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Biomedical subjects

H Halkin

Publications and source records attributed to H Halkin.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1987

Reduction of redundant hospital stay through controlled intervention.

With the aim of reducing redundant hospital stay through controlled intervention, preset criteria for inpatient care were applied on a medical ward. The proportion of unjustified hospital stay days fell by 52.6% and the average length of stay on the experimental ward declined from 6.3 days to 4.6 days. On a control medical ward there was practically no change. At one-month follow-up, patients from the two wards did not differ in death rate, readmission rate, or subjective evaluation of health status.

Age Factors↗
PubMed1987

Decline of proteins C and S and factors II, VII, IX and X during the initiation of warfarin therapy.

Oral anticoagulants achieve an antithrombotic effect only several days after initiation of treatment. A rapid decline of the vitamin-K dependent natural anticoagulants (proteins C and S) during this period might result in a prothrombic phase. We addressed this question by measuring the rates of decline of these proteins, as well as the vitamin K dependent procoagulants, in two groups of patients: A "high dose group" (n = 7), who received a single 40 mg dose of warfarin, and a "low dose group" (n = 20), who received daily individually adjusted doses. In the high dose group an early and marked decline of factor VII:C and protein C antigen was observed, while levels of the other vitamin K dependent factors were still relatively high. In the low dose group, all these proteins declined more gradually. Mean +/- SD of protein C antigen level at 46 hr was 56 +/- 12% in the low dose group, and only 44 +/- 6% (p less than 0.05) in the high dose group. We conclude that during the initiation of warfarin therapy there is a transient prothrombotic phase, which is less marked in patients given daily adjusted doses.

Blood Coagulation Factors↗
PubMed1987

Elevated serum uric acid--a facet of hyperinsulinaemia.

In a representative sample of the adult Jewish population in Israel (n = 1016) excluding known diabetic patients and individuals on antihypertensive medications, serum uric acid showed a positive association with plasma insulin response (sum of 1- and 2-hour post glucose load levels) in both males (r = 0.316, p less than 0.001) and females (r = 0.236, p less than 0.001). This association remained statistically significant in both sexes (p less than 0.001) after accounting by multiple regression analysis for age and major correlates of serum uric acid i.e. body mass index, glucose response (sum of 1- and 2-hour post load levels), systolic blood pressure and total plasma triglycerides. The net portion of the variance of serum uric acid attributable to insulin response was 12% in males and 8% in females, the total variance accountable by all these variables being 17% and 19% respectively. We conclude that elevated serum uric acid is a feature of hyperinsulinaemia/insulin resistance.

Adult↗
PubMed1987

Hyperinsulinemia--a link between glucose intolerance, obesity, hypertension, dyslipoproteinemia, elevated serum uric acid and internal cation imbalance.

A representative sample (n = 1211) of the Jewish population in Israel age 40-70 (excluding known diabetics), underwent a glucose tolerance test. Insulin response was found to be independently and positively associated with the GOH conditions--glucose intolerance (p less than 0.001), obesity (p less than 0.001), and hypertension (p less than 0.01) and with elevated serum uric acid (p less than 0.001) after accounting for the effects of sex, age, serum creatinine and use of antihypertensive medications. In a representative subgroup of 542 individuals, total VLDL and LDL fractions were estimated by standardized values (based on the reference group--individuals free of the GOH conditions), of their cholesterol and triglyceride components. Hyperinsulinemia was characterized by jointly elevated VLDL and LDL with reduced HDL. The risk ratio for this pattern (adjusted for the effects of age, sex, smoking and presence of any of the GOH conditions) was 3.4 (p less than 0.001). There was no further association of this disturbed lipoprotein profile with the GOH conditions. Cation concentrations were determined in a stratified subsample (n = 89) of the study group. The subsample comprised 30 individuals in the reference group, and 59 representing each of the seven possible combinations of abnormal glucose tolerance, obesity and hypertension (GOH group). Rate of cation imbalance defined as presence of at least one of three cation concentration--red blood cell sodium greater than or equal to 7.0 mEq/l, red blood cell potassium less than 92.5 mEd/l or plasma potassium greater than or equal to 4.5 mEq/l was 88.1% in the GOH, compared to 40.0% in the reference group (p greater than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The negative impact of biological variation in the effect and clearance of warfarin on methods for prediction of dose requirements.

Within-individual variation over time in the clearance (Cl) and effect (PT%) of warfarin, was measured in 25 inpatients (group I) studied after standard single or individualized split loading doses and 1-3 times (n = 16) 8-16 weeks later during maintenance. Mean Cl (2.5 +/- 0.9 ml/min) was similar in both phases but significant changes occurred in 6/16 patients, exceeding those expected from within-individual variation alone (defined by its 95% tolerance limits -24% to +62%). Initial PT% (21 +/- 5) was unaffected by dosing schedule, total or free plasma warfarin, varying between patients by only 18-24%. Mean initial and maintenance dose-PT% ratios (8.2 mg/d: 21% and 4.1 mg/d: 40%) were similar but significant changes in sensitivity to warfarin occurred in 4/16 patients. In group I and 64 other outpatients on maintenance therapy, between-individual variability was 36-52% for Cl and 49-56% for effect. PT% correlated best (r = 0.56) with free and total plasma warfarin but poorly with dose (r = 0.29), with only 30% of PT% variance explained at best, due to high between patient variability. Warfarin dose prediction whether based on extrapolation from initial effects to the maintenance phase, or on iterative methods not allowing for between- or within-patient variation in warfarin clearance or effect which may occur independently over time, have not improved on empirical therapy. This, due to the elements of biological variability as well as the intricacy of the warfarin-prothrombin complex interaction not captured by any kinetic-dynamic model used for prediction to date.

Biological Availability↗
PubMed1986

Effect of past and concurrent body mass index on prevalence of glucose intolerance and type 2 (non-insulin-dependent) diabetes and on insulin response. The Israel study of glucose intolerance, obesity and hypertension.

A representative sample (n = 2140) of the Israeli Jewish population aged 40-70 (excluding known diabetic patients), whose body mass index had been measured 10 years earlier, underwent an oral glucose tolerance test and redetermination of body mass index. Irrespective of weight changes, high concurrent and high past body mass index values (greater than or equal to 27) were associated with similarly increased rates of glucose intolerance as compared with body mass index values less than 27 at both time-points (rate ratio 1.76, 90% confidence limits 1.56-1.99). Glucose intolerance here includes borderline and impaired tolerance as well as Type 2 diabetes. The rate of Type 2 diabetes increased only with increasing past body mass index, while concurrent body mass index had no effect [rate ratios: 2.36 (1.48-3.75) and 1.99 (1.48-2.68) respectively for the medium-(23-26.9) versus-low (less than 23) and high- (greater than or equal to 27) versus-medium past body-mass-index categories]. Weight reduction was associated with only slightly reduced rate of glucose intolerance and had no effect on the rate of diabetes. Mean sum insulin (summed 1 and 2 h levels, mU/l) increased significantly with increasing concurrent body mass index (123, 150 and 190 in the low, medium and high categories) with no effect of past body mass index. It also increased significantly (p less than 0.001) in all concurrent body mass index categories from normal tolerance through borderline to impaired tolerance, and decreased significantly (p less than 0.001) in diabetes relative to impaired tolerance, although it remained above normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Mechanism of warfarin potentiation by amiodarone: dose--and concentration--dependent inhibition of warfarin elimination.

Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25-30% of control and its kinetics were compared to those in 20 control patients who received warfarin alone. Potentiation occurred in 28/30 patients, presenting as a 35%-65% reduction in the required dose of warfarin, and was correlated with the dose of amiodarone (r = 0.77, p less than 0.01). The free warfarin fraction was not affected by amiodarone (1.8% vs 1.6% in the controls). Warfarin clearance was lower in amiodarone-treated patients than in the controls (1.4 vs 3.1 ml/min, p less than 0.01) with similar plasma concentrations (1.5 vs 1.2 micrograms/ml) despite administration of lower doses (23.3 vs 39 mg/week respectively). The amiodarone concentration was significantly correlated with the warfarin concentrations independent of the effect of amiodarone on the dose of warfarin. Amiodarone hat no effect on prothrombin other than through its actions on the dose and plasma concentration of warfarin. The mechanism of the amiodarone-warfarin interaction is pharmacokinetic through dose - and concentration - dependent inhibition of warfarin elimination.

Adult↗
PubMed1985

Pharmacokinetic differences between peripheral and central drug administration during cardiopulmonary resuscitation.

Advanced resuscitation techniques are dependent on drug therapy to increase survival. Because drugs must reach their site of action instantaneously, the choice of appropriate route of administration may be critical. To study the pharmacokinetics of drug administration by peripheral and central venous routes during resuscitation, nine mongrel dogs were studied. Arterial blood pressure and electrocardiograms were monitored continuously. Cardiac output was evaluated before resuscitation to determine control levels. After thoracotomy and fibrillation of the heart, cardiac massage was started with a frequency of compression maintained at 60/min. Bolus injections of two different radioisotopes were given simultaneously through a peripheral and a central vein. Isotope activity was sampled through a catheter in the right femoral artery at 5 second intervals for 90 seconds and at 30 second intervals for 210 seconds. The major differences between the two routes of administration were that central injection produced a 270% higher peak concentration (p less than 0.001) and significantly shorter lag times to the first appearance of tracer (16 +/- 7 versus 38 +/- 13 seconds, p less than 0.05) and times to peak concentration (13 +/- 5 versus 27 +/- 12 seconds, p less than 0.01). In contrast, there were no significant differences in area under the time-counts curve, mean residence time, total body clearance and steady state volume of distribution. The central compartment volume of distribution was significantly smaller after central than after peripheral injection (26.1 +/- 56 versus 76.3 +/- 16.5 ml, p less than 0.01). The therapeutic implications of these findings must be investigated for individual drugs used during cardiorespiratory resuscitation to determine the most appropriate route and dosage for each agent.

Animals↗
PubMed1985

Apathetic thyrotoxicosis due to hemorrhage into a hyperfunctioning thyroid nodule after excessive anticoagulation.

Hyperfunctioning thyroid nodule was diagnosed in a 72-year-old woman. When the nodule reached a diameter of 3.5 cm, overt thyrotoxicosis of the apathetic type was precipitated by hemorrhage into the nodule during a period of excessive anticoagulation. All abnormal physical signs and symptoms as well as laboratory findings returned to normal within a month, without any specific treatment. It was possible to follow this process by repeated B-mode sonographic examinations and thyroid scans.

Adenoma↗
PubMed1985

Hyperinsulinemia. A link between hypertension obesity and glucose intolerance.

Hypertension and glucose intolerance, determined in a random population sample (n = 2,475), showed a highly significant (P less than 0.001) association from the mildest levels of both conditions, independent of the confounding effects of age, sex, obesity, and antihypertensive medications. Summary rate ratios for hypertension were 1.48 (1.18-1.87) in abnormal tolerance and 2.26 (1.69-2.84) in diabetes compared with normal tolerance. Altogether, 83.4% of the hypertensives were either glucose-intolerant or obese--both established insulin-resistant conditions. Fasting and post-load insulin levels in a representative subgroup (n = 1,241) were significantly elevated in hypertension independent of obesity, glucose intolerance, age, and antihypertensive medications. The mean increment in summed 1- and 2-h insulin levels (milliunits per liter) compared with nonobese normotensives with normal tolerance was 12 for hypertension alone, 47 for obesity alone, 52 for abnormal tolerance alone, and 124 when all three conditions were present. The prevalence of concentrations (milliequivalents per liter) of erythrocyte Na+ greater than or equal to 7.0, K+ less than 92.5, and plasma K+ greater than or equal to 4.5 in a subsample of 59 individuals with all combinations of abnormal tolerance obesity and hypertension was compared with those in 30 individuals free of these conditions. Altogether, 88.1% of the former vs. 40.0% of the latter group presented at least one of these three markers of internal cation imbalance (P less than 0.001). We conclude that insulin resistance and/or hyperinsulinemia (a) are present in the majority of hypertensives, (b) constitute a common pathophysiologic feature of obesity, glucose intolerance, and hypertension, possibly explaining their ubiquitous association, and (c) may be linked to the increased peripheral vascular resistance of hypertension, which is putatively related to elevated intracellular sodium concentration.

Adult↗
PubMed1985

Phenytoin bioavailability assessed by steady state serum concentrations.

The effect of a change in bioavailability of phenytoin sodium formulations on steady state serum concentrations was assessed in two groups of neurosurgical patients (n = 20 and 12). One group was studied in 1980 while on the old formulation, the other in 1983 while on the new formulation. Data were also obtained from routine therapeutic-level monitorings in 85 ambulatory patients receiving the new formulation during 1984. Phenytoin levels on the 400-mg/day dose were 10.9 +/- 4.1 (SD) and 16.1 +/- 5.6 micrograms/ml on the old and new formulations, respectively (P less than 0.01) in the neurosurgical patients. Routinely monitored levels on the 300-mg/day dose were 6.9 +/- 4.9 and 12.1 +/- 6.8 micrograms/ml, respectively (P less than 0.01). The maximum elimination rate of phenytoin, estimated from steady state dose-concentration pairs, was significantly higher on the old formulation (9.5 +/- 2.8 vs. 7.2 +/- 1.1 mg/kg per day, P less than 0.025) even though there was no difference in the estimates of the Michaelis-Menten constant. The proportion of subtherapeutic levels on ostensibly equal doses fell from 85 to 45% on 300 mg/day of the two formulations (P less than 0.01), and to 28% on 400 mg/day of the new formulation. Steady state concentrations may be used to assess increased bioavailability of drugs with capacity-limited metabolism, such as phenytoin.

Adult↗
PubMed1984

Effectiveness of glycosylated hemoglobin, fasting plasma glucose, and a single post load plasma glucose level in population screening for glucose intolerance.

Five shortcut methods of population screening for glucose intolerance (impaired glucose tolerance and non-insulin-dependent diabetes mellitus) were assessed for effectiveness: 1) glycosylated hemoglobin concentration (HbA1), 2) fasting plasma glucose level, 3) combinations of fasting plasma glucose and HbA1, 4) plasma glucose one hour post oral glucose load, and 5) plasma glucose two hour post oral glucose load. In a sample of the Israeli Jewish population aged 40-70 years, 2040 participants in the Israel Study of Glucose Intolerance, Obesity and Hypertension, who were not known to be diabetic, underwent an oral glucose tolerance test based on three blood samples (fasting, one hour, and two hour post oral glucose load). In 1058 of the subjects, HbA1 was also measured, and was found to increase significantly (P less than 0.001) with increasing glucose intolerance, but with extensive overlap of ranges, even between normals and newly found diabetics. Fasting plasma glucose was more effective than HbA1 in screening for both impaired glucose tolerance and diabetes by its higher specificity and predictive value of a positive test at comparable sensitivity levels. Combinations of HbA1 and fasting plasma glucose did not improve prediction over fasting plasma glucose alone. As observed in other studies, the screening effectiveness of fasting plasma glucose was also unsatisfactory, either post load glucose level being more effective. Plasma glucose level two hour post load was better for detection of diabetes alone. Plasma glucose level one hour post load was more effective at detecting the total group of glucose intolerance, but did not discriminate well between impaired tolerance and diabetes. A cost-risk-benefit evaluation suggests that a full three-sample oral glucose tolerance test is the best method in screening for both intolerance categories.

Adult↗
PubMed1984

Kinetics of intravenous phenytoin in children.

Single-dose intravenous phenytoin (9.4-21.3 mg/kg) effectively eradicated seizures within 3 minutes in 12 out of 13 patients in status epilepticus. Eleven additional patients were treated prophylactically. No adverse effects were observed and neurological status was unaltered in all 24 cases. Phenytoin volume of distribution was found to decline significantly with age from 1.6 L/kg at 1 year to 0.6 at 10 years (P less than 0.01). Estimates of Vmax, the maximal rate of phenytoin metabolism, were obtainable in 8/24 patients and were in the expected range (10.6 +/- 4.2 mg/kg/day) for their age (6.6 +/- 2.8 years). Therapeutic serum concentrations (initial post distribution values 17.9 +/- 9.0 micrograms/ml) were maintained for more than 10 hours in 15/24 patients. Single-dose intravenous phenytoin is both effective and safe in the treatment and prevention of epileptic seizures in pediatric patients.

Adolescent↗
PubMed1983

Unsuspected urethral stricture presenting as acute water intoxication.

We report a case of an unsuspected urethral stricture that caused acute water intoxication with generalized convulsions. The patient drank excessive amounts of water in an attempt to relieve obstruction. Osmolality, water balance and renal function returned to normal after relief of obstruction. A urethral stricture should be considered in the diagnosis of a patient with severe dilutional hyponatremia.

Acute Disease↗