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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 559 records · Page 31Linked to original sources
PubMed1990

Expression of glycolipid receptors to Shiga-like toxin on human B lymphocytes: a mechanism for the failure of long-lived antibody response to dysenteric disease.

Fresh and transformed human B lineage cells were found to be sensitive to the cytotoxic action of Shiga-like toxin (SLT), a bacterial cytotoxin. The toxin was specifically bound by the glycolipids globotriosylceramide and galabiosylceramide expressed on the surface of sensitive cells. Mutant Daudi cells selected for resistance to SLT cytotoxicity (SLTR20) were deficient in SLT-binding glycolipids and failed to bind SLT to their surface, suggesting a role for these glycolipids in the mediation of SLT cytotoxicity. Of a number of normal and transformed lymphoid and myeloid cells screened for SLT sensitivity, only B lymphoid cells were susceptible to SLT action. Moreover, B lymphoid cells were the only cells expressing the SLT binding glycolipids. In vitro B cell activation studies with Epstein-Barr virus and pokeweed mitogen both indicated that the vast majority of SLT-sensitive B cells belong to the IgG and IgA committed subset, whereas most IgM and IgM/D producing cells were resistant to SLT toxicity. The selective elimination of IgG and IgA committed cells may explain the production of only IgM class anti-SLT antibodies in Shigella-infected humans leading to the failure of long-term immunity to dysenteric disease.

Antibodies, Bacterial↗
PubMed1990

Treatment of transfusional iron overload.

Advances in the treatment of iron overload hold the promise of making long-term transfusion therapy a safer approach to the management of thalassemia major, sickle cell disease, and numerous other hematologic disorders. The responsibility now placed on the treating physician is to monitor iron stores carefully, to begin chelation therapy at an appropriate time, and to encourage regular use of deferoxamine. For the clinical investigator, the success of chelation therapy with deferoxamine should prompt an intensive search for new chelators. These new chelators should be not only effective but also inexpensive, readily available, safe, and easy to administer.

Administration, Oral↗
PubMed1990

Steroid-tipped leads versus porous platinum permanent pacemaker leads: a controlled study.

There is little data directly comparing steroid-tipped permanent pacemaker leads to otherwise state-of-the-art porous platinum leads. Eighteen patients receiving unipolar generators capable of low voltage outputs were randomized at the time of implant to receive either steroid-tipped leads or porous platinum leads. All leads were unipolar, tined, passive fixation, and placed in the right ventricular apex or atrial appendage. This study is single center. At implant, threshold pulse width was determined at 3 voltages (2.5, 1.5, and 0.8 V). Follow-up thresholds were determined at weeks 1, 2, 3, and 4, and at 3 and 6 months. There was no difference in implant thresholds or amplitudes for sensing. By 2 weeks postimplant, lower thresholds were noted for the steroid leads, and this discrepancy grew more significant with time. There was no significant postimplant rise in threshold for steroid-tipped leads. At 6 months, the average threshold pulse width for ventricular steroid leads at 0.8 V was 0.3 +/- 0.1 msec. In contrast, five patients with standard leads did not capture at maximum pulse width at 0.8 V (P less than 0.0001). There was no significant difference in the amplitude of the chronic atrial electrogram. This study shows steroid-tipped leads to offer a significant advantage in reducing thresholds early postimplant and chronically.

Aged↗
PubMed1990

Comparison of propranolol and sotalol pharmacokinetics in obese subjects.

Six obese subjects (mean +/- s.d. : 145.1 +/- 16.7% of ideal body weight) were randomly assigned to a single i.v. dose either of (+/-)-propranolol base (0.108 mg kg-1 of ideal body weight) or of (+/-)-sotalol base (1.06 mg kg-1 of ideal body weight). Each subject received the other drug 7 days later. Pharmacokinetic parameters were compared with those obtained previously in non-obese control subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were comparable with those measured in controls (total body clearance = 9.4 +/- 2.9 L h-1; volume of distribution during the terminal phase = 79.8 +/- 19.8 L or 0.9 +/- 0.2 L kg-1; terminal half-life = 6.2 +/- 1.6 h). For propranolol, total clearance (44.3 +/- 15.9 L h-1) and volume of distribution (230.5 +/- 48.2 L or 2.7 +/- 0.7 L kg-1) were significantly less than control values. The terminal half-life (3.9 +/- 1.1 h), was not significantly increased. These results could be explained by altered tissue blood flow and a decreased metabolic capacity of the liver in obese subjects.

Adult↗
PubMed1990

Isolation, identification, and characterization in Israel of Brucella melitensis biovar 1 atypical strains susceptible to dyes and penicillin, indicating the evolution of a new variant.

During characterization by conventional biotyping tests of numerous Brucella melitensis isolates obtained in Israel in the last 2 years, we identified several strains of the biovar 1 serotype that are atypically susceptible to dyes and penicillin. Their coisolation from two brothers in a family that rears sheep and from the milk of one of their sheep and the prevalence of such strains in two distinct geographical zones in Israel provide epidemiological support for the notion that a new variant has been identified.

Animals↗
PubMed1990

Prolonged duration of blood pressure response to enalkiren, the novel dipeptide renin inhibitor, in essential hypertension.

The effects of sustained renin inhibition by repeated administration of enalkiren (A-64662), the novel dipeptide renin inhibitor, were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study of 32 inpatients (eight per group) with essential hypertension who were maintained on a diet containing 60 meq/day sodium. Three different dosage regimens of enalkiren were studied: 1) 1.2 mg/kg quotid., 2) 0.3 mg/kg q.i.d., and 3) 0.1 mg/kg q.i.d. Each patient received an intravenous infusion every 6 hours for 1 week. Placebo infusions were used to mimic the 4 times/day dosing schedule. Blood pressure was measured periodically via 24-hour automated monitoring equipment. Mean plasma renin activity in the patient groups ranged from 1.58 to 2.68 ng angiotensin I/ml/hr. Plasma renin activity was promptly suppressed in all groups receiving enalkiren. Prolonged duration of plasma renin activity suppression (greater than or equal to 24 hours) was demonstrated after the administration of 1.2 mg/kg enalkiren. The 0.3 mg/kg q.i.d. and 1.2 mg/kg quotid. regimens produced statistically significant reductions (p less than or equal to 0.05) in systolic and diastolic blood pressures with clear evidence of persistent antihypertensive activity for 12 hours or more when compared with the placebo group. Despite relatively large reductions in mean systolic and diastolic blood pressure, mean pulse rates were essentially unchanged. The prolonged reduction in blood pressure with enalkiren without evidence of tachyphylaxis after 1 week of treatment suggests that renin inhibitors may emerge as useful therapeutic agents for the treatment of hypertension.

Adult↗
PubMed1990

Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33.

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.

Adult↗
PubMed1990

Effect of adrenalectomy at different pregnancy stages on maternal and fetal serum corticosteroid binding globulin and corticosterone in the rat.

The response of pregnant rat corticosteroid binding globulin to maternal adrenalectomy was studied as a function of the stage of pregnancy. Non-pregnant or pregnant rats were deprived of their adrenal glands during 4 days. In non-pregnant animals, adrenalectomy led to undetectable corticosterone levels and to the doubling of corticosteroid binding globulin. In pregnant rats adrenalectomized at 12 days and studied at 16 days, the serum corticosterone was likewise undetectable and the corticosteroid binding globulin was doubled as compared with pregnant rats of the corresponding age. In contrast, adrenalectomy from day 14 to 18 or from day 16 to 20 did not deplete the maternal serum corticosterone and the corticosteroid binding globulin remained unchanged. Under these conditions neither fetal corticosteroid binding globulin nor fetal corticosterone were modified. However, when the pregnant rats adrenalectomized from day 16 to 20 also received an injection of 30 mg of metyrapone on days 19 and 20 in order to inhibit fetal adrenal secretion, the maternal response was again a depletion of serum corticosterone together with an increase in corticosteroid binding globulin. Under these conditions, the fetus also reacted by a fall of corticosterone and a rise of corticosteroid binding globulin. Our results suggest that the maternal response of corticosteroid binding globulin to adrenalectomy depends on the pregnancy stage inasmuch as it may be influenced by a supply of corticosterone from the fetus during late pregnancy. Moreover, they show that in this late period, fetal corticosteroid binding globulin is regulated independently.

Adrenal Glands↗
PubMed1990

Development of competence in clerkship.

Students' perceptions of their educational experience on Surgery and Medicine rotations of a clerkship program were analysed. Six components of the education process, namely (1) frequency of individual teaching, (2) quality of contact with staff-clinicians, (3) appropriateness of responsibility for patient care, (4) appropriateness of supervision received, (5) frequency of admissions reviewed and (6) frequency of opportunity to follow-up patients admitted, were correlated with students' confidence in their ability to function competently. Mean scores of clerks' confidence in their competence was the same for both rotations. Breakdown by sex revealed females to feel more competent on medicine, and males on surgery. On the medicine rotation a moderate relationship was found between two of the components tested and the dependent variable; on surgery, strong correlations were found between four of the components tested and the dependent variable. Regression analysis demonstrated appropriateness of responsibility for patient care to have a low predictor value for achievement of competence on medicine, while quality of contact with staff-clinician and appropriateness of supervision received were strong predictors of achievement of competence on the surgery rotation.

Attitude of Health Personnel↗
PubMed1990

Mortality of cellulose fiber production workers.

Mortality was studied among 1271 employees of a cellulose fiber production plant in Rock Hill, South Carolina, in the United States. Each subject was employed for at least three months between 1 January 1954 and 1 January 1977 in jobs that entailed exposure to the highest concentrations of methylene chloride. In the cohort 122 deaths were identified through 1 September 1986, and mortality rates for the cohort were compared with mortality rates for York County, South Carolina. Deficit mortality was observed for cancers of the respiratory system, breast, and pancreas and from ischemic heart disease. Excess mortality was observed for cancers of the buccal cavity and pharynx and the liver and biliary tract, and for melanoma as well. The largest relative excess was for liver and biliary tract cancers. There were only four deaths in this category; however, three of the four deaths were cancer of the biliary tract (3 observed, 0.15 expected, standardized mortality ratio 20).

Biliary Tract Neoplasms↗
PubMed1990

Immunoblotting of plasma in a pregnant patient with hereditary angioedema.

Hereditary angioedema (HAE), an autosomal disorder caused by a deficiency of C1 inhibitor, is characterized by attacks of localized swelling, laryngeal edema, or abdominal pain. Plasma samples from one pregnant patient were studied serially by functional and quantitative immunochemical assays as well as immunoblot assays for high molecular weight kininogen (HMWK) and/or prekallikrein/kallikrein (PK/K). An immunoblot of this patient's HMWK from plasma obtained before she became pregnant and when she was well revealed that it was mostly an intact protein of 120 kd, similar to immunoblot results of normal plasma HMWK. In plasma samples taken throughout her pregnancy, before, during, and after clinical attacks of angioedema, all of her plasma HMWK was shown to be cleaved into the 45 kd light chain form. After delivery of the infant the 120 kd form of intact plasma HMWK returned to her plasma. In comparison, immunoblot studies on 21 normal and abnormal pregnancies revealed that plasma HMWK was an intact protein at 120 kd. That this patient's plasma during her pregnancy was contact activated was determined by additional immunoblot studies for PK/K. Immunoblot assay for plasma PK/K revealed kallikrein-alpha 2-macroglobulin complexes and a 50 kd PK/K form seen only in activated plasma samples. The findings of kallikrein-alpha 2-macroglobulin complexes and a 50 kd PK/K form disappeared after delivery. These combined studies on this patient show that the structures of HMWK and prekallikrein as indicated by immunoblot assays were altered during pregnancy. Immunoblot assays for detection of changes in the structure of HMWK and prekallikrein may be objective laboratory studies for documenting clinical attacks of hereditary angioedema, their onset, and their resolution.

Adult↗
PubMed1990

[Study of valvular prostheses by Doppler echography].

Doppler echocardiography is a reliable non-invasive method of following up patients with prosthetic heart valves. Transthoracic M mode and two-dimensional echo allow evaluation of the movement of the mobile element of the prosthesis and of the size of the cardiac chambers. Doppler studies (transprosthetic pressure gradient, valve surface area, trans- and periprosthetic regurgitation) give an indication of the hemodynamic profile of the prosthesis. Transesophageal echocardiography is especially useful when there are abnormalities suggestive of prosthetic valve dysfunction (fever, systemic embolism, clinical symptoms, haemolysis...).

Aortic Valve↗
PubMed1990

[The value of recording the pulmonary insufficiency flow by continuous Doppler for the evaluation of systolic pulmonary artery pressure].

Systolic, diastolic and mean pulmonary artery pressures can be evaluated by Doppler recordings of the maximal velocity of tricuspid regurgitation and early and late diastolic pulmonary regurgitant flow. The aim of this study was to assess the reliability of the calculation of systolic pulmonary artery pressure from pulmonary regurgitant flow by comparing the values with those obtained from the tricuspid regurgitant flow in the same patient. With this objective in mind, we investigated 70 patients with an average age of 45 +/- 34 years, in sinus rhythm, all of whom had tricuspid and pulmonary regurgitant jets which could be recorded with continuous wave Doppler. Systolic pulmonary artery pressure was calculated as follows: from tricuspid regurgitation: maximum pressure gradient + 10 mmHg; from pulmonary regurgitation: 3 x early diastolic gradient - 2 x late diastolic gradient + 10 mmHg. The systolic pulmonary artery pressures calculated from tricuspid and pulmonary regurgitation were: 42 +/- 16 mmHg and 43 +/- 17 mmHg respectively (r = 0.97) with an estimated standard error of 4.7 mmHg. These results show that the recording of pulmonary regurgitation by continuous wave Doppler allows accurate estimation of pulmonary artery pressures. The calculation by the two methods using tricuspid and pulmonary regurgitant jets increases the reliability of the results and provides a means of internal validation of the Doppler technique.

Adolescent↗
PubMed1990

[Dynamic left ventricular obstruction increased by nitroglycerin in elderly patients with hypertension and concentric left ventricular hypertrophy].

Left ventricular outflow tract (LVOT) obstruction has been observed in elderly patients with concentric hypertrophic hypertensive cardiomyopathy (HHCM) and no significant valvular disease or regional wall motion abnormalities. In order to determine whether nitroglycerin (NTG) can increase the intraventricular obstruction, we performed echocardiographic (echo) and doppler studies, before and during administration of sublingual NTG (0.8 mg). Twenty patients (n = 20) with long-standing hypertension (19 women and 1 man, mean age 78 +/- 8 yr, mean duration of hypertension 13 +/- 10 yrs were examined. The clinical findings in 17 patients were: angina 5 (29%), dyspnea 9 (53%), syncope or malaise 4 (23%). Electrocardiographic criteria of left ventricular hypertrophy was present in 4 patients and an increased cardio-thoracic ratio (greater than 0.5) in 9 cases. The following echo parameters were determined using M-mode echocardiograms: LV end-diastolic (LVID) and systolic diameter (LVIS), fractional shortening (FS), ventricular septum thickness (IVST), posterior wall thickness (PWT) and the ratio ISVT/PWT (less than 1.3 in all patients). LVM could be calculated in 15 patients and was corrected for body surface area (LVMI). Pulsed and continuous wave Doppler study showed a characteristic late-peaking velocity waveform. We localized the elevated velocities in the LVOT and determined before and during administration of NTG: LVOT peak velocities (V) and peak intraventricular gradients (G) using simplified Bernoulli equation. Results were as follows: [table: see text] Mild mitral regurgitation was observed in 14 patients (70%) and mitral annular calcifications in 11 (55%). Systolic function, as assessed by FS, was normal in all patients. NTG induced a significant acceleration of the LVOT velocities in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[A submucosal hematoma of the esophagus. A clinical case].

Spontaneous intramural hematoma of the esophagus (SIHE) is a rare condition usually affecting middle-aged or elderly women. It presents as acute substernal or epigastric pain, typically accompanied by dysphagia or hematemesis. SIHE is not usually associated with vomiting, and is therefore clearly distinguishable from hematogenic esophageal disorders, such as the Mallory Weiss lesion and the Boerhaave syndrome. The pathogenesis is in dispute. We present a case of SIHE without a discernible mucosal breach, suggesting a primary intramural bleed as the initiating event. Its diagnosis relies on the history and a barium swallow. Instrumentation can result in further damage to the esophagus. Treatment is conservative and results in resolution of the hematoma and return to normal swallowing. A favorable prognosis is the rule.

Aged↗
PubMed1990

Current status of iron chelation therapy with deferoxamine.

Long-term chelation therapy with deferoxamine is an effective and generally safe method for removing excessive iron, preventing iron-induced organ damage and improving survival of patients with transfusion-dependent disorders. The current treatment of iron overload is an important standard against which new forms of therapy, such as oral chelators, should be measured to ensure that their risks and benefits compare favorably with deferoxamine. Until new treatments are available, continuing studies of deferoxamine will help to define its long-term efficacy and toxicity for patients with thalassemia major and other hematologic disorders.

Chelation Therapy↗