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Biomedical subjects

R Zaidenstein

Publications and source records attributed to R Zaidenstein.

At least 19 recordsLinked to original sources

Clonal variability of group B Streptococcus among different groups of carriers in southern Israel.

A high prevalence of maternal group B Streptococcus (GBS) carriage and an extremely low incidence of invasive neonatal disease have been reported from southern Israel. In order to obtain insight into this discrepancy, this study was performed to determine the population structure of GBS from asymptomatic pregnant women living in this area. Seventy-two strains from maternal GBS carriers were characterized using multilocus sequence typing (MLST). Epidemiologic characteristics of the carriers and their newborns, including demographic variables, obstetric status, and general health parameters, were collected by means of a postpartum interview and a review of the relevant medical records. The MLST analysis grouped the bacteria into six different lineages (clonal complexes). Lineage ST-2 was prevalent among Bedouin-Arabs (p=0.01) and lineage ST-22 among Jews (p=0.001). Lineage ST-17 was prevalent among carriers who emigrated after 1997 from western nations of the former USSR (p<0.001). Lineage ST-22 was associated with carriage of surface-protein C (p=0.01) and lineage ST-17 with surface-protein R (p<0.01). Lineage ST-2 was prevalent among consumers of antibiotics (p=0.02) and was associated with erythromycin-resistant strains (p<0.001). Each subgroup of the southern Israeli maternal population has a different distribution of GBS clones. The clones prevalent among the Bedouin-Arabs and the Jews are known to be of low virulence. Lineage ST-17, which is associated with invasive disease, is prevalent among women who emigrated from western Soviet nations. Therefore, a different policy of GBS prophylaxis, resembling the one executed in endemic areas, should be considered in this population.

Arabs↗

Serum magnesium aberrations in furosemide (frusemide) treated patients with congestive heart failure: pathophysiological correlates and prognostic evaluation.

OBJECTIVES: To determine the prevalence of hypomagnesaemia and hypermagnesaemia, to discern various factors associated with abnormal serum magnesium, and to estimate prognostic significance of serum magnesium aberrations in patients with congestive heart failure. DESIGN: Observational study. SETTING: Medical department of a university hospital (tertiary referral centre). PATIENTS: 404 consecutive patients admitted with congestive heart failure as one of the diagnoses and previously treated with furosemide (frusemide) for at least three months. MAIN OUTCOME MEASURES: Clinical, biochemical, and electrocardiographic variables were analysed with respect to serum magnesium aberrations. Following discharge, mortality rates, including sudden death, were registered. RESULTS: Hypomagnesaemia was found in 50 patients (12.3%) and 20 (4.9%) were hypermagnesaemic. Female sex (p < 0.04), diabetes mellitus (p < 0.006), hypocalcaemia (p = 0.03), hyponatraemia (p < 0.05), malignant disease (p = 0.05), and high fever (p = 0.05) were statistically associated with hypomagnesaemia. Renal failure, severe congestive heart failure, and high dose furosemide treatment (> 80 mg/day) were associated with hypermagnesaemia (p < 0.001, p = 0.05, and p < 0.03, respectively). Hypermagnesaemic patients were older and weighed less. On follow up (median duration 43 months), 169 (41.8%) died, with 22 (13%) sudden deaths. Mortality was highest with hypermagnesaemia, lowest with normomagnesaemia, and intermediate with hypomagnesaemia. After adjustment for renal failure, old age, and severity of congestive heart failure, hypomagnesaemia but not hypermagnesaemia emerged as being significantly associated with shorter survival (p = 0.009). No statistical association was found between sudden death and magnesium concentrations. CONCLUSIONS: While hypermagnesaemia seems to represent a prognostic marker only, hypomagnesaemia appears to have an adverse pathophysiological effect. The subgroup of patients at risk for hypomagnesaemia requires frequent serum magnesium determinations and magnesium replacement for as long as hypomagnesaemia persists.

Aged↗

The effect of Losartan on insulin resistance and beta cell function in chronic hemodialysis patients.

Insulin resistance (IR) is prevalent in hemodialysis patients. IR and hyperinsulinemia have an important role in the development of atherosclerosis, which is the most common cause of morbidity and mortality in hemodialysis patients. Thus, antihypertensive drugs that lower IR, may have an additional beneficial effect in the treatment of cardiovascular diseases in these patients. In this preliminary study we examined the effect of Losartan (an angiotensin II receptor antagonist) treatment on IR and beta cell function in five hypertensive non-diabetic chronic hemodialysis patients. All other known causes of IR in end stage renal failure were excluded. After a washout period of two weeks, Losartan 50 mg, was administered for 6 weeks. Fasting blood glucose (FBG) and insulin levels were measured before and after the treatment IR and beta cell function were calculated using the "homeostasis model assessment"-HOMA. Systolic and diastolic blood pressure (BP) have not changed significantly throughout the study. FBG increased significantly from 76 mg/dL +/- 1 to 89 mg/dL +/- 4 (p < 0.01), however, insulin levels have not changed significantly. Calculated IR values did not show a difference, but calculated beta cell function decreased significantly after Losartan treatment from 291% +/- 50 to 146% +/- 10, (p < 0.016). These preliminary results suggest that in chronic hemodialysis hypertensive non-diabetic patients short treatment with Losartan has deleterious effect on glucose homeostasis mediated via a decrease in beta cell function.

Aged↗

Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers.

Grapefruit juice (GJ), a cytochrome P450 (CYP) 3A4 inhibitor, may affect the pharmacokinetics of drugs metabolized through CYP 3A4. Losartan, an angiotensin II antagonist, is converted into its main active metabolite E3174 by CYP 3A4 and CYP 2C9. The effect of GJ on losartan pharmacokinetics was assessed in a randomized crossover trial. Losartan was given to 9 volunteers with and without GJ. Concentrations of losartan and its E3174 metabolite were determined in serum by a high-performance liquid chromatography method (HPLC). Significant differences were observed in some of the pharmacokinetic parameters of losartan and its metabolite E3174 after losartan administration with and without co-administered GJ. The lag time (time to drug appearance in serum) of losartan increased significantly with co-administered GJ. The mean residence time (MRT) and half-life (t(1/2)) of the E3174 metabolite were significantly longer and the area under the concentration--time curve (AUC) of the E3174 metabolite was significantly smaller after concomitant GJ administration. The ratio AUC(losartan)/AUC(E3174) was significantly increased after concurrent grapefruit juice intake. The increased lag time of losartan and the increased MRT and t1/2 and decreased AUC of E3174 were considered indicative of simultaneous CYP 3A4 inhibition and P-glycoprotein activation. The significantly increased AUC(losartan)/AUC(E3174) ratio, however, indicates reduced losartan conversion to E3174 by CYP 3A4 metabolism as a result of co-administered GJ.

Adult↗

[The approach to a patient with hypokalemia].

Potassium is the most important intracellular cation in a humans body. Potassium gradient between the intracellular fluid to the extra cellular fluid is crucial for normal nerve-muscle activity. Hypokalemia is a frequent abnormality among patients, exposing them to fatigue and arrhythmia. Understanding the pathophysiology of hypokalemia may help the clinician to treat it properly. The approach to the patient with hypokalemia is presented through the description of a 25-year-old woman who was admitted to the department due to palpitation and hypokalemia. A simple primary investigation is suggested in these cases.

Adult↗

L-NMMA (a nitric oxide synthase inhibitor) is effective in the treatment of cardiogenic shock.

BACKGROUND: The objective was to assess the safety and efficacy of L-NMMA in the treatment of cardiogenic shock. METHODS: We enrolled 11 consecutive patients with cardiogenic shock that persisted after >24 hours from admission, despite coronary catheterization and primary percutaneous transluminal coronary revascularization, when feasible, and treatment with mechanical ventilation, intraaortic balloon pump (IABP), and high doses of catecholamines. L-NMMA was administered as an IV bolus of 1 mg/kg and continuous drip of 1 mg. kg(-1). h(-1) for 5 hours. Treatment with catecholamines, mechanical ventilation, and IABP was kept constant throughout the study. RESULTS: Within 10 minutes of L-NMMA administration, mean arterial blood pressure (MAP) increased from 76+/-9 to 109+/-22 mm Hg (+43%). Urine output increased within 5 hours from 63+/-25 to 156+/-63 cc/h (+148%). Cardiac index decreased during the steep increase in MAP from 2. 0+/-0.5 to 1.7+/-0.4 L/(min. m(2)) (-15%); however, it gradually increased to 1.85+/-0.4 L/(min. m(2)) after 5 hours. The heart rate and the wedge pressure remained stable. Twenty-four hours after L-NMMA discontinuation, MAP (+36%) and urine output (+189%) remained increased; however, cardiac index returned to pretreatment level. No adverse events were detected. Ten out of eleven patients could be weaned off mechanical ventilation and IABP. Eight patients were discharged from the coronary intensive care unit, and seven (64%) were alive at 1-month follow-up. CONCLUSIONS: L-NMMA administration in patients with cardiogenic shock is safe and has favorable clinical and hemodynamic effects.

Aged↗

Metabolic and clinical effects of oral magnesium supplementation in furosemide-treated patients with severe congestive heart failure.

BACKGROUND: Magnesium depletion and hypomagnesemia are common among furosemide-treated patients with chronic congestive heart failure. HYPOTHESIS: This investigation evaluated clinical and metabolic effects of oral magnesium supplementation. METHODS: Ten patients with severe congestive heart failure maintained on high dose furosemide (> or = 80 mg/day) received a supplement of oral magnesium citrate 300 mg/daily for 30 days. Clinical parameters were followed, and peripheral blood mononuclear cell magnesium and zinc content, serum and urine magnesium, potassium, zinc, calcium, phosphorus, and creatinine were assessed. RESULTS: Peripheral blood mononuclear cell magnesium content and serum potassium rose significantly at the end of the study (2.09 +/- 1.89 to 3.99 +/- 2.26 micrograms/mg cell protein, p < 0.05, and 4.17 +/- 0.38 to 4.39 +/- 0.27 mEq/l, p < 0.05, respectively), while the other parameters remained unchanged. CONCLUSION: In some of these patients, oral magnesium supplementation is effective in achieving substantial increments in intracellular magnesium and serum potassium which, in turn, may have cardioprotective effects.

Administration, Oral↗

Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: the effect of no treatment and high-dose amiodarone. A randomized, placebo-controlled study.

BACKGROUND: Spontaneous conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm occurs commonly and is not affected by low-dose amiodarone treatment. METHODS: In a randomized, placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset (<48 h) we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour (total 3 g) and intravenous placebo. Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy. RESULTS: Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients (64%) in the placebo group, most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension, ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm, ejection fraction below 45% or significant mitral regurgitation. However, in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present. In such patients the spontaneous conversion rate was approximately 90%. The conversion rate during 24 h of treatment in the amiodarone group was 92% (P=0.0017, compared to the placebo group). In this group, the conversion rate was largely unaffected by baseline characteristics. Of the 18 patients who did not convert with placebo, 15 (85%) converted after being crossed over to amiodarone. All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month. In patients still in atrial fibrillation after 8 h of treatment, the pulse rate decreased significantly more in the amiodarone as compared to the placebo group (83+/-15 vs 114+/-20 beats. min(-1), P=0.0014). CONCLUSION: The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90% in specific clinical and echocardiographically defined subgroups. Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation. However, such treatment should be reserved for patients with unfavourable risk factor profiles, not converting during 8 h of observation or requiring rate control.

Aged↗

Usefulness of losartan, captopril, and furosemide in preventing nitrate tolerance and improving control of unstable angina pectoris.

Sixty consecutive normotensive patients with unstable angina pectoris, who were on continuous intravenous isosorbide dinitrate (ISDN) treatment and had not previously received angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, or diuretics were randomly assigned to treatment groups receiving intravenous ISDN for 72 hours. No additional treatment was given to group A (n = 15). Captopril, in a test dose of 6.25 mg, and followed by 12.5 mg 3 times daily for 24 hours and 25 mg 3 times daily for the next 24 hours, was given to group B (n = 15). The same dose of captopril plus 40 mg of furosemide in the morning were given to group C (n = 15). Losartan, in a single dose of 25 mg/day and increased to 50 mg after 24 hours was given to group D (n = 15). Nitrate tolerance was evaluated at 24-hour intervals at trough levels of each of the drugs by administering intravenous ISDN (1 mg bolus dose every 4 minutes) and recording the total ISDN test dose required to decrease the mean arterial blood pressure by > or =10%. Treatment with continuous ISDN only (group A) induced nitrate tolerance. The ISDN (mean +/- SD) test dose was 3.5 +/- 1.8 mg at baseline, increasing to 4.9 +/- 2.4 mg at 24 hours, and 8.0 +/- 3.0 mg at 48 hours. The addition of increasing doses of captopril to the continuous ISDN treatment (group B) completely prevented nitrate tolerance. Losartan, however, did not attenuate nitrate tolerance at 24 hours and attenuated it only partially at 48 hours. The addition of furosemide to captopril had no further effect on nitrate tolerance. Of 15 patients in group A (ISDN only), 4 (27%) experienced recurrent ischemic events requiring urgent coronary catheterization. No such events were recorded in group B (captopril), but did occur in 1 patient in each of group C (captopril plus furosemide) and D (losartan) (p = 0.083). Thus, the addition of captopril to the ISDN treatment regimen prevented tolerance to nitrates and improved angina control with apparent safety. Losartan also decreased nitrate tolerance, although to a lesser extent, and also improved angina control. The addition of furosemide to captopril conferred no further benefit.

Adult↗

Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema.

BACKGROUND: Nitrates and furosemide, commonly administered in the treatment of pulmonary oedema, have not been compared in a prospective clinical trial. We compared the efficacy and safety of these drugs in a randomised trial of patients with severe pulmonary oedema and oxygen saturation below 90%. METHODS: Patients presenting to mobile emergency units with signs of congestive heart failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and morphine 3 mg bolus. 110 patients were randomly assigned either to group A, who received isosorbide dinitrate (3 mg bolus administered intravenously every 5 min; n=56) or to group B, who received furosemide (80 mg bolus administered intravenously every 15 min, as well as isosorbide dinitrate 1 mg/h, increased every 10 min by 1 mg/h; n=54). Six patients were withdrawn on the basis of chest radiography results. Treatment was continued until oxygen saturation was above 96% or mean arterial blood pressure had decreased by 30% or to below 90 mm Hg. The main endpoints were death, need for mechanical ventilation, and myocardial infarction. The analyses were by intention to treat. FINDINGS: Mechanical ventilation was required in seven (13%) of 52 group-A patients and 21 (40%) of 52 group-B patients (p=0.0041). Myocardial infarction occurred in nine (17%) and 19 (37%) patients, respectively (p=0.047). One patient in group A and three in group B died (p=0.61). One or more of these endpoints occurred in 13 (25%) and 24 (46%) patients, respectively (p=0.041). INTERPRETATION: High-dose isosorbide dinitrate, given as repeated intravenous boluses after low-dose intravenous furosemide, is safe and effective in controlling severe pulmonary oedema. This treatment regimen is more effective than high-dose furosemide with low-dose isosorbide nitrate in terms of need for mechanical ventilation and frequency of myocardial infarction.

Acute Disease↗

Unrecognized major bleeding following thrombolysis for acute myocardial infarction presenting with syncope.

Complete atrioventricular block and syncope sometimes are the presenting signs of acute myocardial infarction. In a presyncopal attempt to assume sitting position, the patient may fall and suffer consequent trauma. Once in hospital, this sequence of events may be overlooked by both the patient and admitting physicians. Moreover, physical examination initially may not be revealing. We report on two such patients who developed massive subcutaneous bleeding following thrombolytic and heparin treatment. We conclude that these patients constitute a specific group with a relatively high risk of trauma and bleeding at the gluteal region following thrombolytic therapy. Special attention must be given to these patients.

Accidental Falls↗

The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil.

OBJECTIVE: To investigate the effect of grapefruit juice (GJ) on the pharmacokinetics of orally administered verapamil in hypertensive patients. METHODS: Ten hypertensive patients on chronic verapamil treatment participated in a two-day study. On day 1 200 ml of water was given 1 hour before, and together with the morning verapamil dose; on the day 2, water was replaced by GJ in the same order. Serial blood samples were collected and the concentrations of verapamil and its main dealkylated metabolite (D-617) were determined by high-performance liquid chromatography (HPLC). The area under the concentration versus time curve of verapamil (AUCv) and its metabolite D-617 (AUCM) were calculated before and after GJ ingestion. The peak serum concentration (Cmax) and the time until its appearance (tmax) were also determined. RESULTS: GJ did not affect Cmax, tmax, AUCv or AUVm. The AUCv/AUCm ratio (AUCR) was slightly, but significantly, increased after GJ (1.67 vs 1.92). CONCLUSIONS: A single administration of GJ with short-acting verapamil has no significant effect on the pharmacokinetics, of verapamil.

Administration, Oral↗

Effects of captopril and enalapril on zinc metabolism in hypertensive patients.

OBJECTIVE: To investigate the effect of chronic captopril and enalapril treatment on zinc metabolism in hypertensive patients by assessing zinc levels in serum, urine and monocytes. METHODS: Patients with newly diagnosed essential hypertension were randomly divided into two treatment groups: those treated with captopril only (n = 16) and those treated with enalapril only (n = 18). Ten healthy subjects served as controls. Prior to the start of treatment and again 6 months later, zinc was assessed in the serum, in urine collected over 24 hours, and in peripheral blood monocytes. RESULTS: Significant enhancement of 24-hour urinary zinc excretion (micrograms/24 hour) after 6 months of treatment was observed only in the captopril-treated group (p < 0.01). However, intramonocytic zinc levels decreased significantly in both of the treated groups over the same period (p < 0.01 and P < 0.04 in the captopril- and enalapril-treated groups, respectively). CONCLUSION: Treatment of hypertensive patients with captopril or enalapril may result in zinc deficiency.

Angiotensin-Converting Enzyme Inhibitors↗

[Quinidine-induced rheumatic toxicity].

2 women with quinidine-induced lupus are presented. This condition is rare; only about 30 cases have been reported in the English literature. Both our patients had arthritis of the wrist, antinuclear antibodies with homogenous pattern and elevated ESR. Anti-double stranded DNA antibodies were present in 1 patient, and a petechial rash in the other. Complete resolution of arthritis occurred within a few days after quinidine withdrawal, but antinuclear antibodies persisted for several months.

Aged↗

Conservative treatment for Brucella endocarditis.

Endocarditis is the most devastating complication of brucellosis. The accepted treatment for Brucella endocarditis (BE) is a combination of valve replacement and antibiotics. Conservative antibiotic treatment alone is not recommended by most authors, as it is considered ineffective, risking fatality. We describe a patient with BE, in whom antibiotic treatment alone resulted in complete recovery. On reviewing the literature, we found 12 additional such cases. We compared this group of 13 patients with data from 49 published cases treated with a combination of surgery and antibiotics, with a favorable outcome. Absence of congestive heart failure or a prosthetic valve, relatively mild extravalvular cardiac involvement, and a somewhat shorter disease history until initiation of treatment were characteristic of the group treated conservatively in comparison with patients who underwent surgery. In selected patients with BE, conservative antibiotic treatment may be a valid alternative to surgery.

Anti-Bacterial Agents↗

Increased toxicity of high-dose furosemide versus low-dose dopamine in the treatment of refractory congestive heart failure.

OBJECTIVE: To evaluate the safety and efficacy of low-dose dopamine, high-dose furosemide, and their combination in the treatment of refractory congestive heart failure. METHODS: Twenty consecutive patients with refractory congestive heart failure were randomized to receive intravenous low-dose (4 micrograms/kg/min) dopamine combined with low-dose (80 mg/day) oral furosemide (group A; n = 7), intravenous low-dose dopamine with medium-dose furosemide (5 mg/kg/day through continuous intravenous administration; group B; n = 7), or high-dose furosemide (10 mg/kg/day through continuous intravenous administration; group C; n = 6). RESULTS: The three groups showed similar improvement in signs and symptoms of congestive heart failure, urinary output (2506 +/- 671 ml/24 hr, mean +/- SD) and weight loss (3.3 +/- 2.3 kg) after 72 hours of therapy. Mean arterial blood pressure (MAP) decreased by 14% +/- 8% and 15% +/- 6% in groups B and C, respectively, but increased by 4% +/- 15% in group A (p = 0.017). Renal function deteriorated significantly in groups B and C: creatinine clearance decreased by 41% +/- 23% and 42% +/- 23%, respectively, but increased by 14% +/- 35% in group A (p = 0.0074). MAP decrease was positively correlated with the decrease in creatinine clearance (r = 0.7; p = 0.0007). Patients in group B and C had more hypokalemia than group A. Two patients in group C sustained acute oliguric renal failure and one patient in group B died suddenly while sustaining severe hypokalemia. CONCLUSION: Combined low-dose intravenous dopamine and oral furosemide have similar efficacy but induce less renal impairment and hypokalemia than higher doses of intravenous furosemide taken either alone or with low-dose dopamine. The renal impairment induced by intravenous furosemide is probably related to its hypotensive effect in patients with refractory congestive heart failure.

Acute Kidney Injury↗

Benign familial microcytic thrombocytosis with autosomal dominant transmission.

Familial thrombocytosis is an extremely rare disorder, so far reported in only a handful of families. In the majority of cases the characteristics were of essential thrombocythemia. Most patients presented with a platelet count above 800,000/mm3, were diagnosed as having a myeloproliferative disease, and some required chemotherapy. We describe a benign form of familial thrombocytosis with autosomal dominant inheritance in five healthy members of three generations of a family, all of whom had moderate thrombocytosis within the range 422,000-662,000/mm3, characterized by low mean platelet volume. A careful medical history and a 5-year follow up of the subjects did not reveal any untoward clinical development. This variant of familial thrombocytosis is therefore of a benign nature. Possible mechanisms linking thrombocytosis with platelet microcytosis in this family are discussed.

Adolescent↗

Chylothorax following median sternotomy.

Reports of chylothorax (CT) following median sternotomy are rare, amounting so far to 16 cases in the English literature, of which 6 were cases of postcoronary artery bypass grafting (CABG). This report deals with an additional case of a 70-year-old woman who developed left pleural chylous effusion following CABG. It is suggested that the incidence of this type of pleural effusion is considerably greater than the few cases hitherto reported. Moreover, as CT may produce serious pulmonary and/or pleural functional impairment, it is proposed that a diagnostic tap be performed more often in cases of post CABG pleural effusion and that preventive drainage be instituted when CT is diagnosed.

Aged↗