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Biomedical subjects

K de Meer

Publications and source records attributed to K de Meer.

At least 19 recordsLinked to original sources
PubMed2000

[Favorable effects of vitamin A in measles infection].

The recent measles epidemic that hit the Netherlands in 1999 resulted in numerous hospitalisations and several fatalities, and resembled the previous epidemic of 1987-1988 in numbers and severity. The triple (parotitis epidemica, measles, and rubella) vaccine used in the nationwide, free-of-charge immunization programme is highly effective, but is not accepted for ideological reasons by specific groups in the Dutch community. High oral doses of vitamin A have been shown to reduce mortality and pulmonary and gastrointestinal complications of measles in children in developing countries, but this treatment option is little known to physicians in the Netherlands. The appropriate dose regimens for safe administration of vitamin A in complicated measles are: age under 6 months 50,000 IU, age between 6 months and 2 years 100,000 IU, and age over 2 years 200,000 IU, administered by mouth upon admission. A repeated dose can be administered on the following day. In the Netherlands, and elsewhere, universal measles immunisation remains the first goal in the fight against this highly contagious disease.

Child, Preschool↗
PubMed2000

Determination of isotopic enrichments of [1-13C]homocysteine, [1-13C]methionine and [2H3-methyl-1-13C]methionine in human plasma by gas chromatography-negative chemical ionization mass spectrometry.

We describe a reliable method for the simultaneous determination of isotopic enrichments of [1-13C]homocysteine, [1-13C]methionine and [2H3-methyl-1-13C]methionine in human plasma. Accurate [1-13C]homocysteine calibration standards were prepared by chemical conversion via thiolactonisation of [1-13C]methionine standards. Based upon anion-exchange chromatography, (di)acetyl-3,5-bis-trifluoromethylbenzyl derivatives, preparation of accurate calibration curves and gas chromatography-negative chemical ionization mass spectrometry, isotopic enrichments in human plasma could be determined with TTR (%) <+/-0.2% (N=3) for [1-13C]homocysteine (enrichment range 0-8%), [1-13C]methionine (enrichment range 0-3%) and [2H3-methyl-1-13C]methionine (enrichment range 0-12%). The method was applied in a [2H3-methyl-1-13C]methionine tracer infusion study in a biological model.

Carbon Isotopes↗
PubMed2000

Nephrotic proteinuria has No net effect on total body protein synthesis: measurements with (13)C valine.

In nephrotic syndrome, significant amounts of plasma proteins, mostly of hepatic origin, are lost in urine. Total hepatic protein synthesis increases, suggesting that other protein pools must be conserved to maintain steady state. This can be accomplished either by decreased amino acid oxidation or decreased protein synthesis in other organs to replace lost liver-derived proteins. To determine the effect of nephrotic syndrome on total-body protein metabolism, we compared whole-body valine use in seven nephrotic patients and five controls using a primed continuous infusion of [1-(13)C]-valine, with additional priming of NaH(13)CO(3). Plasma [(13)C]-valine, (13)C alpha ketoisovaleric acid, and the expired (13)CO(2) enrichments were used to assess whole-body valine flux, valine oxidation, and nonoxidative valine disposal (NOVD). The valine flux into the blood compartment (97.7 +/- 3.0 versus 95.3 +/- 3.3 micromol/kg/h), oxidation of valine (19.4 +/- 1.9 versus 21.2 +/- 2. 8 micromol/kg/h), and NOVD (78.3 +/- 2.5 versus 74.2 +/- 2.7 micromol/kg/h) were not statistically different in patients compared with controls. Valine oxidation correlated positively with urinary urea excretion (r = 0.70; P = 0.01) in all subjects. Compared with control subjects who have similar urinary urea excretion, nephrotic subjects do not compensate for urinary loss of protein by decreased amino acid oxidation or decreased nonoxidative valine disposal. Previous studies have shown that synthesis of several hepatic proteins increases when subjects are fed the same dietary regime, whereas the present study shows that total-body protein synthesis does not increase. This would imply reduced synthesis of nonhepatic protein pools.

Adult↗
PubMed1999

[Missed infections in immigrant children].

Three African children who migrated to the Netherlands developed serious infections after they arrived. The first patient, a girl of 3 years adopted from the Zaire, was discovered to be a chronic hepatitis B carrier. Advice to vaccinate her whole adoption family was not followed. Her adoptive mother became infected with hepatitis B. The second patient, an Ethiopian girl of 13 years, was not adequately screened for infections on arrival. She was a chronic hepatitis B carrier and infected her adoptive mother. Seven years later she developed pulmonary tuberculosis with cavity formation and infected four contacts. The third patient, a 15-year-old political refugee from Zaire, who developed paediatric aids and later died of it, was not screened according to the screening protocol advised for immigrating children. All immigrating children should be fully and adequately screened for infectious diseases upon arrival in the Netherlands.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Determination of extracellular and intracellular enrichments of [1-(13)C]-alpha-ketoisovalerate using enzymatically converted [1-(13)C]-valine standardization curves and gas chromatography-mass spectrometry.

We report a validated method for the determination of extra- and intracellular [1-(13)C]-alpha-ketoisovalerate ([1-(13)C]-KIV) enrichments by gas chromatography-mass spectrometry. Standardization curves were prepared by enzymatic oxidation of [1-(13)C]-valine enriched standards of known composition. Slopes of [1-(13)C]-valine standardization curves (mean+/-SD: 0.99+/-0.02, n=5) and [1-(13)C]-KIV standardization curves (mean+/-SD: 0.98+/-0.01, n=7) were not significantly different. The method was applied for the determination of [1-(13)C]-KIV enrichments in plasma and tissues during [1-(13)C]-valine infusion in a piglet. [1-(13)C]-KIV enrichment could be determined+/-0.1 MPE (C.V. 1%), and extracellular [1-(13)C]-KIV enrichment was a reliable estimate of intracellular (skeletal muscle, bone growth plate) [1-(13)C]-KIV enrichment.

Animals↗
PubMed1999

Outpatient exercise training in children with cystic fibrosis: physiological effects, perceived competence, and acceptability.

Exercise training is currently advocated as part of the treatment of patients with cystic fibrosis (CF). However, data are few that document physiologic benefits or changes in patients' perceptions of long-term training programs in children with CF. The aim of this study was to investigate the effects and acceptability of a home cycling program in children with CF. Fourteen patients (9 boys, 5 girls) with CF, mean (SD) age 14.1 (2.0) years, with mild to moderate impairment of lung function (forced expiratory volume in 1 s, mean (SD) 58.3 (16.3)% of predicted) were studied for 1 year. The first half of the study year was used to obtain baseline values at 0 and 6 months. During the second half of the year, a cycle program was carried out 5 times a week, for 20 min each day at a level of work that resulted in a heart rate of 140-160 beats/min. Once a week the cycle program was supervised by a physiotherapist. Measurements were repeated at 12 months. Effects of the exercise program were measured in terms of lung function, nutritional status, growth, muscle strength, exercise performance, perceived competence, and attitude towards the training program. Differences between the changes during the 6-month training period as compared to the 6-month control period were analyzed by multivariate statistics and nonparametric tests. Statistically significant differences (P < 0.05) between the two periods were found with respect to muscle strength of knee extensors and ankle dorsiflexors, and with respect to maximal oxygen consumption per kg body weight as well as per kg fat free mass. All changes were positive. No adverse effects were found. Perceived competence showed significant positive changes in feelings about physical appearance, general self-worth, and Total Perceived Competence Score. Scores concerning perceived acceptability of the program were significantly lower at the end of the training period; however, patients reported that they did want to continue with other sorts of training. We conclude that an exercise training program in the home can produce beneficial effects on oxygen consumption, muscle force, and perceived competence in children with CF. However, acceptability of the program was low, suggesting that long-term adherence would be poor, and hence, other sorts of training need to be identified.

Adolescent↗
PubMed1999

Skinfold measurements in children with cystic fibrosis: monitoring fat-free mass and exercise effects.

UNLABELLED: Monitoring fat free mass (FFM), an indicator of nutritional status and a predictor of exercise performance in children, is particularly important in patients with cystic fibrosis (CF). We assessed validity of the skinfold method for measuring FFM, and its changes with exercise training, in children with CF. A total of 14 children with moderately severe symptoms of CF (age 10-18 years) were followed longitudinally and measured three times, before (at 0 and 6 months) and after exercise training (at 12 months). Separately, single measurements were conducted in 12 children with mild symptoms of CF and in 13 healthy controls. FFM was calculated from four skinfold measurements, and compared with estimations from total body water measured with deuterium dilution. The FFM calculated from skinfolds was 1.7% (P < 0.05) and 3.3% (P < 0.005) higher than that estimated with deuterium oxide dilution in patients with CF and controls, respectively. Limits of agreement were similar in patients with moderate and mild symptoms and in controls. The measurements in patients with moderate symptoms showed similar bias and limits of agreement at 6 and 12 months as compared to 0 months. Changes in FFM measured with both methods were significantly correlated before exercise (r = 0.82, P < 0.0005), and after exercise training (r = 0. 60, P < 0.05). CONCLUSION: In children with cystic fibrosis, skinfold measurements are applicable to monitor fat free mass irrespective of clinical severity of the disease, and repeated measurements at intervals of 6 months are applicable to monitor changes in fat free mass during exercise training.

Adolescent↗
PubMed1999

Effect of folic acid and betaine on fasting and postmethionine-loading plasma homocysteine and methionine levels in chronic haemodialysis patients.

OBJECTIVES: To study fasting and postmethionine-loading (increment and decrement) plasma homocysteine levels in end-stage renal disease (ESRD) patients in relation to B-vitamin status and after folic acid treatment without or with betaine. DESIGN: Plasma total homocysteine (tHcy) and methionine levels were measured in chronic haemodialysis patients after an overnight fast, and 6 and 24 h after an oral methionine load (0.1 g kg-1). The patients were subsequently randomized to treatment with folic acid 5 mg daily with or without betaine 4 g daily, and the loading test was repeated after 12 weeks. The patients were then re-randomized to treatment with 1 or 5 mg folic acid daily for 40 weeks, after which a third loading test was performed. SETTING: Haemodialysis unit of university hospital and centre for haemodialysis. SUBJECTS: Twenty-nine consecutive maintenance (> 3 months) haemodialysis patients, not on folic acid supplementation, 26 of whom completed the study. RESULTS: At baseline, the mean fasting, the 6 h postload and the 6 h postload increment plasma tHcy levels were increased as compared with those in healthy controls (46.8 +/- 6.9 (SEM), 92.8 +/- 9.1 and 46.0 +/- 4.2 mumol L-1, respectively) and correlated with serum folate (r = -0.42, P = 0.02; r = -0.61, P = 0.001 and r = -0.54, P = 0.003, respectively), but not with vitamin B6 or vitamin B12. At week 12, these variables had all decreased significantly. Betaine did not have additional homocysteine-lowering effects. At week 52, fasting and postload tHcy levels did not differ significantly between patients on 1 or 5 mg folic acid daily. Plasma tHcy half-life and plasma methionine levels after methionine loading were not altered by folic acid treatment. CONCLUSIONS: In chronic haemodialysis patients, fasting as well as postmethionine-loading plasma tHcy levels depend on folate status and decrease after folic acid therapy. Increased postload homocysteine levels in these patients therefore do not necessarily indicate an impaired transsulphuration capacity only; alternatively, folate may indirectly influence transsulphuration. The elucidation of the complex pathogenesis of hyperhomocysteinaemia in chronic renal failure requires further investigation.

Adult↗
PubMed1999

In vivo research with stable isotopes in biochemistry, nutrition and clinical medicine: an overview.

Tracers and kinetic modelling provide the opportunity to follow the movement and to quantify the metabolic fates of biological compounds in vivo. For studies in children and for repeated studies in adults, the use of stable isotopically labelled substrates are preferable and safe. Measurement of isotopic enrichment in biological molecules is highly specific and can be extremely precise. This allows the development of models of biological system dynamics in cells and organs that are otherwise inaccessible for sampling. Applications in biochemistry, nutrition and clinical medicine show the potential of stable isotopes in vivo. Methodology is of paramount importance and includes the choice of bolus studies, (primed) continuous infusions, use of multiple tracers and use of isotopomer information and intrinsic labels. There is no limit to the number and kind of compounds that can be traced. Topics include intermediate metabolism (lipids, proteins and carbohydrates) using hydrogen, carbon and nitrogen labels. In clinical medicine, 13C-breath tests are available for detection of Helicobacter pylori ([13C]urea breath test), and for assessment of a variety of gastro-intestinal and hepatic functions (e.g. [13C]octanoate and mixed [13C]triglyceride breath tests for studies of gastric emptying and fat absorption, respectively). Because theoretical, methodological, physiological and practical aspects are intertwined, in vivo research with stable isotopes demands close collaboration between the clinical researcher and the chemist responsible for the mass spectrometry.

Adult↗
PubMed1999

Peripheral muscle weakness and exercise capacity in children with cystic fibrosis.

Exercise intolerance in cystic fibrosis (CF) is attributed to diminished nutritional and pulmonary function. We studied the pathophysiology of such intolerance in relation to muscle force and fat-free mass (FFM), in 15 children with moderately severe symptoms of CF (FEV1 < 80% predicted and/or weight for age < -1 SD of reference median), 13 children with mild symptoms of CF (FEV1 and weight above these thresholds), and 13 healthy controls. Cycle maximal workload (Wmax) and V O2max were assessed. Maximal peripheral muscle force was measured, and FFM was calculated from skinfolds. Patients with mild CF, as compared with matched controls, had lower values of Wmax per kilogram of FFM (3.9 +/- 0.5 versus 4.6 +/- 0.3 W/kg [mean +/- SD], respectively; difference = 0.7 [95% CI = 0.4 to 1.1]), and diminished maximal muscle force (2.7 +/- 0.4 kN versus 3.1 +/- 0.7 kN; difference = 0.44 [95% CI = 0.03 to 0.87]), but similar V O2max. Patients with moderate CF had lower FFM, muscle force, and exercise tolerance than did the other groups. Oxygen cost of work was elevated in both groups of CF patients. Muscle force showed a strong positive correlation with Wmax in patients and controls, with disproportionately lower regression slopes in the CF patients. In children with CF, muscle force is decreased and associated with diminished maximal work load, even in the absence of diminished pulmonary or nutritional status.

Adolescent↗
PubMed1999

Resting energy expenditure and nutritional status in children with juvenile rheumatoid arthritis.

OBJECTIVE: Undernutrition is frequently encountered in children with juvenile rheumatoid arthritis (JRA). We assessed resting energy expenditure (REE) in relation to nutritional status and body composition in patients with JRA. METHODS: We selected 33 children (age 6 to 18 yrs) with JRA (13 oligoarticular, 10 polyarticular, 10 systemic JRA) and 17 controls matched for age and sex. Nutritional status was assessed for height, weight, and fat-free mass (FFM), and REE was measured with indirect calorimetry. RESULTS: Nutritional status in the patients with systemic JRA was diminished compared to the controls for height (140 vs. 159 cm; p<0.01) and FFM (28 vs. 38 kg; p = 0.03). Oligo and polyarticular patients with JRA had normal height and FFM. No significant differences existed in crude REE among the groups. However, after correcting REE for body weight and FFM, the patients with systemic JRA, compared to controls, had 18% higher REE per kg body weight (159 vs. 134 kJ/kg/day; p<0.01) and 21% higher REE per kg FFM (196 vs. 162 kJ/kg/day; p<0.01). Oligo and polyarticular JRA patients had 8% increased values for REE per kg body weight or FFM, but these differences were not statistically significant. CONCLUSION: Patients with systemic JRA show stunting, low FFM, and a significantly increased REE when nutritional status is taken into account. These data suggest that assessment of individual energy requirements should include correction for fat-free mass in the treatment of malnutrition in patients with systemic JRA.

Adolescent↗
PubMed1998

Determination of delta13C values of valine in protein hydrolysate by gas chromatography-combustion isotope ratio mass spectrometry.

A gas chromatographic-combustion isotope ratio mass spectrometric (GC-C-IRMS) method for the determination of [1-13C]valine enrichments in protein hydrolysates is described. Using a quick derivatization method, delta13C values of the N-methoxycarbonyl methyl ester of valine can be determined from baseline separated GC peaks. Evaluation studies with respect to precision, accuracy, linearity, reduction capacity of the CuO combustion furnace and isotope dilution as a result of derivatization, showed that our GC-C-IRMS system allows robust measurement of enrichments of [1-13C]valine in the range 0 to 1.5 MPE (S.D.+/-0.01 MPE, n=3). Therefore this method is suited to determine fractional synthetic rates (FSRs) of proteins as low as one-tenth of the FSR of human albumin, in studies using a primed, continuous (6 h) infusion with [1-13C]valine plasma enrichments of approximately 15 MPE and an hourly sampling schedule.

Carbon Isotopes↗
PubMed1998

Proportionate increase of fibrinogen and albumin synthesis in nephrotic patients: measurements with stable isotopes.

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are scarce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, proteinuria 12 g/day) and healthy control subjects (N = 8) using a primed/continuous infusion of the stable isotope L-[1-13C]valine for six hours. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the nephrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls to 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly correlated with the ASR of fibrinogen (P = 0.0046). Plasma alpha 2-macroglobulin was also elevated and correlated with the albumin synthesis rate, whereas plasma serum amyloid A and C-reactive protein were not elevated. These data suggest that in nephrotic patients the increased albumin synthesis is associated with an increase in synthesis of a specific and coordinated group of proteins, among which is fibrinogen.

Adult↗
PubMed1998

No net renal extraction of homocysteine in fasting humans.

BACKGROUND: The pathophysiological mechanism of hyperhomocysteinemia in chronic renal failure in humans is unknown. The loss of a putative renal homocysteine extraction in chronic renal failure has been hypothesized as significant homocysteine uptake has been demonstrated in the normal rat kidney. We studied homocysteine extraction in the normal human kidney. METHODS: We measured plasma total (free and protein-bound) and free homocysteine (tHcy and fHcy, respectively) in arterial and renal venous blood sampled from the aorta and right-side renal vein during cardiac catheterization in 20 fasting patients with normal renal function. Renal homocysteine extraction was calculated as the arteriovenous difference divided by the arterial levels times 100%. RESULTS: No significant renal extraction was demonstrated either for tHcy: 0.9% (SD 5.8; 95% CI -1.8 to +3.6) or for fHcy: -0.2% (11.0; -5.4 to +4.9). CONCLUSIONS: We conclude that no significant net renal uptake of homocysteine occurs in fasting humans with normal renal function. The loss of such uptake, therefore, cannot cause hyperhomocysteinemia in patients with renal failure.

Aged↗