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Biomedical subjects

J H Souverijn

Publications and source records attributed to J H Souverijn.

At least 19 recordsLinked to original sources
PubMed2001

Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease.

BACKGROUND: In animal models, HMG-CoA reductase inhibitors were able to improve renal function and endothelium-dependent vascular reactivity. In various experimental renal diseases, including autosomal dominant polycystic kidney disease (ADPKD), HMG-CoA reductase inhibitors improved the rate of decline in renal function. We studied the effect of simvastatin on ADPKD patients. METHODS: In a double-blind cross-over study, 10 normocholesterolaemic ADPKD patients were treated in random order for 4 weeks with 40 mg simvastatin or placebo daily. After each treatment period, we investigated the effect of simvastatin on renal blood flow and endothelium-dependent vascular reactivity. These periods were separated by a 4-week wash-out period. RESULTS: After treatment with simvastatin, glomerular filtration rate (GFR) significantly increased from 124+/-4 ml/min to 132+/-6 ml/min (P<0.05). Simultaneously, effective renal plasma flow (ERPF) increased significantly from 494+/-30 ml/min to 619+/-67 ml/min after simvastatin treatment (P<0.05). These renal effects were accompanied by a significantly enhanced vasodilator response to acetylcholine in the forearm after simvastatin treatment. Total serum cholesterol levels were significantly reduced after treatment with simvastatin, from 4.24+/-0.32 to 3.17+/-0.22 mmol/l (P<0.001). CONCLUSION: We concluded that simvastatin treatment can ameliorate renal function in ADPKD patients, by increasing renal plasma flow, possibly via improvement of endothelial function. Long-term clinical trials with HMG-CoA reductase inhibitors are needed to confirm these results and to establish a chronic inhibiting effect of HMG-CoA reductase inhibitors on the progression towards end-stage renal disease in ADPKD patients.

Acetylcholine↗
PubMed2000

The hypolipidemic action of bezafibrate therapy in hypertriglyceridemia is mediated by upregulation of lipoprotein lipase: no effects on VLDL substrate affinity to lipolysis or LDL receptor binding.

Fibrates are regarded as drugs of choice in hypertriglyceridemia (HTG). Downregulation of apolipoprotein (apo) C-III gene expression and upregulation of lipoprotein lipase (LPL) gene expression have been suggested to explain the hypolipidemic action of fibrates. This study was designed to study the effects of bezafibrate therapy on very low density lipoprotein (VLDL) susceptibility to lipolysis, VLDL binding to the low density lipoprotein (LDL) receptor and postheparin LPL activities in patients with HTG. VLDL lipolysis was studied with heparan sulfate proteoglycan-bound LPL. Binding affinity of VLDL to the LDL receptor was determined in J774 cells with 125I-labeled control LDL. Eighteen HTG patients were randomized to receive, in a double-blind placebo-controlled cross-over fashion, 400 mg bezafibrate once daily for 6 weeks. In response to bezafibrate therapy, plasma triglyceride and apoC-III levels decreased by 69 and 42%, respectively. HTG VLDL was lipolyzed less efficiently compared to control VLDL, and lipolysis did not improve by bezafibrate therapy. VLDL binding affinity to the LDL receptor was comparable between the control group and HTG group, and did not change upon bezafibrate therapy. However, the post-heparin LPL activity in the HTG patients increased from 153 to 192 U/l (P = 0.025). A strong inverse relation was observed between the change in LPL activities and the change in triglyceride levels (r = -0.62, P = 0.006). In conclusion, the hypolipidemic action of bezafibrate therapy in HTG may be attributed to increased LPL activity, whereas VLDL susceptibility to lipolysis and LDL receptor binding are not affected.

Adult↗
PubMed1999

Effect of acute hyperglycemia on basal, secretin and secretin + cholecystokinin stimulated exocrine pancreatic secretion in humans.

Pancreatico-biliary secretion is reduced during acute hyperglycemia. We investigated whether alterations in pancreatico-biliary flow or volume output are responsible for the observed reduction in duodenal output of pancreatic enzymes and bilirubin during hyperglycemia. Eight healthy subjects were studied on two occasions during normoglycemia and hyperglycemia (15 mmol/l). Pancreatico-biliary output was measured by aspiration using a recovery marker under basal conditions (60 min), during secretin infusion (0.1 CU/kg.h) for 60 min and during secretin + CCK (0.5 IDU/kg.h) infusion for 60 min. Secretin was infused to stimulate pancreatico-biliary flow and volume output. Secretin significantly (P<0.005-P<0.05) increased volume and bicarbonate output and CCK significantly (P<0.01) increased the output of bilirubin, pancreatic enzymes, bicarbonate and volume, both during normoglycemia and hyperglycemia. During hyperglycemia basal, secretin stimulated and secretin + CCK stimulated total pancreatico-biliary output were significantly (P<0.005-P<0.05) reduced compared to normoglycemia. The incremental outputs, however, were not significantly different between hyper- and normoglycemia. Pancreatic volume output was significantly (P<0.05) reduced during hyperglycemia compared to normoglycemia under basal conditions (31+/-16 m/h versus 132+/-33 m/h) during secretin infusion (130+/-17 ml/h versus 200+/-34 m/h) and during secretin + CCK infusion (370+/-39 ml/h versus 573+/-82 ml/h). Plasma PP levels were significantly (P<0.05) reduced during hyperglycemia. It is concluded that 1) hyperglycemia significantly reduces basal pancreatico-biliary output 2) the incremental pancreaticobiliary output in response to secretin or secretin + CCK infusion is not significantly affected during hyperglycemia, 3) a reduction in volume output contributes to the inhibitory effect of hyperglycemia on pancreatico-biliary secretion, 4) hyperglycemia reduces PP secretion suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion and volume during hyperglycemia.

Adult↗
PubMed1999

Does jejunal feeding activate exocrine pancreatic secretion?

BACKGROUND: The upper small bowel is of pivotal importance for the stimulation of exocrine pancreatic secretion in response to a meal. We hypothesize that more distal delivery of nutrients into the small intestine will result in less activation of pancreatic secretion. MATERIALS AND METHODS: Eight healthy subjects (3 male, 5 female; age 23 +/- 1 years) participated in two experiments, performed in random order. Subjects were intubated with a 4-lumen tube. Duodenal outputs of pancreatic enzymes and bilirubin were measured by aspiration using a recovery marker. The distal opening was used for continuous administration of a mixed liquid meal and located at either the ligament of Treitz or 60 cm further distally. Gallbladder volume was measured and blood samples were drawn for determination of gastrointestinal hormones. The duration of each experiment was 4 h; with 1 h fasting and 3 h continuous administration of nutrients. RESULTS: During proximal jejunal feeding, pancreatic enzyme output increased significantly over basal levels. No significant increase over basal levels was observed during distal jejunal feeding. Bilirubin output and gallbladder contraction were significantly (P < 0.05) reduced during distal compared to proximal jejunal feeding. No significant differences were found in plasma levels of CCK, PYY and neurotensin between proximal and distal jejunal feeding. CONCLUSION: Continuous feeding in the distal jejunum does not stimulate exocrine pancreatic secretion but maintains gallbladder contraction, although to a lesser extent. These effects are not related to hormonal changes but probably reduced activation of the enteropancreatic reflexes.

Adult↗
PubMed1999

Effect of insulin and glucose on basal and cholecystokinin-stimulated exocrine pancreatic secretion in humans.

Pancreaticobiliary secretion is reduced during acute hyperglycemia. In nondiabetics, this inhibitory effect also may result from hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin (CCK)-stimulated pancreaticobiliary secretion. Nine healthy volunteers (age, 22-52 years) were studied on three occasions in random order during (a) intravenous saline (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mM), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/L, glucose at 4-5 mM). Duodenal outputs of bilirubin, amylase, trypsin, and bicarbonate were measured under basal conditions and during CCK infusion (0.25 and 0.5 IDU/kg/h). Basal pancreaticobiliary secretion was significantly (p < 0.05) reduced during both HG and HI. During low-dose CCK stimulation, HG significantly (p < 0.05) reduced bilirubin and trypsin output compared with control. In contrast, HI did not significantly reduce pancreatic enzyme and bilirubin output during low-dose CCK infusion. During high-dose CCK infusion, neither HI nor HG influenced pancreatic enzyme and bilirubin output. Pancreatic bicarbonate output was not influenced by CCK and remained significantly (p < 0.05) reduced during HI and HG compared with control. It is concluded that during both acute hyperglycemia and euglycemic hyperinsulinemia, basal pancreaticobiliary secretion is significantly reduced. CCK-stimulated pancreatic enzyme and bilirubin output is significantly reduced only during hyperglycemia. The inhibitory effect of hyperglycemia on pancreaticobiliary secretion in healthy volunteers may occur independent of insulin.

Adult↗
PubMed1998

The high alkaline fraction on isoelectric focusing of cerebrospinal fluid is cystatin C.

A high alkaline fraction with a pI of 9.2 is sometimes seen on isoelectric focusing patterns of cerebrospinal fluid. The appearance of this fraction mainly depends on the type of concentrators used to prepare the cerebrospinal fluid samples, prior to isoelectric focusing. The amino acid sequence of the high alkaline fraction showed sequence identity to cystatin C, a cysteine protease inhibitor with a pI of 9.2-9.3 and a molecular mass of 13.4 kDa. In addition, on Western blot the high alkaline fraction was recognized by an antibody, directed against cystatin C. Taken together, the present findings demonstrate that the high alkaline fraction is cystatin C.

Amino Acid Sequence↗
PubMed1998

Effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion in humans.

This study was undertaken to investigate the effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion. Seven healthy subjects participated in two experiments performed in random order during normoglycemia and hyperglycemic clamping at 15 mM. Duodenal outputs of bilirubin, trypsin, amylase, and bicarbonate were measured by aspiration with a recovery marker under basal conditions for 60 min and during continuous infusion of bombesin (1 ng/kg x min) for 60 min. Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were determined at regular intervals. Compared to normoglycemia, during hyperglycemia basal outputs of bilirubin (17 +/- 3 vs. 0.9 +/- 0.4 micromol/60 min), trypsin (24 +/- 4 vs. 4 +/- 1 U/60 min), amylase (12 +/- 1 vs. 3 +/- 1 kU/60 min), and bicarbonate (2.9 +/- 0.5 vs. 1.2 +/- 0.2 mmol/60 min) were significantly p < 0.05) reduced. Bombesin significantly (p < 0.05) increased pancreaticobiliary output during both normo- and hyperglycemia. During hyperglycemia bombesin-stimulated 60-min outputs of bilirubin, trypsin, amylase, and bicarbonate were not significantly different compared to those during normoglycemia. Basal and bombesin-stimulated plasma PP concentrations were significantly (p < 0.05) reduced during hyperglycemia, but plasma CCK levels were not significantly different. It is concluded that acute hyperglycemia reduces basal but does not affect bombesin-induced pancreaticobiliary secretion.

Acute Disease↗
PubMed1998

European multicentre evaluation of the Super Aution SA-4220 urinalysis analyser.

A multicentre evaluation of the urine test strip analyser Super Aution-4220 was carried out in six laboratories. The analytical performance of the instrument with regard to imprecision, linearity, detection limit, drift, carry-over and method comparison was studied. Using the Aution stick 8 test strip the pH, glucose, protein, ketones, bilirubin, blood, urobilinogen and leukocyte esterase were analysed. Specific gravity measurements were performed by refractive index method. Within-run and between-run imprecision determined at three levels of analyte were good. No carry-over was observed. Obtained results were linear through all the described analytical range. No significant drift was detected. Method comparison with some quantitative methods was performed and showed a good correlation with most of the analytes. The study of interferences showed minor interferences by common therapeutic drugs with the measurement of some analytes. During the assessment period of about 6 months no breakdown occurred in any laboratory. The Super Aution urine analyser appeared to be a highly automated analyser of urinary test strips. The operation was simple and the maintenance required only a few minutes a day.

Artifacts↗
PubMed1998

Absence of seasonal variation in the phase of the endogenous circadian rhythm in humans.

Humans may be subject to seasonal variations, as evidenced by the existence of seasonal affective disorder (SAD) and midwinter insomnia. However, some recent studies have shown that the seasonal variation in the phase of the circadian rhythm is relatively weak in healthy humans. In the present study, evidence is found that there is no seasonal variation in the phase of the endogenous circadian rhythm at all. Body temperature, cortisol excretion, and subjective alertness of six subjects recorded under constant routine conditions showed no systematic seasonal variation in circadian phases. This finding indicates that secondary zeitgebers blocked or counterbalanced the seasonal variation in the entrainment effect of the natural photoperiod. The human being may live in an environment in which the photoperiod has lost its status of primary zeitgeber.

Adolescent↗
PubMed1998

Multicenter harmonization of common enzyme results by fresh patient-pool sera.

A region consisting of 19 clinical laboratories harmonized their calibration of seven common enzymes by using fresh patient-pool sera. One of the laboratories was chosen to act as Regional Reference Laboratory (RRL). This laboratory used internationally accepted (mostly IFCC) methods at 37 degrees C, with an intralaboratory CV < or = 2.5%. First, the reference ranges of the RRL were verified by analysis of a reference population and calculation of the results by a parametric method. Next, all laboratories, including the RRL, received six patient-pool sera and analyzed them at the same time on the same date. Enzyme calibration factors at each laboratory were converted on the basis of the slope, and occasionally the intercept, of regression analysis with the RRL and the individual laboratory. Before harmonization, the interlaboratory CVs varied from 16.9% to 61.6%. After harmonization, CVs decreased to between 5.0% and 9.5%. These results proved to be reproducible over a period of more than a year. Using internationally accepted inaccuracy and imprecision criteria, the achieved interlaboratory CVs permit the use of one set of reference ranges by all participating laboratories. Certified Reference Materials were analyzed, resulting in interlaboratory CVs as low as those achieved with patient-pool sera. These materials can act as commutable reference preparations, except for creatine kinase.

Alanine Transaminase↗
PubMed1997

Effect of acute hyperglycemia on basal and cholecystokinin stimulated exocrine pancreatic secretion in humans.

This study was undertaken to investigate the effect of acute hyperglycemia on pancreatico-biliary secretion in healthy subjects. Duodenal outputs of bilirubin, amylase, trypsin and bicarbonate were measured by aspiration using a recovery marker under basal condition for 75 min and during continuous infusion of CCK (0.5 IDU/kg.h for 60 min). Seven healthy subjects participated in two experiments performed in random order during normoglycemia and during acute hyperglycemic clamping at 15 mmol/l. At regular intervals plasma PP levels were determined as an indirect measure of vagal-cholinergic tone. Basal pancreatico-biliary secretion was significantly (p<0.05) reduced during acute hyperglycemia. CCK significantly (p<0.05) increased bilirubin, amylase and trypsin output both during normo- and hyperglycemia. During the initial 30 min of CCK infusion the bilirubin, amylase and trypsin outputs were significantly (p<0.05) inhibited in the hyperglycemic experiment compared to normoglycemia. In the following 30 min of CCK infusion the bilirubin, amylase and trypsin output were not different between hyper- and normoglycemia. Basal and CCK-stimulated plasma PP concentrations were significantly (p<0.05) reduced during hyperglycemia. In summary: 1) basal pancreatico-biliary secretion is significantly reduced during acute hyperglycemia 2) during hyperglycemia CCK-stimulated pancreatico-biliary secretion is also significantly reduced with the pattern of a delayed response 3) hyperglycemia inhibits basal and CCK-stimulated PP secretion suggesting impaired vagal-cholinergic activity during hyperglycemia.

Acute Disease↗
PubMed1997

Effect of acute hyperglycaemia on basal and fat-induced exocrine pancreatic secretion in humans.

1. We have investigated the effect of acute hyperglycaemia on pancreatico-biliary secretion in healthy subjects. Duodenal outputs of trypsin, lipase, amylase, bicarbonate and bilirubin were measured for 90 min under basal conditions and for 90 min in response to intrajejunal fat administration (1 g/h) on 2 separate days: during normoglycaemia (blood glucose 5 mmol/l) and during acute hyperglycaemia aimed at 15 mmol/l. Plasma cholecystokinin levels, as the major hormonal stimulus of pancreatic and biliary secretion, and plasma pancreatic polypeptide levels, as an indirect measure of vagal-cholinergic tone, were determined at regular intervals. 2. In the basal period pancreatico-biliary secretion was significantly (P < 0.05) reduced during hyperglycaemia compared with normoglycaemia. During normoglycaemia and hyperglycaemia intrajejunal fat significantly (P < 0.05) stimulated pancreaticobiliary secretion. However, during hyperglycaemia, fat-stimulated 90 min pancreatico-biliary secretion was significantly (P < 0.05) reduced compared with normoglycaemia: trypsin (23 +/- 7 units versus 66 +/- 20 units), lipase (36 +/- 8 k-units versus 74 +/- 18 k-units), amylase (8 +/- 2 k-units versus 18 +/- 5 k-units) and bilirubin (32 +/- 8 mumol versus 71 +/- 14 mumol). Plasma cholecystokinin levels increased significantly (P < 0.05) during fat administration and were not different between the two experiments. Plasma pancreatic polypeptide levels were significantly (P < 0.05) reduced during hyperglycaemia both in the basal period and during intrajejunal fat administration. 3. It is concluded that basal and fat-stimulated pancreatico-biliary secretion are significantly reduced during acute hyperglycaemia. Acute hyperglycaemia does not affect intrajejunal fat-stimulated cholecystokinin secretion. Acute hyperglycaemia inhibits basal and stimulated pancreatic polypeptide secretion suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion during hyperglycaemia.

Acute Disease↗
PubMed1997

Serum albumin, coronary heart disease risk, and mortality in an elderly cohort.

We investigated associations of serum albumin with the incidence and mortality of coronary heart disease among men from the Zutphen Elderly Study. In 1985, 820 men were randomly selected from a population age 64-84 years and were followed for 5 years. We adjusted relative risks for traditional risk factors (age, body mass index, diastolic blood pressure, total and high-density lipoprotein cholesterol, smoking, and alcohol consumption) and also for baseline health status indicators (white blood cell count, physician's health score, self-rated health, and history of relevant diseases). Albumin was inversely associated with the incidence of coronary heart disease only among men with elevated total cholesterol levels (> or = 6.5 mmol per liter). The relative risk for a 1-standard deviation increase (2.5 gm per liter) in albumin was 0.60 [95% confidence interval (CI) = 0.38-0.96] and was not altered after additional adjustment for baseline health status. In all men, the relative risk for death due to coronary heart disease was 0.67 (95% CI = 0.49-0.92), and the relative risk was reduced to 0.84 (95% CI = 0.61-1.15) after adjustment for health status. We found comparable health status-adjusted relative risks for mortality from cardiovascular diseases (relative risk = 0.83; 95% CI = 0.67-1.02) and for mortality from all causes (relative risk = 0.86; 0.73-0.99). Independent of traditional risk factors, moderately low serum albumin is predictive of coronary heart disease and all-cause mortality in elderly men. Only part of this relation could be explained by baseline health status.

Age Distribution↗
PubMed1996

Effect of apolipoprotein E and insulin resistance on VLDL particles in combined hyperlipidemic patients.

Apolipoprotein (apo) E2 and high insulin levels are associated with the severity of hypertriglyceridemia in patients with combined hyperlipidemia. To study how these determinants affect very low-density lipoprotein (VLDL) in combined hyperlipidemic patients, we characterized VLDL particles in 106 unrelated patients with combined hyperlipidemia. The study was performed after 9 weeks of standardized dietary intake and after an overnight fast. Patients heterozygous for apoE2 had significantly higher mean levels of VLDL cholesterol by 0.71 mmol/l (95% CI, 0.30 to 1.12 mmol/l, P < 0.005) and VLDL triglycerides by 0.88 mmol/l, (95% CI, 0.30 to 1.47 mmol/l, P < 0.005) compared to patients without apoE2. The VLDL triglyceride content per particle and the calculated diameter of the VLDL particles were similar in both groups, which indicate a higher number of circulating VLDL particles in heterozygous apoE2 carriers. Patients with high fasting insulin levels (> or = 80 pmol/l) had a higher mean serum VLDL triglyceride level by 0.56 mmol/l (95% CI, 0.04 to 1.07 mmol/l, P < 0.05). The calculated VLDL diameter was larger by 3.7 nm (95% CI, 1.2 to 6.2 nm, P < 0.005) and the particles contained more triglycerides by 2.7 weight percent (95% CI, 0.3 to 5.1 weight percent, P < 0.05). These insulin-dependent changes in VLDL particles were only present in the absence of apoE2. In conclusion, patients heterozygous for apoE2 have higher numbers of circulating VLDL particles, whereas patients with high fasting insulin levels have larger, triglyceride enriched VLDL particles.

Adult↗
PubMed1995

Predictive value of tetrapolar body impedance measurements for hydration status in critically ill patients.

OBJECTIVE: To design and evaluate a simple and rapid method to predict body hydration status in critically ill patients. DESIGN: Prospective, consecutive sample. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 31 consecutive patients. METHODS: All patients were classified daily for hydration status by the attending physician based on clinical impression, weight changes and laboratory measurements. The hydration status was scored as 'dehydrated', 'euvolemic' or 'edematous'. The total body impedance was measured daily by a tetrapolar impedance technique. RESULTS: Resistances > 700 omega were found in dehydrated subjects and resistances of < 400 omega in edematous patients. Weight gain was observed in dehydrated and weight loss in edematous patients. A discriminant analysis was used to create a predictive model for hydration using the daily impedance and weight measurements. If a cutoff point of 60% for the predicted classification was used to categorize the patient's hydration as dehydrated, euvolemic and edematous, no false positive predictions were observed for the dehydrated or the edematous state. CONCLUSION: Impedance measurements are in close agreement with the clinical impression of hydration of critically ill patients. Future investigations must elucidate the clinical importance.

Adolescent↗