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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 361 records · Page 20Linked to original sources

Hemodynamic criteria for diagnosis of right ventricular ischemia associated with inferior wall left ventricular acute myocardial infarction.

To test the diagnostic value of different hemodynamic indexes for the diagnosis of acute right ventricular (RV) ischemic dysfunction, we studied 2 groups of consecutive patients admitted for an acute left ventricular inferior wall myocardial infarction: 51 patients with (group 1) and 32 patients without (group 2) RV ischemia as determined by coronary angiography. In both groups, we analyzed by right-sided cardiac catheterization right-sided heart pressures, pulmonary capillary wedge pressure, and cardiac index. We also calculated pressure ratios (mean right atrial pressure or RV end-diastolic over pulmonary capillary wedge pressures), pulmonary vascular resistance, and RV stroke work index. We found significant differences (p < 0.01) between the 2 groups when comparing mean right atrial pressure, RV end-diastolic pressure, ratio of these 2 pressures over pulmonary capillary wedge pressure, RV stroke work index, and right atrial and RV pressure waveforms. The best combined sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were found for the right atrial M or W waveform pattern, isolated or combined with a disproportionate elevation of RV end-diastolic over pulmonary capillary wedge pressures (respectively, 92%, 94%, 90%, 87%, and 89%). Volume loading was performed in 27 patients (18 with and 9 without RV ischemia). Right heart pressures and RV stroke work index increased significantly and similarly in both groups. Cardiac index increased significantly only in patients without RV ischemia (p = 0.02). However, volume loading did not significantly modify the diagnostic value of the different hemodynamic criteria studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Interference with thymocyte differentiation by an inhibitor of S-adenosylhomocysteine hydrolase.

Adenosine deaminase (ADA) deficiency causes severe combined immune-deficiency disease in humans. It is believed that the accumulation of the ADA substrate deoxyadenosine affects T cell development through interference with deoxynucleotide metabolism and/or S-adenosylmethionine-mediated methylation processes. In this study, we used a specific inhibitor of methylation, (Z)-5'-fluoro-4',5'-didehydro-5'-deoxyadenosine (FddA), to study the effect of inhibition of methylation on intrathymic T cell development in a murine model for ADA deficiency. FddA causes inhibition of thymocyte differentiation specifically at the CD8low and CD4CD8 double-positive stages. This inhibition is not due to induction of apoptosis, rather it is a result of specific inhibition of regulation of the levels of the mRNAs coding for TCR and CD4 and CD8 co-receptor molecules that normally occurs at these stages of thymocyte differentiation. We hypothesize that the transcription of these T cell-specific molecules is regulated by a common developmental stimulus involving a S-adenosylmethionine-mediated methylation step. Identification of this step will help in understanding the role of methylation in intrathymic differentiation and will also provide a molecular explanation for the tissue and developmental stage specificity observed in severe combined-immune-deficient patients with ADA deficiency.

Adenosine Deaminase↗

Relations between Doppler tracings of pulmonary regurgitation and invasive hemodynamics in acute right ventricular infarction complicating inferior wall left ventricular infarction.

To test the hypothesis that flow characteristics from pulmonary regurgitation (PR) can predict right ventricular (RV) involvement in patients with inferior wall acute myocardial infarction, we prospectively recorded continuous-wave Doppler tracings and right-sided cardiac hemodynamics in 48 consecutive patients with inferior wall acute myocardial infarction and PR. Right heart hemodynamics enabled the identification of 29 patients with (group 1) and 19 without (group 2) RV involvement. In patients with RV involvement, the pulmonary regurgitant flow pattern was characterized by a rapid rise in flow velocity to a peak level followed by an abrupt deceleration in mid-diastole, whereas in patients without RV involvement, the deceleration in mid-diastole was gradual. The pressure half-time of PR (PHTPR) and the lowest mid-diastolic to peak early diastolic velocity ratio were significantly lower in group 1 than in group 2 (91 +/- 31 vs 214 +/- 57 ms [p < 0.001], 0.35 +/- 0.08 vs 0.59 +/- 0.13 [p < 0.001], respectively). The best diagnostic accuracy (95%) was obtained with cut-off values of PHTPR < or = 150 ms and the lowest mid-diastolic to peak early diastolic velocity ratio < or = 0.5: sensitivity 100%, specificity 89%, positive predictive value 94%, and negative predictive value 100%. Using multiple logistic regression analysis, we found that PHTPR was the strongest predictor of RV involvement. Thus, these parameters, derived from pulmonary regurgitant tracings, are useful in the noninvasive bedside diagnosis of RV infarction.

Aged↗

A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells.

Translocations involving chromosomal band 11q23 are associated with leukemias. These translocations fuse the MLL, a gene with sequence homology to the Drosophila trithorax, to genes from a number of other chromosomal loci. We have characterized two t(1;11)(q21;q23) translocations that fuse the MLL gene to a novel gene, AF1q on chromosomal band 1q21, in two infants with acute myelomonocytic leukemia (AMMOL). In one of these patients, der(11) represents an inframe fusion of the N-terminal portion of MLL gene to the complete AF1q open reading frame, whereas der(1) does not give rise to an open reading frame. This observation suggests that the N-terminal portion of MLL gene is critical for leukemogenesis in translocations involving band 11q23. The predicted wild-type AF-1q product is a 9-kD protein with no similarity to any other protein in the data banks. The AF1q mRNA is highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, AF1q was expressed in all leukemic cell lines tested.

Amino Acid Sequence↗

Lateral subcutaneous sphincterotomy for treatment of anal fissure in children.

Twenty-three children, aged between 8 and 168 months, underwent lateral subcutaneous sphincterotomy. All fissures healed by 8 weeks after operation. Two children had recurrent proctalgia and defaecating difficulties after surgery despite a healed fissure. Requirement for stool softener was reduced or abolished in 17 children. The parent-child satisfaction score after operation was more than 70 per cent in 19 of 23 cases. Lateral subcutaneous sphincterotomy is an effective procedure in children.

Adolescent↗

Identification of an ionomycin/cyclosporin A-responsive element within the human T cell receptor gamma enhancer.

Activation through the Ca2+/calcineurin pathway is essential to the transcription of many cytokine genes. The conserved cis-acting sequence, GGAAAA, and transcription factors binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations. Here we report the identification and importance of the same sequence in a non-cytokine gene, the human T cell receptor gamma (TCRG) enhancer. Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin-induced activation of the TCRG enhancer. Our studies provide an explanation for a previous observation that TCRG mRNA levels, but not mRNA levels for T cell receptor alpha and -beta, are increased by ionomycin treatment.

Base Sequence↗

Efficacy and pharmacokinetics of two formulations of cyclosporine A in patients with psoriasis.

The efficacy and pharmacokinetic profiles of two oral formulations of cyclosporine A (Sandimmune and Neoral; Sandoz Pharmaceuticals, East Hanover, NJ) were evaluated in 37 patients with moderate to severe plaque psoriasis in a randomized, double-blind, modified, crossover study. Cyclosporine A (150 mg twice daily), administered in either formulation, reduced the severity of plaque lesions: 94% of all patients reported at least moderate improvement and 70% reported complete clearing. Approximately 2 weeks of therapy were required for drug exposure to stabilize on either formulation. Cyclosporine A exposure from Neoral was significantly greater relative to that from Sandimmune across all study weeks. At the eighth week (before crossover), AUC and Cmax values for Neoral and Sandimmune were 5618 +/- 1705 versus 3202 +/- 596 ng.h/mL and 1283 +/- 337 versus 623 +/- 173 ng/mL, respectively. In crossover analysis at steady state, the relative oral bioavailability of cyclosporine from the Neoral formulation was 54% greater than that from Sandimmune. Some pharmacokinetic parameters showed less variability both between and within groups of patients taking Neoral versus Sandimmune. Both formulations were well tolerated, in that most adverse events were of mild severity.

Chemistry, Pharmaceutical↗

The Jerusalem seventy-year-old longitudinal study. I: Description of the initial cross-sectional survey.

The main objectives of our first cross-section of a longitudinal study of a cohort of 70 year olds in Jerusalem, are to survey the social and medical conditions of the heterogeneous elderly population and to contribute to the knowledge of aging processes for specific age-groups. Whereas, most previous surveys were conducted on homogeneous and stable population groups, the elderly of Jerusalem provide the basis for ethnographic comparisons and for assessing the impact of profound historical and personal changes. From a representative systematic sample (from a geographically sorted electoral register) of 759 persons, 605 persons replied to our home-visit questionnaire gathering data on migration history, dwelling conditions, health status, health service utilization, employment status, activities of daily living, social support, use of drugs and war experience. Later on, 463 persons attended our geriatric research institute where we gathered information from in-depth anamnesis and physical examination, as well as cognitive and psychological tests. In addition, a battery of biochemical and hematological blood tests were performed as well as urine analysis and culture, ECG and pulmonary function tests. The heterogeneity of our cohort population is demonstrated by the finding that 84% were born in 40 different countries outside of Israel. In contrast, in the seventy-year old population studied in Gothenburg, Sweden, only 3% were not native born. In the years 1996, 2001 and 2006, our initial study cohort will be re-examined and compared to control groups representing states of no-survey intervention until ages 75, 80 and 85 years old. This background paper describes the study design, protocols and procedures. The responders were found to be representative of the 70 year old Jewish population in Jerusalem as a whole, in terms of mortality and hospital utilization rates. The results of the study to be reported in subsequent papers will allow conclusions regarding all 70 year old Jews in Jerusalem to be made.

Aged↗

The Jerusalem seventy year olds longitudinal study. II: Background results from the initial home interview.

Basic background information is presented from a representative sample of 605 West Jerusalem Jewish residents aged 70 years in 1990/91. A followup survey of the original cohort is planned for 1996, in addition to a similar sized control group of persons not studied in 1990/91. This paper describes the demographic characteristics, marital status, household composition, migration patterns, language comprehension, education, employment status, religious practices, household conditions, health status, health service utilization, health practices, use of medications, social contacts and activities of daily living of the study population. Only 16% of the study population were born in Israel, the remainder were born in forty different countries in four continents. This article also presents some ethnic comparisons within our cohort. Some significant differences were found between ethnic sub-groups in self-reported chronic diseases. However, many of these differences disappeared when socio-economic covariates were considered. Differences were also found when specific countries were considered. Compared to Polish-born Jews, Moroccan-born Jews had lower economic status, less education, more family contacts and less faith in physicians. Moroccan-born Jews also reported more morbidity for cerebrovascular disorders, emphysema and glaucoma.

Activities of Daily Living↗

[Segmental myocarditis in Churg-Strauss syndrome. Review of the literature apropos of a case].

We describe a 25-year old man in whom segmental myocarditis and pericarditis was diagnosed using two-dimensional echocardiography. Churg-Strauss syndrome was suspected in the presence of asthma and evidence of hypereosinophilia. Early therapy with oral prednisone led to resolution of pericarditis but septal hypokinesia was still present after 4 years. The pathophysiology of segmental myocarditis in the Churg Strauss syndrome is discussed.

Adult↗

Chronic obstructive pulmonary disease in patients undergoing coronary artery bypass grafting.

The purpose of this study was to evaluate the effect of chronic obstructive pulmonary disease on patients undergoing coronary artery bypass grafting. Between June 1991 and June 1993, 651 patients underwent coronary artery bypass grafting: 37 patients (group I) had significant chronic obstructive pulmonary disease. These patients were compared with 37 matched control subjects (group II). Comparison of the groups was made with regard to postoperative morbidity and mortality. Quality of life of survivors was compared at the last follow-up. More patients in group I had preoperative arrhythmias (8 versus 1, p = 0.014). Group I patients had lower values of forced expiratory volume in 1 second (1.366 +/- 0.032 L versus 2.335 +/- 0.49 L, p < 0.0001), lower oxygen tension (63.5 +/- 8.2 versus 79.1 +/- 13.4 mm Hg, p = 0.001), and higher carbon dioxide tension (44.8 +/- 6.5 mm Hg versus 39.7 +/- 3.6 mm Hg, p = 0.001). After operation patients in group I had a longer hospital stay (8.1 +/- 3.6 days versus 6.6 +/- 1.7 days, p = 0.0236) and longer intensive care unit stay (2.64 +/- 0.9 days versus 1.23 +/- 0.49 days, p = 0.0001). More patients in group I required prolonged intubation (7 versus 1, p = 0.0278) and reintubation (5 versus 1, p = 0.088). More patients in group I had significant arrhythmias (27 versus 9, p < 0.0001). During a 16-month follow-up period, five patients in group I died, whereas none in group II died (p = 0.0271). Four deaths were related to arrhythmias. More group I patients were not functionally improved by the operation (17 versus 3, p = 0.0056). The results of coronary artery bypass grafting in patients with significant chronic obstructive pulmonary disease were not favorable in midterm follow-up. A major cause for morbidity and mortality was postoperative arrhythmias.

Aged↗

Histopathologic findings in the clinically uninvolved skin of patients with mycosis fungoides.

Several of the methods of treating plaque-stage mycosis fungoides (MF) advocate treatment of the whole skin, although relatively little information exists on the histologic appearance of clinically uninvolved MF skin. Our study was performed to elucidate the histologic appearance of the clinically uninvolved skin of plaque-stage MF patients. Biopsies were taken from the clinically uninvolved skin of 18 untreated patients with plaque-stage MF, 1 cm (near) and > or = 10 cm (far) from the MF plaques, and from 23 normal, healthy controls. Eight to 12 serial sections from each specimen were examined. The most common histologic finding, which was observed in six (33%) biopsies of near skin and four (22%) biopsies of far skin compared with only one (4%) biopsy of normal control (p = 0.02 and 0.1, respectively), consisted of mononuclear-cell infiltrate around a blood vessel in the papillary dermis, with extension of some of these cells into the overlying epidermis. More diffuse and epidermotropic mononuclear cell infiltrates were seen in an additional three (17%) biopsies of near skin, whereas mild nonepidermotropic superficial perivascular or perifollicular mononuclear cell infiltrates were observed in an additional four (17%) biopsies of the normal controls. In conclusion, the most common histologic finding in our study, which was observed predominantly in the MF group, might represent an earlier stage and clinically undetectable involvement of the normal-looking skin in MF patients.

Adult↗

Enalapril improves glucose tolerance in two rat models: a new hypertensive diabetic strain and a fructose-induced hyperinsulinaemic rat.

1. The present study was undertaken to examine the effect of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on blood pressure and spontaneous blood glucose levels in two rat models: our new diabetic hypertensive rat in which genetic hypertension and diabetes develop following cross-breeding of Cohen diabetic rat (CDR) and spontaneous hypertensive rats (SHR); and a rat in which hypertension, hyperinsulinaemia and hyperlipidaemia were induced by fructose diet. 2. The new strain of animal was fed the usual copper-poor sucrose diet, and for 4 weeks received enalapril. The fructose-induced hyperinsulinaemic animals were fed a fructose-enriched diet for 3 weeks, and enalapril 20 mg per kg per day was added to the drinking water for 2 more weeks. 3. The new strain of diabetic-hypertensive rats that received enalapril showed a significant decrease in blood pressure level. The fructose-fed animals showed a fall in insulin and blood pressure following the introduction of enalapril to their diet. 4. The present study confirms the advantage of the ACE inhibitor enalapril in improving the metabolic parameters of hypertensive diabetic rats, including insulin sensitivity.

Angiotensin-Converting Enzyme Inhibitors↗