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Background: To study whether the Apolipoprotein A-I (apo A-I) promoter region gene polymorphism produces changes in the lipid profile of heart transplant recipients., Methods: One hundred and three heart transplant recipients (93 men and 10 women, with a mean age of 47 +/- 13 yr) receiving triple immunosuppressive therapy were submitted to a genetic study of the apo A-I gene promoter region. Anthropometric and analytical data, including lipid profile, arterial blood pressure, were collected prior to transplantation and 3, 6, 12, and 24 months after transplantation., Results: Sixty-three subjects had the GG genotype and 40 the GA genotype. Carriers of the GA genotype had higher triglyceride levels at 6 months and 2 yr (2.50 +/- 1.20 versus 1.93 +/- 0.98 mmol/L and 2.46 +/- 1.58 versus 1.60 +/- 0.68 mmol/L, respectively, p < 0.001), and a greater rise in LDL-cholesterol at 1 yr than the GG subjects (4.57 +/- 1.16 versus 4.16 +/- 1.18 mmol/L, p < 0.05). Multiple regression analyses showed that genetic variants at the apo A-I promoter region are responsible for 11% of the variability in triglyceride levels at 6 months (p = 0.005)., Conclusions: The GA genotype of the apo A-I promoter region produces a greater rise in plasma triglyceride and LDL-cholesterol levels in heart transplant patients.

Gaucher's disease is a rare condition caused by a deficiency in the lysosomal enzyme called beta-glucocerebrosidase (GBA). The objective of our work was to analyse the clinical, diagnostic and therapeutic characteristics in a group of four patients with Gaucher's disease type 1. The advantages of the new diagnostic and therapeutic techniques are stressed. In all cases the diagnosis was made by means of cyto-histological examination and enzymatic measurement of the beta-glucocerebrosidase activity. A genetic study and genotype determination was made in the four cases. A questionnaire was administered to patients to evaluate their life quality applying the SF36 questionnaire adapted to the Gaucher's disease. All subjects have received enzymatic replacement therapy with the recombinant enzyme imiglucerase (Cerezyme Corporation) with a satisfactory clinical course. Interestingly, eosinophilia was present in one patient, which disappeared after treatment.

Background: There is considerable interindividual variability in the postprandial lipid response to a fat-rich meal, and genetic factors have been considered to account for some of these effects. We previously showed that the G-A mutation 5' to the apolipoprotein (apo) A-I gene was significantly associated with the LDL-cholesterol response to diet., Objective: We evaluated whether this effect is mediated by mechanisms involving postprandial lipoprotein metabolism., Design: Twenty-eight G/G and 23 G/A healthy male subjects, homozygotes for the apo E3 allele, were subjected to a vitamin A fat-loading test. Blood was drawn at time 0 and every hour for 11 h., Results: There was a significant postprandial decrease in plasma cholesterol, LDL cholesterol, and apo B in G/G subjects but not in G/A subjects. A greater postprandial response in large triacylglycerol-rich lipoproteins (TRLs) and a smaller postprandial response in large TRL apo A-IV was observed in G/A than in G/G subjects. Retinyl palmitate in large and small TRL concentrations was similar for both genotypes. No significant genotype effects were detected for triacylglycerol concentrations in plasma, small TRL fraction, and apo A-I and HDL-cholesterol concentrations., Conclusion: Our data suggest that the G-A mutation affects the LDL-cholesterol response to diet by mechanisms involving postprandial lipoprotein cholesterol metabolism.

Aims/hypothesis: Insulin resistance usually precedes the diagnosis of Type II (non-insulin-dependent) diabetes mellitus. However, in most patients, the clinical expression of the disease could be prevented by dietary and lifestyle changes. We investigated the effects of a diet enriched in monounsaturated fatty acids (Mediterranean diet) and a low fat, high-carbohydrate diet on in vivo and in vitro glucose metabolism in 59 young subjects (30 men and 29 women)., Methods: We carried out an intervention dietary study with a saturated fat phase and two randomized-crossover dietary periods: a high-carbohydrate diet and a Mediterranean diet for 28 days each. We analysed the plasma lipoproteins fractions, free fatty acids, insulin sensitivity and glucose uptake in isolated monocytes at the end of the three dietary periods., Results: In comparison to the saturated fat diet, the CHO and Mediterranean diets induced a decrease of LDL-cholesterol (p < 0.001) and HDL-cholesterol (p < 0.001). Steady-state plasma glucose decreased (p = 0.023) and basal and insulin-stimulated 2-deoxiglucose uptake in peripheral monocytes increased in both diets (CHO and Mediterranean), (p = 0.007) indicating an improvement in insulin sensitivity. Fasting free fatty acids plasma values were correlated positively with steady state plasma glucose (r = 0.45; p < 0.0001). In addition, there was an inverse correlation between the mean glucose of the steady state plasma glucose period and logarithmic values of basal (r = -0.34; p = 0.003) and insulin stimulated glucose uptake in monocytes (r = -0.32; p = 0.006)., Conclusion/interpretation: Isocaloric substitution of carbohydrates and monounsaturated fatty acids for saturated fatty acids improved insulin sensitivity in vivo and in vitro, with an increase in glucose disposal. Both diets are an adequate alternatives for improving glucose metabolism in healthy young men and women.

Apolipoprotein IV (apo A-IV) has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. Several polymorphic sites within the gene locus for apo A-IV have been detected. Previous studies have shown that the A-IV-2 isoform produces a different plasma lipid response after the consumption of diets with different fat and cholesterol content. The present study was designed to evaluate whether the apo A-IV 360His polymorphism could explain, at least in part, the interindividual variability observed during postprandial lipemia. Fifty-one healthy male volunteers (42 homozygous for the apo A-IV 360Gln allele (Gln/Gln) and nine carriers of the A-IV-360His allele), homozygous for the apo E3 allele, were subjected to a vitamin A-fat load test consisting of 1 g of fat/kg body weight and 60000 IU of vitamin A. Blood was drawn at time 0 and every hour for 11 h. Plasma cholesterol (C), triacylglycerol (TG), and C, TG, apo B-100, apo B-48, apo A-IV and retinyl palmitate (RP) were determined in lipoprotein fractions. Data of postprandial lipemia revealed that subjects with the apo A-IV 360His allele had significantly greater postprandial levels in small triacylglycerol rich lipoproteins (TRL)-C (P<0.02), small TRL-TG (P<0.01) and large TRL-TG (P<0.05) than apo A-IV 360Gln/Gln subjects. In conclusion, the modifications observed in postprandial lipoprotein metabolism in subjects with the A-IV 360His allele could be involved in the different low density lipoprotein (LDL)-C responses observed in these subjects following a diet rich in cholesterol and saturated fats.

This study evaluates the effect on high-density lipoprotein (HDL) binding activity in cultured granulocytes before and after metabolic control of non-insulin-dependent diabetes mellitus ([NIDDM] type 2 diabetes) patients. In 20 type 2 diabetic patients, diabetic control was accomplished by administration of oral antidiabetic agents and dietary restrictions. Adequate metabolic control was reflected by a decrease in the fasting glucose, glycosylated hemoglobin (HbA1c), mean insulin, and body mass index (BMI). After control of the diabetes, the mean HDL3 cholesterol was increased from 0.918 +/- 0.05 to 1.008 +/- 0.05 mmol/L (P < .05) and apolipoprotein AI (apo AI) was increased from 103 +/- 5.8 to 115 +/- 5.1 mg/dL (P < .01). The HDL3 maximum specific binding was higher after versus before diabetic control, 77 +/- 6 versus 122 +/- 8 ng/mg cell protein (P < .01). This increase was related to an increase in maximum binding ([Bmax] from 4.97 x 10(-10) to 8.3 x 10(-10) mol/L, P < .001), and no significant changes were observed in the Kd (from 1.47 x 10(-7) v 2.04 x 10(-7) mol/L). These results suggest that the metabolic control of type 2 diabetes increases HDL3 binding activity.

Objective: Two dietary regimens recommended for the reduction of coronary risk, by way of their effects on lipid profile, are the diet low in saturated fat and a diet rich in monounsaturated fats (MUFA). However the effects of these diets on carbohydrate metabolism in healthy subjects are not well known. The objective of this study was to compare the effect of both diets on various parameters of carbohydrate metabolism., Methods: 41 healthy young males were submitted to 3 consecutive diets, each for a duration of 4 weeks. The first diet was rich in saturated fat (SAT) (38% fat, 20% saturated). The second was rich in carbohydrates following the recommendations of the NCEP-I (National Cholesterol Education Program type I) (28% fat, 47% carbohydrates). The last one was a diet rich in monounsaturated fatty acids (38% fat, 22% MUFA). At the end of each dietary period, blood pressure (BP) and blood levels of glucose, insulin and free fatty acids were determined. 29 subjects were also submitted to an oral glucose tolerance test (OGTT) at the end of each diet., Results: The SAT diet induced the highest levels of insulin after the OGTT. The consumption of the MUFA diet determined the lowest levels of fasting blood glucose (-0.60 mmol/l [13%], p < 0.0002), insulin (-9 microUl/ml [47%], p < 0.0002) and free fatty acids (-0.11 mmol/l [24%], p = 0.006), compared to the NCEP-I diet. Systolic and diastolic blood pressure were higher in the NCEP-I diet than during the other periods (SBP: +6 mmHg compare with SAT [5%], p = 0.0001; and +5 mmHg compare with MUFA [4%], p = 0.0001; DBP: +20 mmHg compare with MUFA [27%], p = 0.0001) and +6 mmHg compared with SAT [8%], p = 0.0001)., Conclusion: Of the diets most commonly used for the treatment and prevention of arteriosclerosis, a diet rich in monounsaturated fats is the most beneficial for the healthy population from the point of view of carbohydrate metabolism and blood pressure.

Background: To study if the presence of the G/A polymorphism at the apo A-I gene promoter region could determine the lipid profile in patients with hyperlipidemia after heart transplantation, or if it is related with the type of heart disease that determined the transplantation., Patients and Methods: This study included 31 patients with hyperlipidemia after heart transplantation. Anthropometric parameters, basic analytic and lipid study were measured in these subjects. Identification of the G/A mutation in the promoter region of the apo A-I gene was performed., Results: 22 patients had the G/G genotype and 9 the G/A. 14 were transplanted by coronary heart disease and 17 by non ischemic heart disease. Patients with the A allele had higher cHDL (63 [SD 15] vs 53 [10]; p = 0.034) and apo A-I plasma levels (156 [34] vs 132 [24]; p = 0.040) than G/G subjects. The A allele was present in the 18% of the patients transplanted by ischemic heart disease and in the 43% of the transplanted by another etiology (p = 0.073)., Conclusions: The presence of the G/A genotype in the promoter region of the apo A-I gene determines higher plasma levels of cHDL in patients with hyperlipidemia after heart transplantation.

Introduction: Coronary artery disease is a major limiting factor for long-term survival after heart transplantation. Hyperlipidemia is a probable risk factor for coronary artery disease in this kind of patient. Bezafibrate and lovastatin have proved to be effective in lowering total and low density lipoprotein cholesterol. The present study tested the safety and efficacy of both drugs on lipid levels in 21 patients with post-heart transplantation hyperlipidemia., Patients and Methods: Patients maintained the same diet for three months. Then, they were randomized to lovastatin (20 mg/day) or bezafibrate (400 mg/day) for 8 weeks, and then, crossovered to an additional 8 weeks of bezafibrate or lovastatin., Results: Both drugs were effective in lowering total and low density lipoprotein cholesterol and apoprotein B concentrations, but the effect of lovastatin was significantly greater. Only bezafibrate produced a significant reduction in total triglycerides and a significant rise in high density lipoprotein cholesterol and apoprotein AI. The total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratios were decreased under both treatments., Conclusion: Both drugs, bezafibrate and lovastatin appear to be safe, effective and well-tolerated therapies for hyperlipidemia in cardiac transplant recipients.

Castleman's disease is a rare lymphoproliferative disorder with a great range of clinical presentation and localization. It usually appears in young people and its etiology is unknown. Clinical features are not specific: fever, asthenia, hypochromic anemia and hypergammaglobulinemia. We report here two cases of Castleman's disease whose peculiarity lies in the fact that the first sign was fever of unknown origin. In both cases the use of a CT scan was very important for the diagnosis.

Background: Heterozygote familial hypercholesterolemia and combined familial hyperlipemia are associated to a greater risk of coronary disease. Combined familial hyperlipemia has classically been indicated to manifest after the second decade in life. The aim of this study was to establish whether a systematic search would demonstrate the existence of combined familial hyperlipemia earlier and analyze whether the antropometric parameters related with the overweightedness accompany the appearance of the lipid disorders of this disease found at an early age., Patients and Methods: Different lipid parameters were studied in 89 subjects under the age of 18 who were children of patients with heterozygote familial hypercholesterolemia and combined familial hyperlipemia. Likewise the weight, height and waist/hip quotient were evaluated. Hyperlipemia was considered as the presence of cholesterol/LDL and/or triglicerides greater than the 95 percentile for age and sex., Results: Hyperlipemia was observed in 51% and 40% of the children of patients with heterozygote familial hypercholesterolemia and combined familial hyperlipemia, respectively. The body mass index and the waist/hip quotient of the latter children significantly correlated with the cholesterol-HDL values and the LDL/HDL quotient., Conclusions: The patients with known combined familial hyperlipemia have a high percentage of children with hyperlipemia during infancy. These data suggest a possible association between obesity in the appearance of hyperlipemia in the children of patients with combined familial hyperlipemia at this age.

Metabolic mechanisms underlying the observations of elevated cholesterol concentration of low-density lipoprotein (LDL) in organ-transplanted patients on long-term immunosuppressant cyclosporine therapy were explored using cyclosporine-treated rats as an experimental model. As in patients, treatment with cyclosporine induced a significant elevation of plasma cholesterol level, mainly in LDL cholesterol, with a decrease in high-density lipoprotein (HDL) cholesterol level. In an in vivo cross-over study design, differentially radioiodinated homologous LDL from donor cyclosporine-treated rats (Cyc-LDL) and excipient-only-treated control rats (Exc-LDL) were injected into recipient cyclosporine-treated rats (Cyc-rats), excipient-only--treated control rats (Exc-rats), and untreated rats (Unt-rats). From the isotope disappearance curves, the fractional catabolic rate (FCR) and production rate were calculated. The results showed that FCR and production rate were significantly reduced in Cyc-rats compared with control Exc-rats and Unt-rats. The decrease was independent of the donor LDL source. In vitro LDL ligand-receptor assays indicated a twofold higher degradation of Cyc-LDL by cultured rat fibroblasts, and hence could not account for the decreased clearance observed in vivo. These results suggest that the elevated concentrations of LDL cholesterol associated with cyclosporine treatment result not from a cyclosporine-induced modification of the LDL molecule, which could diminish its receptor-mediated clearance/catabolism, but possibly from an in vivo pharmacological property of cyclosporine such as an induced hepatic dysfunction.

The effects of cyclosporin and prednisone on plasma lipid and lipoprotein levels were studied in 20 allogeneic bone-marrow transplantation patients receiving cyclosporin plus prednisone therapy, and in 14 allogeneic patients treated only with cyclosporin during 100 days. Eighteen autologous bone-marrow patients not requiring cyclosporin were used as a control group. Patients were studied 5 days prior to transplantation, and on days 30, 60, and 100 after transplantation. To determine the reversibility of the changes, lipid parameters were analyzed 30 days after completion of the treatment. Nutritional supplementation, conditioning regimens, and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline. Our results indicate that cyclosporin therapy induces a reversible increase of plasma cholesterol, LDL-cholesterol, triglycerides, VLDL-triglycerides, and apolipoprotein B and a decrease of HDL-cholesterol, HDL2-cholesterol, and apolipoprotein A-I. The addition of prednisone to cyclosporin therapy induces a higher increase in plasma cholesterol mainly due to an increase in HDL-cholesterol. Total cholesterol/HDL-cholesterol ratio increased significantly in patients treated only with cyclosporin. No differences were found in this ratio in patients treated with prednisone compared to those submitted to autologous bone-marrow transplantation. Lipid changes observed in this study were reversible 30 days after cessation of cyclosporin treatment.

The effects of cyclosporin on plasma lipoproteins and lipoprotein lipase (LPL) activity were studied in rats treated with different doses of the drug for periods ranging between 7 and 30 days. The treatment with cyclosporin resulted in an increase in plasma triglycerides and non-HDL-cholesterol, and a dose and time-dependent decrease of LPL activity and HDL-cholesterol, mainly because of a fall in the HDL2-cholesterol subfraction. The decrease of LPL activity was positively correlated (p < 0.01) with plasma HDL-cholesterol and HDL2-cholesterol and negatively with plasma triglycerides and non-HDL-cholesterol (p < 0.01). Our results indicate that the decrease in plasma LPL activity may be responsible for the increase in plasma triglycerides and the decrease in plasma HDL-cholesterol found in rats under cyclosporin treatment.

We study the clinical characteristics of 21 heat strokes at admittance, to analyze the clinical features in relationship with prognosis. 15 patients (71%) suffered a classical heat stroke and 6 (29%) an active heat stroke. Global mortality was 33%. Sun exposition was more frequent in patients who survived (p less than 0.05), fact that we relate with earlier withdrawal from noxa. Patients with worse prognosis were showing more frequently coma (p less than 0.05); photomotor (p less than 0.01), oculocephalic (p less than 0.01) and corneal (p less than 0.01) reflexes abolition; together with disorders in spontaneous and induced motility of members (p less than 0.05); areflexia (p less than 0.01) and plantar extensor response (p less than 0.05). However the most discriminatory parameter between the two groups was the response to cooling, because the outcome was always fatal when cooling did not take place (p less than 0.01). From the analytical standpoint, serum bicarbonate was lower in the patients who died (p less than 0.05). We insist in the need to start prevention and treatment programs in those communities with high incidence of this syndrome.

The general practitioner plays a fundamental role in the control of hypercholesterolemia as a risk factor of atherosclerosis; therefore, education about this issue should be an important part of the undergraduate curriculum. Thus, we carried out the present study to investigate whether the curriculum in our medical schools provides the necessary knowledge to the primary care physician to carry out this function. To this end, we distributed a questionnaire to 585 medical students of different years in the Córdoba School of Medicine. Most students have a clear idea of the importance of cardiovascular disease as a cause of death. The level of knowledge about basic pathogenetic aspects of plasma lipoproteins is considerable. The students are acquainted with the adequate dietary interventions for the management of the patient with hypercholesterolemia, and they learn the advantages of consuming blue fish and olive oil. However, the level of knowledge about drug therapy is disappointing. Finally, most of them declared to be in favour of a personal approach to the prevention of atherosclerosis with diet. We conclude that the overall level of knowledge and personal approach of the students of that particular School of Medicine permits an optimistic view in the field of prevention of coronary atherosclerosis.

Serotonin is involved in the control of ACTH secretion, possibly by stimulating corticotropin releasing factor secretion from the hypothalamus. Cushing's disease seems to be due to defective hypothalamic regulation of ACTH release from the pituitary gland. Cyproheptadine is a potent antagonist of serotonin and has been used successfully in some patients with Cushing's disease, although, generally, in women without radiological evidence of pituitary tumors. We report the successful use of cyproheptadine in a 54-year-old man with Cushing's disease due to pituitary basophil adenoma. Significant clinical and biochemical improvement was noted 45 days after treatment began. The results in this patient support our findings that cyproheptadine can be effective in patients with Cushing's disease due to pituitary tumors, as well as in preparing very ill patients for surgery or managing such patients until radiotherapy takes effect.

Salivary gamma-glutamyl transferase (GGT) activity was measured in 116 patients with several diseases that involved the hepatobiliary tract, pancreas, and miscellaneous disorders and in 20 normal subjects. We have found significantly elevated values of salivary GGT in cirrhosis of the liver (8.3 +/- 0.9 [mean +/- SEM] units/L), hepatic tumors (10.4 +/- 1.3 units/L), acute cholecystitis (18.3 +/- 2 units/L), acute pancreatitis (15.1 +/- 2.4 units/L), diabetic ketoacidosis (11.6 +/- 1 units/L), and Sjögren's syndrome (19.6 +/- 4.8 units/L). Salivary GGT activities were unmodified in fatty liver, infectious hepatitis, silent cholelithiasis, and mumps. Several mechanisms explain high salivary GGT activity. Measurement of salivary GGT activity in internal medicine merits further investigations to determine its potential diagnostic value.

Sera from eight patients with biopsy-proven rectal carcinoma were assayed for creatine kinase (CK). Two of the patients had enzyme activity: one with the BB and the other with an MB isoenzyme. We think that our results may be of interest because the detection of anomalous isoenzymes of CK in serum ma serve as a diagnostic marker or as an indicator of the effectiveness of treatment.

Medullary thyroid carcinoma (MTC) is a known apudoma producing calcitonin, prostaglandins and serotonin. It can present itself as a familial or sporadic form or as part of a multiple endocrine adenomatosis. We present here the case of a patient admitted with a four-year history of diarrhea, enlargement of the thyroid and palpable lymph nodes in the right side of the neck. There was no uptake of 131I in the right lobe of the thyroid and the serum calcitonin levels were very high. With the diagnosis of MTC a total thyroidectomy mas performed developping within hours of the surgical procedure a picture of diabetes insipidus with 31 liters of urine output in the first 48 hours. It responded to vasopressin and disappeared spontaneously in two weeks. We have considered the different mechanisms that could explain the development of diabetes insipidus, and after failing to find one, we especulate at prostaglandins could play an important role in the synthesis and/or release of ADH. The sudden depletion of prostaglandins after removal of the neoplasm that produced them could account for the diabetes insipidus in our patient. We have not found any similar case described in the literature. We call attention to the need for a close postoperative observation of patients operated for MTC for the possible onset of diabetes insipidus.

Chronic mucocutaneous candidiasis is a rare cellular immunodeficiency disease, characterized by persistent infections of the mucous membranes, nails, skin and scalp. Candidal granuloma is an uncommon form of mucocutaneous candidiasis of early onset which may ne associated with hypothyroidism. It is difficult to manage as so far no truly effective treatment has been found. We present a 13-year old boy with candidal granuloma associated with primary hypothyroidism who had a favorable response to treatment with thyroid hormone and miconazole. The fungicide was given in tablet form, a single dose per day and patient kept it in his mouth and in contact with his lips for 15 minutes. One and a half year later clinical evolution is good and no side effects related to the miconazole have been observed.

In this work the presence of gamma-glutamyltransferase (GGT), leucine amino-peptidase (LAP) and alkaline phosphatase (AP) is shown in human tear fluid. We studied these levels according to sex, age and some eye refraction defects. The differences between the levels for both sexes are not significant. LAP and AP do not show any differences in either age groups or individuals with some refraction defects. The average level of GGT is higher from 40 years of age upwards (p less than 0.005). In individuals with refraction defects, the enzymatic activity is significantly higher (p less than 0.05) than the activities found in normal subjects. The levels of the three enzymes in serum and tear fluid do not show a significant correlation nor are they significantly modified after the samples have been frozen for a month at -20 degrees C.

While studying the distribution of creatine kinase isoenzymes in the mucosa of the rat digestive tract, we found two predominant patterns, namely the esophageal pattern with predominant MM isoenzyme, and the gastrointestinal pattern with predominant BB isoenzyme. The quantitative distribution of the enzyme was higher in the esophagus, although its role is not clear at present.