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Biomedical subjects

H Halkin

Publications and source records attributed to H Halkin.

At least 19 recordsLinked to original sources
PubMed1992

Computer assisted design of a theophylline dosing regimen in acute bronchospasm: serum concentrations and clinical outcome.

The effect of intravenous theophylline on the outcome of inhospital treatment of acute bronchospasm has been assessed, comparing the results achieved by computer-assisted dosing, designed to achieve and maintain a serum theophylline level of 16 micrograms.ml-1 (10 patients) with those of unaided physicians (15 control patients). The outcome measures compared were clinical improvement, peak expiratory flow rate and serum theophylline concentration. Loading doses of theophylline in the control and computer groups were: 167 and 437 mg, respectively. Initial serum theophylline concentrations, measured 20 min after the loading dose, were 13.6 and 17.0 micrograms.ml-1 in the control and computer groups, respectively. In patients who had not received theophylline prior to admission, loading doses and initial concentrations were: 200 mg and 9.4 micrograms.ml-1 in the control group (n = 5) versus 613 mg and 15.7 micrograms.ml-1 in the computer group (n = 4), respectively. During maintenance therapy, serum theophylline concentrations were kept in the therapeutic range (10-20 micrograms.ml-1) throughout 51% and 77% of the hospitalisation period, in the control and computer groups, respectively. There were no differences between the two groups in the rate or extent of clinical improvement or in change in peak expiratory flow rate. The computer assisted theophylline dosing regimen outperformed that of the unaided physicians in achieving and maintaining therapeutic serum theophylline concentrations in acute bronchospasm. There was no correlation between clinical outcome and serum theophylline concentration, but this may have been due to the small sample size and modest difference in serum theophylline between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

The effect of the plasma levels of proteins C and S on the prediction of warfarin maintenance dose requirements.

OBJECTIVE: Determination of the effects of the vitamin K-dependent anticoagulants, proteins C and S, on warfarin dose requirements and on the prediction error of a bayesian warfarin dose predicting program. METHODS: Patients in the study were consecutive inpatients (n = 18) starting treatment with warfarin who were monitored as outpatients for 4 weeks. The following measurements were taken: repeated (n = 8) prothrombin times, expressed as the international normalized ratio (INR), plasma protein C and S antigen levels (percentage of pooled normal plasma), demographic, clinical and biochemical variables. RESULTS: Maintenance doses (adjusted to INR 2.5) were 6.7 +/- 3.4 mg/day. Protein C decreased to 56.9% +/- 15.3%, protein S to 63.7% +/- 17.3%, INR increased to 2.46 +/- 0.14. Prediction error decreased from 2.84 +/- 2.0 mg/day to 0.95 +/- 0.78 mg/day. Protein C accounted for only 4.2% of the mean maintenance dose but protein C and S levels accounted for 31% of the mean dose prediction error. CONCLUSION: Protein C and S levels affect warfarin doses and predictions significantly but not to a clinically meaningful degree.

Adolescent↗
PubMed1991

Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study.

PURPOSE: To test the hypothesis that long-term furosemide therapy in patients with congestive heart failure (CHF) is associated with clinically significant thiamine deficiency via urinary loss. DESIGN: (1) Biochemical evaluation of thiamine status in hospitalized patients with CHF treated with long-term furosemide and in age-matched control patients. (2) Uncontrolled trial of the effect of intravenous thiamine on cardiac performance in a subset of six patients with CHF. SETTING: General medical ward of a teaching community hospital. PATIENTS: Twenty-three patients with chronic CHF receiving furosemide, and 16 age-matched control patients without heart failure and not taking diuretics. Daily furosemide doses were 80 to 240 mg, and duration of furosemide therapy was 3 to 14 months. Patients with identifiable causes of inadequate thiamine intake, absorption, or utilization or increased metabolic requirements were excluded. INTERVENTION: A 7-day course of intravenous thiamine, 100 mg twice daily, in six consenting patients with CHF. RESULTS: A high thiamine pyrophosphate effect (TPPE), indicating thiamine deficiency, was found in 21 of 23 furosemide-treated patients and in two of 16 controls (p less than 0.001). The mean (+/- SE) TPPE (normal: 0% to 15%) in furosemide-treated and control patients was 27.7 +/- 2.5% and 7.1 +/- 1.6%, respectively (p less than 0.001). Despite the high TPPE, the mean (+/- SE) urinary thiamine excretion in the furosemide-treated patients (n = 18) was inappropriately high (defined as greater than 130 micrograms/g creatinine), 410 +/- 95 micrograms/g creatinine, even in comparison with that in the controls (n = 14): 236 +/- 69 micrograms/g creatinine. In six patients treated with intravenous thiamine, the elevated TPPE decreased to normal, from a mean (+/- SE) of 27.0 +/- 3.8% to 4.5 +/- 1.3% (p less than 0.001), indicating normal thiamine utilization capacity. Left ventricular ejection fraction increased in four of five of these patients studied by echocardiography. CONCLUSIONS: These preliminary findings suggest that long-term furosemide therapy may be associated with clinically significant thiamine deficiency due to urinary loss and contribute to impaired cardiac performance in patients with CHF. This deficit may be prevented or corrected by appropriate thiamine supplements.

Adult↗
PubMed1991

Hyperinsulinemia, sex, and risk of atherosclerotic cardiovascular disease.

BACKGROUND: The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies. METHODS AND RESULTS: In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids. CONCLUSIONS: Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.

Arteriosclerosis↗
PubMed1991

Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs.

Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n = 3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (p less than 0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p less than 0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n = 372) and hyperinsulinemia (n = 190) were determined and were found to be positively associated with a dosage score of two or more (p less than 0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Hyperinsulinemia or increased sympathetic drive as links for obesity and hypertension.

The association of obesity with hypertension has been amply demonstrated in cross-sectional, longitudinal, and dietary-intervention studies, but the mechanisms remain enigmatic. Both conditions are independently characterized by similar metabolic alterations, i.e., glucose intolerance, dyslipoproteinemia, elevated serum uric acid, and inadequate Na+ transport. Obesity, hypertension, and these metabolic alterations are associated with hyperinsulinemia/insulin resistance. The degree of these alterations is lowest in lean hypertensives, intermediate in obese normotensives, and greatest in obese hypertensives, but mortality risk is highest in lean hypertensives. This apparent discrepancy may be related to the divergent hemodynamic characteristics, possibly indicating different etiology, of lean and obese hypertensives, i.e., contracted blood volume, increased total vascular peripheral resistance, and normal sympathetic drive in the former, expanded blood volume, normal peripheral resistance, and increased sympathetic drive in the latter. Current knowledge suggests that the interrelationships of obesity and hypertension with the metabolic alterations could be mediated by high carbohydrate and fat consumption and low physical activity, resulting in obesity and separate pathways in hyperinsulinemia and increased sympathetic drive, leading to a double vicious cycle. In one, hyperinsulinemia and the consequent insulin resistance would compound one another. In the second, the increasing hyperinsulinemia would increasingly stimulate the sympathetic nervous system. This double vicious cycle could result in increasing hemodynamic and metabolic derangements causing hypertension, diabetes, and atherosclerotic cardiovascular disease (ASCVD). The association of lean hypertension with ASCVD may be through other mechanisms, e.g., hemodynamic forces on the vascular endothelium.

Adult↗
PubMed1989

Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis.

STUDY OBJECTIVE: To determine whether a single-dose of thiazide administered to patients with previous thiazide-induced hyponatremia will cause hyponatremia and, if so, to analyze its pathogenesis. DESIGN: Prospective controlled study comparing patients with previous thiazide-induced hyponatremia with two control groups. PATIENTS AND CONTROLS: Eleven patients with thiazide-induced (Kaluril [hydrochlorothiazide, 50 mg; amiloride, 5 mg]) hyponatremia of less than 130 mmol/L at least 1 week before the study. Two groups of controls: 10 young healthy volunteers and 11 elderly hypertensive patients previously treated uneventfully with thiazide. INTERVENTIONS: Administration of a single dose of hydrochlorothiazide, 50 mg, and amiloride, 5 mg. MEASUREMENTS: Blood pressure, pulse rate, body weight, serum urea, creatinine, sodium, potassium, magnesium, osmolality, plasma antidiuretic hormone, renin, aldosterone and also urinary sodium, potassium, osmolality, and cyclic adenosine monophosphate (cAMP) before and 6 to 8, 12, and 24 hours after drug administration. RESULTS: Within 6 to 8 hours serum sodium decreased in patients, young controls, and elderly controls by 5.5 +/- 1.1 (mean +/- SE), 1.2 +/- 0.4, and 1.8 +/- 0.9 mmol/L, respectively (Py less than 0.001 [patients versus young controls], Pe = 0.017 [patients versus elderly controls]). Serum osmolality decreased in patients, young controls, and elderly controls by 14.9 +/- 2.6, 2.8 +/- 1.6, and 6.6 +/- 1.5 mmol/kg, respectively (Py less than 0.001, Pe = 0.012). All patients and only one control subject reached osmolality of less than 280 mmol/kg. At 6 to 8 hours all patients gained weight (0.85 +/- 0.13 kg) whereas young and elderly controls lost weight (0.47 +/- 0.23 and 0.45 +/- 0.2 kg, respectively) (Py much less than 0.001, Pe much less than 0.001). Patients' responses to the drug did not differ from both control groups regarding sodium and potassium urinary excretion, osmolar and free water clearance, and antidiuretic hormone blood levels. Water restriction in one patient attenuated serum sodium reduction. CONCLUSIONS: Use of a single-dose of a thiazide diuretic may predict the development of hyponatremia. Increased body weight apparently due to polydipsia may play a major role in the pathogenesis of thiazide-induced hyponatremia.

Adult↗
PubMed1989

Yield of the admission complete blood count in medical inpatients.

The clinical efficacy of routine admission complete blood count was evaluated in 302 patients admitted to internal medicine wards of a university teaching hospital. Patient medical problems, physical findings and medication history were evaluated by preset criteria to determine the proportion of tests performed for screening and the proportion of test results directly influencing patient management. Of the 282 complete blood counts performed, 80% were ordered routinely with no medical indications (screening tests). An haemoglobin abnormality was found in 16.7% of the patients, leucocyte abnormality in 16.1% and platelet abnormality in 4.6%. However, these results directly influenced patient management in only one case (0.14%). It is concluded that the utility of screening admission complete blood counts in medical inpatients is negligible.

Aged↗
PubMed1989

Smoking accounts for adverse effect of antihypertensive medications on plasma lipids. A population-based study.

Mean plasma levels of total cholesterol, high density lipoprotein cholesterol, total-to-high density lipoprotein cholesterol ratio, and total triglycerides were determined in a representative sample of the adult Israeli Jewish population, excluding known diabetics and individuals with overt atherosclerotic morbidity (n = 1,153). Levels were compared in normotensive and untreated and treated hypertensive individuals by glucose tolerance category and smoking, after adjustment for sex, age, and body mass index. In the presence of normal glucose tolerance, lipid levels in the nonsmoking normotensive and treated hypertensive groups were similar, whereas in the smoking, treated hypertensive group, lipids were significantly affected, as indicated by the respective adjusted mean levels (mg/dl): total cholesterol, 219, 221, and 240; high density lipoprotein cholesterol, 45.0, 43.6, and 42.0; ratio, 5.2, 5.3, and 6.0; and triglycerides, 114, 107, and 144. In individuals with glucose intolerance, trends were the same with the exception of triglycerides, which were significantly elevated in the nonsmoking, treated hypertensive group also; the respective values were 217, 225, and 257 for total cholesterol; 45.1, 44.9, and 41.4 for high density lipoprotein cholesterol; 5.2, 5.5, and 6.8 for the ratio; and 133, 152, and 187 for triglycerides. Lipid disturbances in treated smokers were not due to heavier smoking or differences in dietary intake. We conclude that disturbance of plasma lipid profile in treated hypertensive individuals may be mainly due to an interaction with smoking, with an additional effect of glucose intolerance.

Adult↗
PubMed1989

Evaluation of WHO and NDDG criteria for impaired glucose tolerance. Results from two national samples.

The considerable disagreement in the definition of impaired glucose tolerance (IGT) by National Diabetes Data Group (NDDG) and World Health Organization (WHO) criteria was explored in two independent representative adult population samples in Israel (n = 1119) and the United States (n = 1783). Five categories of nondiabetic glucose tolerance were defined according to fasting plasma glucose (FPG) values (mM) and 1- and 2-h plasma glucose values (PG1 and PG2, respectively) after oral glucose load: 1) normal by WHO and NDDG (FPG less than 6.4 mM, PG1 less than 11.1 mM, PG2 less than 7.8 mM), 2) Normal by WHO, nondiagnostic by NDDG (FPG 6.4-7.7 mM, PG1 less than 11.1 mM, PG2 less than 7.8 mM), 3) normal by WHO, nondiagnostic by NDDG (FPG less than 7.8 mM, PG1 greater than or equal to 11.1 mM, PG2 less than 7.8 mM), 4) IGT by WHO, nondiagnostic by NDDG (FPG less than 7.8 mM, PG1 less than 11.1 mM, PG2 7.8-11.0 mM), and 5) IGT by WHO and NDDG (FPG less than 7.8 mM, PG1 greater than or equal to 11.1 mM, PG2 7.8-11.0 mM). Established markers of abnormal glucose tolerance were also measured, including glycosylated hemoglobulin A1, insulin response, plasma triglycerides, serum uric acid, and rate of hypertension in Israel as well as rates of hypertension, peripheral vascular involvement, family history of diabetes, and history of cholelithiasis in the U.S. Accounting for potential confounders, levels of these markers in both national samples were similar in categories 1 and 2 and in categories 3-5.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Evaluation of an intervention aimed at reducing inappropriate use of preoperative blood coagulation tests.

A multiphase intervention trial based on education, implementation of criteria, and restriction, aimed at modifying the established clinical policy of mandatory preoperative screening for coagulation abnormalities, was carried out on five surgical wards of a general hospital. The education period did not influence the ordering of partial thromboplastin time tests, despite a significant posteducational change in surgeons' attitudes. In contrast, administrative restriction of coagulation test orders led to a 50% decline on four of the five study wards. We conclude that an educational intervention followed by administrative restriction may be considered an acceptable means of overcoming clinician reluctance to change well-established but redundant clinical policy.

Attitude of Health Personnel↗
PubMed1988

Complex interaction of rifampin and warfarin.

Rifampin is known to lower plasma warfarin concentrations by increasing the rate of warfarin clearance. We have described a patient in whom an additional potentiating influence on warfarin effect was observed during treatment with rifampin and isoniazid. After cessation of rifampin and isoniazid, prothrombin time was maintained within the same range by a 50% reduction of warfarin doses, despite a twofold rise in the plasma warfarin concentration. This rise in warfarin concentrations can be explained by the known mechanism by which rifampin increases warfarin clearance. After cessation of rifampin, warfarin fractional clearance decreased from 15.2 to 4.2 ml/min; however, the unchanged prothrombin time in the face of the increased warfarin concentration can be explained only by the removal of a potentiating effect that had been present during the coadministration of rifampin and isoniazid. It is likely that rifampin is responsible for this additional potentiating interaction, probably not through a change in warfarin binding, but through a differential effect on warfarin stereoisomer metabolism or through an altered dynamic effect. The role of isoniazid in this interaction cannot be completely ruled out.

Adult↗
PubMed1988

Altered erythrocyte and plasma sodium and potassium in hypertension, a facet of hyperinsulinemia.

Red blood cell sodium and potassium, plasma potassium, glucose and insulin responses to oral glucose load, serum urate, and plasma triglycerides were determined in a stratified subsample (n = 89) of a representative population sample (n = 1211), comprising 30 nonobese normotensive subjects with normal glucose tolerance (reference group) and 59 subjects representing each of the seven possible combinations of abnormal glucose tolerance, obesity, and hypertension. Rate of cation imbalance (red blood cell sodium greater than or equal to 7.0 mEq/L, potassium less than 92.5 mEq/L, or plasma potassium greater than or equal to 4.5 mEq/L) was 88.1% in subjects with abnormal tolerance, obesity, or hypertension, as compared with 40.0% in the reference group (p less than 0.001). These subjects were also characterized by significantly greater rates of insulin response: 60- and 120-minute postload levels of 100 mU/L or more (88.1 vs 46.7%), plasma triglycerides of 80 mg/dl or more (89.8 vs 53.3%) and serum uric acid of 5.5 mg/dl or more (61.0 vs 26.7%; p less than 0.001 for all). The rate of cation imbalance was significantly associated with each of these three biochemical correlates: insulin response (p less than 0.01), triglycerides (p less than 0.001), and urate (p less than 0.001). In the total population sample, the rate of untreated hypertension increased from 18% to 35% to 55.3% (p less than 0.001), with an increase in the number of biochemical correlates of cation imbalance in combination with glucose intolerance and obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocytes↗
PubMed1988

Significance of high HbA1 levels in normal glucose tolerance.

The significance of high hemoglobin A1 (HbA1) levels (greater than or equal to 8.0%) found in 12.1% of 648 individuals with normal glucose tolerance constituting a part of a representative population sample was examined. Measurement error in HbA1 and/or glucose-tolerance levels was precluded by HbA1 remaining in the same range over 3.5 yr in 89.7% of 29 individuals with initially high and 68.1% of 22 individuals with initially low (less than 6.5%) HbA1. Rate of deterioration to glucose intolerance (6.9%) in the high group during that period resembled the rate (11.8%) in a control group (n = 279). Fasting plasma glucose significantly accounted for only 2.4% of total HbA1-population variance. No correlation of HbA1 was found with other correlates of glucose tolerance or with daily caloric intake and physical activity. A small but significant increment in HbA1 was associated with smoking (7.1 vs. 6.8%, P less than .01) and with clinically overt atherosclerosis (7.3 vs. 6.9%, P less than .01). We conclude that factors unrelated to glucose metabolism are the main determinants of HbA1 level in normal glucose tolerance and play an important role in diabetes as well. These factors have bearing on evaluation of diabetic control by HbA1 and possibly on risk for diabetic complications.

Arterial Occlusive Diseases↗
PubMed1988

Cost-effectiveness of in-hospital evaluation of patients with syncope.

In order to assess the utility of in-hospital evaluation of syncope we reviewed the records of 134 consecutive patients admitted within 6 h of a true syncopal episode, and obtained follow-up information on 130 of them 3 years later. All threatened cardiac rhythm and conduction disturbances were detected on the initial ECG recording. Prolonged ECG monitoring did not contribute additional diagnoses. Other diagnostic tests and procedures performed during the mean 7.5-day hospital stay only confirmed the findings of the initial history, physical and ECG examinations. Diagnostic evaluation was followed by therapeutic intervention in only 33 patients (24%); all interventions were clearly mandated by the initial admission evaluation. There were no cases of sudden death and no association between causes of death, the index syncope episode or prior history of syncope. We therefore propose that the evaluation of patients presenting within hours of a syncopal episode include only history taking, physical examination and the initial ECG recording. Further in-hospital evaluation should be limited to confirming initial positive findings. This approach may allow an estimated 85% reduction in costs involved in the management of similar patients, with probable negligible adverse effects on prognosis.

Aged↗