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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 199 records · Page 11Linked to original sources
PubMed1994

The clinical, serologic and radiologic features of rheumatoid arthritis in ethnic black Zimbabwean and British Caucasian patients.

OBJECTIVE: To compare the clinical, serologic and radiologic expression of rheumatoid arthritis (RA) in UK Caucasian and ethnic black patients from Zimbabwe. METHODS: Standardized protocols and assessment criteria were used to study 84 black patients with no non-Bantu antecedents and 84 UK Caucasian patients with RA (matched for disease duration, sex and age). RESULTS: Articular manifestations of RA were less severe in the black patients with RA from Zimbabwe as shown by less early morning stiffness (p = 0.001), fewer patients with > or = 3 active joints (p = 0.01), fewer joint deformities (p = 0.004) and better grip strength (p = 0.001) in comparison to the white patients with RA from the UK. Caucasian patients had a higher frequency of extraarticular manifestations (p = 1 x 10(-6)) including rheumatoid nodules (p = 0.0001), Raynaud's (p = 0.01) and Sicca syndrome (p = 0.001). Toxic effects from disease modifying antirheumatic drugs occurred less frequently in black patients (p = 0.0002). More white patients had Ro and La antibodies. The radiologic changes in the black patients were less severe than those in the white patients. The distribution of erosions in hands and feet were different in the 2 groups of patients studied. There were no differences between the urban and rural black patients but a more detailed study involving a large number of patients is required to confirm this observation. CONCLUSION: Black patients with RA from Zimbabwe have a disease that is clinically and radiologically less severe with fewer extraarticular features when compared to UK white patients.

Adult↗
PubMed1994

Update on nasopharyngeal carcinoma in northern Israel.

PURPOSE: Because Israel is one of the world's intermediate risk areas for nasopharyngeal carcinoma (NPC), we continue to analyze retrospectively all referred cases. PATIENTS AND METHODS: We previously reported our work with 49 NPC patients, and we now extend our analysis to include an additional 26 patients. All our 75 patients were treated between 1968 and 1991 at the Northern Israel Oncology Center in Haifa. They were typical in the preponderance of male sex (74%), Mediterranean origin (80%) and late stage presentation (91%). All patients received a combination of photon and electron radiotherapy to the tumor site, base of skull and neck, with an average dose to the nasopharynx of 6095 cGy. Nearly 40% of the patients received combined modality treatment (CMT), i.e., cisplatin-based chemotherapy prior to radiotherapy. RESULTS: There was an overall complete response (CR) of 88%, with 44% of the patients experiencing recurrence. Serious complications occurred in 5%. We found a 5-year survival rate of 48% and a 10-year survival rate of 44%, with some indication that CMT was advantageous to later-stage patients with non-keratinizing histologies, but not to earlier stages nor to those with keratinizing squamous cell carcinoma (SCC). Pediatric patients had better survival rates. CONCLUSIONS: 1. The somewhat better survival performance of Arabs and Sephardic Jews may reflect their greater tendency to have the non-keratinizing histological variants (lymphoepithelioma and undifferentiated carcinoma). 2. Ethnicity was consistently prognostic, both as risk and survival factors. 3. The role of CMT in advanced non-keratinizing NPC should be explored in future randomized trials.

Adolescent↗
PubMed1994

Antithrombin III and trauma patients: factors that determine low levels.

A prospective (cohort) study was conducted to determine the incidence of low antithrombin III (AT III) levels and the association with selected clinical variables in adult trauma patients. One hundred sixty AT III levels were obtained on 50 consecutive trauma admissions to a community-based level I trauma center. Antithrombin III levels were drawn as soon after admission as possible and every other day thereafter. Thirty-one patients (62%) had at least one low AT III level (< 80%), whereas 15 concurrently drawn control levels were all > or = 90%. Low AT III levels were more common in patients with one or more of the following: base deficit less than -4 (39% vs. 0, p = 0.002); Injury Severity Score > 15 (48% vs. 16%, p = 0.04); and blood transfusion (32% vs. 5%, p = 0.04). All other variables (shock, surgical intervention, subcutaneous heparin, and sequential compression devices) were not statistically significant, although all six patients with shock had low levels. In conclusion, over 60% of adult trauma patients had low AT III levels at some time during hospitalization and these patients were clearly more severely injured. Further studies are required to determine if these patients are more susceptible to thromboembolic phenomena.

Adult↗
PubMed1994

AIDS-related Kaposi's sarcoma: a review.

Infection with the human immunodeficiency virus (HIV) is the primary cause of AIDS and related disorders. Infection with HIV results in diminished cellular immunity, propensity to opportunistic infections, and an increased incidence of certain neoplasms. Kaposi's sarcoma (KS) is the most common neoplasm in persons infected with HIV. This epidemic, or HIV-related KS, usually follows an aggressive course with involvement of skin, lymph nodes, and internal organs. Normally, the disease has a progressive clinical course despite being responsive to radio- or chemotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Kaposi's sarcoma in renal transplant recipients. Experience at Johannesburg Hospital, 1966-1989.

Between August 1966 and December 1989, 989 renal transplant recipients were followed up at the Renal Transplant Unit of Johannesburg Hospital. Seventy-five (7%) patients developed a total of 95 malignancies of which 5 (6%) were Kaposi's sarcoma. All patients received immunosuppressive agents; steroids, azathioprine and/or cyclosporin A. Clinical presentations included both limited skin involvement (1 patient) and disseminated forms of the disease: necrotic oral lesions (1 patient); disseminated skin involvement and lung metastases (1 patient); and widespread skin lesions with lymphadenopathy (2 patients). Four patients responded with complete tumour regression at all sites upon withdrawal of the immunosuppressive drugs. One patient suffered disease progression, and immunosuppression was continued, albeit at reduced dosages. These cases illustrate a relatively rare complication of immunosuppressive therapy. However, complete withdrawal of immunosuppressive drugs may result in sustained complete regression, despite the presence of advanced KS.

Adult↗
PubMed1993

Pathological stage I endometrial carcinoma: the role for adjuvant radiotherapy.

BACKGROUND: In order to assess the efficacy of adjuvant radiotherapy in the treatment of pathological stage I endometrial carcinoma, we performed a retrospective analysis of 158 patients with this diagnosis who after surgery were either treated with radiation therapy or only followed from January 1980 through December 1987. METHODS: Patients were divided into two prognostic categories, high and low risk, on the basis of three known predictors of survival: histology, differentiation, and depth of myometrial invasion. All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy but only the high risk group received radiotherapy as well. RESULTS: After a median follow up time of 59 months the survival rates of the two groups were similar. The 5-year disease-free survival of the surgery alone group was 92% compared to 89% for the postoperative radiotherapy group. Side effects of treatment were minimal. CONCLUSIONS: Postoperative radiation therapy for high risk pathological stage I endometrial carcinoma is an effective adjuvant therapy and confers an excellent prognosis.

Carcinoma↗
PubMed1993

The management of metastatic spinal cord compression: a radiotherapeutic success ceiling.

PURPOSE: In assessing the effectiveness of the management of metastatic spinal cord or cauda equina compression, we performed a retrospective analysis of 70 patients with this complication whom we treated from 1985 to 1989. METHODS AND MATERIALS: The most frequent primary diagnoses in our series were carcinomas of unknown origin and of the breast, lymphoproliferative disease, lung cancer, and prostatic carcinoma. We used the Findlay classification to group all patients according to their pre-therapeutic functional motor status as Grade I (24 patients or 34%), Grade II (27, or 39%) or Grade III (19 or 27%). Treatment consisted of 30-45 Gy of irradiation (using two different schedules) together with high-dose dexamethasone; in only five cases was there surgical intervention. RESULTS: We found that a powerful predictor of response to radiotherapy was the patient's neurologic status (Findlay grade) at the time of diagnosis: 66% of previously ambulatory patients remained so, whereas 30% of non-ambulatory patients and only 16% of paraplegic patients regained the ability to walk. Another important predictor of response was primary tumor histology, with the most favorable responses to radiation therapy having been observed in lymphoproliferative diseases and in breast cancer, but with some response in other radiosensitive malignancies as well. CONCLUSION: The similarity of our results to those of other centers leads us to conclude that a radiotherapeutic success ceiling of 80% may have been reached for Findlay Grade I patients with metastatic spinal cord compression. In view of this, we suggest that future therapeutic endeavour would be best directed toward early diagnosis of the condition.

Adolescent↗
PubMed1993

Infection with the human immunodeficiency virus in prisoners: meeting the health care challenge.

The magnitude and the scope of health care problems posed by human prison inmates seropositive for the human immunodeficiency virus (HIV) are enormous. Prisoners represent a substantial proportion of HIV-infected individuals in North America. A high proportion of prisoners are intravenous drug users who often have not received appropriate health care or HIV-directed services prior to incarceration. Health care of HIV-seropositive prisoners and follow-up medical care after prison release has often been less than optimal. Among inmates at the prison facility in Rhode Island, 4% of the men and 12% of the women are HIV seropositive. The Brown University medical community, in conjunction with the Rhode Island Department of Health and Corrections, has developed an effective program for the health care of such prisoners, both during incarceration and after release from prison. Academic medical centers are uniquely poised to assume the leading role in meeting this obligation. We believe that this general approach, with region-specific modifications, may be effectively applied in many correctional institutions in North America.

Female↗
PubMed1993

Unusual case of renal Candida fungus balls.

Renal fungus balls are rare in the adult population. A case of asymptomatic renal pelvic fungus balls is presented, and several approaches to treatment are discussed.

Candidiasis↗
PubMed1993

Evidence of ex vivo and in vitro impaired neutrophil oxidative burst and phagocytic capacity in type 1 diabetes mellitus.

In this study neutrophil (PMN) oxidative burst activity was investigated ex vivo and in vitro in comparison to the PMN-phagocytic functions ingestion and bacterial killing in poorly-controlled type 1 diabetic patients. Luminol enhanced chemiluminescence in response to phorbolesters as a measure of oxidative burst was assessed in a parallel detecting microtiterplate luminometer in 40 poorly-controlled type 1 diabetic subjects. PMN ingestion was measured with [3H]thymidine-labelled Staphylococcus aureus in a kinetic radiometric assay. Microbicidal activity was determined by pure plate counting of surviving bacteria (colony forming units, cfu) after defined pmn challenge. PMNs of type 1 diabetic subjects showed a highly significant reduction of peak CL response in response to PMA compared to nondiabetic controls (P < 0.001) and PMN ingestion (51.8 +/- 4.6%) and bacterial killing (28.6 +/- 3.2%) were reduced as well (78.2 +/- 5.2% (IN) and 18.4 +/- 4.1% (BK), P < 0.01, respectively). The in vitro data displayed impaired PMN oxidative burst activity at glucose concentrations > or = 13.8 mmol/l whereas PMN IN and BK were significantly reduced at glucose levels > or = 27.75 mmol/l. In the control group there was a positive correlation of peak CL response and IN as well as BK (P < 0.05); in type 1 diabetic patients this was also true, but did not reach statistical significance. The data obtained in this study clearly demonstrated impaired PMN oxidative burst activity and markedly reduced ingestion and bacterial killing in type 1 diabetic patients ex vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Beta-adrenergic receptor-mediated release of norepinephrine in the human forearm.

Because of difficulties in separating the systemic from local effect, the role of presynaptic beta 2-adrenergic receptors in facilitating the neural release of norepinephrine has not been defined previously in humans in vivo. To determine whether stimulation of presynaptic beta-receptors alters local release of norepinephrine, we examined the effects on norepinephrine kinetics of 60 and 400 ng/min intra-arterial isoproterenol in seven healthy male volunteers. Isoproterenol, 60 ng/min, increased forearm norepinephrine spill-over sixfold from a baseline spillover of 0.45 +/- 0.08 to 2.89 +/- 0.69 ng/min (p < 0.01), whereas 400 ng/min isoproterenol increased forearm norepinephrine spillover to 13.25 +/- 2.49 ng/min (p < 0.005), a 29-fold increase above baseline. Coinfusion of 20 to 40 micrograms/min propranolol with 400 ng/min isoproterenol in four subjects significantly attenuated the isoproterenol-induced increase in local norepinephrine spillover to 2.09 +/- 0.92 ng/min (p < 0.05 versus 400 ng/min isoproterenol). This study shows that presynaptic beta-adrenergic receptors facilitate local release of norepinephrine in vivo in humans.

Adult↗
PubMed1993

Long-term exposure to beta 2-receptor agonist specifically desensitizes beta-receptor-mediated venodilation.

Desensitization of human vascular smooth muscle has not been shown after long-term exposure to agonist. Using the dorsal hand vein compliance technique, we measured the vascular sensitivity to isoproterenol, alprostadil, and nitroglycerin. Nine volunteers were studied after receiving no treatment or after 7 days of the beta 2-agonist terbutaline (5 mg three times daily). Terbutaline pretreatment desensitized the vascular response to isoproterenol, resulting in a fourfold increase in the dose of isoproterenol required to produce 10% vasodilation (geometric mean after terbutaline, 100.8 ng/min; without terbutaline, 26.7 ng/min; p < 0.001). The desensitization was specific for beta 2-receptor-mediated effects. We have therefore shown that dynamic regulation of vascular responsiveness by long-term exposure to beta 2-receptor agonist occurs in humans. This selective desensitization of vascular beta-adrenergic responsiveness will result in mixed alpha- and beta-adrenergic agonists, such as epinephrine, becoming relatively more vasoconstrictive, and it also has important implications in blood pressure response to stress.

Adrenergic beta-Agonists↗
PubMed1993

Secondary structure and protein folding of recombinant chloroplastic thioredoxin Ch2 from the green alga Chlamydomonas reinhardtii as determined by 1H NMR.

The recombinant form of the chloroplastic thioredoxin Ch2 from the green alga Chlamydomonas reinhardtii [Jacquot et al. (1992) Nucleic Acids Res. 20, 617] that preferentially activates the NADP dependent malate dehydrogenase [EC 1.1.1.82] (m-type thioredoxin) through a light promoted reductive system, has been subjected to an extensive two-dimensional 1H NMR analysis. A complete 1H NMR assignment of the resonance lines in both the oxidized and the reduced states at pH 5.8 has been obtained allowing the recognition of the secondary structure patterns and the global protein folding. The single polypeptide chain, made of 106 residues plus one additional Met located at the N-terminal position (11.6 kDa) due to the protein expression system, folds into a pattern characteristic of the open twisted alpha/beta structures already found for Escherichia coli and human thioredoxins for which the protein shares 46 and 20% of sequence identity, respectively. The open alpha/beta structure is made of 5 beta-sheets associated in a parallel (beta 1 to beta 3) and anti parallel manner (beta 3 to beta 5) and surrounded by 4 helices. This represents the first structural exploratory study of the ubiquitous oxido-reductase thioredoxins in a photosynthetic living system.

Amino Acids↗
PubMed1993

Sequence-specific oligonucleotide typing in Shona patients with rheumatoid arthritis and healthy controls from Zimbabwe.

Seventy-two patients with rheumatoid arthritis (RA) and 82 controls have been typed with the XI Histocompatibility Workshop DRB1 and DQB1 sequence-specific oligonucleotide probes. The increase of DRB1*04 corresponds to an increase of the serologically defined DR4, previously found in a small group of Zimbabwean RA patients and we now show that this increase is due to the subtype DRB1*0405 in association with DQB1*0302. In addition there is a clearcut increase of DRB1*1001 equivalent to the serologically defined DR10. There was no increase amongst RA patients of DRB1*0102 which was the predominant DR1 sub-type amongst controls. In the course of our investigation, we observed a DRB1*04 variant which corresponds to DRB1*0412, newly defined in the XIth Histocompatibility Workshop.

Arthritis, Rheumatoid↗
PubMed1993

Diurnal differences in basal and acute stress levels of type I and type II adrenal steroid receptor activation in neural and immune tissues.

To examine diurnal differences in the proportions of receptors that were occupied and activated by basal and stress levels of corticosterone, we measured available type I (mineralocorticoid) and type II (glucocorticoid) adrenal steroid receptor levels in brain, pituitary, and immune tissues of unstressed and acutely stressed rats at the times of day when basal corticosterone secretion was at its trough [morning (AM)] and peak [evening (PM)]. In general, the estimated adrenal steroid receptor activation was greater in brain than in pituitary or immune tissue, and within a particular tissue, there was a greater degree of estimated activation of the adrenal steroid high affinity type I receptor than of the type II receptor. There was a greater activation of brain type II receptors by basal corticosterone in the PM (30-35%) than the AM (5-15%). As acute stress produced similar levels of receptor activation at both times of day (45-50%), the net change in type II receptor activation in the brain after acute stress was much smaller in the PM than in the AM. This suggests that there may be diurnal differences in the role of type II receptors in corticosterone negative feedback on the hypothalamic-pituitary-adrenal axis. In immune tissues, type II receptor activation by acute stress was especially heterogeneous, depending on both the immune compartment and the time of day, suggesting that these are important factors contributing to a differential impact of corticosterone on immune responses during acute stress. Taken together our results suggest that the tonic and phasic influences of corticosterone on target tissue responses very not only with the diurnal and stress secretion patterns of corticosterone, but also with target tissue factors, such as type I and type II receptor expression and hormone bioavailability. All of these factors contribute to considerable selectivity of action for the systemic hormone corticosterone.

Adrenalectomy↗
PubMed1993

Differential expression of type I adrenal steroid receptors in immune tissues is associated with tissue-specific regulation of type II receptors by aldosterone.

We examined the influence of the type I adrenal steroid receptor agonist, aldosterone, on type II adrenal steroid receptor binding in the rat spleen and thymus after adrenalectomy. In the spleen, adrenalectomy was associated with a significant up-regulation of type II receptors, which was blocked by the concurrent administration of aldosterone (1 microgram/h) via sc osmotic minipumps. Neither adrenalectomy nor aldosterone treatment altered type II receptor binding in the thymus. Despite high doses of aldosterone (10 micrograms/h), which resulted in supra-physiological blood concentrations of this hormone, there was no evidence of type II receptor decreases in spleen or thymus below receptor levels found in sham-adrenalectomized rats. The effect of aldosterone on type II receptor binding appeared to be mediated by the type I receptor, since there was no aldosterone effect on the thymus, which did not exhibit detectable levels of type I receptor binding. Moreover, there was no evidence that aldosterone competed for the type II receptor in vivo or in vitro as determined by measurements of the type II receptor dissociation constant in the spleen of adrenalectomized, aldosterone-treated animals. Since selective activation of the type I receptor occurs in the spleen under physiological conditions, these results indicate that type I receptors may play a tonic inhibitory role in type II receptor expression in immune cells which express both receptor subtypes and reside in this tissue. Furthermore, the findings suggest that there may be different mechanisms involved in the up-regulation vs. the down-regulation of type II adrenal steroid receptors, and effects mediated solely via the type I adrenal steroid receptor appear only to influence the former process.

Adrenalectomy↗