NEW YORK, Feb. 14 /PRNewswire-FirstCall/ — Scholastic, the global children’s publishing, education and media company, today announced that it is opening two on-site employee health care facilities in its Jefferson City, MO and New York City locations. The Scholastic Wellness Centers are intended to provide convenient basic health care, improve the rate of early diagnosis resulting in more timely intervention and treatment, and provide coaching on healthier lifestyles to interested employees while effectively managing health care costs. About 2,000 employees and their families in Missouri and 2,000 employees in New York City will have access to medical professionals at the sites.

“Many employees have expressed interest in knowing how they can take better care of their health, and the Wellness Centers will allow them to get practical information and help right on site,” said Chris Cunningham, Vice President, Compensation and Benefits for Scholastic. “By making it easy for employees to seek prompt medical attention, we hope to help them catch small problems before they become big ones and reduce the cost of more expensive treatments that are required if problems go untreated.”

The two Wellness Centers will be managed by Whole Health Management Inc., an award-winning innovator in health care, delivering high quality on-site services to over six million patients at organizations nationwide. Each Center will be staffed by a physician, a nurse practitioner and a medical assistant. A registered nurse will also be on staff in Jefferson City.

The Wellness Centers are part of the company’s “Live Well” campaign, which also includes: employee health assessments; health coaching for employees who want support to lose weight, quit smoking, or just improve their overall health; condition management programs for chronic illnesses; access to fitness facilities; and a full range of medical benefits and employee assistance programs.

Mr. Cunningham added, “Based on early feedback from employees in Jefferson City and the strong turnout of New York City staffers for flu shots this fall, we can see that our employees are enthusiastic about using the services provided by the new Centers and that we are taking important steps toward improving the health of our workforce while managing costs.”

About Scholastic

Scholastic Corporation is the world’s largest publisher and distributor of children’s books and a leader in educational technology. Scholastic creates quality educational and entertaining materials and products for use in school and at home, including children’s books, magazines, technology-based products, teacher materials, television programming, film, videos and toys. The Company distributes its products and services through a variety of channels, including proprietary school-based book clubs, school- based book fairs, and school-based and direct-to-home continuity programs; retail stores, schools, libraries and television networks; and the Company’s Internet site, http://www.scholastic.com/.

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By Cao, Ming; Eshoa, Camellia; Schultz, Christopher; Black, Jennifer; Et al

* Histiocytic sarcoma is a rare, malignant neoplasm of the lymphohematopoietic system that usually occurs in the skin, lymph node, and intestinal tract. Here we describe a unique case of primary central nervous system histiocytic sarcoma that initially showed an indolent clinical course following local resection and radiotherapy. However, relapse of disease within the mediastinum was noted 3 years later. Biopsies of the initial brain lesion and subsequent mediastinal recurrence each revealed an identical, diffuse proliferation of histiocytes with expression of CD45, CD68, and CD163 but not pan-cytokeratin, epithelial membrane antigen, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, ALK-1, PAX- 5, CAM 5.2, S100, CD1a, or glial fibrillary acidic protein. In the literature, central nervous system histiocytic sarcoma portends a poor prognosis with median survival of 4.5 months. To our knowledge, this case represents the first case of ”lowgrade” primary central nervous system histiocytic sarcoma with relatively indolent clinical course. A thorough discussion of the differential diagnosis of histiocytic sarcoma and a review of primary central nervous system histiocytic sarcoma are also presented.

(Arch Pathol Lab Med. 2007;131:301-305)

Histiocytic sarcoma (HS) is a rare, lymphohematopoietic malignant neoplasm composed of tumor cells showing morphologic and immunophenotypic features of mature tissue histiocytes. Histiocytic neoplasms of the lymphohematopoietic system have had various names including histiocytic lymphoma, malignant histiocytosis, histiocytic medullary reticulosis, reticulum sarcoma, and malignant histiocytosis. These tumors were initially considered histiocytic in origin based on morphology alone. Subsequently, it has been recognized that most of these tumors are actually large T-cell, B- cell, or anaplastic lymphomas by modern immunophenotypic techniques.1 In the current World Health Organization classification, the diagnosis of HS requires the verification of histiocytic lineage and exclusion of malignancies of other lymphohematopoietic lineages with extensive immunophenotypic workup including histiocytic markers such as CD68, lysozyme, MAC387, 1- antitrypsin, and 1-antichymotrypsin. However, these markers are not always specific for histiocytic differentiation. Recently, several authors have reported that CD163 (hemoglobin scavenger receptor) may be a more specific marker of the monocytic/histiocytic lineage. 2-5

Histiocytic sarcoma usually arises in lymph nodes, skin, and the intestinal tract.6,7 Primary central nervous system (CNS) HS is extremely rare and all cases reported have shown a very aggressive clinical course with a median survival of 4.5 months (Table).8-10 We describe a unique case of primary CNS HS with what appeared to be a relatively indolent clinical course following local resection and radiotherapy until extracranial relapse was identified 3 years later. A thorough discussion of the differential diagnosis of HS and a review of primary CNS HS are also presented.

REPORT OF A CASE

A 53-year-old woman presented with a left anterior mediastinal mass and a right hilar mass (Figure 1, A through C). Her past medical history was significant for a brain tumor diagnosed 3 years prior to presentation. She presented at that time with numerous CNS abnormalities secondary to the tumor, including significant visual field impairment, a right third cranial nerve deficit with ptosis, double vision, limitations in ocular mobility, difficulty walking, headache, and generalized malaise. The lesion was a multilobulated mass located in the right retro-orbital area with an epicenter in the right cavernous sinus, measuring 3.1 = 2.9 = 2.2 cm. Magnetic resonance imaging showed extension into the sella turcica with complete occlusion of the right internal carotid artery (Figure 1, D and E). Subsequently, a right frontotemporal craniotomy with creation of a bone flap, microscope-assisted decompression, and subtotal removal of the right cavernous sinus tumor were performed. The pathologic diagnosis was reported as chronic inflammation and fibrosis. She received empiric external beam radiation with a total dose of 5400 cGy. After completing therapy, she experienced gradual improvement in symptoms with complete disappearance of tumor. Annual surveillance with magnetic resonance imaging did not show evidence of tumor recurrence in the brain (Figure 1, F).

Clinical evaluation of the new mediastinal mass revealed 4 ovoid lesions on computed tomographic imaging with intravenous contrast scanning of the chest: 2 lesions in the right hilum and 2 lesions in the left chest. The largest tumor measured 9.0 = 7.0 = 8.0 cm. There was a small left pleural effusion. An ultrasound- guided aspiration and biopsy were performed on the left anterior mediastinal mass and the resulting specimen was submitted for pathologic examination. She received 3 cycles of cyclophosphamide, doxorubicin, and vincristine, and prednisone without noticeable improvement. At the same time, she developed bony metastasis in the right hip and thoracic vertebrae. The metastases were treated with radiation but without response. She developed severe respiratory distress, chest pain, and pleural effusion. Subsequent salvation chemotherapy with ifosfamide, carboplatin, and etoposide was administered, but she received only 1 cycle before going to hospice care. She died shortly thereafter, 7 months following the development of the mediastinal masses.

MATERIALS AND METHODS

The brain and mediastinal biopsy specimens were fixed in 10% buffered formalin, embedded in paraffin, sectioned (4 m), and stained with hematoxylin-eosin. Immunohistochemical stains were performed for the following markers: CD1a, CD3, CD15, CD20, CD30, CD43, CD45, CD68, CD79a, CD138, CD163, myeloperoxidase, pan- cytokeratin, epithelial membrane antigen, ALK-1, PAX-5, CAM 5.2, S100, and glial fibrillary acidic protein. Immunoglobulin heavy- chain (IgH) and T-cell receptor = (TCR=) gene rearrangement clonality were determined by polymerase chain reaction using the IgH and TCR= gene rearrangement assays (InVivoscribe Technology, San Diego, Calif) with ABI (Applied Biosystems, Foster City, Calif) fluorescence detection. Polymerase chain reaction was performed in 20-L reaction with consensus primers for framework region 3 (FR3) and JH, 100 ng DNA from paraffin-embedded lymph node tissue, dNTP, Taq polymerase, and 4.0 mM Mg2α using Lightcycler (Roche Diagnostic). The sequences of the primers were 5

RESULTS

Cytologic smears of the mediastinal mass revealed a population of large neoplastic cells with eccentrically situated round to irregular, lobulated nuclei, some with distinctive nucleoli, and abundant cytoplasm (Figure 2, A). There were also many scattered small reactive lymphocytes. The biopsy showed a diffuse infiltrate of large noncohesive polygonal cells with oval to slightly irregular nuclei, distinct nucleoli, vesicular chromatin, and abundant eosinophilic cytoplasm (Figure 2, B). Some cells with more pleomorphic features and occasional giant cells with multilobated nuclei were present. There was focal necrosis, but mitotic figures were rare. Hemophagocytosis or emperipolesis was not identified. There were many scattered small reactive lymphocytes present within the infiltrate. The vast majority of these lymphocytes were of T- cell lineage (CD3α). Tumor cells invaded the adjacent pulmonary parenchyma.

Immunohistochemical staining of the mediastinal masses showed that the neoplastic cells were positive for CD45, CD68 (Figure 2, C), and CD163 (Figure 2, D), but negative for CD1a, CD3, CD15, CD20, CD30, CD43, CD79a, CD138, myeloperoxidase, pan-cytokeratin, epithelial membrane antigen, ALK-1, PAX-5, CAM 5.2, S100, and glial fibrillary acidic protein. There were scattered Ki-67 positive cells (approximately 20%). The IgH and TCR= gene rearrangement studies by polymerase chain reaction showed polyclonal B- and T-cell populations. The bone marrow evaluation revealed no evidence of acute myeloid leukemia, myeloproliferative disorders, myelodysplastic syndromes, or involvement of HS.

Review of the prior brain biopsy demonstrated a diffuse infiltrate composed of neoplastic cells with histomorphologic and immunophenotypic features almost identical to those seen in the mediastinal masses, although the degree of cytologic atypia was less pronounced in the brain tumor (Figure 2, E and F). The background of mixed inflammatory cells, including neutrophils, lymphocytes, and plasma cells, was more prominent in the CNS lesion, which may have been the basis for the previous pathologic impression of an inflammatory infiltrate. The diagnosis of HS in the mediastinum and CNS was then rendered based on the previously described findings.

COMMENT

The differential diagnoses that should be considered in cases of HS are numerous and include hematopoietic and nonhematopoietic lesions. Comprehensive immunohistochemical study excludes many of these diagnoses and confirms the diagnosis of HS. Negative staining for pan\-cytokeratin, epithelial membrane antigen, and CAM 5.2 rules out carcinoma or meningioma. Negative S100 protein staining does not support a diagnosis of melanoma. The absence of CD15, CD20, CD79a, PAX5, CD30, CD3, and ALK-1 expression as well as the lack of clonal IgH and TCR= rearrangement exclude Hodgkin lymphoma, poorly differentiated large B-cell/T-cell lymphoma, and anaplastic large cell lymphoma. Langerhans cell histiocytosis and interdigitating dendritic cell tumors are excluded with negative CD1a and S100 protein. Plasma cell neoplasms are ruled out by a negative CD138. A myeloid malignancy is unlikely in the absence of myeloperoxidase expression. Negative glial fibrillary acidic protein expression contradicts the diagnosis of glial-derived tumors.

The expression of CD45 indicates a hematopoietic neoplasm and many cases of HS are positive for this marker. 1,4,6 Positive CD68 and CD163 staining pattern confirm a tumor of histiocytic origin. In particular, CD163, a hemoglobin scavenger receptor, is a new immunohistochemical marker of monocytes and histiocytes. Its expression is limited to neoplasms of monocytic/histiocytic derivation and is more specific than other monocytic and histiocytic markers such as CD68.2-5 CD68 staining is also found in cells and tumors of other lineages, including angiosarcoma, melanoma, carcinoma, some lymphomas, schwannoma, Langerhans cell tumor, follicular dendritic cell tumor, interdigitating dendritic cell proliferation, and acute myeloid leukemia without monocytic differentiation.3,7 Many earlier reported cases of HS, including all 5 cases of CNS HS, were positive for CD68 but were not evaluated for CD163.6-10 Therefore, true histiocytic origin may be questionable in these cases.

In this case presentation, the diagnosis of the mediastinal mass is relatively straightforward but the brain lesion is comparatively more diagnostically challenging. The suboptimal morphology resulting from fragmentation of a small portion of brain tissue, the mild cytologic atypia of the neoplastic cells, and the profound inflammatory component created the initial impression of a chronic inflammatory process. Prominent inflammatory infiltrates were described in all 5 of the previously reported cases of primary CNS HS.8-10 This finding was also observed, although less frequently, in HS in locations other than CNS.6 Many conditions in the CNS may involve a significant inflammatory process. Inflammatory pseudotumor of the CNS, characterized by fibrotic stromal tissue and a polyclonal mononuclear infiltrate, as well as plasma cell granuloma, characterized by a granulomatous infiltrate composed predominantly of plasma cells, may both mimic HS.12 However, unlike our case, in which histiocytes are the major component, the infiltrates in these conditions are dominated by plasma cells. Furthermore, these lesions are not complicated by extracranial relapse. Other conditions with a prominent inflammatory background include sinus histiocytosis with massive lymphadenopathy (Rosai- Dorfman disease) in the CNS, inflammatory myofibroblastic tumor, primary CNS extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type, and lymphoplasma cell-rich meningioma. These conditions can be readily distinguished from HS with comprehensive histomorphologic and immunohistochemical evaluation.12-15 Follicular dendritic cell sarcoma is another rare neoplasm that should be considered in the differential diagnosis. The tumor cells in this entity express CD21, CD23, and/or CD35. Limited tissue availability precluded examination of these immunohistochemical markers in our study. A few reported cases have also shown absence of CD163 in follicular dendritic cell sarcoma, as compared with positive CD163 expression in HS.2,3 Although it is exceedingly unlikely, we cannot exclude the possibility that the CNS lesion in our case report could represent an unrelated, benign inflammatory process. X-chromosome inactivation pattern analysis could be applied to demonstrate tumor cell clonality in the CNS and mediastinal lesions. However, the available tissue from the brain lesion was exhausted in the course of immunohistochemical study.

Central nervous system histiocytic sarcoma portends a poor prognosis with median survival of 4.5 months in previously reported cases (Table). In contrast, the current case is unique in showing an initial indolent clinical course with response to local resection and radiation treatment, and subsequent relapse to the mediastinum 3 years later. Cases of HS with a favorable long-term outcome were reported in other locations.4,6 In those cases, tumor stage and size were believed to be important factors in the prognosis. In CNS HS, reported tumors vary in size from 0.7 to 1.7 cm, and the tumor in our case measures 3.1 cm.8-10 Therefore, it is still unclear at this point if tumor size and stage are prognostic features in CNS HS, as has been observed in other extranodal sites. In our case, the cytologic atypia is somewhat mild and the mitotic figures are rare in the brain lesion. The mild cytologic atypia may correlate with less aggressive biologic behavior because a much more aggressive course is noted following the mediastinal relapse, which exhibited a higher degree of cytologic atypia. The difference in mitotic activity may not completely explain the variability in the clinical course because mitotic figures were highly variable, ranging from 0 to 16 per high-power field in cases reported thus far.8-10 The degree of cytologic atypia in each case is not specified in these reports. It is necessary to examine a larger subset of CNS HS to make observations about tumor characteristics that correlate with clinical outcome.

In summary, we present a case of CNS HS that demonstrates a less aggressive initial clinical course but with subsequent relapse in an extracranial location, with more aggressive behavior. We used a comprehensive immunophenotyping panel including CD163 as well as molecular studies to establish the true histiocytic nature of these lesions. Additionally, in our case, the brain lesion shows mild cytologic atypia as well as low mitotic activity. Although we cannot make accurate conclusions about the relationship of these findings with clinical behavior in our case, future studies are warranted to determine the prognosis of these lesions.

References

1. Jaffe ES, World Health Organization. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, Oxford: IARC Press; Oxford University Press (distributor); 2001.

2. Lau SK, Chu PG, Weiss LM. CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol. 2004;122:794-801.

3. Nguyen TT, Schwartz EJ, West RB, Warnke RA, Arber DA, Natkunam Y. Expression of CD163 (hemoglobin scavenger receptor) in normal tissues, lymphomas, carcinomas, and sarcomas is largely restricted to the monocyte/macrophage lineage. Am J Surg Pathol. 2005;29:617- 624.

4. Vos JA, Abbondanzo SL, Barekman CL, Andriko JW, Miettinen M, Aguilera NS. Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163. Mod Pathol. 2005;18:693-704.

5. Mikami M, Sadahira Y, Suetsugu Y, Wada H, Sugihara T. Monocyte/ macrophage- specific marker CD163α histiocytic sarcoma: case report with clinical, morphologic, immunohistochemical, and molecular genetic studies. Int J Hematol. 2004;80:365-369.

6. Hornick JL, Jaffe ES, Fletcher CD. Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. Am J Surg Pathol. 2004;28:1133-1144.

7. Pileri SA, Grogan TM, Harris NL, et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology. 2002;41: 1-29.

8. Torres CF, Korones DN, Powers JM, Vadasz AG. Primary leptomeningeal histiocytic lymphoma in a young child. Med Pediatr Oncol. 1996;27:547-550.

9. Cheuk W, Walford N, Lou J, et al. Primary histiocytic lymphoma of the central nervous system: a neoplasm frequently overshadowed by a prominent inflammatory component. Am J Surg Pathol. 2001;25:1372- 1379.

10. Sun W, Nordberg ML, Fowler MR. Histiocytic sarcoma involving the central nervous system: clinical, immunohistochemical, and molecular genetic studies of a case with review of the literature. Am J Surg Pathol. 2003;27:258-265.

11. Vega F, Medeiros LJ, Jones D, et al. A novel four-color PCR assay to assess T-cell receptor gamma gene rearrangements in lymphoproliferative lesions. Am J Clin Pathol. 2001;116:17-24.

12. Hausler M, Schaade L, Ramaekers VT, Doenges M, Heimann G, Sellhaus B. Inflammatory pseudotumors of the central nervous system: report of 3 cases and a literature review. Hum Pathol. 2003;34:253- 262.

13. Andriko JA, Morrison A, Colegial CH, Davis BJ, Jones RV. Rosai-Dorfman disease isolated to the central nervous system: a report of 11 cases. Mod Pathol. 2001;14:172-178.

14. Itoh T, Shimizu M, Kitami K, et al. Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in the CNS. Neuropathology. 2001;21:174-180.

15. Bruno MC, Ginguene C, Santangelo M, et al. Lymphoplasmacyte rich meningioma. A case report and review of the literature. J Neurosurg Sci. 2004;48: 117-124.

Ming Cao, MD; Camellia Eshoa, MD; Christopher Schultz, MD; Jennifer Black, MD; Youli Zu, MD, PhD; Chung-Che Chang, MD, PhD

Accepted for publication October 11, 2006.

From the Department of Pathology, The Methodist Hospital, Weill Medical College of Cornell University, Houston, Tex (Drs Cao, Black, Zu, and Chang); the Department of Pathology, St. Mary’s Hospital of Ozaukee, Mequon, Wis (Dr Eshoa); and the Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee (Dr Schultz).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Ch\ung-Che Chang, MD, PhD, The Methodist Hospital, Pathology, 6565 Fannin St, MS205, Houston, TX 77030 (e-mail: [email protected]).

Copyright College of American Pathologists Feb 2007

(c) 2007 Archives of Pathology & Laboratory Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

By Takei, Hidehiro; Bhattacharjee, Meenakshi B; Rivera, Andreana; Dancer, Yeongju; Powell, Suzanne Z

* Context.-Immunohistochemistry (IHC) has become an important tool in the diagnosis of brain tumors.

Objective.-To review the latest advances in IHC in the diagnostic neuro-oncologic pathology.

Data Sources.-Original research and review articles and the authors’ personal experiences.

Data Synthesis.-We review the features of new, useful or potentially applicable marker antibodies as well as the new uses of already established antibodies in the area of diagnostic neuro- oncologic pathology, focusing on the use of IHC for differential diagnosis and prognosis.We discuss (1) placental alkaline phosphatase, c-Kit, and OCT4 for germinoma, (2) -inhibin and D2-40 for capillary hemangioblastoma, (3) phosphohistone-H3 (PHH3), MIB-1/ Ki-67, and claudin-1 for meningioma, (4) PHH3, MIB-1/Ki-67, and p53 for astrocytoma, (5) synaptophysin, microtubuleassociated protein 2, neurofilament protein, and neuronal nuclei for medulloblastoma, (6) INI1 for atypical teratoid/ rhabdoid tumor, and (7) epithelial membrane antigen for ependymoma. All the markers presented here are used mainly for supporting or confirming the diagnosis, with the exception of the proliferation markers (MIB-1/Ki-67 and PHH3), which are primarily used to support grading and are reportedly associated with prognosis in certain categories of brain tumors.

Conclusions.-Although conventional hematoxylin-eosin staining is the mainstay for pathologic diagnosis, IHC has played a major role in differential diagnosis and in improving diagnostic accuracy not only in general surgical pathology but also in neuro-oncologic pathology. The judicious use of a panel of selected immunostains is unquestionably helpful in diagnostically challenging cases. In addition, IHC is also of great help in predicting the prognosis for certain brain tumors.

(Arch Pathol Lab Med. 2007;131:234-241)

Although conventional hematoxylin-eosin (H&E) staining is crucial for diagnosis, diagnostic neuropathology has benefited in the last 2 decades from the incorporation of, and recent advances in, immunohistochemistry (IHC). A number of markers for IHC have been developed in the area of diagnostic neuro-oncology, since glial fibrillary acidic protein (GFAP), the antibody against which is currently most commonly used in practice, was found by Eng et al1 in 1971 and was later reported as a useful marker antigen for astroglial cells by Kleihues et al2 in 1987.

In general, brain tumors are classified into 2 major groups, primary and metastatic, and the primary brain tumors can be classified further into 3 groups: neuroepithelial (eg, astrocytic, oligodendroglial, ependymal, choroid plexus, neuronal, and pineal parenchymal tumors), nonneuroepithelial (eg, meningioma, nerve sheath tumors, malignant lymphoma, pituitary adenoma, and germ cell tumors), and others (ie, tumors of unknown origin, eg, capillary hemangioblastoma). In neuropathology practice, we routinely use several useful IHC markers that are relatively sensitive and specific for some of these tumors (eg, GFAP for astrocytomas, synaptophysin for neuronal tumors); however, none of these are diagnostic (ie, no absolute sensitivity and specificity).

There have been many recent publications in the area of IHC in brain tumor pathology, with several articles relating to new specific antibodies.3-10 This review will discuss the features of new, reportedly sensitive and specific marker antibodies as well as new uses of already established antibodies in the areas of adult and pediatric, diagnostic neuro-oncology practice, based on recently published reports and our own experience.

GERMINOMA: PLACENTAL ALKALINE PHOSPHATASE, C-KIT (CD117), AND OCT4

Germinoma occurs predominantly in the pineal and suprasellar regions and is composed of lobules or sheets of uniform cells with large vesicular nuclei, prominent nucleoli, well-defined cell boundaries, and abundant clear cytoplasm, admixed with lymphoplasmacytic infiltrates. Given that, characteristically, intracranial germinomas are highly radiosensitive and chemosensitive, allowing for a high cure rate with radiation alone or cisplatin-based chemotherapy followed by low-dose radiotherapy, an accurate diagnosis is critical for patient management. The histologic features are virtually diagnostic when the specimens are sufficient for evaluation and are well preserved without artifact. Immunohistochemistry is of particular use in cases when either the specimen is very small or the lymphocytic infiltrate is predominant.11 As with ovarian dysgerminomas and testicular seminomas, intracranial germinomas are known to show immunoreactivity for placental alkaline phosphatase (PLAP) in a surface membrane or, somewhat less commonly, diffuse cytoplasmic distribution.12 This antigen is a cell surface glycoprotein and is normally expressed in syncytiotrophoblasts and primordial germ cells.13 Although this marker is the mainstay in current neuropathology practice, it has its shortcoming in that PLAP labeling is not a constant feature with variable sensitivity, intensity, and extent of reactivity, 3,12,14 and it can sometimes be difficult to interpret, especially in the cases with heavy inflammatory cell infiltrates and in specimens that were previously frozen.12

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is required in normal spermatogenesis.15 Expression of c-Kit (CD117) has been reported on the cell surface in almost all gonadal seminomas/dysgerminomas (Figure 1, A) but very rarely in nonseminomatous germ cell tumors.15,16 Takeshima et al17 and Sakuma et al18 reported that they studied 16 cases of intracranial germinomas, respectively, and c-Kit was diffusely expressed on the surface of germinoma cells in all cases examined. In addition, Takeshima et al17 reported that stem cell factor (SCF), a specific ligand of c-Kit, was also expressed on the cell surface, the staining pattern of which was identical to that of c-Kit. CD30 and c- Kit (CD117) used in combination are known to be useful to distinguish between embryonal carcinoma and seminoma in the gonads.15 However, to our knowledge, the expression of these markers has not been studied in combination in their intracranial counterparts.

OCT4, also known as POU5F1, OCT3, or OTF3, is a nuclear transcription factor expressed in early embryonic cells and germ cells.19,20 This factor is involved in the regulation and maintenance of pluripotency of these cells19-22 and has been shown to be essential for embryonic stem cell formation and self- renewal.23,24 Cheng et al25 reported that OCT4 was expressed in all 33 cases of ovarian dysgerminomas examined, including metastases, while no immunoreactivity was noted in all 111 cases of ovarian nondysgerminomatous tumors with the exception of 4 of 14 clear cell carcinomas of ovary that showed focal (<10%) positivity. On the other hand, Jones et al26 examined 91 cases of primary testicular neoplasms and reported that there was near 100% staining of the seminoma and embryonal carcinoma cells for OCT4 in all 64 cases of adult mixed germ cell tumors examined, while the other germ cell tumor components (yolk sac tumor, choriocarcinoma, and teratoma) showed no staining. In these 2 studies, the main finding is not only that OCT4 is a highly sensitive and specific marker of ovarian dysgerminoma, and testicular seminoma and embryonal carcinoma, respectively, but also that the OCT4 staining pattern was nuclear (in contrast to PLAP and c-Kit, which show characteristically cell membrane staining), with uniformly strong staining intensity and staining extent of greater than 90%. Hattab et al3 conducted a comparative immunohistochemical study of intracranial germinomas using OCT4 and PLAP with control cases, and concluded that OCT4 is a highly specific and sensitive marker for primary intracranial germinomas (100% sensitivity for OCT4 vs 92% for PLAP). As with the ovarian and testicular counterparts in the previous studies cited above, OCT4 demonstrated characteristically diffuse and strong nuclear staining in the germinoma cells (Figure 1, B),3 which is more easily interpreted than the membranous pattern seen with PLAP immunostaining, especially in very small specimens. Since no intracranial embryonal carcinomas were included in this study,3 OCT4 may not be specific for intracranial germinomas; in other words, intracranial embryonal carcinomas should be excluded with H&E- stained sections and probably with CD30 immunostaining if the tumor is OCT4 positive.

CAPILLARY HEMANGIOBLASTOMA: -INHIBIN (INHIBIN A) AND D2-40

Capillary hemangioblastomas (CHBs) are considered by the World Health Organization (WHO) to be grade 1 tumors of uncertain histogenesis, composed of stromal cells and abundant capillaries and commonly involving the cerebellum and spinal cord.27 The histological differential diagnosis of CHB includes metastatic clear cell renal cell carcinoma (CRCC), paraganglioma, angiomatous meningioma, 28 and capillary hemangioma. The histological distinction of CHB from metastatic CRCC has long been recognized as a particular difficulty because of striking morphologic similarities between them. This difficulty may be compounded in patients with von Hippel-Lindau (VHL) disease, an autosomal do\minant disorder caused by germline mutations of the VHL tumor suppressor gene, in which both CHB and CRCC are among the most commonly encountered tumors. In view of the possibility of both CHB and metastatic CRCC to the central nervous system (CNS) occurring synchronously, metachronously, or both, and tumor-to-tumor metastasis (CRCC metastasizing to CHB)29-31 in patients with VHL disease, their distinction is of particular importance and cannot be overemphasized, since the prognostic and therapeutic signifi- cance is completely different. Capillary hemangioblastoma is a benign tumor and generally has a benign course following resection, whereas metastatic CRCC in the brain carries a dismal prognosis32 and may require more aggressive treatment after surgery. Given that medical history and conventional histological examination with H&E staining alone cannot reliably distinguish between these 2 entities, IHC is crucial for differential diagnosis, and there have been a number of IHC studies to address these concerns.

In general, renal cell carcinomas are immunoreactive for epithelial markers, such as epithelial membrane antigen (EMA) and low-molecular-weight cytokeratins (eg, CAM 5.2),33 whereas CHBs are negative. On the other hand, the stromal cells of CHB have been reported to show variable patterns of immunoreactivity for neuron- specific enolase (NSE), S100 protein, VHL protein, and several growth factors27,34,35; however, all of these immunohistochemical reactions are nonspecific and would not exclude other possibilities in the differential diagnosis of CHB.29 The combined use of the immunohistochemical markersmentioned above is of help for differential diagnosis and often allows for a definitive diagnosis. Since loss of immunophenotype is sometimes encountered during tumor progression, and a definite subset (10%-30%) of CRCC is negative for EMA and CAM 5.2,36,37 other more ”specific” immunohistochemical markers for CHB are needed.

Inhibin, a dimeric 32-kd glycoprotein belonging to the transforming growth factor ÃŽ² family and composed of an ÃŽ± (inhibin A) and a ÃŽ² subunit, is produced mainly by ovarian granulosa cells and testicular Sertoli cells.38 Inhibin A is expressed in the sex cord-stromal tumors and adrenal cortical tumors.39,40 Hoang and Amirkhan4 reported in 2003 that immunoreactivity for inhibin A was demonstrated in all 25 cases of hemangioblastoma with cytoplasmic expression in the stromal cells (Figure 2), in contrast to all 19 cases of renal cell carcinoma, including both primary and metastatic, none of which were positive, and concluded that inhibin A was a helpful marker in distinguishing CHB from metastatic CRCC. In addition, this study included 11 cases of CHB from 8 patients with VHL disease, and there was no difference in the inhibin A staining pattern between the sporadic CHB and those associated with VHL disease. A recent study performed by Jung and Kuo5 demonstrated that CD10 membranous immunoreactivity was seen in all 21 cases of CRCC (5 metastatic, 16 primary) examined, whereas all 22 cases of CHB were negative. They also showed that 91% (20/ 22) of cases of CHB and 24% (5/21) of cases of CRCC expressed inhibin A, and concluded that, in addition to inhibin A, CD10 was a superior marker for the differential diagnosis of CHB (negative) and metastatic CRCC (positive).

D2-40, a novel monoclonal antibody that was initially raised against an oncofetal antigen M2A,41 was recently introduced to diagnostic pathology to help identify lymphatic endothelium.42,43 Apart from lymphatic endothelium, D2-40 has been reported to be immunoreactive in mesotheliomas44,45 and, in the CNS, in choroid plexus epithelium, ependymal cells, subependymal areas, and the leptomeninges. 6 A recent study conducted by Roy et al6 revealed that all 23 cases of CHB examined expressed D2- 40 membranous immunoreactivity in the stromal cells with strong intensity in 19 cases (83%), whereas all 28 cases of CRCC (8 metastatic, 20 primary) failed to show immunoreactivity. There were 3 cases of CHB with VHL disease included in this study, and no difference was seen in D2-40 staining of CHB in patients with or without VHL disease. Although D2- 40 appears to be a very useful marker, we have not experienced constant positivity in several cases of hemangioblastoma examined in our laboratory.

In summary, based on the recent studies, inhibin A and D2-40 are sensitive and specific markers for CHB, while EMA, CAM 5.2, and CD10 mark CRCC. Combined use of at least one of these markers from each group helps to distinguish CHB from metastatic CRCC in patients with or without VHL disease.

We have recently experienced a case of angiomatous meningioma, histologically closely mimicking CHB, which is generally considered to be one of the histological differential diagnoses of CHB.34 Diffuse EMA immunoreactivity and negative inhibin A staining supported the diagnosis of a meningioma and excluded that of a CHB. Metastatic CRCC was included in the differential diagnosis based on the diffuse EMA staining; however, CD10 and CAM 5.2 were negative.

Paraganglioma may mimic CHB and is included in the differential diagnosis of CHB; however, neuroendocrine markers, such as chromogranin and synaptophysin, are usually positive in paragangliomas.

Capillary hemangiomas of the CNS are very rare and show histological features similar to those of lobular capillary hemangiomas of the skin as well as the capillary hemangiomas of infancy,46 with a fibrous pseudocapsule.47 Most examples have been documented recently and appear to arise more commonly in spinal cord.46-51 Central nervous system capillary hemangiomas may mimic CHB, especially a vascular dominant CHB, given that this subtype of CHB may feature a lobular architecture with feeding vessels and a compact growth pattern.52 In order to exclude this unusual subtype of CHB in which the stromal cell component is small to minimal, we should use IHC with markers for the stromal cells (eg, S100 protein, NSE, inhibin A, D2-40) whenever making a diagnosis of CNS capillary hemangiomas. There were several recently reported cases of CNS capillary hemangiomas with no immunohistochemical analysis with these markers.49-51

MENINGIOMA: PHOSPHOHISTONE-H3, MIB-1/KI-67, AND CLAUDIN-1

Meningiomas are among the most common primary neoplasms of the CNS, comprising between 13% and 26% of intracranial tumors.53 According to the WHO classifi- cation, most meningiomas are benign and can be graded into WHO grade 1, and certain histological subtypes are associated with greater likelihood of recurrence and/ or aggressive behavior and correspond to WHO grades 2 and 3.53 Quantifying the proliferative potential is of help in predicting the biologic behavior. One of the WHO criteria other than particular histological subtypes in the assignment of grade in meningiomas is the number of mitotic figures (MFs) per 10 high-power fields (HPFs, defined as 0.16 mm2) in the areas of highest mitotic activity; that is, no less than 4 mitoses per 10 HPFs in atypical (WHO grade 2) meningiomas, and no less than 20 mitoses per 10 HPFs in anaplastic (WHO grade 3) meningiomas.53

Given that it is difficult to distinguish MFs on H&Estained slides from similar chromatin changes occurring in apoptotic cells or secondary to crush, distortion, pyknosis, or necrosis,54 as the diagnostic criterion, MF is not as subjective as usually considered. Ribalta et al7 studied a mitosisspecific antibody against phosphorylated histone H3 (PHH3) (which is negligible during interphase but reaches a maximum during mitosis55,56) in 54 cases of meningiomas and showed a robust positive correlation betweenMF counts performed on traditional H&E-stained slides and those performed on anti-PHH3-immunostained slides. Labeled nuclei are characterized by multiple finger-like projections of immunoreactivity (Figure 3, A). This robust staining of mitoses with a negative background makes mitoses ”stand out.” They concluded that anti-PHH3 immunostaining facilitated rapid reliable grading of meningiomas according to WHO 2000 criteria by permitting quick focus of attention on the most mitotically active tumor area(s) for quantitation and by allowing easy and objective differentiation of MFs from apoptotic and distorted/pyknotic nuclei.7 Although it is uncertain whether or not this seemingly more sensitive and specific method is more useful than the conventional method to predict the biological behavior of meningiomas and further studies are required for this issue, there is no doubt that this immunostaining allows for rapid and accurate identification of MF.

Apart from MFs, an anti-Ki-67 monoclonal antibody MIB-1, which is immunoreactive for the nuclei of cells in non-G0 phases (ie, G1, S, G2, and M phases) of the cell cycle, is commonly used as a useful ancillary study in routine surgical/neuropathological practice to assess the proliferative potential in a given neoplasm. The MIB-1 labeling index (MIB-1 LI), which is calculated as a percentage of the MIB-1-positive cells to the total number of tumor cells, in meningiomas has been reported to correlate well with histologic grade57,58 and clinical tumor recurrence. 58,59 Although MIB-1 LI is not included in the WHO criteria to grade the meningiomas, it is of particular help in tumors that are histologically ”on the fence” with regard to tumor grade. Amatya et al57 studied 146 cases of meningiomas immunohistochemically and reported that the mean MIB-1 LI of benign, atypical, and anaplastic meningiomas was 1.5%, 8.1%, and 19.5%, respectively. They also reported that p53 immunoreactivity (p53 labeling index) correlated with the histologic grade as well. Nakasu et al58 investigated the predictability of tumor growth, assessed radiologically by tumor doubling time, and recurrence in 139 cases of meningiomas by MIB-1 IHC, using 2 different counting methods; that is, counting in the area of the high\est MIB-1 labeling (HL method) and counting in randomly selected fields (RS method). They reported that the MIB-1 LI measured by both methods showed a significant correlation with tumor grade, growth speed, and recurrence rate. Interestingly, they pointed out that focal accumulation of MIB-1-positive cells in meningiomas was not likely to correlate with their biologic aggressiveness and concluded that the RS method was a better predictor of recurrence and tumor growth in meningiomas than the HL method when counting manually. There have been several studies describing the cutoff point of MIB-1 LI for recurrence, although it varied from report to report.58-61 Nakasu et al58 suggested approximately 2% and 3% in the RS and HL methods, respectively. Matsuno et al60 studied the MIB-1 LI of recurrent (n = 54) and nonrecurrent (n = 73) groups of meningiomas using the HL method, and mentioned that a MIB-1 LI of 3% was a cutoff point for recurrence, especially within the first 10-year follow- up periods, although there was a marked overlap of values between the groups. Ho et al61 studied 83 cases of meningiomas with at least a 10-year follow-up by IHC using the HL method and reported that the MIB-1 LI of 10% was a cutoff point for recurrence. Perry et al59 studied prognostic significance of variable parameters by IHC using image analysis in 425 cases of meningiomas, and reported that the MIB-1 LI of 4.2% or more was strongly associated with a decreased recurrence-free survival rate in gross, totally resected meningiomas.

Meningiomas, particularly the fibroblastic type, may be difficult to distinguish from schwannomas with routine H&E-stained sections, especially when located in the cerebellopontine angles and intradural, extramedullary regions of spinal canal. In these tumors, EMA immunoreactivity may be faint and/or focal. Winek et al62 mentioned that because of overlap in S100 protein and EMA reactivity, these markers were unreliable in differentiating meningioma from acoustic schwannoma.

Claudin-1, an integral structural protein of tight junctions, has recently been used as a marker of perineurial cells and has been reported to be often a more robust marker than EMA to distinguish soft tissue perineuriomas from its mimics.63 Bhattacharjee et al8 conducted a comparative IHC study using claudin-1 and EMA in 20 and 10 cases of meningioma and schwannoma, respectively. They reported that claudin-1 and EMA expression was observed in 85% and 100% of meningiomas, respectively, and of the 10 schwannomas, 2 cases showed focal, nonmembranous staining for EMA, while none were positive for claudin-1. They also stressed that the immunoreactive pattern of claudin-1 was unique in the crisp, punctate/ granular membranous reaction (Figure 3, B), which was visually more favorable in contrast to the faint or weak membranous pattern of expression seen in EMA. They concluded that claudin-1 was a very useful adjunct to EMA in meningiomas with equivocal morphologic features or with weak/ focal EMA expression, and that the lack of claudin-1 expression by schwannomas was very useful in the context of differential diagnosis with fibroblastic meningiomas, particularly of cerebellopontine angle tumors. A recent report by Hahn et al9 showed similar results, although the sensitivity was lower, with 21 (53%) of 40 meningiomas being immunoreactive and all other tumors being negative.

ASTROCYTOMA: PHH3, MIB-1/KI-67, AND p53

Diffusely infiltrating astrocytomas include (low-grade) diffuse astrocytoma (WHO grade 2), anaplastic astrocytoma (WHO grade 3), and glioblastoma (WHO grade 4), according to the current WHO classification.64 Distinguishing between WHO grade 2 and 3 infiltrating astrocytomas is particularly important for patient management as well as for prognosis. By current WHO guidelines, this distinction is made primarily by assessment of the proliferation activity of neoplastic cells. There are a few studies demonstrating a significant positive correlation between MIB-1 LI and tumor grade in diffusely infiltrating astrocytomas, classified according to the WHO 2000 classifi- cation system.65,66 A recent large retrospective study of grade 2 and 3 astrocytomas by Colman et al, evaluating the utility of PHH3 staining for determining proliferative activity, demonstrated that the PHH3 mitotic index (per 1000 cells) was significantly associated with the standard mitotic count (mitoses per 10 HPFs) and with the MIB-1 LI and had specific technical advantages over the MIB-1 LI67 because the latter showed significant interlaboratory variability, depending on staining conditions.68 For a practical usage of this marker, they pointed out that the antigenicity seemed to have decreased after 3 to 5 years in their samples. With regard to prognosis, they reported that the PHH3 index was an independent predictor of survival after adjusting for relevant clinical variables in multivariate analysis. Interestingly, they listed specific cutoffs to separate the patients into 2 groups with survival times similar to those established in a previously reported series for grade 2 and grade 3 astrocytomas. The cutoffs (grade 2 vs 3, respectively) were as follows: PHH3 index (⓰¤4 vs >4 per 1000 cells), MIB-1 LI (⓰¤9% vs >9%), and mitoses per 10 HPFs (⓰¤3 vs >3).67 Although the current WHO guidelines do not define such a cutoff to distinguish between grade 2 and 3 astrocytomas, this information on the proliferation markers, in addition to the variable morphologic parameters, can be very useful to grade the tumors.

One of the most common diagnostic dilemmas in neuro- oncologic pathology is a distinction between benign reactive astrocytic lesions (ie, gliosis) and low-grade astrocytomas, especially with small biopsies (eg, stereotactic biopsies). In general, there should be negligible or very low levels of Ki-67/MIB-1 immunoreactivity in the setting of gliosis.68 This pattern of immunoreactivity in gliosis and that seen in some low-grade astrocytomas may overlap. Wild-type p53 is involved in regulation of the cell cycle as well as apoptosis,69 and it has been demonstrated to suppress cell transformation.70 The wild-type p53 protein has a short half-life (5- 30 minutes) because of its rapid turnover, and is not normally detectable by standard immunohistochemical methods.71 Mutation of the gene usually leads to the production of a functionally impaired or altered protein, which retards degradation and thus can be detected via immunohistochemical staining. On the other hand, p53 immunoreactivity is sometimes unaccompanied by gene mutations. This pattern can be seen in the settings, such as binding of wild-type p53 by various oncoproteins (eg, mdm-2)72 and the result of epigenetic changes.73,74 Yaziji et al75 reported that p53 (monoclonal antibody, DO-7; Dako, Carpinteria, Calif; dilution, 1:60) immunoreactivity was seen in 12 (54%) of 22 low-grade astrocytomas and 5 (9%) of 56 reactive astrocytic lesions, all 5 being cases of progressive multifocal leukoencephalopathy. Given unusual p53 immunoreactivity seen in astrogliosis in their study, they concluded that p53 immunostain can help to differentiate reactive from neoplastic astrocytic lesions. In contrast, Kurtkaya- Yapicier et al76 conducted a similar study of 60 nonneoplastic lesions, including gliosis, infarction, demyelination, progressive multifocal leukoencephalopathy, and herpes simplex virus encephalitis, and 50 astrocytomas of WHO grades 2 to 4, using p53 antibody (monoclonal, DO-7; Dako; dilution, 1:200). They showed p53 immunoreactivity in all lesions examined, although the reactivity was low-level in most instances, and concluded that it was not a reliable indicator of astrocytic neoplasia. We believe that this distinction is still best handled on histologic grounds with the clinical, radiologic, and operative findings, although immunohistochemical staining for Ki-67 and p53 may be of help if the expression is significantly high.

MEDULLOBLASTOMA: SYNAPTOPHYSIN, MICROTUBULE-ASSOCIATED PROTEIN 2, NEUROFILAMENT PROTEIN, AND NEURONAL NUCLEI

The medulloblastoma (MDB) is defined as a malignant, invasive embryonal tumor of the cerebellum, preferentially occurring in children and adolescents, with a propensity for leptomeningeal dissemination. Medulloblastomas are the second most frequent brain tumors in childhood after pilocytic astrocytomas, and account for approximately 15% of all pediatric brain tumors.77 The median age at diagnosis is 9 years.77 Medulloblastomas have been chiefly subtyped as classic, nodular (desmoplastic), and large cell/anaplastic based on histologic appearances.78 Of these, the large cell/ anaplastic variant is known to be associated with worse prognosis.78,79

Although MDBs are derived from embryonal precursor cells with a capacity for divergent differentiation, neuronal differentiation is most consistently seen.80,81 This is usually incipient in that it is restricted to the expression of neuronal markers, with rare cases showing overt ganglionic or mature neuronal cells. Synaptophysin has proven to be a reliable marker of neuronal differentiation and is detected in virtually all cases on frozen sections,80,81 with 70% to 80% of cases being positive in paraffin sections. 82 Microtubule- associated protein 2 antibody mirrors synaptophysin but has a more intense granular or punctate pattern of reactivity. It is often helpful in those cases where the synaptophysin staining is weak or equivocal. Neurofilament proteins of low and intermediatemolecular masses (68 kd and 160 kd, respectively), are expressed in proliferating medulloblastoma cells,80 but high-molecularmass neurofilament protein (200 kd) is only expressed in the tumor cells with advanced neuronal differentiation and overt ganglionic or neuronal morphology.83 Neuronal nuclei immunoreactivity is seen focally in the nuclei of cells with advanced neuronal differentiation.84

Glial (astrocytic) cel\l differentiation in MDBs is restricted to small foci of tumor cells without evidence of progressive differentiation to mature astrocytes. When strict criteria are applied for true tumor cells with glial (astrocytic) differentiation, excluding entrapped reactive astrocytes, the incidence is seen in up to 13% of cases.83 True tumor cell glial differentiation is defined as a typical medulloblastoma cell with hyperchromatic nucleus and scant cytoplasm, showing GFAP immunoreactivity restricted to perinuclear cytoplasm, and is associated with a poor prognosis.85

Mesenchymal, epithelial, and melanotic markers are seen in rare variants of MDBs. It should be noted that focal expression of epithelial markers (keratins and EMA) is otherwise rare in MDBs, and in particular, in the case of large cell/anaplastic subtype, raises the possibility of atypical teratoid/rhabdoid tumor.86

ATYPICAL TERATOID/RHABDOID TUMOR: INI1

Atypical teratoid/rhabdoid tumors (ATRTs) may form a histological spectrum from pure rhabdoid to atypical teratoid/ rhabdoid tumors,87,88 and occur most commonly in young children (Figure 4). More than 90% of cases are diagnosed before age 5 years.89 Since their initial description, they have been reported to occur throughout the neuraxis, but the posterior fossa remains a preferred site, in particular the cerebellopontine angle. Neither clinical presentation nor neuroimaging distinguishes the ATRT from medulloblastoma. 90 Microscopically, ATRTs are very cellular tumors that show marked regional heterogeneity, with primitive neuroepithelial, rhabdoid, epithelial, and mesenchymal components. There is often a fibrovascular stroma separating lobules and sheets of tumor cells. The cellular morphology varies from smaller, primitive neuroepithelial type cells, with hyperchromatic nuclei resembling those of a medulloblastoma, to large cells with eosinophilic, pale, or clear cytoplasm and large round nuclei with more open chromatin and prominent nucleoli. Immunohistochemistry reflects the morphological heterogeneity of the tumor. There is immunoreactivity for a range of mesenchymal, epithelial, and neuroectodermal markers, but the tumors are consistently negative for the germ cell markers. Vimentin is consistently expressed. Expression of EMA, keratin, smooth muscle actin, and GFAP is also frequently observed. S100 protein, synaptophysin, chromogranin, neurofilament protein, desmin, and HMB-45 may be variably and focally expressed in ATRTs. Glucose transporter protein 1 (GLUT-1) is expressed by ATRTs, and suggests origin from a stem cell.91 There is a high frequency of monosomy 22 in CNS ATRTs. Molecular cytogenetic screening has shown deletions of chromosome 22q11.2; this region contains the hSNF5/INI1 gene. Most CNS, renal, and extrarenal rhabdoid tumors show homozygous inactivation of INI1 by deletion and/or mutation of the INI gene, with decreased or absent expression at the RNA or protein level. Immunohistochemistry with antibody to INI1 (with absent nuclear staining in tumor cells in ATRT) has been shown to correlate with molecular findings in ATRT.10 The INI antibody may be more useful in analysis of tumors with indeterminate histologic and immunophenotypic profiles, since negative staining (albeit with preserved nuclear expression in normal components such as endothelial cells) is intuitively not as desirable an end result as compared with positive staining. In the diagnosis of ATRTs, a panel of immunohistochemical markers which include vimentin, EMA, keratins, smooth muscle actin, GFAP, and synaptophysin is likely to help confirm the diagnosis in the context of the appropriate morphological appearance. INI1 immunostaining can be used in those cases having indeterminate histological features, or in small biopsies which may not be representative of the morphological heterogeneity typical of ATRTs.

EPENDYMOMA: EMA

Ependymomas account for 3% to 9% of all neuroepithelial tumors.92 They are most often seen in children, adolescents, and young adults, but can be seen in older age groups. In children, they are the third most common CNS tumors after astrocytomas and medulloblastomas.77 Posterior fossa tumors are more frequent than supratentorial, and spinal cord ependymomas occur in older age groups than pediatric tumors. Ependymomas of the fourth and lateral ventricles occur in a ratio of 6:4; their location and growth pattern in the fourth ventricle may influence prognosis. 93 Microscopically, ependymomas are well-demarcated, moderately cellular tumors with a monomorphic nuclear morphology. Characteristic features include perivascular pseudorosettes, which are nearly always seen in these tumors, and ”true” ependymal rosettes. The latter feature is much less frequently seen in ependymomas and is characterized by clusters of ependymal cells arranged around a lumen with some resemblance to the central canal of the spinal cord. Immunohistochemistry in ependymomas reveals their dual nature with glial fibrillogenesis and GFAP expression, and epithelial with EMA expression. GFAP is variably positive in ependymomas, with the tumor cells and processes forming the perivascular pseudorosettes being most consistently positive. Normal mature ependymal cells do not express GFAP, but reactive and neoplastic ependymal cells reacquire the developmentally repressed ability to express GFAP which occurs from the 15th week of gestation, but is lost in adulthood. Other intermediate filaments such as vimentin and desmin are also expressed in neoplastic ependymal cells. EMA expression is useful in that it is consistently and widely expressed in well-differentiated tumors; anaplastic examples were not immunoreactive in one study,94 but in our experience are at least focally expressed. The pattern of EMA immunoreactivity typically is seen as dotlike perinuclear cytoplasmic reaction. Histological features by themselves are not reliable predictors of biological behavior, likely due to tumor heterogeneity. However, ependymomas with 2 or more of the features of hypercellularity, mitotic figures, elevated MIB-1 LI, microvascular proliferation, and necrosis are likely to show aggressive behavior.95 According to the recent study of ependymomas from 103 consecutive patients, Wolfsberger et al96 demonstrated that extent of resection and MIB-1 LI were independent prognostic factors on multivariate analysis. They defined its median value of 20.5% as cutoff point, and showed low (<20.5%) or high (â“°¥20.5) MIB-1 LI predicted favorable (â“°¥5 years’ survival) or unfavorable (<5 years) patient outcome at 79% and 70%, respectively.

CONCLUSIONS

We presented several new IHC markers for supporting and at times confirming the morphologic diagnosis of adult and pediatric brain tumors. These include OCT4 for germinoma, =-inhibin (inhibin A) and D2-40 for CHB, claudin-1 for meningioma, microtubule-associated protein 2 and neuronal nuclei for MDB, and INI1 for ATRT. Of particular importance is the differential diagnosis of CHB from metastatic CRCC because of completely different prognostic as well as therapeutic significance. We stressed the combined use of inhibin A (and D2-40) and epithelial markers (EMA, CAM 5.2, and CD10) for this distinction. INI1 is unique in its negative nuclear staining in ATRTs, and can be used in those cases having indeterminate histological features or in small biopsies that may not be representative of the morphological heterogeneity typical of ATRTs. Another new marker, PHH3, is a mitosis-specific marker, and enables us to provide a quick focus on the most mitotically active areas within the tumor and to facilitate rapid, reliable grading in meningiomas. In astrocytomas, this antibody can be of particular help to differentiate between grade 2 and 3 tumors, compared with MIB-1/Ki-67. With this particular marker, mitotic index will be further investigated in the neoplasms, for which proliferation potential is of relevance to tumor grading and prognosis. We also showed the current data on MIB- 1/Ki-67 LI in prognosis in meningioma, astrocytoma, and ependymoma.

From a practical point of view, an accurate diagnosis of brain tumors is usually possible after careful assessment of routine microscopic features with sufficient clinical and radiological information. Although conventional H&E staining is a mainstay for pathologic diagnosis, IHC has played a major role in differential diagnosis and in improving the diagnostic accuracy in neuro- oncologic pathology. The judicious use of a panel of IHC, whose selection was based on the differential diagnosis rendered after the initial assessment, is unquestionably helpful in diagnostically challenging cases. In addition, IHC is also reportedly of great help to grade and to predict the prognosis in certain brain tumors.

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Hidehiro Takei, MD; Meenakshi B. Bhattacharjee, MD; Andreana Rivera, MD; Yeongju Dancer, MD; Suzanne Z. Powell, MD

Accepted for publication July 7, 2006.

From the Department of Pathology, Baylor College of Medicine, Houston, Tex (Drs Takei, Bhattacharjee, and Rivera); and the Department of Pathology, The Methodist Hospital, Houston, Tex (Drs Dancer and Powell).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Hidehiro Takei, MD, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Suite 286A, Houston, TX 77030- 3498 (e-mail: [email protected]).

Copyright College of American Pathologists Feb 2007

(c) 2007 Archives of Pathology & Laboratory Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

SALT LAKE CITY, Feb. 13 /PRNewswire/ —

"I don't know what to do ... ""I can't afford a personal trainer ... ""I don't have time ... ""I'm bored with exercise ... "

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Each half hour episode is jam-packed with calorie burning exercises, unique cool down methods, and useful fitness, nutritional and health tips. “The series is similar to what users of the Podfitness.com personal training podcasts experience,” says Teri Sundh, CEO and Co-Founder of Podfitness.com, “we want to make getting and staying in shape fun and easy with the best instructions and information customized for each user.” When viewers join the Podfitness.com team each morning, they will see results with a slimmer physique and healthier lifestyle. In addition to Jenkins, Lee, and Mathews, other Podfitness.com celebrity trainers set to appear in the series include: David Kirsch, Kathy Kaehler, Kathy Smith, Ashley Borden, Nancy Kennedy, Valerie Waters and TV star/fitness fanatic Danny Bonaduce.

   The Daily Format:    *  Each morning a Podfitness.com celebrity trainer will conduct a      17 minute workout with students at varying levels demonstrating and      following the steps just like the home viewers.  Viewers will be      receiving world-class personal training and insights into fitness      unlike anything previously seen in daytime television.   *  The trainer will take you through a workout featuring specific      exercises they use with their own celebrity clientele, from cardio to      strength to toning exercises.   *  Each day will include a cool down with a celebrity Yoga instructor,      featuring stretching and relaxation exercises that go far beyond a      typical cool down.   *  Throughout the show guest trainers offer useful tips on smart food      choices, easy workout ideas, new fat burning tips, and fun ways to stay      both mentally and physically healthy.   

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“MY WORKOUT” … powered by Podfitness.com is Executive Produced by Burt Wheeler, Sharon Sussman, and Alan Winters. Wheeler/Sussman Productions currently produce the daily television series “Judge Alex” for Twentieth Television (Fox). Winters was formerly Executive Producer of “The Other Half” for NBC Enterprises.

   For Press Inquires Please Contact:   Laura Ackermann   Much and House Public Relations   323.965.0852 ext. 150 or   [email protected]  

Podfitness.com

CONTACT: Laura Ackermann of Much and House Public Relations,+1-323-965-0852, ext. 150, [email protected], for Podfitness.com

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

By Carly Harrington, The Knoxville News-Sentinel, Tenn.

Feb. 11–Knoxville was still reeling from the World’s Fair when James Foster arrived here in 1982 to interview for a new medical scholarship program aimed at bringing more minority doctors to town.

At the time, there were four black physicians practicing medicine in Knoxville.

“For me, it came down to finances. I just liked the idea of someone giving me a job,” said the Louisville, Ky., native who became the first recipient of the Walter S.E. Hardy Medical Scholarship, named after the long-time Knoxville physician.

Foster, who specializes in internal medicine, was required to spend at least five years in private practice in Knoxville upon graduation and completion of residency training. Eighteen years later, Foster continues to see patients at his office off Magnolia Avenue, where he has watched other black doctors come and go.

For decades, the number of black doctors in Knox County has fluctuated from upward of 30 to as few as two. Today, there are 19, or 1.2 percent of the county’s physicians.

While the area doesn’t have a large minority population — blacks make up less than 9 percent of Knox County’s residents — black community leaders and physicians say the percentage of black doctors should be representative of the black population.

Efforts are under way to recruit a more diverse medical work force to Knoxville, but some question whether the city — with its lower wages and limited cultural activities — will be able to compete with larger metropolitan areas that easily appeal to minorities looking for somewhere to go.

“It’s a problem that can’t be resolved unless you have blacks, but they don’t want to come here. It’s like a dog chasing its tail,” said Bedford Waters, a urologic oncologist and surgeon affiliated with the University of Tennessee Medical Center.

In the 1950s and 1960s, most blacks resided in Mechanicsville or East Knoxville. And when they were sick, they went to see a black physician, whose office was in the heart of the black community.

No longer bound by segregation, black residents live and work throughout the city. Those who want to be a doctor can go to any medical school in the country and pursue a specialized career that was unheard of a half-century ago.

While these opportunities highlight the progress blacks have achieved in the medical field, some say they also have diminished the sense of community that was exemplified by physicians of an earlier time.

“They were role models. You look at the African-American physician population here now, and very few of them live in the African-American community, and very seldom do they get involved in the social life of the community,” said Avon Rollins, executive director of the Beck Cultural Exchange Center.

That’s unfortunate, he said, because young black professionals need a strong support base and want a diverse social outlet that often is lacking in Knoxville.

“That’s not only true for medical doctors but with other professionals as well. Knoxville is not a good place to be. That has been articulated to me,” Rollins said.

Waters, who grew up in Mechanicsville, returned to Knoxville in 2001 from Chicago, but only to be closer to his mother.

“I resisted moving here for years,” Waters, 58, said. “I eventually did because of my mother, but I may not stay here. I may go back to Chicago.”

Waters admits he doesn’t have any answers. But people should be concerned, he said, because a lot of blacks don’t want to locate here, and “that’s a big problem.”

When Evelyne Davidson was growing up, there were three black doctors in Knoxville, and her father, E.V. Davidson, was one of them. Since that time, she said, there really have not been that many black physicians to come in.

“What you would have liked to have seen is as one passed away that perhaps you could have gotten another African-American to come in and take over their practice and basically take their place, which did not happen,” said Davidson, a Knoxville internist for the past 17 years.

In order to attract and retain black physicians, there has to be, she said, something besides medicine to keep them here.

“When you think about Tennessee, it does not sound like it’s a happenin’ state,” Davidson, 45, said. “You need social or cultural things that are appealing to African-American physicians that you would typically have found in a larger city, that we don’t have here in Knoxville.”

Part of the problem, Foster said, is there’s no formal organization for black doctors. He recently was invited to attend a meeting of Asian-Indian doctors who had gathered for a speaker and dinner. The group has 95 members in East Tennessee.

“We can’t do that. We’re not organized,” Foster said.

The black doctors in town, he said, are a “very eclectic group. Everyone does their own thing.”

“I don’t speak on a regular basis with other black physicians,” Foster said. “I don’t know why. I go to church with Evelyne Davidson but probably hadn’t spoken a word to her in three years.”

The area’s lack of diversity didn’t deter 32-year-old Lewis Holmes III, from wanting to come back to Knoxville.

A nephrologist at Renal Medical Association, Holmes moved from Charleston, S.C., seven months ago. With its low cost of living and good school system, Holmes said Knoxville was a perfect fit for his family, though none of his three hometown friends, who also happen to be black doctors, did.

“The others all said, ‘No way am I coming back to that social environment.’ It wasn’t a great concern to me because I had seen other African-American physicians come and thrive,” Holmes said.

John Bell, surgical oncologist and director of the University of Tennessee Cancer Institute, doesn’t view the small black population as an obstacle to recruiting. It’s up to the individual. Some people, he said, see it as an opportunity. Others see it as a challenge.

“There aren’t that many African-American physicians here,” Bell said. “Some come in and say, ‘Where are they?’ I tell them there’s no reason why they can’t fit into this community and make a difference.”

Bell, as well as other hospitals and physician groups, said they recruit the best-qualified doctors they can find regardless of ethnic background or gender.

“For us, it doesn’t really matter what your race is. It’s really about their qualifications,” said Beth Maynard, director of physician recruitment and marketing at East Tennessee Heart Consultants.

In three years, Maynard has talked seriously with three black job candidates. Of its 42 physicians, none are black.

“It’s not by our choice. The candidates are just not out there,” Maynard said. “It’s unfortunate but a reality of the profession and even more so as a specialty.”

When it comes to recruiting, Knoxville has to compete with Atlanta, Birmingham, Memphis, Dallas and other large Southern cities where there are larger black populations, said Mike Fecher, vice president of physician services at St. Mary’s Health System.

“We don’t get a lot of African-American candidates when we do advertise for an opportunity. And we have lost other physicians to other communities. They tend to go to cities with the population they’re looking for,” Fecher said.

St. Mary’s has 250 doctors on active staff. Four of them are black.

To help the hospital recruit and attract more black doctors, St. Mary’s will begin next month to advertise job opportunities in the Journal of the National Medical Association, the largest medical journal that targets black physicians.

It also has started a diversity committee “in an effort to get our staff to reflect the community,” Fecher said.

In an effort to provide mentoring and financial assistance to young people in East Tennessee who are interested in health care, the Tennessee Conference Community Development has launched the Hardy Torch program.

It will include an intern program for minority high school and college students who want to further their education in the medical field, as well as a scholarship program for college and medical students majoring in various health-care fields.

“The whole premise behind it was to spark excitement and energy around the medical field,” said the Rev. David Walker, executive director of the TCCD.

The first scholarship will be awarded this fall.

—–

To see more of The Knoxville News-Sentinel or to subscribe to the newspaper, go to http://www.knoxnews.com.

Copyright (c) 2007, The Knoxville News-Sentinel, Tenn.

Distributed by McClatchy-Tribune Business News.

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SEATTLE, Feb. 12 /PRNewswire/ — The Swedish Neuroscience Institute (SNI) today opened a $30 million clinical complex at Swedish Medical Center’s Cherry Hill (formerly Providence) Campus. Centerpieces of the new facility are four state-of-the-art operating rooms (ORs) that feature the most advanced minimally invasive, computer-assisted neurosurgical and brain-imaging technologies.

(Photo: http://www.newscom.com/cgi-bin/prnh/20070212/SFM171 )

Located on the B Level of the new South Building addition at 17th Ave. and Jefferson St., the operating rooms are 900 square feet each. Four rooms open today and four others are shelled in for future expansion. All are adjacent to the cardiovascular operating rooms in Cherry Hill’s modern surgical pavilion.

“This new facility allows us to perform procedures with new integrated technologies that are not available together anywhere else in the country,” said Marc R. Mayberg, M.D., SNI co-executive director. “In the neurosciences, there are many new minimally invasive approaches to treating brain tumors, head trauma, stroke, spinal disorders and chronic diseases such as Parkinson’s — and now we can employ them all in Seattle.”

   SNI's comprehensive diagnostic and surgical capabilities include:    -- Integrated, GPS-like guidance systems built into every OR that help      surgeons navigate in critical areas of the brain during operations   -- Intraoperative MRI and CT scanners and 3-D angiography that provide      vital images during surgery   -- Brain-mapping capabilities to identify areas of critical brain function      through microelectrode recordings of brain tissue   -- Interventional neuroradiology techniques to block blood flow to tumors      or blood-vessel malformations prior to surgery, place stents (small      wire mesh tubes used for keeping vessels open) in narrowed brain      arteries and repair cerebral aneurysms   

“We have created a center that relies heavily on interventional radiology, endoscopic procedures and other less-invasive technologies, so procedures can be done with less risk and patients can go home as quickly as possible,” said David Newell, M.D., SNI co-executive and medical director. “For that reason, we needed to invest in the most sophisticated imaging and guidance systems available today.”

Four of the major innovations incorporated into the new SNI ORs include:

— PoleStar(TM) interoperative MRI image guidance. This advanced technology from Medtronic Navigation produces real-time interior MRI images of the brain during surgery, so a neurosurgeon can more accurately detect and evaluate tumor boundaries while avoiding healthy tissue. This technique, which is used for both malignant and benign brain tumors, significantly improves effectiveness of tumor removal, lowers the risk of surgery, and decreases the likelihood of the need for additional surgery. The mobile PoleStar system is mounted on a motorized cart and is easily stored in a special walk-in closet when not in use. The MRI’s magnet is completely shielded, so the operating room can be used for other procedures not requiring interoperative imaging.

— Storz OR-1(TM) Integration System. This system allows all of the information available to the surgeon to be integrated and displayed on ceiling-mounted LCD screens for continuous access by the OR team, including pre-operative and intra-operative images, operating microscope views, navigation, and anesthesia monitoring. In addition, the surgeon can transmit images outside the OR for teaching other surgeons, or to consult with colleagues if necessary. Large LCD screens in the rooms also allow clinical visitors, medical students and others to observe a surgery without disrupting the operative field. For the first time, this technology allows all the information critical to a procedure to be instantaneously available at the surgeon’s fingertips.

— CereTom(TM) portable computed tomography (CT) scanner. This new technology allows physicians to do brain scans on critically ill or injured patients in ORs, emergency departments or intensive-care units without moving them. Developed by NeuroLogica of Danvers, Mass., CereTom(TM) gives physicians quick access to high-quality CT images of patients’ internal tissues and blood vessels in the cranium. This is particularly valuable in cases of severe head trauma or stroke, where “time to treatment” is critical in saving a patient’s life, or in situations where moving a patient to an imaging suite before or after surgery could prove fatal. CT scanning is especially helpful for cerebral arterial and cerebral vascular cases, plus deep-brain stimulation procedures for Parkinson’s disease.

— Biplane 3-D neuro-interventional suite. This technology is the most advanced system in the Pacific Northwest for advanced diagnostics and interventional treatment of brain lesions including cerebral aneurysms, arteriovenous malformations, intracranial vessel narrowing, and brain-tumor embolization. Advances in technology including devices such as coils (small- diameter wire for packing cerebral aneurysms to prevent or stop them from bleeding) and stents and new embolic materials that can be introduced through the cerebral vessels can eliminate the need for surgery in many cases. In cases where surgery is needed, such as arteriovenous malformations, selective vessel embolization with micro catheters can make the surgery safer. The Swedish facility is one of the first in the world to bring this angiogram capability into the OR.

SNI was established in 2004 with the goal of becoming the pre-eminent neuroscience provider in the Pacific Northwest and beyond. Today, the Institute is recognized internationally and treats more than 6,000 patients each year from all over the world. A significant percentage of Swedish’s neuroscience patients hail from outside the medical center’s typical Western Washington service area.

Members of the SNI care team include neurosurgeons, neurologists, neuroradiologists, rehabilitation-medicine and pain specialists, neuroendocrinologists, neuro-ophthalmologists, specially trained neuroscience nurses, and many other ancillary and support personnel. A new Neuroscience ICU and a dedicated Neuroscience nursing floor were completed in 2005. The Institute now treats patients suffering from brain and spinal cord tumors, stroke, aneurysms, spinal disorders, epilepsy, movement disorders such as Parkinson’s disease, multiple sclerosis and related conditions.

Work on the new SNI facility began in fall 2005. Callison of Seattle was the project architect and Lease Crutcher Lewis was the general contractor.

For more information on SNI, call 206-320-4144 or 1-800-331-1733 or visit http://www.swedish.org/.

About Swedish

Swedish is the largest, most comprehensive, nonprofit health provider in the Pacific Northwest. Founded in 1910, it now has more than 7,200 employees and a medical staff of more than 2,300 physicians, most of which are private practitioners. Swedish now encompasses three hospital campuses — First Hill, Cherry Hill (formerly Providence) and Ballard — totaling 1,245 licensed beds, a new freestanding emergency room and specialty center in Issaquah, Swedish Home Care Services and Swedish Physicians — a network of 12 primary-care clinics located throughout the Greater Seattle area. In addition to general medical and surgical care, Swedish is known as a regional referral center, providing specialized treatment in areas such as cardiovascular care, cancer care, orthopedics, high-risk obstetrics, neurological care, sleep medicine, pediatrics, organ transplantation and clinical research. For more information, call 1-800-SWEDISH (1-800-793-3474) or visit http://www.swedish.org/.

Photo: NewsCom: http://www.newscom.com/cgi-bin/prnh/20070212/SFM171AP Archive: http://photoarchive.ap.org/PRN Photo Desk, [email protected]

Swedish Neuroscience Institute

CONTACT: Ed Boyle of Swedish Neuroscience Institute, +1-206-386-2748, [email protected]

Web site: http://www.swedish.org/

ATLANTA, Feb. 12 /PRNewswire/ — A clinical study published in the medical journal Obesity (published by NAASO, The Obesity Society) demonstrated that people who drank the equivalent of three Enviga beverages over the course of a day burned 106 extra calories per day. This amounted to a slightly more than four percent increase in the amount of energy each person used compared with people who drank a low-calorie beverage placebo.

The study was conducted by the University of Lausanne, Switzerland, in collaboration with the Nestle Research Center. Researchers concluded that three servings per day of a product prototype of Enviga — a sparkling green tea containing a unique blend of green tea extract and caffeine — noticeably increased the amount of energy study participants used without any negative effects on heart rate or blood pressure.

Following best practices in clinical research, the study looked at 31 healthy men and women non-smokers 18-35 years of age who were of normal weight. Study participants were provided with a diet designed to match calorie intake to calorie burning, and were required to drink a serving of Enviga or a placebo beverage three times per day for three days. On the third day, participants were studied in a metabolic chamber under controlled conditions, which included a combination of sedentary activities and light exercise designed to simulate normal everyday activity.

“Enviga represents the perfect partnership of science and nature, providing an optimum blend of green tea extracts (EGCG) and caffeine,” said Rhona Applebaum, Chief Scientific and Regulatory Officer, The Coca-Cola Company. “Enviga complements — but does not replace — the need for regular physical activity and a moderate, varied and balanced diet. It is not designed as a weight loss product.”

“Energy balance is important, but it is just one part of the human health equation,” said Dr. Hilary Green, Group Manager in the Food-Consumer Interaction Department of Nestle Research Center. “Physical exercise, for example, delivers a range of health benefits above and beyond its contribution to energy expenditure.”

The study was conducted by the University of Lausanne in partnership with the Nestle Research Center. Enviga is a product of Beverage Partners Worldwide (BPW), a joint venture of Nestle and The Coca-Cola Company.

About Beverage Partners Worldwide

Beverage Partners Worldwide operates autonomously while drawing on the capabilities of Nestle and The Coca-Cola Company. It is a global business unit with cross-functional teams located in Atlanta, GA; Zurich, Switzerland; and Bangkok, Thailand. The Americas business unit markets Gold Peak and Nestea ready-to-drink iced teas.

For more information, visit http://www.enviga.com/

Ray Crockett (404) 676-1070 [email protected]

Beverage Partners Worldwide

CONTACT: Ray Crockett, +1-404-676-1070, [email protected]

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

Alere Medical, Inc., one of the leading disease management companies, today announced the opening of its newest call center in Columbus, Ohio to remotely monitor patients with heart failure. The opening will further expand Alere’s capabilities in remote patient monitoring, reflecting the rapid growth of patients enrolled in the company’s programs on behalf of leading health plans.

The Alere heart failure program works by placing its patented DayLink® monitor in a patient’s home when needed to monitor symptoms of heart failure, such as weight changes and shortness of breath. Using the patient’s regular phone line, the information is transmitted automatically to Alere’s call centers, which are staffed by cardiac-trained nurses. The nurses analyze trends that may indicate a change in the patient’s health status, contact the patient to review their condition and, if indicated, notify the treating physician. The Alere program’s daily monitoring allows for real-time nurse-provided education at the point when a patient needs it most, reducing the risk of hospitalization or emergency room visits.

“The clinical and support staff hired for the new Columbus call center are excited about the opportunity to work with Alere’s in-home remote monitoring program for individuals with heart failure,” said Clara Plantz, Clinical Services Manager and a Columbus resident. “This program will give us the ability to assist individuals, improve their quality of life and give them the additional security that nurses are monitoring them daily.”

The new call center will initially manage approximately 3,500 patients, with an anticipated enrollment of approximately 6,500 patients by April 30th, 2007. It officially opened on Monday, February 5th and employs 20 staff members from the Columbus area, comprised of management, nurses and support staff who will monitor patients with heart failure.

Located at 5450 Frantz Road in Dublin, the Columbus call center is Alere’s fourth, joining the company’s other call centers in Reno, Nevada; San Antonio, Texas; and Denver, Colorado.

About Alere Medical Inc.

Alere Medical Incorporated is a leader in specialized disease management services focusing on select high-cost diseases to maximize clients’ return on investment. Alere produces unequalled clinical and cost-saving results by precision-targeting patients who will benefit most from specialty interventions. Alere’s integrated care monitoring system identifies and monitors all medium- and high-risk patients, and prioritizes those patients to facilitate efficient workflow. With published outcomes that exceed those of any competitor, Alere Medical’s disease management programs result in improved clinical outcomes for patients and guaranteed savings for clients.

Alere Medical has received NCQA Patient Oriented Full Accreditation for its heart failure disease management program, as well as for its coronary artery disease (CAD) program. The company has also received Patient and Physician Oriented Full Accreditation for its asthma and COPD Programs powered by National Jewish Research Center (2004-2007). For more information, visit www.alere.com or call (775) 829-8885.

WESTLAKE VILLAGE Calif., Feb. 12 /PRNewswire/ — Jafra Cosmetics International has joined the fight against heart disease, the number one killer of American women. More than 460,000 female deaths in America are the result of cardiovascular disease. Jafra announced its official support of Go Red For Women, the American Heart Association’s (AHA), call to increase awareness of heart disease and to inspire women to take charge of their heart health.

“Jafra has an extraordinary opportunity to demonstrate its commitment to the issue of women and heart disease along the side of the American Heart Association,” said Dyan Lucero, president, Jafra Cosmetics International, U.S.A. “We want our consultants to become aware of heart disease and take the necessary steps to reduce their risk and teach their friends, family members and clients the lessons of the heart.”

As the first direct sales and multi-level marketing cosmetics company to support this cause, Jafra will create heart health awareness with women one-on-one at ultimate spa experience pamper parties across the nation. As the centerpiece of Jafra’s support of Go Red For Women, dedicated pamper parties will encourage Jafra independent beauty consultants to talk to their clients about the disease and steps they can take to improve their heart health.

In addition, from March 1, 2007 through April 30, 2007 Jafra will donate a portion of the proceeds from sales of the at-home Art of Balance spa line to AHA for a total of $25,000 in support of Go Red For Women. The Art of Balance is a complete new line of home aromatherapy products exclusively designed to provide an indulging way to refresh the body, invigorate the senses, and relax the mind.

   Jafra's involvement in the Go Red For Women movement also includes:   *  A link from both Jafra's Internet site http://www.jafra.com/ and Intranet site      http://www.jafrabiz.com/ to the Go Red For Women movement Web site   *  Featured heart health information on collateral materials that reach      hundreds of thousands of independent consultants and their clients   *  The creation of a training DVD that will instruct consultants and their      clients on how to adopt wellness practices for a healthier lifestyle      and the new Art of Balance at-home aromatherapy spa products   *  Consultants will learn more about heart health through the AHA's      presence at Jafra national events throughout the year: National      Leadership Academy, Jafra University, pamper parties and Jafra's annual      recognition summer trip in Nashville Tennessee, at the regal Gaylord      Opryland Resort    About the Go Red  

Since 2004, Go Red For Women has captured the energy, passion, and intelligence of women to work collectively to wipe out heart disease — the No. 1 killer of women. Today, we want millions of women across America to take heart disease personally. Using the simple platform “Love Your Heart,” Go Red For Women engages these women — and the men who love them — to embrace the cause. Healthcare providers, celebrities, and politicians also elevate the cause and spread the word about women and heart disease. For more information about Go Red For Women, please call 1-888-MY-HEART (1-888-694-3278) or visit GoRedForWomen.org. The movement is nationally sponsored by Macy’s.

About Jafra Cosmetics International

Jafra Cosmetics International is a direct sales and multi-level marketing company with a 50-year history of creating innovative, quality products that are backed by a customer satisfaction guarantee. Jafra, one of the world’s largest cosmetics manufacturers of beauty sales, is part of the Vorwerk Group, a billion dollar sales company. Today, Jafra spends extensive time and effort researching and developing effective skin care, beauty and fragrance products to satisfy the needs and preferences of its over 500,000 consultants and their clients worldwide.

Jafra Cosmetics International

CONTACT: Norma Villegas of Jafra Cosmetics International, U.S.A.,+1-805-449-2942, or cell, +1-818-723-6111

Web site: http://www.goredforwome.org/

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

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

By Carla McClain, The Arizona Daily Star, Tucson

Feb. 11–Many Tucson plastic surgeons are performing major surgeries using heavy anesthesia in their offices, with no back-up teams for emergencies, little oversight by the state and no record on their safety.

A Tucson attorney died recently after cosmetic surgery in her doctor’s office. The incident has brought the nationwide controversy home to Tucson, forcing a new look at these doctors’ practices.

Although few details about the death of Kimberley Taylor, 53, after undergoing two cosmetic surgical procedures Dec. 28 have been confirmed, it is known that her surgery was done by Tucson plastic surgeon Dr. Armando Alfaro in his office surgical suite.

During the surgery, Taylor was under a form of anesthesia known as “conscious sedation,” administered by a nurse anesthetist and not a physician anesthesiologist, according to information provided by her family, friends and colleagues.

At some point during the surgery, she stopped breathing and suffered a cardiac arrest. She arrived comatose at Tucson Medical Center’s emergency room and was placed on life support. Taylor died 10 days later.

Taylor’s colleagues originally reported she was undergoing a tummy tuck and a facelift — two major cosmetic surgeries. But her mother said the procedures were more minor — some liposuction around her waist and a tightening of her jaw line.

Arizona does not track patient deaths that occur from out-of-hospital, office-based surgeries, so there is no way to know how often it happens.

But in one state that does keep track — Florida — deaths were occurring at 10 times the rate of deaths during similar surgeries in hospitals or outpatient surgery centers.

That forced a statewide crackdown on the office-based surgical suites that are all the rage among plastic and cosmetic surgeons now, with new laws mandating safety standards and regular safety inspections to ensure they are met.

By contrast, most plastic surgeon surgical suites in Tucson remain unlicensed, unregulated and unchecked by Arizona.

It is estimated that 80 percent of Tucson’s 28 plastic and cosmetic surgeons now operate their own office-based surgical suites, doing everything from mole removals to face-lifts to tummy tucks. Nationwide, nearly half of all surgeries are now done in doctors’ offices, according to the American Society for Aesthetic Plastic Surgery.

Doctors love the privacy they can offer their patients, also the lower fees they can charge and higher profits they make.

“Nobody regulates this. Nobody reports the results. So what’s going on out there? Who’s doing what?” asked Sue Gerard, director of the Arizona Department of Health Services and a former state legislator.

“Now that more and more invasive procedures are being done in physicians’ offices, I definitely think we really need to revisit this issue, for the sake of patient health and safety. We have no idea to this day what is actually happening.”

Not wanting to cast aspersions on their colleagues, two Tucson plastic surgeons who still insist on doing all their surgeries in the hospital declined to comment on their reasons.

But even those who now do many or all of their surgeries in their offices admit to the safety advantages of a hospital.

“In a hospital setting, obviously you are in a place with a lot of doctors and nurses to respond” to a life-threatening emergency, said local plastic surgeon Dr. Gwen Maxwell, who recently opened a state-of-the-art surgical facility, where she performs all her procedures. “You just have a lot more people to manage an airway if the patient stops breathing, which can be tricky. You have the blood supplies if the patient is having major bleeding.

“But if you are a surgeon operating in an office who is not comfortable inserting a breathing tube or doing an emergency tracheostomy — who doesn’t do those things often — and who is not working with an M.D. anesthesiologist, you have a potential problem establishing breathing in an emergency.”

Death from cosmetic plastic surgeries remains rare, occurring in one of 57,000 cases, reports the American Society of Plastic Surgeons. About 2 million such surgeries were done in the United States in 2005.

By far, anesthesia during surgery poses the greatest risk, as it does with any surgery, and can cause abnormal heart rhythm, heart attack, stroke, paralysis, blood clots and airway problems. An unexpected allergic reaction, an undetected cardiac problem, certain medications and even herbal supplements, heavy smoking, asthma, and eating before the surgery all can cause life-threatening trouble under anesthesia.

“When a patient stops breathing, you have nine minutes to brain death,” said longtime Tucson plastic surgeon Dr. Peter Kay, who performs minor procedures in his office, but major surgeries in an outpatient surgery center. “You have to act very quickly.”

Efforts to contact Alfaro — who has always had an excellent reputation as a plastic surgeon — were unsuccessful.

“I know that he is just devastated by this,” Maxwell said.

The Arizona Medical Board has taken no disciplinary actions against Alfaro in the past five years, the most current records available on the board’s Web site show.

Unlike some other local plastic surgeons, he is fully trained in his specialty, has long experience in it, and has a surgical suite accredited by a legitimate private agency that mandates high safety standards — the same standards now required in highly regulated states such as California and Florida.

In other words, despite the state’s lack of oversight, he’s followed the rules that should reassure any patient demanding a safe and competent surgeon.

But despite all that, a healthy and fairly young patient died on his watch while undergoing a totally elective surgery that was not medically necessary.

“Dr. Alfaro is one of Tucson’s very highly respected plastic surgeons,” said Dr. Christopher Maloney, a Tucson plastic surgeon who does most of his major surgeries in an outpatient surgical center, staffed and equipped much like a hospital operating room. “There are a lot of people out there who are not board-certified, and are masquerading as if they are. Alfaro is not one of them.”

Patients who are conscientious enough to ask if a doctor is “board-certified” can be fooled easily, Kay said.

“In Arizona, you can say ‘I’m board-certified,’ but you don’t have to say for what, unlike other states that require you to specify,” he said. “There are dozens of bogus boards out there — like the ‘board of breast surgery’ — that don’t mean anything about your training, only that you’ve paid $25 to get a piece of paper.”

Before the Florida crackdown, doctors with no training in plastic surgery were performing cosmetic procedures in their offices — ER docs, dermatologists, ophthalmologists, family physicians — as they still can in Arizona, he said.

With Alfaro’s credentials so solid, the bottom-line question is, would Taylor have survived in a hospital?

“Maybe, but we don’t know that,” Maloney said. “My sense of this is that it is an outlier case, extremely rare, a tragic accident that could happen to anyone, even in a hospital.”

However, the case has been compared to one of the most famous cosmetic-surgery deaths in recent years — that of Olivia Goldsmith, the author of the best-selling novel “First Wives Club,” about women whose husbands leave them for younger “trophy” wives, and the resulting obsession with cosmetic surgery to try to compete.

Goldsmith, too, had gold-standard care, at least on paper, for her chin tuck — one of the top surgeons in New York City at one of the nation’s premier specialty hospitals, the Manhattan Eye, Ear and Throat Hospital.

Similar to Taylor, she stopped breathing and suffered cardiac arrest while under anesthesia, went into an irreversible coma, and died a week later, in 2004.

But this was not an unavoidable tragedy. In fact, an investigation by the New York health department found “egregious violations” by the hospital, which was fined the maximum, $20,000. Among the failures were inadequate monitoring of her vital signs while under anesthesia and an ineffective response to the emergency.

The potentially fatal risks of anesthesia are why some Tucson plastic surgeons insist on doing all their surgeries with a board-certified physician anesthesiologist, rather than a nurse anesthetist, even though nurse anesthetists are considered an acceptable standard of care for most types of anesthesia.

And that is where they differ from Alfaro, who used a nurse anesthetist in Taylor’s case. Some Tucson plastic surgeons use neither, doing their own anesthesia. That cuts the price for the patient.

“At the end of the day, if you ever have a problem … you want the best in the city,” said Maxwell, who uses only a physician anesthesiologist for surgeries in her office surgery center, which is fully accredited.

“This is surgery. This is not the time to cut corners and try to go cheap.”

As Kay, who also works only with a physician anesthesiologist, puts it: “It’s just that much more training and security.”

However, no one is questioning the credentials of nurse anesthetists to perform anesthesia. It seems to be a matter of comfort with the extra years of training a doctor receives.

“The nurse anesthetists I have worked with have been extremely competent — they can handle even the most complex heart surgeries,” said Tucson anesthesiologist Dr. Brian McCabe. “I really would not say it is more risky. I have tremendous respect for their abilities, especially those with years of experience. They practice at a very high level.”

Even so, all surgeries done in Tucson hospitals use physician anesthesiologists. The strict Florida law mandates physician anesthesiologists for all office surgeries requiring deep sedation or general anesthesia — after finding that less than 15 percent of the office surgery deaths happened under their care.

One of the reasons Arizona’s oversight in this area is so lax is that the state licenses and inspects only office-based surgery suites that use general anesthesia. That’s the deepest level of anesthesia, and it requires the patient be intubated for breathing. The law was passed some years ago, when the only options were local or general anesthesia.

But today, there is a whole range of techniques known as “conscious sedation,” using combinations of tranquilizers and narcotic painkillers to achieve almost the same state of sleep as general anesthesia, but with the patient breathing naturally, without intubation.

Most Tucson plastic surgeons use conscious sedation in their office-based surgeries, as Alfaro did with Taylor, and so do not come under state oversight. And there is no regulation about who should be handling the sedation or anesthesia.

“The law we have in Arizona does not consider these new techniques at all, and we really need to take a look at that,” said Lisa Wynn, deputy assistant director of the licensing division in the state health department.

For starters, Arizona health officials will study the tough Florida and California laws regulating office-based surgeries, director Gerard said.

“Regulation is a hassle — for those being regulated and those doing the regulating,” Gerard said. “But this trend is so widespread now, we have to get a handle on it.”

Is your surgeon board-certified in plastic surgery? To ensure adequate training, the surgeon must be certified by the American Board of Plastic Surgery. To verify a surgeon’s status, contact the board at 1-215-587-9322 or visit www.abplsurg.org

Is your surgeon’s surgical facility accredited for safety by one of three recognized accrediting agencies? Those agencies are the American Association for Accreditation of Ambulatory Surgical Facilities, the Joint Commission for Accreditation of Healthcare Organizations, and the Accreditation Association for Ambulatory Health Care. If the facility is accredited, it will be regularly inspected for safety policies and procedures, recovery room, proper use of advanced patient monitoring devices during surgery, proper medical records and patient evaluation, adequate operating-room staff, advanced emergency equipment and emergency response training and procedures, and safe use of anesthesia only by a board-certified physician anesthesiologist or certified registered nurse anesthetist. To verify accreditation status, contact:

–AAAASF at 1-888-545-5222 or www.aaaasf.org

–JCAHO at 1-630-792-5800 or www.jcaho.org

–AAAHC at 1-847-853-6060 or www.aaahc.org

Do surgeons have hospital privileges to perform the same procedure they’re performing on you in their offices?

Is your surgeon a member of either the American Society of Plastic Surgeons or the American Society of Aesthetic Plastic Surgery? If so, the surgeon will be required to operate only in a fully accredited facility.

What is your surgeon’s plan in the event of an emergency?

Has your surgeon done a complete medical history and physical evaluation of you before surgery?

Is a physician anesthesiologist or a certified registered nurse anesthetist giving and monitoring your anesthesia?

For more detailed safety tips and precautions, go to www.plasticsurgery.org

–Contact reporter Carla McClain at 806-7754 or at [email protected].

—–

Copyright (c) 2007, The Arizona Daily Star, Tucson

Distributed by McClatchy-Tribune Business News.

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.

By Mingione, Matthew J; Pressman, Eva K; Woods, James R

Abstract

Our understanding of the pathophysiologic processes leading to preterm premature rupture of membranes (PPROM) has grown tremendously in recent years. Evidence suggests that there may be a genetic susceptibility to PPROM and that genetic and environmental elements are important cofactors in its development. A number of risk-based protocols have been proposed in an attempt to identify those women at highest risk for PPROM. While we have made advances in the area of predicting PPROM, treatments based on current risk- based systems have failed to distinguish a specific, effective preventive therapy for PPROM. The concept that genetic factors increase susceptibility or decrease resistance to disease has stimulated new work in the field of PPROM. Several maternal and fetal gene polymorphisms have been identified that are associated with an increased risk for PPROM. Patients with ‘susceptible’ genotypes may also have clinical risk factors for PPROM resulting in a synergistic increase in the risk for PPROM, a so-called gene- environment interaction. The concept that these gene-environment interactions represent new targets for our efforts to prevent PPROM is explored.

Keywords: PPROM, prevention, polymorphism, genetics, gene- environment interaction

Introduction

For the practicing clinician, preterm premature rupture of membranes (PPROM) continues to be one of the most frustrating and devastating complications of pregnancy. Our understanding of the pathophysiologic processes leading to PPROM has grown tremendously in recent years and, as a result, has led to advances in the delivery of obstetric and neonatal care. Yet despite these advances, the incidence of PPROM has not changed and PPROM remains a major cause of perinatal morbidity and mortality. Successful strategies for the prevention of PPROM are needed.

Recent evidence suggests that there may be a genetic susceptibility to PPROM and that genetic and environmental elements are important cofactors in its development. In this era of ‘-omics’- based research, we have many new tools for deciphering the pathways that lead to PPROM. In this review we discuss current modalities for the prevention of PPROM. We also consider how gene-environment interactions offer opportunities to improve the efficacy of these preventive efforts by tailoring therapy to suit a patient’s risk profile.

The pathogenesis of PPROM

In the USA, Preterm premature rupture of membranes complicates 140 000 pregnancies annually [I]. The scope of this problem is not difficult to appreciate. Like many obstetric diseases, the etiology of PPROM appears to be multifactorial. A number of clinical risk factors for predicting PPROM have been identified (Table I) [2-6].

Recently, subclinical intrauterine infection has been implicated as the major etiologic factor contributing to the pathogenesis of PPROM [7]. Subclinical infection is the presence of pathogens in tissues that are not producing clinical evidence of overt infection. Most subclinical infections are believed to have ascended from the lower genital tract. The initiating event is likely a change in the normal vaginal flora or introduction of pathogens from an exogenous source into the cervix leading to an inflamed vaginal milieu [8]. The pathogens ascend into the decidua and enter the fetal membrane where they generate a cascade of maternal and fetal inflammatory events that culminate in membrane weakening and rupture.

Table I. Risk factors for PPROM.

Damage to type I collagen, the primary supporting element in the chorioamnion, is believed to represent the final step in the sequence leading to membrane rupture. Normally collagen deposition and degradation in the fetal membranes are balanced continuously until term. Collagen is laid down by fibroblasts and degraded by a family of enzymes called matrix metalloproteinases (MMPs). In anticipation of term labor and delivery, the membrane weakens in response to an up-regulation of matrix metalloproteinase-9 [9]. The action of MMPs is normally held in check by tissue-specific inhibitors of their activity (TIMPs). In the case of PPROM, disruption of the balance between MMP and TIMP activity is the terminal event that results in collagen degradation and eventual membrane rupture.

The clinical risk factors generate PPROM through different pathways that up-regulate the inflammatory process. Infection leads to recruitment of activated neutrophils and macrophages. These cells are capable of killing bacteria by releasing reactive oxygen species (ROS) that destroy the bacterial cell wall. The primary ROS released, hypochlorous acid, is also capable of damaging the fetal membrane directly and acts as a signal for the up-regulation of MMPs.

Smoking and cocaine use generate ROS that induce tissue damage and inflammation via lipid peroxidation [1O]. Subchorionic hemorrhage that is manifested as vaginal bleeding stimulates inflammation and membrane damage by at least three different pathways. First, the iron released from the lysed erythrocytes acts as a catalyst to generate the hydroxyl radical, a potent but short- lived ROS. second, thrombin in the clot directly enhances decidual cell production of MMP-3 [11]. Lastly, platelets in the clot stimulate the release of chemoattractants, via the CD-40 ligand system, that recruit inflammatory cells to the site of bleeding [12].

The resultant increase in local inflammatory mediators such as interleukins-1, 6, and 8 and tumor necrosis factor-alpha (TNF- α) up-regulate MMPs and inhibit TIMPs. This tips the balance of collagen remodeling in favor of degradation and eventual membrane rupture. The interested reader is referred to two recent comprehensive reviews on the role of matrix degrading enzymes in PPROM [13,14].

Current status in the prediction and prevention of PPROM

A number of risk-based protocols have been proposed in an attempt to identify those women at highest risk for PPROM. Additionally, numerous biomarkers, especially the proinflammatory TH-I cytokines, have been associated with an increased risk for PPROM [14]. With these predictive tools, early risk assessment and treatment to prevent PPROM and preterm birth (PTB) have been attempted. There is much debate about the distinction between PTB and PPROM and whether they represent different clinical entities with separate pathophysiologies. That argument is beyond the scope of this review. However, while there are many trials addressing the prevention of PTB there are few that focus on prevention of PPROM specifically. Given that one third of PTBs are the result of PPROM, the possibility that preventing PTB also prevents PPROM is considered [15].

Methods for prevention

Antibiotics

The association between lower genital tract infection and PPROM is well documented. While no study has proved the cause and effect relationship between infection and PPROM, several recent reviews support the treatment of asymptomatic bacteria, gonorrhea and chlamydia to reduce the risk of PPROM [16,17]. The issue of whether bacterial vaginosis (BV) has a role in the pathogenesis of PPROM remains undecided [18]. A recent metaanalysis confirms the widely held belief that there is no utility in screening for asymptomatic BV. However, treatment of symptomatic BV in patients with a history of PPROM or preterm birth (PTB) is indicated as it reduces the risk of recurrent PPROM [19].

Progesterone

Progesterone is rapidly becoming mainstream therapy for the prevention of PTB. There are no trials specifically addressing the role of progesterone in the prevention of PPROM. Evidence for prevention of PTB with the prophylactic administration of progesterone has existed for several years [20,21]. Two recent trials have renewed interest in the administration of progesterone for the prevention of PTB. Meis and colleagues published their results of 463 women randomized in a 2:1 fashion to 17α- hydroxyprogesterone caproate or placebo. All subjects had a history of prior PTB. They demonstrated a reduction in the rate of PTB by 34, 33, and 42% at less than 37, 34, and 32 weeks, respectively. All of these differences were statistically significant [22]. da Fonseca et al. randomized 142 ‘high-risk’ subjects to daily progesterone vaginal suppositories or placebo. The rate of PTB at less than 34 weeks in the treatment group was 2.8%, compared to 18.6% in the placebo group, a statistically significant difference [23]. Despite the fact that the mechanism by which progesterone prevents PTB is unknown, the evidence seems adequate for clinicians to prescribe progesterone therapy for the prevention of PTB, and to a lesser extent PPROM, for patients with a previous PTB.

Cerclage

There are no trials specifically addressing the role of cervical cerclage in preventing PPROM. Cerclage, however, is commonly used in women with a history of PTB. Investigators of four randomized trials have addressed whether PTB could be prevented with cerclage in patients with historic risk factors [24-27]. Each failed to demonstrate a reduction in PTB at less than 37 weeks. Most recently several investigators evaluated the effectiveness of cervical cerclage to prevent PTB in the setting of shortened cervical length detected at a secondtrimester ultrasound. Rust and colleagues randomized 113 women with a cervical length less than 2.5 cm to McDonald’s cerclage and bed rest \or bed rest alone [28]. To and colleagues randomized 253 women with a cervical length less than 1.5 cm to Shirodkar cerclage or no treatment [29]. Both of these large trials failed to demonstrate any benefit of cervical cerclage in the setting of shortened cervical length. Althuisius and colleagues enrolled women with a cervical length less than 2.5 cm who also had either a history of PTB or historic risk factors for PTB. They demonstrated a significant reduction in PTB at less than 34 weeks and a reduction in composite neonatal morbidity. There was no demonstrable benefit in a subset of patients that was randomized to prophylactic rather than therapeutic cerclage [30].

When these studies are considered collectively, it appears that both clinical history or risk factors and a sonographically shortened cervix must be present for cervical cerclage to have any potential benefit in preventing PTB. Whether this can be extrapolated to the prevention of PPROM remains unanswered. In fact, there is evidence that a cerclage may be a risk factor for PPROM. Odibo and colleagues have published data indicating that cerclage placement in a current pregnancy is a risk factor for subsequent PPROM [5].

These findings further diminish the benefit-risk ratio of cerclage for the prevention of PPROM. Thus, cervical cerclage placement should be reserved for those patients with multiple predictors for PTB and likely has little role in specifically preventing PPROM.

Dietary antioxidant therapy

The primary supporting structure within the chorioamnion extracellular matrix is type I collagen. Vitamin C is essential for the formation of collagen and vitamin C deficiency has been associated with PPROM [6,31]. Low tissue concentrations of ascorbic acid have also been associated with an increased risk of PPROM [32]. There are two randomized trials of vitamin C administration for the prevention of PPROM or PTB with disparate conclusions. Steyn and colleagues randomized subjects with a history of preterm labor in a previous pregnancy to vitamin C or placebo. They found a significantly increased rate of PTB in the treatment group and no difference in short-term neonatal outcome [33]. Casanueva and colleagues randomized unselected subjects to vitamin C or placebo and found a significantly lower rate of PPROM in the treatment group with a trend towards lower rates of PTB [34]. While low levels of vitamin C are associated with PPROM and PTB, the current data do not support the routine supplementation of vitamin C to prevent these adverse outcomes.

Unfortunately, treatments based on current riskbased systems have failed to distinguish a specific, effective preventive therapy for PPROM. In fact, the Maternal-Fetal Medicine Units Network has recognized such and consequently not recommended any broad-based screening programs for the prediction of PPROM [2].

New strategies in predicting and preventing PPROM-the role of genetic polymorphisms

The concept that genetic factors increase susceptibility or decrease resistance to disease has stimulated new work in the field of PPROM. This work may provide us with new avenues for prevention.

Individuals may have a specific genotype that places them at greater risk for disease when exposed to environmental factors than could be predicted by the presence of the genotype or exposure alone. When a combination of ‘susceptible’ genotype and the environmental exposure synergistically increase the risk for disease, a gene-environment interaction is said to exist [35].

Concerning PPROM, these ‘susceptible’ genotypes generally represent polymorphisms in genes known to be involved in immune regulation or collagen metabolism. Several maternal and fetal gene polymorphisms have been associated with PPROM (Table II) [36-42]. The example of a polymorphism in the TNF-α gene and symptomatic bacterial vaginosis is reviewed in detail.

Bacterial vaginosis is diagnosed in up to 20% of pregnant women. While it has been associated with PPROM, it is unlikely that such a prevalent condition represents a pathologic state in every patient, particularly when considering the comparatively low incidence of PPROM. Recent work by Macones and colleagues is lending strength to the theory that BV is a significant risk factor for PPROM under the right conditions. They have identified a subgroup of women with symptomatic BV who may have an elevated risk for infection- associated PPROM [36]. In a case-control study, DNA from patients with PPROM was analyzed for the -308 polymorphism in the TNF- gene. This polymorphism results in an overproduction of TNF-α leading to an excessive proinflammatory response. Maternal carriers of this polymorphism had a significantly increased risk for PTB due to PPROM, OR 2.7 (1.7-4.5). When this risk was stratified for the presence or absence of symptomatic BV, those with the ‘susceptible’ genotype and BV had increased risk for PTB, OR 6.1 (1.9-21.0), compared to those without BV, OR 1.7 (1.0-3.1). Further, their multivariable analysis confirmed that the BV-TNFa-308 interaction was the only significant risk factor for PPROM in their population, indicating that there was a geneenvironment interaction. These results may explain why past studies of varied populations have failed to link BV to PPROM consistently [43]. It also provides a plausible explanation for the failure of antibiotic treatment of BV to prevent PPROM in these mixed populations where it has been found to be linked.

Table II. Gene polymorphisms associated with increased risk of PPROM.

Polymorphisms in other non-immune system genes can also be linked to PPROM. Abnormal collagen is a risk factor for PPROM, as observed in patients with Ehlers-Danlos syndrome. As stated above, vitamin C availability is critical to the formation of normal collagen and it has been tested as a preventive therapy for PPROM in previous trials. Regrettably, similar to the treatment of BV, vitamin C therapy for the prevention of PPROM or PTB has yielded mixed results [33,34]. Recently, Erichsen et al. reported an increased risk for PTB among patients who carried a polymorphism in the sodium- dependent vitamin C transporter gene [44]. Homozygotes for the polymorphism had a 2.7-fold increased risk for PTB. The authors concluded that this polymorphism might explain previous dietary associations with PPROM and PTB. If there were a difference in the allelic frequencies of the polymorphic gene in the two study populations, then this could account for the difference in outcomes. Supplementation in patients with dysfunctional or decreased numbers of vitamin C transporters may help to drive ascorbic acid into the cell. Unfortunately, no gene-environment interaction was tested to determine whether this polymorphism might interact with the clinical risk of poor nutrition or oxidant stress.

The role of progesterone for the prevention of PPROM may also be influenced by genetic factors. While there are no studies examining progesterone receptor gene polymorphisms and their possible link to PPROM, there are data that support this premise. Both term and preterm labor have been associated with decreased expression of progesterone receptors [45,46]. There are also data demonstrating that decreased progesterone receptor expression is associated with a reduction in fetal membrane fibrillar collagens [47]. A reduction in membrane fibrillar collagens results in a weakening of the membrane whether under physiologic or pathologic conditions. If a polymorphic progesterone receptor gene results in the decreased expression of progesterone receptors or expression of faulty progesterone receptors, then a ‘weak membrane’ phenotype might be expected.

The genes discussed are primarily involved in immune regulation. As such, for the polymorphism to become clinically apparent, there must be an evoked immune response. Although these gene polymorphisms have been associated with the pathogenesis of PPROM under specific conditions, it is unlikely that possession of these genotypes alone is sufficient to result in the expression of the PPROM phenotype. More likely is the scenario that an environmental exposure (e.g., infection) results in a genotype-specific, exaggerated proinflammatory response that increases the likelihood of PPROM. Using this theory, the genotype, the exposure (clinical risk factor) or both may be used to identify patients at increased risk for PPROM. Identifying the clinical risk factors or predictors of PPROM is currently done in most centers. Genotype analysis for predicting PPROM, however, is not commercially available as a clinically useful tool. Hao and colleagues have recently reported using high- throughput genotyping technology to analyze candidate genes associated with preterm birth [48]. Using this method they were able to identify, quickly and cost-effectively, gene polymorphisms that may be involved in the pathogenesis of PPROM.

As studies of this type continue to be published, more gene polymorphisms linked to PPROM will be discovered. Future gene- environment or genenutrient investigations are likely to reveal that distinct populations (e.g., African-Americans) have specific polymorphisms or differences in gene-linkage disequilibrium patterns that explain why they are at the highest risk for PPROM.

Conclusion

Preterm premature rupture of membranes may soon be considered a disease of the genome that is influenced by environmental and nutritional factors. The PPROM phenotype may be the result of interactions of environmental and genetic elements both of which are potentially identifiable in high-risk patients. If the functional analyses of genotypes susceptible to PPROM are incorporated into a 1PPROM gene chip’ and combined with clinical risk factors, then patients with the highest risk of PPROM can be identified. PPROM may then be preventable with future individualized therapy based on the particular patient’s genotype, clinical risk facto\rs, and known gene-environment interactions.

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MATTHEW J. MINGIONE, EVA K. PRESSMAN5 & JAMES R. WOODS

Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, University of Rochester, Rochester,

New York, USA

(Received 2 August 2006; revised 18 October 2006; accepted 15 August 2006)

Correspondence: Matthew J. Mingione, MD, Assistant Professor, Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, University of Rochester, 601 Elmwood Ave, Box 668, Rochester, NY 14642, USA. Tel: +1 585 273 3242. Fax: +1 585 256 1416. E-mail: [email protected]

Copyright Taylor & Francis Ltd. Dec 2006

(c) 2006 Journal of Maternal – Fetal & Neonatal Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

WALNUT CREEK, Calif. _ On a typical day, five or six patients would fill Dr. Michael O’Brien’s small waiting room, cooling their heels until they got 10 minutes with the Castro Valley, Calif., physician.

Now, his waiting room is often empty. Most patients get in to see him immediately and have 30 minutes or longer per visit.

“I feel better about what I’m doing,” he said.

O’Brien has joined a small but growing number of primary care physicians who have opted for a new form of medical practice, often referred to as concierge, boutique or retainer doctors.

O’Brien prefers “personalized health care.”

The approaches vary, but many require patients to pay annual fees of $1,500 to $2,000. A few charge as much as $15,000.

In return, the physicians limit the size of their practices and provide more personalized, preventive care. Many give out their personal cell phone number and promise same-day or next-day appointments.

Under the most expensive options, some doctors make house calls, deliver medication or accompany patients to see specialists.

A 61-year-old internist who has practiced in Walnut Creek, Calif., for 28 years agonized for months before deciding to switch.

Dr. Ronald Campos has been holding meetings to explain the decision to his patients. When he opens his new practice on Feb. 7, he will drop his patient load from 2,000 to no more than 600. The hardest part will be ending relationships with people he has known for years.

“It was the realization that I didn’t have enough time for patients,” he said last week. “I’m realizing I want to do something better for them.”

O’Brien and Campos have affiliated with MDVIP, a Florida firm founded in 2000. They will each charge annual fees of $1,500. MDVIP will take $500 of that amount.

For their expense, patients will receive a complete annual physical, a credit card-size CD with their medical records, a personal wellness plan, same or next-day appointments lasting a half-hour or longer, and the doctor’s cell phone number with permission to call anytime, night or day.

The annual fee does not cover routine medical bills, including most office visits, lab tests and hospital stays. Those still must be paid by a patient’s insurance company, Medicare or other means.

Most patients will pay the annual fee out of their own pockets because insurance companies and Medicare generally do not cover it.

Nationwide, 300 to 400 doctors now practice some form of concierge or boutique medicine, mainly on the East and West coasts.

The movement grew out of frustration with low reimbursements that many physicians say forces them to squeeze in 20 to 30 patients per day.

It comes at a time when insurance companies and Medicare provide little money for preventive care, while imposing a host of restrictions about what they will cover.

The result: Many physicians say they cannot practice medicine the way they would like.

At age 50, O’Brien operated a solo family practice in Castro Valley, Calif., for 18 years before deciding last fall to become an MDVIP physician.

It worried him, he said, that in his typical five- to 10-minute appointments, he could treat the ailment that brought a patient to his office but often did not have time to notice that someone was overdue for a mammogram or a bone density test.

“In the back of my mind, I knew I was missing things,” he said.

For Campos, one recent patient drove the point home. During a typical hectic day, Campos spent 10 minutes with a 34-year-old man who came in with a sore foot. A week later, the man hanged himself.

“That emphasized what I don’t like _ the fact that I have to hurry, the fact that I don’t have that extra time,” Campos said.

Both he and O’Brien anticipate they may lose money during the first year of their new practice, but say the change will be worth it.

“This is about quality of life, quality of care, time for patients, and going home and having a good feeling that you’ve cleared your desk, that you called everybody back, that you took care of everything, and not questioning in your mind did you forget something,” Campos said.

The trend is controversial, with critics arguing that it aggravates health care disparities and shrinks the pool of physicians available to treat those who cannot afford such service.

“My initial feeling is that it’s sort of outrageous that a doctor would do that,” said Dr. Richard Cooper, senior fellow at the Leonard Davis Institute of Health Economics at the University of Pennsylvania.

“The bad side is you create a two-class society because not everybody can afford that.”

Cooper said he is particularly concerned about doctors shrinking their practice to less than a third of its previous size.

“That means you need three doctors to do what one doctor used to do,” he said. “So now you’ve made the physician shortage even worse.”

But like many critics, Cooper said he understands the frustrations many doctors feel.

“They’re forced by the system to practice the kind of medicine that they don’t even think is right,” he said. “…The bad guy here is the system.”

Rather than making the physician shortage worse, Dr. Edward Goldman, the CEO and co-founder of MDVIP, argues that his firm helps to keep doctors from abandoning the profession.

One recent survey found that 55 percent of primary care doctors age 50 and older were contemplating leaving or limiting their practice within the next three to five years, he said.

They are dropping out at a time when aging baby boomers will need them more than ever.

“We’re sitting with a looming crisis that very few people seem to be talking about,” Goldman said.

He also disagrees with those who say his firm helps to create a two-class health care system. The current system is multi-tiered, he argues, with different rungs on the health care ladder for the uninsured and those on Medi-Cal, Medicare, an HMO, a PPO, and top-notch insurance.

MDVIP has 143 affiliated physicians in 16 states serving more than 50,000 patients. Its business is growing by about 2,500 patients per month.

Dr. Chris Ewin, who heads a professional association for concierge doctors, has developed a different model.

Based in Fort Worth, Texas, he charges about $1,400 annually. That entitles his patients to see him as often as they want, without a co-pay.

But unlike the MDVIP doctors, Ewin does not deal with insurance companies or Medicare. If patients need lab work or X-rays not included in their annual fee, they pay for it and seek reimbursement themselves.

For Ewin, this eliminates the “middleman,” controls costs and avoids mounds of paperwork.

He heads the Society for Innovative Medical Practice Design, a professional association for such doctors formed in 2002.

“What we’ve realized is that we’ve been working for the wrong employer for a long time,” Ewin said. “Instead of working for the insurance company or the government, we would like to work for our patients.”

Castro Valley resident Dong-Hoon Cho and his wife, Oak-Kyung, pay O’Brien annual fees totaling $3,000. They consider the expense well worth it.

At ages 70 and 66, they remain healthy but realize they may develop health problems. For now, they like not having lengthy waits to see O’Brien.

“Money is not that important when I’m thinking about my health and my wife’s health,” said Cho, a retired real estate broker. “Regular doctors are too much rush, rush, hurry, hurry.

“This is like my own private doctor,” he said. “He pays attention to us and gives us plenty of time. We feel like we are VIP patients.”

The Government Accountability Office studied concierge doctors in 2005 and concluded their numbers remain too low to affect access to health care. Federal officials said they will monitor the trend.

The dean of University of California at Berkeley’s school of public health said physicians need better rewards and incentives for providing high-quality, cost-effective care.

“The hope would be,” said Stephen Shortell, “that fewer physicians would see the need to work outside the insurance system in order to get fairly compensated or to have the kind of practice they would like and the way they would like to treat their patients.”

___

CONCIERGE DOCTORS

_ For a list of those affiliated with MDVIP, go to www.mdvip.com or call 866-696-3847.

_ The Society for Innovative Medical Practice Design lists its members at www.simpd.org.

___

(c) 2007, Contra Costa Times (Walnut Creek, Calif.).

Visit the Contra Costa Times on the Web at http://www.contracostatimes.com.

Distributed by McClatchy-Tribune Information Services.

_____

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Concentra Operating Corporation (“Concentra” or the “Company”) today announced that it has signed a definitive agreement to sell its workers’ compensation managed care services business units to Maryland-based Coventry Health Care, Inc. (“Coventry”) (NYSE:CVH). Total consideration in the sale is $387.5 million, to be paid in cash at closing.

The business units that Concentra plans to divest in the transaction are its Workers’ Compensation Network Services (comprising its provider bill review and repricing services, and its FOCUS preferred provider organization), Field Case Management, Telephonic Case Management, Independent Medical Exams, and its Pharmacy Benefit Management business (First Script Network Services). These businesses generated a total of approximately $324 million of revenue in 2006.

The transaction is expected to be completed in 90 to 180 days, subject to closing conditions as well as regulatory and other customary approvals. Concentra estimates that the transaction will result in net after-tax proceeds of approximately $265 million, of which it currently anticipates that approximately $255 million will be used to prepay of a portion of its senior term indebtedness.

Commenting on the announcement, Concentra’s President and Chief Executive Officer, Daniel J. Thomas, said, “We are excited about the prospects for our company in view of this transaction. Our customers will be well served by the combination of Concentra and Coventry’s workers’ compensation services businesses. When the sale is completed, Concentra will continue to own and operate the largest national network of health centers and to be the premier provider of cost-containment, claims review and repricing, and network management services to group health and auto insurers. With our strong position in these growing markets, and with our continuing businesses producing over $1 billion in annual revenues, we expect that our focus on these core business lines will produce attractive growth opportunities for Concentra in the years to come.”

Dale B. Wolf, Chief Executive Officer of Coventry Health Care, added, “We are excited about the opportunities this transaction presents. These Concentra businesses and the talented professionals operating these businesses, when combined with our existing workers’ compensation operations, will result in a well integrated service offering that will be attractive to our customers.”

Coventry Health Care is a national managed health care company based in Bethesda, Maryland, operating health plans, insurance companies, network rental, managed care and workers’ compensation services companies. Coventry provides a full range of risk and fee-based managed care products and services, including HMO, PPO, POS, Medicare Advantage, Medicare Prescription Drug Plans, Medicaid, Workers’ Compensation services and Network Rental to a broad cross section of individuals, employer and government-funded groups, government agencies, and other insurance carriers and administrators in all 50 states as well as the District of Columbia and Puerto Rico. More information is available on the Internet at www.cvty.com.

Concentra Operating Corporation, a wholly owned subsidiary of Concentra Inc., is dedicated to improving the quality of life by making healthcare accessible and affordable. Serving the occupational, auto and group healthcare markets, Concentra provides employers, insurers and payors with a series of integrated services that include employment-related injury and occupational healthcare, urgent care services, in-network and out-of-network medical claims review and repricing, access to preferred provider organizations, case management and other cost containment services. Concentra provides its services to approximately 200,000 employer locations and more than 1,000 insurance companies, group health plans, third-party administrators and other healthcare payors. The Company has 310 health centers located in 40 states. It also operates the Beech Street PPO network.

This press release contains certain forward-looking statements, which the Company is making in reliance on the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that all forward-looking statements involve risks and uncertainties, and that the Company’s actual results may differ materially from the results discussed in the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, changes in nationwide employment and injury rate trends; operational, financing and strategic risks related to the Company’s capital structure, acquisitions and growth strategy; the adverse effects of litigation judgments or settlements; interruption in its data processing capabilities; the potential adverse impact of governmental regulation on the Company’s operations; competitive pressures; adverse changes in market pricing, demand and other conditions relating to the Company’s services; possible fluctuations in quarterly and annual operations; and dependence on key management personnel. Additional factors include those described in the Company’s filings with the Securities and Exchange Commission.

PURCHASE, N.Y., Feb. 8 /PRNewswire-FirstCall/ — PepsiCo announced today that Derek Yach, former Representative of the Director General at the World Health Organization, has been appointed the company’s Director — Global Health Policy, a new position to direct the company’s global health and wellness policy. He will report to Antonio Lucio, the company’s chief Innovation and Health & Wellness officer.

“This move is in keeping with our commitment to develop the world’s most balanced portfolio of convenient food and beverage choices, and to ensure we’re meeting consumer needs for health and wellness,” said Indra Nooyi, PepsiCo president and CEO. “With health and wellness as our primary growth opportunity, we are investing in senior talent who will actively engage external partnerships and government and non-government organizations to arrive at policies that positively impact our strategy.”

Yach, 51, is an internationally recognized public health policy leader and will be responsible for setting the company’s global health and wellness policy. He will work with non-government organizations (NGOs) and inter-governmental organizations to establish productive relationships such as PepsiCo’s 2006 partnership with the William J. Clinton Foundation and the American Heart Association to create a school policy offering healthier choices of beverages and foods/snacks in schools.

“We’re fortunate to have a leader of Derek’s caliber and talent join PepsiCo. Derek has an undisputed track record in driving global health policies that support good nutrition and physical activity — two complementary strategies to combat obesity and other health issues across the globe,” said Nooyi. “I’m confident that his expertise in the global public health policy arena will strengthen and accelerate our health and wellness agenda.”

Over the last 10 years, Yach has held key leadership positions related to global health and the advancement of health, wellness and chronic disease research, prevention and control. These include positions at the World Health Organization (WHO), Yale University and the Rockefeller Foundation. While serving at the WHO, Derek held the positions of Representative of the Director General and the Executive Director, Noncommunicable Diseases and Mental Health. At Yale University, he was a professor of Public Health and division head of Global Health. Most recently, Derek served as Director, Global Health at the Rockefeller Foundation.

PepsiCo is one of the world’s largest food and beverage companies with annual revenues of more than $35 billion. Its principal businesses include Frito-Lay snacks, Pepsi-Cola beverages, Gatorade sports drinks, Tropicana juices and Quaker foods. Its portfolio includes 17 brands that generate $1 billion or more each in annual retail sales.

PepsiCo

CONTACT: Lynn Markley, Vice President – Health & Wellness, PublicRelations & Community Affairs, of PepsiCo, +1-914-253-3059

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

By Anastasia Stephens

On the sheepskin rug, in front of the fire, a dozen or so bodies are lying in spoons, or face to face, or in any position that helps you to hug someone. There’s some stroking and laughter, a few contented sighs. Apart from a little gentle repositioning and head- stroking, not much is happening. In fact, inaction is the flavour of the afternoon.

I’m being spooned by Jason, a photographer, while nestling my head and neck in the armpit of a woman. Three arms are wrapped around me and I’m stroking another arm. This is the outcome of our “canoodle casserole”. Earlier on, we had warmed up by giving each other full one-to-one body hugs.

Despite the strangeness of the situation – I hardly know these people – all the stroking has sent me into a state of jellified contentment, a bit like a blissed-out dog. At the same time, I’m very aware that if a middle-aged neighbour were to walk in, the words “orgy” and “swinging” would spring to mind.

But this has nothing to do with sex. It’s a cuddle party, the antidote to a s n u glestarved society and a prelude to bigger cuddle parties coming to Britain from the United States this month.

That’s right, cuddle parties. Unlike the dinner party, or dance party, instead of pitching up with a bottle of wine, you bring your pyjamas. Then you dive on to the sofa, or into bed, with a bunch of strangers for some carefree caressing.

And we’re all here for the sake of enhancing our emotional wellbeing and health. According to Reid Mihalko and Marcia Baczynski, the relationship coaches who created the Cuddle Party events and website in the US, we are all in desperate need of more physical contact. Cuddling, they say, has positive effects on self- esteem, confidence and anxiety, and is the most direct, physiological way to make a person feel wanted.

“A good hug speaks directly to your body and soul, making you feel loved and special,” Mihalko says. “It overwrites any unworthiness or ‘negative voices’ in your head telling you that you cannot be loved. It’s a great anxiety remedy; held in the arms of another, any tension just drains away.”

Of course, to reassure the wary, there have to be cuddle rules. All parties begin with a welcome circle where people can talk about their reservations. Even then, everyone must ask permission before cuddling – and it is equally important to say no to a hug if it doesn’t feel comfortable.

The problem, Baczynski says, is that we are touchdeprived. “In our society, we get physical affection through relationships.If you’re single, you have to live with a few awkward passes, the odd drunken grope or an o c asional semi-hug from a friend. Even a relationship is no guarantee that you’ll get the affectionate touch you need.”

That’s where cuddle parties come in. They broaden people’s scope for physical intimacy. “There’s a lot of confusion and fear about intimate touch,” Mihalko says. “It doesn’t need to be sexual, and there doesn’t need to be an agenda. You can get it from strangers and it can be very nourishing.”

Their assertions appear to be backed up by research. Studies at the University of North Carolina show that hugging induces positive physiological and emotional changes in the body, mainly by inducing the release of oxytocin the love hormone.

Researchers found that hugging for 20 seconds was enough to boost levels of oxytocin sufficiently to induce emotional and physiological benefits for a whole day. Oxytocin into not only makes you feel good; it also improves heart function, protecting against heart disease. Hugging was found to reduce levels of the stress hormone cortisol, which is associated with anxiety, physical tension, anger and weaker immunity.

These findings support a previous study which found that hugging reduced the emotional effect of stress. When two groups of couples were asked to talk about an angry event, those that hugged first maintained significantly lower heart-rate and blood pressure.

But the benefit of receiving regular hugs could be even more profound. According to Linda Blair, a clinical psy-chologist at Bath University, researchers have now found that touch and hugging are needed for basic positive emotions to develop.

“Touch affects the cerebellar brain system, an area of the brain where basic positive emotions such as trust and affection probably come from,” Blair says. “If you get lots of cuddles early on, you will internalise trust, as well as feelings of bonding and love. If you get no touch, or if the touch is anxious or unfriendly, you will tend to develop mistrust and wariness.”

Marianne Jones, a massage therapist from west London, believes that even if you lacked the benefits of touch early in life, you can make up for it later on. “We never get too old to benefit from positive touch,” she says. “And, for those who get in adulthood what they lacked in childhood, it can be tremendously healing. Cuddle parties could give people the chance to let others come closer, and to give and receive affection. You’d probably see where you hold tension and anxiety from past emotional pain, and grieve for what you didn’t get.”

The benefits of hugging are now so widely recognised that, in the US, it is sometimes prescribed instead of medication. Organisations such as the US Surviving Burns Support Service advocate “hug therapy” as a way to reduce social isolation and depression and to foster feelings of belonging.

“There can’t be a faster, more direct way of making you feel connected, wanted and happy than with a bear-like squeeze,” says Tina Malhotra of Free Hugs, an international campaign group to promote hugging. “That’s why we go on to the streets and offer hugs. Some people are wary, but most find that a quick cuddle is enjoyable and it puts smiles on their faces.”

The canoodle casserole certainly put a smile on my face; first, a snigger at the eccentricity of it all, and then a much deeper, satisfied smile. Despite feeling uncomfortable at times – I felt more at ease with some people than with others, and I wouldn’t let just anyone touch me – the party left me feeling unexpectedly content.

And it opened my eyes to completely new experiences. It’s not every day that you get to stroke another woman’s hair affectionately, or cuddle a man just for the sake of it.

So, as strange as cuddle parties sound, I’d recommend them. With no small talk and plenty of silliness, they beat dinner parties hands down.

How to heal with a hug

Too give a proper heart-warming cuddle, you need to grasp the body language of hugging. The most common hug among the British is the shoulder-clasp. This involves leaning forward, politely touching the huggee’s shoulders and kissing the air on either side of their cheeks.

“With the vast majority of hugs, people hold their bodies back,” says Mike Skileck, be a teacher of biodanza, a danced therapy with an emphasis on hugging. “The lack of contact doesn’t make you feel appreciated.”

Be daring the next time you contemplate a hug. Once in the hugging position, stay there. Enjoy the cuddle rather than try to escape it. For a proper “therapeutic” cuddle, keep hugging for at least a minute. Notice how it makes you feel.

Hugging like this makes some people feel uncomfortable. But once you get used to it, most find that it eases tension, and encourages positive emotions.

The power of touch

Research is confirming that affectionate touch is a good all- round medicine. So what are the benefits?

HEART DISEASE A 20-second daily hug improves heart function and lowers blood pressure by triggering the release of the hormone oxytocin.

IMMUNITY Hugging lowers levels of cortisol, a stress hormone that weakens immunity.

STRESS Positive physical touch has an immediate anti-stress effect, slowing breathing and heart rate.

MOOD A good hug rapidly induces relaxation and wellbeing. The raised level of oxytocin counters negative emotions and boosts feelings of bonding.

INFO The first London Cuddle Party takes place in north London on 11 February, 2-5.30pm ([pound]30 per ticket; e-mail cuddleparty @hotmail.co.uk. See also www.cuddleparty.com; www.free-hugs.com; and www.dancebiodanza.com.

NOVI, Mich., Feb. 5 /PRNewswire/ — Spotlighting an enterprise-wide priority, Trinity Health today announced the appointment of VeLois Bowers as its new Senior Vice President of Diversity and Inclusion. In this newly created role, Bowers will advance Trinity Health’s vision to develop of a culturally competent workforce of more than 45,100 employees across Trinity Health’s nationwide network of 46 hospitals and numerous outpatient and long- term care facilities, home health and hospice programs. Bowers reports directly to Trinity Health President and CEO Joseph Swedish in his role as Chief Diversity Officer.

Bowers will lead the development and implementation of short- and long- term diversity strategies, plans and programs. Bowers also is charged with developing tools, resources and techniques for monitoring and evaluating the effectiveness of Trinity Health’s diversity initiatives.

“We are proud to welcome VeLois Bowers into the Trinity Health family and look forward to the energy and insight she’ll bring in driving our diversity initiatives,” said Swedish. “This new position underscores Trinity Health’s focus on fostering a culturally competent organization reflective of the diverse communities we serve. Our associates expect an inclusive culture and climate to accompany tools, resources and support as elements of what they need to do their best work. That is what diverse organizations provide to their people, and that is what we aspire to.”

Diversity and inclusion are noted in four of the 14 founding principles that were created by the sponsoring congregations of Trinity Health to set its mission and vision. Trinity Health defines diversity and inclusion as valuing divergent perspectives that are founded in individual differences in gender, race, age, national or ethnic origin, sexual orientation, thought, ancestry, religion, marital or parental status, physical or mental disability, education, veteran status, citizenship, genetic makeup, or any other characteristic.

Further, Trinity Health understands that true diversity does not try to assimilate individual members of a group into the dominant culture, but instead embraces the differences that make each of them unique.

“Diversity isn’t just a buzzword – it’s a necessity in establishing an inclusive environment that encourages growth among associates and the enterprise as a whole,” said Bowers. “Providing leadership for a diversity strategy impacting such a wide array of colleagues, medical staff and business partners with the help of our team, led by Joe Swedish, will be an exciting mission to carry out.”

Prior to joining Trinity Health, Bowers served as vice president of diversity and inclusion for the Kellogg Company and vice president of global diversity for Whirlpool Corporation. Her career experience also has encompassed human resources positions at Western Michigan University.

Bowers earned her bachelor’s degree in business administration from the University of Arkansas at Pine Bluff. She’s a member of several professional organizations, including the National Association of African Americans in Human Resources, Diversity and Inclusion Food Group Industry Council, Network for Executive Women, founding member of the Council for World Class Communities, a member of the University of Arkansas Pine Bluff Foundation Board, and the chair of the Conference Board – Diversity and Inclusion Council. Bowers has taught courses and led workshops at several institutions and has been a guest speaker at the University of Notre Dame, Andrews University, Northern Caribbean University, and Lake Michigan College.

About Trinity Health

With hospitals in eight states, Trinity Health is the fourth-largest Catholic health care system in the nation based on total revenue. Headquartered in Novi, Mich., Trinity Health operates 31 owned and 15 managed hospitals, 384 outpatient facilities, numerous long-term care facilities, and home health offices and hospice programs. Employing approximately 45,100 full- time staff, Trinity Health reported $6.1 billion in revenues and $307 million in community benefit ministry in fiscal year 2006. For more information about Trinity Health, visit http://www.trinity-health.org/.

Trinity Health

CONTACT: Kevin DiCola, Manager, Corporate Communications and PublicRelations of Trinity Health, +1-248-489-6032, or pager, +1-248-523-6733, [email protected]

Web site: http://www.trinity-health.org/

BLOOMFIELD, Conn., Feb. 5, 2007 /PRNewswire-FirstCall/ — CIGNA HealthCare has expanded its Healthy Rewards(R) health and wellness discount amenity program to include discounts of up to 60 percent on physical fitness centers, wellness and stress management programs and oral health products. Healthy Rewards provides easy access to a variety of brand name health and wellness products and services at discounted prices to help members get healthy and stay healthy.

“The most recent expansion of the Healthy Rewards program is just one of many ways that CIGNA HealthCare is working to provide the education, motivation and support necessary to help members adopt healthy behaviors that maintain or improve their health,” said Diana Wynne, program manager for CIGNA Healthy Rewards. “We’ve designed Healthy Rewards to not only help members learn new ways to improve their health, but also to provide incentives, such as these discounts, that can help make it easier to make progress. And we continue to add new programs that allow more consumers to engage in ways that are meaningful and valuable to them.”

Healthy Rewards, first launched nationally in 2001, has grown to become one of the nation’s most robust amenity programs, offering discounts on a variety of health and wellness products and services, including but not limited to anti-cavity products, chiropractic care, eyewear, contact lenses, fitness club memberships, guided imagery and mind-body techniques, health and wellness products, hearing care, laser vision correction, magazine subscriptions, massage therapy, natural supplements, tobacco cessation and weight management. The program is available to CIGNA’s medical, dental and behavioral members.

The Healthy Rewards program most recently added a discount on Philips Sonicare(R) power toothbrushes. This new offering promotes the importance of proper oral care in an effort to help keep members healthy. And for every discounted Philips Sonicare toothbrush sold through the Healthy Rewards program, CIGNA Foundation will donate $3 to the March of Dimes(R), an organization devoted to the study of preventing pre-term birth. According to the Surgeon General, our mouths speak volumes about the state of our health(1). In fact, recent research has linked gum disease to complications for pre-term birth, diabetes, heart disease and stroke(2).

Taking action toward living a healthier life can also mean incorporating exercise into daily living. To help members with their personal fitness challenges, Healthy Rewards also now offers a year-round Curves(R) discount. Curves is a fitness club chain geared to women, with over 10,000 locations in the U.S. Healthy Rewards program participants can receive a discounted membership fee when joining Curves. Physical activity is a key strategy in keeping weight in line and staying healthy. Even modest weight losses of 5 to 15 percent of body weight can help reduce the risk of obesity and associated illnesses, including diabetes, high blood pressure, health disease, some forms of cancer and gall bladder disease(3).

Also as part of the recent Healthy Rewards expansion, members can relax and relieve stress with access to over 3,500 spas including day, destination, hotel, and medical spas, through SpaFinder.com. Members can visit the Web site and receive discounted gift certificates with free ground shipping for their personal use or for others. While different spas provide different services, including weight management support, fitness programs or pampering treatments, all spas have one thing in common – they specialize in wellness.

In addition to the latest programs and services added to the program, Healthy Rewards members already receive discounts on products and services offered through these participating vendors: Drugstore.com(TM), Weight Watchers(R), Jenny Craig(R), Yoga Journal, Mayo Clinic books, Just Walk 10,000 Steps a Day(TM), Cooking Light, Health and Prevention magazines, and discounted eyewear and eye exams from LensCrafters(R), Pearle Vision(R), Target, Sears and JC Penney. Members may also get discounted service from networks of registered dieticians, acupuncturists, chiropractors, massage therapists, and LASIK eye surgeons.

*Some of the features of the Healthy Rewards(R) program are not available in all states.

   (1) U.S. Surgeon General's Report, 2000.   (2) American Academy of Periodontology   (3) U.S. Department of Health and Human Services, 2001   

The Healthy Rewards(R) discount program is offered at no additional cost to members, as a way to help enhance their benefit plans and meet the growing demand for complementary care services. It is provided as an advantage of plan participation and is not part of the benefit plan. Healthy Rewards(R) is not a covered benefit or an insurance program. Members do not need referrals, nor do they file claims to obtain discounts. They obtain discounts by presenting their member identification card. The program discounts cannot be applied to any co-payment or coinsurance for services covered under the member’s benefit plan. Program participants schedule appointments directly with service providers and also pay them directly.

CIGNA HealthCare, based in Bloomfield, CT, provides medical benefits plans, dental coverage, behavioral health coverage, pharmacy benefits and products and services that integrate and analyze information to support consumerism and health advocacy. “CIGNA HealthCare” refers to certain operations of Connecticut General Life Insurance Company, which is an operating subsidiary of CIGNA Corporation . Products and services are provided by such operating subsidiaries, and not by CIGNA Corporation. For more information, visit http://www.cigna.com/.

CIGNA HealthCare

CONTACT: Nicole Blatcher, CIGNA HealthCare, +1-215-761-4756,[email protected]

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

Company News On-Call: http://www.prnewswire.com/comp/165050.html

By Mark Washburn, The Charlotte Observer, N.C.

Feb. 5–Melissa Greer, the WBTV meteorologist battling a rare form of cancer while eight months pregnant with her first child, is expected to undergo surgery Tuesday in Iowa.

Doctors plan to deliver her son, Connor, by Caesarean section. They’ll then perform a hysterectomy to get the main tumor, swollen to about the size of a golf ball, on her cervix.

Doctors will also bathe Greer’s liver to break up the tumors that have spread there, husband Roger Polsky said Sunday. The surgery is expected to last at least 10 hours at the University of Iowa Hospital in Iowa City.

Connor is expected remain in the hospital about three or four weeks following his premature delivery, but physicians believe he will do well, Polsky said.

“They predict that he will do fine, with very few complications,” he said.

Greer, weekend meteorologist at Channel 3, learned in November she had large cell neuroendocrine carcinoma, an aggressive cancer so rare that at any given time only a few dozen people in the country have it. She had chemotherapy in Charlotte in December, but the procedure failed to arrest the tumor or the spread of cancer cells to other organs.

Last week, she went to consult with experts at the University of Iowa, who planned this week’s surgeries. Greer and Polsky expect to stay in Iowa City for at least a month to be near Connor and have follow-up care for the cancer surgeries.

How To Help

If you want to donate, a fund has been set up to aid in the temporary relocation and uncovered medical expenses for Melissa Greer Polsky at Tega Cay Financial Center, 2890 Highway 160 West., Fort Mill, S.C., 29708.

—–

Copyright (c) 2007, The Charlotte Observer, N.C.

Distributed by McClatchy-Tribune Business News.

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.

GREAT RIVER, N.Y., Feb. 2 /PRNewswire-FirstCall/ — Netsmart Technologies, Inc. , a leading provider of enterprise-wide software and services for health and human services organizations, today announced that it has signed seven agreements totaling approximately $4 million with behavioral and public healthcare and substance abuse provider organizations in several states. All of these contracts are scheduled to be performed over one year with only one exception which is a multi-year agreement.

“We are pleased to be selected by these organizations as the trusted technology partner for their mission-critical clinical and operational processes,” said James Gargiulo, Netsmart executive vice president, Clients and Solutions. “We look forward to helping them meet their goal of providing high quality care to their patients and clients.”

Princeton House Behavioral Health, a division of Princeton, N.J.-based Princeton Health Care System, will use Netsmart’s CCHIT Certified(SM) Avatar 2006 software Avatar suite, which is designed to provide clinical assessments, progress notes, treatment planning and reporting, and electronic medication management. In addition, Avatar is designed to facilitate practice management processes for Princeton House, including system management, client tracking, scheduling, billing and reporting. Netsmart will provide HL7 integration from Avatar to Princeton House’s admissions, laboratory and order entry systems. Avatar is the first behavioral health and substance abuse software to receive CCHIT certification.

The Ohio Department of Mental Health will use Avatar Clinician Workstation (CWS), which is designed to provide assessments, progress notes and treatment planning. The department will also use Avatar’s RADplus tool, which is designed for security management, modeling and report integration.

Ontrack, Inc., a mental health and substance abuse treatment provider in Medford, Ore., will utilize practice management and clinical capabilities through the Avatar ASP hosting service. Ontrack will also use the Avatar RADplus tool.

Bayonne Medical Center of Bayonne, N.J. will use Avatar software for core system management, client tracking, scheduling and reporting. In addition, Avatar’s clinical capabilities are designed to support progress notes, treatment planning and reporting. Netsmart will provide HL7 integration from Avatar to the Hospital’s admissions and billing systems.

The Lower Eastside Service Center of New York, N.Y. will utilize the Avatar software suite for practice and addiction services management. The center is expected to use Avatar for system management, client scheduling and tracking, reporting and medication dispensing.

The El Paso County, Colo., Department of Health and Environment will utilize Netsmart’s Insight public health software. The county will use Insight to manage a wide range of processes, including patient scheduling, electronic medical record management, case management, immunization and laboratory record tracking, health screening record management, and billing/remittance.

In a five-year agreement, Swanson Center of Michigan City, Ind., a provider of adult and youth mental health services, is expected to utilize Avatar’s clinical and practice management capabilities through Netsmart’s application service provider (ASP) hosting service. Avatar ASP is designed for organizations who want to minimize upfront cost and onsite software upgrades. Swanson Center will also utilize Netsmart’s InfoScriber e-prescribing software, and Quantum financial software from Geneva Software, a Netsmart partner, for Avatar-integrated accounts payable, general ledger, fixed asset management and fixed assets/depreciation management.

For information about Netsmart Technology’s full range of solutions for health and human services organizations, visit http://www.ntst.com/ or call 1-800-421-7503.

About Netsmart Technologies, Inc.

Netsmart Technologies, Inc., based in Great River, N.Y., is an established, leading supplier of enterprise-wide software solutions for health and human services providers, with more than 1,300 clients, including more than 30 systems with state agencies. Netsmart’s clients include health and human services organizations, public health agencies, mental health and substance abuse clinics, psychiatric hospitals, and managed care organizations. Netsmart’s products are full-featured information systems that operate on a variety of operating systems, hardware platforms, and mobile devices, and offer unlimited scalability.

Statement on Behalf of Netsmart Technologies, Inc.

Statements in this press release may be “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipate,””believe,””estimate,””expect,””intend” and similar expressions, as they relate to the company or its management, identify forward-looking statements. These statements are based on current expectations, estimates and projections about the company’s business based, in part, on assumptions made by management. These statements are not guarantees of future performance and involve risks, uncertainties and assumptions that are difficult to predict. Therefore, actual outcomes and results may, and probably will, differ materially from what is expressed or forecasted in such forward-looking statements due to numerous factors, including those described above and those risks discussed from time to time in Netsmart’s filings with the Securities and Exchange Commission. In addition, such statements could be affected by risks and uncertainties related to product demand, market and customer acceptance, competition, pricing and development difficulties, as well as general industry and market conditions and growth rates, and general economic conditions. Any forward-looking statements speak only as of the date on which they are made, and the company does not undertake any obligation to update any forward-looking statement to reflect events or circumstances after the date of this release. Information on Netsmart’s website does not constitute a part of this release.

*Avatar 2006 Version 02 is a CCHIT Certified(SM) product for CCHIT Ambulatory EHR 2006. CCHIT is a Recognized Certification Body in the United States for certifying health information technology products — an independent, not-profit organization that sets the benchmark for electronic health records. The U.S. Department of Health and Human Services (HHS) awarded CCHIT a three-year contract in September 2005 to develop and evaluate certification criteria and an inspection process for ambulatory (office and clinic) EHRs, inpatient (hospital) EHRs and the networks through which they interoperate.

Netsmart Technologies, Inc.

CONTACT: Dave Kishler of Netsmart Technologies, +1-614-932-6723,[email protected]

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

Kindred Healthcare, Inc. (the “Company”) (NYSE: KND) today announced that its subsidiaries have signed an agreement to lease eight skilled nursing facilities from Ocadian, L.L.C., a privately held company based in San Francisco, California.

The nursing centers contain a total of 910 licensed beds and are located in the San Francisco Bay area. Terms of the lease agreement were not disclosed. Kindred currently operates 12 skilled nursing facilities and 3 long-term acute care hospitals in Northern California.

“The Ocadian nursing centers complement and expand our presence in San Francisco and Oakland and the surrounding markets,” said Paul J. Diaz, President and Chief Executive Officer of the Company. “The Ocadian skilled nursing facilities are excellent properties with a reputation for quality services and are located near existing Kindred hospitals and nursing centers, enabling us to further our market-development strategy in Northern California. We are increasingly focusing on the opportunities we have, particularly between our hospitals and nursing centers, to share clinical resources, grow admissions and better educate the marketplace on our ability to care for medically complex post-acute patients.”

About Kindred Healthcare

Kindred Healthcare, Inc. (NYSE: KND) is a Fortune 500 healthcare services company, based in Louisville, Kentucky, with annualized revenues of $4.3 billion that provides services in over 500 locations in 39 states. Kindred through its subsidiaries operates long-term acute care hospitals, skilled nursing centers, institutional pharmacies and a contract rehabilitation services business, Peoplefirst Rehabilitation Services, across the United States. Kindred’s 55,000 employees are committed to providing high quality patient care and outstanding customer service to become the most trusted and respected provider of healthcare services in every community we serve. For more information, go to www.kindredhealthcare.com.

Nemours, one of the nation’s largest children’s health systems, announced today the formation of the Florida Board of Managers (FL BOM). This new entity will provide guidance and report to the Board of Directors. The FL BOM will determine and approve the qualifications for credentialed professional staff for Nemours’ Florida operations in Jacksonville, Orlando and Pensacola.

“The creation of the Florida Board of Managers will allow Nemours to benefit from the leadership and guidance of the Managers, who bring added value to our organization in supporting our overall strategic direction in Florida,” said David J. Bailey, MD, MBA, President and CEO of Nemours. “They will help guide us to better meet the needs of our patients, and to build on the strengths of Nemours’ health professionals to ensure that we have a strong strategic focus in delivering care that is timely, appropriate and safe.”

Nemours expects that the FL BOM will provide invaluable assistance to Nemours in its pursuit of excellence in medical care linked with community-based, integrated health services, for the well being of all of Florida’s children. “The formation of a Florida Board of Managers parallels the governance structure in place in Delaware, where the Delaware Board of Managers has long provided guidance and support for the operations of Nemours’ Alfred I. duPont Hospital for Children in Wilmington,” said Roy Proujansky, MD, Executive Vice President of Patient Operations and COO of Nemours. “The Florida Managers will also serve as the governing body for a future Nemours children’s hospital or for other licensed health care facilities Nemours may operate in Florida.”

“We are honored that these Florida Managers have agreed to contribute their efforts, and that their mission will include supporting Nemours’ goal of bringing a fully integrated children’s health system to Florida,” stated John “Jack” Porter III, Chairman of Nemours’ Board of Directors.

The newly appointed FL BOM includes:

Catherine Brown-Butler — Senior Vice President, Market Development Manager for Bank of America. Manages charitable giving for Central Florida market. A native of Wilmington, Delaware, Brown-Butler attended Simmons College, Boston, Massachusetts and received a Bachelor of Arts in Finance. She earned her Masters in Business Administration from Simmons Graduate School of Management, Boston, Massachusetts.

Gerald F. Banks — Entrepreneur with a concentration in the real estate industry and food and beverage manufacturing industry. He is President and owner of Rowena Corporation in Maitland, Florida. Banks is also President of Action Ice, LLC in Orlando, Florida.

Charles E. Hughes, Jr. — President & CEO, Florida Capital Group, Inc. A graduate of Clemson University with a degree in Economics, Hughes is the former Chairman of Florida National Bank of Jacksonville and Executive Vice President of Florida National Banks of Florida. He is a former Chairman of both Jacksonville Chamber of Commerce and Public Broadcasting Services (WJCT) of Jacksonville, Florida.

Leonard H. Habas — Chairman & CEO, Advance Publishers in Maitland, Florida. Habas received his undergraduate degree in Electrical Engineering from North Carolina State University and his Masters of Science from Northeastern University. He is a former Chairman of the Board of the Central Florida chapter of the Red Cross, and is currently a member of the Orlando Boys and Girls Club Board of Directors.

Donald R. Dizney — Chairman of the Board of United Medical Corporation, and Chairman of Double Diamond Farms in Ocala, Florida. Dizney is past chairman of the University of Central Florida Foundation, the Florida Thoroughbred Breeders’ and Owners’ Association, the past director of the Orlando Museum of Art, past President and Chairman of the Florida Citrus Bowl and past Director of the Orlando Chamber of Commerce.

J. Malcolm Jones, Jr. — Chairman & CEO of Jones Financial Group. He also serves as Vice Chairman of the Board of Florida Capital Group, Inc. Jones previously was the President & CEO of FloridaBanks and a Senior Vice President of the St. Joe Company. He is also past Chairman of The Bolles School and The Greenwood School in Jacksonville, Florida.

To view or download photos of each new FL BOM member, please visit: http://www.nemours.org/internet?url=no/news/releases/2007/070130_FBM_photos_bios.html.

The FL BOM will report to The Nemours Foundation Board of Directors. The Nemours Foundation Board of Directors includes:

 --  John F. Porter III: Chairman of Nemours' Board of Directors. --  John S. Lord: Vice-Chairman of Nemours' Board of Directors. --  Hugh M. Durden: Chairman of the Alfred I. duPont Testamentary Trust. --  Brian P. Anderson: Retired Senior Vice President and Chief Financial     Officer of Baxter International and OfficeMax. --  Leonard L. Berry, Ph.D.: Distinguished Professor of Marketing M.B.     Zale Chair in Retailing and Marketing Leadership Mays Business School,     Texas A&M University. --  Richard T. Christopher: President and Chief Executive Officer of     Patterson-Schwartz Real Estate and Chairman of Nemours Board of Managers-     Delaware. --  Rosa Baumanis Hakala: Senior Vice President, Retail Sector for PWC     Logistics. --  Terri L. Kelly: President and Chief Executive Officer of W.L. Gore. --  J. Michael McGinnis, MD, MPP: Senior Scholar at the Institute of     Medicine of the National Academy of Sciences. --  Robert G. Riney: Chief Operating Officer for the Henry Ford Health     System. --  William T. Thompson III: Immediate past Chairman of Nemours' Board of     Directors. --  Winfred L. Thornton: Immediate past Chairman of the Alfred I. duPont     Testamentary Trust.      

About Nemours

Nemours provides institutions and services to improve the health of children. Employing over 400 pediatric physicians, subspecialists and surgeons, Nemours cared for approximately a quarter of a million children during nearly one million encounters in 2005, making Nemours one of the nation’s largest children’s health systems.

In addition to the many ongoing research, education, health and prevention programs, Nemours owns and operates the Alfred I. duPont Hospital for Children in Wilmington, Delaware, and major children’s specialty centers in Delaware (Wilmington), Florida (Jacksonville, Orlando and Pensacola), Pennsylvania (Philadelphia and Bryn Mawr), New Jersey (Atlantic City and Voorhees) and many primary care pediatric practices throughout Delaware. Additionally, the most visited health care Web site online for parents, kids, and teens, www.kidshealth.org is a project of Nemours.

Nemours is affiliated with the Mayo Clinic, Thomas Jefferson University, University of Florida, University of Delaware, Christiana Care Health System, Main Line Health System, Virtua Health, AtlantiCare Regional Health System, Baptist Medical Center (Wolfson Children’s Hospital), Orlando Regional Medical Healthcare (Arnold Palmer Hospital for Children and Women) and Sacred Heart Children’s Hospital. Additional information can be found at www.nemours.org.

 Odette Struys National Media Relations (904) 232-4186 Contact via http://www.marketwire.com/mw/emailprcntct?id=195E79B9B96643FE  

SOURCE: Nemours

ALEXANDRIA, Va., Feb. 1 /PRNewswire/ — Community MTM Services, Inc. (CMTM) announced today that its pharmacy network now exceeds 39,000 members, doubling its size in the past six months. Network members include independent, chain, long term care, supermarket, and mass merchandiser pharmacies that represent nearly 71 percent of all U.S.-based pharmacies. Additional pharmacies continue to join the network each week.

CMTM’s pharmacy network facilitates the delivery of highly targeted medication management and patient care services, offering program sponsors access to millions of targeted patients via a high-touch, high trust channel: America’s community pharmacists.

CMTM provides its network members a secure Web-based software service that enables pharmacy members to securely deliver high-value targeted patient care services on behalf of program sponsors who compensate for these services. With CMTM, pharmacists provide evidence-based care by working proactively with patients, helping them understand their medications, reducing the risk of adverse drug events, educating them on ways to better manage their chronic conditions, and providing advice on consumer cost-saving opportunities. CMTM also enables pharmacists to participate in the delivery of targeted medication compliance programs and clinical trials recruitment initiatives.

The EPIC Pharmacy Network, representing more than 1,400 independent pharmacies, views CMTM as a valuable tool, enabling pharmacists to expand their roles to include patient care services, such as Medicare Part D medication therapy management (MTM). “Our pharmacies have embraced CMTM as an intuitive and pharmacist-friendly enabler of pharmacy-based medication management services,” said Patrick Berryman, executive vice president of the EPIC Pharmacy Network. “CMTM enabled us to efficiently and effectively deliver, document and bill for MTM services last year, and we look forward to opportunities to use CMTM in new ways as we strive to improve the health of our patients and increase our service-based business throughout 2007 and beyond.”

“The increasing number of pharmacies contracting with CMTM and the rapid adoption of our solution into their existing workflow demonstrates that community pharmacy is ready to expand its business model beyond dispensing to include new patient care services,” said CMTM Chief Operating Officer Kurt Proctor, RPh, Ph.D. “Our network of community pharmacies continues to grow. The interest from program sponsors in reaching this network will result in tremendous new revenue opportunities for these pharmacies, better health outcomes for the patients involved, and cost-savings in health care delivery.”

Among the recent additions to the CMTM pharmacy network are Aurora Pharmacy, Inc., Bel Air, Bi-Lo/Brunos, Brookshire Grocery Company, Duane Reade, EPIC Pharmacy Network, GeriMed LTC Network, Inc., Hartig Drug Stores, H-E-B, IKE’s Pharmacy, Innovatix Network, LLC, Kinney Drugs, The Kroger Co. Family of Pharmacies, May’s Drug Warehouse, Med-X Drug Mart, Nob Hill, Omnicare, Inc., Meijer Pharmacy, Pathmark Pharmacy, Pharmacy Providers of Oklahoma (PPOK), Raley’s, Rite Aid Pharmacy, Super D Drug, USA Drug, several additional national and regional chains, and thousands of independent pharmacies.

There is no charge to pharmacist providers to use the secure Web-based CMTM software service. Pharmacies interested in joining the network can do so at http://www.communitymtm.com/ .

About Community MTM Services, Inc.

Community MTM Services, Inc. (CMTM) delivers innovative patient care solutions. Our Software-as-a-Service technology streamlines the delivery of highly targeted medication management programs and speeds patient recruitment campaigns. The broad-based CMTM pharmacy network serves as the centerpiece of our nationwide, multi-channel program delivery capability. Working with CMTM, program sponsors can harness the high trust pharmacist-patient relationship to achieve superior business and clinical results.

   FOR MORE INFORMATION:   Barbara Byrne   Community MTM Services, Inc.   100 Daingerfield Rd   Alexandria, VA 22314   (703) 600-1257   [email protected]  

Community MTM Services, Inc.

CONTACT: Barbara Byrne of Community MTM Services, Inc., +1-703-600-1257,or [email protected]

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

A HEALTH BOARD was right to sack a mental health worker after concern arose over his English skills, performance and patient safety, the Employment Relations Authority has ruled.

Nazir Maher worked for Counties Manukau District Health Board as a medical officer of special scale in psychiatry — a role below a full psychiatrist — from November 1, 2004, till his dismissal on June 24, 2005.

The authority backed the decision to sack him in a decision that has just been released.

It heard that Dr Maher, who qualified in Pakistan in 1987, had practised medicine in New Zealand for seven years, working in Tauranga, Wanganui, and Invercargill.

After starting at Counties Manukau, Dr Maher learned of restrictions placed on him by the Medical Council. These involved supervision and monitoring during patient interviews. A consultant psychiatrist, Roger Elliot, oversaw Dr Maher.

Dr Elliot’s report questioned Dr Maher’s competence. “He would need to be considerably more skilled in his use of the English language,” he said.

Dr Maher’s work needed intensive monitoring, akin to that given to an intern, Dr Elliot said.

In February, 2005, fears for patient safety arose when Dr Maher failed to record a change he made to a patient’s medication. He could not recall making the change, despite being shown a bottle of medicine with his name as the prescribing doctor.

The head of Counties Manukau’s core adult mental health services, Verity Humberstone, concluded: “A serious risk was posed to the safe treatment of and management of clients in Dr Maher’s care.”

Dr Maher was accused of misleading the board about his performance at Wanganui. A disciplinary meeting found his denial amounted to serious misconduct, and that the restrictions imposed by the Medical Council meant he could not perform the duties he was supposed to.

At the authority, Dr Maher sought his job back, compensation for distress and reimbursement of lost wages. But authority member Marija Urlich found his dismissal was justified, especially given the high level of trust needed in his position.

(c) 2007 Dominion Post. Provided by ProQuest Information and Learning. All rights Reserved.

LANSING, Mich., Jan. 30 /PRNewswire/ — Starting Friday, February 2, hundreds of Michigan Dental Association dentists will provide free dental services on specific dates to low-income children across Michigan. It’s part of the American Dental Association’s fifth annual “Give Kids a Smile” campaign where dentists around the U.S. donate their services that day to children who, because of economic reasons, don’t have access to dental care.

During last year’s “Give Kids a Smile” event in Michigan, over 300 dentists, hygienists, assistants and volunteers provided dental care and oral health education to more than 22,000 children. Nationwide, 500,000 children received dental services at over 2,000 sites valued at $100 million.

“There are thousands of disadvantaged children across Michigan who, for economic reasons, are not able to receive regular dental care,” said Edwin Secord, DDS, MS, president of the Michigan Dental Association. “Through the ‘Give Kids a Smile’ program, we deliver free dental treatment, oral health screenings, education and prevention programs to children who need them most.

“The Michigan Dental Association wants to deliver the message that the dental profession can’t solve the access-to-care problem alone, and that for every child we care for on this day, even thousands more will continue to suffer until dental health becomes a priority funding issue.

“It’s important for lawmakers, as well as the public, to understand that it is absolutely necessary to have proper oral heath care in order to have good overall health. Oral health is primary care,” stressed Secord.

Secord went on to say, “In Michigan we are fortunate to have the Healthy Kids Dental program that provides dental care to children from low-income families in 59 of Michigan’s 83 counties. As a result of this program more children are receiving necessary dental care and are beginning a pattern of regular routine preventive care.”

Healthy Kids Dental was developed by the Michigan Department of Community Health and provides dental benefits to children under 21 years of age who were previously covered by the state’s Medicaid dental program. The program is administered by Delta Dental Plan of Michigan.

It is expected that hundreds of dentists throughout the state will be involved in numerous events for “Give Kids a Smile.” Locations across Michigan where children will receive free oral health care services include:

   Detroit Area:    * Detroit - Saturday, Feb. 3, 8 a.m. to 3 p.m.  University of Detroit      Mercy School of Dentistry, 8200 W. Outer Dr.  Sponsored by the Detroit,      Oakland and Macomb Dental Societies and the UDM School of Dentistry.      Dentists will provide diagnosis and treatment to more than 170      uninsured children.  Call Sherri Doig at (313)871-3500 to schedule an      appointment.  Contact: Dr. Lloyd Lariscy before event at (313)274-8522;      during event at (313)300-3335.     * Shelby Township - Friday, Feb. 2, 9 a.m. to 4 p.m., 55131 Shelby Rd.      Dr. Jonathan Penzien will provide cleanings, exams and fluoride      treatments to children ages 10 and under.  Open to the public.      Contact: Dr. Penzien at (248)650-5500.     * Port Huron - Friday, Feb. 2, Hispanic Outreach Center, 295 W. Huron.      Dr. Melanie Sheils-Vergeldt, with the help of the Catholic Social      Services Hispanic Outreach Center, will provide exams, cleanings, x-      rays, fluoride treatments and sealants to 75 children.  Children in      need of more extensive care will be referred to the University of      Detroit Mercy for follow-up treatment.  Event is full.  Contact:      Therese Costello - (248)646-1381.    Lansing Area:    * Lansing - Friday, Feb. 2, 9 a.m. to 5 p.m., Lansing Community College      Dental Hygiene Clinic, 500 N. Washington Square.  Area dentists will      provide free dental care to 63 children from Lansing's Riddle      Elementary School.  Sponsored by:  Central District Dental Society,      Lansing Community College Dental Hygiene Program, Student American      Dental Hygiene Association, Lansing School District, Delta Dental,      Physician's Health Plan, Capital Area Health Alliance, Central District      Dental Hygienists Society and Central District Dental Assistants      Society.  This event is full.  Contact:  Dr. Greg Komyathy,      517-347-0034 or Sherry Kohlmann, (517)483-1457.    Upper Peninsula:    * Menominee - Friday, Feb. 2, New UP Dental, 4103 10th St. Oral health      education, fluoride treatments, dental sealants for area children.      Event is full.  Contact: (906)863-6381.    Northern Michigan:    * Oscoda - Friday, Feb. 2, 3 p.m. to 5 p.m., Alcona Health Center, 5671      N. Skeel Ave. Comprehensive dental treatment for uninsured children.      Open to the public. Contact: Lea Krause, (989)739-7927.     * East Jordan - Friday, Feb. 2, East Jordan Public Schools. Area      dentists will provide oral health screenings to 650 preschool through      fifth grade children. Parents will receive a report and the dentists      will work with school nurses to locate treatment and financial aid for      those in need. Contact: Debbie, (231)536-2601.     * Big Rapids - Saturday, Feb. 17, Ferris State University Dental Hygiene      Clinic, 200 Ferris Dr.  FSU's Dental Hygiene Clinic will provide      sealants, exams, x-rays, fluoride varnish, cleanings and minor      restorations for uninsured children. Contact: Annette Jackson,      (231)591-2284.    Southwestern Michigan:    * Berrien Springs - Friday, Feb. 2, Berrien Dental, 8383 M-139.      Comprehensive dental treatment for 40 children with follow-up care for      those in need. Event is full.  Contact: Dr. Lisa Christy,     (269)471-4055.     * Benton Harbor - Friday, Feb. 2, 9 a.m. to 3:30 p.m., 1220 E. Napier      Ave. Free preventive dental treatment to uninsured children. Open to      the public. Contact: Michelle, (269)925-2113.    Muskegon Area:    * Muskegon - Friday, Feb. 2, 9 a.m. to 3 p.m., Hackley Community Care      Center, 2700 Baker St., Muskegon Heights.  Muskegon area dentists will      provide dental care to 75 area children. Sponsored by the Muskegon      District Dental Society, Muskegon Family Care, Muskegon County Health      Department and the Muskegon Community Dental Coalition. This event is      full.  Contact: Dr. Connie Verhagen at (231)780-3200 or Lisa at      (231)737-8603.    Grand Rapids Area:    * Grand Rapids - Thursday, February 8th, 5 p.m. - 8 p.m. and Friday,      February 9th, 9:30 a.m. - 3 p.m., Grand Rapids Children's Museum, 11      Sheldon Ave, NE. The West Michigan District Dental Society event for      area children features oral health education through the museum's      interactive oral health exhibit.  Several dental characters in costume      will be present.  Approximately 1,300 children are expected to attend      the event.  This event is open to the public.  Contact: Dr. Amy DeYoung      - (616)447-7900.     * Belmont - Friday, February 9th, 8 a.m. - 1 p.m., 6220 Jupiter Ave.      NE, Ste. B. Dr. John Frey will provide free exams, cleanings, sealants      and oral health education to 50 uninsured children.  Open to the      public.  Contact: Shelly - (616)222-0202.     * Grand Rapids - Friday, February 9th, Peters Family Dentistry, 6651      Crossings Ct. SE.  Free comprehensive dental treatment to 40 uninsured      children from Explorer Elementary School.    Sen. Mark Jansen and Sen.      Bill Hardimann attend.  This event is full.  Contact: Dr. Debra Peters      - (616)698-6663.    Zeeland:    * Zeeland - Friday, Feb. 2, Roosevelt Elementary School, 175 W.      Roosevelt Ave., Zeeland.  Hours:  9 a.m. - 3 p.m. The Ottawa County      Health Department and the "Miles of Smiles" Dental Team will provide      oral health education to 600 children at the school.  In addition, 20      children will receive preventive and restorative dental treatment in      the "Miles of Smiles" mobile dental clinic.  This event is full.      Contact: Lois Havermans - (616)393-5771.    Flint:    * Flint - Friday, Feb. 2, Hamilton Community Health Network, G-5399 N.      Saginaw, 8:30 a.m. - 4 p.m. Free dental services to 75 area uninsured      children.  This event is open to the public.  State Rep. Brenda Clack      will attend this event.  Contact: Hamilton Community Health Network -      (810)785-0863.     * Flint - Friday, Feb. 2, Town Center Family Dental, 4500 Town Center      Parkway. Drs. Lora Thomas and Timothy Vanitvelt, will provide      comprehensive dental treatment for area children.  This event is full.      Contact: Becky - (810)733-1410.    Jackson Area:    * Jackson - Saturday, Feb. 3, 9 a.m. to 3 p.m., Parkside Middle School at      Parkside Fieldhouse. The Jackson Center for Family Health will sponsor      Step Into Health day and will provide free health screenings and prizes      for the family. Children under the age of 19 will receive a free teeth      cleaning, x-ray and screenings. Games, local celebrities, free snacks,      the 30th Annual 5K Groundhog Gallup. Contact: Dr. Jane Grover,      (517)784-1205, ext. 294.     * Jonesville - Friday, Feb. 2, Adams & Dow, DDS, 211 Harley St. Free      exams and cleanings to 30 children from the Hillsdale Head Start      program.  This event is full.  Contact: Dr. Sharon Dow - (517)849-9195.   

Headquartered in Lansing, the Michigan Dental Association has more than 5,800 members in 26 local dental societies and two dental schools. Since its founding in 1856, the MDA has sought to educate the public, enhance its members’ ability to provide high quality care and to promote the science and art of dentistry. For more information on the “Give Kids a Smile” program or other MDA initiatives call 800/589-2632 or log on to http://www.smilemichigan.com/.

Michigan Dental Association

CONTACT: Tom Kochheiser of the Michigan Dental Association,+1-517-346-9422, or cell, +1-517-230-9828, or [email protected]

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

BOCA RATON, Fla., Jan. 30 /PRNewswire/ — Boca Raton Community Hospital (BRCH) today announced that it has received a $75 million donation from the Schmidt Family Foundation — the largest gift ever given to a community hospital and the third-largest among all hospitals and health systems in the United States (based upon information from the Advisory Board for the latest year available, 2005). The donation is an important step in realizing the shared vision of The Schmidt Family Foundation, BRCH, Florida Atlantic University (FAU) and the University of Miami Miller School of Medicine (UMMSOM): The Charles E. Schmidt Medical Center will serve as a model of hospital safety and educate a new generation of medical professionals.

(Photo: http://www.newscom.com/cgi-bin/prnh/20070130/NYTU079)

As the first new academic medical center to be established in the United States in nearly a decade, the hospital will address an anticipated nationwide shortage of health care professionals.

“Our family is looking forward to bringing this standard of quality and safety in health care to the very community in which we live and work and to the U.S. community at large,” said Richard Schmidt, Chairman of the Board of Trustees of Boca Raton Community Hospital. “Our family firmly believes in local activism that will resonate nationally to benefit as many patients as possible.”

A “dream team” of experts led by John Reiling, Ph.D., MHA, MBA, a nationally renowned expert in healthcare safety design, will oversee the planning, design and construction of the new facility. The state-of-the-art hospital, which is expected to be completed in 2011, will feature 530 private patient rooms. The community hospital, known for its medical centers of excellence, will become a standard for hospital safety by improving visibility of patients to staff, standardizing and automating certain tasks and procedures, minimizing physician fatigue and empowering patients’ families to participate in patient care. The hospital’s design will combine best practices in technology, architecture, academia and patient care to pioneer a new era in hospital safety.

The facility will be located on 38 acres of Florida Atlantic University’s Boca Raton Campus. Currently, medical students spend their first two years of training at FAU. The program will now be expanded to a full four-year track, giving students the opportunity to receive a doctor of medicine degree from University of Miami Miller School of Medicine without having to leave the Boca Raton community area.

“This generous gift from the Schmidt Family Foundation is invaluable in helping us break ground on one of the most advanced academic medical facilities in the country, providing the aging population with the biomedical breakthroughs and clinical expertise they need,” said Gary Strack, president and CEO of Boca Raton Community Hospital. “The landmark public-private partnership among BRCH, FAU and UMMSOM, paired with such a landmark donation, will bring research investments, job opportunities and national excellence for decades to come.”

About the Schmidt Family Foundation

The Schmidt Family Foundation (http://www.schmidtfamilyfoundation.org/) began in the shadows of the Great Depression, when 26-year-old University of Chicago graduate Charles E. Schmidt launched a mail-order tractor-parts business. Tractor Supply Co. grew into a publicly traded company with thousands of employees before merging in 1969 with National Industries.

In 1964, Charles and his family moved to South Florida, where he ran two golf courses and assembled 27 banks into Gulf stream Banks, which he ultimately sold. He also became involved in philanthropy, supporting numerous local educational, arts and health care institutions.

Charles first became involved with Boca Raton Community Hospital in 1974 when he joined the Board of Trustees and continued to serve for 15 years, including one year as Board Chair. In 1976, he and his wife, Dorothy, funded an education center, which today remains an integral part of daily hospital operations, providing classrooms for employee and community training. A quarter of a century after its founding in 1982, the Schmidt Family Foundation continues to carry out Charles’ vision for serving the community with the help of the family board which includes Catherine B. Schmidt, Richard L. Schmidt, Barbara M. Schmidt and Raymond J. Webb.

About Boca Raton Community Hospital

Serving the community since 1967, Boca Raton Community Hospital (http://www.brch.com/) has 400 beds and more than 700 primary and specialty physicians with privileges. Areas of expertise include cancer, cardiovascular disease and surgery, geriatrics, minimally invasive surgery, neurological diseases, orthopedics and women’s health.

The Christine E. Lynn Heart Institute opened in September 2006, eliminating the need for patients to travel potentially life-threatening distances to receive comprehensive emergency cardiac care. This was the first time in 22 years that a new open-heart program opened in Palm Beach County.

The Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital has been in operation for 28 years and has developed into one of the largest comprehensive cancer centers in Florida. A new 98,000 square-foot cancer center facility is planned to open in 2008. The new comprehensive cancer center will access a complete continuum of care in a setting of clinical excellence providing the latest in diagnosis, research, technologies and treatments under one roof.

About the University of Miami School of Medicine

Serving a community of more than five million people as the only academic medical center in South Florida, the University of Miami (http://www.miami.edu/) Leonard M. Miller School of Medicine has earned international acclaim for research, clinical care and biomedical innovations. Founded in 1952 as Florida’s first accredited medical school, the Miller School of Medicine provides the medical staff for the nationally renowned University of Miami/Jackson Memorial Medical Center.

About Florida Atlantic University

Florida Atlantic University (http://www.fau.edu/) opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 26,000 undergraduate and graduate students on seven campuses strategically located along 150 miles of Florida’s southeastern coastline. Building on its rich tradition as a teaching university, with a world-class faculty, FAU hosts nine colleges: the Dorothy F. Schmidt College of Arts & Letters, the Charles E. Schmidt College of Biomedical Science, the Charles E. Schmidt College of Science, the Christine E. Lynn College of Nursing, the Harriet L. Wilkes Honors College, the Barry Kaye College of Business and the Colleges of Education, Engineering & Computer Science, and Architecture, Urban & Public Affairs.

   CONTACTS:   Christine Dardet, BRCH   954-636-7162 office   561-866-7922 mobile   [email protected]    Mechal Weiss, Edelman   212-642-7731 office   917-952-4807 mobile   [email protected]  

Photo: NewsCom: http://www.newscom.com/cgi-bin/prnh/20070130/NYTU079AP Archive: http://photoarchive.ap.org/AP PhotoExpress Network: PRN8PRN Photo Desk, [email protected]

Boca Raton Community Hospital

CONTACT: Christine Dardet of BRCH, +1-954-636-7162 office,+1-561-866-7922 mobile, [email protected]; or Mechal Weiss of Edelman,+1-212-642-7731 office, +1-917-952-4807 mobile, [email protected]

Web site: http://www.brch.com/http://www.fau.edu/http://www.miami.edu/http://www.schmidtfamilyfoundation.org/

By Niemi, Tomi T; Salmela, Liisa; Aromaa, Ulla; Pyhi, Reino; Rosenberg, Per H

Background and Objectives: The surgical site for the creation of an arteriovenous fistula at the lateral aspect of the distal forearm may be faster and more effectively blocked with the infraclavicular coracoid approach than with the axillary approach for brachial plexus block.

Methods: Sixty uremic patients scheduled for the creation of an arteriovenous fistula at the forearm were randomized to receive a single-injection brachial plexus block with 35 to 50 mL mepivacaine 0.95% with epinephrine using the infraclavicular coracoid approach (IC group) or the perivascular axillary approach (AX group). A distal muscular contraction elicited by a nerve stimulator at current

Results: At 30 and 45 minutes, complete loss of sensation was observed more often in group IC than AX in the cutaneous distribution of musculocutaneous nerve (62% v 30% [P

Conclusions: Blockade of the musculocutaneous nerve developed faster with the infraclavicular coracoid approach than with the axillary approach. The infraclavicular coracoid approach may be preferable in patients scheduled for the creation of an arteriovenous fistula at the forearm. Reg Anesth Pain Med 2007;32:55- 59.

Key Words: Brachial plexus block, Infraclavicular coracoid, Axillary.

Succesful musculocutaneous nerve block is usually essential in order to provide adequate anesthesia for the creation of an arteriovenous fistula for hemodialysis because this nerve innervates the lateral aspect of the distal forearm. Analgesia of the median and the radial nerve may also be necessary if the exploration of blood vessels is extended distally.

Although sensory block of the musculocutaneous nerve has been found adequate for hand and forearm surgery in 90% of single- injection perivascular axillary brachial plexus blocks,1 73% of patients may not have complete sensory block (i.e., “no sensation” to pinprick) of the musculocutaneous nerve.2 Because the musculocutaneous nerve leaves the brachial neurovascular compartment distal to the coracoid process, blockade of the nerve has been shown to be more consistent by using a lateral infraclavicular approach than a single-injection axillary brachial plexus approach.3,4 We hypothesized that in uremic patients scheduled for arteriovenous fistula creation, the musculocutaneous nerve and the entire surgical field could be more successfully blocked with a single-injection infraclavicular coracoid technique than with the perivascular axillary brachial plexus block technique.

Methods

The study protocol was approved by the Ethics Committee for Surgery of the Hospital District of Helsinki and Uusimaa. Sixty uremic patients, aged 26 to 83 years, scheduled for creation of an arteriovenous fistula for hemodialysis in the lateral antebrachial region gave their written informed consent and were enrolled in the study.

The patients received their regular medication on the morning of surgery. The patients were premedicated with intravenous diazepam before the brachial plexus block. Monitoring consisted of a 5-lead electrocardiogram (ECG), pulse oximetry, and non-invasive blood pressure measurement at 5-minute intervals.

Patients were randomized in 2 groups of 30 to receive either infraclavicular coracoid brachial plexus block (IC group) or axillary brachial plexus block (AX group). Randomization was based on an investigator-generated code that was sealed in sequentially numbered opaque envelopes. The blocks were performed by experienced senior staff members and assessed by an anesthetist who was blinded regarding the block approach.

After infiltration of the skin with 2 to 3 mL of lidocaine 10 mg/ mL, the brachial plexus was identified with a short-beveled electric stimulation needle (Stimuplex, 50 mm; B. Braun Melsungen AG, Melsungen, Germany) connected to a nerve stimulator by using a low current (

After obtaining a peripheral motor response from muscles innervated by 1 of the 4 main nerves at a current ≤0.5 mA, 35 to 50 mL of mepivacaine HCl 9.5 mg/mL with epinephrine 4.8 g/mL (each time a fresh solution was prepared by adding 2.5 mL epinephrine 0.1 mg/mL to 50 mL of mepivacaine HCl 10 mg/mL) was injected slowly in 3 to 5 minutes with intermittent aspiration. The volume of the mepivacaine solution was chosen according to the weight of the patient: 35 mL for 40 to 49 kg, 40 mL for 50 to 59 kg, 45 mL for 60 to 69 kg, and 50 mL for ≥70 kg. The arm was then brought to rest at the patient’s side. In group IC, the arm was resting at the patient’s side during the performance of block and thereafter until surgery.

Skin sensation to pinprick was tested by a groupblinded observer using a 27-gauge short-bevel needle before the block and 5, 15, 30, 45, and 60 minutes after injection of mepivacaine as well as at the end of the surgery. The tests were carried out in 4 areas: in the sensory distribution of median (dorsum of distal phalanx of the middle finger), musculocutaneous (lateral area of frontal forearm), radial (dorsum of proximal phalanx of the thumb), and ulnar nerves (dorsum of distal phalanx of the little finger). Motor power of the hand was tested at the same intervals by grip strength, as well as flexion and extension of the forearm at the elbow. Degree of sensation was graded as “sharp,””blunt,” or “no sensation” and motor power as “normal movement,””decreased movement,” or “no movement.” After surgery, the corresponding tests were performed at 30-minute intervals until 2 of the sensory test territories or motor power of the hand had recovered 1 grade on the test scale.

In case of surgical pain, the surgeon infiltrated lidocaine 10 mg/ mL locally, and 0.05 to 0.15 mg of fentanyl was administered intravenously, as needed. During surgery, intravenous midazolam (maximal dose of 5 mg) or low-dose propofol infusion (after the administration of 5 mg of midazolam) for anxiety was given if needed. Postoperative pain was treated with acetaminophen (intravenously or orally) or oxycodone (intravenously, intramuscularly, or orally), as required. Postoperatively, in the recovery room, the patients were asked to rate their degree of satisfaction about the anesthetic technique and its performance as “dissatisfied,””quite satisfied,””satisfied,” or “very satisfied.”

Statistics

In our previous study, the musculocutaneous nerve block was absent or partial (pinprick sensation “normal” or “decreased”) in 73% of patients receiving a brachial plexus block by the perivascular axillary approach.2 According to the power analysis, we estimated that 25 patients per group would be needed to show a 50% better result (i.e., 36% of patients having absent or partial musculocutaneous nerve block) with an α- and β-error of 0.05 and 0.2, respectively. The results are expressed as mean values with standard deviation or medians with range. An unpaired Student t test or a Mann-Whitney rank sum test were used for comparison of the demographic variables and operative data. For the analysis of the quality of the block, a chi-square or Fisher exact test was used. Differences were regarded as statistically significant if P

Table 1. Patient Characteristics

Results

In group IC, the brachial plexus could not be identified in 1 patient (body mass index 34 kg/m^sup 2^), and the block was successfully performed using the axillary approach. Thus, the number of patients included in the analysis of block development was 29 in group IC and 30 in group AX. The intra- and postoperative data of 2 group IC patients were excluded because the operating room was not available in time for the scheduled patient (delay of 2 and 3 hours, respectively) and of an additional patient in group IC because of unplanned use of a brachial tourniquet requiring general anest\hesia shortly before the end of surgery.

Data regarding patient characteristics are presented in Table 1. Most of the patients underwent primary reconstruction of an arteriovenous fistula. The rest of the procedures were reoperations, including 2 loop-graft procedures in the proximal region of forearm.

Table 2. Development of Sensory Blockade of the Hand With Infraclavicular Coracoid (IC) (n = 29) and Axillary (AX) (n = 30) Approach of Brachial Plexus Block

Nerve stimulation with a visible motor response was achieved at 0.4 (0.3-0.4) or 0.3 (0.3-0.4) mA (median, 25th/75th percentiles) in group IC or AX, respectively (P > .05). Median nerve motor response was observed in 18 patients in group IC and 21 patients in group AX, respectively. Radial and ulnar nerve motor responses were detected in 9 and in 1 patient in group IC, respectively, and in 8 and in 1 patient in group AX.

In group AX, 2 patients developed transient tachycardia after injection of the local anesthetic. A 51-year-old diabetic patient’s heart rate increased from 60 beats/min to 90 beats/min 10 minutes after the injection of 428 mg of mepivacaine with 216 g of epinephrine, and a transient ST depression of – 1.0 mm in V5 lead of an ECG was observed. She also experienced the insertion of block as uncomfortable and painful. The other group AX patient, a 68-year- old man with ischemic heart disease, had a heart rate increase from 60 beats/min to 93 beats/min with a ST depression of -2.2 mm in V5 lead of ECG 15 minutes after the injection of 428 mg of mepivacaine with 216 g of epinephrine. In both cases, metoprolol was administered intravenously, and the tachycardia with ST depression was shortlived. The patients had successful brachial plexus blocks for surgery. Otherwise, there were no druginduced side effects.

Brachial plexus blockade with mepivacaine using either technique provided similar anesthesia for surgery. Adequate surgical anesthesia, defined as “blunt sensation” or “no sensation” to pinprick in test territories of the ulnar, median radial, and musculocutaneous nerves at 60 minutes after injection of mepivacaine, varied between 90% to 97% group IC and 87% to 97% in group AX (P > .05, Table 2). More patients had pinprick analgesia (“blunt” or “no sensation” to pinprick) in the musculocutaneous nerve distribution 30 minutes after injection in group IC compared with group AX (P

Table 3. Development of Motor Power of the Hand With Infraclavicular Coracoid (IC) (n = 29) and Axillary (AX) (n = 30) Approach of Brachial Plexus Block

Complete pinprick analgesia (“no sensation” to pinprick) was also achieved faster in the musculocutaneous nerve distribution by using the infraclavicular coracoid versus the axillary approach (i.e., at 30 minutes 62% v 30% [P

During surgery, comparable amounts of locally infiltrated lidocaine (7 IC and 15 AX group patients, P > .05) and fentanyl IV (9 IC and 12 AX group patients, P > .05) were required in the study groups. The number of patients requiring neither lidocaine nor fentanyl did not differ between the groups (18 IC and 14 AX group patients). The amount of intraoperative midazolam was not different between the study groups. Low-dose propofol infusion was given in 2 patients in group IC and in 3 patients in group AX. The median (25th- 75th percentiles) operation time was 69 (58-94) minutes in the IC group and 75 (57-102) minutes in the AX group (P > .05).

At the end of surgery, the sensory and motor power of the hand was comparable between the groups (Tables 2 and 3). Thereafter, there were no statistically significant differences between the groups in the recovery of the sensory or motor blockade.

The particular patient (group AX) with tachycardia and ST changes in the ECG was dissatisfied with the anesthetic technique. The others were quite satisfied (7 in group IC and 3 in group AX), satisfied (12 in group IC and 15 in group AX), or very satisfied (10 in group IC and 11 in group AX).

Discussion

In the present study, the main finding was a slower onset of musculocutaneous nerve anesthesia with single-injection perivascular axillary block technique when compared with infraclavicular coracoid block in patients scheduled for arteriovenous fistula surgery. The number of patients having complete sensory block of musculocutaneous nerve (“no sensation” to pinprick) at 30- and 45-minute testing was almost twice that seen in group IC than group AX. However, at 45 and 60 minutes after injection of mepivacaine, we achieved similar surgical analgesia (“blunt” or “no sensation” to pinprick) on the lateral forearm with both techniques.

There are important differences in the neural anatomy in the axillary and infraclavicular region. In the infraclavicular area, the cords are lying very close to each other around the axillary artery, whereas in the axilla the terminal nerves are separated and variably located at greater distances from each other. The musculocutaneous and axillary nerves have already left the cords at the level of the coracoid process. Therefore, when anesthesia at the territories of these nerves is required, a single-injection technique by identifying only 1 motor response of a terminal nerve may be more applicable when using the infraclavicular coracoid approach than the axillary approach. In the current study using a single-injection method, faster achievement of block with the coracoid approach in comparison with the axillary approach and similar block at 60 minutes after the injection of mepivacaine support the idea of the proximal migration of mepivacaine when administered in the axilla.

An interesting observation in the present study was mild tachycardia with ST depression of the electrocardiogram in 2 of our axillary group patients 10 to 15 minutes after the administration of the total dose of the local anesthetic. The relatively late appearance of symptoms suggests that the reactions were caused by epinephrine absorbed from the injected solution. Similar complications have been reported before.6,7 In our study, the total dose of epinephrine was relatively large, 168 to 240 g (i.e., larger than suggested by Raj and coworkers8 as the maximum recommended dose of 1.5 g/kg/10 min). Intravascular injection of the local anesthetic solutions, a possible complication of both the axillary and the lateral infraclavicular approaches,4,9,10 did not occur in our patients. This raises the question of the risks and benefits of the use of epinephrinecontaining solutions in brachial plexus anesthesia.

The single-injection technique may shorten the duration of the block performance9 and lessen patient distress caused by needle punctures and muscle twitches. On the other hand, anesthesia of the cutaneous lateral nerves of the forearm and of the arm is inconsistently achieved with single-injection IC block techniques. In contrast to the conclusion by Rodrguez and coworkers11 of a low success rate by using single-injection infraclavicular coracoid block (i.e., surgical analgesia in on average 81% of the 7 tested nerve distribution areas), we observed surgical analgesia in 90% to 97% of the test territories of the ulnar, median radial, and musculocutaneous nerves. The difference may be because of the relatively short follow-up period (i.e., 20 minutes) in the study by Rodriguez and coworkers. In the present study, the maximum block was not achieved until 45 minutes, a finding typical when single- injection technique is used.1,2 In addition, a motor stimulation response of median nerve in single-stimulation infraclavicular coracoid approach to brachial plexus appears to be associated with good sensory block of the radial nerve, which may have enabled pain- free surgery also in the innervation area of that nerve.11 In fact, in lateral infraclavicular approaches, the initial motor response is often from the median nerve stimulation,12 and single injection of a large local anesthetic dose (volume) provides analgesia also of the ulnar and radial nerves.1 ‘Nearly all of our patients were very satisfied or satisfied with their regional anesthesia. Only one of our axillary group patients (i.e., the one with an epinephrine- induced acute cardiovascular episode) experienced the placement of the block as uncomfortable.

We conclude that a brachial plexus block with 333 to 475 mg of mepivacaine develops faster by a single-stimulation/injection technique using the infraclavicular coracoid than with the axillary approach, but both have a similar efficacy for surgery in patients scheduled for creation of an arteriovenous fistula of the forearm.

Acknowledgment

We are grateful to Pekka Tarkkila, M.D., Ph.D., for helpful comments and suggestions during the preparation of the manuscript.

References

1. Pere P, Salonen M, Jokinen M, Rosenberg PH, Neuvonen PJ, Haasio J. Pharmacokinetics of ropivacaine in uremic and nonuremic patients after axillary brachial plexus block. Anesth Analg 2003;96:563-569.

2. Liisanantti O, Luukkonen J, Rosenberg PH. Highdose bupivacaine, levobupivacaine and ropivacaine in axillary brachial plexus block. Acta Anaesthesiol Scand 2004;48:601-606.

3. Kapral S, Jandrasits O, Schabernig C, Likar R, Reddy B, Mayer N, Weinstabl C. Lateral infraclavicular plexus block vs. axillary block for hand and forearm surgery. Acta Anaesthesiol Scand 1999;43:1047-1052.

4. Koscielniak-Nielsen ZJ, Rotboll Nielsen P, Risby Mortensen C. A comparison of coracoid and axillary approa\ches to the brachial plexus. Acta Anaesthesiol Scand 2000;44:274-279.

5. Wilson JL, Brown DL, Wong GY, Ehman RL, Cahill DR. Infraclavicular brachial plexus block: Parasagittal anatomy important to the coracoid technique. Anesth Analg 1998;87:870-873.

6. Dhunr KG, Harthon JG, Herbring BG, Lie T. Blood levels of mepivacaine after regional anaesthesia. Br J Anaesth 1965;37:746- 752.

7. Koscielniak-Nielsen ZJ. An unusual toxic reaction to axillary block by mepivacaine with adrenaline. Acta Anaesthesiol Scand 1998;42:868-871.

8. Raj PP, Pai U, Rawal N. Techniques of regional anesthesia in adults. In: Raj PP, ed. Clinical Practice of Regional Anesthesia. New York: Churchill Livingstone; 1991:272.

9. Deleuze A, Gentili ME, Marret E, Lamonerie L, Bonnet F. A comparison of a single-stimulation lateral infraclavicular plexus block with a triple-stimulation axillary block. Reg Anesth Pain Med 2003;28:89-94.

10. Gaertner E, Estebe JP, Zamfir A, Cuby C, Macaire P. Infraclavicular plexus block: Multiple injection versus single injection. Reg Anesth Pain Med 2002;27:590-594.

11. Rodrguez J, Taboada-Muniz M, Barcena M, Alvarez J. Median versus musculocutaneous nerve response with single-injection infraclavicular coracoid block. Reg Anesth Pain Med 2004:29:534- 538.

12. Jandard C, Gentili ME, Girard F, Ecoffey C, Heck M, Laxenaire MC, Bouaziz H. Infraclavicular block with lateral approach and nerve stimulation: Extent of anesthesia and adverse effects. Reg Anesth Pain Med 2002;27:37-42.

Tomi T. Niemi, M.D., Ph.D., Liisa Salmela, M.D., Ulla Aromaa, M.D., Ph.D., Reino Pyhi, M.D., Ph.D., and Per H. Rosenberg, M.D., Ph.D.

From the Department of Anesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland.

Accepted for publication September 21, 2006.

Supported by Helsinki University Hospital Research Grants (EVO).

Reprint requests: Tomi T. Niemi, M.D., Ph.D., Department of Anesthesiology and Intensive Care Medicine, Helsinki University Hospital, PO Box 340, FI-00029 HUS, Helsinki, Finland. E-mail: [email protected]

2007 by the American Society of Regional Anesthesia and Pain Medicine.

1098-7339/07/3201-0001$32.00/0

doi: 10.1016/j.rapm.2006.09.010

Copyright Churchill Livingstone Inc., Medical Publishers Jan/Feb 2007

(c) 2007 Regional Anesthesia and Pain Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

DENVER, Jan. 29 /PRNewswire-FirstCall/ — Air Methods Corporation announced today that Sacred Heart Health Systems, based in Pensacola, Florida, has selected Air Methods to assume operations of its AIRHeart air ambulance service serving Northwest Florida and parts of South Alabama. The Sacred Heart helicopter program was transferred to Air Methods as part of its community-based operations. This represents the first expansion of Air Methods’ community-based model into Northwest Florida. The specific terms of the asset purchase were not disclosed and the AIRHeart trademark will continue as a d/b/a of Air Methods subsidiary operations. The recently closed transaction was effective January 1, 2007.

AIRHeart currently serves communities across Northwest Florida from bases in Walton County and Marianna, Florida, and expects to expand its services as an operation of Air Methods. “We are pleased we were able to develop a relationship with the nation’s largest air medical provider, and we believe their capability and stellar reputation provide an excellent fit with our AIRHeart service,” stated Ron Mosley, flight program director for AIRHeart.

Ken Grimes, Regional Vice President of Air Methods’ Community Based Division stated, “AIRHeart will use twin-engine BO105 and EC135 and single-engine EC130 helicopters. We are pleased to include the AIRHeart program with our Florida operations, and are excited that the transition includes plans to expand the geographic coverage of our air ambulance service in Northwest Florida.”

Sacred Heart Health System is Northwest Florida’s most preferred hospital and the region’s leader in providing high quality, compassionate health care to children and adults. Key services at Sacred Heart’s 458-bed hospital in Pensacola include: a Regional Heart and Vascular Institute, Children’s and Women’s Hospital, a Level II Trauma Center, a Cancer Center affiliated with M.D. Anderson Physicians Network, a home health agency, and a large network of primary care doctors and specialists that stretches from Foley, Alabama to Panama City Beach, Florida. In 2003, the Health System also added Sacred Heart Hospital on the Emerald Coast, a 50-bed community hospital in Walton County, east of Destin, Florida.

Air Methods Corporation (http://www.airmethods.com/) is a leader in emergency aeromedical transportation and medical services. The Air Medical Services Division is the largest provider of air medical transport services for hospitals. The LifeNet Division is one of the largest community-based providers of air medical services. The Products Division specializes in the design and manufacture of aeromedical and aerospace technology. The Company’s fleet of owned, leased or maintained aircraft features over 200 helicopters and fixed wing aircraft.

CONTACTS: Aaron D. Todd, Chief Executive Officer, (303) 792-7413 or Joe Dorame at Lytham Partners, LLC, at (602) 889-9700. Please contact Christine Clarke at (303) 792-7579 to be included on the Company’s fax and/or mailing list.

Air Methods Corporation

CONTACT: Aaron D. Todd, Chief Executive Officer of Air MethodsCorporation, +1-303-792-7413; or Joe Dorame of Lytham Partners, LLC,+1-602-889-9700, for Air Methods Corporation

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

Kindred Healthcare, Inc. (the “Company”) (NYSE: KND) today announced that the Centers for Medicare and Medicaid Services (“CMS”) issued late yesterday proposed regulatory changes regarding Medicare reimbursement for long-term acute care (“LTAC”) hospitals. The proposed rule would be effective for discharges occurring on or after July 1, 2007 through June 30, 2008. The proposed rule is subject to a 60-day public comment period.

The CMS proposed rule projects an overall decrease in payments to all Medicare certified LTAC hospitals of 2.9%. Included in this proposed decrease are (1) an increase to the standard Federal Payment Rate of .71%; (2) revisions to payment methodologies impacting short stay outliers which reduce payments by .9%; (3) adjustments to the wage index component of the federal payment resulting in projected reductions in payment of .5%; and (4) an extension of the policy known as the “25 Percent Rule” to all LTAC hospitals, which CMS projects will reduce payments by 2.2%.

The proposed short-stay outlier revisions would create a new category for cases having lengths of stay less than the average of a patient in a short-term hospital with the same diagnosis. Payment for such cases would be based on the payment that the short-term acute care hospital would have received.

Currently, CMS has regulations governing payment to LTAC hospitals that are co-located with another hospital. Most co-located hospitals can admit up to 25% of its patients from its host hospital and be paid according to the Long-Term Care Prospective Payment System (“LTC PPS”). Admissions that exceed the 25% limit are paid using the short-term hospital payment system. CMS is currently phasing-in this policy with it becoming fully effective after September 1, 2008.

CMS is now proposing to expand this policy to all LTAC hospitals, regardless of whether they are co-located with another hospital. Under this proposal, all LTAC hospitals will be paid LTC PPS rates for admissions from a single referral source up to 25%. Admissions beyond 25% would be paid using the short-term hospital payment system. Under the proposal, the 25% threshold would not apply immediately to certain LTAC hospitals. Hospitals having fiscal years beginning on or after 7/1/07 and before 10/1/07, including most of Kindred’s hospitals, will have their admission cap initially set at 50%. For most Kindred hospitals, this 50% cap would apply until September 1, 2008, after which the cap would be reduced to 25%.

CMS is also proposing that the annual update to the Long-Term Care Diagnostic Related Groups (“LTC DRG”) classifications and relative weights would be done in a budget neutral manner, effective October 1, 2007. As such, the estimated aggregate LTC PPS payments would be unaffected by the annual recalibration of LTC DRG payment weights.

Kindred’s President and Chief Executive Officer, Paul Diaz, characterized the CMS proposed rule as “anticipated,” but commented that leaders in Congress have expressed a strong preference to define the appropriate role for LTACs through certification criteria, not through further changes to the payment system: “While we are not surprised by CMS’s proposals, we are disappointed that there continue to be changes to the LTAC payment system that do not advance rational policy in the post-acute space. Leaders in both houses of Congress have introduced legislation that would ensure that patients admitted to LTACs need the unique, intensive services only we can provide. Both H.R. 562, introduced by Congressmen English and Pomeroy, and S. 338 introduced by Senators Conrad and Hatch, not only advance policy by ensuring appropriate placement of patients, both pieces of legislation would save the Medicare program an estimated $1.5 billion over the next five years. We agree with Congressional leaders that clinical certification criteria, not payment cuts, is the appropriate policy course for LTACs.”

Mr. Diaz also commented on CMS’s proposal to extend the LTAC Hospital within Hospital 25% rule to freestanding LTACs. “Dictating where medically complex patients can obtain needed care based exclusively on arbitrary admission limits ignores the clinical and quality of care considerations that should be the primary determinant of access to LTAC care.” Mr. Diaz commented further, “While we continue to analyze CMS’s proposal, I would emphasize that the actual impact of a 25% rule will vary widely depending on the operating model that specific freestanding LTACs use. For the most part, Kindred’s freestanding LTACs are deeply rooted in their communities and have long-standing relationships with a number of referral sources. In addition, we continue to develop relationships with non-Medicare private payer sources to the point that the percentage of our Hospitals’ revenue coming from private payers is approximately 30%.”

Mr. Diaz also commented, “Kindred supports CMS’s decision to re-weight the LTC-DRGs in a budget neutral manner as is done for acute care hospitals. Not only is this fair, it will help LTACs achieve a level of payment stability that is vital to plan for consistent care delivery. Over the past two years DRG re-weighting has reduced LTAC rates by nearly 6%, so this is a welcome change to the payment system.”

Kindred plans to submit comments to CMS within the 60-day public comment period and will provide further information to the public as it becomes available.

This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements regarding Kindred’s expected future financial position, results of operations, cash flows, financing plans, business strategy, budgets, capital expenditures, competitive positions, growth opportunities, plans and objectives of management and statements containing the words such as “anticipate,””approximate,””believe,””plan,””estimate,””expect,””project,””could,””should,””will,””intend,””may” and other similar expressions, are forward-looking statements.

Such forward-looking statements are inherently uncertain, and stockholders and other potential investors must recognize that actual results may differ materially from Kindred’s expectations as a result of a variety of factors, including, without limitation, those discussed below. Such forward-looking statements are based upon management’s current expectations and include known and unknown risks, uncertainties and other factors, many of which Kindred is unable to predict or control, that may cause Kindred’s actual results or performance to differ materially from any future results or performance expressed or implied by such forward-looking statements. These statements involve risks, uncertainties and other factors discussed below and detailed from time to time in Kindred’s filings with the Securities and Exchange Commission.

In addition to the factors set forth above, other factors that may affect Kindred’s plans or results include, without limitation, (a) Kindred’s ability to operate pursuant to the terms of its debt obligations and its master leases with Ventas, Inc.; (b) Kindred’s ability to meet its rental and debt service obligations; (c) Kindred’s and AmerisourceBergen Corporation’s ability to complete the proposed merger of their respective institutional pharmacy operations, including the receipt of all required regulatory approvals and the satisfaction of other closing conditions to the proposed transaction; (d) adverse developments with respect to Kindred’s results of operations or liquidity; (e) Kindred’s ability to attract and retain key executives and other healthcare personnel; (f) increased operating costs due to shortages in qualified nurses, therapists and other healthcare personnel; (g) the effects of healthcare reform and government regulations, interpretation of regulations and changes in the nature and enforcement of regulations governing the healthcare industry; (h) changes in the reimbursement rates or methods of payment from third party payors, including the Medicare and Medicaid programs, changes arising from and related to the Medicare prospective payment system for long-term acute care hospitals, including the final Medicare payment rules issued in May 2006, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, and changes in Medicare and Medicaid reimbursements for Kindred’s nursing centers; (i) national and regional economic conditions, including their effect on the availability and cost of labor, materials and other services; (j) Kindred’s ability to control costs, including labor and employee benefit costs; (k) Kindred’s ability to successfully pursue its development activities and successfully integrate new operations, including the realization of anticipated revenues, economies of scale, cost savings and productivity gains associated with such operations; (l) the increase in the costs of defending and insuring against alleged professional liability claims and Kindred’s ability to predict the estimated costs related to such claims; (m) Kindred’s ability to successfully reduce (by divestiture of operations or otherwise) its exposure to professional liability claims; (n) Kindred’s ability to successfully dispose of unprofitable facilities; and (o) Kindred’s ability to ensure and maintain an effective system of internal controls over financial reporting. Many of these factors are beyond Kindred’s control. Kindred cautions investors that any forward-looking statements made by Kindred are not guarantees of future performance. Kindred disclaims any obligation to update any such factors or to announce publicly the results of any revisions to any of the forward-looking statements to reflect future events or developments.

About Kindred Healthcare

Kindred Healthcare, Inc. (NYSE: KND) is a Fortune 500 healthcare services company, based in Louisville, Kentucky, with annualized revenues of $4.3 billion that provides services in over 500 locations in 39 states. Kindred through its subsidiaries operates long-term acute care hospitals, skilled nursing centers, institutional pharmacies and a contract rehabilitation services business, Peoplefirst Rehabilitation Services, across the United States. Kindred’s 55,000 employees are committed to providing high quality patient care and outstanding customer service to become the most trusted and respected provider of healthcare services in every community we serve. For more information, go to www.kindredhealthcare.com.

Salix Pharmaceuticals’ antibiotic Xifaxan was approved by the FDA for the treatment of traveler’s diarrhea (TD) in 2004. However, the majority of Xifaxan use is accounted for by off-label indications, growth in which is essential to its revenue potential. Taking this into account, Datamonitor forecasts sales of $106 million in 2008, ahead of Wall Street expectations of $76 million in 2008.

Xifaxan is an orally administered rifamycin antibacterial that is poorly absorbed by the gastrointestinal (GI) tract, thereby acting as a topical antibiotic in the gut. As a result, it has the potential to cause less adverse effects than systemic antibiotics.

Xifaxan is used extensively off-label in various GI diseases, with a recent physician survey suggesting that 31% of prescriptions are for the treatment of irritable bowel syndrome (IBS) with an additional 43% split primarily among hepatic encephalopathy (HE), C. difficile-associated diarrhea (CDAD) and Crohn’s disease (CD).

However, the survey also suggested that in its current approved indication of TD sales growth is limited as discounted generic formulations are widely available. As such, the continued increase in use in other GI diseases is crucial for sales growth.

Overwhelmingly, the most commonly identified barrier to use of Xifaxan by surveyed physicians is the limited third party reimbursement for use in off-label indications. On average surveyed physicians estimated that 46% of the patients to whom they would choose to prescribe Xifaxan do not receive the drug because of financial issues. As such, label expansion into various GI diseases is essential for long-term growth.

Xifaxan can be expected to receive FDA approval for the treatment of HE and CDAD in mid 2009, driving prescription growth in these indications. Surveyed physicians estimated that use of Xifaxan in HE could increase 350% over its current penetration with FDA approval, compared to peaking at 120% growth without FDA approval. Likewise, FDA approval for CDAD could increase its use by 412% compared to 80% growth through off-label use only.

Even if the drug does not receive approval for the treatment of IBS or CD within the forecast timeframe – which could increase the prescriptions of Xifaxan by more than 500% – Datamonitor still predicts sales above market expectations. Datamonitor forecasts 2006 sales of $49 million growing to $82 million in 2007 and $106 million in 2008, ahead of Wall Street expectations of $47 million in 2006, $68 million in 2007 and $76 million in 2008.

SAN FRANCISCO and MINNEAPOLIS, Jan. 25 /PRNewswire/ — LifeMasters Supported SelfCare, Inc., a leading provider of disease management programs and services in the nation, and PreferredOne Community Health Plan today announced a three-year agreement to provide PreferredOne members with disease management services for chronic obstructive pulmonary disease, diabetes, congestive heart failure, asthma and coronary artery disease.

As a health benefits administrator, PreferredOne offers a full-range of products, services and networks to brokers, employers, members, insurance companies and third-party administrators throughout Minnesota and the Upper Midwest. Under the three-year contract, more than 50,000 PreferredOne members will have access to LifeMasters’ customized disease management program designed to help them better manage their health conditions. Program participants will receive coaching and regular telephonic support from their own personal health coach. They will learn how to monitor their vital signs and symptoms to detect early changes in their health status. An integral part of the program includes integrating the members’ physicians by alerting them to significant changes in their patient’s health between office visits so they can intervene early to avoid emergency room visits and hospitalizations.

“We are pleased to offer this much needed service to our members and the community especially since it is well aligned with everyone’s increasing desire to stay healthy while minimizing out of pocket expenses,” said Marcus Merz, President and CEO at PreferredOne Community Health Plan. “We chose LifeMasters because of their expertise and track record at delivering disease management solutions that improve health outcomes while significantly reducing costs.”

LifeMasters currently provides disease management services to eligible members enrolled in the PreferredOne Community Health Plan. This program is also available to PreferredOne ASO groups who are interested in providing support and education to help their employees manage their chronic conditions.

“We are pleased to support PreferredOne in offering its members an innovative and personal approach to achieving and maintaining optimal health,” said David R. Strand, president and chief executive officer at LifeMasters. “And, we look forward to contributing to the health and well-being of Minnesotans with them.”

About PreferredOne

PreferredOne is a health benefits administration company offering TPA, HMO (including HSAs) qualified high-deductible individual plans & PPO products & services in Minnesota and the Upper Midwest. PreferredOne health care networks provide access to more than 14,000 physicians, 1,600 primary care clinics and 260 hospitals. PreferredOne is headquartered in Golden Valley, MN with a staff of 330 employees. More information about PreferredOne can be found at http://www.preferredone.com/ or by calling 1-763-847-4007.

About LifeMasters Supported SelfCare

LifeMasters Supported SelfCare, Inc. is a leading provider of disease management programs and services that create health partnerships among individuals, their physicians and payors. Its mission is to empower individuals to achieve and maintain optimal health. The programs improve quality of care for people with chronic illnesses, reduce chronic-disease costs for payors and provide decision-support tools for physicians. LifeMasters offers programs for individuals with diabetes, congestive heart failure (CHF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), hypertension and asthma (all of which are fully accredited by the National Committee for Quality Assurance (NCQA) and URAC) and musculo-skeletal pain. LifeMasters’ programs are holistically focused, support co-morbidities such as depression and facilitate lifestyle changes such as smoking cessation and weight loss. LifeMasters provides services to nearly 650,000 people throughout the nation.

Founded in 1994 by a physician, LifeMasters works with some of the nation’s leading health plans, employers, retirement systems and governmental organizations, including Aetna, BlueCross BlueShield of Tennessee, State Teachers Retirement System of Ohio, and Presbyterian Health Services in New Mexico. More information about LifeMasters can be found at http://www.lifemasters.com/ or by calling 1-800-777-1307.

   Contacts:   Barbara Gideon                      John Frederick, M.D.   LifeMasters                         Chief Medical Officer   (650) 829-5287                      PreferredOne   [email protected]             (763) 847-3051                                       [email protected]  

LifeMasters Supported SelfCare, Inc.

CONTACT: Barbara Gideon of LifeMasters, +1-650-829-5287,[email protected]; or John Frederick, M.D., Chief Medical Officer ofPreferredOne, +1-763-847-3051, [email protected]

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

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

DAYTON, Ohio, Jan. 22 /PRNewswire/ — Anthem National Accounts announced today its venture with General Motors on an electronic prescribing pilot that includes physicians and health information technology providers to help reduce medication errors and simplify the prescribing process. The pilot, which will involve 100 physicians, will benefit thousands of patients in two Ohio communities regardless of their health plan affiliation.

Specifically, the ePrescribing pilot will equip participating physicians in Dayton and Warren/Youngstown with computer hardware and software that provides instant access to current health plan formularies and patient medication history available through claims data. This will allow the physicians to send prescriptions electronically to both retail and mail-order pharmacies instantaneously.

“Electronic prescribing has been proven to reduce errors, help prevent harmful drug interactions and streamline prescribing processes for physicians and patients,” said Sam Nussbaum, M.D., executive vice president and chief medical officer. “Unfortunately, this technology is underutilized. Our ePrescribing pilot is designed to encourage physician adoption of this potentially life-saving and time-saving technology.”

Currently, less than 22 percent of physicians nationwide use the basic capabilities of electronic prescribing, according to the Center for Medicare and Medicaid Services (CMS). CMS estimates that the use of such technology could eliminate as many as two million harmful drug events each year. Other electronic prescribing pilots have demonstrated that up to 2 percent of all prescriptions are changed due to alerts for potential safety issues that are delivered real time to physicians.

“This pilot is another example of our commitment to advancing the health of our members and improving the quality, delivery and affordability of health care to our customers,” said Ken Goulet, president of Anthem National Accounts.

The ePrescribing pilot will provide real-time prescription support to physicians, including access to formularies, drug-drug and drug-allergy alerts, and a patient’s medication history including medications prescribed by physicians outside of the practice.

“It’s our expectation that this pilot will help reduce medical errors and improve patient safety by providing drug-specific information that helps eliminate confusion among drug names and improve communication between physicians and pharmacists,” said Nussbaum.

The technology will also allow physicians to send new prescriptions electronically to the pharmacy of the patient’s choice as well as electronically process refill requests.

Anthem National Accounts’ collaborator in the pilot, General Motors (GM), is the largest private purchaser of health care in the United States. GM pays the health care costs of 1.1 million employees, retirees and dependents. A significant number of GM employees, retirees and dependents live in the area in which the pilot program is being conducted.

“We expect the ePrescribing pilot will help physicians provide better, more efficient care for patients in this area, but health care consumers nationwide will also benefit,” said Bruce Bradley, director of Healthcare Strategy and Public Policy, General Motors Corporation. “Physicians who adopt the ePrescribing program in their practices will be able to use it for all patients, not just Anthem members or GM employees.”

Anthem is working with a number of organizations to implement the program, including:

   *  MedPlus(R), the health care information technology subsidiary of Quest      Diagnostics,  to implement the ePrescribing pilot with its      Care360(TM) physician portal;   *  RxHub(R), LLC, which is providing the technology infrastructure that      supports the secure exchange of patient-specific prescribing      information between physicians and pharmacy benefit managers (PBMs) and      the transmission of the electronic prescriptions to mail-order      pharmacies;   *  SureScripts(R), operators of the Pharmacy Health Information      Exchange(TM), which facilitates the electronic connection between      community pharmacies and physicians; and   *  WellPoint NextRx, Anthem's pharmacy benefit management company, which      plays a key role by helping to ensure physician access to information,      including benefits, eligibility, formularies and medication history.   

Incentives are available to all physicians who ePrescribe and are eligible to participate in the company’s pay-for-performance programs in the pilot areas.

“The current ePrescribing pilot further illustrates Anthem Blue Cross and Blue Shield’s ongoing commitment to collaborating with physicians and our employer customers to deliver innovations in health care by piloting new programs in local markets to evaluate their effectiveness,” said Goulet.

This program follows the announcement of the Anthem Care Comparison online cost transparency tool, which was introduced in Dayton late last year.

About Anthem National Accounts

The Anthem National Accounts business unit serves members of Anthem Blue Cross and Blue Shield in the 11 states of Colorado, Connecticut, Indiana, Kentucky, Maine, Missouri (excluding 30 counties in the Kansas City area), Nevada, New Hampshire, Ohio, Virginia (excluding the Northern Virginia suburbs of Washington, D.C.) and Wisconsin, in addition to Blue Cross of California, Blue Cross Blue Shield of Georgia, and Empire Blue Cross Blue Shield in the state of New York (Empire Blue Cross Blue Shield in 10 New York City metropolitan counties and as Empire Blue Cross or Empire Blue Cross Blue Shield in selected upstate counties only). All are independent licensees of the Blue Cross Blue Shield Association. (R) Registered marks Blue Cross and Blue Shield Association. Additional information about Anthem is available at http://www.anthem.com/.

Anthem National Accounts

CONTACT: Investor Relations: Wayne S. DeVeydt, +1-317-488-6390, Media:Cindy Sanders, +1-404-842-8406, or Jim Gavin, +1-317-287-6051, all of AnthemNational Accounts

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