Biomedical subjects
K Widhalm
Publications and source records attributed to K Widhalm.
Prostacyclin synthesis stimulating plasma factor in patients with primary hyperlipoproteinemia--effect of dietary and drug treatment.
Recent data have demonstrated a possible pathogenetic influence of the prostacyclin synthesis stimulating plasma factor (PF) in various diseases. Studying this PF in 26 patients with primary hyperlipoproteinemia (HLP) we examined patients suffering from types IIa (n = 8), IIb (n = 6) and IV (n = 12) classified according to Fredrickson. Plasma was withdrawn at the detection of the HLP, 4 weeks after a dietary intervention and again 4 weeks after the beginning of a drug treatment. Using various test models such as rat and minipig aortic tissue, human aorta and saphenous vein as well as cultured endothelial and smooth muscle cells, the data reveal an in part significant improvement of PF running parallel with the improvement of HLP. These findings suggest that even though a significant difference between healthy controls and patients suffering from severe atherosclerosis has not been found, there occurs a significant improvement of PF in hyperlipidemic patients after successful treatment. Thus, it can be concluded that normalization of PF is one of the many factors improving the hemostatic balance in patients undergoing beneficial dietary or drug treatment.
Influence of type IIa, IIb and IV-hyperlipoproteinemia on platelet prostaglandin sensitivity, plasma thromboxane B2 and platelet half-life.
It is generally accepted that in hyperlipoproteinemia (HLP) the vascular prostacyclin formation is diminished. We wondered, whether HLP is also associated with changes in platelet sensitivity to antiaggregatory prostaglandins. Therefore, we examined the platelet sensitivity to the prostaglandins PGI2 and PGD2 as well as plasma thromboxane B2 (TXB2)-levels in 24 patients with HLP type IIa, IIb and IV. We found a marked decrease of platelet sensitivity to PGI2 in all the patients examined, which was more pronounced in type IIb than in types IIa and IV. Platelet sensitivity to PGD2 showed no difference in the hyperlipemic patients. Plasma TXB2-levels were significantly increased in comparison to a control group, the changes being most pronounced in patients with type IV HLP. Platelet half-life was significantly shortened in the HLP-patients. This in-vivo platelet function parameter was found to be reduced in patients with type IIa HLP to the greatest extent. Our findings suggest that platelet deposition in HLP is promoted not only by diminished vascular PGI2-formation, but also by decreased sensitivity of the platelets to antiaggregatory prostaglandins. The high TXB2-levels and the shortened platelet half-life reflect the in-vivo activated platelet population in these patients.
Platelet half-life in comparison to other in-vivo platelet function parameters such as thromboxane B2, beta-thromboglobulin and platelet factor 4 in patients with atherosclerotic lesions with and without hyperlipoproteinemia.
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Platelet plasma membrane changes in human type IIa hypercholesterolemia.
We have examined platelets collected from hypercholesterolemic (HC) young patients (n = 12) and from normocholesterolemic young volunteers (n = 9) by means of freeze fracture. The mean value of the surface density per square micrometer of the openings of the surface-connected canalicular system was significantly higher (p less than 0.03) in the HC patients (2.4 +/- 0.6) compared with the controls (1.8 +/- 0.5). It was also positively correlated with the low-density lipoprotein cholesterolemia/total cholesterol ratio (p less than 0.005) and inversely correlated with the high-density lipoprotein cholesterolemia/total cholesterol ratio (p less than 0.01). These data indicate that the circulating platelets of HC type IIa patients appear changed at ultrastructural level and that their modification may be somehow related to the atherogenetic processes.
[Vitamin status of 11- to 17-year-old healthy adolescents. Data from a longitudinal study].
In order to find out whether any age- or sex-related changes in vitamin nutrition or if any vitamin deficiencies can be detected in apparently healthy school children, blood vitamins (A, B1, B2, B6, C, and E) were determined in 111 children (54 boys and 57 girls), who took part in a longitudinal nutritional program. Most of the adolescents were examined yearly 5 times every year and afterwards two years later; at the begin of the study their age was 11 years, at the end 17 years. The results of vitamin determinations show for the most parameters age dependent changes, levels for Vitamin A, B1, and B2 becoming higher with increasing age, for Vitamin C in contrast markedly unfavorable. Using the criteria for risk for deficiency from adults a comparatively high percentage of adolescents must be considered to be at risk for deficiency (up to 30% for Vitamin B6). As this study shows partly statistically significant correlations between growth and some vitamin levels (e.g., for Vitamin A and E), age and sex related criteria for the assessment of vitamin status in adolescents should be made available. The results in general show that also in apparently healthy school-children subclinical biochemical vitamin deficiencies can be detected. This fact however, should be taken in consideration in planing and providing guidelines for an optimal nutritional program in adolescence.
Apolipoproteins and lipoproteins in children with type I diabetes: relation to glycosylated serum protein and HbA1.
Serum levels of cholesterol (C), triglycerides (TG), lipoprotein-C and apolipoproteins (apo) A-I, A-II and B were measured in 30 children with type I diabetes mellitus (16 boys, 14 girls, aged 11-14 years) and in 26 healthy controls (15 boys, 11 girls, aged 10-13 years). For 19 diabetics controls matched for age, sex and relative body weight were selected. The diabetic patients were considered to be in fair metabolic control according to HbA1 levels and glycosylated serum protein concentrations. Mean serum apo A-I, A-II and B, C, TG, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) did not differ significantly between diabetic nondiabetic children. Very low density lipoprotein cholesterol (VLDL-C) was significantly higher in diabetic children than in controls. Serum C and LDL-C levels showed close univariate linear correlations with glycosylated serum protein (LDL-C: r = 0.53, p less than 0.01, C: r = 0.58, p less than 0.01) in diabetics. The ratio LDL/HDL-C was significantly correlated to HbA1 levels (r = 0.47, p less than 0.01). By canonical and multiple linear correlation analysis significant relations of a selected set of variables concerning the control and therapy of diabetes (serum glucose, HbA1, glycosylated serum protein, insulin dose) with a set of lipoprotein variables (C, TG, VLDL-C, HDL-C, LDL-C, apo A-I, A-II, B) could be demonstrated. From these data we conclude that significant relations between atherogenic serum lipids and lipoproteins (C, LDL-C) and the degree of metabolic control exist in diabetic children, even in the absence of marked dyslipoproteinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipids, lipoproteins and alpha-tocopherol: relationship and changes during adolescence. A longitudinal study.
From May 1976 until June 1982 a longitudinal study in 54 apparently healthy Austrian schoolchildren with a mean age of 11.2 years at their first visit was performed. The aim of this study was to determine if there are any age-related changes in serum lipids, lipoproteins and alpha-tocopherol concentrations during adolescence and whether a permanent relationship between lipoproteins and alpha-tocopherol can be observed. Total cholesterol showed a significant decrease from age 11 to 14 years in boys (from 195.5 +/- 42.2 to 147.9 +/- 40.3 mg/dl) as well as in girls (from 181.9 +/- 29.7 to 144.1 +/- 23.4 mg/dl); thereafter, a slight increase could be shown. Similar changes could be observed for LDL cholesterol. No significant sex differences were found either in total or in LDL cholesterol, whereas in HDL cholesterol concentrations, a decrease in boys between 12 and 14 years (from 58.4 +/- 18.3 to 41.7 +/- 10.8 mg/dl) and an increase in girls from 13 years onwards led to significantly lower values in boys than in girls from the age of 16 years onwards. No consistent changes could be shown for alpha-tocopherol blood levels. Nevertheless, a close relationship between total cholesterol and alpha-tocopherol could be observed during all our investigations (0.4695 less than or equal to 0.7300, p less than 0.05) and, to a lesser degree, between LDL cholesterol and alpha-tocopherol. Significant correlations between alpha-tocopherol and HDL cholesterol and between alpha-tocopherol and triglycerides occurred only occasionally.
Nutritional support in pediatrics.
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Changes of alkaline phosphatase, inorganic phosphorus and total calcium in sera of 11 to 17 year old healthy adolescents, and their relationship to growth.
A semi-longitudinal study in 111 healthy school children, 11 years old, was started in May 1976 to evaluate age-related "normal-ranges" of two so-called "routine" blood parameters during adolescence. Follow-up examinations were performed at one-year intervals until 1982. In this paper growth velocity is described and results of estimations of alkaline phosphatase, inorganic phosphorus (Pi) and total calcium (Ca) are presented and compared with values in the literature. Peak growth velocity in girls (5.94 +/- 1.92 cm/year) occurred between 11 and 12 years, in boys (7.73 +/- 2.4 cm/year) between the age of 12 and 13 years; from the age of 14 years onwards boys were significantly taller than girls. A strong relationship (p less than 0.05) between growth and alkaline phosphatase could be shown throughout the period observed. Alkaline phosphatase activity varied within a wide range and reached mean peak values at the age of 11 years in girls (470.9 +/- 114.8 U/l) and the age of 13 in boys (514.4 +/- 135.7 U/l). Afterwards, alkaline phosphatase activity decreased towards adult levels. Inorganic phosphorus constantly decreased in both boys and girls until the age of 16, while from the age of 16 to 17 years a significant increase could be observed in both sexes. Total calcium values showed a significant increase between 12 and 13 years in boys and between 13 and 14 years in girls; after the age of 14 values decreased significantly in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of diet on serum lipoproteins in children with various forms of hyperlipidemias.
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The natural history of serum lipids and lipoproteins during childhood.
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[Obesity in childhood--diagnosis and therapy].
Obesity during childhood represents one of the most common nutritional disorders in industrialized countries. The duration of obesity in childhood correlates well with the probability to become an obese adult. Diagnosis of obesity requires reference weight for height tables and the measurement of skinfolds with the caliper technique. Using this method a differentiation between overweight and overnutrition can easily be performed also in an outpatient clinic. For therapeutic purpose a longterm dietary regime with a hypocaloric nutrition has to be reached. Some other dietary regimes ("Protein-modified fast" and "very low calorie diets") are presented and their clinical practicability discussed. The earlier treatment starts for obese children and adolescents the higher is the likelihood for longterm-success. It is emphasized that even pediatricians should focus their interest on prevention of obesity by means of prudent diet education.
[Diagnosis and effective therapy with plasmapheresis in a patient with homozygous familial hypercholesterolemia].
The case of a 17-year-old boy with the homozygous form of familial hypercholesterolaemia is reported. The patient presented tuberous and tendinous xanthomas, arcus lipoides, complete occlusion of the LAD of the coronary arteries, a characteristic family history, and total cholesterol levels greater than 600 mg/dl. Among the available therapeutic regimens we decided to perform plasma exchange treatment, which was introduced by Thompson in 1973 as therapy of this metabolic disorder. After each plasmapheresis, performed so far 7 times, the cholesterol and LDL-cholesterol concentrations dropped to normal levels; they increased again within the next 3 weeks, without, however, reaching the pretreatment levels. Undergoing this treatment, the xanthomas decreased markedly; there are reasons to assume that atherosclerotic lesions might also decrease during this treatment.
[Age and sex dependence of the diameter of the lumen of the ascending, thoracic and abdominal aorta].
The quantitative estimation of luminal diameter of 102 aortas (ascending, thoracic and abdominal aorta) from neonates to adults of 80 years showed a continuous increase with a marked change until the age of 15. From the 20th up to the 80th year we observed a further enlargement of the inner vessel-diameter of about 50%.
Inhibition of alkaline phosphatase activity by glucose.
Non-enzymatic glycosylation (NEG) of alkaline phosphatase (AP) was studied after short- and long-term incubation with glucose and other carbohydrates. Glucose and amino sugars clearly inhibited the enzyme activity; this was in contrast to reducing and non-reducing disaccharides, which had an enhancing effect. After AP had been incubated with 18 nmol/l glucose for 180 minutes (short-term incubation), a subsequent extensive dialysis revealed full recovery of the enzymatic activity. This, plus the demonstration of a [3H]sodium borohydride-reducible glucose-protein adduct, indicated that initially a labile aldimine (Schiff base) had been formed. Binding experiments with [14C]glucose and failure of dialysis to achieve a recovery of enzymatic activity after long-term incubation suggested that subsequently a stable ketoamine product had been formed. This was further confirmed by the thiobarbituric acid test, which revealed 0.65 nmol 5-hydroxymethylfurfural/mg protein for glycosylated AP compared to 0.11 for the non-glycosylated control. Preliminary results further suggest that NEG of AP also occurs in vivo. Streptozotocin diabetic rats had significantly lower serum AP activities than did non-diabetic controls (mean +/- SD: 153.7 +/- 28.4 vs. 760.5 +/- 95.7 U/l; p less than 0.001). Blood glucose levels and serum AP activity, which had been determined simultaneously during an oral glucose tolerance test, showed without exception an inverse relationship in each of 32 healthy children studied. The biological significance of these findings remains to be established.
[Endocrine studies on the Prader-Labhart-Willi syndrome: puberty induction in a 19-year-old boy after long-term treatment with an LHRH analog].
In two girls (14 and 16 years) and one boy (19 years) with PLW-syndrome and pronounced obesity (240, 210 and 77% overweight) endocrine function tests were carried out. Growth hormone secretion was decreased but normalized after reduction of weight. Thyroxin levels as well as basal and TRH stimulated TSH concentrations were normal. HCG application in the boy induced no rise of the normal basal testosterone levels. Oral glucose tolerance test demonstrated an increased stimulation of insulin in two cases, no other symptoms of diabetes mellitus were found. In the LHRH test an insufficient rise of gonadotropins was found. However, after two weeks of pernasal application of an LHRH analogue (D-Leu6-des-Gly10-EA) the gonadotropin stimulation was distinctly improved and onset of puberty was induced in the male patient. These results are indicative of a hypothalamic disturbance in patients with PLW-syndrome.
Serum apolipoproteins and lipoprotein (a) during the first week of life.
The levels of apolipoproteins, A-I, A-II, B and E, lipoprotein (a) and of total cholesterol and triglycerides were determined in cord serum and in capillary serum at the fifth day of life in a group of 44 term newborns. Additionally, cord serum lipoproteins were estimated. Sera from 26 healthy adults were studied for comparison. The concentrations of lipids and lipoproteins in cord serum were diminished as compared to adult levels. The occurrence of lipoprotein (a) in cord serum in concentrations significantly lower than in adults could be established. Serum apolipoproteins A-I, A-II and B were significantly lower at birth than in the adult, whereas apolipoprotein E levels did not differ from adult concentrations. During the first five days apolipoprotein B levels more than doubled, apolipoprotein A-I increased moderately and apolipoprotein E rose slightly. In contrast, serum lipoprotein (a) and apolipoprotein A-II did not change significantly. Unlike serum cholesterol, the levels of apolipoproteins B and E at day five were significantly correlated to those measured at birth in the same infants. The changes of the apolipoprotein pattern during the first week of life reflect the evolution of the lipid transport system of the newborn and may be related to the increasing utilisation of fat and to hormonal factors.