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Biomedical subjects

J Sobra

Publications and source records attributed to J Sobra.

At least 19 recordsLinked to original sources
PubMed1996

[Hyperhomocysteinemia].

Similarly as in other inborn metabolic diseases the cause of hyperhomocysteinaemia are interactions between genetically conditioned changes most frequently due to reduced cystathionine-beta synthase activities and negative factors of the external environment. Negative environmental factors include above all a high dietary animal protein consumption which is the main methionine donor and a low intake of protein of plant origin. Another negative factor is a low intake of foods of plant origin. Fruits and vegetables are among others important sources of folic acid and pyridoxine. Substitution therapy with vitamin preparations is essential in homozygotes and in high risk heterozygotes of cystathionine beta-synthase. This treatment is also necessary during the periconception period in hyperhomocysteinaemic fertile women to reduce the risk of neurotubal defects in their future children. So far investigations are lacking which would provide evidence of a reduced risk of ischaemic heart disease and other cardiovascular diseases in isolated treatment of mildly elevated levels of plasma homocysteine. To elucidate the part played by hyperhomocysteinaemia in hastening of the atherogenetic process further studies are essential, focused on the interaction of elevated homocysteine plasma levels, dyslipoproteinaemias, hyperfibrinogenaemia and other metabolic indicators in this process.

Arteriosclerosis↗
PubMed1996

[Analysis of nutritional habits in patients with familial combined hyperlipidemia].

BACKGROUND: Our objective was to analyze dietary habits of patients with the IIb phenotype of familial combined hyperlipidaemia. These patients were instructed on the proper composition of their diet and they thought that they adhered to these recommendations. METHODS AND RESULTS: The authors examined 41 patients with IIb phenotype of familial combined hyperlipidaemia. Based on their seven-day dietary records their daily intake was calculated and compared with recommended daily allowances as regards energy intake, intake of plant and animal proteins, fats, linoleic acid, carbohydrates, calcium, iron, potassium, fibre, vitamin A, thiamin, pyridoxine, vitamin C, E, cholesterol and NaCl (Progana programme). With the above results the total serum cholesterol, serum triglyceride, HDL and LDL serum cholesterol and nutritional status (body mass index, percentage of body fat and waist hip/ratio) were compared. When the energy intake was acceptable (99% of the recommended allowance), the fat intake was excessive (138%) as well as the intake of animal protein (148%), cholesterol (145%) and NaCl (159% of the recommended allowance), while the intake of plant proteins and fibre and some vitamins was inadequate. A statistically significant relationship was revealed only as regards the linoleic acid intake and total serum cholesterol (inverse relationship at the 95% probability level, r = 0.43), the other investigated relationships were insignificant. The body mass index values (in men and women 26) and the percentage of body fat (22% in men and 34% in women) are above the recommended range. CONCLUSIONS: Dietary errors in the investigated group thus did not pertain, to the quantity of the diet but its composition. From the results ensures that doctors should pay great attention to explaining dietary principles to their patients.

Adult↗
PubMed1995

[Silent myocardial ischemia in outpatients being treated for hyperlipoproteinemia].

BACKGROUND: Hyperlipoproteinaemias, in particular those associated with hypercholesterolaemia, are in a causal relationship with the development and acceleration of atherogenesis. One of the serious forms of coronary heart disease is silent myocardial ischaemia--an asymptomatic objectively confirmed ischaemic episode. The objective of the present study was to 1. assess the prevalence of this disease in subjects with hyperlipoproteinaemia and 2. to assess the optimal diagnostic procedure to detect it. METHODS AND RESULTS: The group comprises 57 subjects selected at random (23 men and 34 women) from the out-patient department for genetics and treatment of hyperlipoproteinaemias. In all subjects an ergometric loading test was made and 24-hour ambulatory ECG monitoring. Suspected silent myocardial ischaemia (i.e. positive results of the two examinations) was confirmed by load scintigraphy of the heart muscle. Silent myocardial ischaemia was proved in 3 of 23 examined men (13%) and in 4 of 34 women (11.8%). CONCLUSIONS: Prevalence of silent myocardial ischaemia is significantly higher in high risk subjects--with hyperlipoproteinaemia than in the general asymptomatic population. The best screening test for its detection is a loading test and ambulatory ECG monitoring, supplemented by loading scintigraphy of the heart muscle.

Adult↗
PubMed1995

[Decrease in common carotid artery intimal thickness after hypolipemic therapy].

BACKGROUND: In recent years evidence was provided that it is possible to assess sonographically the thickness of the intima of the common carotid artery, whereby an increase of the thickness of the intima is considered an early stage of atherosclerosis. In the submitted work the authors tried to assess whether it is possible to influence the thickness of the intima by therapy. METHOD AND RESULTS: In 32 patients with familial hyperlipoproteinaemia sonographic control examinations of the common carotid artery were performed after 27 months of comprehensive treatment. In 21 subjects with familial hypercholesterolaemia the thickness of the intima decreased from 0.83 mm to 0.68 mm (p < 0.01), in 8 subjects with familial combined hyperlipoproteinaemia from 0.77 mm to 0.74 mm (a decline was recorded in half the subjects). In the whole group the greatest decrease was recorded in subjects treated with statins and a smaller decrease in those treated with fibrates. CONCLUSIONS: The authors assume that the decrease of the thickness of the intima of the common carotid artery recorded in hyperlipoproteinaemic patients after hypolipidaemic treatment is a manifestation of regression of atherosclerosis.

Adult↗
PubMed1995

[Simvastatin in the treatment of familial hypercholesterolemia].

BACKGROUND: The association between hypercholesterolemia and premature atherosclerosis is almost universally accepted. Treatment of hyperlipoproteinemias represents a reasonable approach in preventive cardiology. The aim of the study was to prove a hypolipidemic effect of simvastatin, Zocor tablets à 10 mg, produced by MSD, U:S.A. in patients with familial hypercholesterolemia. METHODS AND RESULTS: 29 familial hypercholesterolemia heterozygotes have been treated with increasing dose of simvastatin (10 and 20 mg/day with the evening meal) for three months. All patients have been on AHA step I diet. The basic parameters of lipid and lipoprotein metabolism have been measured, as well the concentrations of apolipoproteins A-I and B, and the level of lipoprotein(a). Concentration of total cholesterol decreased after treatment with 10 and 20 mg of simvastatin by 20%, resp. 26%. The hypolipidemic effect was even more pronounced in LDL-cholesterol level, which was reduced by 24% respectively 34%. On the other hand therapy with simvastatin did not influence HDL-cholesterol at all. Also triglycerides concentration did not changed very significantly after administration of simvastatin (triglycerides levels were reduced by 7% respectively by 18%). Decline of LDL-cholesterol has been accompanied by decrease of apolipoprotein B concentration by 24%, resp. 26%. The concentration of lipoprotein (a) has not been statistically significantly influenced, even its level increased slightly. The body weight of the patients did not changed during the study. Simvastatin treatment has been well tolerated by the patients. CONCLUSIONS: Simvastatin, Zocor, seems to be powerful hypolipidemic drug, which is to be used even in the treatment of familial hypercholesterolemia heterozygotes, who are usually very resistant to the therapy. The dose of 10 mg of simvastatin is usually sufficient to influence plasma lipids and lipoproteins. A double dose intensifies the hypolipidemic effect but this additional effect is not so expressive. Zocor is tolerated well by the patients and in safety laboratory we did not notice any important undesirable result.

Adult↗
PubMed1995

[DNA analysis in heterozygotes in familial hypercholesterolemia].

BACKGROUND: Accuracy of clinical diagnosis of heterozygotes with familial hypercholesterolemia (FH) is limited. The aim of our study was to demonstrate possibilities of progressive diagnostic approach, DNA analysis, LDL receptor gene (LDLR) and apolipoprotein B (ApoB) in case of our study, and compare our results with the data obtained in other populations. METHODS AND RESULTS: The low density lipoprotein receptor (LDLR) gene RFLP frequencies for restriction endonucleases AvaII, HincII, NcoI, PvuII and StuI were determined in the sample of 52 FH patients and in the group of 37 healthy individuals. Using PCR, the LDLR gene was then tested for Pro664-Leu and Val408-Met point mutations. The first DNA diagnosis of familial defective apolipoprotein B-100 (FDB) using point mutation PCR analysis of 26. exon of ApoB gene in Czech Republic was performed. LDLR gene RFLP frequencies for restriction endonucleases AvaII, HincII, NcoI, PvuII and StuI in he sample of 52 FH patients were 0.48, 0.52, 0.73, 0.31 and 0.93 respectively. LDLR gene RFLP frequencies for enzymes AvaII, HincII, NcoI, PvuII and StuI in the group of 37 healthy individuals were 0.39, 0.50, 0.70, 0.22 and 0.99 respectively. In the group of FH patients no point mutations Pro664-Leu and Val408-Met were detected. However, there was found 110bp insertion in the 9th exon of LDLR gene in two FH patients during studies of Val408-Leu mutation. Two FDB probands in the FH group and another 7 FDB individuals in probands families were detected. FDB frequency in the sample of FH patients was 3.8%. CONCLUSIONS: LDLR gene RFLP frequencies and FDB frequency in our group of FH patients did not differ from that of FH patients in other Caucasian populations. DNA analysis is advantageous complementary method for diagnosis of FH and is irreplaceable for the detection of FDB.

Adult↗
PubMed1994

[Monitoring plasma levels of vitamin D metabolites in simvastatin (Zocor) therapy in patients with familial hypercholesterolemia].

BACKGROUND: Simvastatin is a hypolipidaemic agent, a statin which inhibits cellular cholesterol synthesis by blocking 3HMG CoA reductase. The authors present a report on levels of plasma metabolites of vitamin D after treatment with 10 and 20 mg simvastatin daily in 13 patients, heterozygotes with hypercholesterolaemia during a five-week period. METHODS AND RESULTS: During simvastatin treatment in all patients plasma levels, of the sum of hydroxylated vitamin D metabolites and 1,25-dihydroxyvitamin D after five weeks of treatment with 10 and 20 mg hypolipidaemic drug were examined. For assessment of vitamin D metabolites radioassay was used which assesses the sum of hydroxylated vitamin D metabolites, and radioimmunoanalysis for assessing the 1,25-dihydroxyvitamin D plasma level. For statistical evaluation the non-parametric Friedman test and simultaneous testing was used. CONCLUSIONS: Simvastatin raises the plasma levels of the sum of hydroxylated vitamin D metabolites and 1,25-dihydroxyvitamin D in a dose-dependent ratio. The authors recommend to monitor the plasma levels of vitamin D metabolites over a longer time period.

Adult↗
PubMed1993

[Therapy with fibrates and vitamin D metabolism].

The authors investigated in 29 patients with familial hyperlipoproteinaemia the effect of fibrate treatment (Duolip forte, Merckle, and Lipanthyl, Richter) on vitamin D metabolism. In 10 patients treated for 6 months with daily oral doses of 500 mg Duolip forte they did not prove changes of plasma levels of 25-hydroxyvitamin D, however, they recorded a rise of the 1,25-dihydroxyvitamin D3 plasma level. In 19 patients who were given for 6 months 300 mg Lipanthyl per day by the oral route they proved a significant decline of the 25-hydroxyvitamin D plasma levels and a rise of 1,25-dihydroxyvitamin D3 plasma levels. The authors maintain that fibrates influence plasma concentrations of vitamin D metabolites either directly or indirectly by reducing cholesterol plasma levels.

Adult↗
PubMed1993

[Duolip Forte--experience during a 6-month period of administration].

Duolip forte (ethophylline clofibrate, tablets à 500 mg) produced by Merckle Austria was administered to 20 patients with different types of hyperlipoproteinaemia for a 6-month period in amounts of 500 mg/day. Before onset of treatment and during treatment the patients adhered to a defined hypolipidaemic diet. The total cholesterol level during administration increased from 7.71 +/- 1.71 mmol/l to 8.23 +/- 1.34 mmol/l (p = 0.05). The LDL cholesterol level rose from 4.93 +/- 1.70 mmol/l to 5.53 +/- 1.34 mmol/l (n.s.). Apolipoprotein B declined from 1.99 +/- 0.39 g/l to 1.80 +/- 0.30 g/l (n.s.). HDL cholesterol rose from 1.09 +/- 0.32 mmol/l to 1.53 +/- 0.56 mmol/l (p = 0.01). The triglyceride level declined from 5.71 +/- 5.60 mmol/1 to 3.72 +/- 4.32 mmol/1 (n.s.). The lipid metabolism parameters were evaluated already after three months of Duolip treatment but the values did not differ significantly from values assessed after 6 months of administration; therefore only the final values are given. In the course of six months of Duolip administration the body weight of the patients did not change and no serious side-effects were observed which would call for discontinuation of treatment. Duolip forte is evaluated as a safe, but as compared with other available drugs of the clofibrate series, less effective hypolipidaemic agent.

Adult↗
PubMed1993

[Carotid artery and femoral artery disease in asymptomatic patients with various types of hyperlipoproteinemias and in healthy persons].

The authors examined by means of the sonograph Siemens Quantum 2000 the carotid and femoral arteries of 21 controls and 91 asymptomatic subjects with different types of hyperlipoproteinaemia (HLP). 46 patients suffered from familial hypercholesterolaemia, another 19 patients with hypercholesterolaemia suffered from ischaemic heart disease, 21 patients had familial combined hyperlipoproteinaemia and 5 patients had familial dysbetalipoproteinaemia. In the controls no plaques or stenoses were detected. In the different groups with HLP plaques and stenoses on the carotid artery were found in 15-36%, on the femoral artery in 24-63%. In patients with HLP on the common carotid artery in different groups a detectable intima was found more frequently, a statistically highly significantly wider intima (0.73 +/- 0.17 mm to 0.84 +/- 0.31 mm) and a lower maximum rate (79 +/- 18 cm/s to 98 +/- 24 cm/s) than in controls (0.41 +/- 0.14 mm and 121 +/- 30 cm/s resp.). On the common carotid the authors found a significant direct correlation between age and the cholesterol level and between age and the width of the intima and an indirect correlation between age and the maximal rate. The differences in the width of the intima and maximum rate were preserved even when the groups were adjusted for age. Changes of the femoral artery were less marked.

Adult↗
PubMed1993

[Familial hypercholesterolemia from the aspect of DNA analysis].

The authors summarize their first experiences with DNA analysis of defective low density lipoprotein receptor (LDLR) gene of the familial hypercholesterolemia heterozygotes that were selected from the III. Medical Clinic of the 1st Medical Faculty in Prague patients group. First genotype studies of unrelated FH individuals were performed by restriction fragment length polymorphism (RFLP) method. Relative allele frequencies of PvuII (0.69) and StuI (0.91) restriction enzymes agree with the world literature datas, in the ApaLI (0.69) case the higher value may be caused by, for the present, small number of analyzed patients. Possibilities of DNA analysis for pedigree FH diagnosis were demonstrated on the PvuII restriction enzyme case. By the use of polymerase chain reaction (PCR) DNA diagnosis of the familial defective apolipoprotein (Apo) B-100 (exon 26) was performed. 43 unrelated FH individuals were screened and none defective ApoB-100 gene was recorded.

Apolipoprotein B-100↗
PubMed1993

[The intima of the common carotid artery in patients with hyperlipoproteinemia].

Using sonography, the common carotid artery was examined in patients with hyperlipoproteinaemia and in controls. In 21 controls, the intima was present in 62%, intimal thickness was 0.41 +/- 0.14 mm. In patients with familial hypercholesterolaemia free of ischaemic heart disease (46 patients), the intima was demonstrable in 89%, intimal thickness was 0.74 +/- 0.21 mm. In patients with ischaemic heart disease (19 patients), the intima could be demonstrated in 100%, its thickness was 0.84 +/- 0.31 mm. In 21 patients with familial combined hyperlipoproteinaemia, the intima was present in 90%, intimal thickness was 0.73 +/- 0.17 mm. Intimal thickness was significantly greater (p < 0.001) in all groups of patients with hyperlipoproteinaemia than in the control group. A significant correlation between cholesterol levels and intimal thickness (p < 0.01) was demonstrated.

Adult↗
PubMed1992

[Diseases of civilization from the aspect of evolution of the human diet].

The authors discuss contemporary views regarding the causes of diseases of civilization which developed on an epidemic scale in industrial societies during the last 60-70 years. They are due to the immense changes of lifestyle adopted by these societies. On the whole this lifestyle is a marked deviation from optimal conditions for humans. The genetic equipment of man which determines the evolutional advantages and function of different metabolic processes which ensure the homeostasis of the healthy organism is conservative and is entirely adapted to the human genome which developed in the course of hundreds of thousands of years. The aim of preventive medicine is to analyze, point out and enforce diminution of the effect of risk factors, as an important way towards improvement of the general health status of the population.

Diet↗
PubMed1992

[Combined therapy of hyperlipoproteinemia. Colestipol and gemfibrozil in the treatment of heterozygous familial hypercholesterolemia].

Combined concurrent treatment with two or more hypolipidaemic agents is a modern trend in the pharmacotherapy of hyperlipoproteinaemias. Aggressive treatment of hyperlipoproteinaemias can lead not only to the arrest of progression but also to regression of the atherosclerotic process. The authors submit experience assembled with the treatment of 14 heterozygotes with familial hypercholesterolaemia by a combination of colestipol (Colestid Upjohn, Belgium) with gemfibrosil (Loped Parke-Davis, USA), 15 g and 1200 mg resp. per day. One month of administration of this combination of hypolipidaemic agents led to a drop of total cholesterol by 21% and of LDL-cholesterol by 30%. At the same time the authors recorded a marked and statistically significant increase of HDL-cholesterol by 23%. Favourable changes were observed also as regards apolipoprotein concentrations. The apolipoprotein A-1 level increased by 32%, while the level of the atherogenic apolipoprotein B declined by 30%. The triglyceride level declined also. It did not prove possible even by combined treatment to reduce the level of apolipoprotein(a). Combined treatment with colestipol and gemfibrosil was well tolerated by the patients and in none of the patients treatment had to be discontinued because of undesirable side-effects.

Adult↗
PubMed1992

[Colestipol in the treatment of heterozygous familial hypercholesterolemia].

In the specialized clinic for disorders of the lipid metabolism 27 patients, 8 men and 19 women, heterozygotes with familial hypercholesterolaemia were treated for 8 weeks with Colestid (colestipol bags a 5 g, Upjohn, Belgium). The administered dose was 15 g colestipol per day. After colestipol treatment the authors recorded a statistically significant decline of total cholesterol by 18% and of LDL-cholesterol by as much as 27%. The apolipoprotein B concentration declined during treatment by 9% and concurrently there was a favourable rise of apolipoprotein A-1 by 20%. The authors recorded also a slight rise of the HDL-cholesterol concentration which, however, was not statistically significant. The serum triglyceride level increased slightly after colestipol treatment. It did not prove possible to influence the lipoprotein(a) level by colestipol administration. As compared with other hypolipidaemic agents from the group of ion exchange resins, the patients tolerated Colestid surprisingly well. Only one female patient discontinued treatment because of dyspeptic complaints, severe constipation.

Adolescent↗
PubMed1991

Influence of testosterone isobutyrate on serum lipoproteins during replacement therapy of hypogonadal men.

Replacement therapy of hypogonadal men with testosterone isobutyrate, 100 mg by the i.m. route every two weeks, does not lead to a permanent significant change of the lipoprotein spectrum and to an increased risk of stereogenesis. The expected changes in the liver lipase activity and in the lipoprotein spectrum under the influence of the administered androgens are obviously suppressed by the antagonistic action of estrogens formed by conversion from androgens.

Adult↗
PubMed1990

[Nutrition and metabolic diseases with a mass incidence].

Metabolic diseases with a mass incidence (simple obesity, arterial hypertension, hyperlipoproteinaemia, type II diabetes and gout) are the main risk factors for the manifestation of cardiovascular diseases which can be influenced, as has been reliably proved. They are at present the cause of 56% of all deaths in Czechoslovakia. It is important to emphasize that we are living and dying in an epidemic of cardiovascular diseases. The founder of morbid anatomy, Rudolf Virchow, stated more than 100 years ago: "If the prevalence of a certain disease in a population becomes epidemic, it reflects always a disorder of human culture". It is a fact that a great proportion of the population in Czechoslovakia has adopted during the past decades and still practices an unsound dietary regime and there are other negative lifestyle factors (obesity, smoking, little exercise, high alcohol consumption) for which we pay at present by a declining life expectancy, unnecessary human suffering and the nation as a whole by immense economic losses. The question arises: who and what prevents us from starting in Czechoslovakia as rapidly as possible expedient, comprehensively conceived prevention on a wide front, making use of all findings and advances of world science in this field?

Cardiovascular Diseases↗