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Biomedical subjects

M Steiner

Publications and source records attributed to M Steiner.

At least 127 records · Page 7Linked to original sources

TIMP-2 growth-stimulatory activity: a concentration- and cell type-specific response in the presence of insulin.

In addition to proteinase-inhibitory activities, growth-stimulatory activities have been described for all three known members of the tissue inhibitors of the metalloproteinase (TIMP) family, TIMP-1, TIMP-2, and ChIMP-3, believed to be the chicken homologue of TIMP-3. However, the mechanism by which the TIMPs stimulate cell growth is unclear. In this report we have demonstrated that rTIMP-2 was growth-stimulatory for human foreskin fibroblasts (HSF4, HSF43, HS68), lung adenocarcinoma cells (A549), human melanoma cells (WM115), and the Burkitt's lymphoma cell line RAMOS, and this stimulatory response was concentration-dependent, with the greatest stimulation occurring a 10-30 pM rTIMP-2 in [3H]thymidine incorporation assays and at 20-100 pM in cell growth assays. Normal human colon (18Co) and lung (37Lu) fibroblasts showed no response to rTIMP-2. [3H]Thymidine incorporation was inhibited by rTIMP-2 treatment in the nonadherent cell line HL60. These studies also demonstrated that for the cell types tested, TIMP-2 alone was insufficient for a growth stimulatory response requiring, at a minimum, the presence of insulin. In the absence of any "co-factor(s)," such as insulin, TIMP-2 treatment was inhibitory.

Cell Division↗

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors.

Adult↗

[Temporary keratoprosthesis, vitrectomy and autokeratoplasty in endophthalmitis treatment].

Postsurgical endophthalmitis frequently requires emergency vitrectomy. Loss of corneal transparency can preclude vitreoretinal surgery. Due to the narrow time frame in which surgical treatment needs to be performed, donor corneas are often not available for grafting. In addition, the risk of primary graft failure is higher in eyes with acute endophthalmitis. Later regrafting after primary graft failure carries a higher risk of graft rejection. By a clinical case of endophthalmitis after cataract surgery, we demonstrate the surgical technique of combined pars plana vitrectomy, keratoprosthesis, and autokeratoplasty. Loss of corneal transparency precluded standard pars plana vitrectomy with fundus contact lenses. The cornea was trephined and replaced by a keratoprosthesis. The trephined cornea was stored in tissue culture medium and pars plana vitrectomy was performed. At the end of the procedure, the keratoprosthesis was removed and the patient's own cornea was re-implanted. The transparency of the cornea improved during the postoperative course, permitting slit-lamp biomicroscopy of the anterior segment.

Aged↗

Measuring contraceptive effectiveness: a conceptual framework.

We present a conceptual model that outlines the four measures of how well a contraceptive method works: 1) efficacy, 2) effectiveness, 3) perfect-use pregnancy rate, and 4) typical-use pregnancy rate. Moreover, we illustrate how four variables influence these measures: 1) capacity to conceive, 2) frequency and timing of intercourse, 3) degree of compliance, and 4) inherent protection of the method. Because of inter-individual as well as intra-individual variability of the first three variables, generalizing results from a contraceptive clinical trial to other populations is problematic. There is a hierarchy of generalizability of the four outcome measures, with the typical-use pregnancy rate the least generalizable but the easiest to measure, and efficacy the most generalizable but the most difficult to measure. These four variables should be considered in the design and analysis of future contraceptive clinical trials. Finally, this article illustrates why the terms "pregnancy rate" and "failure rate" are not synonymous and why we recommend that the latter term not be used.

Clinical Trials as Topic↗

An integrated regional emergency psychiatry service.

This paper presents a model of an integrated Psychiatric Emergency Service serving Hamilton, a community of 450,000 in Southern Ontario. It describes the evolution of the service and how it has integrated five separate, hospital-run Emergency Psychiatric Services into a single service. The principles of the service and ways in which it operates are outlined and the advantages and drawbacks of the model are discussed. The authors conclude that such a model leads to a more efficient use of resources and is adaptable to most urban communities with a similar, or even larger population.

Delivery of Health Care, Integrated↗

Premenstrual dysphoric disorder. An update.

The recent inclusion of research criteria for premenstrual dysphoric disorder (PMDD) in the DSM-IV should help physicians recognize women with symptoms of irritability, tension, dysphoria, and lability of mood which seriously interfere with their lifestyle. PMDD can be differentiated from premenstrual syndrome (PMS) which is primarily reserved for milder physical symptoms and minor mood changes. The use of DSM-IV criteria in conjunction with prospective daily charting for at least two cycles is now accepted as common practice in confirming the diagnosis. Treatment options range from conservative lifestyle and stress management to treatment with psychotropic medications and hormonal or surgical interventions to eliminate ovulation for the more extreme cases. Results from several randomized placebo-controlled trials have clearly demonstrated that selective serotonin reuptake inhibitors as well as medical or surgical oophorectomy are very effective in treating PMDD. Taken together, these data indicate that treatment may be accomplished by either eliminating the hormonal trigger or by reversing the sensitivity of the serotonergic system.

Depressive Disorder↗

HIV-1 upregulates Fas ligand expression in CD4+ T cells in vitro and in vivo: association with Fas-mediated apoptosis and modulation by aurintricarboxylic acid.

CD4+ T-lymphocyte apoptosis has been associated with human immunodeficiency virus (HIV)-1 infection in vitro, paralleling the expression of Fas (APO-1, CD95) on peripheral blood mononuclear cells from patients with HIV disease. However, the link between Fas induction, T-cell activation, and cell death is unclear. We document, for the first time, marked upregulation of expression of mRNA for the ligand for Fas in peripheral blood mononuclear cells from HIV seropositive individuals, and demonstrate the ability of HIV infection to induce such expression in CD4+ T cells in vitro. We also define the relevance of this expression to HIV-mediated CD4+ T cell death. Our ability to downregulate Fas ligand message and suppress HIV-mediated apoptosis with aurintricarboxylic acid, a clinically used protease inhibitor with known activity against programmed cell death in other systems, may open up a new area of therapy for HIV infection.

Apoptosis↗

When death comes: where should patients die?

This study examines demographic, medical, and psychosocial variables in relation to preference regarding place of death on the part of 171 patients and their families treated at the Home Care Unit of the Oncology Department at Linn Clinic in Haifa, Israel, in 1992-93. Women who had breast cancer, and patients aged 50-59 with few mobility problems, preferred to die at home. Families with support from an extended family and those who communicated with the patients about the illness preferred to treat the patients at home. The patient's age, type of cancer, communication about dying, and the number of days hospitalized affected the place of death. Patients with prostate and brain cancer and patients aged 60 and older spent the most time (1-3 weeks) in a nursing home and tended to die there. Patients who were in a hospice tended to speak less about death than other patients.

Adult↗

A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids.

A double-blind crossover study comparing the effect of aged garlic extract with a placebo on blood lipids was performed in a group of 41 moderately hypercholesterolemic men [cholesterol concentrations 5.7-7.5 mmol/L (220-290 mg/dL)]. After a 4-wk baseline period, during which the subjects were advised to adhere to a National Cholesterol Education Program Step I diet, they were started on 7.2 g aged garlic extract per day or an equivalent amount of placebo as a dietary supplement for a period of 6 mo, then switched to the other supplement for an additional 4 mo. Blood lipids, blood counts, thyroid and liver function measures, body weight, and blood pressure were followed over the entire study period. The major findings were a maximal reduction in total serum cholesterol of 6.1% or 7.0% in comparison with the average concentration during the placebo administration or baseline evaluation period, respectively. Low-density-lipoprotein cholesterol was also decreased by aged garlic extract, 4% when compared with average baseline values and 4.6% in comparison with placebo period concentrations. In addition, there was a 5.5% decrease in systolic blood pressure and a modest reduction of diastolic blood pressure in response to aged garlic extract. We conclude that dietary supplementation with aged garlic extract has beneficial effects on the lipid profile and blood pressure of moderately hypercholesterolemic subjects.

Adult↗

Geographic factors and plasma selenium in uremia and dialysis.

The importance of selenium (Se) as an essential trace element for man has been increasingly recognized. Blood Se levels in chronic uremic patients are frequently reported to be lower than in controls. Definitive determination of the Se status in uremic patients, however, is hampered by the wide range of blood Se content in humans from different parts of the world. The present study was designed to assess and compare the Se status in two European populations from Rostock (Germany) and Chieti (Italy). Plasma Se levels were evaluated in healthy controls, chronic renal failure nondialyzed patients (CRF) and hemodialysis patients (HD). All Se determinations were performed in a single laboratory. The Se concentration was significantly higher (p < 0.005) in Italian healthy controls than in German healthy controls. In contrast, Se levels were similar in both CRF and HD patients from both cities. In both countries, the Se concentration in CRF and HD patients was significantly lower (p < 0.001) than in their corresponding controls, but no difference between CRF and HD was found. CRF and HD patients from the two countries showed quite similar laboratory and anthropometric data. In CRF patients in Chieti, a significant (p < 0.05) negative correlation between plasma Se and serum creatinine was found. In both HD groups, the length of time on HD and type of membrane dialyzer used did not influence the Se status. A significant positive correlation (p < 0.01) between Se levels and the protein catabolic rate was found in both HD groups. Uremia seems to be a strong factor which overrules the difference in Se levels that is present in healthy adults from different European countries. Uremia in itself may influence and level the Se concentration in patients with geographic diversity.

Adult↗

Effects of electroconvulsive therapy on peripheral adrenoceptors, plasma, noradrenaline, MHPG and cortisol in depressed patients.

BACKGROUND: The mechanism of the antidepressant action of electroconvulsive therapy (ECT) remains unknown. Based on previous work with antidepressant drugs and their effects on the noradrenergic system, we undertook this study to further determine the effects of ECT on selected indices of peripheral adrenoceptor function in depressed patients. METHODS: Binding parameters (Bmax and Kd) of platelet alpha 2- and leukocyte beta 2-adrenoceptors, plasma noradrenaline (NA), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and cortisol levels were determined in 18 patients, prior to treatment and 14 days after the last of a series of ECTs, and compared with samples obtained from 18 matched control subjects. RESULTS: Platelet alpha 2-adrenoceptor sites were significantly elevated in untreated patients compared with controls (P < 0.03), but leukocyte beta 2-adrenoceptor numbers did not differ. Treatment with ECT led to a significant reduction in platelet alpha 2-adrenoceptor numbers, whereas leukocyte beta 2-adrenoceptor densities increased. Pre-ECT plasma NA, MHPG, and cortisol levels were elevated in patients, compared with controls, and decreased following ECT, but these differences were not statistically significant. Post-ECT plasma NA and beta 2-adrenoceptor numbers were significantly, negatively correlated (P < 0.05). CONCLUSIONS: These results suggest that platelet alpha 2-adrenoceptors are supersensitive in depressed patients and treatment with ECT results in down-regulation of these receptors, which may be interpreted as a primary therapeutic, "normalising' effect. The post-ECT changes in leukocyte beta 2-adrenoceptors are probably only secondary to the lower circulating plasma NA levels.

Adult↗