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Biomedical subjects

M J Janssen

Publications and source records attributed to M J Janssen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fish oil and glycemic control in diabetes. A meta-analysis.

OBJECTIVE: Hypertriglyceridemia is associated with cardiovascular disease in diabetes. Fibrates effectively lower, but do not always normalize, serum triglyceride levels. Fish oil supplements may then be added to lower serum triglyceride levels. Doubt remains whether the net effect of fish oil intake on glycemic control is beneficial in diabetes. We therefore performed a meta-analysis from published clinical trials. RESEARCH DESIGN AND METHODS: Data sources were Medline (Cologne, Germany), Excerpta Medica, Current Contents, review articles, and published reference lists. Publications of 26 trials were selected, and all trials included more than five diabetes (IDDM and NIDDM) patients and addressed the effects of fish oil (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) on serum lipids and glucose tolerance. We (C.E.F., M.J.F.M.J.) extracted data independently based on predetermined criteria. Studies were classified according to design. RESULTS: All studies combined showed a decrease in mean triglyceride concentrations in association with fish oil: -0.60 mmol/l (95% CI, -0.84 to -0.33, P < 0.01) and a slight but significant increase in serum LDL cholesterol: 0.18 mmol/l (95% CI, 0.04-0.32, P = 0.01), with both findings most prominent in NIDDM. No significant changes in HbA1c percentages occurred in diabetic subjects treated with fish oil. Fasting blood glucose levels were increased with borderline significance in NIDDM subjects (0.43 mmol/l [95% CI, 0.00-0.87], P = 0.06) and were significantly lower in IDDM subjects (-1.86 mmol/l [95% CI, -3.1 to -0.61], P < 0.05). Significant dose-response effects of EPA (g/day) on HbA1c and triglycerides and of DHA (g/day) on fasting blood glucose levels, HbA1c, and triglycerides were demonstrated only in NIDDM subjects. CONCLUSIONS: The use of fish oil has no adverse affects on HbA1c in diabetic subjects and lowers triglyceride levels effectively by almost 30%. However, this may be accompanied by a slight increase in LDL cholesterol concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

Blood Glucose↗
PubMed1997

Stability of solubilized benzodiazepine receptors.

According to the observations of other researchers, benzodiazepine receptors solubilized with sodium deoxycholate are unstable, but stability can be improved by exchanging deoxycholate for Triton X-100. In our experiments we conclude that the choice of detergent is not the restrictive factor for the stability of the solubilized receptors, but the storage conditions are. Solubilized receptors, either stored in sodium deoxycholate or in Triton X-100, were stable for at least 2 months when stored at -80 degrees C, but both preparations were strongly unstable when stored at -20 degrees C. Alternatively, sodium deoxycholate-solubilized receptors may be lyophilized and then stored at -20 degrees C.

Animals↗
PubMed1997

Endothelium-dependent vasodilatation and distensibility of large arteries in chronic haemodialysis patients.

BACKGROUND: Cardiovascular mortality is increased in chronic haemodialysis (HD) patients and is not completely explained by common cardiovascular risk factors. Hyperhomocysteinaemia and chronic HD per se may play a role, because these factors may adversely affect endothelial function and distensibility of conduit arteries, which are important determinants of the risk of atherosclerosis, thrombosis and cardiac hypertrophy. METHODS: A vessel wall movement detector system was used to investigate endothelium-dependent, flow-mediated and endothelium-independent, glyceryl trinitrate-induced vasodilatation in the brachial artery and compliance and distensibility coefficients (CC and DC) in the common carotid artery in 28 chronic HD patients and 28 control subjects. RESULTS: Endothelium-dependent, but not endothelium-independent, vasodilatation was markedly reduced in the HD group (3.7 +/- 1.1 vs. 9.7 +/- 1.2%; P = 0.001). The DC was reduced only in a subgroup of patients aged < 50 years: 16.9 +/- 1.5 vs. 22.4 +/- 2.0 10(-3)/kPa (P = 0.032) and was not related to endothelium-dependent vasodilatation. CC did not differ between the groups. Plasma total homocysteine was elevated in the HD patients, but was neither related to endothelium-dependent vasodilatation, nor to DC. CONCLUSION: Chronic renal failure and (or) chronic haemodialysis are associated with impaired endothelium-dependent vasodilatation, which may reflect an increased susceptibility for the development of atherosclerosis and thrombosis.

Adult↗
PubMed1996

Efficacy of low-dose desferrioxamine for the estimation of aluminium overload in haemodialysis patients.

In haemodialysis patients the desferrioxamine (DFO) test is an accepted method for estimating the body content of aluminium. However, toxic side effects have been frequently reported with the high-dose (30 or 40 mg/kg) DFO tests. To study if a low-dose (500 mg) DFO test was also useful and free of side effects, we compared it with a high-dose DFO test in 22 patients on regular haemodialysis. During the first two hours of dialysis, 500 mg DFO in 100 ml 0.9% NaCl were administered intravenously. Before dialysis and after 48 hours aluminium concentration was determined in serum. In 14 patients the low-dose DFO test was considered positive. In 11 of those 14 patients the high-dose (30 mg/kg) DFO test was positive too. Analysis of the results showed a significant correlation (p < 0.05) between the outcome of the two DFO tests in the same patient. Compared to the high-dose DFO test, the low-dose test revealed a sensitivity of 79% and a specificity of 63%. In contrast with the high-dose DFO test might be a reliable and safe method for the estimation of the body content of aluminium in patients on regular haemodialysis.

Adult↗
PubMed1996

The bleeding risk in chronic haemodialysis: preventive strategies in high-risk patients.

Haemodialysis (HD) patients are at an increased risk of bleeding because of uraemic bleeding tendency and systemic anticoagulation caused by intermittent heparinization. Additional risk factors may be aspirin or coumarin use for the prevention of fistula thrombosis, diffuse intravascular coagulation, recent trauma, postsurgical state, inadequate control of hypertension, gastrointestinal lesions, diabetic retinopathy, renal cystic disease, and uraemic pericarditis. In HD patients with an active bleeding focus blood transfusion, desmopressin acetate (DDAVP), conjugated oestrogens, and dialysis treatment can limit the bleeding risk. Strategies to reduce the bleeding risk conveyed by systemic anticoagulation during HD are regional heparin anticoagulation and minimal heparinization. In our opinion, dialytic modalities that completely preclude systemic anticoagulation, i.e. peritoneal dialysis (PD), heparin-free HD, and HD with regional anticoagulation with prostacyclin, mesilates, or citrate, are indicated for patients who are actively bleeding, or who are within 3 days from a bleeding episode, or a surgical or accidental wound, or who are less than 2 weeks from cerebral or retinal haemorrhage, and for patients with incompletely treated proliferative diabetic retinopathy or uraemic pericarditis.

Cerebral Hemorrhage↗
PubMed1996

Solubilized benzodiazepine receptors for use in receptor assays.

In the development of non-radioactive receptor assays for benzodiazepines, employing fluorescent ligands, it was observed that the fluorescence measurements were hampered by the background fluorescence of the receptor preparation. This receptor preparation is a brain tissue homogenate in which the benzodiazepine receptors are membrane-bound. To minimize the influence of the receptor material on the fluorescence detection, the benzodiazepine receptors were solubilized with 0.5% sodium deoxycholate. The binding characteristics of the receptors were examined after solubilization and compared with membrane-bound receptors. The Kd and Bmax values for membrane-bound receptors were 1.20 nM and 1.01 pM mg-1 protein and for solubilized receptors they were 4.1 nM and 0.54 pM mg-1 protein respectively. Inhibition curves with the benzodiazepine antagonist flumazenil and the agonist lorazepam revealed that their affinities for the solubilized receptor as compared to the membrane-bound receptor were also reduced from 0.67 nM to 3.2 nM and from 1.49 nM to 8.4 nM respectively. The detection limits for the two benzodiazepines, however, were not affected by the solubilization. Furthermore, three different methods to separate the fraction of free labelled ligand and the fraction bound to the solubilized receptor were compared, namely polyethylene glycol precipitation/filtration, ion exchange filtration and charcoal adsorption. Polyethylene glycol precipitation/filtration gave the highest yield for the bound fraction and the best reproducibility.

Adsorption↗
PubMed1996

Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients.

Citrate and nadroparin calcium, a low molecular weight heparin (LMWH), were compared in a randomized cross-over trial in 21 chronic hemodialysis patients regarding anticoagulation, calcium and magnesium kinetics, biocompatibility, dialysis efficiency, and aluminum contamination. Citrate was infused into the arterial line at a minimum rate of 0.68 mmol/min, combined with a calcium and magnesium-free dialysate and intravenous supplementation of calcium and magnesium at rates of 0.22 and 0.10 mmol/min, respectively. Seven patients with a dialysis session of six hours, received 2/3 of the nadroparin dose predialysis, and 1/3 after 2.5 hours (divided dose (DD) group). A single predialysis bolus injection of nadroparin was administered to eight patients not on coumarins [single dose (SD) group] and to six patients on coumarins [single dose + coumarins (SD + C) group], all with a dialysis session of four hours. Nineteen patients received a nadroparin dose of 200 ICU/kg. Two patients with a single dose, one of them on coumarins, received a dose of 150 ICU/kg because of a hematocrit < 0.30. With citrate systemic whole blood activated clotting time (ACT) remained unchanged, indicating efficient regional anticoagulation. After two hours of dialysis with nadroparin, systemic ACT increments, that is, the increase compared to predialysis, of the DD, SD, and SD + C groups were 8.8 +/- 1.5, 18.7 +/- 4.7, and 33.3 +/- 6.1 seconds, respectively (mean +/- SEM). Postdialysis ACT increments in these groups were 1.5 +/- 3.4, 17.7 +/- 6.8, and 30.3 +/- 8.0 seconds. Two hour increments of systemic activated partial thromboplastin time (APTT) of the DD, SD, and SD + C groups during nadroparin were 5.0 +/- 1.2, 15.1 +/- 2.7, and 32.2 +/- 5.5 seconds, respectively, and the corresponding postdialysis APTT increments were 2.9 +/- 1.4, 7.8 +/- 2.4, and 15.8 +/- 2.6 seconds. Two-hour anti-Xa increments of the DD, SD, and SD + C groups amounted to 0.34 +/- 0.07, 0.67 +/- 0.07, and 0.80 +/- 0.08 IU/ml. The respective postdialysis anti-Xa increments were 0.21 +/- 0.06, 0.58 +/- 0.06, and 0.71 +/- 0.08 IU/ml (All ACT, APTT and anti-Xa increments were significant; P < 0.05), except for the ACT increments and the postdialysis APTT increment of the DD group). These increments, together with unchanged prothrombin fragments 1 and 2 (PTF1 + 2), indicate systemic anticoagulation with nadroparin. The increments of serum calcium and magnesium during citrate were comparable to the increments observed with a dialysate containing 1.5 mmol/liter calcium and 0.75 mmol/liter magnesium used in combination with nadroparin. Ionized calcium increments during citrate were significant after the end of dialysis, while the dialysate containing 1.5 mmol/liter calcium induced significant increments during and postdialysis. No differences were observed between citrate and nadroparin regarding biocompatibility), (expressed as dialysis-induced leukopenia and thrombocytopenia), and dialysis efficiency [measured as dialyzer urea and creatinine clearance, normalized weekly whole body urea clearance (Kt/Vurea) and time averaged urea concentration (TACurea)]. The citrate solution, if sterilized in glass bottles, contained 2 to 3 micrograms aluminum per mmol citrate, the nadroparin solution 0.009 microgram per 1,000 ICU. Aluminum contamination of the citrate solution was prevented by sterilizing the solution in polypropylene bottles. In conclusion, citrate anticoagulation is regional and is indicated for hemodialysis patients with an active or recently active bleeding focus. However, the citrate solution should be sterilized in polypropylene containers to prevent aluminum contamination. LMWHs induce systemic anticoagulation during hemodialysis, and this effect is enhanced by concomitant coumarin use and mitigated by a divided LMWH dose regimen. For hemodialysis patients not at risk of bleeding, LMWHs provide a simple anticoagulation regimen.

Aluminum↗
PubMed1996

Folic acid treatment of hyperhomocysteinemia in dialysis patients.

We measured fasting total plasma homocysteine (Hcy) in 10 chronic hemodialysis (HD) and 10 chronic peritoneal dialysis (PD) patients. Mean (+/- SEM) Hcy was 55.7 +/- 10.1 and 50.5 +/- 14.3 mumol/l, respectively (normal range 6-19 mumol/l). Hemodialysis treatment lowered Hcy by about 30%. Daytime Hcy concentrations were stable in the PD patients. Six weeks of treatment with folic acid (FA) significantly lowered Hcy in HD and PD patients to 24.0 +/- 1.8 and 21.0 +/- 3.6 mumol/l, respectively. After withdrawal, Hcy rose slowly, in parallel with the gradually decreasing plasma FA concentrations, which were greatly elevated during treatment. Chronic treatment with FA of another group of patients showed a similar effect on Hcy. Preliminary results of oral methionine loading in chronic dialysis patients were compatible with delayed homocysteine metabolism via the transsulfuration pathway. Further studies on the optimal treatment of hyperhomocysteinemia in chronic dialysis patients are needed.

Adult↗
PubMed1996

Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients.

BACKGROUND AND METHODS: Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used. RESULTS: Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium acetate and calcium carbonate-treated patients (1.28 +/- 0.15 g versus 1.09 +/- 0.19 g; n.s.). The incidence of hypercalcemic episodes (albumin-corrected serum calcium levels above 2.80 mmol/l) in the calcium acetate-treated group was 18% versus 31% in the calcium carbonate-treated group (p < 0.005). None of the aluminum hydroxide-treated patients experienced hypercalcemic episodes. Mean serum concentrations of alkaline phosphatase, intact parathormone, and aluminum did not differ between the groups. CONCLUSIONS: In chronic intermittent hemodialysis patients, per gram administered elemental calcium phosphate binding with either calcium acetate or calcium carbonate is equivalent, provided that calcium carbonate is taken on an empty stomach a few minutes before meals. The number of capsules calcium carbonate, but also the total amount in grams, necessary to keep serum phosphate and intact parathormone levels into an acceptable range then is significantly less. This might improve patient compliance.

Acetates↗
PubMed1995

Hyperhomocysteinaemia: a role in the accelerated atherogenesis of chronic renal failure?

Moderate hyperhomocysteinaemia has recently been established as an independent risk factor for atherothrombotic disease. It might be caused by heterozygosity for cystathionine beta-synthase deficiency, an enzyme involved in the conversion of methionine to cysteine through the transsulphuration pathway or by inherited thermolability of the enzyme which remethylates homocysteine into methionine. In chronic renal failure (CRF) homocysteine levels are significantly elevated at a relatively early stage. The normal kidney possibly plays an important role in homocysteine catabolism, which cannot be performed in CRF. Alternatively, decreased extrarenal catabolism can contribute to the hyperhomocysteinaemia in this disease state. Treatment with folic acid, 5 mg daily, significantly lowers homocysteine levels in chronic renal patients.

Adult↗
PubMed1995

Autonomic, ischaemic, circadian and rhythmic factors as causes of the spontaneous variability of ventricular arrhythmias.

Ventricular arrhythmias present with strongly varying intensity. This spontaneous variability makes it difficult to use one of the existing arrhythmia grading systems for risk or therapy efficacy studies. We attempted to explain the variability by the changing autonomic, ischaemic, circadian, and rhythmic factors. Four (two learning, two test) 24-h Holter tapes were made within one month in 31 patients with chronic frequent ventricular ectopic beats of miscellaneous aetiology and under constant drug regimen. The data were segmented into 5-min episodes, in which ectopy (dependent variable) was measured, together with heart rate, amount of heart rate variability, fraction low-frequency heart rate variability, ST depression, and clock time (independent variables). Forty-three percent of the fluctuations in arrhythmia incidence could be explained with a multiple regression procedure, and more than 50% of the variance in arrhythmia incidence could be explained in 36% of the cases. Our study demonstrates that much of the spontaneous variability of ventricular arrhythmias can be attributed to the varying conditions. This method of dealing with arrhythmia variability might lead to an alternative to the current arrhythmia grading systems used in risk and drug efficacy studies.

Adult↗
PubMed1994

Citrate anticoagulation and divalent cations in hemodialysis.

Anticoagulation with citrate in combination with a calcium-free, magnesium-containing dialysate (Ca-Mg+) and intravenous supplementation of calcium is a safe procedure in renal failure patients at high risk of bleeding. Since magnesium may antagonize the anticoagulant effect of citrate by forming complexes with citrate, we studied the in vitro and in vivo interactions of calcium and magnesium on citrate anticoagulation. In the in vitro studies the activated partial thromboplastin time (APTT) was 88 s, both after addition of 3.0 mumol magnesium and after addition of 1.0 mumol calcium. The combination of 2.4 mumol magnesium and 1.0 mumol calcium achieved similar APTT values of about 35 s as 3.5 mumol calcium alone. Moreover, in a Lee-White blood clotting time, the anticoagulant effect of 7 mumol citrate was neutralized by either 10.5 mumol of a mixture of the two cations or 10.5 mumol calcium chloride alone. In 6 chronic hemodialysis patients the in vivo interactions of calcium and magnesium on citrate were measured. At the dialyzer outlet, the whole blood activated clotting time (ACT) was significantly (p < 0.05) shorter during dialysis with a Ca-Mg+ dialysate than during dialysis with a calcium- and magnesium-free dialysate (Ca-Mg-). With the Ca-Mg- dialysate the ACT at the dialyzer outlet was still significantly longer than the ACT in the arterial line before citrate infusion. We also compared the serum concentrations of calcium and magnesium during the Ca-Mg- dialysate which was used in combination with intravenous calcium and magnesium supplementation - 0.18 and 0.08 mmol/min respectively--and during a conventional calcium- and magnesium-containing dialysate (Ca+Mg+).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Supine and standing sympathovagal balance in athletes and controls.

Differences in autonomic nerve activity between athletes and controls during supine rest and standing were investigated by recording the cardiac rhythm in 18 professional cyclists and 11 controls. We computed four indexes of autonomic control: the standard deviation (SD) of the interbeat intervals, the coefficient of variance (CV) of the interbeat intervals, the percentage of successive intervals differing by more than 50 ms (pNN50), and the fraction low-frequency (0.07-0.14 Hz) spectral power (LF), and we also measured the mean interbeat interval (MI). Significant differences (Student's t-test, P < 0.005) between the athletes and the controls in the supine position were found for pNN50 [mean 52.6 (SEM 2.5) vs 37.1 (SEM 3.4)%], LF [mean 32.2 (SEM 1.6) vs 40.7 (SEM 2.1) normalized units], and MI [mean 1241 (SEM 20) vs 1021 (SEM 25) ms]. A significant difference between the athletes and the controls in the standing position was found for MI [mean 888 (SEM 13) vs 801 (SEM 23) ms]. These results would suggest that there is a parasympathetic predominance in athletes in the supine, but not in the standing position. The finding that pNN50 and LF, but not SD and CV, differed between the athletes and the controls, would seem to demonstrate that the differences in autonomic control between the athletes and the controls are reflected in the quality (balance between slow and fast heart rate fluctuations) rather than in the quantity of heart rate variability.

Adult↗
PubMed1993

Methods in heart rate variability analysis: which tachogram should we choose?

We investigated the practical impact of the representation of the cardiac rhythm--the cardiotachogram--on two elementary spectral indexes in heart rate variability analysis: the low-frequency (0.07-0.14 Hz) and high-frequency (0.14-0.40 Hz) powers. Five commonly used tachograms (inter-beat interval function/series, counts, instantaneous heart rate function/series) were compared. Measurements were done on seven volunteers in the supine and standing positions. Ratios, and their deviations from 100%, of alternative power values were calculated. Mean low-frequency and high-frequency ratio deviations ranged from 0 to 5% and from 6 to 37%. The spectrum of counts yielded on average more (15-37%) high-frequency power. Spectra were incomparable without normalization of the tachogram with respect to heart rate. In conclusion, (i) the choice of a particular spectrum may lead to differing conclusions on the vagal contribution to heart rate variability and (ii) inconclusive results from studies using different tachogram variants can partly be due to the omission of normalization.

Adult↗