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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 19 recordsLinked to original sources
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↗
PubMed1992

The value of postoperative irradiation in renal cell cancer.

This is a retrospective analysis of 147 evaluable patients, with histologically proven renal cell carcinoma, who were referred to our center between 1977 through 1988. All patients with disease limited to the kidney underwent nephrectomy. Post-operative megavoltage irradiation, with a median dose of 46 Gy, was given to 56 patients, using parallel opposing portals, or multiple field technique. Five and 10 year actuarial survivals in irradiated patients (Rt+) were 50 and 44%, respectively, and in non-irradiated patients (Rt-) 40 and 32%, respectively. The disease recurred locally in a total of 19 patients; 16 had tumor bed recurrence and three had scar recurrence. Local recurrence by stage was as follows: T2 N0M0: RT+ 0/17, RT- 2/28; T3 N0M0: RT+ 4/37 (10%), RT- 11/30 (37%) (p less than 0.05); T4 N0M0: RT+ 1/2, RT- 1/5. Two of the local recurrences in irradiated patients developed in a surgical scar which was not included in the treatment volume. Significant toxicity developed in three patients (5%). It is concluded that post-operative irradiation can reduce local recurrence rate in T3 N0M0 renal cell carcinoma. It is recommended that the surgical scar should always be included in the treatment volume and irradiated to a full dose.

Actuarial Analysis↗
PubMed1992

Viscosity and social cohesion in temporal lobe epilepsy.

Clinical case reports suggest that viscosity, the behavioural tendency to talk repetitively and circumstantially about a restricted range of topics, is common in patients with temporal lobe epilepsy (TLE). Such patients are also reported to exhibit heightened levels of social cohesion, the tendency to become interpersonally "clingy". This "sticky" interpersonal style may be particularly common in TLE patients with a left sided temporal lobe seizure focus. To test this hypothesis, self-report and observer rating scales were developed to assess both viscosity and social cohesion. Subjects consisted of patients with right, left, or bilateral temporal lobe seizure foci, absence or primary generalised tonic-clonic seizures, psychiatric controls (panic disorder patients), and normal controls. Elevations on the viscosity scale were observed primarily in TLE patients with left or bilateral seizure foci. Viscosity scores also correlated with seizure duration and left handedness. No group differences were observed on the social cohesion scale. These findings are consistent with the hypothesis that viscosity results from subtle interictal language disturbances, although other pathogenetic mechanisms are discussed.

Anomia↗
PubMed1992

Pneumatic reduction of intussusception: 5-year experience.

Pneumatic reduction of 246 intussusceptions was attempted in 219 patients over a 5-year period. The mean age of the patients was 15.4 months. Successful reduction was achieved in 199 cases (80.9%). Bowel perforation occurred in seven cases (2.8%), requiring needle decompression of tension pneumoperitoneum in one case. Recurrence of intussusception occurred in 27 cases (11%). The mean fluoroscopy time was 3.5 minutes +/- 0.2 in successful reductions and 9.3 minutes +/- 0.9 in failed reductions (P less than .001). Logistic regression analysis helped identify four independent predictors of failure, as follows: (a) ileoileocolic intussusception (P less than .001), (b) long duration of symptoms (P less than .001), (c) rectal bleeding (P less than .01), and (d) failed reduction with barium at another institution (P less than .05). Predictors of bowel perforation were a younger age (P less than .05) and long duration of symptoms (P less than .05). Surgery was performed in 48 cases (19.5%), 16 of which required bowel resection. Transmural necrosis of bowel wall was found in nine specimens. The most important predictor of outcome in this series was a long duration of symptoms. Pneumatic reduction is a useful substitute for barium in the management of pediatric intussusception.

Air↗
PubMed1992

Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes.

OBJECTIVE: In this study, ingestion of Staphylococcus aureus and "bacteria killing" (BK) were measured to evaluate polymorphonuclear leukocyte (PMN) phagocytic functions and chemiluminescence response (CL) to phorbol-myristic acetate (PMA) as respiratory burst activity with regard to metabolic control parameters in diabetic patients. RESEARCH DESIGN AND METHODS: PMN phagocytic functions were assessed in 40 diabetic patients, all receiving insulin and in poor metabolic control, with 3H-thymidine-labeled Staphylococcus aureus in a modified radiometric assay. Bacteria killing was determined by pure-plate counting of surviving bacteria (colony-forming units [cfu]) and luminol-enhanced CL in response to PMA as a measure of respiratory burst. PMN function data were correlated to HbA1 as parameter of recent metabolic control. RESULTS: PMN of diabetic patients showed a significant reduction in Staphylococcus aureus (50.7 +/- 4.1%) and BK (29.4 +/- 4.2%) compared with healthy nondiabetic control subjects (76.6 +/- 4.6% and 16.3 +/- 3.1%, respectively, P less than 0.001), and PMN CL response was markedly reduced in diabetic patients also. Linear regression analysis showed a highly significant negative correlation of HbA1 versus Staphylococcus aureus (r = -0.67, P = 0.001) and a positive correlation for BK (r = 0.73, P less than 0.001). This was also true for CL, although this did not reach statistical significance (P = 0.06). CONCLUSIONS: The data obtained demonstrate impaired PMN phagocytic functions and CL response in diabetic patients. These findings suggest inhibitory effects of elevated glucose concentrations on PMNs, a possible role of protein glycosylation for impairing PMN function, thus contributing in part to altered host defense.

Adult↗