS.

DISCUSSION

Because of the prolonged periods within the confined, closed, recirculated atmosphere of a submarine, attention must be directed vigilantly toward atmospheric purity. The toxic diesel exhaust exposure might have exposed the submariners to CO poisoning.21 Submarines are equipped with H2CO burners to scavenge CO produced while the submarine is underway. Submarines use centralized atmospheric monitoring systems that monitor CO levels, emitting alarms if threshold limit values (TLVs) are exceeded. Unfortunately, the system was inoperable, given pier-side operations, and CO levels were unavailable. Neither trace gas analysis nor Draeger tube monitoring of select contaminants was available. Fortunately, no submariner experienced loss of consciousness or neurologic deficits. Prompt treatment with 100% normobaric oxygen or hyperbaric oxygen may avert potential morbidity, cognitive deficits, and neuropsychologic sequelae resulting from significant CO exposure.21 No subjects presented with significant rhinitis warranting nasal steroid treatment, indicating the existence of a reactive upper airways dysfunction syndrome.

Clinical manifestations of acute irritant exposures that may lead to RADS include the onset of a burning sensation in the eyes, nose, throat, and lungs, dyspnea, pleuritic chest pain, coughing, wheezing, hemoptysis, rhinitis, dizziness, headache, and nausea.1,10,22,23 Symptoms occur acutely, within 24 hours (often within minutes), without an accompanying latency period after the exposure (as differentiated from occupational asthma), and persist for at least several months when leading to RADS.14

The pathogenesis of RADS involves an isolated respiratory insult that produces respiratory epithelial injury and mucosal damage (loss of epithelial integrity, desquamation, and denudation).15 Most patients recover from a toxic insult with normalized pulmonary function. In patients predisposed to RADS, there is an exaggerated epithelial injury, with derangement of the healing process. Recovery is accompanied by a chronic, nonspecific, airway inflammatory response, architectural changes, airway remodeling, and activation of neuronal reflexes, in a self-sustaining perpetual inflammatory cascade.10,14,24 The bronchial mucosal reepithelialization and reinnervation after the pulmonary inflammatory injury may alter the threshold of the subepithelial irritant receptors, rendering them hyper-reactive to reexposure to the inciting insult, as well as other subsequent irritants (e.g., cold, exercise, dusts, and various fumes and vapors).1,10,15 The increased airway hyper-reactivity is not specific to RADS but has been identified after various pathologic pulmonary injuries, including adult respiratory distress syndrome and pulmonary infections, resulting from the pulmonary inflammatory process. Patients with RADS may exhibit less airway reversibility than patients with asthma (occupational asthma), which supports the distinct airway remodeling and pathophysiologic injury inflicted in this disease.24

RADS diagnosis is formally defined according to the American College of Chest Physician consensus statement as (1) documented absence of preceding respiratory complaints; (2) onset of symptoms after an isolated exposure; (3) identification of the exposure as a gas, smoke, fume, or vapor present in high concentrations, with inherent irritant qualities; (4) symptom onset within 24 hours and persistence for at least 3 months; (5) symptoms simulating asthma (cough, wheezing, and dyspnea); (6) PFTs demonstrating airflow obstruction or nonspecific bronchial hyper-responsiveness (positive methacholine challenge test results); and (7) exclusion of alternative 0 diagnoses.10,15 RADS treatment is primarily supportive, with the use of bronchodilators and possibly inhaled anticholinergic agents and inhaled and/or orally administered corticosteroids.15

Presently, there is no permissible exposure limit promulgated by the Occupational Safety and Health Administration for diesel exhaust as a unique hazard. However, there are permissible exposure limits imposed upon many of its constituents (both gaseous and paniculate fractions) that are known to contribute to the respirable occupational and environmental pollutant burden. There are no imposed limitations on diesel exhaust paniculate matter, which may constitute 6% to 10% of total paniculate matter; however, it is limited indirectly via the limitations on total environmental paniculate matter established by the National Ambient Air Quality Standard designated by the Environmental Protection Agency.3,25

As stated above, there is a paucity of literature investigating the potential efficacy of prompt and/or protracted prophylactic corticosteroid treatment in circumventing RADS development resulting from inhalational irritants. Although we cannot prove that early intervention with corticosteroids prevented RADS, we think that the prompt prophylactic treatment might have expedited symptom resolution and prevented RADS, on the basis of previous historical control data. This assertion stems from documentation of a duration of diesel exhaust exposure similar to that experienced by our cohort (with the acknowledgment this is merely a surrogate for the concentration and total amount of exposure), which ultimately yielded the diagnosis of RADS.1 Unfortunately, this investigation, like most such publications, can only infer the total composite exposure on the basis of surrogate measures such as the total duration of exposure, given the absence of concentration measurements during the acute, isolated, unanticipated exposure. This assertion is offered with the acknowledgment that specific subjects who develop RADS after an isolated exposure might have experienced numerous previous subclinical exposures, which might have conditioned them (although this is only speculative). Although it was not statistically significant, the qualitative observation that more smokers were represented in the cohort that sought early treatment and manifested significant decrements in PFT results is noteworthy; it suggests smoking as a risk factor for the acute development of respiratory symptoms resulting from nonspecific environmental insults, which is likely attributable to reduced pulmonary reserve and the presence of baseline, nonspecific, bronchial hyper-reactivity.10 This assertion is consistent with documentation that premorbid pulmonary pathologic conditions and smoking may be risk factors for the development of RADS.15

We hope to emphasize the importance of education and training to prevent future incidences and to optimize treatment. We specifically wish to eliminate delays in treatment or transfer to higher-echelon medical care, where potentially efficacious therapies can be administered. We advocate training of medical support personnel to remain vigilant in recognizing scenarios that place shipmates at risk for inhalational incidents and to execute strategies to prevent such situations. Practical measures suggested include real-time monitoring of the submarine atmosphere for carbon dioxide, CO, and nitrogen oxides by using Draeger tubes or portable gas analyzers, continued development of particulate monitors, and implementation of such monitors when the submarine is operating on the diesel engine, particularly when the centralized atmospheric monitoring system is nonfunctional. Suggested policy implementations include (1) administrative controls yielding regulations in work practices to minimize deleterious exposures, including the establishment of 8- hour TLVs for nitrogen oxides and other diesel exhaust constituents, with alarms when TLVs are exceeded that mandate punctual donning of respiratory protection (EABs); (2) engineering controls, including measures to eliminate the risk of diesel exhaust entry into the submarine compartment and institution of filtering units to decrease levels of particulate and volatile organic materials1,13; and (3) education in personal protective controls (training to recognize the acrid odor or visual haze suggesting excessive atmospheric diesel exhaust and necessitating personal isolation or donning of an EAB).

Finally, we advocate acute administration of inhaled and/or orally administered corticosteroids, potentially coupled with inhaled bronchodilator therapy and anticholinergic treatment, with 100% normobaric oxygen therapy (to treat concomitant CO exposure) during transfer to higher-echelon medical care, until definitive, evidence-based studies become available. We hope to promote vigilance in identifying opportunities to perform controlled studies investigating the utility of inhaled and/or orally administered corticosteroids in mitigating pulmonary symptoms and decreasing the severity and incidence of RADS after significant respiratory exposures. With the acknowledgment that most cases of acute, chemically induced pneumonitis/bronchitis would be treated with corticosteroids, investigations may be predicated predominantly on pursuing the utility of protracted courses in expediting symptom resolution and preventing RADS development. Future investigations may identify the exposures, clinical manifestations, biomarkers, genetic polymorphisms, PFT results, and comorbidities that predict subsequent development of RADS and may identify potential chemoprotectants to mitigate its severity, to expedite its resolution, and to circumvent its development.26,27

CONCLUSIONS

There were no cases of RADS diagnosed at 6-month follow-up evaluations among submariners with uncontrolled, isolated, heavy diesel exhaust exposure, despite the manifestation of many initial symptoms that portended the diagnosis. To our knowledge, this is the largest reported case study of corticosteroid treatment initiated with the expressed intention to prevent the development of RADS after an isolated diesel exhaust exposure. Although we cannot prove that early intervention with corticosteroids prevented RADS, we think that the implementation of prompt prophylactic treatment expedited symptom resolution and might have prevented the development of RADS, on the basis of previous historical control data. RADS resulting from diesel exhaust may be an important public health issue, and our hope is to promote increased recognition of the diagnosis, which often is not suspected upon initial presentation but is delayed by up to several years. Increasing awareness may prompt pursuit of more-aggressive interventions with acute and protracted corticosteroid treatment and execution of the necessary controlled trials to establish treatment efficacy in mitigating the severity and/or circumventing the development of RADS.

Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708-2197.

This manuscript was received for review in August 2007. The revised manuscript was accepted for publication in March 2008.

REFERENCES

1. Wade JF III, Newman LS: Diesel asthma reactive airways disease following overexposure to locomotive exhaust. ACOEM 1993; 35: 149- 54.

2. Nordholm AF, Ritchie GD, Malcolm WJ, et al: Repeated exposure of rats to JP-4 vapor induces changes in neurobehavioral capacity and 5-HT/5-HIAA levels. J Toxicol Environ Health 1999; 56: 471-99.

3. U.S. Environmental Protection Agency: Health Assessment Document for Diesel Engine Exhaust. Washington, DC, Environmental Protection Agency, 2002. Available from National Technical Information Service, Springfield, VA and http://www.cpa.gov/ncea.

4. McCreanor J, Cullinan P, Nieuwenhuijsen MJ, et al: Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med 2007; 357: 2348-58.

5. Wichmann HE: Diesel exhaust particles. Inhal Toxicol 2007; 19(Suppl 1): 241-4.

6. Mills NL, Tornqvist H, Gonzales MC, et al: Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med 2007; 357: 1075-82.

7. Riedl M, Diaz-Sanchez D: Biology of diesel exhaust effects on respiratory function. J Allergy Clin Immunol 2005; 115: 221-8.

8. Sallie B, McDonald C: Inhalation accidents reported to the Sword Surveillance Project 1990-1993. Ann Occup Hyg 1996; 40: 211- 21.

9. American Thoracic Society: Single-breath carbon monoxide diffusing capacity (transfer factor): recommendations for a standard technique: 1995 update. Am J Respir Crit Care Med 1995; 152: 2185- 98.

10. Brooks SM, Weiss MA, Bernstein IL: Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high level irritant exposures. Chest 1985; 88: 376-83.

11. Bherer L, Cushman R, Courteau JP, et al: Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill, part II: follow up of affected workers by questionnaire, spirometry, and assessments of bronchial responsiveness 18 to 24 months after exposure ended. Occup Environ Med 1994; 51: 225.

12. Emad A, Rezaian GR: The diversity of the effects of sulfur mustard gas inhalation on respiratory system after a single, heavy exposure: analysis of 197 cases. Chest 1997; 112: 734-8.

13. Henneberger PK, Derk SJ, Davis L, et al: Work-related reactive airways dysfunction syndrome cases from surveillance in selected U.S. states. J Occup Environ Med 2003; 45: 360-8.

14. Tilles SA, Jerath-Tatum A: Differential diagnosis of occupational asthma. Immunol Allergy Clin North Am 2003; 23: 167- 76.

15. Alberts WM, do Pico GA: Reactive airways dysfunction syndrome. Chest 1996; 109: 1618-26.

16. Slavin DE: A Longitudinal Study of Lung Function and Symptoms of 34 Royal Navy Submariners Exposed to Diesel Exhaust Fumes. Faculty of Occupational Medicine of the Royal College of Physicians, Doctoral Dissertation, London, U.K., 1998.

17. Lemiere C: Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment. Eur Respir J 1997; 10: 241-4.

18. Lemiere C, MaIo JL, Boulet LP, Beutet M: Reactive airways dysfunction syndrome induced by exposure to a mixture containing isocyanate: functional and histopathologic behavior. Allergy 1996; 51: 262-5.

19. do Pico GA: Toxic gas inhalation. Curr Opin PuIm Med 1995; 1:102-8.

20. Demnati R, Fraser R, Martin JG: Effects of dexamethasone on functional and pathological changes in rat bronchi caused by high acute exposure to chlorine. Toxicol Sci 1998; 45: 242.

21. Weaver LK, Hopkins RO, Chan KJ, et al: Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002; 347: 1057-67.

22. Cullinan P, Acquula S, Dhara VR: Respiratory morbidity 10 years after the Union Carbide gas leak at Bhopal: a cross sectional survey. BMJ 1997; 314: 338.

23. Meggs WJ: RADS and RUDS: the toxic induction of asthma and rhinitis. J Toxicol Clin Toxicol 1994; 32: 487-501.

24. Gautrin D, Boulet LP, Boulet M, et al: Is reactive airways dysfunction syndrome (RADS) a variant of occupational asthma? J Allergy Clin Immunol 1994; 93: 12.

25. Environmental Protection Agency, Integrated Risk Information System: Diesel engine exhaust. Available at http://www.epa.gov/iris/ subst/ 0642.htm; accessed March 2007.

26. Bobb AJ, Jederberg WW: JV-Acetylcysteine as a Provisional, Commercial Off-the-Shelf (COTS) Chemoprotectant against Sulfur Mustard. Publication NHRC/TD TOXDET-03-01. San Diego, CA, Naval Health Research Center Detachment, 2003.

27. Banauch GI, Dhala A, Alleyne D, et al: Bronchial hyperreacctivity and other inhalation lung injuries in rescue/ recovery workers after the World Trade Center collapse. Crit Care Med 2005; 33(Suppl): S102-6. LCDR Christopher A. Duplessis, USN; CAPT Barton Gumpert, USN

Copyright Association of Military Surgeons of the United States Jul 2008

(c) 2008 Military Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

Retinol-Binding Protein 4 and Lipocalin-2 in Childhood and Adolescent Obesity: When Children Are Not Just "Small Adults"

By Kanaka-Gantenbein, Christina Margeli, Alexandra; Pervanidou, Panagiota; Sakka, Sophia; Mastorakos, George; Chrousos, George P; Papassotiriou, Ioannis

BACKGROUND: Although there is much evidence regarding the physiologic and pathogenic roles of the newly described adipokines retinol-binding protein 4 (RBP4) and lipocalin-2 as potential promoters of insulin resistance in obese adults, relatively little information exists regarding their roles in obese children. METHODS: We investigated the circulating concentrations of RBP4 and lipocalin- 2 in 80 obese girls (ages 9-15 years) and their relationships with high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin. We divided participants by their body mass index standard deviation scores (BMI SDSs) into 4 groups of 20 girls each: overweight [mean BMI SDS (SD), 1.8 (0.4)], obese [2.2 (0.4)], morbidly obese [3.6 (0.4)], and lean controls [-0.11 (0.4)]. We measured plasma-soluble RBP4, the RBP4-binding protein transthyretin, lipocalin-2, hs-CRP, leptin, and adiponectin and calculated the homeostatic assessment model (HOMA) index from fasting glucose and insulin concentrations.

RESULTS: Unexpectedly, plasma RBP4 and lipocalin-2 concentrations were correlated negatively with BMI SDS values (P = 0.005, and P

CONCLUSIONS: Although the correlations of leptin, adiponectin, and hs-CRP concentrations with BMI in children are similar to those of adults, the correlations of RBP4 and lipocalin-2 with BMI in children are the inverse of those observed in adults. Thus, although systemic inflammation and mild insulin resistance are present in childhood obesity, RBP4 and lipocalin-2 concentrations are not increased in children as they are in obese adults with long- standing severe insulin resistance and type 2 diabetes.

(c) 2008 American Association for Clinical Chemistry

Adipose tissue is no longer considered merely an energy-storing depot but is now thought to be a metabolically active endocrine organ that secretes many information-carrying molecules, some of which, such as leptin and adiponectin, confer insulin-sensitizing action, whereas others, such as resistin and tumor necrosis factor a, promote insulin resistance (1, 2). Recent animal and human studies have suggested that the soluble form of retinol-binding protein 4 (RBP4),4 initially thought to be only a retinol (vitamin A) transporter, is a major circulating adipokine implicated in systemic insulin resistance (3 ). RBP4 is a small 21-kDa protein that circulates as an 80-kDa protein complex with transthyretin that is not easily filtered through the kidneys (3).

Increases in the serum concentration of RBP4 have been observed in obese adults with insulin-resistant type 2 diabetes, whereas reductions in the circulating concentrations of this adipokine have been associated with improved insulin action (3, 4). Furthermore, increased RBP4 concentrations have been observed in lean individuals with insulin resistance (4, 5), and regulatory single-nucleotide polymorphisms of the RBP4 gene have recently been described in Mongolian patients with type 2 diabetes mellitus (6). Another study, however, did not confirm the presence of increased serum RBP4 concentrations in obese postmenopausal women compared with women of normal weight (7). Although it is not yet clear whether RBP4 is the cause and/or the consequence of systemic insulin resistance or is merely a biomarker of the systemic insulin-resistant state (3-7), this protein appears to be an important adipokine implicated in the interplay between obesity and insulin resistance. Two recent studies of adolescent obesity found increased RBP4 concentrations (8, 9), although RBP4 concentration showed no clear correlation with the homeostatic assessment model (HOMA) index in the obese youngsters (8).

Table 1. Patients’ family histories and clinical profiles.

Lipocalin-2 belongs to the same protein family as RBP4 and is a known inflammatory biomarker that is positively correlated with body mass index (BMI) and other variables of the metabolic syndrome (10, 11). Lipocalin-2 was found in a recent study to promote insulin resistance, a result resembling findings for RBP4 (12).

We investigated the circulating concentrations of RBP4 and lipocalin-2 in overweight, obese, and morbidly obese female children and adolescents and compared the results with those of lean, healthy age-matched controls. We studied the correlations of concentrations of these adipokines with BMI, markers of inflammation such as high- sensitivity C-reactive protein (hs-CRP), and the concentrations of the well-studied adipokines leptin and adiponectin. We elected to include only girls in this study to control for sexual dimorphism, because the RBP4 concentration, like leptin and adiponectin concentrations, shows sex-related differences (8, 13).

PARTICIPANTS AND METHODS

The children and adolescents included in this study were recruited from the outpatient Obesity Clinic of the Division of Endocrinology, Diabetes and Metabolism of the First Department of Pediatrics of the University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece. No participant was receiving any medication, and all individuals were in a good general condition. The categories of overweight and obesity were defined on the basis of BMI (weight in kilograms divided by the square of the height in meters) according to WHO criteria (14) and modified for childhood and adolescent obesity as suggested by Cole et al. (15). We categorized the girls, ages 9-15 years, on the basis of their BMI standard deviation score (SDS) values (z score) into 4 groups of 20 girls each: overweight [mean BMI SDS (SD), 1.8 (0.4)], mildly obese [2.2 (0.4)], morbidly obese [3.6 (0.4)], and healthy, lean agematched controls [-0.11 (0.4)] (Table 1). Weusedthe recent Hellenic BMI charts for BMI SDS calculations (16). The Ethics Committee of the “Aghia Sophia” Children’s Hospital approved the study protocol, and girls were included in the study only after informed consent had been obtained from their parents. Table 1 summarizes the participants’ family histories and clinical profiles. All girls underwent a full physical examination, including measurements of weight, height, BMI, arterial blood pressure, and pubertal status.

After the participants had fasted overnight, we withdrew venous blood and measured their fasting glucose and insulin concentrations. The HOMA index was used as a marker of insulin resistance and was calculated as: HOMA Index = [(Fasting Insulin Concentration) x (Fasting Glucose Concentration)]/161, where the insulin concentration is expressed in picomoles per liter and the glucose concentration is expressed in millimoles per liter (17). We also obtained a lipid profile, which included measurements of total cholesterol, triglycerides, and HDL and LDL cholesterol, for all participants. Finally, we measured RBP4, transthyretin, lipocalin- 2, hs-CRP, leptin, and adiponectin concentrations in all individuals.

Table 2. Fasting serum glucose and insulin concentrations, HOMA index values, lipid profiles, and circulating concentrations of RBP4, transthyretin, lipocalin-2, hs-CRP, leptin, and adiponectin in the 4 BMI groups.a

Serum concentrations of glucose, total cholesterol, triglycerides, and HDL and LDL cholesterol were measured with the Siemens Advia 1650 Clinical Chemistry System (Siemens Healthcare Diagnostics), and serum insulin concentrations were measured via chemiluminescence detection with the automated Siemens ACS 180 System Analyzer (Siemens Healthcare Diagnostics).

To measure RBP4 concentrations in serum, we used a sandwich ELISA assay (Immunodiagnostik) identical in protocol and reagent composition with that from ALPCO Diagnostics [as tested by Graham et al. (18)]. Serum samples were diluted so that absorbance measurements fell in the middle of the linearity range for this assay. According to the manufacturer, intraassay and interassay CVs for RBP4 measurements are 5.0% and 9.7%, respectively.

Serum lipocalin-2 concentrations were measured with a solid- phase ELISA (R&D Systems). Intraassay and interassay CVs were 3,1%- 4.1 % and 5.6%-7.9%, respectively, according to the manufacturer.

Transthyretin and hs-CRP were measured on the BN ProSpec nephelometer (Dade Behring, Siemens Healthcare Diagnostics) with fully automated latex particle-enhanced immunonephelometric assays. The intraassay and interassay CVs were

STATISTICAL ANALYSIS

Differences between groups were evaluated with the Mann-Whitney C7-test. The Spearman rank correlation test was used to examine the relationships between various variables. All P values are the results of 2-sided tests. Statistical analyses were performed with the STATGRAPHICS PLUS version 5.1 for Windows (Statpoint). Results

Table 2 summarizes the results for fasting glucose and insulin concentrations, the HOMA index, lipid variables, and RBP4, transthyretin, Iipocalin-2, hs-CRP, leptin, and adiponectin concentrations for the 4 groups.

All children and adolescents in all 4 groups had nonpathologic fasting glucose values; however, insulin resistance, as expressed in the HOMA index, was significantly increased in the obese and morbidly obese children and adolescents, compared with the lean control individuals (P

The lean and overweight groups were not significantly different with respect to RBP4 concentration (P > 0.21), nor were the lean and obese groups (P > 0.97). RBP4 concentrations in the morbidly obese group, however, were significantly decreased compared with the obese, overweight, and control groups (P

Transthyretin concentrations in the obese and morbidly obese groups were not significantly different from those in the lean control group (P > 0.06, and P > 0.72, respectively; Table 2).

Both hs-CRP and leptin concentrations were significantly increased in the overweight/obese groups compared with the controls (P

An evaluation of the correlation of BMISDS with all of the measured variables revealed that both RBP4 and lipocalin-2 concentrations were negatively correlated with the BMISDS [r = – 0.350 (P 0.08), whereas RBP4 concentration and BMI SDS showed a statistically significant negative correlation after menarche (r – – 0.35; P

Discussion

Both RBP4 and lipocalin-2 concentrations were significantly negatively correlated with the BMI SDS in children and adolescents. Additionally, hs-CRP and leptin concentrations were positively correlated with the BMI SDS, whereas the adiponectin concentration was negatively correlated. Similar studies of RBP4 and lipocalin-2 in obese adults, however, have yielded opposite results; that is, RBP4 and lipocalin-2 concentrations were positively correlated with BMI (3, 4, 10-12). On the other hand, the correlations of the hs- CRP, leptin, and adiponectin concentrations with BMI in this study were similar to the results found in previous studies of both adult and pediatric populations (2, 19-23).

RBP4 has recently been proposed to be the circulating adipokine that confers systemic insulin resistance to skeletal muscle and liver in obese adults (35, 24). In mice and in some human studies (3, 4), RBP4 was found to be negatively correlated with GLUT4 production in adipose tissue (3, 4, 24-26), although other studies of humans by Janke et al. (7) found a robust positive correlation between RBP4 and GLUT4 concentrations that was completely independent of confounding variables. This finding has subsequently been confirmed at the mRNA level in human adipocytes (27) and challenges the assumption of the unequivocal accuracy of extrapolating findings from murine models to human pathophysiology (28).

Quantitative western blotting standardized to the full-length RBP4 protein is generally accepted as the gold standard method for measuring RBP4 (18), although the various commercially available kits for RBP4 may perform differently. In the present study, we measured the serum RBP4 concentration with an Immunodiagnostik sandwich ELISA that is identical in protocol and reagent composition with the ALPCO Diagnostics ELISA validated by Graham et al. (4, 18). Serum concentrations of RBP4 are lower in females than in males (8, 13), and postmenopausal obese women do not demonstrate the same increases in RBP4 concentration observed in premenopausal obese women (7). To circumvent the known sex-related differences in RBP4 concentration and to study the impact of sex steroids and menarche on RBP4 concentration, we included only girls in this study and further subdivided our cohort into pre- and postmenarche populations. We found no significant correlation between RBP4 concentration and the BMI SDS in premenarche girls (r = -0.30; P > 0.08), whereas the correlation was significant after menarche (r = – 0.35; P

Treatment of adult mice with fenretinide, a drug that disrupts the interaction of RBP4 with transthyretin and causes increased renal RBP4 excretion, was found to lead to enhanced insulin sensitivity. Although whether fenretinide also has a beneficial effect in humans is not yet clear, the RBP4-transthyretin interaction has been proposed as a new target for the development of drugs for combating insulin resistance (3, 5, 29). In our study, we hypothesized that reduced transthyretin concentrations might have led to increased renal clearance of RBP4 and thereby produce the lower RBP4 concentrations in our morbidly obese group (29, 30); however, we observed no significant reductions in transthyretin concentration in our obese and morbidly obese participants compared with the lean control individuals (P > 0.06, and P > 0.072, respectively).

Fig. 1. Correlations between BMI SDS and circulating concentrations of RBP4 (r = -0.350; P

RBP4 concentration is positively correlated with BMI and insulin resistance in obese adults, and increases in the RBP4 concentration precede the development of frank diabetes (4, 13). Moreover, RBP4 concentrations are increased in healthy nonobese individuals who are genetically susceptible to diabetes because of having at least one first-degree relative with type 2 diabetes (4). One may therefore argue that if the girls in our lean group had a higher incidence of first-degree relatives with type 2 diabetes, they would be genetically more susceptible to developing diabetes and thus would Have higher RBP4 concentrations; however, the incidence of first- degree relatives with type 2 diabetes was lower in our lean, overweight, and obese groups and higher in the morbidly obese group, which had the lowest RBP4 concentrations.

In this study, all the children in all BMI categories had nonpathologic fasting glucose concentrations, a finding that excluded any severe glucose intolerance at this period of their lives. In new-onset type 1 diabetes, serum RBP4 concentrations are reduced and return to typical concentrations after insulin treatment (4, 31); however, the enhanced osmotic diuresis in such patients because of hyperglycemic and the resulting polyuria might lead to renal loss of RBP4, a phenomenon that is reversed with insulin treatment. This explanation cannot account for the reduced RBP4 values found in our morbidly obese participants, who had neither hyperglycemia nor enhanced diuresis.

In our cohort, insulin resistance, as expressed in the HOMA index, was significantly increased in the obese and morbidly obese individuals compared with the lean control individuals (P

We found no correlation in our cohort between the concentration of circulating RBP4 and the leptin or adiponectin concentration in any group, although such correlations have been described for adults (33).

We found a negative correlation between lipocalin-2 concentration and BMI similar to that found between RBP4 concentration and BMI. Our data and analyses show that lipocalin-2 and RBP4 are markedly similar on all counts. Studies of these 2 adipokines in different populations and health states are definitely needed to obtain a better functional profile of these highly related proteins. In conclusion, whereas hs-CRP, leptin, and adiponectin demonstrated relationships with BMI in children that were similar to those observed in adults, the concentrations of RBP4 and lipocalin-2 in these young individuals appeared to have relationships with BMI that were the inverse of those found in adults, suggesting the existence of substantial physiological differences between children and adults. It is also possible that the discrepancies between the findings for the children in our study and those for adults in previously published studies may also indicate that an increased RBP4 concentration is simply a consequence of advancing age, a long- standing period of insulin resistance, or even type 2 diabetes. Although subtle insulin resistance, as indicated by the HOMA index, and systemic inflammation, as indicated by an increased hsCRP concentration, are already present in childhood obesity, they may not have been present for a sufficiently long time to lead to an increase in the RBP4 or lipocalin-2 concentration.

Therefore, if increases in RBP4 and lipocalin-2 concentrations are causally related to severe insulin resistance, given that temporality (i.e., a cause preceding an effect) may be a prerequisite for causality as suggested by van Dam et al. (11), then prospective studies that assess these biomarkers are critical. Of utmost importance, therefore, will be to study young obese and morbidly obese individuals longitudinally to determine the critical time after RBP4 and lipocalin-2 concentrations have increased that these factors become coupled to severe insulin resistance and, ultimately, to glucose intolerance and type 2 diabetes mellitus.

Grant/Funding Support: Funding was received from Athens University Medical School (Ioannis Papassotiriou) and the A. G. Leventis Foundation, Athens, Greece (George P. Chrousos). The funding sources played no role in the study design, nor did they influence the collection, analysis, and interpretation of the data, the writing of the report, or the decision to submit the report for publication.

Financial Disclosures: None declared.

4 Nonstandard abbreviations: RBP4, retinol-binding protein 4; HOMA, homeostatic model assessment; BMI, body mass index; hs-CRP, high-sensitivity C-reactive protein; SDS, standard deviation score.

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27. Yao-Borengasser A, Varma V, Bodies AM, Rasouli N, Phanavahn B, Lee MJ, et al. Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation and response to pioglitaione. J Clin Endocrinol Metab 2007;92: 2590-7.

28. McTeman PG, Kumar S. Retinol binding protein 4 and pathogenesis of diabetes. J Clin Endocrinol Metab 2007;92:2430-2.

29. Monaco HL. The transthyretin-retinol binding protein complex. Biochim Biophys Acta 2000;1482: 65-72.

30. Naylor HM, Newcomer ME. The structure of human retinol- binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP. Biochemistry 1999; 38:2647-53.

31. Basu TK, Sasualdo C. Vitamin A homeostasis and diabetes mellitus. Nutrition 1997;13:804-6.

32. Gavi S, Stuart LM, Kelly P, Melendez MM, Mynarcik DC, Gelato MC, McNurlan MA. Retinolbinding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes. J Clin Endocrinol Metab 2007;92:1886-90.

33. Shin MJ, Kang SM, Jang Y, Lee JH, Oh J, Chung JH, Chung N. Serum retinol binding protein 4 levels are associated with serum adiponectin levels in non-diabetic, non-obese subjects with hypercholesterolemia. Clin Chim Acta 2007;378: 227-9.

Christina Kanaka-Gantenbein,1 Alexandra Margeli,2 Panagiota Pervanidou,1 Sophia Sakka,1 George Mastorakos,3 George P. Chrousos,1 and Ioannis Papassotiriou2*

1 First Department of Pediatrics, Division of Endocrinology, Metabolism and Diabetes, Athens University Medical School, Athens, Greece, 2 Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens, Greece, 3 Endocrine Unit, Second Department of Obstetrics and Gynecology, Athens University Medical School, Athens, Greece.

* Address correspondence to this author at: Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, 11527 Athens, Greece. Fax 30-210-746-7171; e-mail biochem@paidon- agiasofia.gr or [email protected].

Received October 11, 2007; accepted April 4, 2008.

Previously published online at DOI: 10.1373/clinchem.2007.099002

Copyright American Association for Clinical Chemistry Jul 2008

(c) 2008 Clinical Chemistry. Provided by ProQuest Information and Learning. All rights Reserved.

Estimating Glomerular Filtration Rate in Black South Africans By Use of the Modification of Diet in Renal Disease and Cockcroft-Gault Equations

By van Deventer, Hendrick E George, Jaya A; Paiker, Janice E; Becker, Piet J; Katz, Ivor J

BACKGROUND: The 4-variable Modification of Diet in Renal Disease (4-v MDRD) and Cockcroft-Gault (CG) equations are commonly used for estimating glomerular filtration rate (GFR); however, neither of these equations has been validated in an indigenous African population. The aim of this study was to evaluate the performance of the 4-v MDRD and CG equations for estimating GFR in black South Africans against measured GFR and to assess the appropriateness for the local population of the ethnicity factor established for African Americans in the 4-v MDRD equation. METHODS: We enrolled 100 patients in the study. The plasma clearance of chromium-51-EDTA (^sup 51^CrEDTA) was used to measure GFR, and serum creatinine was measured using an isotope dilution mass spectrometry (IDMS) traceable assay. We estimated GFR using both the reexpressed 4-v MDRD and CG equations and compared it to measured GFR using 4 modalities: correlation coefficient, weighted Deming regression analysis, percentage bias, and proportion of estimated GFR within 30% of measured GFR (P^sub 30^).

RESULTS: The Spearman correlation coefficient between measured and estimated GFR for both equations was similar (4-v MDRD R^sup 2^ = 0.80 and CG R^sup 2^ = 0.79). Using the 4-v MDRD equation with the ethnicity factor of 1.212 as established for African Americans resulted in a median positive bias of 13.1 (95% CI 5.5 to 18.3) mL/ min/1.73 m^sup 2^. Without the ethnicity factor, median bias was 1.9 (95% CI -0.8 to 4.5) mL/min/1.73 m^sup 2^.

CONCLUSIONS: The 4-v MDRD equation, without the ethnicity factor of 1.212, can be used for estimating GFR in black South Africans.

(c) 2008 American Association for Clinical Chemistry

Globally, chronic kidney disease (CKD)4 is recognized as an important public health problem (1). In South Africa, the high prevalence of hypertension, diabetes, and infection with HIV results in a significant risk for CKD (2); it is therefore important to detect kidney dysfunction as early as possible in this population. Current guidelines define CKD as the presence, for 3 or more months, of either kidney damage as defined by structural or functional abnormalities of the kidney or a glomerular filtration rate (GFR)

GFR can be measured as the renal clearance of exogenous markers such as inulin, chromium-51-EDTA (^sup 51^Cr-EDTA), technetium- Iabeled diethylene-triaminepentacetate (^sup 99m^Tc-DTPA), and iohexol. These exogenous markers are impractical for routine use, however. Endogenous GFR markers include creatinine and cystatin C. Creatinine is the most commonly used marker in the clinical laboratory to assess GFR, but it has multiple limitations (11 )-for example, it is also affected by factors such as muscle mass, diet, sex, and age (12, 13).

To overcome some of these limitations, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative and Kidney Disease: Improving Global Outcomes guidelines recommend the estimation of GFR (eGFR) using prediction equations based on serum creatinine (S-Cr) (3, 4). The 2 most commonly used prediction equations are the 4-variable Modification of Diet in Renal Disease (4-v MDRD) (14) and Cockcroft-Gault (CG) (15) equations. The MDRD equation was derived in the United States by analysis of data from 1628 patients (651 women and 195 African-Americans) with known kidney disease using ^sup 125^I-iothalamate clearance to measure GFR as the reference procedure (mean GFR 40 mL/min/1.73 m^sup 2^) and was based on 6 variables: age, sex, serum creatinine, urea, albumin, and ethnicity (16), Subsequently, a 4-v MDRD equation based on 4 variables-age, sex, serum creatinine, and ethnicity-was proposed to simplify its use in the clinical environment (14). An ethnicity factor of 1.212 was established for African Americans (14,16).

Because of variability in serum creatinine assays, the National Kidney Disease Education Program Laboratory Working Group initiated a creatinine standardization program with creatinine calibration traceable to isotope dilution mass spectrometry (IDMS) creatinine measurement (17). The 4-v MDRD equation was reexpressed for use with the IDMS traceable creatinine measurements (18).

The Cockcroft-Gault equation was derived from 236 hospital inpatients in Canada (4% women, ethnicity not stated) with measured creatinine clearance (CrCl) as the reference procedure (mean CrCl 73 mL/ min) (15).

Neither of these formulae nor the ethnicity factor of 1.212 established for African Americans has yet been evaluated in African or non-American black populations. The applicability of these equations and the factor for ethnicity to black South Africans is therefore unknown. The aim of this study was to examine the applicability of the 4-v MDRD and CG equations for estimating GFR in black South Africans against measured GFR and to evaluate whether the ethnicity factor established for African Americans is appropriate for black South Africans.

Materials and Methods

PARTICIPANTS

We conducted a prospective study of patients seen at Chris Hani Baragwanath Hospital in 2006. Participants, who were recruited after being screened and counseled by their clinicians, were older than 18 years and had established CKD or risk factors for developing CKD, such as hypertension, diabetes, and HIV. Exclusion criteria were pregnancy, acute kidney injury, and edema. We enrolled 100 black South Africans with varying degrees of renal function. All participants gave informed consent after being educated with regard to potential benefits, risks, and study procedures. The study was approved by the Human Research Ethics Committee of the University of the Witwatersrand.

TEST METHODS

Age (years), standing height (centimeters), weight (kilograms), and sex were recorded for all participants. Before GFR measurement, we collected a 5-mL blood sample for serum creatinine measurement using an alkaline picrate rate-blanked compensated kinetic assay (Roche Modular analyzer; Roche Diagnostics) with calibration traceable to IDMS. To assess possible calibration differences, we used a calibration panel of 40 serum samples (Cleveland Clinic Foundation), with values assigned by a Roche enzymatic assay (Creatinine Plus; Roche Diagnostics), that has been independently validated as traceable to IDMS (19).

GFR MEASUREMENTS

We used ^sup 51^Cr-EDTA plasma clearance as a reference method for measuring GFR. GFR was measured according to guidelines adopted by the British Nuclear Medicine Society (20) and calculated with the slope intercept method (21), corrected with the BrochnerMortensen equation (22), and normalized to body surface area (BSA) using the DuBois method: BSA (m^sup 2^) = [71.84 x weight (kg)0.425 x height (cm)0.725]/ 10 000 (23). This value is referred to as measured GFR (mGFR). (For a detailed description of the GFR measurements, see the Data Supplement that accompanies the online version of this article at www.clinchem. org/content/vol54/issue7.)

GFR ESTIMATIONS

GFR was estimated using the following equations:

* reexpressed 4-v MDRD equation (18, 24): eGFR (mL/min/1.73 m^sup 2^) = 175 x [S-Cr ([mu]mol\L)/ 88.4]^sup -1.154^ x age (years)^sup -0.203^ x (0.742 if female) x (1.212 if African American)

* Cockcroft-Gault equation (15 ) normalized to 1.73 m^sup 2^: eGFR (mL/min/1.73 m^sup 2^) = [(140 – age in years) x weight (kg) x (0.85 if female) x 1.73 (m^sup 2^)]/[S-Cr ([mu]mol/L) x 0.814 x BSA (m^sup 2^)]

To assess the validity of the 4-v MDRD equation with the African American factor in the black South African population, GFR was estimated both with and without this factor. The CG equation was normalized to 1.73 m to allow comparison with the 4-v MDRD equation and measured GFR. This is in keeping with most studies but is unlikely to reflect standard clinical practice (25 ). Because the CG equation was developed with CrCl as the reference procedure and a creatinine assay not traceable to current IDMS values, bias is to be expected for the CG equation. To minimize this bias, we established a correction factor for the CG equation, determined from the dataset of 100 patients by minimizing the sum of the squared residuals (the difference between eGFR and mGFR).

STATISTICAL METHODS

Statistical analysis was conducted using Analyze-it for Microsoft Excel. We used the Shapiro-Wilk test to test for normality. Continuous data variables are expressed as mean (SD) if parametric and median [interquartile range (IQR)] if nonparametric. We assessed the performance of the 4-v MDRD equation, both with and without the ethnicity factor, and the Cockcroft-Gault equation normalized to 1.73 m^sup 2^ relative to that of mGFR by use of Spearman correlation coefficient, weighted Deming regression analysis, median percentage difference between estimated and measured GFR (percentage bias), and proportion of eGFR within 30% of mGFR (P^sub 30^). We used weighted Deming regression analysis to take into account random error in both measured GFR and serum creatinine measurement (24). Results

PARTICIPANTS

Between August 2006 and November 2006, 100 black South Africans (51 men and 49 women) were enrolled in the study. All participants were inpatients at the Chris Hani Baragwanath hospital or were being followed up at the renal unit outpatient department at the hospital. The study population had a median (IQR) age of 47 (26) years, range 18-86 years. Participants suffered from a wide range of different diseases, the most common of which included hypertension (n = 36), diabetes (n = 25), and HIV (n = 20). Other diagnoses included renal calculi, deep venous thrombosis, meningitis, multiple myeloma, nephrotic syndrome, and epilepsy. Participants being worked up for possible kidney donation were also included (n = 7). The median mGFR was 61.5 (49.6) mL/min/1.73 m^sup 2^, range 3-132 mL/min/1.73 m^sup 2^. (See Supplemental Table 1.)

CREATININE CALIBRATION

Evaluation of S-Cr calibration was based on 39 observations, after excluding one of the samples with a difference between the assigned value and the measured value of >3 SDs from the mean difference. The measurements were done in triplicate in 3 separate runs, with measured S-Cr values ranging from 44 to 398 [mu]mol/L. The correlation between the Cleveland Clinic Foundation (CCF) assigned values and the South African (SA) measured values was high (R^sup 2^ = 0.999). Deming regression analysis was used to calculate the slope, 0.964 (95% CI 0.952 to 0.975), and intercept, 0.039 (95% CI 0,010 to 0.068), of the regression equation, with y = CCF- assigned values and x = SA-measured values. Because of mis small but significant regression slope, measured S-Cr (SA) values were standardized to CCF values with the following equation: standardized S-Cr = 0.039 + [0.964 x S-Cr (SA)]. Standardized S-Cr values were used in all calculations.

COMPARISON OF MEASURED GFR TO THE 4-v MDRD EQUATION

The Spearman correlation coefficient between mGFR and the 4-v MDRD equation was 0.90 (95% CI 0.85 to 0.93). Weighted Deming regression analysis showed a significant proportional bias of 1.24 (95% CI 1.09 to 1.38, P = 0.001) but no significant constant bias [0.24 (95% CI -5.91 to5.43,P= 0.93)] when the established ethnicity factor of 1.212 was used. Without the ethnicity factor, weighted Deming regression analysis showed no significant proportional bias [1.02 (95% CI 0.90 to 1.14, P = 0.73)] or constant bias [0.02 (95% CI -4.61 to 4.65, P = 0.99)]. The percentage bias (median percentage difference between eGFR and mGFR) for the 4-v MDRD equation with the established ethnicity factor of 1.212 was 27%. Without the ethnicity factor, percentage bias was 5%. With the ethnicity factor of 1.212, P^sub 30^ for the 4-v MDRD equation was 52% vs 74% without the ethnicity factor (Fig. 1).

COMPARISON OF MEASURED GFR TO THE CG EQUATION

The Spearman correlation coefficient between mGFR and CG normalized to 1.73 m^sup 2^ was 0.89 (95% CI 0.85 to 0.93). Weighted Deming regression analysis comparing the CG equation to mGFR showed a significant proportional bias of 1.13 (95% CI 1.03 to 1.23, P = 0.01) but no significant constant bias [2.38 (95% CI -1.37 to 6.13, P = 0.21)]. Percentage bias for the CG equation was 19%, and P^sub 30^ was 58%. The factor calculated to minimize bias of the CG equation in this dataset was 0.82 (95% CI 0.78 to 0.85). Correcting the CG equation for bias, eGFR (mL/min/1.73 m^sup 2^) = 0.82 x CG (mL/min/1.73 m^sup 2^), improved P^sub 30^ to 71%.

Fig. 1. Difference plot: 4-v MDRD equation and measured GFR.

(A), With African American ethnicity factor (1.212). (B), Without African American ethnicity factor.

PERFORMANCE OF EQUATIONS AT DIFFERENT STAGES OF RENAL DISEASE

For each of the eGFR equations, the dataset was split into 3 groups: eGFR 60 mL/min/ 1.73 m^sup 2^. In each of these groups, the median difference between eGFR and mGFR (bias), percentage bias, IQR of the difference between eGFR and mGFRs, and root mean squared error were calculated. For each of the equations, bias, IQR, and root mean squared error increased at higher levels of eGFR (Table 1).

Discussion

CKD is increasingly recognized as a global public health problem (1 ). The high prevalence of hypertension, diabetes, and HIV in sub- Saharan Africa has resulted in a high risk for CKD (2). Early detection of CKD using simple laboratory tests and GFR prediction equations, such as the CG and 4-v MDRD equations, is important for the prevention of long-term complications.

Neither the CG nor the 4-v MDRD equation has previously been validated in Africa. The 4-v MDRD equation has also not been validated in a black population with a different body habitus than that of African Americans. Our results show that both the CG (after correcting for bias) and the 4-v MDRD (without the ethnicity factor established for African Americans) can be used for estimating GFR in black South Africans.

Many recent articles have underscored the importance of creatinine standardization (17). For this study, we used an alkaline picrate rate-blanked compensated kinetic assay (Roche Diagnostics) with calibration traceable to IDMS. In a study by Miller et al. (26), this method showed minimal bias compared with an IDMS value. We also assessed and corrected for possible calibration differences by using a calibration panel with values assigned by the Roche enzymatic assay (Cleveland Clinic Foundation). Because the S-Cr results were traceable to IDMS, we used the reexpressed 4-v MDRD equation (14).

The correlation coefficient for the 4-v MDRD equation was similar those of studies done in other population groups (27-29). The 4-v MDRD equation using the ethnicity factor of 1.212 as suggested for African Americans overestimated mGFR in black South Africans. Without the ethnicity factor (thus using the same equation as established for whites in the MDRD study), median overestimation was minimal and there was no significant proportional bias. Accuracy within 30% of mGFR was 52% with the ethnicity factor of 1.212 and 74% without the ethnicity factor.

Goldwasser et al. (30) showed that African Americans have higher renal creatinine excretion per kilogram body weight than whites and concluded that this may be related to differences in body composition, muscle metabolism, or diet. Lewis et al. (31) showed higher serum creatinine levels and urinary creatinine excretion rates for a given GFR in African Americans compared with non- African Americans. This may not be true for black South Africans, as the 2 populations have different origins (32).

Creatinine generation is determined primarily by muscle mass and dietary intake (6 ). Differences in the ethnicity factor established for African Americans and black South Africans may be attributed to differences in muscle mass and body composition as well as differences in diet. Various studies have shown that West African athletes have less body fat and thicker thighs than whites, and this difference is even more striking between East and West Africans (33). Mean weight and BSA for the MDRD study population were 79.6 (16.8) kg and 1.91 (0.23) m^sup 2^, respectively (16); for the MDRD African American study population, 84.1 kg and 1.96 m^sup 2^ (31); for the African-American Study of Kidney disease and hypertension (AASK), 90.2 kg and 2.02 m^sup 2^ (31); and for our study, 69.5 (13.8) kg and 1.76 (0.17) m^sup 2^. Differences in dietary intake are difficult to quantify, but it is likely that black South Africans consume less creatinine-generating food than African Americans owing to poorer socioeconomic circumstances.

Table 1. Performance of equations.a

The CG equation is still commonly used for estimating creatinine clearance as an indicator of GFR and was therefore included in the analysis. The correlation coefficient for the CG equation was similar to those of studies done in other population groups (27,28). The positive bias observed for the CG equation may be attributed to the CG equation being established using creatinine clearance as a reference procedure, which overestimates GFR owing to the tubular secretion of creatinine (6). It may also be attributed to calibration biases between creatinine measurement for the original CG study and this study, as well as the CG equation being established in a different population group.

The study population included 20 patients who were known to be infected with HIV. In South Africa, the Nelson Mandela/Human Sciences Research Council survey estimated the prevalence of HIV in the adult population (15-49 years old) to be 15.6% (34). Chronic kidney disease is increasingly being recognized as an important complication of HIV infection (35), and the estimation of GFR in this population group is therefore important. Further studies are needed to evaluate the performance of the 4-v MDRD equation in patients infected with HIV.

Limitations of the study were as follows: a) The study has a relatively small sample size, b) It was conducted at only one geographical site, which does not adequately represent all population groups in South Africa. Further studies for these population groups are needed, c) The characteristics of the study population differed from that of the MDRD study population. The study population included hospitalized patients and participants who were known to be infected with HIV. In these participants, creatinine production may differ and they may have reduced creatinine excretion compared with the MDRD study population, which consisted of outpatients with CKD who were otherwise healthy, d) In this study, plasma sampling was done at 2 and 4 h for patients with eGFR >30 mL/min/1.73 m^sup 2^ and at 3 and 5 h for patients with eGFR

Grant/Funding Support: The authors wish to acknowledge the National Health Laboratory Service for funding the study.

Financial Disclosures: None declared.

Acknowledgment: M. Lawson, University of the Witwatersrand, Nuclear Medicine department, is acknowledged for ^sup 51^Cr-EDTA measurement.

4 Nonstandard abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate; 51Cr-EDTA, chromium-51-EDTA; eGFR, estimated GFR; S-Cr, serum creatinine; 4-v MDRD, 4-variable Modification of Diet in Renal Disease; CG, Cockcroft-Gault; IDMS, isotope dilution mass spectromelry; CrCI, creatinine dearance; BSA, body surface area; mGFR, measured GFR; IQR, interquartile range.

References

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16. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-70.

17. MyersGL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, et al. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 2006;52:5-18.

18. Levey AS, Coresh J, Greene T, Marsh J, Stevens U, Kusek J, Lente FV. Expressing the MDRD study equation for estimating GFR with IDMS traceable (gold standard) serum creatinine values [Abstract]. J Am Soc Nephrol 2005;16:69A.

19. Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, Van Lente F. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007;53:766-72.

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28. Froissart M, Rossen J, Jacquot C, Paillard M, Mouillier P. Predictive performance of the Modification of Diet in Renal Disease and CockcroftGault equations for estimating renal function. J Am Soc Nephrol 2005;16:763-73.

29. Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med 2004;141:929-37.

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31. Lewis J, Agodoa L, Cheek D, Greene T, Middteton J, O’Connor D, et al. Comparison of cross- sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate. Am J Kidney Dis 2001;38:744-53.

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Hendrick E. van Deventer,1* Jaya A. George,1 Janice E. Paiker,1 Piet J. Becker,2 and Ivor J. Katz3

1 Department of Chemical Pathology and NHLS, University of the Witwatersrand, Johannesburg, South Africa; 2 Biostatistks Unit, South African Medical Research Council and School of Therapeutic Sciences, University of the Witwatersrand, South Africa; 3 Division of Nephrology, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa.

* Address correspondence to this author at Department of Chemical Pathology, Wits Medical School, 7 York Road, Parktown 2193, South Africa. E-mail [email protected].

Received October 29, 2007; accepted April 7, 2008.

Previously published online at DOI: 10.1373/clinchem.2007.099085

Copyright American Association for Clinical Chemistry Jul 2008

(c) 2008 Clinical Chemistry. Provided by ProQuest Information and Learning. All rights Reserved.

Acupuncture: A Useful Tool for Health Care in an Operational Medicine Environment

By Spira, Alan

ABSTRACT Acupuncture is a form of medical care that originated in China; it has evolved and progressed over thousands of years to become one of the most commonly used forms of health care throughout the world. Allopathic (Western) medicine has begun to seriously investigate and to use this system only in the past three decades. Although acupuncture’s mechanisms for healing are not fully understood, it helps many conditions. Using acupuncture reduces or eliminates the need for expensive medications and the potential risk of adverse events resulting from medications, with cost savings and health benefits to patients. During a deployment of naval combat engineers to Iraq in support of Operation Iraqi Freedom, acupuncture was used in the health care of sailors, Marines, and soldiers. It objectively and subjectively improved the health of troops in the field. Troops were able to function while being treated, reducing or avoiding sick in quarters or light limited duty status and saving operational man-days. Acupuncture in the right hands can serve as a health force multiplier (amplifying a provider’s clinical impact) and can be integrated into routine health care, whether in garrison or in the field. INTRODUCTION

Five hundred Seabees from Naval Mobile Construction Battalion 18 were mobilized during the summer of 2006, for a 9-month deployment in support of Operation Iraqi Freedom. As a reserve battalion, these sailors were generally older (median age, 38 years) and less fit than their active duty counterparts, as noted in the medical literature12 and by the battalion medical officer during mobilization. As naval combat engineers, they operated in physically demanding conditions in Al Anbar province, performing construction and security duties in an austere environment. They sustained combat- related injuries (including one death), work-related injuries, environmental illnesses, and routine illnesses. The battalion had an echelon I battalion aid station (BAS), where the majority of medical care was administered. In addition to standard allopathic medical treatment, sailors were offered acupuncture to complement their therapy; more than two thirds of the patients agreed to acupuncture. As word of acupuncture therapy spread, the BAS was visited by sailors, Marines, and soldiers from other units on the base who attended the growing acupuncture practice, which was offered thrice weekly.

Acupuncture is an ancient form of medical care that began in China more than two millennia ago. Because the Chinese lacked the scientific method, acupuncture evolved through trial and error and was described in cultural and poetic terms, which in some ways have been hurdles to acceptance in the Western medical community. In the past several decades, increasing numbers of scientific studies have been undertaken to evaluate and to elucidate how acupuncture works. There are difficulties in study design because many of the benefits are nonspecific (and thus difficult to measure, although they should not be discounted) or subjective; furthermore, sham acupuncture treatments yield some positive benefits. A true double-blind study cannot be conducted with the application of needles through the skin.3 The mechanisms of action have yet to be fully elucidated but appear to include increased capillary blood flow at needle insertion sites, slow electrical conductivity stimulation of fascial electrolytes, opioid peptide release in the spinal cord, neuropeptide anti-inflammatory effects, pathway stimulation in the central nervous system, segmental nervous system effects, and autonomie nervous system regulation.3-6 Studies have shown that brain activation and deactivation occur in specific and largely predictable areas when specific acupuncture points are stimulated.7

Simplistically, in the Chinese paradigm, energy (qi) flows in patterns throughout the body; when the flow is disrupted or blocked, pain or disease arises. Acupuncture, through the insertion of needles in specific points, restores the flow of qi, which leads to healing.

Clinically, acupuncture has shown great promise. The National Institutes of Health created a branch dedicated to complementary medicine, the National Center of Complementary and Alternative Medicine. The National Institutes of Health has set a precedent by taking a position endorsing the growing use of acupuncture for several conditions and is open to adding to that list as science on the matter expands.3 The National Institutes of Health acknowledges the positive benefits of acupuncture for treating various pain problems, including epicondylitis, menstrual cramps, fibromyalgia, headaches, and dental pain, as well as nausea and vomiting; it also notes that the incidence of adverse events is substantially lower than with many comparable drugs or procedures.3 Various studies have shown that acupuncture is beneficial for treating musculoskeletal ailments (including strains, arthritis, low back pain, and neck pain), for general pain control, for treating respiratory diseases (such as asthma, bronchitis, and chronic obstructive pulmonary disease), certain infections (such as sinusitis), gastrointestinal conditions (such as inflammatory bowel disease), and headaches, and for rehabilitation after nerve injury, among other applications.8- 13 However, few studies on the cost-effectiveness of acupuncture have been conducted.14,15 The use of acupuncture as a complementary health care system has also been addressed by the White House, which instituted the White House Commission on Complementary and Alternative Medicine in 2000 and has increasing support from the Department of Health and Human Services.16 The military is just beginning to investigate the utility of acupuncture for the care of troops (which has been overwhelmingly performed in hospitals and not the field).17 Nevertheless, military patients, notably veterans, already seek and value acupuncture as a form of medical care.18 The medical use of acupuncture has rapidly expanded in the past decade, with the creation of a medical acupuncture board examination and the American Academy of Medical Acupuncture; these developments are aimed at integrating acupuncture into mainstream medical care and augmenting patient therapies, in conjunction with traditional Western medical regimens.

METHODS

Subjects

Five hundred sailors in Naval Mobile Construction Battalion Eighteen deployed to Iraq during Operation Iraqi Freedom from September 2006 through March 2007. Sailors, Marines, soldiers, and Special Forces personnel located on the assigned bases were also seen for acupuncture care. Patients were verbally offered acupuncture care in lieu of or in conjunction with allopathic medical care and were informed about the process, as well as the potential risks and benefits. The medical officer, who was board- certified in emergency medicine, was also board-certified in medical acupuncture by the American Academy of Medical Acupuncture and had practiced acupuncture for nearly a decade. The Force Medical Officer at the division level supported the use of acupuncture for patient care. Patients were seen primarily in the BAS at Al Asad Marine Corps Air Station in Al Anbar Province, Iraq, or at the shock trauma platoon located at the base hospital; treatments were also performed in the BAS at Camp Fallujah and at forward operating bases and combat outposts.

Materials

Sterile acupuncture needles were used once, discarded into biohazard sharps dispensers, and disposed of at the base hospital with standard sharps items such as syringe needles. The needles used were primarily C & G (CT5-3215, 0.25 x 40 mm) and Carbo (CB 1.25 x 40 and CB 1.25 x 75 for deep therapy; Helio Supplies, San Jose, CA). Helio ear seeds with processed vaccaria seeds on surgical tape were used for ear seed pressure therapy. Electroacupuncture was conducted with an Ito electroacupuncture stimulator (Helio Supplies). Moxabustion was performed by using traditional pure moxa rolls (Artemesia vulgaris, also known as mugwort; Helio Supplies).

Procedures

Acupuncture treatments were primarily given according to traditional Chinese medicine methods, but the tendinomuscular method, percutaneous electrical nerve stimulation, and the French style were also used. Sterile needles were placed through the skin until the sensation of de qi (“grabbing” of the needle, usually at the fascial level) was noted by either the physician or the patient or, according to the traditional site location, with the depth varying from a single millimeter to several centimeters. Needles were left alone, intermittently manually stimulated, attached to electrodes, or heated with a moxa roll. Electrostimulation was performed either according to the French system or with the percutaneous electrical nerve stimulation method, a more-effective therapy than the morefamiliar transcutaneous electrical nerve stimulation. Needles were typically left in place for 10-20 minutes; some therapies, particularly those for chronic pain reduction, were left in place longer. Interestingly, there is no need to sterilize the skin before needle insertion. If no cellulitis or other skin infection is present and the needles are sterile, then acupuncture therapy does not cause infection. Patients who expressed concern had their acupuncture sites treated with alcohol swabs. Patients were encouraged not to take nonsteroidal anti-inflammatory drugs during their treatments. RESULTS

A total of 435 acupuncture treatments were administered to 132 different patients during deployment to Operation Iraqi Freedom. Patients in this population group were very willing to try acupuncture instead of taking medications when the theory and practice of acupuncture were described to them. Many expressed a dislike for the ubiquitous use of ibuprofen by Navy medicine and were interested in trying an alternative form of therapy. More than 80% of the acupuncture patients did not take medications (notably anti-inflammatory and analgesic medications) for the condition for which acupuncture therapy was being administered, upon the advice of the medical officer. A total of 3,563 needles were used for these 132 patients; 11.1 treatments were conducted weekly, using a 3-day week when acupuncture was offered, with ~6 h/wk dedicated to such care. Patients averaged 3.3 visits, with 2.3 treatments per condition, over the course of the deployment in Iraq. An average of 7.9 needles per treatment were used.

Most conditions treated arose from injury rather than illness (Fig. 1). Injuries in this population were typically related to construction work, particularly with repetitive-motion injuries such as with hammering, using screwdrivers, or carrying materiel.

There was a nearly even distribution of those presenting with acute vs. chronic conditions; there was a slight predominance of chronic conditions, defined as persisting >10 days (Fig. 2). Acute exacerbations of chronic conditions were included in the acute category. When patient presentations were examined according to ailment category, the overwhelming majority of acupuncture treatments were for orthopedic conditions (Fig. 3). Considering that the population consisted primarily of construction workers in a combat zone, this is hardly surprising. When problems were divided according to different body areas, the majority of patients presented with back and spine conditions (Fig. 4). After this, most treatments were given for hip or pelvis complaints or neck or cervical spine-related ailments, followed by shoulder or elbow conditions. Nineteen sprains and fractures were treated, and acupuncture hastened return to duty by an average of 2 days for all sprains, compared with troops who chose conventional therapy, during this deployment. A case of eye strain in a helicopter pilot accounted for the only ophthalmic condition, with inconclusive results.

Treatment outcomes were divided into three categories, namely, significant improvement, improvement, or no improvement. Significant improvement was defined as a patient requiring fewer than three treatments or subjective improvement with the patient indicating >/ =50% reduction in pain or >/=50% improvement using a pain scale of 1 to 10 (Fig. 5). Improvement indicated that more than three treatments were necessary or there was

DISCUSSION

This was a noncontrolled study that arose from a treatment option offered to troops, which was eagerly accepted and sought out. Although it was not a randomized, double-blind, controlled trial, it still has great value; indeed, for complex interventions such as acupuncture, which at times produces nonspecific results, such studies may not be as useful.19 In this preliminary descriptive study, the data acquired provide encouragement regarding the utility of acupuncture in operational environments. This should lead to more- advanced and more-frequent comparison studies, to gain the acceptance of acupuncture by the military medical community. As in the civilian community, patients appear more interested and open to complementary health care methods than their health care providers. Among the reasons expressed by troops for using acupuncture were avoidance of medication treatments with which they found it difficult to comply in the tactical environment, avoidance of side effects, ease of treatment, and beneficial results of therapy. The elimination or reduction of medication usage might be particularly advantageous for the aviation community, allowing pilots to avoid grounding by flight surgeons if specific medications might interfere with flying.

An additional benefit to using acupuncture is the low cost of treatment. Consider the following exercise. The price of needles ranges from $0.06 to $0.50 per needle. The majority of the needles used during this deployment were in the low end of the range, ~$0.10 per needle, for a total expense of ~$375. With an average of 7.9 needles per treatment, the average treatment cost was $0.79. Considering 2.3 visits per condition, the cost of needles for each treatment course was $1.82. In comparison, the cost of ibuprofen ($0.48 for 800 mg) for 1 week is $10.08 (using prices acquired directly from TAMMIS Customer Assistance Module (TCAM)) and the cost of celecoxib ($1.47 for 100 mg) for 1 week is $20.58 (using prices acquired directly from the TCAM). The relative cost of treating mild/ moderate pain syndromes is by far lowest using acupuncture (Table I). By avoiding nonsteroidal anti-inflammatory drugs, the potential complications of gastritis, gastric perforation, and renal damage (among others) are avoided. As an example, during the deployment one member declined acupuncture for a stiff knee, choosing to take ibuprofen instead. After 5 days of therapy, she developed severe abdominal pain and was admitted to the shock trauma platoon for 24 hours of observation and treatment. Because of the limited capabilities of the echelon II facility, no esophagogastroduodenoscopy was performed, but her blood tests (complete blood count, liver enzyme profile, amylase measurement, serum chemistry profile, and pregnancy test), urinalysis, acute abdominal series, and ultrasound results were normal. The patient was given intravenously administered ranitidine overnight ($24.96 for intravenous therapy; 50-mg intravenous piggyback every 8 hours at $4.16 for 25 mg/mL), followed by oral therapy (150 mg twice per day at $1.42 per tablet; $85.20 per month). In addition, the cost of a 24-hour hospitalization with an average overseas inpatient rate is ~$3,958.20 The cost of treating this single patient exceeded the cost of the treatment she would have required with acupuncture by a factor of 2,139 ($3,958/$ 1.82) and the cost of all acupuncture needles used during the entire deployment by a factor of 10.5 ($3,958/$375). The cost difference between the medication needed for gastritis therapy and acupuncture therapy was $108.34 ($110.16 $1.82). If hospitalization could have been avoided through outpatient acupuncture therapy, then the cost savings to the Department of Defense would have been $3,956.18 ($3,958.00 – $1.82) for this single patient. This cost savings is a benefit above that of returning a member to duty sooner or avoiding sick in quarters status and, as such, provides commanders with reduced lost man- days. This is therefore an operational force multiplier, expanding the clinical capability of providers in operational environments. Cost savings by postponing or reducing the need for expensive procedures can also be predicted. For example, the average costs of ambulatory surgical visits for spinal fusion and laminectomy are $18,600 and $10,700, respectively.21 If these procedures could be limited or eliminated, then substantial savings could be experienced by the Department of Defense and the Department of Veterans Affairs.

From this study, it can be seen that acupuncture is a useful practical adjunct for therapy in operational environments, but further studies are clearly needed. A commission established by the White House came to the same conclusion.16 Although acupuncture has been used for nearly 3,000 years, it has only begun to be studied with the scientific method. Acupuncture provides good pain relief and assists in minimizing illness. It is quite safe; a PubMed search (National Library of Medicine) revealed only 18 articles on acupuncture medical errors, whereas there were 57,184 articles for standard medical errors. The Institute of Medicine published a report revealing that preventable adverse events are a leading cause of death in the United States. With extrapolation to the >33 million annual admissions to U.S. hospitals, between 44,000 and 98,000 patients die in U.S. hospitals each year as a result of medical errors.22 This does not include those who suffer morbidity only, which would naturally be an even greater number. Medical errors carry high financial costs as well; the Institute of Medicine report estimated that medical errors cost ~$37.6 billion each year, with ~$17 billion associated with preventable errors. Approximately one- half of the expenditures for preventable medical errors are for direct health care costs.

Patients are interested in acupuncture therapy when it is available and often prefer it to standard modalities. Acupuncture has been used by at least 8 million U.S. civilians and is entering mainstream medical care.3,16,23,24 It should be considered by the Department of Defense as an additional medical modality for military health care providers.

CONCLUSIONS

Acupuncture is a valuable tool that can be safely used to augment the health care of troops in operational field environments. Acupuncture helps save commanders man-days by reducing lost work time and shortening the interval from injury or illness to return to duty. It is inexpensive, carries little overhead, can be used nearly anywhere, and saves money. Providing acupuncture services in garrison and during deployment is beneficial for both troops and commands. ACKNOWLEDGMENTS

I thank LT David Carlson for his invaluable assistance in making this article become a reality. In addition, I thank CAPT Robert Koffman, USN.

Naval Mobile Construction Battalion Eighteen, Fort Lewis, WA 98433.

There is no financial relationship between the author and any of the suppliers of the acupuncture materiel. All equipment and supplies were purchased from the author’s personal funds.

The views in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, or the U.S. government.

This manuscript was received for review in March 2007. The revised manuscript was accepted for publication in April 2008.

Reprint & Copyright (c) by Association of Military Surgeons of U.S., 2008.

REFERENCES

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2. Carrol DA, Cowan DN: The reserve components: medical and related issues of mobilization. In: Military Preventive Medicine: Mobilization and Deployment, Vol 1, pp 129-43. Edited by Lounsbury DE, Bellamy RF, Zajtchuk R. Washington, DC, U.S. Army, Borden Institute, 2003.

3. Ramsay DJ, Bowman MA, Greenman PE, et al: Acupuncture. NIH Consens Statement 1997; 15: 1-34.

4. Helms J: Acupuncture Energetics. Berkeley, CA, Medical Acupuncture Publishers, 1995.

5. Moffet HH: How might acupuncture work? A systematic review of physiologic rationales from clinical trials. BMC Complement Altern Med 2006; 7: 25-33.

6. Zijlstra FJ, Berg-de Lange I, Huggen FJPM, Klein J: Anti- inflammatory actions of acupuncture. Mediators Inflamm 2003; 12: 59- 69.

7. Lewith GT, White PJ, Pariente J: Investigating acupuncture using brain imaging techniques: the current state of play. eCAM 2005; 2: 315-9.

8. Scharf HP, Mansmann U, Strelberger K, et al: Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med 2006; 145: 12-20.

9. Thomas KJ, MacPherson H, Thorpe L, et al: Randomised controlled trial of a short course of traditional acupuncture compared with usual care for persistent non-specific low back pain. BMJ 2006; 333: 623.

10. Ratcliffe J, Thomas KJ, MacPherson H, Brazier J: A randomised controlled trial of acupuncture care for persistent low back pain: cost effectiveness analysis. BMJ 2006; 333: 626.

11. White P, Lewith G, Prescott P, Con way J: Acupuncture versus placebo for the treatment of chronic mechanical neck pain: a randomized, controlled trial. Ann Intern Med 2004; 141: 911-9.

12. Joos S, Rosemann T, Szecsenyi J, et al: Use of complementary and alternative medicine in Germany: a survey of patients with inflammatory bowel disease. BMC Complement Altern Med 2006; 6: 19- 25.

13. Jobst KA: A critical analysis of acupuncture in pulmonary disease: efficacy and safety of the acupuncture needle. J Altern Complement Med 1995; 1: 57-85.

14. White A, Tough E, Cummings M: A review of acupuncture clinical trials indexed during 2005. Acupunct Med 2006; 24: 39-49.

15. Canter PH, Coon JT, Ernst E: Cost-effectiveness of complementary therapies in the unit systematic review. Evid Based Complement Altern Med 2006; 3: 425-32.

16. The White House: The White House Commission on Complementary and Alternative Medicine Policy Final Report. Washington, DC, Government Printing Office, 2002.

17. Niemtzow RC, Gambel J, Helms J, et al: Integrating ear and scalp acupuncture techniques into the care of blast-injured United States military service members with limb loss. J Altern Complement Med 2006; 12: 596-9.

18. McEachrane-Gross FP, Liebschutz JM, Berlowitz D: Use of selected complementary and alternative medicine (CAM) treatments in veterans with cancer or chronic pain: a cross-sectional survey. BMC Complement Altern Med 2006; 6: 34-44.

19. Paterson C, Dieppe P: Characteristic and incidental (placebo) effects in complex interventions such as acupuncture. BMJ 2005; 330: 1202-5.

20. White House Office of Management and Budget: Cost of hospital and medical care treatment furnished by the United States. Available at http://clinton4.nara.gov/OMB/fedreg/2000.html; accessed March 19, 2007.

21. Owens PL, Russo CA, Stocks C: Ambulatory Surgery in U.S. Hospitals, 2003: HCUP Fact Book No. 9. Rockville, MD, Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project, January 2007. Available at http://www.ahrq.gov/data/hcup/ factbk9; accessed March 30, 2008.

22. Institute of Medicine: To Err Is Human: Building a Safer Health System. Washington, DC, National Academies Press, 2000.

23. Barnes PM, Powell-Griner E, McFann K, Nahin RL: Complementary and alternative medicine use among adults: United States, 2002. Adv Data 2004; (343): 1-19.

24. Braverman SE: Acupuncture education and integration in the PM&R residency. Phys Med Rehabil Clin N Am 1999; 10: 755-65.

CDR Alan Spira, MC USN

Copyright Association of Military Surgeons of the United States Jul 2008

(c) 2008 Military Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

Dr. Jarvik Doesn’t Row

By Anonymous

DR. ROBERT JARVIK doesn’t row. The spokesperson for Pfizer’s cholesterol-lowering medication Lipitor also isn’t a cardiologist, nor is he licensed to practice medicine. And former colleagues even contest his claim to be the “inventor of the Jarvik artificial heart.” After a Congressional committee began looking into the misrepresentation of Jarvik’s credentials, Pfizer pulled long- running Lipitor commercials featuring Jarvik off the air in February. Pfizer spent more than $258 million on advertising for Lipitor over the past two years, the majority of it on the Jarvik campaign. A Congressional investigation revealed that Pfizer agreed to pay Jarvik a minimum of $1.35 million for a two-year contract to act as a Lipitor spokesperson.

The Lipitor commercials depict Jarvik as an accomplished rower – when in reality a body double was called in – and tout Jarvik as the inventor of an artificial heart. According to the New York Times, during a conference in December 2007, a former colleague of Jarvik’s, Dr. Clifford S. Kwan-Gett, said that Jarvik’s artificial hearts were simply different versions of prototypes Kwan-Gett had designed more than a year earlier. Perhaps most importantly, given his role in encouraging consumers to “talk to their doctor” about Lipitor, Jarvik is not licensed to practice medicine and can’t legally prescribe medication.

The House Committee on Energy and Commerce’s Subcommittee on Oversight and Investigations started an investigation in January into “false and misleading statements and the use of celebrity endorsements of prescription medications in direct-to-consumer advertising.”

“We are taking a hard look at the deceptive tactics of drug companies in their direct-to-consumer advertising,” says Representative Bart Stupak, D-Michigan, the subcommittee chairman. “Drug companies should know that they will be held accountable for the representations made in their ads,” he says.

“The way in which we presented Dr. Jarvik in these ads has, unfortunately, led to misimpressions and distractions for our primary goal of encouraging patient and physician dialogue on the leading cause of death in the world – cardiovascular disease,” says Ian Read, president of worldwide pharmaceutical operations for Pfizer. “We regret this. Going forward, we commit to ensuring there is greater clarity in our advertising regarding the presentation of spokespeople.”

Copyright Multinational Monitor Jul/Aug 2008

(c) 2008 Multinational Monitor. Provided by ProQuest Information and Learning. All rights Reserved.

Highly Sensitive Cardiac Troponin T Values Remain Constant After Brief Exercise- or Pharmacologic-Induced Reversible Myocardial Ischemia

By Kurz, Kerstin Giannitsis, Evangelos; Zehelein, Joerg; Katus, Hugo A

BACKGROUND: Using a new precommercial high-sensitivity cardiac troponin T (hsTnT) assay, we evaluated whether hsTnT increases after reversible myocardial ischemia. METHODS: In 195 patients undergoing nuclear stress testing (ST) using single-photon emission computed tomography (SPECT) for suspected ischemic heart disease, we measured hsTnT before and 18 min, 4 h, and 24 h after the stress test. Thirty patients were excluded before ST because of cardiac troponin T (cTnT) >30 ng/L (0.03 [mu]g/L) as measured by the fourth-generation commercial test. Another 65 patients were excluded because of a combination of fixed and reversible perfusion defects (PDs) after SPECT.

RESULTS: We studied 18 patients with reversible PDs, 41 patients with fixed PDs, and 41 patients without any PDs. Of these 100 patients, 61 received dynamic ST and 39 pharmacological ST. Median baseline hsTnT concentrations (25th, 75th percentile) were comparable in patients with reversible, fixed, and no PDs [5.57 (2.47, 12.60), 8.01 (4.55, 12.44), and 6.90 (4.63,10.59) ng/L, respectively]. After ST, median hsTnT concentrations did not change in the reversible, fixed, or no PD groups from baseline to 18 min [- 0.41 (-0.81, 0.01), 0.01 (-0.75, 0.79), and 0.36 (-0.42, 1.01) ng/ L] or from baseline to 4 h [-0.56 (-1.82, 0.74), 0.24 (-0.60, 1.45), and 0.23 (-0.99, 1.15) ng/L]. Median baseline hsTnT concentrations tended to be higher in patients undergoing pharmacological vs dynamic ST; however, there were no significant increases in hsTnT concentrations after either type of ST.

CONCLUSIONS: Elevation of cTnT is rather a consequence of irreversible myocyte death than reversible myocardial ischemia after exercise or pharmacologic myocardial ischemia.

Cardiac troponin (cTn) is the preferred biomarker for detection of myocardial cell injury. Reasons for increased cTn include irreversible myocardial necrosis in patients with an acute coronary syndrome (ACS) and, in the absence of ischemia, any direct or indirect myocardial cell damage (1-3). Although it has been speculated that reversible membrane leakage may lead to an egress of non-structurally bound cTn (4-7), experimental data clearly demonstrate that cTn release is restricted to irreversible cell damage (8). To clarify this question, ultrasensitive cTn assays could provide useful information.

We studied patients with suspected significant or confirmed coronary artery disease (CAD) who were undergoing routine stress testing. We used single-photon emission computed tomography (SPECT) to objectively document transient reversible ischemia. For detecting cTn, we used a newly developed precommercial troponin T assay with improved sensitivity (hsTnT).

Materials and Methods

We screened 195 consecutive patients who underwent thallium SPECT. The protocol was approved by the ethics committee of the University of Heidelberg, and all patients gave informed consent. Patients either underwent bicycle exercise or received weight- adjusted dipyridamole. Two cardiologists unaware of biomarker results categorized the SPECT images. Differences in opinion were resolved by consensus. Based on differences between the images taken at rest and under stress in each individual, tracer uptake was categorized as none, only reversible, only fixed, or a combination of reversible and fixed perfusion defects. Regional tracer uptake of reversible defects was visually graded as 3, normal; 2, mildly reduced; 1, severely reduced; and O, absent. A summed score was obtained by adding the scores of all 17 segments for a maximum score of 51 (9). We excluded patients with a combination of fixed and reversible defects to avoid difficulties in estimating the degree of reversibility at the edges of predominantly fixed defects.

cTnT

All laboratory measurements were performed in the research laboratory of Roche Diagnostics in Penzberg, Germany, using the latest precommercial version of the hsTnT assay. The lower detection limit of this assay was 2 ng/L (0.002 [mu]g/L). Improvement of sensitivity and precision was achieved by a) increasing the sample volume to 50 [mu]L, b) optimizing the degree of ruthenylation of the signal antibody, and c) optimizing the buffer composition to reduce background signal.

Table 1. Baseline characteristics.(a)

As described previously (10), the interassay CV was 8% at 10 ng/ L and 2.5% at 100 ng/L, and the intraassay CV was 5% at 10 ng/L and 1% at 100 ng/L. Preliminary data demonstrated detectable concentrations in 2 normal reference populations with a 99th percentile value of 12 ng/L (personal communication, Hallermayer, Roche Diagnostics, Penzberg, Germany, data on file).

cTnT was measured using the fourth-generation commercial 1-step enzyme immunoassay based on electrochemiluminescence technology. The lower detection limit is 0.01 [mu]g/L, with a recommended diagnostic threshold of 0.03 /ig/L (11).

STATISTICAL ANALYSIS

We compared continuous variables using t test or Mann-Whitney U test. We tested changes of hsTnT from baseline using Wilcoxon test for paired samples and categorical variables using chi^sup 2^ or Fisher exact test. For all analyses, a P value

Results

BASELINE CHARACTERISTICS

Of 195 patients screened, 30 (15.4%) were excluded because of a positive baseline conventional cTnT related to recent myocardial infarction and 21 (10.8%) because the sample volume was too low to allow measurement of hsTnT. Of the remaining 144 patients, 18 were found to have reversible perfusion defects, 41 had fixed perfusion defects, and 41 showed no perfusion defects. Table 1 presents baseline characteristics and stress test data of the study group,

hsTnT CONCENTRATIONS IN PATIENTS WITH AND WITHOUT INDUCIBLE ISCHEMIA

Baseline hsTnT concentrations were comparable in patients with reversible perfusion defects, fixed perfusion defects, and without perfusion defects [median (25th, 75th percentile]: 5.57 (2.47, 12.60), 8.01 (4.55, 12.44), and 6.90 (4.63,10.59) ng/L). After stress testing, hsTnT concentrations for the 3 patient groups did not change from baseline to 18 min [-0.41 (-0.81, 0.01), 0.01 (- 0.75, 0.79), and 0.36 (-0.42, 1.01) ng/L, respectively] or from baseline to 4 h [-0.56 (-1.82, 0.74), 0.24 (-0.60,1.45), and 0.23 (- 0.99,1.15) ng/L] (Fig. 1).

Fig. 1. Box plot showing hsTnT in patients with fixed perfusion defects, reversible perfusion defects, and no perfusion defects after nuclear stress testing.

No significant changes were noted within and between groups at all time points.

hsTnT AND SEVERITY OF REVERSIBLE ISCHEMIA

In patients with reversible perfusion defects, semi-quantitative analysis of SPECT yielded a median of 3 segments showing stress- induced perfusion defects. The mean (SD) summed score (n/17 segments) was calculated as 2.78 (0.10) with individual scores ranging from 2.78 to 2.59, suggesting a mild to moderate degree of ischemia. There was no significant correlation between the summed score and hsTnT change at 18 min [r = 0.167 (-0.374-0.625), P = 0.535] or 4 h [r = -0.193 (-0.642-0.354), P = 0.47].

hsTnT AFTER REVERSIBLE ISCHEMIA RELATED TO TYPE OP STRESS

Of the 100 patients, 61 (61%) received dynamic stress (DS) tests and 39 (39%) pharmacological stress (PS) tests. Compared to patients receiving DS tests, patients receiving PS tests were older [71.51 (9.13) years vs 65.90 (10-40), P = 0.01] and had a lower glomerular filtration rate (GFR) [64.72 (29.03) vs 80.95 (31.90), P = 0.01]. Median baseline hsTnT levels (25th, 75th percentile) tended to be higher in those receiving PS vs DS tests: 8.09 (4.76, 15.13) vs 6.12 (3.80, 10.30) ng/L, P = 0.07. There was no significant increase of hsTnT concentrations after any type of stress.

Discussion

In this study, we evaluated the effect of reversible myocardial ischemia on concentrations of cTnT measured with a new precommercial hsTnT assay. Our key rinding is that reversible ischemia does not induce a significant change of hsTnT. Baseline concentrations of hsTnT were not found to be different in patients without perfusion defects compared to those with fixed and reversible perfusion defects and did not change after 18 min and 4 h in either group.

In this study, SPECT was performed for objective identification of reversible myocardial perfusion defects. To test the effects of reversible myocardial ischemia, we used a precommercial hsTnT assay with a 5-fold lower detection limit than the standard assay. The finding that hsTnT does not increase after reversible myocardial ischemia supports the experimental results of Fishbein et al. (8) demonstrating that troponin release was restricted to irreversible myocyte necrosis. Our results are also supported by the findings of Schulz et al. (12), who tested a sensitive cTnl assay on 47 outpatients undergoing stress testing for stable CAD. Detectable cTnl concentrations below the 99th percentile remained unchanged 3 and 5 h after exercise in patients with and without detectable ischemia. Baseline values, however, were higher in patients who later developed stress-induced myocardial ischemia. In our study, there was a trend toward higher baseline values, but hsTnT did not change significantly after either stress type. Previously, Venge et al. (13 ) reported an age-dependent increase in cTnl in patients without CAD, raising the question as to the reason for higher cTnl. Later, Zethelius et al. (14) found that low cTnl predicted death and first coronary event hi seemingly healthy persons. Similar findings were reported for patients presenting with possible ACS (15) and in patients with stable CAD who had stress-inducible myocardial ischemia (12). Conversely, Wu et al. (16) found extraordinarily low concentrations of cTnl in patients without evidence of heart disease. Consistently in our study, patients deemed unable to perform or complete a DS test and were therefore referred to PS testing by their physicians demonstrated a trend to higher baseline hsTnT values. These patients were older and had more impaired renal function, suggesting more cardiovascular morbidity. These findings are preliminary, however, and should prompt further investigations into whether hsTnT may be useful for identifying different levels of subclinical cardiovascular disease. Interestingly, several studies, mainly on professional and recreational athletes, found short reversible increases of cTnT or cTnl and speculated on a release of non-structurally bound cTn through reversible membrane leakage (17). The reasons for these increases of cTn in apparently healthy athletes remain controversial. Given that risk of cardiovascular disease increases with age and that the ages of participants of popular ultraendurance events are rising disproportionally, subclinical cardiovascular disease might be unmasked by strenuous exercise. In this study, the presence of reversible ischemia was documented objectively using SPECT, and semi-quantitative classification of the perfusion defects demonstrated only a mild to moderate degree of ischemia. We used a standard stress protocol applying strict criteria for discontinuation of stress after the first evidence of myocardial ischemia. Therefore, we cannot exclude the possibility that longer or more severe myocardial ischemia could have caused troponin release. In addition, it remains unclear whether our findings apply to cTnl, which is smaller and thus potentially better membrane-permeable, or whether our results may be extrapolated to other advanced-generation cTnl assays, particularly when measured more sensitively using advanced technology such as the single-molecule fluorescent detector assay (Singulex) (18). At the moment, recent data on a sensitive cTnl assay (12 ) and our results on hsTnT are consistent in suggesting that ischemia alone is not capable of causing troponin release, or that more severe or more prolonged ischemia is required. Moreover, the degree of modification of the troponin molecule may be different in naturally occurring ischemia than in brief induced ischemia (19).

STUDY LIMITATIONS

The duration and severity of reversible myocardial ischemia induced by our protocol stress tests may have been too small to identify cTnT release from membrane leakage. Semiquantitative assessment of the severity of myocardial ischemia demonstrated mild to moderate reversible perfusion defects. second, blood was collected before and at 3 time points after stress. Although we may have missed an increase of cTnT by measuring as early as 4 h after ischemia, recent data have demonstrated that lowering the decision cutoff from ROC cutoff to the 10% CV or even to the 99th percentile will shorten the time to appearance in blood significantly to

Grant/Funding Support: The study was sponsored by Roche Diagnostics Inc, Mannheim, Germany. Roche Diagnostics Inc had no role in the study design; collection, analysis, or interpretation of data; or report writing.

Financial Disclosures: Evangelos Giannitsis has received financial support for clinical trials from Roche Diagnostics and MSD Germany. He is consultant to Bristol-Myers Squibb and receives honoraria for lectures from Takeda, MSD, Roche, Lilly, Novartis, BMS, Astra, and Sanofi-Aventis. Hugo A. Katus developed the cTnT assay and holds a patent jointly with Roche Diagnostics. He has received grants and research support from several companies and has received honoraria for lectures from Roche Diagnostics, MSD, Roche, Lilly, Novartis, BMS, Astra, and Sanofi-Aventis. Kerstein Kurz and Joerg Zehelein have no conflict of interest to disclose.

References

1. Jeremias A, Gibson M. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded Ann Intern Med 2005;142:786-91.

2. Korff S, Katus HA, Giannitsis E. Differential diagnosis of elevated troponins. Heart 2006;92: 987-93.

3. Hamm CW, Giannitsis E, Katus HA. Cardiac troponin elevations in patients without acute coronary syndrome. Circulation 2002;106:2871-2.

4. Neumayr Q, Oaenzer H, Pfister R, Sturm W, Sdiwanacher SP, Eibl G, et al, Plasma levels of cardiac troponin I after prolonged strenuous endurance exercise. Am J Cardiol 2001:87:369-71, A10.

5. Choragudi NL, Aronow WS, Prakash A, Kurup SK, Chiaramida S, Lucariello R. Does ttie serum cardiac troponin I level increase with stress test-induced myocardial ischemia? Heart Dis 2002;4: 216-9.

6. Altdemir 1, Aksoy N, Aksoy M, Davulogtu V, Dinckal H. Does exercise-induced severe ischemia result in elevation of plasma troponin-T level in patients with chronic coronary artery disease? Acta Cardiol 2002:57:13-8.

7. Siegel AJ, Sholar M, Yang J, Dhanak E, Lewandrowski KB. Elevated serum cardiac markers in asymptomatic marathon runners after competition: is the myocardium stunned? Cardiology 1997;88:487- 91.

8. Fishbein MC, Wang T. Matijasevic M, Hong L, Apple FS. Myocardial tissue troponins T and I: an immunohistochemical study in experimental models of myocardial ischemia. Cardiovasc Pathol 2003;12:65-71.

9. Cerqueira M, Weissman N, Dilsizian V, Jacobs A, Kaul S, Laskey W, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. American Heart Asseciation Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Circulation 2002;105:539-42.

10. Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, et al. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation 2007;116:1242-9.

11. Katus HA, Remppis A, Neumann F), Scheffold T, Diederich KW, Vinar G, et al. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation 1991;83:902-12,

12. Schulz O, Paul-Walter C, Lehmann M, Abraham K, Berghofer G, Schimke I, Jaffe AS. Usefulness of detectable levels of troponin, below the 99th percentile of the normal range, as a due to the presence of underlying coronary artery disease. Am J Cardiol 2007;100:764-9.

13. Venge P, lagerqvist B, Diderholm E, Lindahl B, Wallentin L. Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC Il substudy). Am J Cardiol 2002;89:1035-41.

14. Zethelius B, Johnston N, Venge P. Troponin I as a predictor of coronary heart disease and mortality in 70-year-old men: a community-based cohort study. Circulation 2006:113:1071-8.

15. Kavsak PA, Newman AM. Lustig V, MacRae AR, Palomaki GE, Ko DT, Tu JV, Jaffe AS. Long-term health outcomes associated with detectable troponin I concentrations. Clin Chem 2007;53: 220-7.

16. Wu AH, Fukushima N, Puskas R, Todd J, Goix P. Development and preliminary clinical validation of a high sensitivity assay for cardiac troponin using a capillary flow (single molecule) fluorescent detector. Clin Chem 2006;52:2157-9.

17. Wu AH, Feng YJ. Biochemical differences between cTnT and cTnl and their significance for diagnosis of acute coronary syndromes. Eur Heart J 1998; 19 Supp JN:N25-9.

18. Wu AH, Fukushima N, Puskas R, Todd J, Goix P. Development and preliminary clinical validation of a high sensitivity assay for cardiac troponin using a capillary flow (single molecule) fluorescence detector. Clin Chem 2006;52:2157-9.

19. Labugger R, Organ U Collier C, Atar D, Van Eyk JE. Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction. Circulation 2000;102:1221-6.

20. Eggers KM, Oldgren J, Nordenskjold A, Lindahl B. Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction. Am Heart J 2004;148: 574-81.

DOI: 10.1373/dinchem.2007.097865

Kerstin Kurz,[dagger] Evangelos Giannitsis,*[dagger] Joerg Zehelein, and Hugo A. Katus

Department of Medicine HI, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg, Germany; * address correspondence to this author at: Department of Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Fax +49-6221-56-33679; e-mail: evangelos_giannitsis@med. uni- heidelberg.de.f K. Kurz and E. Giannitsis contributed equally.

Copyright American Association for Clinical Chemistry Jul 2008

(c) 2008 Clinical Chemistry. Provided by ProQuest Information and Learning. All rights Reserved.

N-Terminal Pro-B-Type Natriuretic Peptide Concentrations Predict the Risk of Cardiovascular Adverse Events From Antiinflammatory Drugs: A Pilot Trial

By Brune, Kay Katus, Hugo A; Moecks, Joachim; Spanuth, Eberhard; Jaffe, Allan S; Giannitsis, Evangelos

BACKGROUND: We investigated whether higher concentrations of N- terminal pro-B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs. METHODS: NT- proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the therapeutic effect of a novel metalloproteinase inhibitor. We monitored CV-AEs and retrospectively investigated their relationship to the concomitant use of selective cyclooxygenase-2 inhibitors (coxibs), traditional nonsteroidal antiinflammatory drugs (tNSAIDs), and glucocorticoids. CV-AEs included myocardial infarction, stroke, new or worsening of preexisting arterial hypertension, congestive heart failure, and several less severe CV-AEs.

RESULTS: We observed 82 mild to serious CV-AEs during an observational period of 200 days. The risk of such events was 1.95- fold higher in patients who were taking tNSAIDs, glucocorticoids, or coxibs (i.e., any inhibitor) and who had NT-proBNP concentrations >/ =100 ng/L than in patients taking any inhibitor who had NT-proBNP values /=100 ng/L had a 7.41-fold higher risk for CV-AEs than those with baseline values 100 ng/ L had a 3.74-fold higher risk for CV-AEs than those with NT-proBNP values 85% across all treatment groups.

CONCLUSIONS: NT-proBNP may be a useful marker for anticipating cardiovascular risk associated with the use of antiinflammatory drugs for osteoarthritis.

(c) 2008 American Association for Clinical Chemistry

The use of selective cyclooxygenase-2 inhibitors (coxibs)5 and traditional nonsteroidal antiinflammatory drugs (tNSAIDs) has been documented to increase the incidence of myocardial infarction and stroke (13). The coxib rofecoxib has been withdrawn from the market because of its cardiovascular risk (4), Several observational studies have indicated a comparable risk for tNSAIDs (5-8). The prevailing interpretation is that drugs that block the production of cardiovascuIarly protective eicosanoids (e.g., prostacyclin) are associated with increased blood pressure, higher rates of thromboembolic events, and accelerated atherosclerosis. This information prompted the European Medicines Agency and the US Food and Drug Administration to send out alerts indicating that the prescription of coxibs was contraindicated for patients with symptomatic heart failure or a history of cardiovascular disease. Warnings were issued to exert caution before prescribing coxibs or tNSAIDs to individuals with risk factors for heart disease, such as hypertension, hyperlipidemia, diabetes mellitus, smoking, or peripheral arterial disease. Physicians were advised to prescribe the lowest dose for the shortest feasible treatment period. These recommendations were recently reiterated by the American Heart Association (9). Because coxibs are extremely effective in providing excellent pain relief while causing fewer gastrointestinal side effects than tNSAIDs (6), many patients and physicians prefer to continue these agents despite the potential associated cardiovascular risk. The availability of a simple screening test would be helpful for identifying the patients at risk.

Brain natriuretic peptide (BNP) and its stable signal peptide, N- terminal proBNP (NT-proBNP), are released in equimolar quantities from the myocardium after proteolytic cleavage of the precursor molecule, proBNP. Both peptides can be used as markers to detect or exclude heart failure in symptomatic and asymptomatic patients (10- 14). Higher NT-proBNP concentrations have been correlated with functional impairment of the heart. NTproBNP has potent prognostic significance as a marker and may permit the monitoring of heart failure therapy (15). Increased NT-proBNP concentrations also predict cardiovascular events across the entire spectrum of ischemic heart diseases (16-19). We thus hypothesized that higher NT-proBNP concentrations might indicate greater cardiovascular risk when coxibs were being used and, conversely, that lower concentrations would indicate lesser risk. If so, this strategy could be used to identify patients in whom these potentially important agents could be used more safely. Accordingly, as an initial test we evaluated this strategy with samples from a small study of coxib use that prospectively identified cardiovascular adverse events (CV-AEs).

Materials and Methods

STUDY DESIGN

The study cohort was originally enrolled in a clinical trial designed and conducted by Hoflrnann-La Roche (internal data based on Roche Pharma Clinical Study Protocol NI15713 F + C), which was designed to investigate the effects of a novel matrix metalloproteinase inhibitor, Ro 113-0830, on the progression of primary osteoarthritis (OA). The study was of a double-blind, randomized, 5-arm, placebo-controlled, parallel-group, multicenter design and was a dose-ranging trial. The study was designed for a period of 24 weeks (168 days, 8 visits) followed by a final safety visit after 200 days. Adverse events were recorded during these periods.

Patients. We enrolled 433 patients in the study. All patients gave informed consent for additional scientific analyses of the collected blood samples. Inclusion criteria were primary OA of the knees with or without OA of the hands, as diagnosed according to clinical and radiographie criteria. Exclusion criteria were a history of significant active gastrointestinal disease (e.g., erosions, ulcers, bleeding), major abnormalities of a hematologic, cardiac, pulmonary, metabolic, renal, or hepatic system, and/or other comorbidities that could compromise the patient’s safety or participation in the study. The primary endpoint was the scoring of pain for knee OA according to the Western Ontario and McMaster Universities (WOMAC) score. The use of analgesics, steroids, or NSAIDs was permitted as rescue medication. The study protocol stipulated that any analgesic/NSAID should be taken for 1 week before switching to another analgesic/NSAID. Rescue therapy was to start with acetaminophen at up to 650 mg 4 times a day. Then, low- dose NSAIDs, fulldose NSAIDs, full-dose NSAIDs plus acetaminophen, and finally full-dose NSAIDs plus acetaminophen plus narcotic drugs could be prescribed in a stepped approach. Low-dose aspirin (e.g., =325 mg/day) was permitted.

Patient groups. The study population consisted of groups of patients who received rescue analgesic/ NSAID/steroid medication and those who did not. Patients who did not receive rescue medication or who took only analgesics but no NSAIDs or steroids were assigned to the comparison group (n = 180). Patients on coxibs, tNSAIDs, or glucocorticoids formed the any-inhibitor group (n = 253). Patient assignment was unrelated to the original study medication.

The any-inhibitor group included patients who received 1, 2, or even 3 types of antiinflammatory drugs. Table 1 displays the composition and numbers of patients in these subsets. Patients who used coxibs alone (stratum 2) or together with other inhibitors (strata 5, 6, and 8) formed the coxibs group (n = 55). Patients who received tNSAIDs alone (stratum 3) or together with other inhibitors (strata 5, 7, and 8) formed the tNSAIDs group (n = 177). Patients who received glucocorticoids alone (stratum 4) or together with other inhibitors (strata 6-8) formed the glucocorticoids group (n = 99). Patients who received only 1 inhibitor constituted the one- inhibitor group (n = 184), whereas those who received 2 or more inhibitors constituted the multiple-inhibitor group (n = 69).

Cardiovascular endpoints. Cardiovascular events were tabulated from the investigator-documented records of adverse events, which medical professionals classified according to regulatory standards into different categories by means of the Medical Dictionary for Regulatory Activities (MedDRA). Adverse events assigned to a cardiac or vascular category formed the target composite and were termed CV- AEs. The recording of CV-AEs was part of the standard safety documentation of the study drug, and it was conducted completely independently of the use of rescue medications.

Table 1. Composition of the patient groups and factors of regression models.a

All CV-AEs were reconciled by 2 cardiologists who were not part of this trial and who were blinded to the NT-proBNP results. CV-AEs of special clinical focus included acute myocardial infarction, new diagnostic Qwaves or bundle branch block, stroke, the onset or worsening of heart failure as suggested by edema or worsening of preexisting edema of the lower extremities, rales on auscultation or pulmonary congestion documented by fluoroscopy, new onset of arterial hypertension or worsening of preexisting arterial hypertension, and confirmed venous thrombosis. Other electrocardiographic changes, unilateral edema, and isolated edema of the upper extremities did not qualify as CV-AEs. We used the entire set of CV-AEs for the statistical analysis. NT-proBNP measurements. As part of the study design, 2 10-mL samples of venous blood had been collected into separate plain glass tubes, centrifuged, and stored at -70 [degrees]C at the Central Sample Office in polystyrene storage racks. NT-proBNP was measured with a highly sensitive and specific electrochemiluminescence immunoassay (Elecsys proBNP; Roche Diagnostics, Basel, Switzerland). The measurement range is 535 000 ng/L. The minimal detectable concentration is 5 ng/L, and the CV is 5.7% at 64 ng/L (20).

STATISTICAL ANALYSIS

Assessment of the comparability of the rescue-medication groups. The rescue-medication groups were described and compared on the basis of available baseline data, including demographics, history, laboratory values, vital signs, NT-proBNP values, and study status.

NT-proBNP cutoff value. We used established NTproBNP cutoff values of 125 ng/L (450 ng/L for patients older than 75 years) and 300 ng/L in the analysis for excluding patients with chronic and acute heart failure, respectively (13,21 ). We did not use cutoff values based on an age older than 75 years or on renal function because the proportion of patients older than 75 years was only 6.93% (30 patients) and patients with an impaired renal function had already been excluded from the study. Unlike heart Mure, NT-proBNP has not previously been studied in an OA population. Therefore potential cutoff values had to be determined to stratify cardiovascular risks. We used Cox regression analysis to plot hazard ratios (high vs low NT-proBNP concentration) against all possible cutoff values for each of the rescue-medication groups. We compared the cutoff values with the lowest P values and confirmed the optimal cutoff value with ROC curve analysis ( see Fig. 1 in the Data Supplement that accompanies the online version of mis article at http://www.clinchem. org/content/vol54/issue7). Because this cutoff value (100 ng/L) was dose to 125 ng/L, we compared sensitivities and negative predictive values in a secondary analysis.

Core analyses, interactions, and covariate adjustments. We used survival analysis to evaluate CV-AE risk, because the censoring and event times could be variable. CV-AE rates over time are displayed as Kaplan-Meier graphs. We used Cox regression (i.e., the Cox proportional hazards model) to investigate the time to first CV-AE to assess the predictive value of baseline NTproBNP values and their interaction with the rescuemedication groups.

Table 2. Baseline characteristics of the patient groups.a

We used different regression models (M1-M3) with the factors detailed in Table 1. All involved the comparison group plus Ml (any- inhibitor factor), M2 (the 3 overlapping factors coxibs, tNSAIDs, and glucocorticoids), and M3 (the one-inhibitor and multiple- inhibitor factors). All models contained interaction terms (interaction of the respective medication factor with NT-proBNP status) that were formally tested. By the inclusion of interaction terms, the regression models also produced hazard ratios vs the comparison group that were based on NT-proBNP status, as well as hazard ratios for comparisons of NT-proBNP groups for a cutoff value of >/=100 ng/L based on the specific medication factor(s).

To evaluate the independent predictive value of NT-proBNP relative to covariates and potential confounders, regression analysis with the factors described above without additional covariates (set A) was supplemented with analyses with adjusted regression models that used 4 additional different sets of covariates: the effect of the randomized study drug Ro 113-0830 at incremental doses (set B); relevant clinical covariates, including age, systolic blood pressure, diabetes mellitus (set C); previous and concomitant use of antithrombotic agents, antiplatelet drugs, antihypertensive drugs, and statins/ fibrates (set D); and a panel of baseline laboratory results for variables (leukocytes, platelets, cholesterol, sodium, potassium, and serum glutamic-pyruvic transaminase) with potential relevance to patients with cardiovascular disease (set E).

Metric covariates were dichotomized with the best cutoff value for predicting CV-AEs (found by Cox regression, similar to that of the search for the NT-proBNP cutoff value). The choice of this data- adapted dichotomization allowed the covariates to present an optimized competitor to challenge the predictive power of NTproBNP concentration. A test result was considered statistically significant when the P value was =0.05. Because the study was hypothesis-generating, we deemed that no adjustment for multiple testing was necessary.

The study was not powered to detect differences in CV-AE rates (no control for beta error). Therefore, the lack of statistical significance does not disprove the presence of significant effects or interactions.

Table 3. Cox proportional hazards regression for time to first CV- AE during 200-day follow-up.a

Results

STUDY PARTICIPANTS

Table 2 summarizes the baseline characteristics of the 433 study patients. The median NT-proBNP value at baseline for the entire study cohort was 64 ng/L (quartile 1,31 ng/L; quartile 3,125 ng/L). The distributions of baseline NT-proBNP values for the comparison group and the rescue-medication groups did not differ markedly. The proportions of patients who received rescue medication consisting of coxibs, tNSAIDs, or glucocorticoids were similar across all incremental doses of the study drug Ro 113-0830 and placebo controls (data not shown). We observed 82 mild to serious CV-AEs during an observational period of 200 days. CV-AE incidence was not related to the dosage levels of the study drug (data not shown).

NT-proBNP and CV-AEs. Of the 433 study patients, 144 patients had increased NT-proBNP values (above the 100-ng/L cutoff value). Sixty- two of these patients were in the comparison group, and there were 7 CV-AEs in this group (11.3%). Twenty-two (26.8%) of the 82 patients with NT-proBNP values > 100 ng/L in the any-inhibitor group experienced a CV-AE overall (see Table 1 in the online Data Supplement), with 19 of these CV-AEs occurring within the first 200 days.

Table 3 also presents hazard ratios obtained from the Cox regression models for the occurrence of CV-AEs in the rescue- medication groups vs the comparison group and in the patients with NT-proBNP concentrations >/=100 ng/L vs patients with NT-proBNP concentrations /=100 ng/L than in the comparison group (difference not statistically significant). The coxibs group, however, had a 3.65-fold higher risk for CV-AEs than the comparison group (P

The risk (i.e., hazard ratios) for CV-AEs in patients with NT- proBNP values >/=100 ng/L was 1.95-fold higher in the any-inhibitor group (P

Table 4. Sensitivities, specificities, and negative and positive predictive values for predicting any CV-AE with an NT-ProBNP cutoff value of 100 ng/L.a

Conversely, very few events occurred in patients if their NT- proBNP values were

The effects of the interactions between the comparison group and all rescue-medication groups and NT-proBNP status (>/=100 ng/L or /=100 ng/L and /=100 ng/L and occurred earlier in the patients in the rescue-medication groups than in the comparison group.

An NT-proBNP cutoff value of 100 ng/L vs 125 ng/L A clinically more conservative cutoff value of 100 ng/L was slightly superior to 125 ng/L for stratifying CV-AE risk in these patients. Compared with the 125-ng/L cutoff value, the 100-ng/L cutoff exhibited higher sensitivities (75.0% vs 58.3%) and higher negative predictive values (90.9% vs 86.1%) in the coxib group. Given its higher negative predictive value, we considered the 100-ng/L cutoff to be better suited for identifying those individuals who might be treated safely with coxibs. Discussion

The results of our pilot study suggest that the NT-proBNP concentration may be useful in determining the extent of the cardiovascular risk in OA patients who are treated with antiinflammatory agents. NT-proBNP values >/=100 ng/L at baseline identified patients at increased cardiovascular risk when treated with these agents. Specifically, patients who had received coxibs (alone or in combination with tNSAIDs or glucocorticoids) demonstrated the highest risk increase for CV-AEs (7.41fold higher) when the NT-proBNP concentration was >/=100 ng/L. Patients treated with 2 or more antiinflammatory drugs (i.e., the multiple-inhibitor group) were exposed to considerable risk (3.6-fold higher) when the NT-proBNP concentration was increased

Fig. 1. Hazard ratios for the risk of CV-AEs associated with the use of antiinflammatory drugs and NT-proBNP values >100ng/L.

Set A, without further covariates; set B, adjusted for randomized study groups; set C adjusted for age (/=70 years), systolic blood pressure (/=144 mmHg), diabetes mellitus (no vs yes); set D, adjusted for premedkation with antithrombotics, anti-ischemics, antihypertonics, statirts/ fibrates; set E, adjusted further for values of the following baseline laboratory variables: leukocytes (/ =5.5 x 10^sup 9^/L), platelets (/=185 x 10^sup 9^/L), cholesterol (/=4.40 mmol/L), sodium (136 mmol/L), potassium (/=4.3 mmol/ L), and serum glutamic-pyruvic transaminase (/=21 U/L); comparison group, no use of antiinfiammatory drugs. Error bars indicate 95% CIs. Glucocs, glucocorticoids.

Conversely, CV-AEs rates did not appear to be increased by the use of antiinflammatory drugs in patients with NT-proBNP values 85% convincingly indicate. Our study lacks the power to say that these results definitively exclude an effect, especially in “harder” endpoints such as mortality and myocardial infarction, but it does provide a template for evaluating NT-proBNP in larger data sets. If these results are confirmed, a strategy that uses NTproBNP concentration as a marker could improve the safety of treatment with antiinflammatory agents.

The use of drugs that interfere with the production of cyclooxygenase-2- derived eicosanoids (i.e., coxibs, tNSAIDs, and glucocorticoids) appears to affect the production of prostacyclin (22-25) and thus shifts the balance between cardioprotective and prothrombotic prostanoids (26, 27). Our finding that increased CVAEs occurred only in patients with NT-proBNP values >/=100 ng/L is most likely related to this balance. It is well known that the concentrations of these regulators of vascular and kidney function (28) are often abnormal in the presence of cardiovascular disease and that evaluating NT-proBNP is an excellent way to unmask subclinical cardiovascular impairment and thus predict cardiovascular events (15-19). Coxibs and tNSAIDs both cause water and salt retention (29, 30), increase ventricular wall tension, and impair cardiac function. Individuals with increased NT-proBNP values constitute a group much more likely to have subclinical cardiovascular impairment and therefore more likely to anticipate specific or nonspecific CV-AEs than those without increased NT- proBNP concentrations. The CV-AEs observed in the present study included the development of edema, worsening of arterial hypertension, heart failure, angina pectoris, and a number of less severe CV-AEs. We did not have a large number of highly morbid events. The small number of major CVAEs is probably due to exclusion of patients with overt cardiac or vascular diseases, the liberal use of aspirin, and the relatively short observation period of only 200 days. In the APPROVe trial, the excess of CV-AEs in patients treated with rofecoxib did not occur before 18 months (4).

Fig. 2. Kaplan-Meier estimates for the time to first CV-AE.

(A), Patients with NT-proBNP values /=100 ng/L at baseline.

The need for an effective risk-stratification paradigm is highlighted by a recent nested case-control study of a cohort of 486 378 patients. Even patients who had no history or symptoms of coronary artery disease, hypertension, or diabetes mellitus and were receiving coxibs or tNSAIDs had a higher risk of acute myocardial infarction (31 ). Thus, screening patients for traditional risk factors may not be an effective strategy (32). Monitoring the NTproBNP concentration, which can reveal both overt and subclinical cardiovascular impairment, may be more suitable (33, 34).

STUDY LIMITATIONS

Antiinflammatory drugs were not allocated randomly in this study; however, the fact that drug administration was driven by bone pain and not by cardiovascular status allowed a study of the relationship of drug therapy to CV-AEs. Despite this limitation, it is notable that the negative predictive values of NT-proBNP concentrations were still robust.

The observational structure of our analysis is another limitation. We attempted to control aggressively for possible confounders, and the effects remained stable, even with these adjustments. At the time of this study, the use of antiinflammatory drugs appeared to be safe with respect to CV-AEs; hence, these drugs may have been used with less caution than they would be used today. Therefore, the total number of CV-AEs, particularly for nonserious AEs (e.g., silent ischemia, worsening of heart failure, or hypertension) as well as other subclinical events, such as deep venous thrombosis or pulmonary embolism, might have been underestimated.

Finally, we used an NT-proBNP cutoff value derived from our OA study population, because prior data in this area were lacking. The cutoff value chosen (100 ng/L) is close to the 125-ng/L cutoff value established for the exclusion of heart failure. Given the high degree ofbiologjcal variation in NT-proBNP measurements, we acknowledge that this value should be considered not as an absolute but rather as a guide to clinicians (34). Finally, we acknowledge that our investigation was a hypothesis-generating study and that there is a need to examine additional, larger data sets so that harder endpoint events can be evaluated more definitively.

Grant/Funding Support: This study was funded by a grant from Roche Diagnostics, Germany.

Financial Disclosures: K. Brunes is Doerenkamp Professor for Innovations in Animal and Consumer Protection. He has been and is a consultant to MSD, Novartis, and Pfizer. He received research support from the same companies. E. Giannitsis has received financial support for clinical trials from Roche Diagnostics and MSD Germany. He is a consultant to Bristol-Myers and receives honoraria for lectures from Takeda, MSD, Roche, Lilly, Novartis, BMS, Astra, and Sanofi-Aventis. H. Katus has developed the cardiac-specific troponin T assay and holds a patent jointly with Roche Diagnostics. He has received grants and research support from several companies and has received honoraria for lectures from Roche Diagnostics, MSD, Roche, Lilly, Novartis, BMS, Astra, and SanofiAventis. J. Moecks is a former employee of Roche Diagnostics and presently is a statistical consultant for Roche Phamiaceuticais. E. Spanuth is a former employee of Roche Diagnostics. A. Jaffe is a consultant to and receives research support from Dade Behring, Beckman Coulter, and Ortho Diagnostics. He is or has been a consultant to most of the major diagnostic companies, including Roche.

Acknowledgments: We are indebted to Roche Diagnostics for making the results of the study (Roche Pharma Clinical Study Protocol NI 15713 F + C) available to us and for assessing NT-proBNP in the frozen serum samples.

5 Nonstandard abbreviations: coxib, cydooxygenase-2 inhibitor; tNSAID, traditional nonsteroidal antiinflammatory drug; BNP, B-type natriuretic peptide; NT-proBNP, N-terminal proBNP; CV-AE, cardiovascular adverse event OA, osteoarthritis.

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Kay Brune,1 Hugo A. Katus,2 Joachim Moecks,3 Eberhard Spanuth,3 Allan S. Jaffe,4* and Evangelos Giannitsis2

1 Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany; 1 Department of Internal Medicine, University Hospital of Heidelberg, Heidelberg, Germany; 3 DIAneering GmbH, Diagnostics Engineering, Research and Know-How Services, Heidelberg, Germany; 4 Cardiovascular Division, Department of Internal Medicine and Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Medical School, Rochester, MN.

* Address correspondence to this author at Mayo Clinic Gonda Bldg., 5th Floor, 200 first St., Rochester, MN 55905. E-mail [email protected].

Received September 5, 2007; accepted April 4, 2008.

Previously published online at DOI: 10.1373/dinchem.2007.097428

Copyright American Association for Clinical Chemistry Jul 2008

(c) 2008 Clinical Chemistry. Provided by ProQuest Information and Learning. All rights Reserved.

Mate Availability and Unmarried Parent Relationships*

By Harknett, Kristen

Theoretically, a shortage of males in a local marriage market may influence the formation, quality, and trajectory of unmarried parent relationships. To test these hypotheses, I combine city-level sex ratio data from the U.S. census with microdata on unmarried couples who recently had a child from the Fragile Families and Child Wellbeing study. A shortage of men in a marriage market is associated with lower relationship quality for unmarried parents. Male shortages are associated with lower rates of marriage following a nonmarital birth, in part because of the mediating influence of relationship quality. A shortage of men is not significantly related to the economic quality of male, nonmarital childbearing partners. In many U.S. cities, single women in their 20s and 30s outnumber men. These sex ratio imbalances come about because of differential migration by sex and higher rates of mortality for males than females (Case and Paxson 2005). Sex ratio imbalances have been exacerbated in recent decades by an exponential increase in incarceration, which has disproportionately affected young and African American men (Pettit and Western 2004). Sex ratios for different racial/ethnic groups vary widely across localities, offering the opportunity to examine the influence of sex ratio imbalances on social demographic outcomes.

Research has shown that a shortage of men relative to women in a local marriage market is associated with lower rates of ever marrying as well as higher rates of nonmarital childbearing and divorce (Fossett and Kiecolt 1993; Lichter et al. 1992; Lichter, LeClere, and McLaughlin 1991; South and Lloyd 1992; South, Trent, and Shen 2001). This article considers some potential consequences of male shortages that have not been examined previously: do women have children with less economically desirable men in marriage markets where men are in short supply? Do unmarried parents have lower quality relationships in contexts where men are in short supply? Connecting these analyses with prior research on ever marrying, I also consider whether male shortages inhibit marriage following the birth of a child because they are associated with lower quality childbearing partners (in economic terms) and lower quality relationships.

If marriage markets affect the economic quality of childbearing partners, the quality of parent relationships, and marital transitions after a birth, these processes have implications for child well-being. In recent years, over one-third of children were born outside of marriage in the United States (Sutton and Matthews 2004). If women have children with economically undesirable men in places where men are in short supply, children are more likely to grow up in economically insecure households. If parent relationships are low quality when men are in short supply, fathers in these contexts may be less involved with their children (Erel and Burman 1995), and child well-being may be compromised (Howes and Markman 1989). If male shortages inhibit transitions to marriage, children born in these contexts will be less likely to be raised by two parents. Therefore, in marriage markets that are unfavorable for women, children born to unmarried parents may be particularly prone to the disadvantages associated with single-parent families and father disengagement (Amato and Gilbreth 1999; McLanahan and Sandefur 1994).

To examine the influence of marriage markets on partner economic quality, relationship quality, and transitions to marriage, I combine marriage market data from the U.S. census with data from the Fragile Families and Child Wellbeing study on unmarried parents. The study includes 20 cities that vary widely in their marriage market characteristics, offering the opportunity to test theoretical predictions about how marriage markets influence mate selection and union formation processes.

THEORY AND PRIOR RESEARCH

Theoretical Expectations

Individuals search for romantic partners in particular marriage market contexts that may be relatively more or less favorable. Research typically assumes that marriage markets are segmented by racial/ethnic group, age group, and geographic area, and that individuals search for partners within these boundaries. Consequently, some men and women will face favorable marriage markets in which they have a relatively large number of partners from which to choose and with relatively little competition for these partners, but others will face unfavorable markets in which partners are in short supply and competition for these partners is stiff.

Marriage markets and partner quality. Many authors have drawn parallels between job search and marital search processes (Becker 1981; England and Farkas 1986; Hutchens 1979; Oppenheimer 1988). For example, the strength of the labor market influences the job that one can get and one’s minimum standards for a job. Along these lines, marriage markets can be predicted to influence the quality of the partner that one can attract and the minimum quality partner that one will accept. Similar to the search for a job in a particular labor market, the search for a romantic partner involves gathering information about the distribution of opportunities and then choosing the best available opportunity, given one’s own qualifications and attractiveness. In an unfavorable marriage market, an individual may be unable to attract a high quality partner and thus may lower his or her standards required for a partner. The process of lowering standards when faced with an unfavorable marriage market is similar to lowering one’s reservation wage in an unfavorable labor market. In theory, women can be expected to accept less economically desirable childbearing partners when faced with a shortage of potential partners and to find more economically desirable partners when potential partners are in relative abundance. In any marriage market context, one’s own characteristics also affect the quality of partner that one can attract.

In the case of a job, salary, hours, and working conditions all contribute to quality. Although the quality of a childbearing partner is more subjective, prior research gives some indication of the attributes that are in demand on the marriage market. Research has consistently shown that men’s earnings and earning potential are positively related to marriage and marital stability (Lichter et al. 1991; Sweeney 2002; Xie et al. 2003). All else equal, men who are employed and have more earning power and education are expected to be more desirable partners. These are by no means the only measures of childbearing partner quality, but these attributes can be used to test theoretical predictions about marriage markets and partner quality.

The formation of a relationship requires the cooperation of both parties. Notably, taking the male or female perspective yields the same predictions about marriage market influences on partner quality. In an unfavorable marriage market, women may be more willing to have a child with a man who is unemployed or earns a low wage, and they may have a harder time attracting an economically desirable man because of the stiff competition for this type of partner. Meanwhile, in this context, men may perceive that many opportunities for romantic partners are available to them; consequently, they may be less willing to commit to fatherhood or marriage.

To summarize, theory predicts that a shortage of males may lead to partnerships between women and economically unattractive male partners. Alternatively, the local supply of partners may have no effect on the economic quality of male childbearing partners. Women may prolong their search and postpone childbearing until they find a partner who meets their standards (Oppenheimer 1988). Some women may expand their search by going outside their local marriage market to find a suitable partner. Other women may forgo childbearing if they never find an adequate partner (Heaton, Jacobson, and Holland 1999). Therefore, an alternative hypothesis is the null hypothesis that marriage market conditions will not influence the economic desirability of male childbearing partners.

Marriage markets and relationship quality. In addition to influencing the economic quality of male partners, marriage markets may influence the quality of couple relationships. Theoretically, the sex in short supply will have more bargaining power in their relationships because alternative romantic partners are relatively easy to come by (Guttentag and Secord 1983). Household bargaining models suggest that the pool of alternative partners influences relationship quality. If one partner perceives that his or her utility would be higher outside the relationship given other available partners, this can lead to a noncooperative equilibrium within the relationship, reflected by lower relationship quality (Lundberg and Pollak 1996). England and Folbre (2002) argued that children tip the bargaining scales in men’s favor. Women’s greater attachment to children and their custodial responsibility for children decreases women’s utility outside of marriage and makes women’s investments in their relationship relatively insensitive to marriage market conditions. Qualitative research supports the asymmetry in bargaining power in relationships when children are involved. Anderson’s (1989) ethnographic account of young, inner- city adults described women’s aspirations for a middle class, nuclear family juxtaposed against men’s desires for casual sex and to avoid responsibility for children. Therefore, one can predict that relationship quality will be better in marriage markets that favor women. Relationship quality is multifaceted and has been measured in many ways in prior research (Norton 1983). Recent research using the Fragile Families and Child Wellbeing study derives a supportiveness scale based on the perceptions that a partner is fair, loving, supportive, and not often critical (Carlson and McLanahan 2006; Carlson, McLanahan, and England 2004). This same research has operationalized low relationship quality as frequent conflicts in common areas of disagreement for couples: time, money, sex, substance abuse, pregnancy, and faithfulness. In this article, a father’s presence at the hospital during or after baby’s birth is also taken as an indicator of some amount of commitment to the mother and child. A final, indirect indicator of relationship quality is the father’s multipartnered fertility. Prior quantitative research suggests that a father’s children from prior relationships detract from the time and resources that he can devote to his new family (Cooksey and Craig 1998; Manning and Smock 1999, 2000). Prior qualitative research suggests that a father’s having children from prior relationships creates tension in his relationship with the mother of his most recent child (Monte 2007). Marriage markets that favor women are expected to be associated with better relationship quality on each of these measures.

Marriage markets and transitions to marriage. Marriage markets in which men are in short supply are theoretically expected to inhibit marriage. The literature on male shortages and rates of marriage generally focuses on two explanations. First, a numeric shortage of men will constrain women’s ability to marry because there are too few men to go around (Wilson 1987). This mechanism is not relevant for the current article because all women in the sample have found men with whom to have children. Instead, this article focuses on the quality and trajectory of the parent relationships. Second, shortages of men are expected to affect marriage by influencing bargaining power and commitment in relationships ( Guttentag and Secord 1983; Lundberg and Pollak 1996). Men are expected to be less committed to their female partners and less likely to marry when they perceive that available alternative dating opportunities are plentiful (Willis 1999; Wilson 1996). I examine this mechanism later in the analysis of marriage markets and relationship quality. A third possibility that has received less attention in the literature is that women are more likely to form relationships with low quality men in unfavorable marriage markets. In unfavorable marriage markets, women may have children with men whom they do not deem marriageable (Edin and Kefalas 2005) and with men who are unwilling to commit to marriage (Anderson 1989). I examine this third mechanism later in the analyses of the economic quality of male partners and of transitions to marriage.

Prior Empirical Research

An extensive body of research has examined the relationship between marriage markets and marriage rates (Fossett and Kiecolt 1993; Kiecolt and Fossett 1995; Lichter et al. 1992; Lichter et al. 1991; South 1996; South and Lloyd 1992). In general, this research suggests that shortages of males are associated with lower rates of ever marrying. This research has typically measured marriage markets using crude sex ratios defined by age, race/ethnicity, and locality. Although these assumed marriage market boundaries are an oversimplification, prior research has demonstrated that crude sex ratios are more strongly predictive of social demographic outcomes than more refined marriage market measures, such as availability ratios (Fossett and Kiecolt 1991; Goldman, Westoff, and Hammerslough 1984; Lampard 1993). Therefore, crude sex ratio measures of marriage markets continue to prevail in marriage market research.

Most prior research on marriage markets and marriage rates has focused on rates of ever marrying in the aggregate or on individual- level transitions to marriage without taking children into account. In contrast, this article focuses in particular on parental relationships and transitions to marriage following a birth. One prior study found evidence that un favorable marriage markets inhibited transitions to marriage following a nonmarital birth (Harknett and McLanahan 2004). Although this prior study was primarily focused on explaining racial and ethnic differences in marriage, the authors presented some evidence that marriage markets are correlated with partner and relationship quality. The current article builds upon this earlier work by (1) analyzing these correlations in a multivariate context, controlling for a range of mother characteristics; (2) using an appropriate, multilevel modeling approach; and (3) examining the mediating role of partner and relationship quality in the relationship between marriage markets and marriage transitions.

Research linking marriage market characteristics to the quality of male partners or the quality of relationships is scarce. The existing research focuses on marital relationships that may or may not include children. Trent and South (2003) combined data from the National Survey of Families and Households with census data and found no relationship between marriage market conditions and reported marital happiness. Lichter, Anderson, and Hayward (1995) combined data from the National Longitudinal Survey of Youth with census data and found mixed evidence on the relationship between marriage markets and the quality of marital partners. In unfavorable marriage markets, women were more likely to marry men with relatively low economic status. However, the strength of the marriage market was not related to educational assortative mating; unfavorable marriage markets did not lead more women to marry down in terms of education.

By focusing on unmarried parents who recently had a child, this article provides evidence on how marriage markets affect the quality of children’s fathers. A recent book by Edin and Kefalas (2005) analyzed qualitative interviews with 162 unmarried mothers, shedding light on women’s marriage and childbearing decisions in an unfavorable marriage market. These authors found that low-income women place a high value on children and are unwilling to forgo childbearing if they do not find a marriageable man. Quantitative research has also suggested that low-income women are the most likely to have children outside of marriage and that voluntary childlessness is far more common among women with higher incomes (Abma and Martinez 2006; Ellwood and Jencks 2004). Qualitative evidence from the male perspective has suggested that men are reluctant to commit to a relationship when alternative partners are relatively numerous (Wilson 1996). Together, this research has suggested that women-at least, low-income women-may settle for low quality childbearing partners when faced with an unfavorable marriage market and that male partners in these contexts may be reluctant to marry. This article focuses on unmarried parent couples in urban areas, a population that tends to be relatively economically disadvantaged.

Based on prior research, this article tests the following set of hypotheses. First, unfavorable marriage markets for women will be associated with less economically desirable male, nonmarital childbearing partners. Second, unfavorable marriage markets for women will be associated with lower relationship quality among unmarried parents. Third, in unfavorable marriage markets, unmarried parents will be less likely to marry following a nonmarital birth in part because male partners are less economically desirable and relationships are lower quality.

DATA AND METHODS

This article uses recent data from the longitudinal Fragile Families and Child Wellbeing study (hereafter referred to as the Fragile Families study). The study oversampled unmarried parents, and the analysis in this article is based exclusively on the unmarried sample. I use data from baseline interviews with unmarried mothers and fathers who had just had a baby and from follow-up interviews with mothers both 1 year and 30 months after the birth. The baseline interviews were conducted between 1998 and 2000 in 20 large U.S. cities. Response rates to the baseline survey were 87% for unmarried mothers and 75% for unmarried fathers. Of those unmarried mothers included in the baseline survey, 90% responded to the 1-year follow-up survey, and 88% responded to the 30-month follow-up survey. Cities were randomly selected for inclusion in the study from among U.S. cities with populations of over 200,000 and were stratified by policy and labor market context. The Fragile Families unmarried sample is representative of nonmarital births in large U.S. cities. For more details on the design of the Fragile Families study, see Reichman et al. (2001).

One city in the study, Norfolk, VA, is an outlier on the main independent variable-the crude sex ratio-because a mostly male military base is located in that city. Therefore, couples in Norfolk (n = 74) are excluded from the analysis sample. Parents who were not African American, Hispanic, white, or Asian are excluded from the sample because of small cell sizes or because sex ratio data could not be determined for other ethnicities (n = 311). Cases missing data on any dependent variable are excluded (n = 944). After these sample restrictions, the analysis is based on 2,382 unmarried couples.

Dependent Variables

Measures of partner quality. The fathers’ economic quality is measured at baseline by variables indicating that the father was employed in the week before the child’s birth (0/1), that the father completed some college (0/1), and the father’s predicted hourly wage. The father’s predicted hourly wage is based on fathers’ self- reports of their earnings at their current job or the last time they worked. About one-third of fathers were missing wage data because they were nonrespondents to the baseline survey, did not volunteer wage information, or had never worked. For all fathers, predicted hourly wages were estimated based on a regression of fathers’ reported hourly wages (for those with nonmissing wage data) on fathers’ characteristics, such as age, education, race/ethnicity, and city of residence. In this analysis, predicted wages are used for all fathers, even those who had nonmissing wage data. The predicted wage measure should be interpreted as an estimate of the father’s earning potential rather than as a measure of his actual wages. Father quality is also measured relative to the mother’s characteristics at baseline. The two measures of relative quality are the ratio of father’s to mother’s predicted hourly wages, and whether the father has as much or more education than the mother (0/ 1). For the wage ratio measure, mothers’ predicted hourly wages are estimated in the same way as for fathers (as explained earlier). The relative education variable is based on four levels of educational attainment: less than a high school diploma, high school diploma only, some college, and college degree or higher. If a father and mother fell into the same educational category or if the father had a higher level of educational attainment than the mother, the father was coded as having as much or more education as the mother. Table 1 presents descriptive information on the economic quality of unmarried fathers. Most fathers are employed and have as much or more education than their female partners. Only about one-fourth of fathers have some college education. The average father in the sample could earn about $11 per hour if employed, and father’s predicted wages exceeded mother’s by about one-third.

Measures of relationship quality. Following Carlson et al. (2004), relationship quality is measured using a scale that combines mother and father reports of whether the other parent is fair, loving, helpful, and critical based on the following questions:

Thinking about your relationship with [BABY’S FATHER/MOTHER], how often would you say that:

S/he is fair and willing to compromise when you have a disagreement?

S/he expresses affection or love for you?

S/he encourages or helps you to do things that are important to you?

S/he insults or criticizes you or your ideas?

Parents answered these questions on scale of 1 to 3 representing “never,””sometimes,” or “often,” respectively. The scale for each parent represents the average response to these four questions, with responses to the insults or criticizes question reverse-coded. Therefore, higher values on the scale represent higher relationship quality. In this article, relationship quality is treated as a characteristic of the relationship rather than as a characteristic of an individual mother or father; therefore, mother’s and father’s reports of relationship supportiveness are averaged together. When fathers did not respond to surveys, mothers’ reports of relationship supportiveness are used in place of their average report. The scale has a Cronbach’s alpha reliability of .65. Although mother and father reports of relationship quality do not always agree, analyzing the mother’s and father’s reports of relationship quality separately yields results consistent with the average reports I present.

I include an additional scale measuring conflict in relationships. This scale sums the number of areas in which the parents have frequent disagreements among the following areas: time, money, faithfulness, the pregnancy, sex, and drugs. Mother and father reports are averaged together. The alpha reliability for this scale is .77.

As shown in Table 1, reported relationship supportiveness is high (2.6 out of 3 on the scale), and relationship conflict is low (0.7 out of 6 on the scale). These measures of relationship quality were collected soon after the baby’s birth, when parents may have been unusually positive about their relationships. The interest in this article is not in the level of relationship quality but rather in the comparison of relationship quality across marriage markets. The unique time of data collection may have minimized variation in reports of relationship quality. If so, this analysis may underestimate the difference in relationship quality across marriage markets.

A third measure of relationship quality is a dummy variable indicating whether the father visited the mother in the hospital during or after the birth of their child. The Fragile Families sample was drawn from births in hospitals, so all mothers gave birth in a hospital. Table 1 shows that 83% of fathers visited the mother and baby in the hospital.

A final measure of relationship quality is a variable indicating that the father does not have a child with a previous partner (0/ 1). The measure of the father’s children from previous partners is based on data collected in the 1-year follow-up survey. For fathers who were nonrespondents to the survey, mothers’ reports of father characteristics were used. Table 1 shows that 58% of fathers did not have any children with previous partners, meaning that a large minority of fathers (42%) did have children from prior relationships.

Transitions to marriage. Marriage is measured in the mother’s 30- month follow-up survey and is defined as marriage to the baby’s father. Only 2% of mothers were married to someone other than the father at the 30-month follow-up, and they are coded as not married to baby’s father. Table 1 shows that 15% of unmarried parents were married by the 30-month follow-up interview.

Independent Variable

Measuring marriage markets. I use crude sex ratios to measure the supply of males relative to females in a local marriage market. Consistent with prior research, I focus on heterosexual relationships and make the simplifying assumption that marriage markets are segmented by age, city, and race/ethnicity (Fossett and Kiecolt 1991). The presence of gays and lesbians in the localities I study is a source of imprecision in my measure of the heterosexual marriage market. Crude sex ratios are defined as the ratio of 18- to 34-year-old men to women by city and racial/ethnic group. In this sample, 92% of mothers and fathers fell in this age range at the time of their baby’s birth. The analysis includes 19 cities and 4 racial/ethnic groups, yielding 76 (19 x 4) possible marriage markets. Because some cities did not have any Hispanic or Asian parents in this sample, the analysis includes 64 marriage markets after these empty cells are excluded.

Crude sex ratio data come from the 2000 U.S. census. As shown in Table 1, sex ratios vary widely across cities in the analysis sample: from 0.73 (Milwaukee, WI) to 1.12 (San Jose, CA) for African Americans; from 0.96 (Corpus Christi, TX) to 1.65 (Indianapolis, IN) for Hispanics; from 0.92 (Oakland, CA) to 1.14 (Newark, NJ) for whites; and from 0.86 (Richmond, VA) to 1.25 (Austin, TX) for Asians.

All marriage market research in the United States that relies on census estimates of mate availability faces the problem of the differential undercount. African American men are more likely to be undercounted in the census than men in other racial/ethnic groups or than African American women (Robinson et al. 1993). Some authors argue that those not counted in census enumeration are likely to be excluded from the marriage market because they belong to marginalized subpopulations, such as the homeless (South and Lloyd 1992; Spanier and Glick 1980). The census remains the best source of data on mate availability, but potential bias from the differential undercount should be kept in mind when interpreting results.

For mixed race/ethnicity couples (11% of the sample), the marriage market definition varies for the mother and father. The assumption that marriage markets are segmented by race/ethnicity does not apply to these couples. For the purposes of the analysis, I make two assumptions for mixed race/ethnicity couples. First, the supply of partners from the woman’s perspective will be related to the economic quality of her childbearing partner. If a woman has many alternative partners, she will choose and be able to attract a male partner who is employed, has relatively more earning power, and has relatively more education. Second, the supply of partners from the man’s perspective will be related to relationship quality and to marriage transitions following a nonmarital birth. If a man has many alternative partners, he will be less committed in his relationship with the mother, relationship quality will suffer, and the couple will be less likely to marry. The sex ratio variable for mixed race/ ethnicity couples is defined accordingly in the upcoming analyses. In particular, marriage markets are defined according to mother’s race/ethnicity in analyses of father’s economic characteristics and according to father’s race/ethnicity in analyses of relationship quality and transitions to marriage. The choice of mother’s or father’s racial/ethnic group in defining the marriage market for mixed race/ethnicity couples does not alter the pattern of results.

In this analysis, most incarcerated men are excluded, de facto, from crude sex ratios because the sample is exclusively urban and because prisons are almost exclusively located in nonurban areas. Explicitly excluding incarcerated men and women has very little effect on the sex ratio for this sample. In separate analyses, I tested several alternative measures of the marriage market. Substituting the nonincarcerated male/female ratio, the employed male/female ratio, or the unmarried male/female ratio for the crude sex ratio yielded the same pattern of results presented. Using different age cutpoints (20-34, 20-29, or 20-39 years) for the sex ratio definition also yielded the same pattern of results. Control Variables

In most models, I control for the following characteristics of mothers measured at baseline: age in years, race/ethnicity (African American; Hispanic; with white, non-Hispanic and Asian, non- Hispanic as the reference cell),1 immigrant (0/1), mother and father have a different race/ethnicity (0/1), predicted hourly wage ($), education (high school diploma, some college, with less than high school as the reference cell), received welfare or food stamps in the prior year (0/1), and self-reported fair or poor health (0/1). I also control for the presence of mother’s children from prior partners (0/1) measured at the 1-year followup survey. In models predicting the relative quality of male partners (father’s predicted wages or level of education relative to the mother’s), I omit controls for mother’s wages and education, which are encompassed by the relative quality dependent variables. Regression estimates were used to predict missing values on control variables, and a dummy variable is included in regression models to indicate that data were imputed. No more than 4% of cases were missing on any one variable. Table 1 presents the mean values for individuallevel control variables.

As a test of robustness, I include controls for contextual variables that may be correlated with sex ratios and outcomes: the local divorce rate, nonmarital childbearing rate, unemployment rate, and an estimate of the census undercount in the city. These data were derived from the census, the Bureau of Labor Statistics, and vital statistics. Table 1 summarizes these contextual variables for the 19 cities included in the analysis. Including these contextual control variables does not alter the pattern of results presented. The results from these robustness checks are discussed in the text but are not presented in tables.

Multilevel Modeling Approach

The analytic models that follow combine data measured at the marriage market and the individual levels; therefore, I use multilevel regression models. I use the Stata xtmixed procedure to estimate multilevel linear models for continuous outcomes, and the Stata xtmelogit procedure to estimate multilevel logistic regression models for dichotomous outcomes. I use the Stata xtmepoisson command for the relationship conflict variable because this is a left- skewed count variable. Each of these models is specified with a random intercept and fixed slopes.

An advantage of multilevel models is that they provide estimates of the level-2 variance in dependent variables: in this case, the variance across marriage markets. The null, randomintercept model shows that all of the dependent variables vary significantly across marriage markets. When the crude sex ratio is added as a predictor, the variation in relationship quality across marriage markets is no longer significant. Crude sex ratios also account for most of the variation across marriage markets in transitions to marriage after a nonmarital birth. In contrast, the father’s economic characteristics continue to vary significantly across marriage markets even after controlling for crude sex ratios. The subsequent tables and results focus on the relationships between crude sex ratios and dependent variables.

RESULTS

Table 2 summarizes the relationship between sex ratios and five measures of the economic desirability of male, nonmarital childbearing partners. Sex ratios are expected to be positively associated with each of these measures. For each of the five measures of the economic desirability of male partners, sex ratios have the expected positive sign. However, for only one outcome measure is the relationship statistically significant.

In favorable marriage markets, women are more likely to have a child with a male partner who has at least as much education as they do, and women are less likely to partner down in terms of education. In a favorable marriage market, a woman is no more likely to have a child with a man who is employed or who has higher predicted wages, higher predicted wages relative to her own, or some college education than she is in an unfavorable marriage market. Separate analyses show that the local unemployment rate is also not related to the economic or educational characteristics of fathers.

The economic quality of a male partner has much more to do with mother’s own characteristics than it does with the marriage market or local economy. Mothers’ predicted hourly wage and education are positively correlated with fathers’ employment, predicted wages, and education. Older and immigrant mothers also tend to have partners who are more economically desirable. In contrast, African American mothers as well as mothers who crossed racial/ethnic lines in their relationships have partners with lower predicted wages and who are less likely to be employed, and Hispanic mothers have partners with lower predicted wages and lower levels of education. Mothers’ welfare receipt is also associated with less economically desirable partners. Perhaps surprisingly, mothers who had children with previous partners are more likely to partner up in terms of predicted wages and to partner with a man with as much or more education. This finding is consistent with research from the Fragile Families study showing that women who repartner in the study do so with higher quality men (Bzostek, Carlson, and McLanahan 2007).

Table 3 shows the relationship between sex ratios and four measures of relationship quality. Favorable marriage markets are associated with better quality relationships by all four measures. Marriage markets that favor women are associated with significantly more supportive relationships and less relationship conflict. Additionally, in marriage markets that favor women, fathers are more likely to demonstrate some level of commitment to the mother and baby by visiting the hospital during or after the baby’s birth. Finally, in marriage markets that favor women, fathers are less likely to have children with a previous partner.

In addition to marriage markets, some mothers’ characteristics are also predictive of relationship quality. Immigrant mothers have more supportive relationships and less relationship conflict than nonimmigrant mothers. Older mothers, mixed-race couples, and mothers in poor health have more relationship conflict than their counterparts. As reported in prior research, older mothers and African American mothers are more likely to have children with men who have children from previous partners (Carlson and Furstenberg 2006). Also, mothers with children from a previous relationship are more likely to partner with fathers who also have children from a previous relationship. African American mothers are less likely than other mothers to be visited in the hospital by fathers at the time of the birth.

Table 3 focuses on local sex ratios, but other features of the local context-such as the unemployment rate or the prevalence of divorce and nonmarital childbearing-may be correlated with sex ratios and the quality of unmarried parents’ relationships. Depressed labor markets may lead to male shortages and to low relationship quality. However, in separate analyses (not shown), I find that controlling for the city unemployment rate does not alter the reported relationship between sex ratios and relationship quality. High rates of divorce and nonmarital childbearing may lead to a normative climate of low commitment and less investment in relationships. Controlling for the local divorce rate and the nonmarital birth rate does not alter the positive and significant relationship between sex ratios and better quality relationships. Controlling for the estimated census undercount in a city, which may bias estimated sex ratios, has no effect on the relationship between sex ratios and relationship quality.

Table 4 examines transitions to marriage after a nonmarital birth. Model 1 estimates the relationship between sex ratios and marriage after I control for mother characteristics. Higher sex ratios are positively associated with marriage following a nonmarital birth. Holding mother characteristics constant, moving from a context in which men are in large shortage (sex ratio = .80) to a context in which men are in large surplus (sex ratio = 1.20) increases the predicted probability of marriage from .12 to .20 based on the Model 1 regression estimates. Mother characteristics are related to transitions to marriage in the expected manner: African American mothers, couples of mixed race/ethnicity, and welfare recipients are less likely to marry, whereas mothers with at least a high school education and mothers who are immigrants are more likely to marry.

Model 2 shows that relationship quality and father’s economic characteristics are associated with marriage. The father’s predicted hourly wage is positively associated with marriage, but his employment status, education, and wages and education relative to the mother are not. Couples with more supportive relationships are more likely to marry, but the extent of relationship conflict is not related to marriage. Couples are more likely to marry if fathers visited the hospital at the time of their baby’s birth and if fathers had no children with a previous partner.

Model 3 includes sex ratios, father quality, and relationship quality measures as predictors. The relationship between sex ratios and marriage is still positive and statistically significant but smaller in magnitude after I control for the quality of partners and the quality of relationships. Controlling for other characteristics of localities-divorce, nonmarital childbearing, and unemployment- and for estimates of the census undercount does not alter the reported relationship between sex ratios and marriage. Returning to the hypotheses proposed earlier in this article, the results from Tables 2-4 can be summarized as follows: (1) marriage markets are not associated with the economic desirability of male, nonmarital childbearing partners; (2) marriage markets that favor women are associated with better relationship quality among unmarried parents; (3) unfavorable marriage markets are associated with a lower probability of marriage following a nonmarital birth in part because of the lower quality of unmarried parents’ relationships in these contexts.

DISCUSSION

Marriage markets have been linked in prior research to marriage, divorce, and nonmarital childbearing. Marriage markets may also influence unmarried parent relationships in a number of ways. This article considers whether local marriage markets affect the economic quality of male childbearing partners, the quality of unmarried parent relationships, and the chance that unmarried parents will marry after a birth. The results in this article are generalizable to unmarried parents in large cities.

In marriage markets that favor women, unmarried parents’ relationships seem to be of better quality. As predicted by Guttentag and Secord (1983), parents’ relationship quality seems to suffer when men have many alternative partners but seems to improve when women have many alternative partners. This gender asymmetry in marriage market dynamics suggests that men and women exercise their marriage market advantage very differently: men invest less in the relationship with the mother, but women strengthen the relationship with the father. Norms of maternal attachment and maternal custody may make investments in the parental relationship a higher priority for mothers than for fathers (England and Folbre 2002). These findings are also consistent with research showing that the presence of children weakens women’s position in the remarriage market (Qian, Lichter, and Mellott 2005). Because my analysis measures relationship quality at one point in time, I cannot determine whether unmarried parent relationships are lower quality from their inception in the context of male shortages (a selection effect) or whether unmarried parent relationships deteriorate over time in these contexts (a household bargaining effect).

The measures of relationship quality in this article have important implications for families and children but are not comprehensive. This article measures relationship quality in terms of relationship supportiveness, relationship conflict, the father visiting the mother in the hospital, and the father having no children from previous relationships. These measures of relationship quality could be broadened to include direct measures of relationship satisfaction. Also, relationship quality is not static, and incorporating repeated measures of relationship quality in future research would be useful.

This article finds that marriage markets are not related to the economic quality of male childbearing partners. The article measures the quality of male, nonmarital childbearing partners in terms of fathers’ predicted wages, employment, and education as well as fathers’ predicted wages and education relative to mothers. In future research, the quality of male partners could be broadened beyond economic status to include measures such as how helpful men are with housework and child care.

This research on unmarried parents finds a different pattern of results from research on married couples. Whereas Lichter et al. (1995) found that marriage markets that favor women led to marriages with more economically desirable men, I find that marriage markets are not associated with the economic characteristics of unmarried fathers. Whereas Trent and South (2003) found that marriage markets were not associated with marital happiness, I find that marriage markets are associated with the quality of unmarried parent relationships. A key difference between this article and these two studies is that I analyze unmarried parents, and those studies analyzed married couples who may or may not have had children. The differing results suggest that marital status, parental status, or both are important moderators of marriage market effects.

This article also examines whether the economic quality of male partners or relationship quality may be the mechanisms through which marriage markets inhibit transitions to marriage. I find evidence consistent with a theoretical model in which unfavorable marriage markets lead to lower quality relationships, which, in turn, inhibit marriage. Nevertheless, only 15% of unmarried parents in this sample were married at the 30-month follow-up in spite of high average reports of relationship quality. The low rates of marriage in the overall sample cannot be understood simply in terms of marriage markets or the parent and relationship characteristics measured in this article. Unfavorable marriage markets and low relationship quality explain only a small portion of nonmarriage in this study.

Because of my focus on new parents, the findings have direct implications for children’s living arrangements and childrearing. My findings show that marriage markets appear to influence the characteristics of unmarried parent relationships and the transitions to marriage following a nonmarital birth. From these observations, one can speculate that children with unmarried parents will face disadvantages in unfavorable marriage markets: their parents’ relationships are lower quality, and their parents are less likely to get married after their birth. Based on this research, one can predict that children born to unmarried parents in marriage markets that favor women will fare relatively better than their counterparts in marriage markets that favor men, which is a proposition that can be empirically tested in future research.

1. White and Asian groups were combined in the reference cell because the Asian sample size is small and white and Asian groups are similar in their means on outcomes and predictors.

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*Kristen Harknett, Department of Sociology, 3718 Locust Walk, 271 McNeil Building, Philadelphia, PA 19104; E-mail: [email protected]. The author acknowledges the support of the National Institutes of Health-National Institute on Aging Grant No. P30 AG12836, B.J. Soldo, P.I.; the National Institutes of Health- National Institute of Child Health and Development, Grant No. R24 HD044964, H.L. Smith, P.I.; and the Boettner Center for Pensions and Retirement Security-all at the University of Pennsylvania. This research was also supported by a grant from the University of Pennsylvania Research Foundation. The author gratefully acknowledges comments from Kathryn Edin, Frank Furstenberg, Jean Knab, Hugh Louch, Sara McLanahan, Tod Mijanovich, Julien Teitler, and Jane Waldfogel.

Copyright Population Association of America Aug 2008

(c) 2008 Demography. Provided by ProQuest Information and Learning. All rights Reserved.

Increase in Number of Diabetes Sufferers is Linked to Obesity Rise

By Nadia Stone

More people are being diagnosed with diabetes in Devon as figures for obesity continue to grow.

The latest figures from the Devon Primary Care Trust for diabetes show 27,657 sufferers in the county, compared to 25,667 the previous year. This is an increase of nearly eight per cent in a year.

Currently there are 3,805 people in Exeter diagnosed with diabetes.

Devon Primary Care Trust said national figures for diabetes showed the total of 2.35m current sufferers was set to rise to more than 2.5m by 2010, and that part of the rise was related to the increasing numbers of obese people.

The trust also acknowledges that the predicted growth in child obesity was likely to lead to an increase in the numbers of type 2 diabetes.

Ninety per cent of all diabetes sufferers have type 2 diabetes, which is caused when too little insulin in the body is produced or cells do not react properly to the insulin. Type 1 diabetes is when no insulin is produced at all.

Steve Brown, assistant director of public health at Devon Primary Care Trust, said: “Obese young children are more likely to be obese young adults and what that brings is a whole raft of potential issues, such as diabetes, which affects diet and drugs.”

As the Echo has previously reported, more than a quarter of 10 and 11-year-olds in Devon are either obese or overweight, while a fifth of four and five-year-olds are also either overweight or obese.

Nationally about five per cent of total NHS spending is on people with diabetes, which suggests costs could rocket as the population gets fatter.

The charity Diabetes UK has argued that there are already 3,300 admissions to A&E departments every year for children suffering from diabetic ketoacidosis.

This condition, which can occur if Type 1 diabetes is undiagnosed, can lead to a coma if not treated quickly.

Douglas Smallwood, chief executive of Diabetes UK, said: “The number of children being rushed to A&E with such a life-threatening complication is shocking. In previous research by Diabetes UK, specialist diabetes staff reported that cuts in diabetes services resulted in an increase in emergency hospital admissions.”

The Royal Devon & Exeter Hospital says it has three paediatric diabetic nurses who looked after about 200 youngsters with diabetes.

One of the nurses, Suzie Hammersley, said: “We provide a seven- day-a-week service where our young patients and their families can get in touch with us for advice and support.

“Without a doubt this service has prevented patients from having to be admitted to the hospital emergency department.

(c) 2008 Express & Echo (Exeter UK). Provided by ProQuest Information and Learning. All rights Reserved.

Grateful Grandparents Organise Charity Concert

THE grandparents of a toddler whose life was saved by a heart transplant hope to raise thousands of pounds for the hospital which carried out the operation.

Last year Martha Andersen’s family were told she had just hours to live, but now the two-year-old is full of life after a transplant at Newcastle’s Freeman Hospital.

Martha’s family have finally been given the all-clear to take her home to join twin sister Matilda and brother Harry, six.

Parents, Carl, 37, and Gillian, 35, from Edmundbyers, County Durham, endured an agonising wait for a heart donor until their prayers were answered.

Grandfather Gordon Gipson, 64, of Gosforth, Newcastle, said his family would be eternally grateful to medical staff at the hospital and has organised a charity concert in aid of the Freeman’s paediatric intensive care unit.

Mr Gipson said: “By way of showing our family’s appreciation we’ve organised a charity night and hope to raise up to pounds 8,000 for the paediatric intensive care unit to help youngsters who will use the service in the future.”

The charity concert is taking place at the People’s Theatre, Newcastle, on November 10, and includes performances from North East comedian Brendan Healey, jazz singer Jason Issacs, actress Libby Davison and The Klack Band – made up of medical professionals.

Tickets are pounds 20 from Mr Gipson, tel.(0191) 284-2603 or (0797) 361-7907 or the theatre box office, tel. (0191) 265-5020.

(c) 2008 The Journal – Newcastle-upon-Tyne. Provided by ProQuest Information and Learning. All rights Reserved.

Goodroe Healthcare Solutions Earns First Office of the Inspector General Approval for Orthopedic and Spine Gainsharing Project

Goodroe Healthcare Solutions, LLC (http://www.goodroe.com/), a VHA company that helps hospitals improve their clinical quality and economic performance, announced that the U.S. Department of Health and Human Services’ Office of the Inspector General (OIG) has approved an orthopedic and spine gainsharing project for procedures performed by orthopedic surgeons and neurosurgeons. This is Goodroe’s eleventh OIG approval and its first approval for an orthopedic and spine project.

Gainsharing allows hospitals to share cost savings with participating physicians who achieve operational efficiencies. Currently, Goodroe’s gainsharing model is used in clinical areas where physicians control the majority of costs, such as cardiac catheterization procedures, open heart surgery and orthopedic and spine procedures.

While arrangements with individual hospitals vary, most allow participating physicians to be paid as much as 50 percent of the savings generated through increased hospital and physician collaboration to decrease overall costs while demonstrating quality patient outcomes. Goodroe has used the approved gainsharing methodology to identify nearly $75 million in savings for hospitals while ensuring the best quality of care for patients.

“We are very excited because this is the OIG’s first approval for a project involving orthopedic surgeons and neurosurgeons. This important step demonstrates that the government is committed to expanding use of our gainsharing methodology to improve patient care and save money,” said Joane Goodroe, founder of Goodroe Healthcare Solutions and senior vice president of VHA Inc.

Goodroe’s gainsharing model is based on documented patient information collected by Goodroe’s proprietary software and database while the patient is receiving care. The comprehensive system measures costs, identifies waste-saving opportunities and uses nationally accepted benchmarks and standards to assure quality patient care.

Acknowledging its continued interest in gainsharing and quality-focused initiatives the Centers for Medicare and Medicaid (CMS) proposed an exception to the Physician Self-Referral law (commonly referred to as “Stark”) in the CY 2009 Medicare Physician Fee Schedule issued on July 7, 2008 for Incentive Payment and Shared Savings Programs. In that proposal, CMS renamed gainsharing programs “shared savings programs,” proposed a set of standards for shared savings programs and incentive programs and outlined its philosophy requiring transparency, quality controls and safeguards against payments for referrals. Finalizing this proposal would be the first Stark Law guidance issued from CMS about these types of programs.

About Goodroe Healthcare Solutions, LLC: Since 1994, Goodroe Healthcare Solutions, a VHA company, has been on the forefront of providing cutting-edge information management technologies and processes to help hospitals reduce costs and improve quality. The company has been nationally recognized for its innovative solutions that enable hospitals to increase margins in high-cost specialty areas. In 2001, Goodroe obtained approval for its gainsharing model from the United States Office of Inspector General (OIG). Since this landmark decision, Goodroe has secured ten additional approvals for gainsharing programs in hospitals throughout the United States. To date, Goodroe has the only gainsharing model approved by the OIG. VHA, Inc. acquired Goodroe Healthcare Solutions in October 2005 to help its member hospitals improve their clinical and economic performance in high-cost specialty service areas. Although Goodroe is owned by VHA, Goodroe’s gainsharing solutions are marketed to both VHA members and non-VHA member hospitals across the United States.

 Media Contacts: Jenn Riggle (757) 640-1982, ext. 25 Email Contact

SOURCE: VHA

Charlotte Children’s Hospital Gets a Delivery From Aethon’s Train-Themed Robot This Fall

PITTSBURGH, Aug. 8 /PRNewswire/ — Aethon Inc. today announced general availability of its train-themed “JR” autonomous mobile robot to children’s hospitals across the country. Also, Aethon will make a donation to the national Make-A-Wish Foundation for each JR TUG that is deployed. The JR TUG was initially introduced at the University of California — San Francisco (UCSF) Children’s Hospital, and is currently delivering equipment to patients at Children’s Hospital of Wisconsin.

In addition, Levine Children’s Hospital in Charlotte, North Carolina, has agreed to place a JR TUG into service early this fall. Levine Children’s Hospital, one of the newest and most technologically sophisticated specialty hospitals in the country, opened its doors to pediatric patients in December. The Levine robot is being funded by a grant from the Dreamcatcher Society, a local philanthropic organization that supports the hospital.

Modeled after the title character in the children’s book “The Little Engine that Could,” JR was originally developed to help grant a wish for Jericho Rajninger, a seven-year old leukemia patient from Larkspur, California, and was donated to UCSF Children’s Hospital through the Make-A-Wish Foundation.

As part of his chemotherapy treatment Jericho had to take more than 4,000 pills. He realized that the prospect of all that medicine could be frightening for other children. Jericho believed that having the medications delivered by a robot modeled after a train might make the prospect of all those pills more pleasant.

“We were honored to make Jericho’s wish to help other sick children a reality,” said Aldo Zini, CEO of Aethon. “We are extremely pleased that the JR robots are being deployed in other children’s hospitals and hope that they will in some sense help sick children and their parents nationwide cope with a difficult experience.”

JR is based on Aethon’s TUG, a mobile autonomous robot that transports medical equipment and supplies. JR has drawers in its “caboose” from which medications can be drawn by nurses. The robot also features a conductor who speaks to children with the voice of legendary voice over actor Don LaFontaine. “Look out, here I come,””Thanks, from the bottom of my caboose,””Pardon my caboose, I’m turning around,””Engines revved and ready to go,” and “Choo choo, gotta run” are among the phrases JR speaks.

“Our JR TUG makes the delivery of equipment and supplies more efficient while offering some cheer to our young patients,” said Tom Lausten, director of Pharmacy Services at Children’s Hospital of Wisconsin. “In addition, staff is able to focus on patient care without having to worry about the logistics of delivery.”

Children’s hospitals interested in purchasing JR should visit http://www.aethon.com/contact.html.

About Aethon

Based in Pittsburgh, Pa., Aethon is a leader in affordable autonomous mobile robots for healthcare supply chain management. In healthcare, the company’s patented technology platform is redefining hospital supply chain logistics by automating the location, delivery and recovery of key assets. The net result of Aethon’s low-cost, easy-to-install, RFID-based asset utilization solution is improved caregiver efficiency and satisfaction, increased asset utilization, decreased equipment rentals, increased patient safety and satisfaction, and improved regulatory compliance. Nearly 100 hospitals nationwide have deployed Aethon’s TUG and HOMER robots. For more information, visit http://www.aethon.com/.

About Levine Children’s Hospital

Levine Children’s Hospital (LCH) is a 234-bed hospital located on the main campus of Carolinas Medical Center (CMC) in Charlotte, North Carolina. Offering more than 30 pediatric specialties, LCH is the most comprehensive children’s hospital located between Atlanta GA and Washington DC. Levine Children’s Hospital is part of Carolinas HealthCare System, the largest healthcare system in the Carolinas and the third largest public system in the nation. For more information visit (http://www.levinechildrenshospital.org/)

Aethon Inc.

CONTACT: Joe Costa of Aethon, +1-412-322-2975, [email protected]; orLisa Tristano of MARC USA PR for Aethon Inc., +1-412-562-1189,[email protected]

Web site: http://www.aethon.com/http://www.levinechildrenshospital.org/

Lothians Hospitals Winning the Battle Against Superbugs

By Gareth Rose

C.diff rate for NHS Lothian this year was down a third

THE NUMBER of hospital deaths linked to the C.diff superbug has fallen dramatically in the Lothians.

New figures show the Edinburgh Royal Infirmary and Western General are performing well compared to most major hospitals in Scotland, with some of the lowest death rates in the country.

According to the new Health Protection Scotland report, C.diff was the underlying cause of six deaths over the last six months, and present in a further 17 cases.

NHS Lothian has worked hard to minimise the threat of C.diff, which has overtaken MRSA as the most feared superbug in Scotland.

The C.diff rate for NHS Lothian in January to March of this year was down a third on the same months in 2007, from 2.06 cases per 1000 occupied bed days by people over 65 – who are the most vulnerable – to 1.26 cases.

The Scottish Government demanded a report with new figures from all health boards following an outbreak at the Vale of Leven Hospital, in Greater Glasgow and Clyde, which claimed the lives of 13 people and was a factor in five other deaths.

NHS Lothian has also been the victim of its own vigilance.

The Western General and Edinburgh Royal Infirmary have the highest rates of C.diff among patients under the age of 65, but the report said this was probably due to higher testing rates compared to other health boards.

NHS Lothian also believes there has been some inaccurate reporting by junior doctors and the true figure is lower.

HPS praised NHS Lothian’s plans to reduce the use of antibiotics – which kills good bacteria leaving the body vulnerable to infection – saying it should have an impact on C.diff cases. So far it has been shown to halve the number of cases.

The health board has also piloted voice-boxes that remind hospital staff, patients and visitors to wash their hands, and ultraviolet lights which show whether they have been washed effectively.

It believes it is winning the war on C.diff and the other deadly superbug, MRSA. The two contributed to the deaths of 375 people in Lothian hospitals over seven years.

Dr Alison McCallum, director of public health and health policy at NHS Lothian, said: “We are pleased to see external experts recognising the strength of our surveillance systems on healthcare- associated infection and suggesting that other boards might like to put similar arrangements in place. While screening of all cases of C.diff infections in people over 65 is mandatory, NHS Lothian goes further and tracks all cases from the age of one up.

“We already comply with the recommendations made, and will work with the Scottish Government on any new developments. For instance, we already have computerised tracking systems to detect cases and we already review severe cases to see where lessons can be learned.”

MRSA rates in Lothian have dropped by nearly 20 per cent since October 2007, having been stable for the previous five years.

Originally published by Gareth Rose Health Reporter.

(c) 2008 Evening News; Edinburgh (UK). Provided by ProQuest Information and Learning. All rights Reserved.

ViaViente Demonstrates Cardiovascular Benefits in New Human Trial

BOSTON, Aug. 8 /PRNewswire/ — Francis, 50, never imagined that drinking a high anti-oxidant fruit beverage every day could help protect his health — in just 1 week. That’s what he found out after participating in a clinical trial near his home in Los Angeles, Calif.

A new study conducted by Bell Ventures, shows that after just 7 days, platelet aggregation, a known indicator of cardiovascular disease (CVD), was significantly reduced in many of the participants who took the anti-oxidant product, ViaViente, twice a day.

David Bell, President of Bell Ventures, said, “These results are important because they show how a natural anti-oxidant and anti-inflammatory product like ViaViente can help protect against one of our most serious health concerns.”

Health experts recommend a daily intake of anti-oxidants, especially in their natural form. Oxidative stress causes damage to cells and contributes to aging and disease. Anti-oxidants combat effects of oxidative stress such as inflammation.

A recent independent report, A Consumer Conscious Look at Six Premium Anti-Oxidant Products, by Frank Ervolino, ND, shows that ViaViente outperformed other popular products using ORAC — an industry standard for anti-oxidant testing. This is an important indication of quality and potential benefits.

Clinical research shows the connection between what’s in the product and actual outcomes in human health.

The ViaViente study takes direct aim at the benefits to cardiovascular health of consuming a non-drug, natural food product. It correlates the consumption of ViaViente to platelet inhibition — a marker of CVD.

Why is cardiovascular health so important? The American Heart Association reports that approximately 80 million people in the United States have CVD; nearly 2,400 people die of CVD every day; more people die from CVD than from cancer, auto accidents, and Type 2 diabetes combined; an estimated 1.2 million Americans will have new or recurrent heart attacks in 2008.

Little wonder cardiovascular care is one of our most serious health concerns.

The study uses an established test to measure the reduction of thromboxane in human metabolism. Thromboxane contributes to vasoconstriction, which can increase blood pressure, and platelet stickiness which can lead to clot formation. Both are associated with higher incidence of serious cardiovascular events. Reducing the production of thromboxane can help reduce vasoconstriction and platelet stickiness.

Experts agree that there is a well established relationship between thromboxane and cardiovascular function. In fact, clinical research on it was pioneered by drug companies looking for its relationship to aspirin therapy.

Research indicates that natural anti-oxidants can be effective in reducing thromboxane. The objective of this study was to measure the effectiveness of a proven antioxidant product, ViaViente, at reducing thromboxane in humans, and having a demonstrable benefit to cardiovascular health.

The study investigated the effects of the recommended daily dose of ViaViente for 1 week after a washout period. Sixteen subjects successfully completed the protocol.

Results fell into two categories: significant improvement or no significant change. After just one week, 38% of the subjects showed significant improvement: an average of 16%.

The research team is planning a second phase that will measure results in the same subjects over one month. Bell said that he expects to see an even greater benefit among more participants.

In the mean time, Francis plans to continue taking ViaViente every day.

Kathleen J. Burkhalter is currently in the Masters in Journalism program at Harvard University. She lives in Massachusetts. You can contact the author at [email protected].

   Contact:   David Bell   [email protected]  

Bell Ventures LLC

CONTACT: David Bell of Bell Ventures LLC, [email protected]

Web site: http://www.bellventures.com/

Impax’s Spasticity Drug Meets End Point in Phase III Study

Impax Laboratories has announced that IPX056, an investigational extended-release formulation of baclofen, has met its clinical endpoints in a Phase III study of spasticity in multiple sclerosis patients.

In a 173-patient, placebo and active comparator-controlled double blind Phase III study with a seven-week open label follow on, IPX056 was shown to be effective versus placebo in reducing spasticity in multiple sclerosis patients.

IPX056 is an extended-release formulation of baclofen, the drug of choice in the treatment of spasticity, which has the potential to offer improved control of symptoms and dosing convenience.

Impax has also filed an investigational new drug application (NDA) for IPX066, a controlled-release formulation of Carbidopa/Levodopa in July 2008. The company expects to initiate studies in Parkinson’s disease patients by the end of 2008 and is targeting a new drug application submission in mid-2011.

Russia to Be Blamed for Explosion of Baku-Ceyhan Oil Pipeline – Azeri Papers

Azerbaijan’s independent newspaper does not rule out a “Russian trace” in the explosion of the Baku-Tbilisi-Ceyhan (BTC) oil pipeline near the Turkish town of Erzincan on 5 August adding that Russia has always said that the BTC is not a secure route for exporting oil to world markets.

The paper also points to traditional “warm relations” between Russian intelligence service and Kurdish organizations and reminds that immediately after the blast Russian energy route Baku – Novorossiysk pipeline was put into work.

Another opposition daily Azadliq believes that Russia and South Ossetian separatists are involved in the explosion of the pipeline quoting Georgian pundits as saying that a day before the incident, the de facto South Ossetian president’s envoy to Russia, Dmitriy Medoyev, voiced threats to explode the pipeline.

Commissioned in 2006, 1,767-km-long BTC pipeline is capable of transporting 1m barrels of oil per day.

Originally published by Zerkalo, Baku, in Russian 8 Aug 08, p 3; Azadliq, Baku in Azeri 8 Aug 08 p 6.

(c) 2008 BBC Monitoring Central Asia. Provided by ProQuest Information and Learning. All rights Reserved.

VSP Vision Care Petitions U.S. Supreme Court for Hearing on Tax-Exempt Status

RANCHO CORDOVA, Calif., Aug. 8 /PRNewswire/ — America’s largest not-for-profit eyecare benefits provider VSP(R) Vision Care and its legal team led by former U.S. Solicitor General Kenneth W. Starr today petitioned for a writ of certiorari with The Supreme Court of the United States.

VSP wants to make a final plea to the Supreme Court to regain its federal tax-exempt status. As stated directly in the VSP Supreme Court petition filed today:

“‘This case presents a critically important, recurring question regarding the standards governing the tax-exempt status of nonprofit health care enterprises, particularly nonprofit health maintenance organizations (HMOs),’ said Ken Starr, former U.S. Solicitor General.

“Without any change in statutory or regulatory law, and without any change in the operations of VSP, the IRS overturned its longstanding position, revoking VSP’s tax exemption in 2002.

“Under the common law, which this Court has held is reflected in section 501(c) of the Internal Revenue Code, nonprofit health care organizations are deemed ‘charitable’ entities that promote the ‘social welfare,’ and are thus entitled to tax-exempt status, as long as the class of subscribers is not so small that the public benefits are insubstantial. Consistent with the common law, the IRS has long taken the position that nonprofit HMOs, including petitioner Vision Service Plan (VSP), are eligible for tax-exempt status. Indeed, the IRS granted VSP a tax exemption in 1960.

“According to the IRS, a nonprofit health care organization that limits its benefits to a class of subscribers is no longer eligible for tax-exempt status, unless it also provides some as-yet-unquantified, unspecified amount of ‘community benefits.’ By condoning the IRS’ unfounded departure from the common law in a cursory, unpublished decision, the Ninth Circuit has cast tax exemption law into turmoil, introducing unprecedented uncertainty in a nonprofit industry that relies on tax exemptions in order to fulfill its basic mission of providing health care for the benefit of the community to all applicants. Indeed, the Ninth Circuit’s ruling calls into question the tax exemptions for all nonprofit health care organizations, including not just otherwise qualified health plans and HMOs, but also hospitals, nursing homes, and others.

“‘The IRS’s revocation of VSP’s tax-exempt status, over 40 years after it was initially granted, represents an unauthorized departure from the established law of charitable trusts and from the specific judgment of the 1986 Congress,’ states VSP President and CEO Rob Lynch.

“As a nonprofit entity providing care to a large segment of the community, VSP pursues a goal of maximizing delivery of health care services within the limits of its financial capacity, rather than maximizing net income:

— In 2003, the tax year in question, VSP had over 6 million enrollees, more than 40% of whom were poor or elderly beneficiaries of Medicaid, Medicare, or similar state programs;

— VSP provides millions of dollars in free vision services to uninsured or underinsured children and victims of disasters;

— even for those subscriber groups who participate at full rates, VSP has negotiated discounts with its contract providers of 20% or more off the providers’ usual and customary rates, with even deeper discounts for services provided to Medicare and Medicaid patients;

— over a third of the providers in VSP’s network are in medically underserved communities;

— VSP has no blackout provisions on enrollment and no limitation for pre-existing conditions;

— VSP has a substantial program of community outreach and patient education on the health benefits of annual comprehensive eye examinations;

— VSP uses its accumulated surplus and reserves for the purpose of providing a business safety net and improving the cost effectiveness and quality of the eye care services it provides;

— no part of VSP’s net revenues or assets can inure to any private person or be distributed as dividends; VSP’s by-laws preclude such inurement; and

— VSP’s Articles of Incorporation affirm its nonprofit business model: the Articles require that if the organization dissolves, its remaining assets are to be distributed ‘to an educational, research, scientific or health institution, organization, or association to be expended in the advancement of the science and art of optometry.”

“‘The IRS’s changed position – now condoned by the Ninth Circuit – makes it much more difficult for a nonprofit health care organization to qualify for an exemption under sections 501(c)(3) or 501(c)(4),’ said Thomas A. Fessler, VSP’s vice president and general counsel. ‘Despite the fact that the basic mission of these organizations is a charitable one – the promotion of health care – the IRS now requires something more in the way of “community benefits” or “public benefits” in order to qualify for an exemption.'”

About VSP

VSP’s family of companies includes VSP Vision Care, the only not-for-profit managed vision care company in the United States serving 55 million members; VSP Labs, industry leaders in new technologies, production processes, service and logistics; Altair, the only eyewear company that exclusively supports private-practice eye doctors; and Eyefinity(R), offering private practices innovative solutions to improve overall practice management and the patient experience.

Since 1997, VSP has provided more than 470,000 low-income, uninsured children with free eyecare. Through relationships with the American Diabetes Association, Prevent Blindness America and the Center for Health Transformation, VSP promotes the importance of annual eye exams for maintaining eye health and overall wellness.

   CONTACTS:    Andrea Collins   KCSA Strategic Communications   212-896-1232   [email protected]    Pat McNeil   VSP Vision Care   916-851-4287   [email protected]  

VSP

CONTACT: Andrea Collins of KCSA Strategic Communications,+1-212-896-1232, or [email protected]; or Pat McNeil of VSP Vision Care,+1-916-851-4287, or [email protected]

I Would Offer This Scheme to Anybody – It’s a Brilliant Experience

Amy Semper (18), from Washingborough, has graduated from the scheme and secured a place at Nottingham Trent University

I applied after finishing school and I would say to anyone that it’s a really good experience.

You think 16 is quite young but you have all the support from nursing professionals as well as the cadet scheme leaders.

It’s a first-hand experience into care and really helps you to get into further education and find out whether university is right for you.

I always wanted to help people from being little. I went for work experience in a care home when I was in year eight at school and that really made me want to get into nursing.

Being a cadet gives you a broad view of the profession and helps you make sure it’s what you want to do because there is such a high drop-out rate at universities.

People do not know what the workload is like and find it difficult on placements because you are seen as a healthcare professional.

The scheme has really made me mature. I would offer the scheme to anybody – it’s a brilliant experience.

I’m now hoping to work in mental health at an acute centre.

(c) 2008 Lincolnshire Echo. Provided by ProQuest Information and Learning. All rights Reserved.

Physicians’ Group Responds to Smear Tactics By American Meat Institute and Tobacco/Meat Industry Front Group

WASHINGTON, Aug. 7 /PRNewswire-USNewswire/ — The Physicians Committee for Responsible Medicine (PCRM) responds to news releases published recently by the “Center for Consumer Freedom” (CCF), a group funded by the tobacco, meat, and junk food industries, and the American Meat Institute (AMI), a meat-industry organization that promotes consumption of processed meats and other unhealthful products.

Both organizations, which are funded by the meat industry, aim to confuse consumers about the genuine health risks posed by processed meats. Those risks are supported by extensive scientific research, including a recent landmark report from two prestigious cancer organizations — the American Institute for Cancer Research (AICR) and the World Cancer Research Fund. The AICR report concluded that when it comes to colon cancer, there is absolutely no amount of processed meat that’s safe to eat. In fact, according to researchers, just one 50-gram serving of bacon, sausage, deli meats or other processed meat daily increases our risk of colorectal cancer, on average, by 21 percent.

Other cancer organizations, including the American Cancer Society and the National Cancer Institute, have also flagged processed meats as a cancer risk and recommend that consumers avoid processed meats or reduce their consumption of these products.

According to exposes in major media outlets, CCF was founded by tobacco lobbyist Rick Berman with more than $3 million from Philip Morris and continues to receive funding from industries that market unhealthful products. Through CCF and other front groups, Berman has fought against stricter limits on legal blood-alcohol levels, improvements in minimum wage, health information for consumers, and other progressive efforts that his commercial clients view as contrary to their interests.

Over the past few years, CCF has escalated its attacks against organizations that warn the public about the health risks associated with alcohol, meat, and other junk food products. Berman has admitted publicly that his MO is to “shoot the messenger” by trying to disparage the credibility of his opponents. His employees do not attempt reasoned discussion of the scientific issues about health. The long list of public health advocates in CCF’s line of fire includes former New York Mayor Rudy Giuliani for speaking out against drunk driving, the Centers for Disease Control and Prevention for tackling food safety, the World Health Organization for addressing obesity, and Mothers Against Drunk Driving.

As to CCF’s and AMI’s false statements about PCRM, here’s the truth. Founded more than 20 years ago, PCRM is a nonprofit 501(c)(3) organization working to promote good nutrition and higher standards in both human and animal research. PCRM both conducts clinical nutrition research and helps educate the public about preventive medicine, especially the multitude of health benefits possible with low-fat and vegetarian diets. PCRM also opposes unethical research. PCRM exposed experiments in which short, healthy children were to be injected with genetically engineered growth hormone in an attempt to make them taller. PCRM also exposed the practice of using massive estrogen doses to suppress height in tall adolescent girls. In addition, PCRM vigorously promotes alternatives to the use of animals in medical education and research through a variety of innovative programs.

PCRM’s physicians, dietitians, and scientists are leaders in their fields. They publish their work in peer-reviewed academic journals, present their findings before scientific conferences, and serve as consultants on government panels. PCRM’s president Neal Barnard, M.D. (http://www.nealbarnard.org/), for example, is a respected nutrition researcher whose research has been funded by the National Institutes of Health and published in major peer-reviewed journals. PCRM experts are also popular with lay audiences. PCRM doctors and nutritionists are frequent guests in the national and international media and popular writers in the lay press.

These industry organizations sometimes mistakenly charge that the American Medical Association (AMA) disagrees with PCRM’s nutrition policies or with vegetarian diets. This is patently untrue. PCRM did have disagreements with the AMA in the early 1990s (PCRM favored vegetarian diets, while the AMA was initially skeptical), but in February 2004, the AMA released a statement saying that its previous criticisms of PCRM’s stance on vegetarianism do not represent current AMA opinion or policy (http://www.pcrm.org/news/statement040218.html). There is no longer any acrimony between the groups. Many PCRM members are also AMA members. PCRM president, Neal D. Barnard, MD, is an AMA Lifetime Member.

CCF and other meat-industry organizations also allege that PCRM acts as a “front” for other groups. This is another unfounded and defamatory claim. While CCF is indeed an industry front, PCRM is an independent, nonprofit organization, and has been since its founding in 1985. PCRM works with a wide range of organizations promoting human health, scientific research, medical education, and protection of animals in laboratories, as well as consumer groups, hospitals, universities, corporations, and other health charities. For more information about PCRM or an interview with one of our senior staff, please call PCRM’s Communications Department at 202-686-2210, ext. 316.

Exposes and other background information about the Center for Consumer Freedom:

   -- The San Francisco Chronicle   http://tinyurl.com/5ebzk2    -- The Washington Post   http://tinyurl.com/6xfht3    -- USA Today   http://www.usatoday.com/news/opinion/editorials/2005-05-04-name-edit_x.htm    -- The American Prospect   http://www.prospect.org/cs/articles?articleId=8984    -- ABC-TV, San Francisco   http://abclocal.go.com/kgo/story?section=politics&id=4140447    -- Source Watch   http://www.sourcewatch.org/index.php?title=Center_for_Consumer_Freedom    Background information about processed meats and cancer risk:   

— The American Institute for Cancer Research advises consumers to “avoid processed meats.” http://www.aicr.org/site/PageServer?pagename=dc_recs_05_avoid_processed_meats

— A study conducted by American Cancer Society researchers concludes that “[p]eople who ate the most processed meats were 50% more likely to develop colon cancer and 20% more likely to develop rectal cancer compared to those who ate the least.”

http://tinyurl.com/2fvsec

— The American Cancer Society encourages people to “[l]imit intake of processed and red meats.”

http://tinyurl.com/5kgtma

— The National Cancer Institute: “Red meat and processed meat are associated with an increased risk of colorectal cancer, and there is also suggested evidence for some other cancers, such as prostate cancer.”

http://tinyurl.com/6bypbg

— A meta-analysis in Journal of the National Cancer Institute concludes that “Increased consumption of processed meat is associated with an increased risk of stomach cancer.”

http://jnci.oxfordjournals.org/cgi/content/abstract/98/15/1078

— USA Today article: “Put down that bacon! Report emphasizes cancer-fat links” http://www.usatoday.com/news/health/2007-10-31-cancer_N.htm

Physicians Committee for Responsible Medicine

CONTACT: Jeanne McVey of the Physicians Committee for ResponsibleMedicine, +1-202-686-2210, ext. 316; [email protected]

Web Site: http://www.pcrm.org/

Orexigen(R) Therapeutics Announces Second Quarter 2008 Financial Results

SAN DIEGO, Calif., Aug. 7 /PRNewswire-FirstCall/ — Orexigen(R) Therapeutics, Inc. , a biopharmaceutical company focused on the treatment of central nervous system disorders, including obesity, today announced unaudited financial results for the three and six months ended June 30, 2008.

Three Months Ended June 30, 2008

As of June 30, 2008, Orexigen held $35.3 million in cash and cash equivalents and an additional $88.4 million in investment securities, available-for-sale, for a total balance of cash and cash equivalents of $123.6 million. Orexigen does not have any auction rate securities on its balance sheet, and intends to continue to avoid this class of investments in the future.

For the three months ended June 30, 2008, Orexigen reported a net loss of $23.1 million, or $0.67 per share attributable to common stockholders, as compared to a net loss of $11.6 million, or $0.63 per share attributable to common stockholders, for the comparable period in 2007.

Total operating expenses for the three months ended June 30, 2008 were $23.7 million compared to $12.5 million for the comparable period in 2007. The increased operating expenses were due primarily to a $9.4 million increase in research and development expenses related to an increase in planned expenses in connection with our four Contrave(R) Phase III clinical trials, related proprietary product formulation work and consulting activities. In addition, general and administrative expenses increased by $1.7 million due primarily to increases in facilities expenses, stock-based compensation expense and costs related to sales and marketing activities, as well as an increase in salaries and personnel related costs.

Six Months Ended June 30, 2008

For the six months ended June 30, 2008, Orexigen reported a net loss of $46.3 million, or $1.40 per share attributable to common stockholders, as compared to a net loss of $23.8 million, or $2.28 per share attributable to common stockholders, for the comparable period in 2007.

Total operating expenses for the six months ended June 30, 2008 were $47.7 million compared to $25.0 million for the comparable period in 2007. The increased operating expenses were due primarily to a planned $20.0 million increase in research and development expenses associated with activities across the four Contrave Phase III studies, related proprietary product formulation work and consulting activities, as well as an increase in salaries and personnel related costs. In addition, general and administrative expenses increased by $2.7 million due primarily to increases in stock-based compensation expense, salaries and personnel related costs, facilities expenses and costs related to sales and marketing activities.

“The second quarter was marked by continued strong execution and progress in clinical development,” said Gary Tollefson, M.D., Ph.D., President and CEO of Orexigen. “As we announced during the second quarter, we have now completed enrollment in all four of our Phase III trials for Contrave. As a result, we continue to expect to be in position to file an NDA for Contrave in late 2009. We were also pleased to initiate our second Phase IIb trial of Empatic in recent weeks, keeping the Empatic program moving ahead on schedule.”

   Recent Highlights    Contrave  

— The Company has completed enrollment in all four of its planned Phase III clinical trials. Each of these trials has been designed to address key aspects of this product candidate, including the safety and efficacy of Contrave in combination with intense diet, exercise and behavior modification (NB-302), the safety and efficacy of the combination in obese diabetics (NB-304), as well as safety and efficacy of doses above and below the primary dose to provide a range of potential alternatives to physicians and patients.

— The Company was issued U.S. Patent Number 7,375,111 by the U.S. Patent and Trademark Office. This patent covers sustained release compositions of bupropion and naltrexone combined in a single dosage form. This patent, which we refer to as the Weber/Cowley composition patent, extends patent protection for Contrave in the United States by 12 years, until 2025.

— In addition, the European Patent Office, or EPO, has issued a patent covering compositions and uses of bupropion and naltrexone for effecting weight loss which has been registered in a number of EPO countries.

Empatic(TM)

— The Company initiated the second Phase IIb study of Empatic. The trial is designed to build on the safety and efficacy results from a previous Phase IIb trial of Empatic, which demonstrated robust weight loss at 48 weeks ranging from approximately 11% to 15% in obese patients completing the trial and a discontinuation rate due to adverse events that was not significantly different than placebo. Orexigen expects the results of this trial to be available in the second half of 2009.

Pipeline Programs

— Orexigen continues to make progress in the planning stages for OREX-003 for the mitigation of antipsychotic-induced weight gain and OREX-004 for the treatment of obsessive-compulsive disorder. The Phase II proof-of-concept trial for OREX-003 is expected to be initiated in this quarter. The Phase II proof-of-concept trial for OREX-004 is expected to be initiated in the second half of 2008.

Conference Call Today at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time)

The Orexigen management team will host a teleconference and webcast to discuss the second quarter 2008 financial results and recent business highlights. The live call may be accessed by phone by calling (800) 860-2442 (domestic) or (412) 858-4600 (international). The webcast can be accessed live on the investor relations section of the Orexigen web site at http://www.orexigen.com/, and will be archived for 14 days following the call.

About Orexigen Therapeutics

Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the development of pharmaceutical product candidates for the treatment of central nervous system disorders, including obesity. The Company’s lead combination product candidates targeted for obesity are Contrave, which is in Phase III clinical trials, and Empatic, which is in the later stages of Phase II clinical development. Both product candidates take advantage of the Company’s understanding of how the brain appears to regulate appetite and energy expenditure, as well as the mechanisms that come into play to limit weight loss over time. Each product candidate is designed to act on a specific group of neurons in the central nervous system with the goal of achieving appetite suppression and sustained weight loss. Further information about the Company can be found at http://www.orexigen.com/.

Forward-Looking Statements

Orexigen cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “believes,””anticipates,””plans,””expects,””indicates,””will,””intends,””potential,””suggests,””assuming,””designed” and similar expressions are intended to identify forward-looking statements. These statements are based on the Company’s current beliefs and expectations. These forward-looking statements include statements regarding the enrollment, timing, execution and completion of clinical trials of its product candidates, the timing of an NDA submission for Contrave, the potential to obtain regulatory approval for, and effectively treat obesity with, Contrave and Empatic, and the scope and duration of protection of issued patents relating to the Company’s product candidates. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risk and uncertainties inherent in the Orexigen business, including, without limitation: the progress and timing of the Company’s clinical trials; the potential that earlier clinical trials may not be predictive of future results; the ability for Contrave or Empatic to receive regulatory approval on a timely basis or at all; the potential for adverse safety findings relating to Empatic or Contrave to delay or prevent regulatory approval or commercialization, or result in product liability claims; the ability of Orexigen and its licensors to obtain, maintain and successfully enforce adequate patent and other intellectual property protection of its product candidates; and other risks described in the Company’s filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Orexigen undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

                        Orexigen Therapeutics, Inc.                       (a development stage company)                               Balance Sheets             (In thousands, except share and par value amounts)                                                   June 30,       December 31,                                                    2008              2007                                                (Unaudited)   Assets     Current assets:       Cash and cash equivalents                  $35,266           $28,967       Investment securities,        available-for-sale                         88,373            56,487       Prepaid expenses and other current        assets                                      1,563             2,471     Total current assets                         125,202            87,925     Property and equipment, net                    2,269               924     Restricted cash                                1,125             1,125     Other assets                                     941             1,346     Total assets                                $129,537           $91,320    Liabilities and stockholders' equity     Current liabilities:       Accounts payable and accrued expenses      $16,878            $8,454       Deferred revenue, current portion               88                88       Long-term debt, current portion              6,239             4,735     Total current liabilities                     23,205            13,277     Deferred revenue, less current      portion                                       1,103             1,147     Long-term debt, less current portion           7,644            11,072     Other long-term liabilities                    1,204               941     Commitments and contingencies     Stockholders' equity:       Preferred stock, $.001 par value,        10,000,000 shares        authorized at June 30, 2008 and        December 31, 2007; no shares issued        and outstanding at June 30, 2008 and        December 31, 2007                              -                 -       Common stock, $.001 par value,        100,000,000 shares authorized at        June 30, 2008 and December 31, 2007;        34,315,036 and 26,982,601 shares        issued and outstanding at June 30, 2008        and December 31, 2007, respectively            34                27     Additional paid-in capital                   249,500           171,571     Accumulated other comprehensive     income                                           109               220     Deficit accumulated during the      development stage                          (153,262)         (106,935)   Total stockholders' equity                      96,381            64,883   Total liabilities and stockholders'    equity                                       $129,537           $91,320                           Orexigen Therapeutics, Inc.                       (a development stage company)                          Statements of Operations                  (In thousands, except per share amounts)                                (Unaudited)                                                                 Period from                           Three Months           Six Months    September 12,                              Ended                 Ended           2002                             June 30,              June 30,    (Inception) to                          2008       2007       2008      2007  June 30, 2008   Revenues:     Collaborative      agreement            $-         $-         $-         $-       $174     License revenue       22         22         44         44        309   Total revenues          22         22         44         44        483   Operating expenses:     Research and      development      19,585     10,149     40,272     20,277    130,129     General and      administrative    4,092      2,347      7,411      4,708     29,582   Total operating    expenses           23,677     12,496     47,683     24,985    159,711   Loss from    operations        (23,655)   (12,474)   (47,639)   (24,941)  (159,228)   Other income    (expense):     Interest income      939      1,121      2,138      1,478      7,702     Interest expense    (397)      (277)      (826)      (336)    (1,736)   Total other     income    (expense)             542        844      1,312      1,142      5,966   Net loss           (23,113)   (11,630)   (46,327)   (23,799)  (153,262)   Accretion to    redemption    value of    redeemable    convertible    preferred    stock                   -         (3)         -        (11)       (78)   Deemed dividend    of  beneficial    conversion    for Series C    preferred    stock                   -          -          -          -    (13,860)   Net loss    attributable    to common    stockholders     $(23,113)  $(11,633)  $(46,327)  $(23,810) $(167,200)    Net loss per    share    attributable    to common    stockholders    - basic    and diluted        $(0.67)    $(0.63)    $(1.40)   $ (2.28)    Shares used    in computing    net loss    per share    attributable    to common    stockholders    - basic    and diluted        34,311     18,518     33,126     10,462  

Orexigen Therapeutics, Inc.

CONTACT: Graham Cooper of Orexigen Therapeutics, Inc., +1-858-875-8600,Media, Liz Frank, +1-212-301-7216, or Lori Rosen, +1-212-301-7173, both forOrexigen Therapeutics, Inc.

Web site: http://www.orexigen.com/

Legacy of Life ; Family of Heart Swap Girl to Help Others

By HELEN RAE

THE grandparents of heart-swap toddler Martha Andersen hope to raise thousands of pounds for the hospital which gave their child a second chance of life.

Just last year the youngster’s family was told she had only a few hours to live.

But today the two-year-old is a picture of happiness after undergoing a life-saving transplant at Newcastle’s Freeman Hospital when her tiny heart failed beyond repair.

After months in hospital, Martha’s family were finally given the all-clear to take her home to join twin sister Matilda and brother Harry, six.

Their parents, Carl, 37, and Gillian, 35, from Edmundbyers, County Durham, had endured an agonising wait for a heart donor. But on March 9, 2007, their prayers were answered when a family in the Midlands decided to donate the heart of their son.

Medics raced it to the Freeman within four hours and during a gruelling eight-hour operation Martha was given the gift of life.

Grandfather Gordon Gipson, 64, said his family would be eternally grateful to medical staff at the hospital and has organised a charity concert in aid of the Freeman’s Paediatric Intensive Care Unit.

Speaking from his home in Gosforth, Mr Gipson said: “Martha means the world to us and for her to be given a second chance of life is the best gift anyone could have asked for. She has been through so much in her little life, but she just gets on with it with a huge smile on her face. I’m so proud of how well she’s coped.

“All the medical staff at the Freeman have been unbelievable and we’re overwhelmed with what they’ve done. By way of showing our family’s appreciation we’ve organised a charity night and hope to raise up to pounds 8,000 for the paediatric intensive care unit to help other youngsters who will use the service in the future.”

The charity concert is taking place at The Peoples Theatre, in Newcastle, and includes performances from North East comedian Brendan Healey, jazz singer Jason Issacs, actress Libby Davison and The Klack Band – made up of medical professionals. Part of the money raised will go to Cancer Research UK.

The event is on November 10. Tickets are pounds 20 from Mr Gipson: (0191) 2842603 or 07973617907 or the theatre box office (0191) 265 5020.

(c) 2008 Evening Chronicle – Newcastle-upon-Tyne. Provided by ProQuest Information and Learning. All rights Reserved.

March of Dimes Mobile Health Centers Providing Care to Moms in Gulf Coast Areas Still Lacking Public Health Services

To: NATIONAL EDITORS

Contact: Robert Storace, +1-914-997-4622, [email protected], or Todd Dezen, +1-914-997-4608, [email protected], or Elizabeth Lynch, +1-914-997-4286, [email protected], all of the March of Dimes

NEW ORLEANS, Aug. 7 /PRNewswire-USNewswire/ — Three years after the hurricanes of 2005, four March of Dimes Mom & Baby Mobile Health Centers(R) are bringing much-needed maternal and infant health care to the Greater New Orleans and Gulf Coast area, especially aiding new Spanish-speaking residents who came to help rebuild the region that still is plagued by limited access to public health services.

Although almost all of the hospitals in Jefferson Parish have reopened, fewer than two-thirds are operating in Orleans Parish, and none have reopened in St. Bernard Parish.

Since their launch in 2007, the March of Dimes Mom & Baby Mobile Health Centers have provided more than 3,000 patient visits to the areas hardest hit by the hurricanes: New Orleans; its suburbs St. Bernard Parish and the Lower 9th Ward; the Lake Charles area; and Biloxi, Mississippi. The program is on target to provide more than 15,000 visits in three years.

These four March of Dimes mobile health centers bring preconception, prenatal and well-baby medical care to pregnant women, new mothers and babies who desperately need it, said Dr. Jennifer L. Howse, president of the March of Dimes. Because our centers are mobile, we can bring quality health care where its needed most, like St. Bernard Parish.

The March of Dimes Mom & Baby Mobile Health Centers continue to bring doctors, nurses, medical supplies, the latest technology and information directly to mothers and their babies, an important component of rebuilding communities. Providing access to high- quality medical care is vital to improving birth outcomes in the region.

For example, in 2004, before the hurricanes, Louisianas preterm birth rate was 15.6 percent, nearly 25 percent above the national average. In 2005, the states preterm birth rate increased to 16.5 percent. Mississippis preterm birth rate increased to 18.8 percent in 2005, from 17.9 percent in 2004.

As workers moved to the Gulf Coast to rebuild, the Spanish- speaking population significantly expanded, and access to health care is limited for them.

Many of our patients are Spanish-speaking, and because we are bi- lingual we can offer these women access to quality health care, says Rosa Bustamante-Forest, RN, MPH, MN, program director for the Mom & Baby Mobile Health Center in New Orleans. Were seeing repeat patients from last year who are pregnant again, which speaks volumes to the quality of care we offer.

The Mom & Baby Mobile Health Centers were funded through the March of Dimes Hurricane Assistance Fund that included a $3 million gift from the people of Qatar. The mobile health centers are staffed by the Daughters of Charity Services of New Orleans, Southwest Louisiana Area Health Education Center and Coastal Family Health Center.

Inside, the Mom & Baby Mobile Health Centers look like a regular healthcare providers office, with private exam areas, waiting areas and nurses station. They are equipped with fetal monitors, ultrasound and other equipment, and a backup generator. The handicap accessible centers have bilingual staff, including an obstetrician, nurse practitioner or midwife, a nurse, lab technician and an outreach worker. The vehicles have a fixed schedule at consistent locations each week so services will be dependable and expected.

The March of Dimes is the leading nonprofit organization for pregnancy and baby health. With chapters nationwide, the March of Dimes works to improve the health of babies by preventing birth defects, premature birth and infant mortality. For the latest resources and information, visit marchofdimes.comor nacersano.org.

SOURCE March of Dimes

(c) 2008 U.S. Newswire. Provided by ProQuest Information and Learning. All rights Reserved.

‘Benefits of Stem Cell Research Outweigh the Ethical Concerns’

By Steffan Rhys

CONTROVERSIAL stem cell research is crucial to the potential discovery of cures for some of the country’s most devastating illnesses, a Welsh scientist will argue today.

Dr Arwyn Jones, of Cardiff University, will tell an audience at the Eisteddfod’s main science lecture that the technology could cure diseases such as cancer, diabetes and Parkinson’s, as well as help understand conditions such as infertility.

He will say that the staunch ethical concerns of groups such as the Catholic Church, anti-abortion groups and some MPs are outweighed by the research’s potential benefits, and that some of these concerns may now diminish with the development of adult stem cell technology.

Human embryonic stem cells are usually derived after IVF treatment from a structure called a blastocyst that forms a few days following fertilisation but before it attaches to the womb and develops into an embryo.

These cells have the potential to develop into any of the tissues and organs of the body and could therefore be used as seeds to make new cells and tissues for patients suffering from many diseases. Some of the pioneering work in this field is currently being done at Cardiff University by Nobel Prize winner Professor Sir Martin Evans.

But opponents say the practice compromises the sanctity of human life as it means deriving benefits from the destruction of human embryos: fertilised eggs in early stages of development.

More extreme viewpoints say the practice is tantamount to murder, abortion, “playing God” and even paves the way for cloned human beings.

“One of the ethical arguments raised is that if you are growing stem cells you are growing a new human being. I totally dismiss that argument,” said Dr Jones, a senior lecturer in molecular cell biology at the Welsh School of Pharmacy, whose lecture is backed by the Wellcome Trust.

“The Human Fertilisation and Embryology Act does not allow scientists to work on cells past 14 days.

“But that doesn’t remove the ethical concerns. Some people believe a fertilised egg is the beginning of life and should not be tampered with in any shape or form. That is very much the view from Rome and from the White House.

“The majority of scientists working in the field would totally disagree. The potential to cure diseases outweighs these issues.

“They want to study the development of the embryo for issues like fertilisation and their potential to cure diseases. They have no interest in cloning a human being or anything as ridiculous as that.

“However, there have to be very strict guidelines as to how long we can grow stem cells or embryos in a laboratory and these are formally set out in the Act.”

The research is legal in the UK, where it is among the most advanced in the world. It is also legal in the US but no federal funding is allocated to it, following staunch opposition from the Bush administration.

Stem cells are derived from embryos not required for IVF treatment, but one of the major hurdles to the research is their limited supply.

This has led to debate on using human cells in animal embryos, another controversial practice which has provoked outrage among opponents who have painted a vision of monstrous half-animal, half- human creatures, another vision Dr Jones dismisses as absurd.

“Think of the health of society and you think of things like heart disease and cancer, and stem cell technology has the potential to cure some of them, as well as others that won’t spring immediately to mind, like blindness,” he said.

“Stem cells have the potential to assume any type of cell in the body. That is their job.

One of the uses of new technology could be to use those cells to grow new tissue.

“A person suffers from Parkinson’s due to a loss of dopamine in the brain. If you could put those cells back into a human being, then you have one way of treating Parkinson’s.

“But one of the most important aspects is that we now know that adults have stem cells in their own bodies and, therefore, there may not be a need to always use embryos.

“It is a case of finding where they are, how many different types we have, and growing those as opposed to using embryos.

“The hope is that adult stem cells will replace embryonic stem cells. But there are differences between them, the most obvious being the fact that adult stem cells have been in the body for a number of years and may not have the full potential of embryonic stem cells.

“Further, it used to be the case that you had to destroy the embryo to isolate the cell.

This is no longer the case in some cases and that alleviates some of the problems with having to destroy an embryo and, essentially, a human being, to grow stem cells.”

Yesterday, the Society for the Protection of Unborn Children (SPUC)called for embryonic stem cell research to be immediately abandoned.

“The potential for stem cell research is quite amazing and research on ethically obtained stem cells is already showing results,” said SPUC’s Paul Danon.

“But with embryonic stem cells the more serious issue is the destruction of human life.

“You are talking about an embryo that can’t give consent even if it wanted to. They are paying with their lives for this research.

Fewpeople would say the objectives justify the price of a human life to achieve it.

“You can no more justify it than you can any other abuse of a human being.”

(c) 2008 Western Mail. Provided by ProQuest Information and Learning. All rights Reserved.

John A. Vander Doelen Appointed to the Hazardous Materials Information Review Commission

The Honourable Tony Clement, Minister of Health, today announced the appointment of John A. Vander Doelen to the Hazardous Materials Information Review Commission (HMIRC) for a three-year term.

“I am confident that Mr. Vander Doelen’s extensive experience in operations and policy, along with his background in management, will be great assets to HMIRC,” said Minister Clement. “His knowledge of occupational health and safety as well as legislative and regulatory changes make him well suited for this position.”

Mr. Vander Doelen has a master’s degree of science in kinesiology from the University of Waterloo. Throughout his career, he spent seven years as the Ontario director of the Quebec Labour Mobility Policy Secretariat where he coordinated the development and implementation of a multi-ministry enforcement program related to construction labour mobility between Ontario and Quebec. Mr. Vander Doelen also spent four years as the provincial coordinator of the Industrial Health and Safety Program where he advised senior management on operational and program policy needs and issues.

Since 2000, Mr. Vander Doelen has been director of Occupational Health and Safety Policy and Program Development where he oversees the development of the occupational health and safety workers compensation policy and subsequent legislative and regulatory changes. He also represents the Ministry on external committees and in stakeholder meetings.

Health Canada news releases are available on the Internet at www.healthcanada.gc.ca/media

Egalement disponible en francais

 Contacts: Media Inquiries: Office of the Honourable Tony Clement Federal Minister of Health Laryssa Waler 613-957-0200  Public Enquiries: 613-957-2991 1-866-225-0709  

SOURCE: Health Canada

Lincoln Doctor Faces Drug Charges

LINCOLN — A Lincoln doctor has been arrested on drug charges and allegedly admitted to investigators that he is addicted to prescription painkillers.

Food and Drug Administration agents searched Dr. Jibran Khan’s office Friday and arrested him for possession of a controlled substance and possession of a habit-forming narcotic without a valid prescription.

Investigators said Kahn admitted that he was addicted to Fentanyl, a synthetic opiate. The police say that he got the drug by writing prescriptions for fake patients and pilfering medication from real ones.

Khan, an internist whose office is at 20 Cumberland Hill Rd., Woonsocket, has voluntarily surrendered his medical license, according to Dr. Robert S. Crausman, chief administrative officer of the state Board of Medical Licensure and Discipline. Crausman declined to answer questions about the case, saying that board investigations are confidential. If the medical board takes action, its order will be made public after its Aug. 13 meeting, he said.

— With reports from staff writer Felice J. Freyer

(c) 2008 Providence Journal. Provided by ProQuest Information and Learning. All rights Reserved.

Trading a Trip to the Doc for a Trip to the Docks

By KAREN GOULART

FISHING EXPEDITION

HINGHAM

Just moments earlier, Dr. Lori Lerner was cracking jokes with the service members gathered for Hingham’s fourth annual veterans’ fishing trip. But as she watched them head for the boats that whisk them off for a few hours of fun and relaxation on Hingham Harbor on Tuesday, tears ran from her eyes.

In her seven years as a surgeon with the VA Boston Health Care System, she has seen scores of veterans with an array of injuries.

She wonders what their lives are like outside hospital walls, these men and women who have seen and felt the worst life has to offer and say they’d do it all again.

So Lerner “jumped” at the chance to spend social time with them.

“We see patients when they come in with health problems, to be able to step out of that environment … it’s so valuable,” Lerner said. “This makes it worthwhile. I don’t know how you can care for a patient and not try to gain some appreciation for what their life is like. … To see something like this, you kind of see what you’re taking care of them for.”

The event, organized by Hingham Veterans Agent Michael Cunningham, included a breakfast provided by Carpenters Local 424, lunch from South Shore Baptist Church and a ceremony during which the veterans received citations and words of thanks. Local boat owners, the Lincoln Maritime Center, harbormasters from Hull, Weymouth and Quincy and the Coast Guard helped out on the water.

“This is a great occasion to show our brave service people gratitude for placing themselves in harm’s way on our behalf,” said Selectmen Chairman John Riley. “It’s only a small token, but it’s something they enjoy and we enjoy doing it for them.”

First Lt. Melinda Nekervis, of Sterling, was glad to be in Hingham on Tuesday. Nekervis spent 18 months at Al Asad Air Base in northern Iraq, where she was a flight and ICU nurse with the 399th Combat Support Hospital.

Nekervis tore a rotator cuff lifting an injured soldier. Part of the Wounded Warrior Project, a nonprofit support program for service members, she was encouraged to participate in the event.

“It’s just a good opportunity to talk to fellow soldiers about our experiences and go out and have a fun day,” Nekervis said. “This is just one day I don’t have to worry about going to any doctor appointments.”

Karen Goulart is at [email protected].

Originally published by By KAREN GOULART, The Patriot Ledger.

(c) 2008 Patriot Ledger, The; Quincy, Mass.. Provided by ProQuest Information and Learning. All rights Reserved.

Get Some Bluegrass at Allison Creek

By Mary Jo Balasco

Allison Creek Bluegrass resumes at 6:30 tonight with the Newfire Bluegrass Band of Simpsonville at Allison Creek Presbyterian Church, 5780 Allison Creek Road, York. Donations are accepted.

For details, visit www.allisoncreekbluegrass.com.

Skintonz will perform at Main Street Live

Main Street Live in downtown Rock Hill will be from 5:30 to 9 p.m. today at the end of Main Street from Wachovia to the Gettys Center. The Skintonz will perform. Admission is free. In the event of rain, the concert will be rescheduled for the following Thursday.

Teacher exhibit is open at local arts council

The Arts Council of York County has the following exhibits:

* Teacher exhibition, through Sept. 25 in the Perimeter Gallery and Edmund D. Lewandowski Classroom Gallery, Center for the Arts, 121 E. Main St., Rock Hill. Gallery hours are 9 a.m. to 6 p.m. Monday through Thursday, 9 a.m. to 5 p.m. Friday, 10 a.m. to 2 p.m. the second and fourth Saturday, and 2 to 4 p.m. the second and fourth Sunday. For details, call 328-2787.

* Robin Y. Zavada painting exhibition, through Aug. 31 at the City Hall Rotunda Gallery, 155 Johnston St., Rock Hill. Hours are 8 a.m. to 5 p.m. Monday through Friday.

Two local churches host Christian concerts

The following concerts will be at area churches:

* Christian rock band Within the Red will perform at 6 p.m. Sunday in the Core at St. John’s United Methodist Church, 321 S. Oakland Ave., Rock Hill. Admission is free. For details, visit www.myspace.com/shawnbilton.

* Gospel group Voices in Praise, comprised of youth from South Pointe High School, will perform at 4 p.m. Sunday at Nazareth Baptist Church in Rock Hill. Admission is free.

PRT travel group planning Vermont trip

The Rock Hill Parks, Recreation and Tourism’s Happy Travelers group is accepting registration for the Vermont Culinary Masterpiece trip Oct. 16 through 21. Cost is $845 per person. Registration has been extended to Sept. 1 at the PRT office at City Hall from 8 a.m. to 5 p.m. Monday through Friday or mail to City of Rock Hill, Carolyn Snyder, P.O. Box 11706, Rock Hill, S.C. 29731. For details, call Carolyn at 329-5626 or 329-5620 or visit www.rockhillrocks.com.

Back to school bash is planned at library

York County Library will have its third annual Back to School Bash from 2 to 4 p.m. Saturday at the library, 138 E. Black St., Rock Hill. The event will feature crafts, refreshments, information on library resources, door prizes and free school supplies. For details, call 981-5860.

River Ramblers series continues at museum

The Museum of York County will have the next installment in the River Ramblers series, Worth Mountain Park and Pinckneyville, from 9 a.m. to 4 p.m. Saturday. For details, call Steve Fields at 329-2121 or e-mail him at [email protected].

Cost is $20 CHM members; $25 non-members. Register by calling Barbara Ardrey at (803) 981-9182 or e-mail [email protected].

Auditions planned by Yorkville drama group

The Young Yorkville Players will have auditions for “Charlotte’s Web” at 7 p.m. Aug. 11 and 12 at the McCelvey Center, 212 E. Jefferson St., York. Play rights are pending. If rights cannot be obtained, the production will be “Aladdin.” Adults and young actors are needed. For details, call (866) 334-0064 or visit www.yorkvilleplayers.com.

Pottery center hosts Aug. 16 workshop

The Peter Rose Pottery workshop will be from 10 a.m. to 5 p.m. Aug. 16 at the Rock Hill Pottery Center, 201 E. Main St. Cost is $50. Registration deadline is Aug. 13. For details, call the center at 980-3888 or the Arts Council at 328-2787 or visit www.yorkcountyarts.org.

Vehicle auction is Saturday in York

York County will have a vehicle auction at 9 a.m. Saturday on S.C. 5 in York, beside the York County Animal Shelter. For details, call 684-8520 or visit the purchasing department site at www.yorkcountygov.com.

Bearcat band has parent preview

Rock Hill High School Band of Distinction will conclude band camp with a parent and public preview at 7:30 p.m. Friday at the school,320 W. Springdale Road, Rock Hill.

Benefits planned at area locations

These events are happening:

* Miracle Treat Day, from 10 a.m. to 10 p.m. today at Dairy Queen, 2260 Cross Pointe Drive, Rock Hill, across from the Rock Hill Galleria. All store profits from today will be donated to Children’s Miracle Network. For details, call the store at 980- 1006.

* A fundraising barbecue and raffle to repair weather damage to the Pilgrims’ Inn building will be from 11 a.m. to 2 p.m. Saturday at the Wachovia building on Main Street in downtown Rock Hill. The event is sponsored by Fire and Ice HVAC and Omni Fitness.

* A benefit ride for Randy Ashworth, to help with medical expenses related to a liver transplant, will be Saturday at the Ponderosa, 3040 Cherry Road, Rock Hill. Sign up is from 11 a.m. to 1 p.m. Cost is $15 single and $20 couple. For details, call Vicky Starnes at (803) 287-2336 or the Ponderosa at 366-2258.

* ERA Wilder Realty of Rock Hill will have a yard and bake sale from 7:30 a.m. to noon Saturday at the office, 850 Cherry Road, Rock Hill. Proceeds benefit the Muscular Dystrophy Association. For details, e-mail [email protected] or call 329-2151.

* A benefit concert presented by Music for Humanity in partnership with Habitat for Humanity of York County will be at 7:30 p.m. Saturday in Barnes Recital Hall, Conservatory of Music, Winthrop University. Local singer Kristopher Irmiter, artist Audrey Babcock and others will perform. Tickets are available for a minimum donation of $10 each and are available at the Habitat for Humanity ReStore, 825 N. Anderson Road, Rock Hill or the administrative office, 1034 Charlotte Ave., Rock Hill. For details, call 328-1728.

* Alpine Lodge No. 208 will host a hot dog sale from 10 a.m. to 1 p.m. Saturday at Alpine Masonic Lodge, 502 N. Main St., Clover. Hot dogs are $1.25 each and can be made to order. Eat-in or carry- out are available. For details, call Kathy Wallace at 222-3516.

* A charity car wash to help with medical expenses for the family of Matthew Fuller Yarbrough will be 8 a.m. to 2 p.m. Saturday at the car wash at Cherry and Dorchester Roads in Rock Hill. Tickets are $8. For more information, call (803) 280-6309 or visit www.caringbridge.org/visit/matthewyarbrough.

Families, school grads are planning reunions

The following families/alumni announce information:

* The Childers family will have a reunion at 11 a.m. Saturday at Trinity United Methodist Church, 22 E. Liberty St., York. Admission is $10 adults, $7 ages 6 and older and free for children younger than 6. Payment should be mailed to J. W. Childers at 7213 Coachmaker Road, Columbia SC 29209. For details call Childers at (803) 776-0488 or [email protected].

* The Emmett Scott class of 1969 will meet at 4 p.m. Sunday at the Trinity Baptist Church annex, 803 Crawford Road, Rock Hill. For details, call Betty Gordon at 328-2283 or Addie Clyburn at (803) 817- 7574.

Back to school seminar offered at church

Youth Outreach Ministries at Boyd Hill Baptist Church will have a seminar, Spiritual Preparation for Back to School, from 10 a.m. to 1 p.m. Saturday at the church Family Life Center, 315 Glenn St., Rock Hill. For transportation call (803) 322-3722; for details, call the church 327-2422.

Local Shrine group id hosting dance

The York County Crescent Shrine Club will not have steak night during August. A 10 K dance will be Aug. 16 with entertainment by the Looks EZ Band. Steak night will resume Sept. 20 and every third Saturday of each month. For details, call Barry at 684-4117.

Catawba Nation reschedules meeting

Catawba Indian Nation has canceled its general council meeting scheduled for Saturday. It is rescheduled for 10 a.m. Aug. 23.

communitynews@

heraldonline.com

Deadline for the Thursday columns is 5 p.m. Monday. Deadline for Sunday is 5 p.m. Wednesday.

(c) 2008 Herald; Rock Hill, S.C.. Provided by ProQuest Information and Learning. All rights Reserved.

Henry Ford Hospital Performs State’s First Laparoscopic Living-Donor Liver Transplant

DETROIT, Aug. 7 /PRNewswire/ — Henry Ford Hospital performed the state’s first laparoscopic surgery for living-donor liver transplantation, another milestone in the hospital’s transplant program.

The surgical team, headed by Marwan Abouljoud, M.D., used the minimally invasive procedure to remove a section of the liver from Amy Frankford, 26, of Milford, who donated the organ to save the life of her ailing father, Michael Frankford, 51, also of Milford, who battled hepatitis C since 1986.

Traditional surgery was used to transplant the donated organ. The transplant was performed June 9.

The milestone was the third in 12 years involving Henry Ford’s Transplant Institute, which also performed Michigan’s first split-liver transplant in 1996 and Michigan’s first adult-to-adult, living donor liver transplant in 2000.

In 2007, Henry Ford performed the most liver transplants in Michigan with 114 patients.

Laparoscopic surgery is a growing field in medicine because it’s a less invasive procedure for patients, who recover faster and experience less post-operative pain than traditional open surgery. Henry Ford has used laparoscopic surgery for living-donor kidney transplants since 1999 and for removing liver tumors since 2002.

“The laparoscopic technique for living-donor liver transplantation is relatively new because the surgery is more complex given the need to preserve the integrity of the blood vessels in the liver,” says Marwan Abouljoud, M.D., director of Henry Ford’s Transplant Institute and Amy Frankford’s surgeon.

Atsushi Yoshida, M.D., part of the surgical team, was Michael Frankford’s surgeon.

Laparoscopic surgery is performed through three small holes in the abdomen. The surgical instruments and the laparoscope (a long, slender optical instrument containing a miniature camera) are placed through these holes, and the surgeon removes the organ through a 4-inch abdominal incision.

Henry Ford Hospital

CONTACT: David Olejarz (Radio-TV), Maria Seyrig (Print),+1-313-876-2882, both for Henry Ford Hospital

Web site: http://henryford.com/

CDC Reports Emergency Room Use on Rise: Carena House Calls One Way to Reduce ER Use

Carena:

 What:          The Centers for Disease Control and Annals of Emergency Medicine recently published studies that show two key trends. First, overall use of the ER rose 36 percent in the past decade, with about 20 percent of all visits for preventive care. Second, the number of ER visits by patients who came to the ER because they couldn't get an appointment with their primary care provider is on the rise.  Seattle-based Carena offers a service that is helping reduce the strain on ERs - by reinventing the traditional medical house call. Working in partnership with employers like Microsoft, Carena primary care physicians provide urgent care to employees/family members in the home, any time of night or day, giving them access to care without the need for the ER. Since inception in 2000, Carena has delivered more than 20,000 house calls.  Who:           Ralph Derrickson, CEO of Carena, is available to discuss the business model for Carena and how it lowers costs for employers, improves care and outcomes for patients and reduces stress on the ER system.  When:          Ralph is available to speak via phone, by appointment  Where:         Carena is based in Seattle and currently offers its house calls in the Seattle and Louisville/Frankfort, Kentucky areas.  Media Opportunities: Carena can provide access to corporate customers, house call patients, industry analysts, b-roll of house call, b-roll of executives & doctors  Contacts:      John Williams, Scoville PR for Carena, 206.625.0075 ext. 1 or 206.660.5503 (cell) 

About Carena

Carena, Inc., www.CarenaMD.com, offers a new model for health care delivery — its physicians treat patients at their work or home. This unique “point-of-patient” model eliminates the cost of medically unnecessary trips to the hospital emergency room. By providing unmatched access to high-quality care and information, Carena helps employees manage their health, which increases employee productivity and reduces overall health care costs for employees and their employers.

— Studies available at http://www.cdc.gov/nchs/pressroom/08newsreleases/visitstodoctor.htm (CDC) and http://www.annemergmed.com/article/S0196-0644(08)00365-X/abstract (AEM)

Inverness Medical Innovations Announces 4th Generation Rapid HIV Test – Determine(TM) HIV-1/2 Ag/Ab Combo

WALTHAM, Mass., Aug. 7 /PRNewswire-FirstCall/ — Inverness Medical Innovations, Inc. , a leading provider of near-patient diagnostics, monitoring and health management solutions, has announced the introduction of its new 4th generation rapid HIV diagnostic test, the Determine HIV-1/2 Ag/Ab Combo, at the International AIDS conference (AIDS 2008) in Mexico City. The test will be introduced to the developing world during the third quarter, and in certain other markets during 2009.

What differentiates this test is that it is capable of detecting HIV infections earlier than HIV antibody only tests. The Determine HIV-1/2 Ag/Ab Combo is the first rapid diagnostic which enables simultaneous detection of HIV p24 antigen (Ag) and antibodies (Ab) for HIV-1 and HIV-2 in human serum, plasma or whole blood.

The p24 antigen is present during the first few weeks of HIV infection and can be identified before HIV antibodies are produced, making it an ideal marker to aid in early HIV detection. By targeting p24 antigen as well as the HIV antibody response, Determine HIV-1/2 Ag/Ab Combo improves the ability to detect and diagnose acute (early) HIV infection.

Identifying acute HIV infection is a matter of global health concern. It is estimated that a significant number of newly acquired HIV infections are transmitted by those acutely infected, most unaware of their HIV status.

The Determine HIV-1/2 Ag/Ab Combo is a rapid, point-of-care lateral flow test which provides clear visual results in 20-minutes. The simple to use format enables HIV testing to be conducted in a broad range of clinical settings, from the physician’s office to the most remote environments of the developing world.

Ron Zwanziger, Inverness’ Chief Executive Officer, stated, “We are pleased with the overwhelmingly positive response to our introduction of the Determine HIV-1/2 Ag/Ab Combo at AIDS 2008. We believe this product will make a significant contribution in the quest to identify early HIV infection and prevent further spread of the epidemic.”

The introduction of the Determine HIV-1/2 Ag/Ab Combo reflects the commitment by Inverness Medical Innovations to develop and bring to market innovative diagnostics to identify infectious disease.

By developing new capabilities in near-patient diagnosis, monitoring and health management, Inverness Medical Innovations enables individuals to take charge of improving their health and quality of life. A global leader in rapid point-of-care diagnostics, Inverness’ products, as well as its new product development efforts, focus on infectious disease, cardiology, oncology, drugs of abuse and women’s health. Inverness is headquartered in Waltham, Massachusetts.

For more information about Inverness Medical Innovations, please visit our website at http://www.invernessmedical.com/.

This press release may contain forward-looking statements within the meaning of the federal securities laws, including statements regarding timing of the product release and benefits of the new product. These statements reflect Inverness’ current views with respect to future events and are based on its management’s current assumptions and information currently available. Actual results may differ materially due to numerous factors including, without limitation, risks associated with market acceptance of the product; Inverness’ ability to successfully manufacture and distribute the product; Inverness ability to secure and maintain the regulatory approvals or clearances necessary to sell the product in various markets; and the risks and uncertainties described in Inverness’ annual report on Form 10-K, and other factors identified from time to time in its periodic filings with the Securities and Exchange Commission. Inverness undertakes no obligation to update any forward-looking statements contained herein.

Inverness Medical Innovations, Inc.

CONTACT: Doug Guarino, Director of Corporate Relations of InvernessMedical Innovations, Inc., +1-781-647-3900

Web site: http://www.invernessmedical.com/

Destroy Back-to-School Cold and Flu Woes With Duraban’s Antibacterial, Antimicrobial Barrier Solution

WEST PALM BEACH, Fla., Aug. 7 /PRNewswire/ — According to the U.S. Centers for Disease Control and Prevention (CDC), the common cold is one of the most common causes of absenteeism at work and school, with up to 22 million school days lost each year in the U.S. Children are at a much higher risk for catching an illness because they are more likely to put their hands and other objects in their mouths — especially those whose days are spent in communal play.

As children return to school this fall, parents can proactively protect them from the infestation of cold-and-flu-causing bacteria. Duraban’s unique antibacterial, antimicrobial formula is the first step in the prevention of microbe invasion. Duraban (licensed by BDA Industries) kills 99.9 percent of bacteria and goes even further, providing a covalently-bonded barrier that protects against viruses and bacteria like MRSA, HIV B, Influenza A, Salmonella, Staph, E-Coli and SARS and more than 40 strains of yeast, algae and fungi.

“Direct contact is responsible for the spread of many common childhood illnesses like chickenpox, cold sores, ringworm, impetigo, scabies and pinkeye,” remarked Scott Gilman, President of BDA Industries. “Some illnesses are spread by sneezing, coughing, dripping or exhaling; these include the flu, the common cold, meningitis, Rubella, Strep throat, Scarlet Fever, pneumonia, mumps, and whooping cough. Duraban’s unique formula protects against the growth of all these bacteria and viruses. Parents can worry less about what their children are being exposed to.”

Duraban offers four unique germ-killing products to combat the spread of viruses and bacteria:

— Children can carry the convenient DuraClean On-the-Go pocket-sized spray-bottle to kill infectious microbes on virtually any surface.

— Washing apparel, blankets, and other textiles with Duraban Laundry Rinse will prohibit the growth of germs and keep items fresher for longer.

— Wipe down all hard surfaces with Duraban Hard Surface spray to prevent the spread of contaminants on tables, doorknobs, and other surfaces.

— Use Duraban Fabric Spray on colorfast fabrics that can’t go in the wash – items like backpacks, draperies, carpets, and upholstery — to stop unwanted microbes from multiplying on the textile surface.

Duraban’s EPA registered formula is based on surface-modifying technology that forms antimicrobial chemical cross-links with the treated surface, creating a non-leaching and durable sword-like microbial barrier. Microorganisms like bacteria, mold, mildew and viruses are destroyed by simple surface contact, and the strength and efficacy of the bonds will not diminish over time. Conventional antimicrobials migrate and leach, wearing away over time and releasing toxic chemicals into the environment; in contrast, Duraban’s bonds will not leach or migrate, allowing for enduring, eco-friendly protection.

For more information on Duraban’s environmentally-friendly proactive cleaning solution, please visit http://www.durabanantimicrobial.com/.

About Duraban

Duraban International Inc. is an emerging global innovator of built-in antimicrobial / anti-bacterial product protection, engineering safe and durable antimicrobial solutions for consumer, industrial and medical products around the world. Duraban’s antimicrobial product protection inhibits the growth of microbes, such as bacteria, mold, mildew, fungus and algae that can cause stains, odors and product deterioration.

About BDA Industries

BDA Industries, LLC is a leading DRTV products company that brings innovative products used in and around the home to consumers throughout the globe. The company’s goal is to bring new products to market that provide its customers with better, faster, and safer ways of experiencing family life.

BDA Industries, LLC

CONTACT: Kell Benson of SS|PR, +1-847-415-9348, [email protected], forBDA Industries, LLC

Web site: http://www.durabanantimicrobial.com/

Catholic Health East Selects Mediture’s EHR Software for PACE Programs

Mediture, a developer of healthcare information management software for Programs of All-Inclusive Care for the Elderly (PACE) programs, today announced that Newtown Square, Pa.-based Catholic Health East has purchased its TruChart LIFEconnect(R) suite of products for use at the system’s headquarters and 5 PACE sites in three states.

“Mediture will help us design and implement a standardized software solution to support our Regional Health Corporations’ expansion in the PACE model of care. It will promote the use of best practices across all stakeholders within Catholic Health East,” said Donette Herring, Chief Information Officer for Catholic Health East.

The multi-institutional Catholic health system will use a number of Mediture’s products and services including:

 --  TruChart LIFEconnect(R) to manage care for participants in its PACE     facilities; --  TruChart LabConnect(R) to manage laboratory test requisition and results     electronically; --  TruChart RxConnect(R) to connect with pharmacies for medication     management.      

Catholic Health East will utilize Mediture’s suite of products to coordinate and manage health care services for the elderly for MercyLIFE in Philadelphia, PA; LIFE St. Francis in Trenton, NJ; LIFE at Lourdes in Camden, NJ; LIFE St. Mary in Langhorne, PA; and St. Joseph of the Pines PACE, Southern Pines, NC. With Mediture’s TruChart product, new CHE PACE programs will begin operations with a complete electronic medical record that will contribute to optimal care management and outcomes.

Catholic Health East’s Continuing Care Management Services Network, which was initiated to support operational performance and strategic execution of its continuing care ministries, is working with Mediture and the PACE programs on this implementation.

“We are honored that a prestigious organization like Catholic Health East has placed such a high level of confidence in our ability to manage operations for their PACE providers,” said Kiran Simhadri, Chief Technology Officer of Mediture.

About Catholic Health East

Catholic Health East is a multi-institutional Catholic health system, which is co-sponsored by 10 religious congregations, and Hope Ministries, a Public Juridic Person within Catholic Health East. Based in Newtown Square, Pa., the System provides the means to ensure the continuation of the Catholic identity and operational strength of the sponsors’ health ministries, which are located within 11 eastern states from Maine to Florida. In addition to 33 acute care hospitals, the system includes four long-term acute care hospitals, 36 freestanding and hospital-based long-term care facilities, 12 assisted living facilities, five continuing care retirement communities, eight behavioral health and rehabilitation facilities, 25 home health/hospice agencies, and numerous ambulatory and community-based health services. Catholic Health East facilities employ approximately 50,000 full-time employees as partners in ministry. Visit www.che.org

About Mediture

Mediture provides customized software systems and services for healthcare information management. Mediture’s TruChart suite of products is a comprehensive, web-based solution for PACE programs, senior care facilities, clinics, pharmacies and laboratories. Mediture is based in Eden Prairie, MN and is privately held. Visit www.mediture.com

 Contact: Brenda Vatland Mediture, LLC 952-400-0306 [email protected]

SOURCE: Mediture

Wind Energy Development Path Cleared in South Texas

HOUSTON, Aug. 7 /PRNewswire/ — Babcock & Brown, a leader in wind energy, today announced that a federal court in Texas dismissed a final lawsuit, clearing the path to bring wind energy to South Texas.

Babcock & Brown’s wind farm on the Texas Gulf Coast, which will provide enough clean and renewable energy to power 80,000 Texas homes, will be completed and operational later this year. The wind farm is located on the property of the Kenedy Memorial Foundation, a non-profit organization that will utilize the royalties to support charitable purposes in South Texas.

“From the initiation of our development efforts with the Kenedy Foundation, Babcock & Brown has been committed to the responsible development of a world-class wind farm for South Texas,” said Hunter Armistead, head of Babcock & Brown’s North American energy group. “Our intention has always been to deliver the benefits of renewable energy while minimizing any impact to the environment. We were meticulous in the way we approached the development of this wind farm, which we believe will be used as a model for future wind farms around the country.”

“The winds of South Texas are one of the largest and most attractive renewable energy resources in the country, representing a tremendous clean and never-ending power supply,” said John Calaway, Babcock & Brown’s chief development officer for North America. “Our Gulf Wind Farm will provide critical power when it is needed most because the coastal winds in South Texas blow the hardest at the same time our state’s demand for electricity peaks.”

The development of Babcock & Brown’s Gulf Wind Farm has created approximately 300 construction jobs, in addition to approximately 20 ongoing permanent and maintenance positions. The wind farm will also provide significant annual tax benefits to the local area. Once operational, the wind farm will consist of 118 wind energy turbines with a total output capacity of more than 283 megawatts (MW).

Babcock & Brown currently operates more than 20 wind farms throughout the United States, including one of the largest wind farms in the country, located in Sweetwater, Texas. In addition, Babcock & Brown has more than 25 wind energy projects across the country in various stages of development. In Texas, Babcock & Brown has offices in Houston, Austin and Dallas, where the company’s 24-7 wind farm monitoring headquarters is located.

About Babcock & Brown

Babcock & Brown is an international investment and specialized fund and asset management group with longstanding capabilities in the creation, syndication and management of asset and cash flow-based investments.

Babcock & Brown is one of the top five wind energy developers and operators in the world with more than 20 years of experience in wind energy. Babcock & Brown operates 20 wind farms across nine states throughout the country, totaling nearly 1600 MW of installed capacity, which is enough clean and renewable energy to power more than 400,000 American homes.

Babcock & Brown was founded in San Francisco in 1977. For further information about Babcock & Brown please see our website: http://www.babcockbrown.com/.

    Contact:    Matt Dallas    Babcock & Brown    212-796-3918    [email protected]  

Babcock & Brown

CONTACT: Matt Dallas of Babcock & Brown, +1-212-796-3918,[email protected]

Web site: http://www.babcockbrown.com/

IMPAX Reports Positive Results in Phase III Trial With IPX056

IMPAX Laboratories, Inc. today announced that IPX056, an investigational extended-release formulation of baclofen, has met its clinical endpoints in a Phase III study of spasticity in multiple sclerosis patients. The Company also is providing an update on its brand pharmaceutical product program, which resides in its IMPAX Pharmaceuticals Division.

In a 173-patient, placebo and active comparator-controlled double blind Phase III study with a seven-week open label follow on, IPX056 was shown to be effective versus placebo in reducing spasticity in multiple sclerosis patients. IPX056 is an extended-release formulation of baclofen, the drug of choice in the treatment of spasticity, which has the potential to offer improved control of symptoms and dosing convenience.

“We are very excited with the results of this study, and are planning to meet with the U.S. Food and Drug Administration (FDA) in the fourth quarter of this year to discuss the results of this study and determine the next steps in the submission of a new drug application (NDA) for IPX056,” said Larry Hsu, Ph.D., president and chief executive officer of IMPAX Laboratories. “Such spasticity treatments represent a $1.6 billion market in the U.S. and IPX056 may fill an unmet medical need in these patients.”

The IMPAX Pharmaceuticals division of IMPAX Laboratories currently has two products in its development pipeline, directed to neurology as a therapeutic focus, with four other central nervous system (CNS) specific products undergoing feasibility assessment. The Company filed an Investigational New Drug application for IPX066, a controlled-release formulation of Carbidopa/Levodopa in July 2008, and expects to initiate studies in Parkinson’s disease patients by the end of this year and is targeting an NDA submission in mid-2011.

Michael Nestor, divisional president of IMPAX Pharmaceuticals said, “We are very pleased with the progress we have made in advancing our proprietary, brand products and expect to continue this progress with an expansion in our R&D staff this year. The CNS space is ideally suited to our core competency in drug delivery, as so many products are candidates for improved dosing and administration and the market is large and growing at almost 10% annually, faster than the total U.S. pharmaceutical market. In addition, the neurology market is readily addressable by a small and focused sales force, given the concentration of physicians writing prescriptions. We currently have 66 specialty sales representatives to market our products, and to serve as a contract force for others,” Mr. Nestor added.

As previously announced on July 31, 2008, Arthur A. Koch, Jr., senior vice president and chief financial officer of IMPAX Laboratories, will present at the Bank of America 2008 Specialty Pharmaceuticals Conference today at 9:30 a.m. Eastern time. The conference will be held at the Southampton Inn, Long Island, New York.

Individuals may listen to the live or an archived presentation made at the conference, which will be posted in the investor relations section of the Company’s web site at www.impaxlabs.com. To listen to the live presentation, please go to the web site 15 minutes prior to its start to register, download, and install the necessary audio software. This presentation will be archived on the Company’s web site for 90 days. The Company’s regular Corporate presentation will be updated and posted on the Company’s web site today as well.

About IMPAX Laboratories, Inc.

IMPAX Laboratories, Inc. is a technology based specialty pharmaceutical company applying its formulation expertise and drug delivery technology to the development of controlled-release and specialty generics in addition to the development of brand products. IMPAX markets its generic products through its Global Pharmaceuticals division and will market its brand products through the IMPAX Pharmaceuticals division. Additionally, where strategically appropriate, IMPAX has developed marketing partnerships to fully leverage its technology platform. IMPAX Laboratories is headquartered in Hayward, California, and has a full range of capabilities in its Hayward and Philadelphia facilities. For more information, please visit the Company’s Web site at: www.impaxlabs.com.

Girls Enjoy Construction Camp at the University of Portland

By Libby Tucker

On Tuesday afternoon, 14 middle school girls donned safety glasses and tool belts and gathered around a table for a lesson with a chop saw. They watched closely as teacher Katie Hughes explained how to safely operate the saw so that it cuts wood at the perfect length.

“What does zero degrees mean?” asked Hughes, education director for Oregon Tradeswomen Inc., waiting for an answer. “That’s right, straight up and down.”

Hughes marked the board with her pencil and speed square and lined it up on the saw, explaining everything as she prepared to start the saw. The girls braced for the noise, drawing back from the table and stiffening, and then stared transfixed as the blade sliced through the wood. When the sawdust cleared, the girls crowded around the table to see the result – a clean 7 inches.

Playing with tools isn’t a typical summer activity for middle school and high school girls. But for one full week, Oregon Tradeswomen Inc.’s construction camp is teaching girls how to use a tape measure, swing a hammer, and operate a table saw among many other skills.

OTI, a nonprofit training and mentorship program for women interested in construction, began the camp last year as a way to introduce girls to carpentry, sheet metal, masonry and painting. This year, the camp also included highway trades.

“These girls are in middle school; they’re too young to think about jobs,” said Hughes. “My goal is to show them they’re good at this stuff and they enjoy it.”

This week, 14 middle school girls gathered at the University of Portland campus to finish building a pair of sheds that will be donated to the Portland Parks and Recreation community gardens. High school girls in two previous weeks of the camp framed the sheds, and the middle school girls were putting on the finishing touches.

“I like giving back to the community and all,” said Ingrid Ayala, 16, an 11th-grader from the high school camp who volunteered at the middle school camp. “Last year we made a play house and once you finish, it’s really fun that feeling of accomplishment and just knowing I can do it.”

Ayala offered pointers and helped the girls as they measured boards to make trim for the sheds and carried them to the table for cutting. Now it was their turn to try what they learned.One by one, the girls marked a 2-inch piece of the board, lined it up and chopped it off. They approached the saw cautiously, pulling the trigger and slowly lowering the blade. Some of them jumped when it hit the wood. Onlookers plugged their ears. But afterward, they were all smiles.

“At first I thought it was scary and I would cut my hand off, but I didn’t,” said Rosita Rendon, 12, after her turn at the chop saw. Rendon, who will enter seventh grade this fall, says she’s attending the construction camp because she “wanted to see if women are strong.””Yes,” she said, holding her 2-inch slice of wood. “It was fun.”

Originally published by Libby Tucker.

(c) 2008 Daily Journal of Commerce (Portland, OR). Provided by ProQuest Information and Learning. All rights Reserved.

NIH Funds $1M Research at Quest Product Development and University of Colorado for New Digitally-Controlled Endoscopes

DENVER, Aug. 7 /PRNewswire/ — Quest Product Development, with partner University of Colorado, has been awarded a $1,000,000 Small Business Technology Transfer grant by the National Institutes of Health (NIH) to continue the development of a next-generation endoscope. MicroFlex technology, derived from aerospace engineering, uses shape metal alloys and micro-actuators that allow active control over the shape of the scope for minimally invasive surgery. Surgeons will guide this ultra-slim 3mm (1/8″) diameter scope via a joystick-like control, and can reach previously inaccessible spaces to visualize and diagnose problems. Specialized tools fit through the scope for therapeutic and surgical procedures. Dr. Dale Lawrence, University of Colorado Professor and inventor of the technology, says, “We’re excited about the potential of this technology to access small areas of the anatomy.”

MicroFlex endoscopes may provide easier out-patient surgery for patients suffering from chronic sinusitis. The sinus application, the first of many potential uses of this technology, was selected due to the prevalence of chronic sinusitis, which effects 33 million Americans, and the challenge of surgery and treatment in these difficult anatomical structures.

Development is being done by Dr. Lawrence’s research group at CU Boulder, physicians at the Health Sciences Center and an engineering team from Quest Product Development. A second NIH grant funded research demonstrating that MicroFlex devices can be fabricated as small as 1mm (0.04″) diameter, which will allow access deep into areas of the lungs not currently possible, for diagnosis and treatment of lung cancer. Ultimately, MicroFlex technology may provide a useful tool for diagnostic and surgical care for a variety of medical uses including ear-nose-throat, lung, neurosurgery, neonatal and cardiac applications.

MicroFlex is innovative technology with the potential to revolutionize minimally invasive surgeries. Alan Kopelove, Quest Director for Technology, says, “MicroFlex scopes could improve healthcare by improving surgeon access, reducing treatment costs, reducing patient trauma and improving recovery times.” Quest Product Development, a specialized engineering and product development company focusing on medical products and Colorado bioscience, teams with universities and companies to develop new technologies.

Quest Product Development

CONTACT: Alan Kopelove of Quest Product Development Corporation,+1-303-670-5088, x11, [email protected]

Covidien Acquires CardioDigital Inc. Technology

Covidien (NYSE: COV, BSX: COV), a leading global supplier of healthcare products, today announced the acquisition of technology assets from CardioDigital Inc., a company specializing in the development of advanced signal processing techniques for patient monitoring. The technology, which will be used by Covidien’s Respiratory and Monitoring Solutions business unit, reflects the Company’s strong commitment to making investments in clinically relevant product innovations designed to improve patient outcomes. Terms of the transaction were not disclosed.

“The acquisition of CardioDigital’s technology is an exciting opportunity for us to strengthen our patient monitoring business as we partner with our customers to improve outcomes. We believe that the technology will enable significant improvements in current patient monitoring techniques, resulting in enhanced patient care and safety,” said Joe Almeida, President, Medical Devices, Covidien.

CardioDigital’s innovative technology will complement Respiratory and Monitoring Solution’s market-leading Nellcor pulse oximetry platform. In addition, Almeida said, “This acquisition sets the stage for more of these types of growth opportunities in the future.”

About Covidien

Covidien is a leading global healthcare products company that creates innovative medical solutions for better patient outcomes and delivers value through clinical leadership and excellence. Covidien manufactures, distributes and services a diverse range of industry-leading product lines in four segments: Medical Devices, Imaging Solutions, Pharmaceutical Products and Medical Supplies. With 2007 revenue of nearly $9 billion, Covidien has more than 42,000 employees worldwide in 57 countries, and its products are sold in over 130 countries. Please visit www.covidien.com to learn more about our business.

About CardioDigital Inc.

CardioDigital Inc., based in Portland, Oregon, provides commercialization of near-to-market technologies developed by its research organization, CardioDigital Ltd., located in Edinburgh, Scotland.

Forward-Looking Statements

Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on our management’s current beliefs and expectations, but are subject to a number of risks, uncertainties and changes in circumstances, which may cause actual results or Company actions to differ materially from what is expressed or implied by these statements. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, our ability to effectively introduce and market new products or keep pace with advances in technology, the reimbursement practices of a small number of large public and private insurers, cost-containment efforts of customers, purchasing groups, third-party payers and governmental organizations, intellectual property rights disputes, complex and costly regulation, including healthcare fraud and abuse regulations, manufacturing or supply chain problems or disruptions, recalls or safety alerts and negative publicity relating to Covidien or its products, product liability losses and other litigation liability, divestitures of some of our businesses or product lines, our ability to execute strategic acquisitions of, investments in or alliances with other companies and businesses, competition, risks associated with doing business outside of the United States, foreign currency exchange rates, potential environmental liabilities or increased costs after the separation from Tyco International or as a result of the separation. These and other factors are identified and described in more detail in our filings with the SEC. We disclaim any obligation to update these forward-looking statements other than as required by law.

IPC The Hospitalist Company Enters Ohio and Pennsylvania Markets

NORTH HOLLYWOOD, Calif., Aug. 7 /PRNewswire-FirstCall/ — IPC The Hospitalist Company, Inc. , a leading national hospitalist physician group practice company, announced today that it has signed hospitalist service agreements with Toledo Children’s Hospital in Toledo, Ohio and Good Samaritan Hospital in Lebanon, Pennsylvania. These agreements establish IPC’s operations in two additional northeastern states, expanding its national presence to 18 states.

“With our expansion into Ohio, we are providing the Toledo Children’s Hospital with the services of skilled pediatric hospitalists,” said Skip Strauchman, IPC’s regional executive director. “IPC’s proprietary technology platform and support infrastructure will enable our hospitalists to deliver high quality pediatric care by efficiently coordinating with clinical teams across this leading children’s hospital.”

Serving counties in northwest Ohio and southeast Michigan, the 151-bed Toledo Children’s Hospital is dedicated to caring for children and adolescents. It is part of the ProMedica Health System, which was ranked the most integrated health network in the United States among 570 systems by the 2008 Verispan assessment of integrated healthcare networks.

Good Samaritan Hospital in Lebanon, Pennsylvania, is a 196-bed acute care community hospital serving south central Pennsylvania. Part of the Good Samaritan Health System, the hospital recently earned the Get With The Guidelines(SM) Heart Failure (GWTG-HF) Silver Performance Achievement Award from the American Heart Association.

“Good Samaritan Hospital’s selection of IPC is a testament to our experienced leadership and the ability of our technology platform to support our hospitalists in providing efficiency in addition to excellent quality and continuity of care,” said Ed Crandell, regional executive director of IPC.” This contract is further evidence of the success of our proven growth strategy to grow our footprint nationwide by adding new facilities while remaining committed to our high standards for patient care.”

About IPC The Hospitalist Company, Inc.

IPC The Hospitalist Company, Inc. is a leading national hospitalist physician group practice company focused on the delivery of hospitalist medicine services. IPC’s physicians and affiliated providers manage the care of hospitalized patients in coordination with primary care physicians and specialists. The Company provides its hospitalists with the comprehensive training, information technology, and management support systems necessary to improve the quality and reduce the cost of inpatient care in the facilities it serves. For more information, visit the IPC website at http://www.hospitalist.com/.

   Media Contact:                        Investor Contacts:   Scott Public Relations                The Ruth Group   Elaine Murphy                         Stephanie Carrington/Jared Hoffman   818.610.0270                          646.536.7017/7013   [email protected]       [email protected]                                         [email protected]  

IPC The Hospitalist Company, Inc.

CONTACT: Media, Elaine Murphy of Scott Public Relations,+1-818-610-0270, [email protected]; or investors, StephanieCarrington, +1-646-536-7017, [email protected], or Jared Hoffman,+1-646-536-7013, [email protected], both of The Ruth Group

Web Site: http://www.hospitalist.com/

National Congressional Leaders and Pfizer Join Community Health Centers of Arkansas to Honor Community Health Center Caregivers

To: STATE EDITORS

Contact: Sip Mouden, CEO, CHC of Arkansas, +1-501-517-2591, [email protected]; Lisa Weaver, CHC of Arkansas, +1-501-517-1743, [email protected]; Tory Archibald, +1-646-218-8748, [email protected], for CHC of Arkansas

National Health Center Week 2008 Dedicated to Good Health through Health Care Heroes

LITTLE ROCK, Ark., Aug. 7 /PRNewswire-USNewswire/ — Community Health Centers of Arkansas, Inc. announced that it will be joined at the Arkansas Primary Care Association Conference this week by the Honorable Governor Mike Beebe, U.S. Congressman Mike Ross (AR-4), U.S. Congressman Vic Snyder (AR-2), U.S. Congressman Marion Berry (AR-1), National Association of Community Health Centers and Pfizer Inc. to celebrate National Health Center Week 2008, and all of the contributions and accomplishments the Community Health Centers have made in the State of Arkansas. A celebration ceremony will recognize and salute the many health care heroes on staff at the Community Health Centers located across Arkansas.

Community Health Centers provide uninsured, underserved and low- income people with access to affordable quality primary and preventive care services. Health centers have a significant impact on our national health care system, saving between $9.9 billion and $17.6 billion ($89-159 million in Arkansas) each year by helping patients avoid the use of emergency rooms by providing primary and preventive services, as well as chronic disease management. Arkansas has 58 Community Health Centers which employ just over 700 staff, and provide affordable, comprehensive, quality health care services to 120,000 Arkansans who call Community Health Centers their Health care Home.

This years National Health Center Week theme, Americas Health Centers: Home of Americas Health Care Heroes, honors the men and women who dedicate their lives to caring for patients who rely on community-based health services. Fridays celebration ceremony will acknowledge the vital role and significant contributions of the many health center staff devoted to improving the health and welfare of underserved Arkansans. A special Health Care Hero Award will be given to one health center provider who has shown an outstanding dedication to service and excellence in quality of care.

Arkansas is fortunate to have so many dedicated health center staff committed to improving the health and well-being of others. The quality of patient care provided by our Arkansas Community Health Centers is further enhanced through its public/private partnership with Pfizer, said Sip Mouden, CEO for Community Health Centers of Arkansas, Inc.

Pfizer supports Community Health Centers through one of its patient assistance programs called Sharing the Care, which was launched in 1993 to make Pfizer medicines available for free to eligible health center patients. Through Sharing the Care, Pfizer partners with 15 Community Health Centers in Arkansas. In just the past five years, Pfizer has provided nearly 9.6 million prescriptions, valued at more than $780 million, to more than 2.4 million community health center patients across the United States.

Due to rising health insurance premiums and an increasing number of employers dropping health benefits, more and more of our colleagues, friends and neighbors are turning to and calling Community Health Centers their Health care Home, said Mouden. Since our partnership began more than a decade ago, Pfizer has proven to be a committed ally in our efforts to make better health an attainable goal for Arkansans who, through no fault of their own, may not otherwise get the care they need when they need it.

Pfizer is dedicated to supporting community service organizations that improve access to quality health care. We are fortunate to have partners in this mission, like Community Health Centers of Arkansas – a fixture of Arkansas health care community – and Congressman Mike Ross, Congressman Vic Snyder and Congressman Marion Berry who have persisted in their efforts to improve the health of Arkansans, said Gary Pelletier, director of Pfizer Helpful Answers. Last year, Pfizer distributed more than $2 million worth of free medicines to 8,000 patients of Arkansas Community Health Centers.

Event Specifics

This weeks celebration ceremony will take place at 12:00 p.m., August 8th at the Peabody Hotel (Salon B) located at Three Statehouse Plaza. U.S. Congressman Mike Ross and U.S. Congressman Vic Snyder will speak at the special ceremony.

The celebration ceremony will occur in conjunction with the Arkansas Primary Care Associations Annual Conference, CHCs: The Healthcare Home of Choice – A Key Solution to the Health Crisis, (August 7-8, 2008) at which the Honorable Governor Mike Beebe will be on hand to kick-off the conference on day one, and Arkansas Surgeon General, Joe Thompson, M.D., will kick-off the conference on day two. U.S. Congressman Marion Berry will provide a special Salute to Arkansas CHCs. Throughout the conference, several health center patients will share their stories on how health centers have made a difference in their quality of life.

For more information about these events, visit www.chc-ar.orgor www.healthcenterweek.org, or call 501-374-8225.

About Community Health Centers of Arkansas

Community Health Centers of Arkansas, Inc. (CHCA), Arkansas Primary Care Association, is dedicated to increasing access to affordable, quality, and comprehensive primary and preventive health care services. CHCA represents 12 Community Health Center Organizations in Arkansas and their 58 locations.

About the National Association of Community Health Centers

Founded in 1970, NACHC is a non-profit organization whose mission is to enhance and expand access to quality, community-responsive health care for Americas medically underserved and uninsured. In serving its mission, NACHC represents the nations network of over 1,000 Federally Qualified Health Centers (FQHCs) which serve 17 million people through 6,300 sites located in all of the 50 states, Puerto Rico, the District of Columbia, the U.S. Virgin Islands and Guam.

About Pfizer Sharing the Care

Pfizer Sharing the Care is part of Pfizer Helpful Answers, a family of programs that helps people without prescription coverage save on many Pfizer medicines, no matter their age or income. People with limited income may even qualify to get their Pfizer medicine for free. Consumers without prescription drug coverage who need a Pfizer medicine can call the Pfizer Helpful Answers toll-free number, 1-866-706-2400, or visit the Web site, www.PfizerHelpfulAnswers.com. Pfizer Helpful Answers is a joint program of Pfizer Inc. and the Pfizer Patient Assistance Foundation(TM).

SOURCE Community Health Centers of Arkansas

(c) 2008 U.S. Newswire. Provided by ProQuest Information and Learning. All rights Reserved.

Albanian Doctors Warn of “Alarming” Shortage of Medicines

Text of report by Albanian independent centre-right newspaper Albania, on 2 August

[Report by Emanuela Sako: “Doctors at Hospital Centre of Tirana University Complain of Shortages of Medicines and Obsolescent Equipment”]

Shortages of medicines and obsolescent equipment are among the major problems of the country’s biggest hospital centre – the Hospital Centre of Tirana University [QSUT], with adverse repercussions on the quality of services in this centre. The head of the QSUT Surgical Emergency Service, Ylli Zicishti, says that the centre has to battle with many difficulties and that, in particular, an immediate intervention is necessary to ensure the supply of medicines which would, in turn, contribute to the improvement of the image of its doctors.

The doctors say that the situation has become alarming and an immediate intervention is indispensable. According to them, shortages of medicines have become chronic, and they do not know when these difficulties will be surmounted. Besides, in some QSUT wards, as for example that of heart surgery, viruses have appeared that cannot easily be extirpated.

Problems

Zicishti mentions some of the more acute problems. Apart from shortages of medicines, equipment has become obsolete, or there is lack of materials for its operate it.

He says that the immediate commissioning of the sanatorium would be among the most urgent measures for the proper functioning of the hospital centre, as this would divert from the QSUT part of the daily flow of patients.

Patients

The patients are the first victims of this state of things. They have little trust in either the QSUT’s treatment capabilities or the reliability of its doctors who, when it comes to the prescription of medicines, frequently refer them to pharmacies they patronize. With all their reservations, however, they say they cannot go to private hospitals which, regardless of the better quality of their services, are too expensive.

Until this moment nothing has been done to cope with this situation.

Originally published by Albania, Tirana, in Albanian 2 Aug 08.

(c) 2008 BBC Monitoring European. Provided by ProQuest Information and Learning. All rights Reserved.

Familiar Faces Edwardsville Exhibit Takes a Personal Look at the Community

By Teri Maddox, Belleville News-Democrat, Ill.

Aug. 7–Dan Anderson is at it again.

The man who created an art exhibit out of 300 coffee cups last fall is inviting the public to see 400 faces.

His new show at Edwardsville Arts Center consists of 400 photographic portraits of people who live and work in Edwardsville and Glen Carbon.

“There’s no common denominator,” said Anderson, a retired art professor at Southern Illinois University Edwardsville and president of the center’s board.

“But they’re all part of the fabric of our community. There are politicians, farmers, mechanics, teachers, kids and store owners. And, of course, every town has its characters.”

Edwardsville goodwill ambassador Marvin “Preach” Webb will be represented in the exhibit, as well as folks you see in restaurants and grocery stores but don’t know by name.

“Faces: Portraits of the Community” runs through Sept. 21. A Sneak Peek fundraiser from 5 to 7 p.m. Friday will be followed by an opening reception from 7 to 9 p.m.

Anderson recruited about 20 amateur and professional photographers to shoot the portraits, reflecting their own styles and viewpoints.

One is Madison County State’s Attorney Bill Mudge.

“(He) is a hell of a photographer,” Anderson said. “Not many people know that. His occupation is state’s attorney. His avocation is photography.”

Another exhibitor is Edwardsville police Lt. Scott Evers, who has a part-time photography business.

He specializes in nature and wildlife themes and rural and urban landscapes, which don’t involve asking people to pose for the camera.

“I’d rather go to the dentist and have my teeth drilled without Novocain than (shoot portraits),” Evers said. “But I did it because I wanted to help Dan, and I think it’s going to be a really neat show.”

Several of Evers’ subjects are city employees. He caught up with Mayor Gary Niebur outside the Edwardsville YMCA Esic Center, where he serves as executive director.

Evers also captured the image of Fire Chief Brian Wilson.

“I had him lean against a fire truck, and his uniform is reflected in the truck,” he said. “It’s just a quick, casual shot, but I like the way it looks.”

Anderson is a ceramic artist, but he enjoys photography, so he contributed 40 portraits to the exhibit.

One of his favorite subjects is Jerry Legow, owner of Imber’s Men’s Wear.

Legow has become a community icon because of his 58 years in business and his role as Edwardsville Halloween Parade announcer.

The photo shows him looking in a three-way mirror, which reflects neatly organized clothing racks and wooden shelves.

“He personifies our Main Street,” Anderson said. “His dedication and passion are unsurpassed.”

Anderson also shot Mike Campbell, Edwardsville Township supervisor and farmer; Charlie Cox and Sam Smith, legendary SIUE photographer and news director, now retired; Joe Rios, a landscaper commonly seen riding around town on his bike or pushing his son in a stroller; Bob Grinstead, a gardener who sells lotus blossoms at the Land of Goshen Community Market; and Tom Pile, former Edwardsville High School history teacher and baseball coach.

Customers of Sacred Grounds coffee house will recognize owner Jennifer Courtney, standing at the stove in her ponytail and green apron.

“As far as I’m concerned, Jennifer is single-handedly responsible for generating the new activity on North Main Street,” Anderson said. “She brought it back to life.”

The idea for “Faces: Portraits of the Community” came from former Edwardsville Arts Center board member Julie Bond, who saw it as a way to get more local residents involved.

The opening will include a wine tasting by Mary Michelle Winery in Carrollton. It’s free and open to the public.

Admission to the Sneak Peak fundraiser is $35. Tickets can be purchased at the door. Hors d’oeuvres will be served by Amy Zipanci, who is preparing to open Fond in October.

The new restaurant will occupy a storefront in the historic Bohm Building. Its seasonal, American menu will emphasize fresh ingredients and locally produced meat, poultry, eggs and produce.

On Friday, Zipanci will serve chickpea crackers with humus and chermoula, gruyere and proscuitto with pickled pepper relish and lemon and rosemary shortbread.

“The exhibit is a real local exhibit with all the faces, and hopefully (the restaurant) will become a face in the community,” she said. “It’s like my debut.”

Edwardsville Arts Center is at 310 Hillsboro Ave. Photographs will be available for purchase. For more information, call 655-0337 or visit the Web site at www.edwardsvilleartscenter.org.

Contact reporter Teri Maddox at [email protected] or 345-7822, ext. 26.

‘Faces: Portraits of the Community’

Where: Edwardsville Arts Center, 310 Hillsboro Ave.

When: Friday through Sept. 21.

Regular hours: 11 a.m. to 5 p.m. Wednesday through Friday and 11 a.m. to 4 p.m. Saturday.

Opening reception: 7 to 9 p.m. Friday; free.

Preview fundraiser: 5 to 7 p.m. Friday; $35.

Information: Call 655-0337 or visit the Web site at www.edwardsvilleartscenter.org.

—–

To see more of the Belleville News-Democrat, Ill., or to subscribe, visit http://www.belleville.com.

Copyright (c) 2008, Belleville News-Democrat, Ill.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

Vegetarian Times Implements Cover-to-Cover Redesign

EL SEGUNDO, Calif., Aug. 7 /PRNewswire/ — In its September issue, Vegetarian Times (vegetariantimes.com), the country’s leading vegetarian magazine, debuts its cover-to-cover redesign. From new editorial departments to a new logo, the redesign gives readers more how-to information, cutting-edge coverage on the health benefits of vegetarian food, and a cleaner, modern, more inviting look.

   The redesign features:    -- A sleeker, updated and larger logo.   -- Clearer, easier-to-read recipes.   -- More location photography.   -- Elegant, more sophisticated fonts and color palette to complement the      natural brightness of vegetarian food.   -- A new tagline -- "Eat Green, Live Well," reflecting the magazine's      message that eating fresh vegetarian food is not only pleasurable, it's      also good for you and the world around you.    

In addition, the redesign features new editorial departments including the following:

   -- "Technique" Shows readers how to hone their cooking skills and how to      choose and use specific kitchen tools.   -- "Peak Season" Tells shoppers how to select the best available in-season      produce.   -- "Healing Foods" Offers cutting-edge coverage on the health-boosting      powers of natural foods, plus "Supplement Savvy" sidebars that guide      consumers in choosing and using healing foods in supplement form.    

“As the only epicurean magazine dedicated to vegetarian cooking and health, we wanted to create a fresh, modern look and feel that would truly inspire as it informs,” says VT Editor in Chief Elizabeth Turner. “The addition of more cooking how-to’s, recipes and tips from leading green chefs, and expert advice on shopping smart and eating healthfully, will give readers the concrete information they need to make delicious, smart food choices.”

“I wanted to give Vegetarian Times a modern, friendly look,” says VT Creative Director Daphna Shalev. “Our goal was to showcase the beautiful food photography and make the magazine more readable and accessible.”

“Vegetarianism is no longer a niche, it’s a movement,” says VT Vice President and Publisher Bill Harper. “People are eating a more plant-based diet for moral, political, environmental, and health reasons, and as a result, our readership and sales are skyrocketing. Because of our unique editorial product and low duplication with other epicurean or women’s service magazines, we expect a strong increase in advertising pages over the next few years!”

The redesign comes amidst strong sales for the magazine. Over the previous year, newsstand sales are up 25 percent, subscription sales are up 5 percent, and ad pages have grown 13 percent. The increased sales figures reflect the growing popularity of vegetarian food. According to the Vegetarian Times “Vegetarianism in America” survey, 3.2 percent of U.S. adults, or 7.3 million people, follow a vegetarian-based diet, and 10 percent of U.S. adults, or 22.8 million people, say they largely follow a vegetarian-inclined diet.

About Vegetarian Times: For over 30 years, Vegetarian Times has been at the forefront of the healthful-living movement, providing recipes, expert wellness information, and environmentally sound lifestyle solutions to vegetarians, vegans, and nonvegetarians alike.

The magazine was acquired by Active Interest Media (aimmedia.com) in 2003. Based in El Segundo, Calif., AIM is a consumer enthusiast media company that serves a base of loyal constituents through print, events, and online products. The company was formed in October 2003 by Efrem “Skip” Zimbalist III and the private equity investment firm Wind Point Partners.

In addition to its Healthy Living Group-which includes Yoga Journal, Backpacker, Vegetarian Times, Better Nutrition, Optimum Wellness, SNEWS(R) and Whole Foods Market(R) magazine-the company also publishes Southwest Art, American Cowboy, Log Home Design, Log Home Living, Timber Home Living, Building Systems, Black Belt, and Yachts International. AIM produces and markets videos and books and produces 12 shows on log homes and more than two dozen building seminars. The company also produces the Fort Lauderdale International Boat Show(R), the largest boat show in the world.

Vegetarian Times

CONTACT: Dayna Macy, +1-415-591-0555, ext. 304, [email protected], forVegetarian Times

Web site: http://www.yogajournal.com/

Aging Population Makes for More Visits to the Doctor’s Office

By Nanci Hellmich

The aging of the U.S. population is translating into many more visits to doctors’ offices and hospitals, a reality that is taxing weak spots in the health care system, a government report said Wednesday.

People made an average of four visits a year to doctors’ offices, emergency rooms and hospital outpatient departments in 2006, a total of 1.1 billion visits.

The number of medical visits increased 26% from 1996 to 2006, significantly higher than the 11% population growth during that period.

Older people are more likely to seek medical care, says Catharine Burt of the Centers for Disease Control and Prevention’s National Center for Health Statistics. And today’s seniors make more visits to the doctor than older people did 10 years ago, she says.

“Older people represent a larger proportion of the hospital inpatient case load,” Burt says. “They have more complications and have to have more done for them. So that makes the job of the nurses and people taking care of hospital patients much harder than it was 30 or 40 years ago.”

Meanwhile, patients waited an average of about 56 minutes to see a doctor in the emergency room in 2006, up from 38 minutes in 1996.

The longer wait may be because more patients are going to a declining number of hospital emergency departments, Burt says.

But the wait statistic can be misleading because it is affected by statistics from large urban hospitals where it’s not unusual to wait longer than an hour. A typical wait is about 30 minutes, she says. People usually don’t wait very long in smaller communities.

The most common reasons adults give for going to the emergency room include chest pain, abdominal pain, back pain, headache and shortness of breath.

The most common reasons for emergency room visits for children under 15 are fever, cough, vomiting, earache and injuries to the head, neck and face.

Other findings:

*Half of all trips to doctors’ offices were made by people with chronic medical conditions. High blood pressure was the most common ailment, followed by arthritis, high cholesterol, diabetes and depression.

*Seven of 10 visits to doctors’ offices, emergency rooms and hospital outpatient departments resulted in at least one medication being either provided, prescribed or renewed for a total of 2.6 billion prescriptions. Painkillers were the most commonly prescribed medication and were the ones used most at primary-care facilities and in emergency rooms.

*The rate of knee replacement surgeries doubled for people ages 45-64 from 2000 to 2006.

For more health reports from the CDC, visit cdc.gov/nchs. (c) Copyright 2008 USA TODAY, a division of Gannett Co. Inc. <>

St. Baldrick’s Foundation Announces 2008 Grant and Fellowship Recipients

More than $12.6 million awarded for pediatric oncology research

For St. Baldrick’s Foundation

Jayme Burnett, 919-334-3779

[email protected]

Logo: http://www.StBaldricks.org

The St. Baldrick’s Foundation, a non-profit organization dedicated to raising money for childhood cancer research, announced today the organization’s first round of 2008 research grants, pediatric oncology fellowships and career development awards. St. Baldrick’s began as a challenge between friends, and has exploded into the world’s largest volunteer-driven fundraising program for childhood cancer research. Worldwide, 160,000 children are diagnosed with cancer each year and in the United States, cancer is the leading cause of death by disease among children.

The St. Baldrick’s Foundation coordinates worldwide head-shaving events, with volunteer “shavees” raising money to support childhood cancer research. Since 2000, head-shavings have taken place in 18 countries and 48 U.S. states, raising more than $48.5 million, and shaving more than 71,000 heads.

In June, grants and fellowship awards totaled more than $12.6 million and 2008 is the first year that St. Baldrick’s has awarded the newly-created Career Development Awards. Created to further the research of promising pediatric oncologists by bridging the funding- gap between their fellowships and sources of funding available to more established researchers, the Career Development Awards will provide much-needed research funding to twelve doctors during this critical stage of their careers.

All funding applications were evaluated by the foundation’s Scientific Advisory Committee and other expert reviewers, who made funding recommendations to the St. Baldrick’s Foundation’s Board of Directors. Research grants are awarded for a period of one year, pediatric oncology fellowships last for two years, with the possibility of being extended for a third year, while career development awards are of three year’s duration with a possible two year extension. A second round of grants for 2008 will be issued this fall.

“These grants were made possible by the extraordinary efforts of 34,244 St. Baldrick’s volunteers and more than 217,290 donors who have worked so hard and given so much to help children with cancer,” says Kathleen Ruddy, executive director, St. Baldrick’s Foundation. “The ever-increasing generosity of our supporters has enabled us to fund more grants and fellowships while introducing both the Career Development Award and funding the promising new Translational Genomics in Neuroblastoma research. We hope these grants lead the way to major developments in how childhood cancer is diagnosed and treated – giving kids a longer, higher quality of life. Our ultimate goal is to find cures for all childhood cancers.”

New St. Baldrick’s fellowships in pediatric oncology research were awarded at:

— University of Florida, Gainesville, Fla.

— The University of Chicago, Chicago, Ill.

— Children’s Hospital Boston, Boston, Mass.

— Dana-Farber Cancer Institute, Boston, Mass.

— Johns Hopkins University School of Medicine, Baltimore, Md.

— Children’s Hospital of Michigan, Detroit, Mich.

— University of Minnesota – Twin Cities, Minneapolis, Minn.

— Washington University in St. Louis, St. Louis, Mo.

— The Feinstein Institute for Medical Research, New Hyde Park, N.Y.

— Rainbow Babies and Children’s Hospital, Cleveland, Ohio

— The Children’s Hospital of Philadelphia, Philadelphia, Pa.

Continuing St. Baldrick’s fellowships were funded at:

— Mattel Children’s Hospital at UCLA, Los Angeles, Calif.

— University of California, San Francisco, Calif.

— Morgan Stanley Children’s Hospital of New York – Presbyterian, New York, N.Y. (Columbia University Medical Center)

— Children’s Hospital Boston, Boston Mass.

— The Children’s Hospital of Philadelphia, Philadelphia, Pa.

— Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas

Career Development Awards in pediatric oncology research were awarded at:

— Children’s Hospital Los Angeles, Los Angeles, Calif.

— University of California, San Francisco, Calif.

— University of Colorado at Denver, Anschultz Medical Campus, Denver, Co.

— Yale University, New Haven, Conn.

— Dana-Farber Cancer Institute, Boston, Mass.

— Johns-Hopkins University, School of Medicine, Baltimore, Md.

— University of Michigan, Ann Arbor, Mich.

— The Feinstein Institute for Medical Research, New Hyde Park, N.Y.

— Case Western Reserve University, Cleveland, Ohio

— Children’s Hospital and Regional Medical Center, Seattle, Wash.

— University of Wisconsin-Madison, Madison, Wis.

— Medical College of Wisconsin, Milwaukee, Wis.

This year’s research grant recipients are:

— The University of California, San Francisco, Calif.

— University of Florida, Gainesville, Fla.

— Indiana University, Indianapolis, Ind.

— Wayne State University, Detroit, Mich.

— Roswell Park Cancer Institute, Buffalo, N.Y.

— University of Rochester, Rochester, N.Y.

— The Feinstein Institute for Medical Research, Manhasset, N.Y.

— The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio

— The Pennsylvania State University College of Medicine, Hershey, Pa.

— The Children’s Hospital of Philadelphia, Philadelphia, Pa.

— Medical University of South Carolina, Charleston, S.C.

— Vanderbilt University, Nashville, Tenn.

— University of Texas Health Science Center, San Antonio, Texas

— Fred Hutchinson Cancer Research Center, Seattle, Wash.

With a $250,000 grant, the St. Baldrick’s Foundation becomes the first funder of a major research project called Translational Genomics in Neuroblastoma (TGiN), with grants awarded to three partner institutions:

— TGEN Foundation, Phoenix, Ariz.

— National Cancer Institute (NCI), Bethesda, Md.

— Children’s Hospital of Philadelphia, Philadelphia, Pa.

Funds raised through St. Baldrick’s events in other countries in 2007 also went to:

— Childhood Cancer Foundation Candlelighters Canada

— Children’s Cancer Foundation, Hong Kong

— CLIC Sargent, Headington, Oxford, U.K.

The largest St. Baldrick’s Foundation grant this year of $6,001,389 was awarded to CureSearch Children’s Oncology Group (COG), for cooperative research on a national scale. Of this, $5,230,000 will be distributed to over 200 institutions to support their participation in COG clinical trials. These include M.D. Anderson Cancer Center, Children’s National Medical Center, Sloan Kettering Institute for Cancer Research and other well-known institutions, as well as many smaller institutions across the country where children receive state-of-the-art treatment for cancer. This past year, participation in the COG’s clinical trials increased dramatically, partly due to St. Baldrick’s funding. This has resulted in more children having access to novel treatments, and it means greater progress into research to find cures for all childhood cancers.

About The St. Baldrick’s Foundation

The St. Baldrick’s Foundation, which became a non-profit organization in late 2004, makes grants to research organizations that meet stringent criteria and share the foundation’s commitment to fiscal responsibility and emphasis on research. St. Baldrick’s research grants help fill crucial funding gaps at medical institutions where children are treated for cancer, ensuring the finest care for every child. St. Baldrick’s fellowships enable some of the most promising new doctors to pursue pediatric cancer research as a career. For more information about St. Baldrick’s, please call 1-888-899-BALD or visit www.StBaldricks.org.

(c) 2008 BUSINESS WIRE. Provided by ProQuest Information and Learning. All rights Reserved.

Oklahoma County Jail’s Death Toll Draws Federal Ire

By Nolan Clay and John Estus, The Oklahoman

Aug. 7–The Oklahoma County jail can be a deadly place.

At least 44 jail inmates have died in the jail’s custody since Jan. 1, 2000, records show.

Several were suicides, often by hanging. A few were beaten to death by other inmates. One may have been killed by detention officers. Many died from natural causes, but sometimes those health problems may have been aggravated by beatings or poor care.

Some of the deaths were actually in the jail. Others occurred after inmates were moved for medical treatment.

Three times — in 1998, 2002 and 2005 — babies born to jail inmates did not survive.

In a year-old report made public this week, the U.S. Justice Department pointed to some of the deaths to justify its conclusion that inmates’ rights are being violated in the jail.

Federal officials removed 160 federal defendants from the jail because of the problems.

Among the factors behind the deaths are “an inordinately high risk of detainee-on-detainee violence,” virtually nonexistent direct supervision of detainees, “deficient suicide prevention” and inadequate health care, the report found. County officials insist improvements already have been made.

One of the examples in the Justice Department report was the 2005 baby death. The Justice Department said the care of the baby’s mother was “unconscionable;” the mother had been handcuffed to a rail for most of 10 hours.

How sheriff responds Oklahoma County Sheriff John Whetsel, who oversees the jail, said the number of deaths doesn’t seem high since the jail books in up to 45,000 people a year.

“The majority of the people who come in here are not those who take care of their health,” Whetsel said. “Even one death is too many, but unfortunately the vast majority of these are heart attacks or just health issues that lead to their death.”

Many inmates have serious drug-related health problems, Whetsel said.

“To us, every life is important regardless of who they are. Even a person who is here on some bad charge. … When they can’t save that life, our detention officers themselves become extremely emotional,” the longtime sheriff said.

Whetsel said suicide prevention procedures have been modified recently to provide closer monitoring of suicidal inmates. Such inmates are given paper gowns instead of cloth gowns to prevent possible hangings. They are checked on by detention officers every 15 minutes.

Typically, 15 to 20 inmates are under suicide watch at any time, Whetsel said.

“What you can’t reduce is the person who is determined to commit suicide but never expresses that,” Whetsel said.

—–

To see more of The Oklahoman, or to subscribe to the newspaper, go to http://www.newsok.com.

Copyright (c) 2008, The Oklahoman

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

WVU Alumni Association Recognizes Chapters

Speakeasy Picnic: Speakeasy Singles will have a picnic starting at 2 p.m. Aug. 24 at Shawnee Park in Dunbar. Hot dogs and Polish sausage will be served. The cost is $4 for members, $6 for non- members. Side dishes and desserts are welcome.

Speakeasy Dance: The Speakeasy Singles group is having a dance at 8 p.m. Aug. 9 in the Dunbar National Guard Armory. DJ Randy Justice will provide music. The cost is $8 for members, $10 for non- members. For more information, visit www.speakeasy singles.com or call (304) 345-7180 and leave a message.

NARFE Picnic: The National Association of Active and Retired Federal Employees Charleston Chapter 0166 will have their annual picnic Friday, Aug. 8, at the Southeast Nazarene Church Fellowship Hall, 5102 MacCorkle Ave., S.E., Kanawha City, at 1:30 p.m. For additional information, contact Robert Hardesty, (304) 346-5250.

Quick Community Center Yard Sale: Quick Community Center will host a yard sale on Saturday, Aug. 9. Tables for the sale will rent at $10 for inside tables and $5 for outside tables. Breakfast and lunch will also be available for sale. For more information or for rentals, call Melva Agee at (304) 965-7073.

New Beginnings Preschool: New Beginnings Preschool at The Charleston Baptist Temple will begin its 2008-2009 school year on Sept. 2. New Beginnings offers a faith-based academic curriculum for children ages 2 through 5. To enroll your child for one of the remaining class spots, call (304) 395-4311.

Health Care Employment Seminar: A free Health Care Career Seminar and review session for the Nursing Entrance Test will be conducted from 8:30 a.m. to 3:30 p.m. Saturday, Aug. 23, in Wallace Hall, Room 420, at West Virginia State University in Institute. Guest speakers include representatives from CAMC and the Kanawha County Schools/ RESA III SPOKES program, who will discuss employment and training opportunities in the Kanawha Valley. The session also includes a review for the NET test, which is required for entrance into the West Virginia State Community and Technical College Nursing Program or the Garnet Career Center Licensed Practical Nursing program. Registration is required by calling (304) 755-5536 and leaving your name, telephone number and the name of the workshop for which you are registering.

Family Swim & Movie: The Martin Luther King Jr. Community Center is hosting Family Swim and Movie Night on Friday, Aug. 8. Swimming will be from 6 to 7 p.m., followed by a movie from 7:30 to 9 p.m. The free event also features popcorn and drinks. For more information, call Kris Lawrence, (304) 348-6404.

Girl Scout Cookies: The Girl Scouts of Black Diamond Council Service Center are selling Girl Scout cookies – Thin Mints, Samoas, Tagalongs and many others – through Aug. 8. Cookies are $3.50 per box or $42 for a mixed case (12 boxes). You may also purchase cookies to donate to a local food pantry. Visit the center at 210 Hale St. in Charleston or call (304) 345-7722 to order or obtain more information.

Christian Women’s Brunch: Charleston Christian Women are sponsoring the “Back To School in Style” brunch from 11 a.m. to 12:30 p.m. Wednesday, Aug. 20, in the Chilton House restaurant, 2 Sixth Ave., St. Albans. Jean Heindel, owner of Childhood Treasures, will present a children’s style show. Marilou Johnson, a former elementary school teacher from Lock Haven, Pa., will speak on the topic “Find Your Way Through Fear, Stress and Disappointment.” Free nursery is available by reservation. The cost for brunch is $12. For reservations, call Tina at (304) 744-6914 or (304) 546-8212, or send e-mail to cwvcw@yahoo .com. Deadline for reservations is Aug. 15.

Greece/Italy Trip: A 10-day trip to Greece and Italy is being organized for area residents during students’ 2009 spring break. The cost is $2,336 per student and $2,696 per adult. Additional excursions are available, including Florence ($95) and a Greek evening out ($60). A $90 deposit is required, and prices will change in late September. For more information, contact Gloria Swecker, (304) 965-1193.

EBHS Alumni Band: The East Bank High School Pioneer Alumni Band will play at the annual EBHS Alumni Dinner Saturday, Sept. 27, at the Charleston Civic Center. Anyone who was in the band, including majorettes, is invited to participate. Rehearsals will start at 7 p.m. each Monday, beginning Aug. 25 (no rehearsal on Sept. 1, Labor Day) at East Bank Middle School. An extra rehearsal begins at 10 a.m. Saturday, Sept. 13. No auditions are necessary; just bring your instrument or baton. For more information, contact the alumni band director, Jim Anderson, at [email protected].

Book Festival Volunteers: Organizers of the West Virginia Book Festival are seeking volunteers to assist with the Oct. 11-12 event at the Charleston Civic Center. Volunteers will help in a variety of ways, including set-up, break-down, assisting authors and presenters and assisting with the used book sale, Festival Marketplace, children’s programs, crafts and information tables. The deadline for volunteers to apply is Aug. 15. Volunteer applications are available online at www.wvbook festival.org or call (304) 343-4646, ext. 246, for more information.

Punt, Pass & Kick: Charleston Parks and Recreation will host the 2008 Punt, Pass and Kick competition at 10 a.m. Saturday, Sept. 20, at the Martin Luther King Jr. Community Center in Charleston. For more information, call Kris Lawrence (304) 348-6404.

Clendenin Fall Festival: The GFWC Clendenin Woman’s Club is busy planning for the 29th Annual Fall Festival, which will be held on Sept. 27. All crafters, clubs, church groups and food vendors are invited to participate. Spaces are $20 until Sept. 15 and $25 afterward. To reserve space or receive more information, call Cindy Dye at (304) 548-6577 or Becky McLaughlin at (304) 548-8104. The club would also like to extend an invitation to anyone interested in participating in the parade. There will be a float contest with cash prizes for first and second place.

Gardening Workshops: The West Virginia State University Extension Service Agriculture and National Resources Program will present a series of workshops through October, with locations to be determined. They include “Food Storage & Preservation” ($10) on Aug. 26, “Drip Irrigation Basics” ($20) on Aug. 19, “Rain Garden Design” (free) on Sept. 24 and “Composting 101” ($20) on Oct. 22. To register or receive more information, call (304) 766-5711.

‘Nutcracker’ Auditions: The Charleston Ballet will hold auditions for roles in the Dec. 19-20 production of “The Nutcracker Ballet” at the Clay Center for the Arts & Sciences. Auditions will be held at the Charleston Ballet studios on Virginia Street East from 4 to 5:30 p.m. Thursday, Aug. 14. Students auditioning must be enrolled as a student at the American Academy Ballet, at least 9 years old and should be dressed for ballet class (leotards, etc.). Roles are available for various ages from 9 through teens. Students must have had some previous ballet training and be able to attend all specified rehearsals. Call the Charleston Ballet for more information at (304) 342-6541.

Dance Workshop: Gerard Murphy, a line dance choreographer and instructor from Nova Scotia, Canada, will conduct a one-day line dance workshop on Saturday, Sept. 27, at the Elks Lodge in Charleston. Registration begins at 9 a.m. The workshop will begin at 9:30 a.m. The cost is $40, which includes lunch and the evening dance. For more information, contact Becky Stone at (304) 949-3973 (e-mail: [email protected]) or Sandy Crist at (304) 779-9109 (e- mail: [email protected]).

YMCA After-School Program: Registration for the Charleston YMCA after-school program for students in kindergarten through eighth grade is underway. Middle school students will be housed at St. Mark’s Church in Charleston. Pick-up service will be available at Chamberlain Elementary School, Charleston Catholic High School, Holz Elementary, Horace Mann Middle, J.E. Robins Elementary, John Adams Middle, Kanawha City Elementary, Kenna Elementary, Mountaineer Montessori and at Overbrook, Piedmont, Ruffner, Sacred Heart, St. Agnes, Watts and Weberwood elementary schools. Immunization records are required at registration. For more information, call Michelle Lewis, 340-3535.

Health Class: As part of FamilyCare Health Center’s expanding education program, certified diabetes educator/registered dietitian Grace Gibson will present “Cooking With Grease: How Bad Can It Be? Trans Fats, Cholesterol and Others” on Wednesday, Aug. 27. The free program runs from 1 to 3 p.m. at the Family Enrichment Center, 1701 Fifth Ave., Charleston. Refreshments and door prizes will be available. To reserve a seat or find out more, call Suzanne Riley, 720-4851, Ext. 8131.

SHS ’88 Reunion: Sissonville High School Class of 1988 members are requested to visit www.shs20.com for information regarding the 20th-year reunion. It will be held Aug. 15 through Aug. 17. Activities include dinner for adults and a picnic for the family. If you have not been contacted, call Becky Anderson Stricklen at 984- 2888 or e-mail [email protected], or Laura Boggess Casto at 988- 0528 or e-mail [email protected]. You can also register on the Web site.

Pooches’ Pool: The North Charleston Community Center, 2009 Seventh Ave., will open its swimming pool to dogs from 5 to 7:45 p.m. Monday, Aug. 11, through Friday, Aug. 15, and 10 a.m. to 4 p.m. Saturday, Aug. 16. There is no fee to participate, although donations of dog food and supplies will be accepted for the Kanawha Charleston Humane Shelter. For more information, contact Cheryl Gaynor at 348-8008 or [email protected]

Aluminum Donations: The Ronald McDonald House collects aluminum tabs from soda cans, old telephones and used computer ink cartridges. They can be dropped off between 9 a.m. and 9 p.m. at 302 30th St., Charleston (near CAMC Memorial).

Preschool Openings: Christ Church United Methodist’s preschool, The Growing Place, 1221 Quarrier St., Charleston, has openings for the coming school year. The Growing Place offers W.Va. Pre-K. For more information, contact Kim Kristic at 342-0192.

Zumba: Two new Zumba fitness classes are beginning at North Charleston Community Center, 2009 Seventh Ave., in Charleston. The classes will be: Beginner’s Zumba, Tuesdays from 5:30 to 6:30 p.m., with instructor Fran Anderson – this class will feature Zumba combining Latin rhythms with cardiovascular exercise to create an aerobic routine that is fun and easy to follow; Zumba Basics and Toning, Thursdays from 6 to 7 p.m., with instructor Debbie Sizemore – this class will feature modifications to accommodate all fitness levels from the young to the very young at heart, and is a low- impact fitness program that combines Latin rhythms with fun, simple movements to provide a safe cardiovascular exercise. Either class is $20 for four weeks. Contact Tonya at 348-6884 for information.

Brazilian Jiu-Jitsu: North Charleston Community Center, 2009 Seventh Ave., will be hosting Brazilian Jiu-Jitsu classes Mondays and Wednesdays from 6:15 to 8 p.m. The classes are for ages 15 to adult. The cost is $30 for four weeks, one night weekly and $55 for four weeks, two nights weekly. The instructor will be Butch Hiles, highest-ranked Brazilian Jiu-Jitsu instructor in the area. Contact Tonya Cummings at 348-6884 for more information.

Pre-K Program: The Learn and Play Center in the Schoenbaum Family Enrichment Center is accepting applications for its Pre-K and child- care program. Students must be 4 years old on or before Sept. 1. For information, call Sharon Bowles, 414-4420.

Cabin Creek Book: “Pictorial History of Cabin Creek,” a 223-page book with more than 400 photographs and a brief history of each community, is available at Billo’s in Eskdale and Chelyan and Frog Creek Books, Capitol Market, Charleston, or it may be ordered directly from author Dale Payne, Route 3, Box 75, Fayetteville, W.Va. 25840. Each book is $25, plus $4 shipping/handling.

Cabin Creek Photos: More vintage photographs of the Cabin Creek area and the different communities, especially pictures of the schools, churches, businesses or different events on Cabin Creek are being sought by a Fayette County author/historian. If you have any of these that you would like to share with others or old family photographs from the first part of the 1900s that you would like to see appear in “A Pictorial History of Cabin Creek Vol. II, contact Dale Payne, Route 3, Box 75, Fayetteville, W.Va. 25840; 304-574- 3354 or [email protected]

Preschool Enrollment: The Bream Center at Bream Memorial Presbyterian Church at 317 Washington St. West, Charleston, is enrolling for the 2008-2009 school year. Preschool classes for ages 2 to 5 are available, with early arrival and after-school care. For more information, contact Georgeanne Leake at 346-2551.

First Presbyterian Preschool: First Presbyterian Church Preschool on Leon Sullivan Way in downtown Charleston is accepting registrations for its 1-year-old classes. To be eligible for the class, children must be 1 year old by Sept. 1, 2008. Classes meet once a week from 9:15 a.m. to 12:15 p.m. Call the preschool office for more information, 343-8961, ext. 128 or e-mail at [email protected].

School Enrollment: Bible Baptist Christian School is accepting enrollment applications for the 2008-2009 school year. Bible Baptist Christian School encompasses grades K-12.

Public Notice: Lower Elk River Ministry Association Food Pantry, 1 Timberdale Lane, Pinch, W.Va. 25156, provides USDA Commodities. In accordance with civil rights policy, the USDA prohibits discrimination in all its programs and activities on the basis of race, color, national origin, sex, religion, age, disability, political beliefs, sexual orientation, or marital or family status. Any person who believes he or she has been discriminated against by any USDA-related activity should write to the USDA, Director: Office of Civil Rights, Room 326, W. Whitten Bald, 1400 Independence Ave., S.W., Washington, D.C. 20250-9410. Tom Knopp, director.

DuPont Retirees: The DuPont retirees breakfast club meets at 7 a.m. on the first Monday of each month in the Shoney’s restaurant on the boulevard in Charleston. “Koolie” is the host. For more information, call Don Bibbee, 744-8810, or Koolie in the evenings at 965-1623.

EBHS ’60s Reunion/Dance: On Friday, Sept. 26, the second Annual Reunion Dance for the East Bank High School graduates of 1960 through 1969 will be held at the Beni Kedem Shrine Center, beside the Charleston Civic Center. Sixties-era dance music will feature the Fabulous Esquires (Larry Kopelman) and the Rhapsody Variety Band (Jim Anderson). Dress is casual. A free tailgate party will include barbecues, hot dogs and nachos. Special recognition will be given to the EBHS Classes of 1963 and 1968. Door prizes will be awarded. The cost is $25 per person (which includes food). Participants may also BYOB and snacks. To find out more, contact Carol O’Meara (Carpenter) at 949-2036; 13517 Nancy Ave., Chesapeake, W.Va. 25315; or [email protected]. Reservation forms are available from the class contacts, on-line from Jim Anderson at [email protected] or by mail from Larry Kopelman, 9 Pennsylvania Ave., Charleston, W.Va. 25302.

EBHS Dinner/Dance: The annual East Bank High School Alumni Dinner/ Dance will be held on Saturday, Sept. 27, at the Charleston Civic Center. A social hour will start at 5:30 p.m., followed by the dinner/dance. Anyone who attended or graduated from EBHS or who taught there is invited; reservations are required, and reservation letters will be mailed in August. James K. McCune, Class of 1963, will be the Alumnus of the Year. For more information, call Nancy Pat Maloney, (304)-595-1040 or Hope Stanley, (304)-949-2931. Visit the Pioneer Web site: http://[email protected]/Pioneers71/index.html

EBHS Golf Tournament: The East Bank High School Alumni Association will host a golf tournament on Friday, Sept. 26, at Little Creek Park. Tournament proceeds will go to the Dana and Ethel Irving Scholarship Fund. For more information, contact Sallie Pat Tackett at 595-1626.

YMCA Preschool: Registration for the Charleston YMCA of the Kanawha Valley’s 2008-2009 preschool, for ages 3 to 5, is underway. Enrollment will be ongoing until classes are full. For more information, call 304-340-3535.

Tyler Mtn. Y Preschool: The Tyler Mountain YMCA, 5113 Rocky Fork Road, Cross Lanes, is accepting fall 2008 half-day preschool registrations for ages 3 to 5. The registration fee is $35 (one- time-only fee). For more information, call Jason Wilson, 776-3323.

Cookbook: The Arc of The Three Rivers, a nonprofit organization that provides services to individuals with intellectual and developmental disabilities, is selling a fundraising cookbook titled “A Recipe Collection.” The cookbooks are $12 or buy three or more for $10 apiece. All proceeds will go toward client activities and programs. Cook for a good cause with The Arc. Contact Nicky Richard at 344-3403 or [email protected] to purchase your copy.

Infant Care Class: FamilyCare offers a two-hour class to help new parents learn to care and feed their newborn babies. Topics discussed include diapering, swaddling, SIDS prevention, bathing, signs of illness, cord and circumcision care, breastfeeding and more. The class meets once a month. To register, call Debi Ellis at 757-6999 ext. 80 or e-mail at [email protected].

Childbirth Classes: FamilyCare is offering ongoing childbirth education classes in the Charleston area. The classes discuss birth options, the labor process, medications and more. This class series meets for two Thursdays each month from 6 to 8:30 p.m. Registration is required, and Medicaid patients are welcome. To register, contact Debi Ellis at 757-6999 ext. 80 or [email protected].

Overeaters Anonymous: Overeaters Anonymous meets at 7 p.m. on Thursdays in the Salvation Army Citadel Church, 301 Mary St., Charleston. For more information, call Jane at 344-0042.

Cookbook: Central United Methodist Church, 731 Bigley Ave., on Charleston’s West Side, has compiled a cookbook of recipes from members and friends of the church. The cost is $10, with proceeds going to the United Methodist Women for missions. For more information or to purchase a copy of the book, contact the church at 343-3059, Doris Parkins at 343-1935, or Mary Lucas at 965-5247.

Free Clothing: Jordan Light Missionary Baptist Church, 801 Upper Wills Creek Road, Elkview (bottom of Jordan Hill), has a clothes closet for anyone needing free clothes. The closet is open the first Saturday of each month from 9 a.m. to 3 p.m. and at other times by appointment. Contact Carol Holley or Ruth Dawson for more information.

Kickboxing Classes: Kickboxing classes are offered from 7 to 8:30 p.m. on Tuesdays and Thursdays in the North Charleston Community Center, 2009 Seventh Ave., Charleston. The class is suitable for learning self-defense or for fighting competitively. The cost is $20 a month for one class a week, $35 a month for twice a week.

Elk River Exercise Room: Elk River Community and Education Center’s Exercise Room has a wide variety of treadmills, elliptical trainers and weight equipment available for use by the public. The cost to use the exercise room is $1 per session. Volunteers are on- site to assist with the equipment and any questions. Call 965-3722 for more information on the Elk River Community and Education Center’s Exercise Room, which is open Monday through Friday from 10 a.m. to noon and Monday through Thursday evenings from 6 to 8 p.m.

Entertainment Books: The Charleston West Lions Club is selling entertainment books containing coupons good at area restaurants and other businesses. Books are $25 each, with money from sales going to the Lions Club’s sight fund. To purchase a book, call Evelyn Coleman, 768-7400, or Phyllis Fisher, 344-2260.

Debt Management: The Kanawha Institute for Social Research & Action Inc. is accepting applications for the KISRA Debt Management Program. Anyone interested in participating should call 768-1300 for more information. This program is sponsored in part by The Greater Kanawha Valley Foundation. KISRA, a HUD-certified Housing Counseling Agency and Community Housing Development Organization, is also the faith-based and community-serving initiative of Ferguson Memorial Baptist Church.

KISRA Savings: The Kanawha Institute for Social Research & Action Inc. is accepting applications for an Individual Development Savings Program. Anyone interested in participating should call 768-1300 for more information. KISRA, a HUD-certified Housing Counseling Agency and Community Housing Development Organization, is also the faith- based and community-serving initiative of Ferguson Memorial Baptist Church.

Kanawha History Book: “Kanawha Co., WV Deaths 1853-1900” is available from the West Virginia Genealogical Society, P.O. Box 249, Elkview, WV 25071. “Volume 1 A-L” and “Volume II M-Z & Slaves” are $28 each, which includes shipping and handling. For more information, call 304-965-1179 Monday or Wednesday from 10 a.m. to 7 p.m.

Youth Science Class: David Hartley, West Virginia Extension 4-H Youth Development agent, will be holding a monthly program/class in the Science Room at the Elk River Community Center. All youth from local communities are welcome to participate. Dates and times will be announced in the near future. If you are interested or need more information, call the center at 965-3722.

Army Reserves Cookbook: The U.S. Army Reserves 38th RSG Family Readiness Volunteers are selling cookbooks containing over 400 of their favorite recipes. All proceeds benefit their Family Support Group. To order, send $15 to 101 Lakeview Drive, Charleston, W.Va. 25313 Attn: Family Support. Make checks payable to 38th ODGP. The cookbook will be mailed directly to you within a few weeks.

SoLife Singles: The SoLife Christian singles group for ages 30 to 55 meets on the first Friday of each month in churches throughout Kanawha and Putnam counties. For more information about SoLife, call 727-4907 or e-mail [email protected].

Problem Eaters Anonymous: Has everything else failed? Problem Eaters Anonymous is a 12-step solution based on the text of Alcoholics Anonymous. The group meets from 7 to 8 p.m. on Mondays in the Nitro Baptist Church and from noon to 1 p.m. Thursdays at 1601 Virginia St. East in Charleston. There are no dues or fees. For directions or questions, call Jane M. at 755-1173.

Utility Assistance: If you are having a problem with a utility company and been unable to resolve the problem, the Public Service Commission of West Virginia maintains a staff of consumer affairs technicians who can answer questions and may be able to help. For more information, call 1-800-642-8544 or log on to www.psc.state.wv.us.

MADD: The Mothers Against Drunk Driving Southeastern Affiliate is seeking volunteers to work with families who have been injured or experienced a loss due to drunk driving. Volunteers are also needed to help with public awareness events, prevention education, activism, office support, court monitoring, and to serve on the affiliate advisory committee. For more information, call 776-0222.

Literacy Speakers: Literacy Volunteers of Kanawha County, Inc., is making speakers available to area organizations to discuss the group’s work with its clients, and the availability of opportunities for service to improve the quality of life for those clients. Literacy Volunteers have from three to four training classes a year to train volunteer tutors to work one-on-one with clients. For more information, call 343-7323 (343-READ) or e-mail Literacy Volunteers at [email protected].

Quilters Needed: Patches and Pieces Quilting Club is looking for quilters to add to the club. Beginners are welcome. The club is starting a new project now. For more information, call Betty Witt at 346-7600.

Quilters Needed: The Peacemakers quilting group at the Elk River Community Center is seeking quilters to help with a backlog of quilts and a special quilting project. The Peacemakers donate all receipts to charitable and non-profit causes. Anyone interested in more information should call coordinator Mildred Lyons at 965-1961 or 965-3722.

Book Donations: The Elk Valley Branch Library is accepting donations of paperback and hardback fiction books. For more information, telephone the library at 965-3636.

GED Class: The Kanawha County Schools/RESA III Adult Basic Education program is offering a free GED and basic skills class from 5:30 to 8:30 p.m. Monday and Thursday at the Elk River Community Center in Elkview. To enroll in the class, call 755-5536 and leave your name and a telephone number where you may be reached.

Genealogy Assistance: The Church of Jesus Christ of Latter-Day Saints offers genealogical help at its facility on McClure Parkway, Charleston, next to Flinn Elementary School. Workers will help with research, and there are computers, microfilm and microfiche readers and books available. The service is free, although there is a small charge for films ordered from Salt Lake City. Hours are from 5 to 9 p.m. Wednesday, 9 a.m. to 9 p.m. Thursday and 10 a.m. to 3 p.m. Saturday. For more information, call Betty Y. Montgomery at 984- 9292.

Second Seating: The YWCA of Charleston is seeking donations of new and good quality used furniture and household items to sell at its Second Seating store at 412 Elizabeth St. in Charleston. Quality gently used furniture or household items, and donations of upholstered items and dressers, beds, bedroom suites and wall art are also needed. Store hours are 10 a.m. to 5 p.m. Monday through Saturday. To arrange for pick-up of larger pieces of furniture, call 344-1348. Donations are tax-deductible.

Genealogy Books: The West Virginia Genealogical Society has many books for researching for sale (census, births, deaths, cemeteries). For a complete listing and prices, call (304) 965-1179, Monday and Wednesday 10 a.m. to 7 p.m. and Saturday 10 a.m. to 2 p.m.

Cemetery Upkeep: Donations for the upkeep of the Reed-Stephenson Cemetery may be made to the Reed-Stephenson Cemetery Fund at the Clay County Bank in Clay.

LERMA: The Lower Elk River Ministry Association will be open each Tuesday from 9 a.m. to noon with food and clothing. For more information, call Ellen at 965-6703 or Joyce at 965-0345.

Sight & Sound Program: The Elk Lions Club accepts donations of hearing aids and eyeglasses at the following locations: Kroger at Crossings Mall, Elk River Community and Education Center, Gibson’s Dental Office, St. Andrew Presbyterian Church, Whittington’s Optometry, Charleston Elks Lodge #202, the Elk Valley Public Library and Elkview Middle School. For more information about donations to this charitable effort or joining the Elk Lions Club, call 965- 3125.

Elk History Book: The Elk-Blue Creek Historical Society’s two- volume, hardback history books are available for purchase. Volume I is $40 and Volume II is $48, with no duplications in the stories. The books include general, family, business and service histories. The Elk-Blue Creek Historical Society is a nonprofit volunteer organization. To order, call 984-3616, 965-5016 or 562-4717.

Exercise Group: The Elk Valley Exercise Group meets at Trinity United Methodist Church, 2626 Pennsylvania Ave., Charleston, from 9 to 10 a.m. each Monday, Wednesday and Friday.

Line/Pattern Dancing: The Extreme Country Dance Club sponsors a line and patterned partner dance and classes every Friday evening at the Elk Elementary Center in Crede. Beginning and intermediate line dance classes are conducted from 6:30 to 7:30 p.m. Patterned partner classes are held from 7:30 to 8 p.m. An open dance is held from 8 to 10:30 p.m., with music supplied by a DJ. Admission is $5 for nonmembers and $3 for members. For further information, e-mail [email protected] or call 949-3973, 779-9109 or 346-7467.

(c) 2008 Charleston Gazette, The. Provided by ProQuest Information and Learning. All rights Reserved.