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Biomedical subjects

A Weinstein

Publications and source records attributed to A Weinstein.

At least 37 records · Page 2Linked to original sources

Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma). METHODS: A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary. RESULTS: Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION: Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

Administration, Oral↗

Lymphocyte-reactive autoantibodies in human immunodeficiency virus type 1-infected persons facilitate the deletion of CD8 T cells by macrophages.

The number of peripheral blood CD8 T cells declines in advanced stages of human immunodeficiency virus (HIV) infection coinciding with the transition from a clinically asymptomatic state of infection to AIDS. Although blood monocytes/macrophages exhibit cytotoxicity for CD4 T cells soon after HIV infection, cytotoxicity against CD8 T cells occurs at the time when HIV infection advances. The cytotoxic reaction is mediated by immunoglobulins that bind to T cells and which can be eluted from them. The immunoglobulins enable macrophages from noninfected persons to destroy healthy T cells in tissue culture. Lymphocyte-reactive autoantibodies (LRAs) occur physiologically as a result of chronic allo- or self-antigen stimulation. Lymphopenic, autoimmune lupus erythematosus patients exhibit LRAs that facilitate the deletion of T cells by macrophages. It is proposed that LRAs represent an immunoregulatory cytotoxic mechanism that is activated after chronic immune stimulation and is engaged by HIV to deplete host lymphocytes.

Antilymphocyte Serum↗

Integrating the cognitive and physiological aspects of craving.

'Craving is generally considered a significant factor in opiate addiction that is associated with drug-dependence and in relapse to drug use after treatment'-ARC expert consensus (Pickens and Johanson, Drug and Alcohol Dependence 30: 127-131). There are however difficulties in defining craving and urges to use drugs and in associating craving with drug use and relapse. Tiffany [Psychological Review 97(2): 147-168] has reviewed a considerable number of studies that associated reports of craving with consumption measures of drugs and revealed only an overall modest correlation of 0.4. These findings call into question the general assumption that subjective cravings are invariably associated with drug use. Furthermore, it led to Tiffany's provocative argument that cravings are not necessary for drug use. We have addressed these issues by using a range of complementary techniques derived from research in related fields such as the cognitive psychology of anxiety and depression, physiological response measurements and positron emission tomography (PET) neuro-imaging. Initially we developed computerized assessments to probe cognitive dysfunction in addiction that related to biased processing of automatic thoughts and beliefs about craving and drug use in opiate-dependent subjects and alcoholics. Subsequently in an attempt to develop a reliable method of inducing craving we explored an imagery-based technique that relied on the memory of craving experiences. These experiments were conducted both in opiate addicts who had achieved abstinence and in those undergoing detoxification. Finally, we have begun a study to understand the neural mechanisms of craving using imagery-based procedures at the same time as performing PET studies of regional blood flow using the O15-labelled water technique.

Alcoholism↗

What makes alcohol-dependent individuals early in abstinence crave for alcohol: exposure to the drink, images of drinking, or remembrance of drinks past?

Craving is a major factor in addiction, predicting poorer outcome to treatment To improve our understanding of craving for alcohol, we have compared in the laboratory the effects of inducing craving for alcohol by exposure to the sight and the smell of an alcoholic beverage, imagery of craving scripts, and recall of autobiographical memories of craving. We used subjective measures of craving, together with autonomic measures, in 14 abstinent alcohol-dependent individuals in the first month after detoxification. All subjects reported a significant increase in ratings of urges after exposure to alcoholic drinks, following the imagery of craving and after recalling autobiographical memories of craving. Physiological measures have shown that craving imagery as well as memory induction were equally effective as exposure to alcoholic drinks in modestly increasing autonomic arousal (indicated by systolic blood pressure). Our preliminary findings support the existing evidence in nicotine and opiate dependence that images and memories are as effective as in vivo exposure in eliciting craving for drugs.

Adult↗

Laboratory evaluation in the diagnosis of Lyme disease.

PURPOSE: To provide a qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis. DATA SOURCES: A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996. DATA EXTRACTION: Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis. DATA SYNTHESIS: Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease. CONCLUSIONS: Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.

Bacteriological Techniques↗

Imagery of craving in opiate addicts undergoing detoxification.

Craving is a significant factor in opiate addiction that is associated with drug-dependence and in relapse to drug use after treatment. In order to better understand the psychological and physiological mechanisms of craving for opiates, we have developed an imagery-based procedure using personal verbal descriptions of craving in abstinent opiate addicts. Thirteen opiate addicts in detoxification were required to imagine and describe their craving experiences while autonomic measures of heart rate and arterial pressure were taken. Subjects displayed a significant increase in systolic blood pressure and heart rate while describing drug craving compared with neutral descriptions. Furthermore, an increase in systolic blood pressure during imagery of craving descriptions compared with neutral descriptions was observed. These results provide preliminary evidence that imagery is powerful in eliciting craving for opiates, as indicated by subjective ratings and autonomic measures. The implications of the results of this paper for the cue-exposure paradigm and contemporary models of addiction are being discussed.

Adult↗

Effect of glutathione depletion on the cytotoxicity of cisplatin and iproplatin in a human melanoma cell line.

Previous studies from our laboratory have indicated that glutathione (GSH) may affect the cytotoxicity of iproplatin to a greater extent than four other platinum agents tested including cisplatin. Therefore we studied the effect of GSH depletion by buthionine sulfoximine (BSO) on the cytotoxicity of iproplatin and cisplatin in a human melanoma cell line SK-MEL-2. Depletion of GSH was dependent on the concentration and time of incubation with BSO. BSO (100 microM) depleted GSH by 85% at 24 h and by 91% at 48 h. BSO (10 to 100 microM) by itself was not cytotoxic to SK-MEL-2 cells. At 85% depletion of GSH, cytotoxicity of iproplatin was increased by a factor of > 7 and that of cisplatin by < 2. These results confirm the previous finding that GSH interferes with the cytotoxicity of iproplatin to a significantly greater extent than that of cisplatin. Equitoxic IC65 and IC90 values of cisplatin (2 microM and 5 microM) or iproplatin (25 microM and 50 microM) had no effect on the intracellular GSH levels in SK-MEL-2 cells. Also, depletion of GSH by BSO had no effect on the accumulation of platinum from either cisplatin or iproplatin in this cell line. Our results suggest that the effect of GSH on the cytotoxicity of cisplatin and iproplatin in this cell line was not a consequence either of differences in GSH-Pt conjugate formation, or of differences in platinum accumulation induced by GSH depletion. GSH may have modulated the cytotoxicity of these platinum complexes by other means such as effects on DNA repair, apoptosis, free radical scavenging or through other yet unidentified mechanisms.

Antineoplastic Agents↗

Breast cancer risk and alcohol consumption: results from a large case-control study.

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.

Adult↗

Clinically occult avascular necrosis of the hip in systemic lupus erythematosus.

OBJECTIVE: To study the natural history of clinically occult avascular necrosis (AVN) of the hip in patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE (without symptoms referable to the hip) receiving at least 5 mg/day prednisone for > or = 6 months were screened by magnetic resonance imaging (MRI) for AVN of the hip. A complete MRI evaluating class and percentage of femoral head involvement, AP and lateral radiographs of the hips, bone scan, and physical examination were performed for patients with positive MRI. Medical records were reviewed for serologic and clinical variables that might predict AVN. Repeat MRI were obtained at 3, 6, and 12 months to assess possible progression or resolution of the lesion. Patients with negative screening MRI underwent repeat screening after one year to assess the one year incidence rate. RESULTS: Eleven asymptomatic hips (8%) in 8 patients (12%) had MRI documented AVN. The percentage of femoral head involvement ranged from 1 to 46%. One lesion was MRI class B, the remaining lesions were class A. The radiographic stage of 10 hips was stage 1, the MRI class B hip was stage 2. Risk factors for clinically occult AVN included Afro-American origin, Raynaud's phenomenon, migraine headaches, and a maximal corticosteroid dose of at least 30 mg/day. After 12 months, 43 of 58 patients with an initially negative MRI underwent repeat screening examinations; no new lesions were observed. CONCLUSION: Clinically occult AVN of the hip is common in patients with SLE. The short term natural history of these lesions appears stable without spontaneous healing or clinical or radiographic progression. Risk factors for these asymptomatic lesions are similar to the risks for symptomatic AVN and surgical intervention appears not to be indicated in these patients.

Adolescent↗

Traditional risk factors and ischemic stroke in young adults: the Baltimore-Washington Cooperative Young Stroke Study.

OBJECTIVE: To determine the association of hypertension, diabetes, and cigarette smoking with incidence of ischemic stroke in young adults. DESIGN: Case-control study. SETTING: Population-based sample of cases and controls. SUBJECTS: The study included 296 cases of incident ischemic stroke among black and white adults aged 18 to 44 years in central Maryland counties from the Baltimore-Washington Cooperative Young Stroke Study and 1220 black and white adults aged 18 to 44 years from the Maryland Behavioral Risk Factor Survey, a telephone survey of a random sample of the same region, to serve as controls. MAIN OUTCOME MEASURES: Logistic regression models were developed to determine the age-adjusted odds ratios for each risk factor. Population-attributable risk percent were computed based on the odds ratios and prevalence of each risk factor. RESULTS: The age-adjusted odds ratios (95% confidence intervals) for white men (WM), white women (WW), black men (BM), and black women (BW) were as follows: current cigarette smoking: WM, 2.0 (1.1-3.8), WW, 2.1 (1.1-4.3), BM, 3.3 (1.6-6.6), and BW, 2.2 (1.3-3.9); history of diabetes mellitus: WM, 22.9 (5.8-89.6), WW, 6.2 (1.9-20.2), BM, 4.2 (0.8-21.9), and BW, 3.3 (1.4-7.7); and history of hypertension: WM, 1.6 (0.7-3.2), WW, 2.5 (1.1-5.9), BM, 3.8 (1.8-7.9), and BW, 4.2 (2.4-7.5). The population-attributable risk percent (95% confidence intervals) were as follows: current cigarette smoking: WM, 22.6 (3.1-38.2), WW, 17.2 (4.0-34.0), BM, 40.5 (23.1-54.0), and BW, 29.1 (13.5-41.9); history of diabetes mellitus: WM, 19.0 (8.2-28.5), WW, 15.8 (3.8-26.3), BM, 13.2 (5.3-20.4), and BW, 22.1 (12.5-30.7); and history of hypertension: WM, 21.7 (6.2-34.6), WW, 21.3 (5.4-34.5), BM, 53.5 (39.0-64.4), and BW, 50.5 (37.1-61.1). CONCLUSIONS: Hypertension, diabetes mellitus, and current cigarette smoking are important risk factors in a biracial young adult population. Cigarette smoking and hypertension, the 2 most modifiable risk factors, were particularly important risk factors in young blacks.

Adolescent↗

Effects of the low-osmolality contrast medium ioversol (Optiray) on renal function in a geriatric population.

PURPOSE: To assess the incidence of nephrotoxicity following i.v. injection of the iodinated low-osmolality contrast medium ioversol 300 (Optiray) in a geriatric population compared with a control group aged under 60 years, neither group presenting any associated risk factors. MATERIAL AND METHODS: CT with i.v. bolus injection of ioversol 300 mg I/ml was performed at a mean dose of 1.36+/-0.06 ml/kg (range 1-2 ml/kg b.w.) in 47 patients aged over 69 years. Serum creatinine level was measured and creatinine clearance was calculated at 24, 48 and 72 h after the examination, and compared to a reference serum creatinine value taken before CT. The findings were compared with a control group of 44 patients aged under 60 years. RESULTS: No significant increase in serum creatinine (+0.6 mmol/l) or in creatinine clearance (+0.7 ml/min) was found during the course of 3 days after the injection. Only one patient (aged 82) presented an increase of 25% in serum creatinine (109 mmol/l). CONCLUSION: The trial did not demonstrate any significant difference between the 2 groups, although the elderly patients had a subclinical renal impairment revealed by the decrease of the initial creatinine clearance. The use of low-osmolality ioversol makes it possible to perform examination with an iodinated contrast agent without increasing the incidence of nephrotoxicity in elderly subjects.

Age Factors↗