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Biomedical subjects

M Weinstein

Publications and source records attributed to M Weinstein.

At least 37 records · Page 2Linked to original sources

Provider-sponsored networks in public sector behavioral health.

Numerous behavioral health and social service providers (primarily not-for-profit community mental health and chemical dependency treatment centers) have been joining forces on a local and regional basis to create their own managed care contracting entities, referred to as provider-sponsored networks. Even though these networks are emerging as an alternative managed care model, little is known about them. This descriptive survey provides baseline information about the status of these networks. Using a structured interview questionnaire, a random sample of 15 networks from 12 states was surveyed. Participants were asked about various organizational characteristics of networks, reasons for formation, managed care readiness, obstacles to success, differential value of networks, and recommendations for success. Findings suggest that regional networks are making gradual progress, although many of the assumed benefits have been elusive.

Behavior Therapy↗

Gluteal necrotizing myofascitis: an unusual delayed complication of abdominal sacrocolpopexy.

Persistent low back pain developed in a 51-year-old woman after she had undergone abdominal sacrocolpopexy. Four months postoperatively, necrotizing myofascitis developed in her gluteal muscles. The infected mesh, which had eroded into the vagina, was removed. Cultures of the infected mesh and abscesses grew common vaginal flora, including Gardnerella vaginalis and Actinomyces.

Back Pain↗

Esophagatis and perinatal cytomegalovirus infection.

A 6-week-old male infant presented to hospital with a large upper gastrointestinal hemorrhage. Endoscopic biopsies of his esophagus and duodenum showed cytomegalovirus (CMV) inclusions and CMV early antigen was detected by immunohistochemistry. There were no other signs of congenital CMV infection. This case adds to the clinical spectrum of perinatal CMV infection and may be more common than is currently recognized.

Cytomegalovirus↗

Greater collaboration across the disciplines: challenges and opportunities.

This paper reports a panel discussion--Opportunities for and Limitations to Greater Collaboration Across the Disciplines--held at the conference. It highlights the need for greater collaboration between demographers and epidemiologists and notes the institutional and disciplinary challenges to and opportunities for promoting greater cooperation.

Demography↗

Smad proteins and hepatocyte growth factor control parallel regulatory pathways that converge on beta1-integrin to promote normal liver development.

Smads serve as intracellular mediators of transforming growth factor beta (TGF-beta) signaling. After phosphorylation by activated type I TGF-beta receptors, Smad proteins translocate to the nucleus, where they serve as transcription factors and increase or decrease expression of TGF-beta target genes. Mice lacking one copy each of Smad2 and Smad3 suffered midgestation lethality due to liver hypoplasia and anemia, suggesting essential dosage requirements of TGF-beta signal components. This is likely due to abnormal adhesive properties of the mutant hepatocytes, which may result from a decrease in the level of the beta1-integrin and abnormal processing and localization of E-cadherin. Culture of mutant livers in vitro revealed the existence of a parallel developmental pathway mediated by hepatocyte growth factor (HGF), which could rescue the mutant phenotype independent of Smad activation. These pathways merge at the beta1-integrin, the level of which was increased by HGF in the cultured mutant livers. HGF treatment reversed the defects in cell proliferation and hepatic architecture in the Smad2(+/-); Smad3(+/-) livers.

Active Transport, Cell Nucleus↗

An orange a day keeps the doctor away: scurvy in the year 2000.

Scurvy has been known since ancient times, but the discovery of the link between the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its incidence over the past half-century. Sporadic reports of scurvy still occur, primarily in elderly, isolated individuals with alcoholism. The incidence of scurvy in the pediatric population is very uncommon, and it is usually seen in children with severely restricted diets attributable to psychiatric or developmental problems. The condition is characterized by perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We describe a case of scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.

Ascorbic Acid↗

Predicting prostate specific antigen outcome preoperatively in the prostate specific antigen era.

PURPOSE: We evaluated the ability of previously defined risk groups to predict prostate specific antigen (PSA) outcome 10 years after radical prostatectomy in patients diagnosed with clinically localized prostate cancer during the PSA era. MATERIALS AND METHODS: Between 1989 and 2000, 2,127 men with clinically localized prostate cancer underwent radical prostatectomy, including 1,027 at Hospital of the University of Pennsylvania (study cohort) and 1,100 at Brigham and Women's Hospital (validation cohort). Cox regression analysis was done to calculate the relative risk of PSA failure with the 95% confidence interval (CI) in patients at intermediate and high versus low risk. The Kaplan-Meier actuarial method was used to estimate PSA outcome 10 years after radical prostatectomy. RESULTS: Compared with low risk patients (stages T1c to 2a disease, PSA 10 ng./ml. or less and Gleason score 6 or less) the relative risk of PSA failure in those at intermediate (stage T2b disease or PSA greater than 10 to 20 ng./ml. or less, or Gleason score 7) and high (stage T2c disease, or PSA greater than 20 ng./ml. or Gleason score 8 or greater) risk was 3.8 (95% CI 2.6 to 5.7) and 9.6 (95% CI 6.6 to 13.9) in the study cohort, and 3.3 (95% CI 2.3 to 4.8) and 6.3 (95% CI 4.3 to 9.4) in the validation cohort. The 10-year PSA failure-free survival rate in the 1,020 patients in the low, 693 in the intermediate and 414 in the high risk groups was 83%, 46% and 29%, respectively (p <0.0001). CONCLUSIONS: Based on 10-year actuarial estimates of PSA outcome after radical prostatectomy 3 groups of patients were identified using preoperative PSA, biopsy Gleason score and 1992 clinical T category.

Adult↗

Medicare in the 21st century.

The authors provide an overview of the Medicare program in terms of how the current program operates, the current issues it faces that may shape possible options for reform, and the implications of these features and issues for employment-based health plans. Current issues include adoption of a premium support model, changes in the eligibility age for Medicare benefits, Medigap insurance, benefits covered and customer service.

Age Factors↗

The restricted cellular host range of human herpesvirus 8.

DESIGN: A selection of primary and transformed cell types were evaluated for their susceptibility to infection with human herpesvirus 8 (HHV-8)/Kaposi's sarcoma-associated herpesvirus. METHODS: Sources of HHV-8 included Kaposi's sarcoma lesion punch biopsies that were either cocultured directly with target cells or that were first cocultured with human lymphocytes to derive HHV-8-containing fluids that were inoculated onto target cells. HHV-8 was also obtained from primary effusion lymphoma-derived cell lines. Techniques to detect infection included the PCR, immunofluorescence assays and in situ hybridization. RESULTS: Susceptible cells included human umbilical cord blood mononuclear cells (UCMC), adult CD19 B cells, macrophages and certain endothelial cells of human and animal origin, including some that are transformed with human papilloma virus type 16 E6 and E7 genes. The infection of lymphocytes did not yield established lymphoblastoid cell lines (LCL) and virus infection persisted for only 4-7 days. However, long-term HHV-8 infection of UCMC could be achieved by coinfection with Epstein-Barr virus. HHV-8 could also infect UCMC LCL recently derived by Epstein-Barr virus transformation, but long-established LCL could not be infected with HHV-8. CONCLUSIONS: These data provide further biological evidence in cell culture for the limited cellular host range of HHV-8 to CD19 B cells, macrophages, and certain endothelial cells.

Adult↗

Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4.

Heparan sulfate-regulated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes. Fibroblast growth factor has been implicated in the definition of liver from foregut endoderm where FGFR4 is expressed and stimulation of hepatocyte DNA synthesis in vitro. Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normally in response to partial hepatectomy. However, the FGFR4 (-/-) mice exhibited depleted gallbladders, an elevated bile acid pool and elevated excretion of bile acids. Cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase, the limiting enzyme for bile acid synthesis, was elevated, unresponsive to dietary cholesterol, but repressed normally by dietary cholate. Expression pattern and cholate-dependent, cholesterol-induced hepatomegaly in the FGFR4 (-/-) mice suggested that activation of receptor interacting protein 140, a co-repressor of feed-forward activator liver X receptor alpha, may mediate the negative regulation of cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase transcription by FGFR4 and cholate. The results demonstrate that transmembrane sensors interface with metabolite-controlled transcription networks and suggest that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for cell structures and signal transduction.

Animals↗

Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice.

The tumor suppressor SMAD4, also known as DPC4, deleted in pancreatic cancer, is a central mediator of TGF-beta signaling. It was previously shown that mice homozygous for a null mutation of Smad4 (Smad4-/-) died prior to gastrulation displaying impaired extraembryonic membrane formation and endoderm differentiation. Here we show that Smad4+/- mice began to develop polyposis in the fundus and antrum when they were over 6 - 12 months old, and in the duodenum and cecum in older animals at a lower frequency. With increasing age, polyps in the antrum show sequential changes from hyperplasia, to dysplasia, in-situ carcinoma, and finally invasion. These alterations are initiated by a dramatic expansion of the gastric epithelium where Smad4 is expressed. However, loss of the remaining Smad4 wild-type allele was detected only in later stages of tumor progression, suggesting that haploinsufficiency of Smad4 is sufficient for tumor initiation. Our data also showed that overexpression of TGF-beta1 and Cyclin D1 was associated with increased proliferation of gastric polyps and tumors. These studies demonstrate that Smad4 functions as a tumor suppressor in the gastrointestinal tract and also provide a valuable model for screening factors that promote or prevent gastric tumorigenesis.

Age Factors↗

Do health interview surveys yield reliable data on chronic illness among older respondents?

Previous research evaluating quality of health interview survey data has generally relied upon comparisons of household interview data with medical records or other external sources of information. However, "gold standards" are not always satisfactory or available. This paper illustrates an alternative approach to the evaluation of data quality-examination of the reliability of reports of chronic conditions in longitudinal surveys. The data come from national samples of older Americans (First National Health and Nutrition Examination Survey Epidemiologic Followup Study, 1971-1975, 1982-1984, 1986) and older Taiwanese (Survey of Health and Living Status of the Elderly, 1989, 1993, 1996). The results show that, among respondents who reported a chronic condition at a given interview, the likelihood that the condition was acknowledged at the subsequent interview was higher for hypertension and diabetes than for arthritis and stroke. Low levels of consistency for stroke appear to result partly from the poor wording of questions. In Taiwan, younger, more educated persons and those experiencing severe conditions were somewhat more likely to acknowledge the condition at follow-up compared with their respective counterparts. Women and persons of high cognitive status in the United States and respondents in both countries who used a proxy to report the occurrence of a stroke were also more likely to acknowledge conditions at follow-up.

Adult↗

Radiation and intra-arterial cisplatin: effects on arteries and free tissue transfer.

OBJECTIVES: To determine the histopathologic effect of combined intra-arterial cisplatin administration and hyperfractionated external beam radiation treatment (HYPERRADPLAT) on potential recipient arteries in the neck and to analyze the efficacy of free tissue transfer (FTT) in patients undergoing HYPERRADPLAT. DESIGN: Cisplatin-perfused and nonperfused artery segments were harvested during planned interval neck dissection performed 6 to 10 weeks after HYPERRADPLAT. These segments were evaluated by light microscopy and transmission electron microscopy. All patients undergoing FTT after HYPERRADPLAT were reviewed retrospectively. SETTING: Academic medical center. PATIENTS AND INTERVENTION: Eight patients undergoing HYPERRADPLAT for head and neck squamous cell carcinoma and planned interval neck dissection were prospectively studied. All patients had a perfused artery sampled, and 3 also had a nonperfused (control) artery sampled. Five patients undergoing FTT after HYPERRADPLAT were retrospectively analyzed for outcome of FTT. RESULTS: No consistent histological or ultrastructural differences were detected between injected and noninjected arteries. Both demonstrated intimal thickening, collagen and elastin deposition in the intimal layer, and, occasionally, intimal smooth muscle proliferation. A smaller fraction of the injected and noninjected arteries demonstrated smooth muscle cell vacuolation, elastic fiber degeneration, and calcific deposits. Four of 5 FTTs in patients undergoing HYPERRADPLAT were successful. CONCLUSIONS: The changes seen in the injected and noninjected arteries were characteristic of ionizing radiation. Arteries treated with HYPERRADPLAT had no observable difference from vessels treated with radiation alone. These vessels can be used with caution as recipient vessels for FTT. Further clinical experience is needed to establish the expected results of FTT using these arteries.

Antineoplastic Agents↗

Optical coherence tomography as a method for identifying benign and malignant microscopic structures in the prostate gland.

OBJECTIVES: Optical coherence tomography (OCT) is a new optical imaging technique capable of providing cross-sectional imaging of tissue microstructure in vivo and in real time. OCT was used in the setting of the human prostate ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. METHODS: Multiple samples (3 to 6) were obtained from the radical prostatectomy specimens of 7 men with clinically localized (T1c-2, N0, M0) adenocarcinoma of the prostate. These specimens were 1 cm in length and 1 mm x 1 mm in rectangular cross section. Specimens were first imaged using OCT and then embedded and stained in preparation for histopathologic evaluation. Co-registration of the images obtained using OCT and standard histopathologic evaluation provided the basis for comparison. RESULTS: Structural architecture on the order of 50 to 150 microm within benign glandular epithelium, fibroadipose tissue, and malignant glandular epithelium could be resolved to a depth of approximately 0.5 mm using OCT. CONCLUSIONS: Microscopic resolution is possible in human prostatic tissue using OCT. Further studies using this technique to improve the detection and staging of adenocarcinoma of the prostate are ongoing.

Adenocarcinoma↗