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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 217 records · Page 12Linked to original sources
PubMed1993

Depression, adrenal steroids, and the immune system.

During the past decade, over 30 studies have examined the immune system in depression. While a number of investigators have reported depression-related alterations in peripheral blood immune cell number and function, many researchers have been unable to replicate these findings. The relationship between depression and the immune system has turned out to be much more complex than was initially anticipated. Factors which have complicated the interpretation of the research include the heterogeneity of depressed patients, the variability of immune assays, and the clinical relevance of these assays. In this review we conclude that alterations in the immune system do not appear to be a specific or reproducible biological correlate of depression but may occur in association with other variables which characterize depressed patients including age, sex and severity of depression. Conceptual frameworks for future research on the immune system and depression are discussed and include: (i) depression as a cofactor in the development, course and outcome of diseases involving the immune system; (ii) depression as a neuroimmunological disease; and (iii) depression as a model for studying neuroendocrine-immune interactions in humans. In terms of this third line of research, patients with depression consistently have been shown to display abnormalities in the secretion of adrenal steroids, and new data is presented which indicates that adrenal steroids may play a much more complex role in the modulation of the immune response than has been previously appreciated.

Adrenal Cortex Hormones↗
PubMed1993

Autoantibodies to phospholipids and brain extract in patients with the Guillain-Barre syndrome: cross-reactive or pathogenic?

Guillain-Barre syndrome (GBS) is a transient neurological disorder characterized by an inflammatory demyelination of peripheral nerves. Although the pathogenesis of GBS has not been elucidated, there is increasing evidence pointing to an autoimmune etiology. We have studied the reactivity of GBS sera with various phospholipids which are known to be important constituents of myelin, and serve as autoantigens in other autoimmune conditions. Sixteen Guillain-Barre syndrome (GBS) sera were studied for the presence of autoantibodies to ssDNA, dsDNA, cardiolipin (CL), phosphatidyl-ethanolamine (PE), phosphatidyl-choline (PC), phosphatidyl-serine (PS), and brain extract. Six of the 16 GBS sera had autoantibodies to one or more of the antigens studied. Three of the sera contained autoantibodies to brain extract (p < 0.05), two of the sera had autoantibodies to dsDNA, ssDNA, CL and PE, and one serum had autoantibodies to PC, and PS. As expected a significant proportion of the lupus sera contained autoantibodies to ssDNA and dsDNA, while the frequency of autoantibodies to different phospholipids was significantly high in sera of patients with systemic lupus erythematosus (SLE) and cerebritis. Absorption of GBS sera with cardiolipin, phosphatidyl-choline, or brain extract inhibited the binding of the sera to cardiolipin. Our results demonstrate that some GBS patients produce autoantibodies to various phospholipid and nuclear antigens. However, these autoantibodies are probably produced as a result of the myelin damage rather than cause the demyelination.

Adolescent↗
PubMed1993

Anaplastic seminoma and spermatocytic seminoma--a retrospective analysis.

Through the years 1968-1990, 10 patients with anaplastic seminoma and 7 patients with spermatocytic seminoma were referred to the Northern Israel Oncology Center, Haifa, Israel. These patients represent 20% of a total of 85 seminoma patients referred for treatment and follow-up. All patients underwent orchiectomy. Metastatic work-up revealed stage I disease in all patients. Sixteen patients received postoperative prophylactic radiation therapy to the para-aortic lymph nodes and the ipsilateral iliac region, dose range 25-30 Gy (daily fractionation 200 cGy). With a mean follow-up of 98 months, 15 patients are alive with no evidence of disease or long-term side-effects of treatment. One patient died of ischaemic heart disease without evidence of recurrent tumour. One patient with anaplastic seminoma died from progressive disease. In the light of our experience and a review of the literature, it is suggested that treatment of stage I non-pure seminoma should be based on the extent of disease alone and not on the degree of histological differentiation. Stage I non-pure seminoma has the same good long-term survival and low complication rate as typical seminoma when treated with adjuvant radiotherapy. Prospective, randomised trials are required to evaluate the role of a surveillance policy alone in stage I non-pure seminoma.

Adult↗
PubMed1993

[Impaired function of polymorphonuclear neutrophilic granulocytes in rheumatoid arthritis].

The aim of this study was to investigate the PMN functions ingestion (I), bacterial killing (BK) as well as the chemiluminescence response to phorbol esters (PMACL) as a measure of PMN respiratory burst activity in RA compared to osteoarthritis and controls. Our findings demonstrated a significant reduction of I and BK in RA compared to OA and controls (p < 0.01 resp.) but an enhanced PMACL (p < 0.01). There was no significant difference of I, BK and PMACL in OA and control subjects. These data clearly demonstrated impaired PMN ingestion and bacterial killing yet enhanced PMACL in RA, thus contributing at least in part to altered host defense in these patients.

Arthritis, Rheumatoid↗
PubMed1992

Adrenal steroid receptor activation in rat brain and pituitary following dexamethasone: implications for the dexamethasone suppression test.

The dexamethasone suppression test (DST) has been used extensively to evaluate feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis by adrenal steroids. Nevertheless, it remains unclear at what level of the HPA axis and through which adrenal steroid receptor subtype dexamethasone exerts its inhibitory effect. Because adrenal steroid receptor activation is an important prerequisite for dexamethasone to affect cellular function, HPA axis tissues that exhibit evidence of receptor activation following dexamethasone administration are likely site(s) of action for this synthetic hormone to inhibit HPA axis activity. Therefore, type-I and type-II adrenal steroid receptor activation was assessed in the pituitary, hypothalamus, and hippocampus of intact and adrenalectomized rats after overnight exposure to various oral doses of dexamethasone. Results with dexamethasone were compared to similar studies using corticosterone, the endogenous glucocorticoid of the rat. All dexamethasone doses led to significant type-II receptor activation in the pituitary, whereas only an exceedingly high dexamethasone dose activated type-II receptors in the hippocampus and hypothalamus. Dexamethasone had little effect on type I receptors in any tissue at any dose. In contrast, corticosterone significantly activated type-I receptors in all tissues, whereas it activated type-II receptors in the brain and not the pituitary at physiological concentrations. Because dexamethasone activated pituitary type-II receptors at blood concentrations that did not activate type-II receptors in the brain, these results suggest that the DST in humans may primarily be a measure of type-II adrenal steroid receptor feedback inhibition at the level of the pituitary.

Adrenalectomy↗
PubMed1992

[Multimodal management of bone sarcomas in children].

Osteogenic sarcoma and Ewing's sarcoma are the most common malignant bone tumors in childhood and adolescence. Marked improvement in prognosis and long-term survival have been achieved using combined modality protocols. We present a retrospective analysis of our experience with combined therapy of malignant bone tumors in children. Among 20 (ranging in age from 6-16, mean 11.4 years) with Ewing's sarcoma, 14 (70%) had complete remission by the end of treatment, 5 (25%) had partial response and 1 did not respond. The overall 10-year actuarial survival was 64%. Of the 10 with osteogenic sarcoma, 5 (50%) fully responded and are alive, 4 (40%) died after a partial or no response and 1 is receiving second-line therapy after partial response to primary treatment. The 10-year actuarial survival was 37.5% and the efficacy of combined modality therapy was demonstrated. However, further efforts are needed to arrive at optimal treatment for improved outcome.

Actuarial Analysis↗
PubMed1992

Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation.

Expression of the macrophage mannose receptor is inhibited by interferon gamma (IFN-gamma), a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (IL-4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of IL-4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine IL-4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 125I-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor alpha, mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish IL-4 as a potent and selective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN-gamma, characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion.

Animals↗
PubMed1992

[Experience with endometrial carcinoma].

A series of 261 patients with endometrial carcinoma treated between 1980-1987 was retrospectively analyzed. There were 154 pathological Stage I cases, 37 Stage II, 30 Stage III, and 2 Stage IV. Most patients were treated by surgery combined with radiotherapy; 33 were treated by brachytherapy and/or external irradiation alone. While most received postoperative irradiation, a minority received preoperative irradiation. The actuarial 5-year disease-free survival was 79% for all patients, and 89%, 85% and 60% for Stages I, II, and III patients, respectively; 2 in Stage IV died shortly after diagnosis. The 5-year survival probability for 25 clinical Stage I-II patients treated by radiotherapy alone was 32%. Univariate analysis revealed that prognosticators of survival included histological subtype (papillary carcinoma vs other histological types, p less than 0.001), and degree of differentiation (Grade III vs Grades I-II, p less than 0.001). The prognosis of Stage I patients with deep myometrial invasion was markedly improved by adjuvant irradiation. The disease recurred in 50 patients (19.1%): 3 developed isolated vaginal recurrence, 7 had pelvic recurrence, and 40 developed distant metastases, with or without locoregional failure. The probability of 5-year survival was 50% for those with pelvic recurrence, and 9% for those with metastatic spread; 3 with isolated vaginal recurrence died within less than 40 weeks after diagnosis of recurrence. Risk factors for locoregional and/or distant failure were histologic subtype (papillary vs other histologic types, p = 0.001) degree of malignancy (Grade III vs Grades I-II, p = 0.001) and myometrial invasion (deep vs superficial, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Experience with brain tumors in children].

A series of 74 children with brain tumors treated between 1971-1988 was analyzed retrospectively. The mean age was 8.1 +/- 4.0 years; the m/f ratio was 1.4. In 37 (50%) the tumor originated in a cerebral hemisphere, in 27 (37%) in the cerebellum, in 6 (8%) in the brain stem, and in 4 (5%) in the thalamus. Histological material was obtained in 53 patients (72%). 62 (84%) were treated surgically, 63 (85%) received radiotherapy and 14 (19%) chemotherapy. The actuarial 5-year survival of the whole group was 69%. There were few side effects.

Adolescent↗
PubMed1992

[Primary breast cancer: conservation therapy].

A series of 200 patients with primary breast cancer, treated with breast conservation between 1981 and 1988, was analyzed retrospectively. The mean age was 54 +/- 14 years and mean follow-up 36 months. 58 patients (29%) were in pathological Stage I, 85 (42.5%) in II A, 34 (17%) in II B, and 7 (3.5%) in III. 16 (8%) were in clinical Stages I-II; 40 (20%) had multifocal tumors and 40 intraductal components. 45% of the lesions were excised with good margins, 13.5% with close margins (0.5 cm), 9% with microscopic residual, 4% with macroscopic residual and in 57 (28.5%) margins could not be determined. Level II axillary lymph node dissection was performed in 193 (96.5%). Adjuvant therapy (combined chemotherapy and/or hormones) was given to 105 (52.5%). Radiotherapy usually consisted of 50 GY tangential photon irradiation to the whole breast in 25 fractions. Electron or photon boost to the tumor bed was given to 112 (59%). Most patients received 20 GY, and most node-positive patients 50 GY to the lymphatic drainage. 69% tolerated combined radiotherapy-chemotherapy well and radiotherapy did not have to be interrupted. A year after completion of radiotherapy the cosmetic result was rated as good in 166/173 (96%) and fair in 7 (4%); there were no poor ratings. 11 (5.5%) developed breast recurrence and 5 (2.5%) supraclavicular or axillary lymph node metastases. 1 (0.5%) developed local recurrence and supraclavicular lymph node metastases simultaneously. 50 (10%) developed distant metastases, of whom 2 developed loco-regional recurrences simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Quality of life in persons with human immunodeficiency virus infection: measurement by the Medical Outcomes Study instrument.

OBJECTIVE: To assess the reliability and validity of the Medical Outcomes Study (MOS) Short Form Health Survey as an indicator for quality of life in patients infected with the human immunodeficiency virus (HIV). DESIGN: Patient interview survey. SETTING: The AIDS Health Services Program in seven sites: Newark and Jersey City, New Jersey; Nassau County, New York; Atlanta, Georgia; Dallas, Texas; Fort Lauderdale and Miami, Florida; New Orleans, Louisiana; and Seattle, Washington. PATIENTS: Patients (520) with HIV infection receiving health services at one of the above sites. MEASUREMENTS: All components of the MOS Short Form Health Survey were included in the interview. Minor modifications were made to adapt the survey to the particular circumstances of the study. Measured sociodemographic characteristics included age, sex, race, intravenous drug use, and education. Symptoms were assessed by closed-ended questions concerning memory, seizure, weakness or numbness, fever, chills, diaphoreses, dyspnea, diarrhea, and weight loss. Information on the frequency of symptoms was also collected. History of Pneumocystis carinii pneumonia and Kaposi sarcoma was noted. MAIN RESULTS: The sociodemographic characteristics resemble those of patients with the acquired immunodeficiency syndrome (AIDS) reported to the Centers for Disease Control (CDC): mean age, 36; men, 89%; nonwhite, 31%; intravenous drug use, 34%. Neurologic symptoms (memory trouble, seizures, weakness or numbness) occurred in 71% of patients; constitutional symptoms (fever, chills, night sweats, weight loss) in 69%; dyspnea in 50%; and diarrhea in 47%. Although older age, female sex, nonwhite race, and intravenous drug use were associated with lower MOS scores in several areas, the strongest single or adjusted indicator of lower MOS scores was the presence of symptoms. Finally, patients with HIV infection had significantly lower scores than did previously reported patients with other chronic medical conditions (P less than 0.001). CONCLUSIONS: The MOS survey is a reliable measure of quality of life for patients with HIV infection. These patients tend to have low scores, suggesting validity of the survey. The MOS survey is extremely sensitive to the effect of symptoms, which suggests that it might be useful as a quality-of-life indicator for AIDS clinical drug trials.

Adult↗
PubMed1992

[Anaplastic seminoma of the testis].

Between 1968-1988, 9 patients with Stage I anaplastic seminoma were registered at this oncology center, representing 11% of 83 with testicular seminoma referred for treatment and follow-up. They ranged in age from 33-50, with a mean of 41. In all orchiectomy was performed and 8 of them received postoperative radiotherapy. After a mean of 60 months, 7 were alive with no evidence of disease, 1 had no evidence of disease and was lost to follow-up 152 months following radiotherapy, and 1 had died of metastatic disease. One of the survivors developed widespread metastatic disease but was saved by chemotherapy and is now alive and well. It is suggested that decision as to treatment of anaplastic seminoma should be based mainly on the extent of the disease, rather than the degree of differentiation.

Adult↗
PubMed1992

Second cancer in patients treated for testicular seminoma.

The exact risk of developing a second primary cancer following radiotherapy for testicular seminoma is not known. At the Northern Israel Oncology Center, between the years 1968-1988, 75 patients with early stage (I,IIA) testicular seminoma were treated by orchiectomy followed by radiation therapy. The overall 10- and 20-year survival probability was 95% and 90%, respectively. Eight patients (11%) developed nine second cancers, with a cumulative rate of one case per 1,000 years of follow-up. The second primary cancers were: two bronchogenic carcinomas, one contralateral seminoma, one thymoma, one papillary carcinoma of the thyroid, one carcinoma of the stomach, one transitional cell carcinoma of the urinary bladder, one carcinoma of the colon, and one malignant melanoma. Three of these tumors developed within the irradiated field. Five of these eight patients are alive with no evidence of recurrent cancer. We conclude that patients treated for seminoma have an increased risk of developing a second cancer. There is a need for greater awareness of this possibility. The overall prognosis remains favorable.

Combined Modality Therapy↗
PubMed1992

Causes of death in persons with human immunodeficiency virus infection.

PURPOSE: Pneumocystis carinii pneumonia (PCP) was reported to be the predominant cause of human immunodeficiency virus (HIV)-related deaths prior to 1988, the year that effective prophylaxis against PCP entered routine use. Our study was performed to study the causes of HIV-related death since January 1988 in a region where patient tracking is virtually complete. PATIENTS AND METHODS: We surveyed physicians associated with the Brown University Acquired Immunodeficiency Syndrome (AIDS) Program who cared for greater than 95% of known HIV-positive patients in Rhode Island. These physicians identified all those HIV-infected persons who had died under their care between January 1988 and July 1990, and determined these patients' causes of death by chart review. For comparison, death certificates of identified persons were also reviewed at the Rhode Island Department of Vital Statistics. RESULTS: Among 126 deaths since January 1988, bacterial infections were the most common cause of death (30%), whereas PCP was responsible for only 16% of deaths. Persons not receiving any form of PCP prophylaxis were more likely to die from PCP than were those who received prophylaxis (26% versus 11% [p = 0.04]). Cause of death as recorded on actual death certificates was imprecise, although bacterial infections were again the most common cause indicated. Only one death occurred in a patient with a CD4 count greater than 200/mL, and this was not HIV-related. CONCLUSION: PCP has not been the leading cause of death in our region since January 1988. Bacterial infections contribute substantially to mortality, and this may influence future prophylactic regimens. HIV-related deaths in patients with CD4 counts greater than 200/mL are unusual.

AIDS-Related Opportunistic Infections↗