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Biomedical subjects

D G Struijk

Publications and source records attributed to D G Struijk.

At least 91 records · Page 5Linked to original sources
PubMed1992

Intraperitoneal administration of recombinant human erythropoietin.

OBJECTIVE: To determine the efficacy and safety of intraperitoneal administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients compared to subcutaneous rHuEPO. DESIGN: Prospective analysis of an open, nonrandomized investigation. SETTING: Outpatient CAPD clinics in two university hospitals. PATIENTS: Nine adult CAPD patients receiving rHuEPO intraperitoneally and 8 patients receiving rHuEPO subcutaneously. INTERVENTION: One hundred units of rHuEPO per kilogram of body weight were administered three times a week for 8 weeks or until the target hematocrit of 35% was reached. Thereafter, dosages of rHuEPO were adjusted for response. Intraperitoneal rHuEPO was administered in 1 L of dialysis solution during the night. MEASUREMENTS: Efficacy was assessed by measuring the increase in hemoglobin. Tolerance was assessed by monitoring side effects. RESULTS: In the first 8 weeks of treatment hemoglobin concentration increased from 64.5 +/- 12.9 g/L to 98.3 +/- 16.1 g/L (p < 0.0005) in the intraperitoneally treated group. In the subcutaneously treated group hemoglobin increased significantly faster (p < 0.05) from 72.5 +/- 4.8 g/L to 119.2 +/- 11.3 g/L (p < 0.0005) in the same period. Antihypertensive medication had to be increased or instituted in most of the patients in both groups. The incidence of peritonitis in the intraperitoneally treated group was not increased when compared to the pretreatment incidence. CONCLUSIONS: Subcutaneously administered rHuEPO is superior to intraperitoneally administered rHuEPO with regard to the required dosages. However, the results of this study show that intraperitoneal administration of rHuEPO might be a convenient and safe alternative when subcutaneous administration is undesirable.

Adult↗
PubMed1992

Interleukin-6 in CAPD patients without peritonitis: relationship to the intrinsic permeability of the peritoneal membrane.

We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected all "nightbags" on consecutive days during 2 months for the determination of peritoneal IgG clearance. Serum samples were obtained weekly. IL-6 was determined in the effluent on all occasions where the IgG clearance was less than mean - SD or greater than mean + SD. On these days clearances of beta 2-microglobulin, albumin and alpha 2-macroglobulin were determined as well, to calculate the peritoneal restriction coefficient, i.e. the slope of the power relationship between protein clearances and their free diffusion coefficient in water. This coefficient was used as a parameter of the intrinsic permeability of the membrane. IL-6 was measured by a sensitive and specific bioassay, using the B13.29, subclone 9.9 hybridoma cell assay. Dialysate IL-6 was measured on 43 occasions when IgG clearance was high and on 37 occasions when IgG clearance was low. In all 4 patients indirect evidence was found for local production of IL-6 within the peritoneal cavity: mean dialysate/serum ratios were 15 to 452 times higher than could be expected when IL-6 would enter the dialysate by diffusion only. The patient with the highest dialysate/serum ratio showed higher clearances of albumin, IgG and alpha 2-macroglobulin than the other 3 patients (p less than 0.001) and a lower restriction coefficient (p less than 0.001), indicating a high intrinsic permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Effect of intraperitoneal administration of two different batches of albumin solutions on peritoneal solute transport in CAPD patients.

The effects of intraperitoneal administration of two different batches of human albumin (batch A and batch B) on peritoneal solute transport and dialysate white cell count were studied in 16 CAPD patients. The studies were done on two separate days during a 4-h dwell, one day without and one day with the intraperitoneal administration of 10 g/l human albumin. Marked differences were found between the two batches. The transport of all measured solutes increased during administration of batch A compared to the control experiments: urea 78% +/- 62%, lactate 51% +/- 38%, creatinine 96% +/- 54%, glucose 67% +/- 55%, inulin 27% +/- 33% IgG 126% +/- 80%, mean +/- SD; P less than 0.02). In the experiments with batch A the white cell count of the test bag was greater than that of the effluent ('night bag') before the test (13 +/- 5 vs 194 +/- 61 mm3/l; P less than 0.02). These effects were also observed when the dialysate was buffered to pH = 7.4 before inflow. Albumin batch B showed no effect on solute transport and white cell count. The effects of solute transport and white cell count are probably caused by the greater concentration of prekallikrein activator in batch A when compared to batch B (30.1 vs 0 U/l). Caution is warranted when human albumin is used for simultaneous measurement of peritoneal fluid and solute kinetics.

Absorption↗
PubMed1991

Effects of renal failure on complement C3d levels.

Elevated plasma concentrations of complement split product C3d have been reported to represent activation of the complement system. In the present study the effect of renal function on C3d concentrations was investigated in patients with various degrees of renal impairment, in patients with chronic renal failure and in CAPD patients. It appeared that elevated plasma C3d concentrations were present in patients with plasma creatinine concentrations in excess of 200 mumol/l regardless of the type of kidney disease. It is very likely that this can be attributed to renal handling (i.e. glomerular filtration, tubular reabsorption and renal catabolism) of C3d in a similar way as has been demonstrated for other low molecular weight proteins. The peritoneal permeability to C3d was slightly less than could be expected on the basis of its molecular weight without evidence of local production of C3d. Renal function should be taken into account in the interpretation of elevated plasma concentrations of C3d.

Complement Activation↗
PubMed1991

Functional characteristics of the peritoneal membrane in long-term continuous ambulatory peritoneal dialysis.

Peritoneal transport characteristics of 20 long-term (LT) patients with a mean duration on continuous ambulatory peritoneal dialysis (CAPD) of 60 months were compared with those of 20 matched patients who recently started (RS) CAPD (mean 39 days, range 11-63). Mass transfer area coefficients (MTC) of creatinine, glucose and inulin were higher in the LT group than in the RS group (12.1 versus 9.2 ml/min, p less than 0.01; 9.9 versus 8.3 ml/min, p less than 0.05; 4.1 versus 3.5 ml/min, p less than 0.05). The MTC of alpha 2-macroglobulin were lower in the LT group (13 versus 25 microliters/min; p less than 0.01). The size selectivity of the membrane for the transport of macromolecules, determined as protein MTC ratios, showed a more restricted passage for macromolecules in the LT group. Net fluid removal using glucose 3.86% was lower in the LT patients (487 versus 826 ml/4 h; p less than 0.001). The results indicate the development of a larger effective peritoneal surface area combined with a less permeable peritoneal membrane after many years of CAPD.

Adult↗
PubMed1991

Ototoxicity monitoring with ultra-high frequency audiometry in peritoneal dialysis patients treated with vancomycin or gentamicin.

Ototoxicity affects the higher frequencies first and extends to the lower frequencies during continuation of the ototoxic treatment. Peritonitis due to continuous ambulatory peritoneal dialysis (CAPD) regularly demands ototoxic antibiotic treatment, e.g. with gentamicin and vancomycin. In this study ultra-high frequency audiometry (10-20 kHz), 'normal' audiometry (0.125-8 kHz) and registration of blood concentrations of the antibiotics were used to assess ototoxic hearing loss during treatment of CAPD patients with peritonitis.

Audiometry↗
PubMed1991

Metabolic disturbances in CAPD patients.

CAPD is not a physiological condition. The continuous absorption of glucose from the dialysate and the losses of nutrients like protein in it may cause many metabolic abnormalities. This review deals with some effects of CAPD on carbohydrate, lipid and protein metabolism.

Carbohydrate Metabolism↗
PubMed1991

A fast reliable method for the measurement of intraperitoneal dextran 70, used to calculate lymphatic absorption.

The use of intraperitoneally administered dextran 70 was investigated for measurement of lymphatic absorption in CAPD patients. For this purpose a fast, highly accurate HPLC method was developed, that was not influenced by the high glucose concentration in peritoneal dialysate, nor by the inulin that was added to the dialysate for the measurement of residual volume. Pretreatment of the samples consisted of deproteinization with trichloroacetic acid, followed by incubation at 45 degrees C to hydrolyze inulin. This was followed by a further rinsing step using a Sephadex G-25 PD-10 column. The HPLC was performed on a Bio-Gel XL guard column with refractive index detection. Because of the short guard column the chromatographic analysis was only 5 minutes for one sample. With the method described lymphatic absorption rate was measured in 30 CAPD patients and was found to range from 0.1 to 3.5 mL/min, median 1.0 mL/min.

Absorption↗
PubMed1991

Individual characterization of the peritoneal restriction barrier to macromolecules.

The transport of macromolecules such as proteins and dextrans during CAPD is restricted by the permeability of the peritoneum. When its degree is determined by diffusion characteristics of macromolecules, the intrinsic permeability of the peritoneal membrane can be expressed as the relation between clearance of macromolecules and parameters of diffusion velocity. In order to characterize the peritoneal restriction barrier in individual patients, such a relationship has to meet the following conditions: (a) a good fit to linearity, (b) a low inter- and intra individual variability and (c) similarity for proteins and equal sized dextran fractions. In the present study a comparison is made between the reciprocal plot (RP): C-1 = s (esr) + A and the diffusion plot (DP): C = A'. Ds20,w. In these equations C is clearance, esr is Einstein Stokes radius, D20,w is the free diffusion coefficient in water, A and A' are constants, while s is the slope of the regression line and therefore represents intrinsic peritoneal permeability to macromolecules. The 95% confidence interval of the correlation coefficient r was above 0.95 in all studies for the RP and the DP. In general it was somewhat higher for the DP. The inter-individual coefficient of variation was lower in the DP than in the RP. This was also the case for the intra-individual coefficient of variation of the slope for proteins (DP 4% vs RP 27%, p less than 0.01) and for dextrans (DP 18% vs RP 47%, p less than 0.05). The correlation coefficient between dextran slopes and protein slopes was higher for DP (r = 0.68) than for RP (r = 0.50).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1991

Day-to-day variability of protein transport used as a method for analyzing peritoneal permeability in CAPD.

The transperitoneal transport of macromolecules is dependent on both effective peritoneal surface area and intrinsic permeability of the peritoneum. For passage of small solutes, the effective surface area is the main determinant. We hypothesized that day-to-day variations in peritoneal clearances are caused by changes in the effective surface area and not in the intrinsic permeability. Four CAPD (continuous ambulatory peritoneal dialysis) patients without peritonitis were investigated on 28 consecutive days. Concentrations of beta-2-microglobulin, albumin, IgG, and alpha-2-macroglobulin were determined daily in dialysate (night bags) and weekly in serum. Clearances and their coefficients of variation were calculated. Mean coefficients of the intraindividual variation of protein clearances increased, the higher the molecular weight: they ranged from 12% for beta-2-microglobulin clearance to 22% for alpha-2-macroglobulin clearance. Correlations were present between the clearances of albumin, IgG, and alpha-2-macroglobulin, but not between any of these and beta-2-microglobulin clearance. In all patients, protein clearance (C) was a power function of the free diffusion coefficient in water (D) according to the equation: C = a. Db in which b represents the restriction coefficient of the peritoneum, and thus intrinsic permeability. The coefficient of variation of the restriction coefficient was low (range 4-6%). This supports our assumption that the intrinsic permeability is fairly constant on the short term. Day-to-day variations in protein clearances are thus mainly caused by alterations in the effective peritoneal surface area. Long-term follow-up of the restriction coefficient in individual patients might identify those at risk for the development of structural changes in the peritoneal membrane.

Adult↗
PubMed1991

Continuous ambulatory peritoneal dialysis (CAPD) in patients with diabetic nephropathy.

A 3-centre study was done to analyse the results of 70 patients with end-stage renal disease caused by diabetic nephropathy and treated with CAPD. Fifty patients had insulin-dependent diabetes (mean age 42, mean duration of diabetes 24 yr); 20 had non-insulin-dependent diabetes (mean age 61, mean duration 15 yr). Total treatment time was 1563 months and ranged from one to 83 months (median 18). Patient survival was 86% at 1 yr and 33% at 4 yr. Technique survival was 87% and 63%. Cox's multiple hazard regression analysis showed that age above 45 yr (relative risk 2.2), systolic hypertension (2.6) and cardiac disease (2.2) at the start of CAPD were associated with shorter patient survival. Metabolic control was good. Haemoglobin rose during the first 3 months. Plasma creatinine concentration increased with time, probably due to the loss of residual renal function. HbA1c levels were in the normal range for 60% of the patients. Mean hospital stay was 42 days per year, 26 as a consequence of vascular complications and 16 due to peritonitis and catheter-related problems. We conclude that CAPD is a good renal replacement modality for patients with diabetic renal failure. The patient survival is dependent on age, systolic hypertension and cardiac disease at the start of CAPD.

Adult↗
PubMed1991

Transport kinetics of pseudouridine during hemodialysis and continuous ambulatory peritoneal dialysis.

It has been found that the concentrations of pseudouridine in serum of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are higher than those in patients undergoing hemodialysis. We analyzed whether this could be caused by a lower rate of transport in CAPD when compared with hemodialysis. Mass transfer area coefficients (MTCs) for urea, creatinine, uric acid, and pseudouridine were determined in nine patients undergoing hemodialysis as dialyzer clearances and in 14 patients undergoing CAPD during a 4-hour dwell with 2 L dialysate with glucose, 70 mmol/L. The theoretical MTC of pseudouridine (TPSI), calculated by extrapolation to its molecular weight by use of the MTC of urea, creatinine, and uric acid, was higher than the observed MTC of pseudouridine, both in hemodialysis (136 vs 112 ml/min, p less than 0.025) and in CAPD (6.9 vs 3.4 ml/min, p less than 0.001). The pseudouridine/TPSI MTC ratio was lower during CAPD than during hemodialysis (0.47 vs 0.83, p less than 0.0005), indicating a lower level of transport during CAPD. In vitro experiments with nuclear magnetic resonance spectroscopy supported the hypothesis of glucose-induced molecular association of pseudouridine. Therefore, dialysate containing 10 mmol/L glucose was compared with that containing 70 mmol/L glucose in eight patients undergoing CAPD. The MTC of pseudouridine was higher during the experiments with dialysate containing 10 mmol/L glucose (3.5 +/- 2.0 ml/min vs 2.7 +/- 1.9 ml/min, p less than 0.05). This was also found for the pseudouridine/TPSI MTC ratio (0.61 vs 0.41, p less than 0.02) and the pseudouridine/creatinine MTC ratio (0.33 vs 0.25, p less than 0.02), favoring glucose-induced decrease of MTC-pseudouridine.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1990

Isolation, identification, and analysis of 4-acetylaminophenol-glucuronide in body fluids of dialyzed renal patients; a molecular mass marker for peritoneal diffusive transport.

A noncharacteristic solute, appearing in gradient elution liquid chromatography (HPLC) profiles of body fluids of dialyzed renal patients, was isolated and identified by preparative HPLC, beta-glucuronidase induced enzymatic peak shift, and mass spectrometry. The compound was shown to be p-acetylaminophenol ('paracetamol')-glucuronide (PG). Serum and peritoneal dialysate PG concentrations were determined in a number of patients. Cuprophan in vivo dialyzer clearances were calculated. Peritoneal membrane mass transfer coefficients (MTC) of PG were calculated and compared with those of molecular mass markers for peritoneal diffusive mass transport studies (urea, creatinine, uric acid, and inulin). By extrapolation of an MTC versus molecular mass calibration line for urea, creatinine, and uric acid it is shown that PG behaves as expected from its molecular mass. We suggest that PG (Mr = 327) is suitable as a molecular mass marker for the molecular mass range between Mr 200 and 500. It may also be used as a marker for diffusive solute transport in hemodialysis treatment. The HPLC gradient elution technique used here appears to be suitable for the simultaneous analysis of the molecular mass markers creatinine, uric acid, and paracetamolglucuronide.

Acetaminophen↗
PubMed1990

Chemotaxis of the peritoneal cells and the detection of a chemo-attractant in the effluent from peritoneal dialysis patients.

The migration of peritoneal cells from 25 continuous ambulatory peritoneal dialysis patients and eight healthy women undergoing laparoscopy were studied. Peritoneal cells of continuous ambulatory peritoneal dialysis patients migrated to commonly used chemoattractants, like N-formyl-methionyl-leucyl-phenyl-alanine-methyl- ester and casein, but they also migrated to high concentrations of recombinant interleukin-1 alpha and to endotoxin (lipopolysaccharide). In the peritoneal effluent from continuous ambulatory peritoneal dialysis patients a rather heat stable chemoattractant was found with a molecular weight of 40-200 kDa with an optimal activity at approximately 125 kDa. The chemoattractant is a protein and is not complement factor 5a or interleukin-1 and was only found in peritoneal effluent from continuous ambulatory peritoneal dialysis patients, but not in peritoneal fluid from healthy women undergoing laparoscopy. Therefore, peritoneal dialysis might induce the generation of a chemoattractant. The optimal chemotactic response of peritoneal cells from continuous ambulatory peritoneal dialysis patients to N-formyl-methionyl-leucyl-phenyl-alanine-methyl- ester in medium could be enhanced by replacing the medium by peritoneal effluent. So the chemotaxis of peritoneal cells to the factor in the peritoneal effluent is caused by another mechanism, which might involve different cell surface receptor populations, than the chemotactic response to N-formyl-methionyl-leucyl-phenyl-alanine-methyl-ester.

Adult↗
PubMed1990

The disappearance of macromolecules from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD) is not dependent on molecular size.

The transport of macromolecules from the circulation to the peritoneal cavity is a size-selective restricted process, while the transport of these solutes from the peritoneal cavity is probably mainly by lymphatic absorption. If so, it should be independent of molecular size. Therefore, we studied with a clearance technique the disappearance of intraperitoneally administered inulin and polydisperse dextran 70 in nine continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results with the simultaneously measured appearance clearance of serum proteins. Using gel permeation chromatography 18 dextran fractions with different molecular radii could be analyzed. Inulin clearance (2.94 mL/min) was higher than total dextran clearance (1.30 mL/min). The maximal dextran concentration in all dialysate samples was found in the 50.4 A fraction. The clearances of the dextran fractions were the same of different molecular sizes. All disappearance clearances were higher than the appearance clearances: the protein/dextran clearance ratio ranged from 0.15 for albumin/36 A to 0.04 for alpha 2-macroglobulin/91 A. This confirms that the appearance of a macromolecule, but not its disappearance is dependent on molecular size. It is concluded that the disappearance of macromolecules from the peritoneal cavity is mainly a size independent convective process, possibly by lymphatic uptake. This implies that total dextran 70 clearance can be used for measurement of lymphatic absorption in CAPD patients.

Adult↗