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Biomedical subjects

S Gottlieb

Publications and source records attributed to S Gottlieb.

At least 199 records · Page 11Linked to original sources
PubMed1998

Symptom-oriented nitrate administration and survival after acute myocardial infarction. Israeli Thrombolytic Survey Group.

The effect of nitrates during evolving myocardial infarction is controversial. While previous studies showed that nitrates improve left ventricular function and have a beneficial effect on survival, two recent randomized megatrials showed that nitrates did not alter mortality after acute myocardial infarction (AMI). The present study analyzes the use of nitrates in clinical practice and their impact on mortality in a cohort of unselected consecutive AMI patients admitted to all 25 coronary care units operating in Israel during 2 months in 1994. Among 966 patients in Killip class I-III on admission, 81% (n = 783) received nitrate therapy by intravenous infusion or orally. Baseline characteristics of patients treated with or without nitrates were quite similar. Seven-day mortality was markedly reduced in the nitrate-treated group (5 and 11 %, p < 0.001) in comparison with those who did not receive nitrates. After adjustment for pertinent variables the 7-day relative risk (RR) of mortality was 0.51 [95% confidence interval (CI) 0.25-1.07; p = 0.08], whereas, the 7-day to 1-year mortality after AMI was not altered by nitrate use (RR = 0.97; 95% CI 0.56-1.68; p = 0.92). Nitrate therapy remains a widespread and a valid symptom-oriented therapeutic approach, especially early after AMI, in the community.

Aged↗
PubMed1997

Relation of coronary artery disease to atherosclerotic disease in the aorta, carotid, and femoral arteries evaluated by ultrasound.

This prospective study was conducted to correlate the presence of angiographically significant coronary artery disease (CAD) and atherosclerotic disease in the aorta, carotid, and femoral arteries as measured by ultrasound. One hundred two consecutive patients admitted for coronary angiography for suspected CAD participated in the study. All patients underwent transesophageal echocardiography for the evaluation of thoracic aortic atherosclerosis and B-mode ultrasound for evaluation of carotid and femoral atherosclerosis. Intimal-medial thickness > 1 mm in the thoracic aorta or peripheral vessels was considered as evidence of atherosclerosis. Patients with CAD (n = 64) had a significantly higher incidence of atherosclerotic plaques in the thoracic aorta, carotid, and femoral arteries than subjects with normal coronary arteries: 91%, 72%, 77% vs 31%, 47% and 42%, respectively. Extracoronary plaque was a stronger predictor of CAD than conventional risk factors. Evidence of plaque in patients younger than median age (64 years) had a higher specificity than in patients above median age (77% vs 40%, respectively, p <0.0001). Plaque score of the extracardiac vessels was significantly higher in patients with multivessel CAD than in patients with 1-vessel CAD disease and in subjects with normal coronary arteries (p <0.001). Thus, atherosclerotic plaques in the aortic and femoral arteries and, to a lesser extent, in the carotid arteries are strong predictors of CAD.

Adult↗
PubMed1997

Incidence and mortality from early stroke associated with acute myocardial infarction in the prethrombolytic and thrombolytic eras. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) and Israeli Thrombolytic Survey Groups.

OBJECTIVES: This study sought to compare the incidence of early cerebrovascular events and subsequent mortality in two cohorts of consecutive patients with acute myocardial infarction (AMI), admitted to coronary care units (CCUs) in Israel, in the prethrombolytic and thrombolytic eras. BACKGROUND: During the past decade, substantial changes have occurred in the medical treatment of AMI, and important new therapies have been introduced that could all affect stroke risk and type by diverse mechanisms. Yet the overall impact of these new therapeutic modalities on the incidence of stroke complicating AMI is not clear. METHODS: We compared the incidence and mortality rates of cerebrovascular events complicating AMI within CCUs among 5,839 consecutive patients admitted in the period 1981 to 1983 versus 2,012 patients from two prospective nationwide surveys conducted in all CCUs operating in Israel in 1992 and 1994. RESULTS: The demographic and clinical characteristics of patients with AMI in both periods were comparable. Patients admitted in the period 1981 to 1983 did not receive thrombolysis and reperfusion therapy; those admitted in 1992 and 1994 received thrombolysis (45%) and coronary angioplasty or coronary artery bypass graft surgery (14%), and antiplatelet and anticoagulant treatments were more frequently used. The incidence of early cerebrovascular events was 0.74% (43 of 5,839) in 1981 to 1983 versus 0.75% (15 of 2,012) in the 1992 to 1994 cohort. Patients with an AMI who experienced a cerebrovascular event were somewhat older in both groups and had a high rate of previous cerebrovascular events, congestive heart failure and atrial and ventricular arrhythmias during the hospital period. Mortality declined by one-third between the two periods. However, the mortality rate of patients with AMI who sustained a cerebrovascular event remained high (> or =40% for 30 days, 60% for 1 year). CONCLUSIONS: The overall incidence of early cerebrovascular events complicating AMI remained similar (0.75%) in the prethrombolytic and thrombolytic eras. Mortality rates of patients with an AMI but no cerebrovascular events decreased substantially over the past decade but not in patients with AMI with a cerebrovascular event.

Aged↗
PubMed1997

The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.

In mammals, insulin signalling regulates glucose transport together with the expression and activity of various metabolic enzymes. In the nematode Caenorhabditis elegans, a related pathway regulates metabolism, development and longevity. Wild-type animals enter the developmentally arrested dauer stage in response to high levels of a secreted pheromone, accumulating large amounts of fat in their intestines and hypodermis. Mutants in DAF-2 (a homologue of the mammalian insulin receptor) and AGE-1 (a homologue of the catalytic subunit of mammalian phosphatidylinositol 3-OH kinase) arrest development at the dauer stage. Moreover, animals bearing weak or temperature-sensitive mutations in daf-2 and age-1 can develop reproductively, but nevertheless show increased energy storage and longevity. Here we show that null mutations in daf-16 suppress the effects of mutations in daf-2 or age-1; lack of daf-16 bypasses the need for this insulin receptor-like signalling pathway. The principal role of DAF-2/AGE-1 signalling is thus to antagonize DAF-16. daf-16 is widely expressed and encodes three members of the Fork head family of transcription factors. The DAF-2 pathway acts synergistically with the pathway activated by a nematode TGF-beta-type signal, DAF-7, suggesting that DAF-16 cooperates with nematode SMAD proteins in regulating the transcription of key metabolic and developmental control genes. The probable human orthologues of DAF-16, FKHR and AFX, may also act downstream of insulin signalling and cooperate with TGF-beta effectors in mediating metabolic regulation. These genes may be dysregulated in diabetes.

Alternative Splicing↗
PubMed1997

Usefulness of the Killip classification for early risk stratification of patients with acute myocardial infarction in the 1990s compared with those treated in the 1980s. Israeli Thrombolytic Survey Group and the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.

The classification introduced in 1967 by Killip et al has proved to be a useful method for early risk stratification of patients with acute myocardial infarction (AMI). Over the past 3 decades the overall mortality due to AMI has decreased significantly. The present study evaluates the usefulness of the Killip classification as a method for early risk stratification of patients with AMI in the 1990s. One thousand eight hundred seventy-three consecutive AMI patients were hospitalized in 25 coronary care units operating in Israel, and were followed for 1 year. Higher Killip class was found to be associated with increased in-hospital and 1-year mortality, in thrombolysis- and nonthrombolysis-treated patients (30-day mortality for all patients was 5%, 21%, 35%, and 67% in Killip classes I to IV, respectively). The overall mortality among AMI patients in the 1990s was found to be lower for each Killip class compared with a comparable patient population with AMI, hospitalized in Israel in the 1980s. Thus, the Killip classification is a useful method for early risk stratification of AMI patients in the 1990s.

Aged↗
PubMed1997

Improved outcome of elderly patients (> or = 75 years of age) with acute myocardial infarction from 1981-1983 to 1992-1994 in Israel. The SPRINT and Thrombolytic Survey Groups. Secondary Prevention Reinfarction Israel Nifedipine Trial.

BACKGROUND: The number of elderly patients experiencing acute myocardial infarction (AMI) is growing rapidly, and their hospital mortality rate remains high, although mortality after AMI declined in the 1990s with the introduction of new therapeutic modalities. METHODS AND RESULTS: We compared the management, in-hospital complications, and 30-day and 1-year mortality rates in two cohorts of elderly (> or = 75 years of age) AMI patients in the coronary care units in Israel before and after the reperfusion era. The first cohort of 789 consecutive patients was from the Secondary Prevention Reinfarction Israel Nifedipine Trial registry in 1981-1983; the second 366 patients came from two prospective nationwide surveys in 1992 and 1994. Reperfusion therapies were not used in 1981-1983 but were used in 1992-1994. The 30-day mortality rate declined from 38% in 1981-1983 to 27% in 1992-1994 (odds ratio, 0.49; 95% confidence interval [CI], 0.34 to 0.71), and the cumulative 1-year mortality rate declined from 52% to 38% (hazard ratio [HR], 0.62; 95% CI, 0.50 to 0.76). In the 1992-1994 cohort, the decline in mortality was most marked in patients reperfused by thrombolysis and/or percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery but was also evident in nonreperfused patients: cumulative 1-year mortality rate was 29% in the former (HR, 0.45; 95% CI, 0.31 to 0.67) and 42% in the latter (HR, 0.60; 95% CI, 0.46 to 0.78). CONCLUSIONS: During the last decade, elderly (> or = 75 years) AMI patients experienced fewer in-hospital complications and lower 30-day and 1-year mortality rates, which declined approximately 30%, most markedly in reperfused patients. The favorable outcome in 1992-1994 was related to changes in patient management. Reperfusion therapy is therefore also advocated in elderly AMI patients, unless specific contraindications are present.

Aged↗
PubMed1997

Frequency and distribution of atherosclerotic plaques in the thoracic aorta as determined by transesophageal echocardiography in patients with coronary artery disease.

The frequency, distribution, and severity of thoracic aortic plaques were evaluated by transesophageal echocardiography in 152 consecutive patients undergoing coronary arteriography. Coronary artery disease (CAD) was defined as > or = 50% stenosis of > or = 1 major branch. Atherosclerotic plaques were detected in the aorta in 90 of the 97 patients (93%) with CAD, but in only 12 of the 55 patients (22%) with normal coronary arteries. Atherosclerotic plaques in patients with CAD were found predominantly in the descending aorta (in 93%) and in the aortic arch (in 80%), whereas the ascending aorta was the least involved (in 37%). In the descending aorta, 58% of the plaques were complex (>3 mm thick, ulcerated, mobile, or calcified), and in the aortic arch, 40% of the plaques were so classified. Complex plaques were not found in the ascending aorta. The presence of an atherosclerotic plaque in the descending aorta had a sensitivity and a specificity for the prediction of CAD of 93% and 78%, respectively. In the ascending aorta, the sensitivity was lower (37%) but the specificity was higher (100%). The sensitivity of aortic plaques for the prediction of CAD was high in all age groups. Its specificity in subjects >63 years was lower than in younger subjects: 64% versus 90%, respectively. Multivariate logistic regression analysis showed that aortic plaques were a stronger predictor of CAD than were conventional risk factors.

Adult↗
PubMed1997

Gonadotropin secretion in prepubertal normal and agonadal children evaluated by ultrasensitive time-resolved immunofluorometric assays.

To analyze a possible gonadal effect on the control of gonadotropin secretion during the prepubertal period, we have measured the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) serum concentrations in children with primary gonadal failure (PGF). We measured them using an ultrasensitive immunofluorometric assay (IFMA) in a single daytime serum sample and compared the results with those obtained with a radioimmunoassay (RIA) technique. The patients were 22 children with PGF (13 girls and 9 boys) aged 0.56-15.4 years and 58 normal children (28 girls and 30 boys) aged 0.08-16 years. In the normal group there were significant changes in serum LH and FSH concentrations in relation to sex and pubertal development. These changes were more evident especially in LH concentrations when using IFMA. We observed that during the prepubertal period the normal LH levels (mean +/- SD) were detectable with this method at concentrations well below the limit RIA could detect (girls 0.026 +/- 0.012 IU/l, and boys 0.025 +/- 0.01 IU/l), while at the onset of puberty these LH levels rose significantly in both sexes (girls 1.0 +/- 0.79 IU/l, boys 1.7 +/- 0.7 IU/l; p < 0.01 vs. prepubertal group), reaching similar values to those observed in FSH concentrations (prepubertal girls 1.9 +/- 0.89 IU/l, boys 0.73 +/- 0.41 IU/l; early pubertal girls 3.1 +/- 0.9 IU/l, boys 2.6 +/- 1.3 IU/l). At prepubertal age, most PGF patients showed normal gonadotropin serum levels (particularly LH) when measured by RIA. However, these same samples-when measured by IFMA-showed LH and FSH levels clearly higher than normal in almost all-10 of 12-patients (PGF girls, n = 8, LH 1.1 +/- 1.0 IU/l, FSH 34 +/- 30 IU/l; PGF boys, n = 4, LH 0.13 +/- 0.12 IU/l, FSH 6.5 +/- 5.7 IU/l). We conclude that, during the so-called 'juvenile pause' when the gonadotropin concentrations could be reliably measured, supranormal gonadotropin levels could be observed during a single daytime serum sample in patients with PGF. These findings suggest that during this period of life the gonads contribute to the negative feedback regulation of gonadotropin levels.

Adolescent↗
PubMed1997

The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL) homeobox gene that is expressed early in human development.

The majority of patients with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) have deletions of chromosomal region 22q11.2. The abnormalities observed in these patients include conotruncal cardiac defects, thymic hypoplasia or aplasia, hypocalcemia, and characteristic facial features. To understand the genetic basis of these disorders, we have characterized genes within the region that is most consistently deleted in patients with DGS/VCFS, the minimal DiGeorge critical region (MDGCR). In this report, we present the identification and characterization of a novel gene, GSCL, in the MDGCR, with homology to the homeodomain family of transcription factors. Further, we provide evidence that this gene is expressed in a limited number of adult tissues as well as in early human development. The identification of GSCL required a genomic sequence-based approach because of its restricted expression and high GC content. The early expression, together with the known role of homeobox-containing proteins in development, make GSCL an outstanding candidate for some of the abnormalities seen in DGS/VCFS.

Abnormalities, Multiple↗
PubMed1996

Smoking and prognosis after acute myocardial infarction in the thrombolytic era (Israeli Thrombolytic National Survey).

OBJECTIVES: This study sought to compare the relation between smoking and the 30-day and 6-month outcome after acute myocardial infarction in an Israeli nationwide survey. BACKGROUND: Studies before and during the thrombolytic era reported similar or lower early mortality after acute myocardial infarction in smokers than in nonsmokers. This finding is intriguing and may be misleading because numerous epidemiologic studies have clearly shown that smoking is an independent risk factor for atherosclerosis, myocardial infarction and death. METHODS: The study cohort comprised 999 consecutive patients with an acute myocardial infarction from a prospective nationwide survey conducted during January and February 1994 in all coronary care units operating in Israel. The prognosis of 367 patients (37%) who were smokers (current smokers and those who smoked up to 1 month before admission) was compared with that of 632 nonsmokers (past smokers or those who never smoked). RESULTS: Smokers were on average 10 years younger and were more frequently men and patients with a family history of coronary heart disease and inferior infarction and less frequently patients with a previous infarction or a history of angina, hypertension and diabetes than nonsmokers. Smokers also had a lower incidence of congestive heart failure on admission or during the hospital period. Thrombolytic therapy (49% vs. 40%, p < 0.01) and aspirin (89% vs. 80%, p < 0.001) were administered more frequently in smokers than nonsmokers. The crude 30-day (6.0% vs. 15.7%) and cumulative 6-month (7.9% vs. 21.5%) mortality rates were significantly lower (p < 0.0001 for both) in smokers than nonsmokers, respectively. However, after adjustment for age, baseline characteristics, thrombolytic therapy and invasive coronary procedures, the lower 30-day (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.43 to 1.29, p = 0.30) and 6-month (hazard ratio 0.84, 95% CI 0.54 to 1.30, p = 0.42) mortality rates in smokers and nonsmokers were not significantly different. The model had a power of 0.80 for OR 0.50, with alpha 0.1. CONCLUSIONS: In our nationwide survey, the seemingly better prognosis of smokers early after acute myocardial infarction was no longer evident after adjustment for baseline and clinical variables and may be explained by their younger age and a more favorable risk profile. Smokers develop acute myocardial infarction a decade earlier than nonsmokers. Efforts to lower the prevalence of smoking should continue.

Aged↗
PubMed1996

The outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy. Israeli Thrombolytic Survey Group.

PURPOSE: The aim of this study was to determine the proportion of patients with acute myocardial infarction (AMI) excluded from thrombolytic therapy on a national basis and to evaluate the prognosis of these patients by reasons of ineligibility and according to the alternative therapies that they received during hospitalization. PATIENTS AND METHODS: During a national survey, 1,014 consecutive patients with AMI were hospitalized in all the 25 coronary care units operating in Israel. RESULTS: Three hundred and eighty-three patients (38%) were treated with a thrombolytic agent and included in the GUSTO study. Ineligible patients for GUSTO were treated: (1) without any reperfusion therapy (n = 449), (2) by mechanical revascularization (n = 97), or (3) given 1.5 million units of streptokinase (n = 85) outside of the GUSTO protocol. The inhospital and 1-year post-discharge mortality rates were 6% and 2% in patients included in the GUSTO study; 6% and 5% in those mechanically reperfused; 15% and 10% in those treated with thromoblysis despite ineligibility for the GUSTO trial, and 15% and 13% among patients not treated with any reperfusion therapy. CONCLUSIONS: Ineligibility for thrombolysis among patients with AMI remains high. Patients ineligible for thrombolysis according to the GUSTO criteria, but nevertheless treated with a thrombolytic agent were exposed to an increased risk.

Actuarial Analysis↗