Tirofiban in unstable coronary disease.
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Biomedical subjects
Publications and source records attributed to M Liron.
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OBJECTIVE: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. DESIGN: Case control study over three years. SETTING: An 800 bed general municipal hospital. SUBJECTS: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. INTERVENTIONS: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. MAIN OUTCOME MEASURE: Postprandial lipoprotein metabolism. RESULTS: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) mumol/l.h; 95% confidence interval of difference 4.37 to 11.82). CONCLUSION: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.
A study of 8 Israeli population groups for the ORM1 polymorphism included 1242 serum samples: 156 samples from Arab Moslems, 139 from Arab Druzes, and 947 from 6 Jewish groups. The two most frequent alleles in Europeans and Asians, ORM1*F1 (ORM1*1) and ORM1*S (ORM1*2) were found in Jews and Arabs at frequencies similar to those in Europe. Unique to Arab and Jewish populations were polymorphic frequencies of two ORM1 slow electrophoretic variants, designated ORM1*S1 and ORM1*S2. These were formerly observed only in Europe, where two individuals with *S1 and two with *S2 have been observed so far. The Chueta community of converted Majorcan Jews is the only previously studied group that, like the other studied Jewish groups, has polymorphic frequencies of both ORM1*S1 and ORM1*S2. In this study we associate the Chuetas with the Israeli groups, as a population of Middle Eastern origin. Published data on ORM1 in Europe and East Asia together with the present data, making a total of 47 populations, were subjected to a discriminant analysis that resulted in a correct classification of 93.6% of the populations. Results of this analysis suggest that ORM1 is a useful polymorphic marker for anthropological studies.
The selection of the most appropriate therapy for hypertension remains a controversial issue. Little information is available regarding the prescribing patterns of antihypertensives in the primary care setting in Israel. The use of antihypertensives in 200 patients of the Maccabi Health Fund was, therefore, examined from April to June 1994. Sixty-four per cent of patients received monotherapy and 36% combination therapy. The most commonly prescribed medication for monotherapy were angiotensin-converting enzyme (ACE) inhibitors (33.6%), followed by beta-blockers (28.1%) and calcium channel antagonists (26.6%). Diuretics were prescribed to 7.0% of the patients. Analysis of overall drug utilization showed that diuretics were used in 21.5% of patients, beta-blockers in 39.5%, calcium channel blockers in 46% and ACE inhibitors in 40% of patients. Despite the growing evidence of the benefits of diuretics and beta-blockers, our results show a low utilization of these agents in comparison to other countries. It may be speculated that the lack of national guidelines, the absence of utilization reviews by third party providers as well as differences in patient population and climate conditions may all contribute to the current prescribing habits of physicians in the Israeli community.
Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.
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Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridemia using the vitamin A loading test. This method investigates specifically postprandial lipoprotein metabolism. The determination of vitamin A ester level retinyl palmitate (RP) differentiates the circulating plasma chylomicron and chylomicron remnant fractions from the endogenous VLDL and IDL. Subjects with normal renal function with or without fasting hypertriglyceridemia served as control groups. Dialysis patients have significantly higher level of chylomicron remnants for a more prolonged period of time than controls, irrespective of their fasting triglyceride levels. The area below retinyl palmitate chylomicron remnants curve was 26308 +/- 12422 micrograms/liter.hr in the normolipidemic dialysis patients, significantly higher than (6393 +/- 2098 micrograms/liter.hr; P < 0.0001) in the normolipidemic controls. The retinyl palmitate chylomicron remnants curve of the hypertriglyceridemic dialysis patients was 21021 +/- 4560 micrograms/liter.hr, which was higher than 12969 +/- 2215 micrograms/liter.hr (P < 0.0001) in the hypertriglyceridemic controls. Moreover, the hypertriglyceridemic dialysis patients had an additional defect in the lipolysis metabolic step, that is, accumulation of chylomicrons in circulation. These findings show a severe defect in postprandial lipoprotein metabolism in chronic renal failure patients. The prolonged exposure of the vascular wall to high chylomicron remnant concentrations might be an important pathogenetic factor in the accelerated atherosclerosis seen in chronic dialysis patients.
Postprandial lipoprotein metabolism may play an important role in the development of atherosclerosis. It is widely believed that in healthy octogenarians, the atherogenic process occurs very slowly. In the present study, postprandial lipoprotein metabolism was examined in 14 octogenarian subjects (mean age, 84 +/- 4.2 years) and 19 younger controls (mean age, 50 +/- 4.8 years) using the vitamin A-fat loading test, in which intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Results indicated that mean peak chylomicron remnant RP levels and the areas below the chylomicron remnant RP curve were significantly lower in the octogenarian group than in the controls (625 +/- 329 vs 1321 +/- 688 micrograms/L and 3740 +/- 1078 vs 6162 +/- 1063 micrograms/L.h, respectively; p < .0001). No differences were found between the two groups in chylomicron RP levels or in lipolytic activity. The study suggests that octogenarians do not exhibit the decrease in chylomicron lipolysis that usually accompanies aging. In addition, these subjects have significantly lower levels of chylomicron remnants in the circulation. Since accumulation of these particles has been implicated in the development of atherogenesis, our findings may indicate a major mechanism of atherosclerosis prevention in healthy octogenarians.
To study post-prandial lipoprotein metabolism in normolipidemic and hypertriglyceridemic subjects, a vitamin A fat loading test was used. This method specifically labels dietary fat particles with retinyl palmitate (RP). Following RP concentrations, metabolic behavior of chylomicrons and chylomicron remnants were studied. In normal subjects, post-prandial lipoproteins were present for more than 10 h. Total RP increased rapidly between 1 and 4 h, peaked at 6 h and declined rapidly between 6 and 10 h. The chylomicron and chylomicron remnant fractions behaved differently, showing precursor product relationship. The hypertriglyceridemic patients demonstrated a very severe defect in chylomicron clearance. This fraction was 2.8-fold higher than in normal subjects, which was 7,260 vs. 2,600 micrograms/l, respectively. The large magnitude and long duration of post-prandial lipemia in normal and hypertriglyceridemic patients support the hypothesis that these atherogenic particles may play a role in the development of coronary heart disease.
Two hundred and sixteen unrelated Bulgarian Jews were typed for the following genetic systems: ABO, MNS, Rh, Kell and Duffy of the blood groups; ADA, AK1, ACP1, ESD, GLO, PGD, PGM1 and PGM2 of the red-cell enzymes, and for the serum proteins HP, GC and PI. A comparison of observed gene frequencies with those of two other Sephardi Jewish groups, from Libya and Morocco, disclosed significant heterogeneity in several systems. This was mostly due to Moroccan Jews differing from Bulgarian or from both the Libyan and Bulgarian Jews. A comparison of gene frequencies in Bulgarian Jews with those in Oriental Jews from Iraq and in Ashkenazi Jews from Poland disclosed a similarity between the three groups in Rh, ADA, GLO, PGM1 and HP. The frequencies for the above systems in the three groups were closer to those of Middle Easterners than to those of Europeans. A different pattern was observed for GC and PI, in which Bulgarian resembled Polish Jews and differed significantly from Iraqi Jews. This probably reflects an outcome of convergent adaptive processes.
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A woman developed congestive heart failure after a normal delivery. The underlying disease was diagnosed as calcific constrictive pericarditis, and the patient underwent pericardiectomy.
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Two elderly female patients developed symptoms and signs of encephalitis, coincident with a cutaneous zoster eruption ("shingles"). One recovered slowly with mild residual motor dysfunction, and the other died. Varicella-zoster virus was isolated from the cerebrospinal fluid of the two patients. Review of the literature revealed only eight previously described patients in whom herpes zoster virus was isolated from the cerebrospinal fluid.
The signs, symptoms, and bone marrow findings of the recently described virus-associated hemophagocytic syndrome was seen in a patient we treated. The manifestations of this syndrome may not be specific to viral infections and may possibly occur in other infectious processes. Autopsy findings in the present case showed it to be associated with disseminated miliary tuberculosis. Concomitant viral infection was excluded. To our knowledge, only one similar patient has previously been described.
A patient with rheumatoid arthritis developed nephrotic syndrome with reversible renal failure following gold therapy. Histological examination of renal biopsy disclosed the typical picture of membranous nephropathy. After prolonged treatment with steroids and cyclophosphamide, complete recovery was achieved. The likely mechanism involved and the clinical implications are discussed.