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Biomedical subjects

D Gavish

Publications and source records attributed to D Gavish.

At least 19 recordsLinked to original sources
PubMed2006

The effect of a rapid weight loss induced by laparoscopic adjustable gastric banding on arterial stiffness, metabolic and inflammatory parameters in patients with morbid obesity.

OBJECTIVE: To determine the effect of drastic weight loss on arterial compliance, inflammatory and metabolic parameters in patients with morbid obesity with and without cardiovascular risk factors who underwent laparoscopic adjustable gastric banding (LAGB). DESIGN: Open prospective study, morbidly obese subjects divided into low- and high-risk group were evaluated before and 4 months after LAGB. SUBJECTS: Forty-one Caucasian subjects aged between 16 and 55 years, with morbid (grade 3) obesity (20 low- risk and 21 high-risk subjects) who underwent LAGB and completed a 16-week follow-up. MEASUREMENTS: Patients were evaluated at baseline and 4 months after LAGB for body mass index (BMI), arterial blood pressure (BP), metabolic factors including lipid profile, HbA1C, insulin, C-peptide, fibrinogen, hs-C reactive protein (CRP) and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity of large and small arteries was evaluated using pulse-wave contour analysis method (HDI CR 2000, Eagan, Minnesota) at baseline and after 4 months. RESULTS: Body mass index reduction induced by LABG, from 43.55+/-5.11 to 35.10+/-4.87 in low-risk patients and from 42.90+/-3.22 to 35.00+/-3.24 in high-risk patients, significantly improved small artery elasticity (SAE) from 6.30+/-2.74 to 7.25+/-1.85, in morbidly obese patients with multiple cardiovascular risk factors (high-risk group). Improvement in SAE was accompanied by improvement of arterial BP, glucose and lipid metabolism, and reduction of CRP values. CONCLUSION: Although dramatic weight reduction induced by surgical intervention was associated with similar changes in body weight and significant improvement of metabolic and inflammatory parameters in two groups of obese patients, SAE improved only in high-risk patients.

Adolescent↗
PubMed2006

Long-term thyrotropin-suppressive therapy with levothyroxine impairs small and large artery elasticity and increases left ventricular mass in patients with thyroid carcinoma.

BACKGROUND: Exogenous subclinical hyperthyroidism, caused by long-term thyrotropin (TSH)-suppressive treatment with levothyroxine (LT(4)), is associated with several cardiovascular abnormalities. In order to assess the effect of long-term thyroid hormone-suppressive therapy on the blood vessels and myocardium, we determined the arterial elasticity, using the pulse wave contour analysis. METHODS AND RESULTS: Twenty-six athyreotic patients receiving TSH-suppressive LT(4) therapy for periods ranging from 3 to 21 years at a mean daily dose of 2.25 +/- 0.5 microg/kg per day were included in the study. Twenty six age- and gender-matched healthy subjects served as controls. Arterial elasticity of large and small arteries was evaluated using pulse wave contour analysis method (HDI CR 200, Eagen, MN). Cardiac structure was assessed by two-dimensional echocardiography. We found decreased large artery elasticity in subclinical hyperthyroidism (sHT) patients compared to controls (14.14 +/- 3.38 versus 10.53 +/- 2.43 L/mm Hg x 100, p < 0.000). Small artery elasticity was also lower in patients than in controls (5.42 +/- 1.82 versus 4.30 +/- 1.75 mL/mm Hg x 100, p < 0.056). The echocardiographic data showed significantly increased left ventricular (LV) mass index (101.90 +/- 18.61 versus 88.03 +/- 22.01 g/m(2), p < 0.049) and interventricular septum thickness (10.61 +/- 1.46 versus 9.11 +/- 1.13 mm, p < 0.002) in LT(4)-treated patients compared to controls. CONCLUSIONS: We found impaired vascular elasticity of large and small arteries and increased LV mass in patients receiving long-term TSH-suppressive therapy with LT(4).

Arteries↗
PubMed2003

The Ashkelon Hypertension Detection and Control Program (AHDC Program): a community approach to reducing cardiovascular mortality.

BACKGROUND: Blood pressure (BP) reduction is crucial in reducing cardiovascular (CV) morbidity and mortality in the community. Subjects aged 20-65 seldom visit the primary care clinics, so they are unlikely to be detected without an active outreach screening program. The aim of the project was to prepare a professional doctor-nurse screening team, who will instruct those found to be at high risk in control of their risk factors, in order to reduce CV morbidity and mortality. METHODS: During a 10-year period (1980-1990), teams examined 12,202 subjects, (mean age 51 +/- 7 years, range 20-65 years) accounting for 23.4% of the total regional population. High risk subjects underwent an intensive CV risk factor control program. RESULTS: Subjects (3,506 or 28.6%) were found to have one or more CV risk factors (hypertension, obesity, smoking, hypercholesterolemia). During an average of 2 years, follow-up BP, weight reduction, and smoking cessation remained statistically significant. Total cholesterol was unchanged. Over this period, the standardized mortality ratio (SMR) in the area for acute MI fell from 100 to 76 (P < 0.01), for CV disease from 129 to 107 (P < 0.0001), and for hypertension from 121 to 87 (P < 0.1 NS). The project saved many life-years at no additional net cost to society, and cost effectiveness analysis showed positive results. CONCLUSIONS: A community approach with mainly nonpharmacological treatment is feasible and cost effective in reducing CV morbidity and mortality.

Adolescent↗
PubMed2003

Risk factor profile and achievement of treatment goals among hypertensive patients from the Israeli Blood Pressure Control (IBPC) program--initial cost utility analysis.

AIMS: Blood pressure (BP) reduction is crucial in reducing cardiovascular morbidity and mortality. The IBPC (Israeli Blood Pressure Control) program was initiated in order to enhance the control of modifiable risk factors among high-risk hypertensive patients under follow-up by general practitioners in Israel. The cost effectiveness of an intervention program is an important factor in the decision-making process of its implementation and therefore was evaluated here. The objective of this evaluation is to estimate the costs, monetary savings and benefits in terms of QALYs (quality-adjusted life years) that would be expected if the program were to be expanded to 100 clinics nationwide, enabling around 14800 persons to be treated. METHODS: Hypertensive patients were screened in 30 general practice clinics, supervised by specialists in family medicine, each seeing 1000-5000 patients; 50-250 hypertensive patients were diagnosed at each participating clinic. BP levels, body mass index (BMI), lipid and glucose levels, as well as target organ damage and medications were recorded for all patients. RESULTS: A total of 4948 (2079, 42% males) were registered. Mean age was 64.8 +/- 12 years. After 1 year of follow-up versus baseline, the various parameters were as follows: BP control was achieved in 46.4% vs 29% of all hypertensive patients. LDL control (JNC VI criteria) was achieved in 41.7% vs 31.2% of all patients. Fasting plasma glucose control (glucose < 126 mg/dl) was achieved in 22% vs 19% of diabetic patients and 5.2% vs 3.1% of the diabetics had fasting plasma glucose levels > 200 mg/dl. Obesity (BMI > 30 kg/m2) was noted in 36.7% vs 43.8% at baseline. The cost utility analysis of the reduction in risk factors was calculated based on the international dicta applied to the reduction in risk factors as a result of treatment. For 100 clinics nationwide and 14800 persons to be treated the net saving to health services would be $977993 and the increase in QALYs would be 602 years. CONCLUSIONS: Better risk factor control in hypertensive patients by general practitioners could reduce morbidity and mortality as well as be cost effective.

Aged↗
PubMed2001

Treatment with atorvastatin improves small artery compliance in patients with severe hypercholesterolemia.

BACKGROUND: We studied the effect of atorvastatin on arterial compliance in patients with severe hypercholesterolemia. METHODS: Seventeen patients with low-density lipoprotein cholesterol levels above 170 mg/dL, were included in the study, none of whomever received hypolipidemic medication or had other risk factors. Patients were followed for five visits, every 4 weeks. RESULTS: After 20 weeks of treatment, lipid profile improved significantly. Large artery elasticity index did not change significantly, but small artery elasticity index increased by 21% (4.6+/-0.5 to 5.6+/-0.9, P < .01). Although none of our patients suffered from hypertension, both systolic and diastolic blood pressure (BP) decreased significantly (6 mm Hg and 3 mm Hg, respectively). CONCLUSIONS: We conclude that atorvastatin improves the elasticity of small arteries and reduces systolic and diastolic BP in patients with severe hypercholesterolemia.

Adult↗
PubMed2001

[Atherosclerosis as an autoimmune disease].

The first medical conference on the subject of atherosclerosis and the immune system was held this year in Geneva Switzerland (8-11/3/2001) and included presentations by leading researchers in this field. Briefly, the discussions concluded that the immune system has a major role in the induction of atherosclerosis, at the beginning, and in the initiation of the atherosclerotic plaque rupture, in the end. Moreover, modifications in the inflammatory system have been shown (only in experimental models) to reduce the rate of the development of atherosclerosis. It might be assumed that some part of the role that statins in this event reduction can be attributed to the anti-inflammatory property of the drug. It is clear that better understanding of this issue will evolve, and in the future, new modalities of treatment will develop that will act by influencing the inflammatory system.

Arteriosclerosis↗
PubMed2000

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Aged↗
PubMed2000

Bezafibrate and simvastatin combination therapy for diabetic dyslipidaemia: efficacy and safety.

OBJECTIVE: To determine the efficacy and safety of a statin-fibrate combination in diabetes patients. DESIGN.: An open 21-month trial in which each patient first received the single drug for 6 months and then a combination of the two for 1 year. SETTING: Three lipid clinics in university-based tertiary care hospitals. PATIENTS: One hundred and forty-eight patients with type 2 (non-insulin-dependent, NIDDM) diabetes mellitus under stable control for 3 months by means of diet and oral hypoglycaemic medication. INTERVENTION: Patients from one clinic (n = 48) received bezafibrate slow release (400 mg day-1), and patients from the other two clinics (n = 100) received simvastatin 20 mg day-1. Six months later, all patients were switched to a daily combination of 400 mg bezafibrate slow release and 20 mg simvastatin for 1 year. RESULTS: The combination of statin and fibrate led to a 23% reduction in total cholesterol, 42% reduction in triglycerides, 29% reduction in LDL-c, 25% increase in HDL-c, 10% decrease in fibrinogen and 19% reduction of Lp(a) levels, and a decrease in the cholesterol/HDL-c ratio (from 8.9 to 5.4) in all 148 patients. Cardiovascular (CV) event rate was significantly reduced from 9.5% during the first 6 months of the study to less than 2% during the last year of the study (whilst on combination Rx). Side-effects with all treatments included only two patients who developed myopathy when on the combined regimen and one on the single statin regimen. However, plasma creatinine phosphokinase (CPK) levels doubled (but remained within the normal range) in most of the patients on combination therapy, compared with only a mild increase in patients receiving a single medication. CONCLUSIONS: The statin and fibrate combination was found to be more efficacious than a single medication for treatment of diabetic dyslipidaemia, as evidenced by improvement in the lipoprotein profile, reductions in Lp(a), fibrinogen and CV event rate, and almost no clinically significant side-effects.

Aged↗
PubMed2000

Medical history of hypercholesterolaemia adversely affects the outcome of out-of-hospital cardiopulmonary resuscitation; the 'Shahal' experience in Israel.

AIMS: To evaluate the impact selected risk factors for cardiac death may have on the success rate in a large cohort of subscribers to 'SHAHAL' who were resuscitated from out-of-hospital cardiac arrest. METHODS AND RESULTS: In this medical facility currently serving 50 000 subscribers, data were prospectively gathered from between 1987-1998. The information retrieved from the patients' medical records included a medical history of hypertension, diabetes, hypercholesterolaemia (>220.mg. dl(-1)) smoking, angina, previous myocardial infarction, and congestive heart failure. A total of 998 patients aged 74+/-12 years (mean+/-1 SD) were included. Death was announced at the scene for 659 (66%) victims, while 339 (34%) patients were taken to hospital. Of these 140 (14% of the total cohort) survived and were discharged from the hospital. A comparison of various selected parameters between survivors and non-survivors of resuscitation revealed that survivors were younger, had a higher rate of pulseless ventricular tachycardia/ventricular fibrillation, more were among the arrests witnessed by the 'SHAHAL' team, and that more had a shorter time lag to initiation of cardiopulmonary resuscitation than non-survivors. None of the studied risk factors predicted the outcome of cardiopulmonary resuscitation, with the exception of hypercholesterolaemia, which carried a significantly worse prognosis for cardiopulmonary resuscitation (P=0.009). CONCLUSIONS: A medical history of hypercholesterolaemia appears to be an important risk factor which adversely affects the outcome of cardiopulmonary resuscitation.

Aged↗
PubMed1996

Diurnal heterogeneity in structure and function of low density lipoproteins of normolipidemic males.

Structural changes in low density lipoproteins (LDL) have been shown to alter their metabolism and atherogenic potential. We investigated the diurnal changes in size and composition of LDL in seven healthy, non-obese, normolipidemic male volunteers consuming a standard diet (14.5% protein, 31.9% fat, 53.6% carbohydrate and 383 mg cholesterol/day) and continuing their daily routine. The food was divided into three meals and three snacks, and blood samples were obtained at 7 AM (after 12 h fasting), noon, 8 PM, midnight and 3 AM. LDL were isolated by both sequential and density gradient ultracentrifugation (d = 1.019 - 1.050 g/ml), and analyzed for lipids, apolipoproteins, size, and affinity to LDL receptors. Diurnal LDL preparations differ from fasting LDL in both chemical and physical parameters. The former get richer in triglyceride (TG/cholesterol weight ratio 0.23 vs. 0.16), larger in diameter (21.2 +/- 0.2 vs. 22.4 +/- 0.1 nm), and enriched in a more buoyant fraction (74.0 +/- 4.6 vs. 41.9 +/- 3.8% of LDL cholesterol in d = 1.019 - 1.035 g/ml). These structural changes in LDL were associated with enhanced affinity to LDL receptors in both human skin fibroblasts and HepG2 cells, as demonstrated by competition experiments with fasting human 125I-LDL. The observed diurnal heterogeneity in both the structure and the function of LDL may be attributed to the absorptive state as it did not occur during prolonged fasting. These diurnal changes may be important for better understanding LDL metabolism in vivo and for the elucidation of the atherogenic process.

Adult↗
PubMed1995

The effect of lovastatin on early restenosis.

The effect of lovastatin given before percutaneous coronary angioplasty (PTCA) on early restenosis was investigated in men with mild to moderate hypercholesterolemia. Thirty-four hypercholesterolemic patients (serum LDL cholesterol 130-200 mg/dL) undergoing their first PTCA completed a 6-month prospective, double-blind, placebo-controlled trial. Eighteen received lovastatin 20 mg/day (Lo group) and 16 placebo (P1 group), beginning 10 to 21 days before PTCA. All underwent a thallium-201 quantitative exercise test 5 to 7 days after PTCA. Endpoints for restenosis were either 50% narrowing of the dilated artery on coronary angiography, performed in symptomatic patients or, in asymptomatic patients, the appearance of newly developed reversible filling defects in the vascular territory of the dilated artery on a second thallium scan done 6 months after PTCA. The hypocholesterolemic change observed in the Lo group was not accompanied by a reduction in early restenosis risk. The authors conclude that effective hypocholesterolemic therapy before PTCA does not affect early restenosis rate in men with mild to moderate hypercholesterolemia.

Adult↗
PubMed1994

Diurnal changes in plasma lipoproteins of free-living healthy men consuming a standard diet.

Although it is well established that plasma lipoproteins are involved in atherogenesis, most patients with coronary heart disease have normal or nearly normal fasting plasma lipid and lipoprotein levels. As most of the human life is spent in the fed state we elected to investigate the changes occurring in plasma lipids and lipoproteins during normal daily activities. We studied 12 healthy, normolipidemic and non-obese subjects on a standard diet divided into three meals and three snacks. This method was found to be accurate and reproducible in four subjects who underwent repeated studies. The major diurnal changes were observed in plasma triglyceride level and in the composition of plasma lipoproteins. The degree and pattern of these changes differed among subjects but was specific and constant for each individual. The extent of these diurnal changes, which correlated positively with fasting plasma triglyceride and inversely with plasma HDL2 levels, may play an important role in the pathogenesis of atherosclerosis.

Activities of Daily Living↗
PubMed1991

Plasma lipoprotein(a) concentration is controlled by apolipoprotein(a) (apo(a)) protein size and the abundance of hepatic apo(a) mRNA in a cynomolgus monkey model.

The cynomolgus macaque was used as a model to study lipoprotein(a) (Lp(a)). Antibodies to Lp(a) were used in Ouchterlony and Western blot analysis to show that cynomolgus monkey and human Lp(a) were similar immunochemically. Monkey Lp(a) levels were measured by a quantitative sandwich enzyme-linked immunosorbent assay in 117 animals, and Lp(a) varied in concentration from 1 to 64 mg/dl. Individual monkeys had apo(a) glycoprotein sizes as either single- or double-band phenotypes that ranged from 400 to 750 kDa. Monkey apo(a) transcript lengths varied from 8.5 to 13.6 kilobases. The Lp(a) concentration, apo(a) glycoprotein size, and apo(a) transcript length distributions were similar to those in humans. In the monkeys, there was a very high correlation between apo(a) transcript size and apo(a) protein size (R = 0.93, p = 0.0001). This variation in apo(a) transcript and protein size was shown to be due to the number of kringle IV repeats in apo(a) mRNA and DNA. Monkey plasma Lp(a) concentrations correlated inversely with apo(a) glycoprotein size (R = 0.43, p = 0.0016) and directly with hepatic apo(a) mRNA abundance (R = 0.54, p = 0.004). Apo(a) transcript lengths did not correlate with hepatic apo(a) mRNA levels. This suggests that apo(a) size and mRNA levels have major independent effects on plasma Lp(a) concentration. In multivariate analysis, they account for up to 58% of the variability in Lp(a) concentration. In summary, these data provide insight into the regulation of Lp(a) levels and suggest that the cynomolgus monkey is a suitable model in which to study the role of Lp(a) in the pathogenesis of atherosclerosis.

Animals↗
PubMed1991

Lipoprotein(a) reduction by N-acetylcysteine.

Lipoprotein(a), a complex of low-density lipoprotein linked by disulphide bridges with apo(a), is associated with atherosclerotic disease when present at very high plasma concentrations. In vitro, N-acetylcysteine (NAC) dissociates this complex. In two patients with high Lp(a) levels NAC lowered plasma Lp(a) from 58 to 20 mg/dl and from 59 to 18 mg/dl: reductions of this order have not hitherto been achieved either by drugs or by diet.

Acetylcysteine↗
PubMed1990

Cellular metabolism of human plasma intermediate-density lipoprotein (IDL).

The cellular metabolism of human plasma intermediate-density lipoprotein (IDL) was investigated in cultured human skin fibroblasts and hepG-2 cell in the absence and presence of exogenous recombinant or plasmatic apo E-3. IDL (d 1.006-1.019 g/ml) and LDL (d 1.019-1.063 g/ml) were prepared by centrifugation from the plasma of apo E-3/3 or 4/3 normolipidemic human subjects. Without added apo E-3, IDL binding and cell association are similar or slightly reduced while their degradation is one third to one half. This results in degradation to binding ratios for IDL that are half those for LDL. Exogenous apo E-3 enhances binding, association and degradation of IDL by 50-150%, but the degradation to binding ratio remains low. Exogenous apo E-3 also increased the ability of IDL but not LDL, to down-regulate the incorporation of [14C]acetate to sterol by the cells. The optimal concentration of apo E-3 is 4 micrograms protein/10 micrograms IDL protein and at that concentration appreciable amounts of the apo E are found associated with the lipoprotein. Apo E-2 has no effect on the cellular metabolism of IDL and apo E-3 is not effective in receptor-negative human fibroblasts. Monoclonal antibodies that block apo E binding to B,E (LDL) receptor (1D7) abolish the cellular metabolism of IDL while antibodies against B-100 (4G3) are ineffective. In competitive binding experiments, IDL is slightly more effective than LDL in displacing 125I-LDL from receptors in hepG-2 cells and appreciably more effective than LDL when tested against 125I-IDL. Apo E-3 increases the capacity of IDL to compete with either 125I-LDL or 125I-IDL. Addition of apo E-3 also increases the binding affinity of IDL to hepG-2 receptors, with Kd values of 2.50, 0.93 micrograms protein/ml, respectively. The study demonstrates the essential role that functional apo E molecules play in the interaction of human IDL with cellular receptors. Yet, in spite of presence of apo E in IDL (2-3 molecules/particle) and enrichment of IDL with apo E-3 (to 4-5 molecules/particle) the proteolytic degradation of the lipoprotein by specific cellular receptor is similar to LDL.

Antibodies, Monoclonal↗
PubMed1989

Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis.

Endothelial cells play a critical role in thromboregulation by virtue of a surface-connected fibrinolytic system. Cultured endothelial cells synthesize and secrete tissue-type plasminogen activator (t-PA) which can bind to at least two discrete sites on the cell surface. These binding sites preserve the catalytic activity of t-PA and protect it from its physiological inhibitor (PAI-1). N-terminal glutamic acid plasminogen (Glu-PLG), the main circulating fibrinolytic zymogen, also interacts specifically with the endothelial cell surface. Binding is associated with a 12-fold increase in catalytic efficiency of plasmin generation by t-PA which may reflect conversion of Glu-PLG to its plasmin-modified form, N-terminal lysine plasminogen (Lys-PLG). Lipoprotein(a) is an atherogenic lipoprotein particle which contains the plasminogen-like apolipoprotein(a) bound to low density lipoprotein. We report here that lipoprotein(a) interferes with endothelial cell fibrinolysis by inhibiting plasminogen binding and hence plasmin generation. In addition, we demonstrate lipoprotein(a) accumulation in atherosclerotic lesions. These findings may provide a link between impaired cell surface fibrinolysis and progressive atherosclerosis.

Apolipoproteins↗