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R Collins

Publications and source records attributed to R Collins.

At least 109 records · Page 6Linked to original sources
PubMed1996

Desmosomal cadherin binding domains of plakoglobin.

Plakoglobin is a major component of both desmosomes and adherens junctions. At these sites it binds to the cytoplasmic domains of cadherin cell-cell adhesion proteins and regulates their adhesive and cytoskeletal binding functions. Plakoglobin also forms distinct cytosolic protein complexes that function in pathways of tumor suppression and cell fate determination. Recent studies in Xenopus suggest that cadherins inhibit the signaling functions of plakoglobin presumably by sequestering this protein at the membrane and depleting its cytosolic pool. To understand the reciprocal regulation between desmosomal cadherins (desmoglein and desmocollin) and plakoglobin, we have sought to identify the binding domains involved in the formation of these protein complexes. Plakoglobin comprises 13 central repeats flanked by amino-terminal and carboxyl-terminal domains. Our results show that repeats 1-4 are involved in binding desmoglein-1. In contrast, the interaction of plakoglobin with desmocollin-1a is sensitive to deletion of either end of the central repeat domain. The binding sites for two adherens junction components, alpha-catenin and classical cadherins, overlap these sites. Competition among these proteins for binding sites on plakoglobin may therefore account for the distinct composition of adherens junctions and desmosomes.

Amino Acid Sequence↗
PubMed1996

Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy.

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.

Fibrinolytic Agents↗
PubMed1996

Glycolipids and myelin proteins in human oligodendrogliomas.

We studied myelin proteins and glycolipids in 24 human oligodendrogliomas (16 pure, eight mixed), including two grade I, 13 grade II, five grade III, and four grade IV. Tumours with a 1b ganglioside content (GD1b, GT1b and GQ1b) over 30% of total gangliosides occur more frequently in the WHO grade I and II (47%) and grade III (40%) than in the grade IV (25%) group; there was no difference in the amounts of total ganglioside or individual gangliosides between pure and mixed oligodendrogliomas. The presence of 6'-LM1 correlated with higher grades of tumours (chi 2 P approximately 0.02); however, 3'-LM1 and total neolacto-series gangliosides did not correlated with grade. Immunohistochemical studies of oligodendrocyte and myelin markers (GalCer, sulfatide, 2',3' -cyclic nucleotide phosphodiesterase, myelin basic protein and proteolipid protein) using specific antibodies showed only a very small proportion of tumour cells staining. These data do not support the hypothesis that tumours classified as oligodendrogliomas are derived from mature oligodendrocytes.

Brain Neoplasms↗
PubMed1996

Quality of care: issue or oversight in health care reform?

BACKGROUND: Health care reform is not dead but merely on hiatus. The vehicle for the reform is managed care, in particular health maintenance organizations (HMOs). HMOs employ primary care physicians as gatekeepers to act as regulators and points of entry into the health care system. It is through these gatekeepers that most dermatologic care is rendered. OBJECTIVE: Our purpose was to assess (1) the level of dermatology training of family practice physicians compared with dermatologists and (2) the impact on the delivery of quality dermatology services. METHODS: a national study of university residency programs was undertaken. Twenty color Kodachromes of typical cutaneous diseases were analyzed by the two physician groups. A questionnaire was used to evaluate the average formal dermatology training received, the number of primary dermatology patients examined by family practitioners, the correct response rates to the questions, and the dermatologic procedures performed by family practitioners. A total of 723 family practice physicians and 443 dermatologists responded. RESULTS: Our results indicate that, in comparison to dermatologists, primary care physicians significantly are deficient in their ability to recognize common and serious dermatoses. CONCLUSION: this study provides data emphasizing the need for reevaluation of the dermatology curriculum in medical schools and family practice residencies. Most important, it suggests that direct access to dermatologists provides better quality of care to members of HMOs and hence indirectly is most cost effective for the provision of dermatology services.

Cost-Benefit Analysis↗
PubMed1996

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study. Oxford Cholesterol Study Group.

1. It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2. Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44-129 weeks) after randomization. 3. The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4. No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5. This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.

Adult↗
PubMed1996

Allogeneic blood cell transplantation without posttransplant colony-stimulating factors in patients with hematopoietic neoplasm: a phase II study.

PURPOSE: There is limited experience with allogeneic blood cell transplantation (BCT). In an earlier pilot study, the combination of bone marrow and blood did not produce severe acute graft-versus-host disease (GVHD). We now report the results of a phase II study using blood stem cells alone in 19 patients. PATIENTS AND METHODS: The median age was 40 years. All patients had hematopoietic malignancies and received transplants from HLA-identical sibling donors. GVHD prophylaxis consisted of cyclosporine plus prednisone. Posttransplant colony-stimulating factors were not administered. Donors were mobilized with subcutaneous granulocyte colony-stimulating factor (G-CSF; 16 microg/kg/d) for 5 days. Apheresis was performed on 2 consecutive days. RESULTS: The median cell content of the two apheresis was 11.9 x 10(8) WBC/kg, 3.2 x 10(8) CD3/kg, and 8.3 x 10(6) CD34/kg. The median time to achieve an absolute neutrophil count (ANC) > or = 500/microL was 13 days, and 14 days to a platelet count > or = 50,000/microL. All patients engrafted. Platelet recovery was faster in marrow historic control groups. Blood cells in all tested cases contained more than 95% donor cells on day 30. The actuarial incidence of acute GVHD was 37%, and 13% for grade II-IV GVHD. Limited, corticosteroid responsive, chronic GVHD developed in 33% of assessable patients. At a median follow-up of 192 days, actuarial survival was 75%. CONCLUSION: Transplantation of a high number of stem cells may lead to rapid engraftment without the use of posttransplant colony-stimulating factors. GVHD does not appear to be more severe than in similarly treated patients undergoing bone marrow transplantation. For allogeneic transplantation, mobilized blood cell collections are an alternative to bone marrow collections.

Adult↗
PubMed1996

Comparison of four cytokine regimens for mobilization of peripheral blood stem cells: IL-3 alone and combined with GM-CSF or G-CSF.

Improved methods for mobilization may reduce the number of aphereses required to collect adequate numbers of peripheral blood stem cells (PBSC) and hasten engraftment following high-dose therapy. Mobilization with cytokines alone enables engraftment after myeloablative therapy. The optimal cytokine regimen for mobilization has not been established. The study evaluated the effects of four interleukin-3-containing cytokine regimens administered during steady state hematopoiesis on PBSC mobilization in 30 patients with breast cancer or lymphoid malignancies. These regimens included IL-3 alone (Arm 1), sequential IL-3 --> G-GSF (Arm 2), sequential IL-3 --> GM-CSF (Arm 3) and combined IL-3 + G-CSF (Arm 4). Consecutive days of apheresis were performed until a target of 4-6 x 10(8) mononuclear cells/kg were collected. All patients received intravenous GM-CSF after PBSC infusion. Median days to an ANC > or = 500/ microliters in Arm 3(22 days) was significantly slower than for patients in Arm 2 (13 days) but not significantly different from patients in Arm 1 or Arm 4. There was no significant difference in platelet engraftment or days of hospitalization between the study arms. Addition of GM-CSF to IL-3-containing mobilization regimens results in collection of PBSC that lead to delayed engraftment. Further development of Arms 1, 2, and 4 appear warranted.

Adult↗
PubMed1996

Maternal serum screening for birth defects: results of a Connecticut regional program.

Second trimester maternal serum screening provides a method to identify pregnancies at high risk for fetal Down's syndrome, trisomy 18, open neural tube defects, and a variety of other chromosomal and nonchromosomal fetal anomalies. Results are presented for a regional program to identify high-risk pregnancies using alpha feto-protein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) analyses (triple marker testing). A total of 27,140 women received screening. Using a midtrimester Down's syndrome risk of 1:270 to define the high-risk group, 5.26% of women of all ages were screen-positive for Down's syndrome resulting in the eventual detection of approximately 72% of the affected fetuses. The detection rate for patients under 35 at estimated date of delivery was 61% and for women 35, or older, the detection rate was 100%. A separate protocol to screen for trisomy 18 identified 0.2% of pregnancies, with 38% of the trisomy 18 cases present in this group. Over 3% of women screen-positive for Down's syndrome or trisomy 18 had a serious fetal chromosome anomaly. In addition, 2.89% of women had an elevated AFP (greater or equal to 2.0 multiples of median). This component of the screening resulted in the identification of 86% of the neural tube defects, 75% of the ventral wall defects, and also some of the other various fetal anomalies present in the screened population. Since both laboratory and clinical data are combined to generate patient-specific risks, there is a need for quality control elements that go beyond that normally required for a clinical laboratory alone. We stress the need for comprehensive follow-up programs to evaluate screening programs and maintain high quality.

Biomarkers↗
PubMed1995

Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14,000 cases and 32,000 controls in the United Kingdom. The International Studies of Infarct Survival (ISIS) Collaborators.

OBJECTIVES: To assess the effects of cigarette smoking on the incidence of non-fatal myocardial infarction, and to compare tar in different types of manufactured cigarettes. METHODS: In the early 1990s responses to a postal questionnaire were obtained from 13,926 survivors of myocardial infarction (cases) recently discharged from hospitals in the United Kingdom and 32,389 of their relatives (controls). Blood had been obtained from cases soon after admission for the index myocardial infarction and was also sought from the controls. 4923 cases and 6880 controls were current smokers of manufactured cigarettes with known tar yields. Almost all tar yields were 7-9 or 12-15 mg/cigarette (mean 7.5 mg for low tar (< 10 mg) and 13.3 for medium tar (> or = 10 mg). The cited risk ratios were standardised for age and sex and compared myocardial infarction rates in current cigarette smokers with those in non-smokers who had not smoked cigarettes regularly in the past 10 years. RESULTS: At ages 30-49 the rates of myocardial infarction in smokers were about five times those in non-smokers (as defined); at ages 50-59 they were three times those in non-smokers, and even at ages 60-79 they were twice as great as in non-smokers (risk ratio 6.3, 4.7, 3.1, 2.5, and 1.9 at 30-39, 40-49, 50-59, 60-69, 70-79 respectively; each 2P < 0.00001). After standardisation for age, sex, and amount smoked, the rate of non-fatal myocardial infarction was 10.4% (SD 5.4) higher in medium tar than in low tar cigarette smokers (2P = 0.06). This percentage was not significantly greater at ages 30-59 (16.6% (7.1)) than at 60-79 (1.0% (8.5)). In both age ranges the difference in risk between cigarette smokers and non-smokers was much larger than the difference between one type of cigarette and another (risk ratio 3.39 and 3.95 at ages 30-59 for smokers of similar numbers of low and of medium tar cigarettes, and risk ratio 2.35 and 2.37 at ages 60-79). Most possible confounding factors that could be tested for were similar in low and medium tar users, with no significant differences in blood lipid or albumin concentrations. CONCLUSION: The present study indicates that the imminent change of tar yields in the European Union to comply with an upper limit of 12 mg/cigarette will not increase (and may somewhat decrease) the incidence of myocardial infarction, unless they indirectly help perpetuate tobacco use. Even low tar cigarettes still greatly increase rates of myocardial infarction, however, especially among people in their 30s, 40s, and 50s, and far more risk is avoided by not smoking than by changing from one type of cigarette to another.

Adult↗
PubMed1995

Allogeneic transplantation combining mobilized blood and bone marrow in patients with refractory hematologic malignancies.

BACKGROUND: Mobilized blood stem cells have been used successfully in autologous transplant recipients to reduce the complications of pancytopenia due to dose-intensive chemotherapy. Reports of cytokine-mobilized blood progenitor cells in allogeneic transplant recipients are rare. STUDY DESIGN AND METHODS: This is a pilot trial of six patients. Patients with advanced hematologic malignancy received bone marrow (median total 2.6 x 10(8) mononuclear cells/kg) followed by four daily transfusions of blood (median total 9.5 x 10(8) mononuclear cells/kg) from HLA-matched sibling donors who were mobilized with recombinant human granulocyte-colony-stimulating factor (5 micrograms/kg/day subcutaneously for 5 days). All patients received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis. RESULTS: An absolute neutrophil count greater than 500 per mm3 was achieved on Day 12, and platelet transfusion independence was achieved on Day 16. The median day of hospital discharge was Day 23 after transplant. All patients achieved 100-percent donor cell engraftment. Acute > or = Grade III GVHD did not develop in any patients, but all patients developed Grade I (n = 4) or Grade II (n = 2) acute GVHD. Chronic extensive GVHD developed in four of six patients. One patient died of pneumonia 263 days after transplant while undergoing immune-suppressive therapy for chronic GVHD. CONCLUSION: The transfusion of blood stem cells in patients undergoing allogeneic bone marrow transplant is well tolerated soon after transplant, but the development of chronic GVHD may limit the general usage of unmanipulated blood stem cells.

Adult↗
PubMed1995

Absence of effect of simvastatin on the progression of lens opacities in a randomised placebo controlled study. Oxford Cholesterol Study Group.

AIMS: A detailed assessment of ophthalmic effects of an HMG CoA reductase inhibitor, simvastatin, was performed. METHODS: Six hundred and twenty one individuals considered to be at increased risk of coronary heart disease were randomised, following an 8 week placebo 'run in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin, or matching placebo. Patients with a baseline corrected visual acuity better than 6/24 and without a history of cataract were eligible for detailed ophthalmic assessment at 6 months (539 patients assessed) and at 18 months (474 patients assessed). RESULTS: No significant differences between the treatment groups were detected at the 6 month or 18 month visit in the refractive condition of the eye or in the mean intraocular pressure. Nor were there clear differences in the Oxford grading system scores for various measures of the major types of cataract (cortical spokes, posterior subcapsular cataract, nuclear brunescence, white scatter) or for other morphological features visible within the lens (fibre folds or focal dots). Scheimpflug slit image photographs and retroillumination analysis of the percentage of cataract within a defined region of the lens were also performed at each visit, with no clear differences observed between the treatment groups. CONCLUSION: This single centre double blind study found no good evidence of any adverse effects of 18 months of simvastatin treatment on lens opacity formation, using a variety of validated techniques to assess cataract development. Routine clinic follow up of visual symptoms and admission to hospital for ophthalmic procedures over 5 years of treatment was also reassuring, with no excess adverse outcomes observed with simvastatin.

Adult↗