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Biomedical subjects

J J van Doormaal

Publications and source records attributed to J J van Doormaal.

At least 37 records · Page 2Linked to original sources

The dietary fatty acids of patients with coronary artery disease and controls in Curaçao. Implications for primary and secondary prevention.

Patients with coronary artery disease are advised to augment their dietary linoleic acid intakes at the expense of saturated fatty acids. We investigated whether the dietary linoleic acid intake of 57 patients with coronary artery disease (47 males, 10 females; ages 61 +/- 10 years) in Curaçao is higher as compared with 77 controls (51 males, 26 females; ages 56 +/- 7 years). For this, we measured plasma cholesterol ester fatty acids, which reflect the dietary fatty acid composition of the preceding weeks. Patients with coronary artery disease and controls had minor differences in cholesterol ester fatty acids. Their cholesterol ester linoleic acid content suggests that the dietary polyunsaturated/saturated fatty acid ratio is far below 1. Comparison with data reported for The Netherlands, Greenland and Crete showed that the dietary fatty acid composition in Curaçao is typically Western with a high intake of saturated fatty acids, a low intake of monounsaturated fatty acids and the consumption of linoleic acid as the predominant polyunsaturated fatty acid. Intake of long chain polyunsaturated fatty acids from fatty fish is low. Reduction of dietary saturated fatty acids, augmentation of fish consumption, and an increase of the alpha-linolenic/linoleic acid ratio are likely to be of benefit to both primary and secondary prevention from coronary artery disease in Curaçao.

Adult↗

Clinical chemistry of common apolipoprotein E isoforms.

Apolipoprotein E plays a central role in clearance of lipoprotein remnants by serving as a ligand for low-density lipoprotein and apolipoprotein E receptors. Three common alleles (apolipoprotein E(2), E(3) and E(4)) give rise to six phenotypes. Apolipoprotein E(3) is the ancestral form. Common apolipoprotein E isoforms derive from nucleotide substitutions in codons 112 and 158. Resulting cysteine-arginine substitutions cause differences in: affinities for low-density lipoprotein and apolipoprotein E receptors, low-density lipoprotein receptor activities, distribution of apolipoprotein E among lipoproteins, low-density lipoprotein formation rate, and cholesterol absorption. Accompanying changes in triglycerides, cholesterol and low-density lipoprotein may promote atherosclerosis development. Over 90% of patients with familial dysbetalipoproteinaemia have apolipoprotein E(2)/E(2). Apolipoprotein E(4) may promote atherosclerosis by its low-density lipoprotein raising effect. Establishment of apolipoprotein E isoforms may be important for patients with diabetes mellitus and several non-atherosclerotic diseases. Apolipoprotein E phenotyping exploits differences in isoelectric points. Isoelectric focusing uses gels that contain pH 4-7 ampholytes and urea. Serum is directly applied, or prepurified by delipidation, lipoprotein precipitation or dialysation. Isoelectric focusing is followed by immunofixation/protein staining. Another approach is electro- or diffusion blotting, followed by protein staining or immunological detection with anti-apolipoprotein E antibodies and an enzyme-conjugated second antibody. Apolipoprotein E genotyping demonstrates underlying point mutations. Analyses of polymerase chain reaction products are done by allele-specific oligonucleotide probes, restriction fragment length polymorphism, single-stranded conformational polymorphism, the primer-guided nucleotide incorporation assay, or denaturating gradient gel electrophoresis. Detection with primers that either or not initiate amplification is performed with the amplification refractory mutation system. Disparities between phenotyping and genotyping may derive from isoelectric focusing methods that do not adequately separate apolipoprotein E posttranslational variants, storage artifacts or faint isoelectric focusing bands.

Apolipoproteins E↗

Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol. The Liver Transplant Group, Groningen.

After orthotopic liver transplantation (OLT) bone mass rapidly declines and vertebral fracture rate increases. We studied bone loss and parameters of bone turnover in 53 consecutive patients. In an attempt to reduce bone loss the patients were prophylactically treated with cyclical etidronate in addition to daily 1 alpha-hydroxyvitamin D3 and calcium. During the first 3 months after transplantation median lumbar spinal bone mineral density (BMD) decreased 4.5%; subsequently no significant changes occurred. Median hip BMD continued to fall during the first post-transplantation year and deteriorated 7% over the whole study period. New vertebral fractures were seen in 25% of the patients, which is not lower than previously reported rates in patients not receiving cyclical etidronate. Parathyroid hormone levels increased after OLT (p = 0.01), but remained within normal ranges. Urinary hydroxyproline levels were increased and normalized in the second half-year after OLT. Elevated fasting calciuria increased further after OLT. 1,25-Dihydroxy-vitamin D3 levels were lowered pre-OLT (25 vs 66 pmol/ 1, p < 0.001) and normalized at 3 months after OLT. Serum osteocalcin concentrations remained unchanged and were reduced compared with levels in healthy controls. In summary, increased bone resorption occurs after OLT with persistent decreased bone formation, leading to vertebral fracture in 25% of patients. Etidronate, 1 alpha-calcidol and calcium treatment did not prevent bone loss.

Absorptiometry, Photon↗

Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil.

The occurrence of rhabdomyolysis is one of the rare side-effects of the cholesterol-lowering agent simvastatin. During the use of lovastatin, an agent related to simvastatin, the risk of this side-effect might be increased when cyclosporin or gemfibrozil are used concomitantly. It is possible that this also applies for simvastatin. We present two patients who developed rhabdomyolysis during the concomitant use of simvastatin and gemfibrozil.

Drug Synergism↗

Method-dependent increase in lipoprotein(a) in insulin-dependent diabetes mellitus during pregnancy.

The current prevalent view is that plasma lipoprotein(a) [Lp(a)] concentrations are under strong genetic control. Most dietary and drug interventions seem to have little or no effect on plasma Lp(a) levels. However, evidence for a possible regulatory rol e of hormones is accumulating, for instance, fluctuations of Lp(a) levels during pregnancy have been reported. Also, in insulin-dependent diabetes mellitus (IDDM) patients, elevated Lp(a) levels have been reported. In the present longitudinal study, plasma lipid concentrations, including Lp(a), were determined in IDDM women before pregnancy, during pregnancy, and 3 months postpartum. In our study population, Lp(a) concentration was not significantly correlated with either hemoglobin A1c (HbA1c) levels of apolipoprotein(a) [apo(a)] phenotype. Changes in other lipid parameters observed during pregnancy in our IDDM population were similar to those reported during normal pregnancy. Lp(a) concentrations were quantified using two different immunochemical methods that possess different sensitivities and specificities: an immunoradiometric assay (IRMA) using two different anti-apo(a) antibodies, and an enzyme-linked immunosorbent assay (ELISA) using an anti-apo(a) and an anti-apo B antibody. Median prepregnancy Lp(a) concentrations were 118 mg/L (range, 15 to 672) as determined with the IRMA and 107 mg/L (range, 21 to 451) as determined with the ELISA. Women with IDDM showed, in general, no significant change in Lp(a) concentration during pregnancy when it was assayed with the IRMA, although a tendency to increased values was observed. When Lp(a) concentrations were determined with the ELISA, a strong and significant increase in Lp(a) from weeks 17 to 24 of pregnancy onward was found. The latter results confirm the prevalent view that during pregnancy Lp(a) levels are increased. However, the present results and those of others and Lp(a) in normal pregnancy strongly emphasize the importance of method selection when determining Lp(a) concentrations.

Adult↗

Triiodothyronine rapidly lowers plasma lipoprotein (a) in hypothyroid subjects.

BACKGROUND: Increases in plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) are well known in primary hypothyroidism, but it is uncertain whether thyroid dysfunction is associated with elevated levels of the atherogenic lipoprotein (a) (Lp(a)). METHODS: The effect of short-term hypothyroidism on plasma Lp(a) was studied in 14 patients who had undergone a total thyroidectomy because of a well-differentiated thyroid carcinoma. They were studied 2 weeks after withdrawal of triiodothyronine (T3) therapy and 7 (5-9) weeks after resumption of T3 treatment (75-100 micrograms T3 daily). Fourteen euthyroid subjects served as controls. RESULTS: In the hypothyroid phase the athyreotic patients had higher levels of Lp(a) (105 [12-536] vs. 42 [1-321] mg/l, p < 0.05), apo-B (p < 0.001) and LDL cholesterol (p < 0.001) as compared with the euthyroid control subjects. T3 therapy lowered Lp(a) by 29% to 50 (12-535) mg/l, p < 0.01. Apo B and LDL cholesterol fell by 42% (p < 0.001) and by 53% (p < 0.001), respectively. After resumption of T3 therapy the levels of Lp(a), apo-B and LDL cholesterol were not different from those of the control subjects. The mean percentual decreases in Lp(a) and in apo-B were similar, although the individual changes in Lp(a) were more variable. CONCLUSIONS: Short-term hypothyroidism increases plasma Lp(a) and T3 therapy rapidly lowers Lp(a) together with apo-B and LDL cholesterol. Our findings support the hypothesis that thyroid hormone regulates plasma Lp(a) and apo-B in a parallel manner. Elevated concentrations of Lp(a) in combination with LDL cholesterol may be involved in the increased risk of cardiovascular disease assumed to be associated with hypothyroidism.

Adult↗

Lipoprotein(a) levels in patients with myocardial infarction treated with anistreplase: no prediction of efficacy but inverse correlation with plasminogen activation in non-patency.

The aim of this study was to investigate whether failure of thrombolytic treatment might be due to inhibition of fibrinolysis by high lipoprotein(a) levels. Fifty-eight patients with acute myocardial infarction were treated intravenously within 4 h after onset of symptoms with anistreplase (30 units) and heparin (30,000 IU/24 h). Blood samples for measurement of coagulation parameters were taken before and 1.5 h after treatment. Coronary angiography was performed after 48 h. Levels of lipoprotein(a) were measured 6 months after discharge from hospital. The patency rate was 74% (43/58). Median lipoprotein(a) levels were not different between the patients with a patent and those with a non-patent vessel (10 and 8 mg/dl, respectively), however, in patients with a non-patent infarct-related vessel, a significant inverse correlation was found between the lipoprotein(a) level and the decrease of plasminogen in the first 1.5 h after treatment. It is concluded that high lipoprotein(a) levels, although not directly associated with a poor outcome of anistreplase therapy, might contribute to insufficient fibrinolysis in patients with a non-patent infarct-related vessel.

Adult↗

Kidney size in infants of tightly controlled insulin-dependent diabetic mothers.

The aim of this study was to evaluate the influence of insulin-dependent diabetes mellitus in pregnant women on the kidney size of their infants. We measured kidney length in the first week of life using ultrasonography in 20 infants of tightly controlled insulin-dependent diabetic mothers and 20 healthy newborn controls, matched for birth weight. In the infants of diabetic mothers, the left kidney length ranged from 3.6 cm to 6.0 cm (4.2 cm +/- 0.5 cm, mean +/- SD). The right kidney length ranged from 3.3 cm to 4.9 cm (4.0 cm +/- 0.4 cm). In the control infants the left kidney length was 3.3 cm to 5.4 cm (4.3 cm +/- 0.6 cm), and the right kidney length was 3.4 cm to 5.3 cm (4.2 cm +/- 0.5 cm). There was no statistically significant difference in right or left kidney length between the two groups. We conclude that in this group of tightly controlled diabetic mothers, the diabetic state does not influence kidney size in their infants.

Birth Weight↗

Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group.

BACKGROUND: Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain. METHODS: Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment. RESULTS: In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids. CONCLUSIONS: No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.

Administration, Inhalation↗

Determination of changes in serum lathosterol during treatment with simvastatin to evaluate the role of lathosterol as a parameter for whole body cholesterol synthesis.

Serum levels of cholesterol and the cholesterol precursor lathosterol were determined in five healthy volunteers who took 20 mg simvastatin daily during 1 week. During this period and for the following 5 days blood samples were collected. Five days after ingestion of simvastatin, serum lathosterol had already reached a steady-state level and its concentration decreased by 55-73%. In contrast, the cholesterol concentration decreased only by 17-29% and did not reach a steady-state level even after 7 days of treatment. After withdrawal of simvastatin, serum lathosterol quickly rose to pretreatment values. From the data a mean half-life of lathosterol could be calculated of 23.5 +/- 6.6 h during treatment with simvastatin and of 28.7 +/- 15.1 h after its withdrawal, taking, respectively, the decrease and increase of serum lathosterol into account. From these data it can be concluded that serum lathosterol is also a good parameter for determining whole body cholesterol synthesis during non-steady-state conditions, although plasma mevalonic acid, another (early) cholesterol precursor, is preferred owning to its much shorter reported half-life.

Adult↗

Milk of patients with tightly controlled insulin-dependent diabetes mellitus has normal macronutrient and fatty acid composition.

The composition of macro- and micronutrients in milk from six patients with tightly controlled insulin-dependent diabetes mellitus [median glycosylated hemoglobin concentrations at parturition of 5.2% (range 4.9-5.3%, reference range 4.9-6.6%) and 6 wk thereafter of 6.1% (range 5.0-6.3%, reference range 5.0-6.4%) was compared with that from five control subjects. Milk samples were collected halfway through a single breast-feeding at days 3-5 (colostrum); 7, 9, and 10 (transitional milk); and 12, 15, 17, 21, 25, 29, and 35 (mature milk). We found no abnormalities in macronutrient (triglycerides, lactose, and protein), cholesterol, glucose, and myoinositol concentrations or fatty acid composition. Two of three longitudinally studied patients showed rather constant ratios between glucose concentrations in milk and capillary blood. The present data suggest that tight control corrects a multitude of milk abnormalities associated with moderate and poor control.

Adult↗

Anaphylactoid shock following Hymenoptera sting as a presenting symptom of systemic mastocytosis.

Systemic mastocytosis is a rare and chronic disorder characterized by a pathologically increased number of mast cells in various tissues and overproduction of mast cell mediators. From a group of 15 patients (10 females, 5 males) with systemic mastocytosis five female patients presented with a history of an anaphylactoid shock reaction to wasp sting. Three of them had no demonstrable specific IgE against wasp or bee venom in serum, and a skin test that was only weakly positive for wasp venom. One patient had specific IgE against wasp venom and a clearly positive skin test to wasp venom. The other patient had specific IgE against both wasp and bee venom and a skin test that was only weakly positive to wasp venom. Two patients had to stop a hyposensitization procedure because of systemic side effects. The five patients did not differ from the other patients with systemic mastocytosis with regard to either clinical symptoms and signs or urinary excretion of histamine metabolites. From the latter group two female and three male patients said they had been stung by a wasp in the past. Thus, anaphylactoid shock after Hymenoptera sting can be a presenting symptom of systemic mastocytosis and may be caused by an IgE- as well as a non-IgE-mediated mechanism. In cases of anaphylactoid reaction to Hymenoptera sting, especially when there is no IgE demonstrable in serum or in cases of intolerance of hyposensitization, the diagnosis of systemic mastocytosis should be considered, also in the absence of the clinical hallmarks of urticaria pigmentosa.

Adult↗

Postnatal glucose kinetics in newborns of tightly controlled insulin-dependent diabetic mothers.

Infants of diabetic mothers are at risk of developing hypoglycemia postnatally. Strict control of blood glucose during pregnancy might result in adequate glucose homeostasis in the neonate. We followed 15 mother-infant pairs from the beginning of pregnancy until birth. Glucose kinetics in the infants were measured on the first day of life, using a stable isotope dilution technique. Furthermore, levels of alternative substrates, FFA, and ketone bodies were measured. All infants received i.v. glucose from birth onward at a rate of 3.4 +/- 0.7 mg/kg/min (mean +/- SD). There was no relationship between the parameters of control of the insulin-dependent diabetes mellitus in the mothers and glucose kinetics in their infants. Glucose turnover was 5.2 +/- 1.1 mg/kg/min, glucose production rate (GPR) was 1.8 +/- 1.1 mg/kg/min. GPR was significantly lower in the infants studied at the end of the first day of life (p < 0.01), irrespective of the glucose infusion rate. Furthermore, the lower GPR was associated with an increased concentration of ketone bodies, suggesting an increased production of ketone bodies in these infants. The relatively high GPR measured in the infants who were studied in the first hours postnatally may be the result of postnatal hormonal stimulation of glycogenolysis and/or gluconeogenesis. From this study, we conclude that glucose kinetics in infants of tightly controlled diabetic mothers appear to be normal. Interestingly, despite the near-optimal insulin therapy in the mothers, there is a relationship between the SD scores of birth weight and the mean 3rd-trimester blood glucose values.

Aging↗

Long-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension.

OBJECTIVE: To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy. RESEARCH DESIGN AND METHODS: We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic clinic. One participant dropped out. A 2-yr randomized prospective study was conducted on 14 patients assigned to an LPD (0.6 g.kg-1.day-1) and 16 patients assigned to continue their UPD. Protein intake was assessed by using urinary urea excretion. Albuminuria (three overnight collections) was measured at baseline and on seven occasions thereafter. GFR and ERPF were measured annually using [125I]iothalamate and [131I]hippuran, respectively. RESULTS: In the LPD group, protein intake decreased from 1.05 +/- 0.32 to 0.79 +/- 0.16 g.kg-1.day-1 (P < 0.005), but only seven participants consumed < 0.8 g.kg-1.day-1. Protein intake was unaltered in the UPD group (P < 0.001 vs. LPD). Baseline albuminuria and renal hemodynamics were not different in the groups. In the LPD group albuminuria decreased from 36 (95% CI, 16-83) to 30 micrograms/min (95% CI, 14-67) (P < 0.05). After adjustment for MAP and diabetes duration, the decrease in albuminuria in the LPD group was 26% (95% CI, 13-36) (P < 0.001), which was significantly different from the 5% (95% CI, -10-22) change in the UPD group (P < 0.005 vs. LPD). Multiple regression analysis showed the actual decrease in protein intake lessened (P < 0.005), whereas prevailing MAP accelerated albuminuria (P < 0.001). Low-protein intake independently reduced ERPF (P = 0.009) and GFR (indirectly via ERPF, P < 0.001) after 1 yr. Only minor changes in renal hemodynamics occurred in the second yr. CONCLUSIONS: This study suggests that long-term dietary protein restriction beneficially reduces albuminuria and renal hemodynamics in IDDM patients with mildly elevated albuminuria. Systemic BP counteracts these effects even in the absence of hypertension. Suboptimal compliance limits diet efficacy.

Adult↗

Optimized determination of malondialdehyde in plasma lipid extracts using 1,3-diethyl-2-thiobarbituric acid: influence of detection method and relations with lipids and fatty acids in plasma from healthy adults.

We investigated the influence of different concentrations of Fe3+, phosphoric acid, butylated hydroxytoluene and glutathione on the production of the malondialdehyde-1,3-diethyl-2-thiobarbituric acid adduct in plasma lipid extracts. Following organic solvent extraction the stable product was analyzed by spectrophotometry (537 nm), fluorometry (547 nm) and high-performance liquid chromatography with fluorometric detection. Using optimized reaction conditions there was good agreement between the three methods, with slightly higher values for the spectrophotometric method. Plasma total lipid malondialdehyde reference values for 24 healthy adults amounted to 1.30 +/- 0.23 mumol/l (spectrophotometric method) and 1.11 +/- 0.31 mumol/l (fluorometric method). Plasma lipid malondialdehyde concentrations correlated significantly with plasma triglycerides (r = 0.527), total cholesterol (r = 0.612) and total fatty acids (r = 0.810) and with the total number of double bonds present in plasma fatty acids with three or more double bonds (r = 0.923).

Adult↗

Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion.

We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated:saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n = 18, two dropouts, analysis was performed in n = 16) or to continue their usual diet (n = 20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/- 4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/- 0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval, 11 to 127) (p less than 0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p less than 0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increased by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection of the Pro664-Leu mutation in the low-density lipoprotein receptor and its relation to lipoprotein(a) levels in patients with familial hypercholesterolemia of Dutch ancestry from The Netherlands and Canada.

From a large cohort of hyperlipidemic patients, who attended the Lipid Research Clinic in Amsterdam, The Netherlands and in Vancouver, Canada, 915 consecutive patients with familial hypercholesterolemia (FH) of Dutch descent, were selected. This group of FH patients was screened for the presence of a cytosine to thymidine nucleotide substitution in exon 14 of the LDL-receptor gene, in order to determine the frequency of this mutation in patients of Dutch descent and to investigate the relationship between the mutation and the level of lipoprotein(a). The mutation was detected in seven individuals. All patients with this mutation shared the same haplotype, which is suggestive of an ancient mutation. The index patients and a large kindred with this mutation were further analyzed at the biochemical and clinical level. Except for total and LDL-cholesterol, there was no statistically significant difference in biochemical parameters between family members with and without FH. In contrast to previous reports, there was no difference in plasma levels of lipoprotein(a) between patients with the mutation in exon 14 and unaffected individuals.

Adolescent↗