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Biomedical subjects

F J Hoek

Publications and source records attributed to F J Hoek.

At least 55 records · Page 3Linked to original sources

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↗

Temporary increase in serum beta 2-microglobulin during treatment with interferon-alpha for AIDS-associated Kaposi's sarcoma.

Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment. However, the increase of serum beta 2-M levels in responders appeared to be more pronounced than in those with progressive disease, but this difference was not significant. The increase was only found during the initial 8 weeks; thereafter, beta 2-M levels declined in patients with continuing clinical improvement during ongoing treatment with IFN alpha. This may have been related to IFN alpha dose modification at 8 weeks for all patients. The initial rise in serum beta 2-M might be related to the immunomodulation properties of IFN alpha. Because serum beta 2-M levels were also enhanced in non-responders, this rise does not demonstrate that immunomodulation by IFN alpha is a mechanism of anti-tumour activity in AIDS-associated Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

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↗

An appraisal of the role of biliary phospholipases in the pathogenesis of gallstone disease.

Human bile contains proteins that influence nucleation of cholesterol. Recently, it has been suggested that activity of phospholipases in bile may play a role in this process. To study the influence of phospholipase on nucleation we have determined the effect of phospholipases A2, C and D on the nucleation time of model bile. Phospholipase C decreased the nucleation time, whereas phospholipase A2 inhibited nucleation. The phospholipases were effective only at relatively high concentrations. Phospholipase D was strongly inhibited in model bile and probably only influenced the nucleation time by an aspecific protein effect. The cleavage products of the different phospholipases were determined in native bile samples of 14 cholesterol gallstone patients, 6 patients without stones and 4 patients with pigment stones. In all samples, choline, phosphorylcholine and free fatty acids (FFA) could be detected. However, there was no significant difference between the three groups of patients. The rate of production of choline, phosphorylcholine and FFA was measured in bile incubated at 37 degrees C. Again, there was no significant difference between the three groups of patients. We conclude that phospholipase activity in bile does not play an important role in the pathogenesis of gallstone disease.

Bile↗

The time course of peritoneal transport kinetics in continuous ambulatory peritoneal dialysis patients who develop sclerosing peritonitis.

The time course of measurements of peritoneal solute transport in four continuous ambulatory peritoneal dialysis (CAPD) patients who developed sclerosing peritonitis is described. Loss of fluid removal capacity was found in all of them. In three, this loss was associated with an increase in peritoneal absorption of glucose from the dialysate and an increase in the transperitoneal transport rates of low-molecular-weight solutes and proteins. In the other patient a decrease in all these parameters was found. This seems to imply that the effective peritoneal surface area was increased in three patients and decreased in one. Peritoneal permeability to macromolecules remained unchanged as judged by the ratio between the clearance of IgG and albumin. Among the possible factors that contribute to the development of sclerosing peritonitis, some are likely to lead to a larger effective peritoneal surface area, like prostacyclin and the formation of new capillaries in poorly vascularized parts of the peritoneum. Others, such as extensive formation of collagen, could lead to a smaller effective surface area. Individual differences in susceptibility to these factors may lead to an increase or decrease in peritoneal solute transport rates. Follow-up measurements of peritoneal solute kinetics are necessary to identify those patients who are at risk.

Adult↗

The peritoneal transport of serum proteins and neutral dextran in CAPD patients.

The peritoneal transport of five serum proteins and intravenously-administered neutral dextran was studied in 13 CAPD patients. In all patients a study was done three hours after the administration of dextran. In nine the study was repeated after 14 hours, and in six also after 38 hours. Using gel permeation chromatography of serum and dialysate it was possible to calculate fractional (relative to inulin) clearances for dextran fractions with Einstein-Stokes radii ranging from 30 to 90 A. In contrast to glomerular transport, we found that peritoneal clearances of serum proteins and corresponding dextran fractions were of a similar magnitude up to a radius of 90 A, especially in the follow-up studies. No evidence was found for a charge-selective barrier function of the peritoneum. It appeared likely that the peritoneal interstitium is probably a third compartment between blood and dialysate in which equilibrium with blood and dialysate is present for serum proteins, but initially not for dextran. For dextran this equilibrium is probably approached 14 to 38 hours after administration. The linear relationship between the reciprocal of fractional clearances and Einstein-Stokes radii indicates that restricted diffusion is the main transport mechanism of macromolecules across the peritoneal membrane. The slopes of the linear regression between the reciprocal of fractional clearances and radii ranged from 0.32 to 6.95 (slope for free diffusion 0.07) and provided an index of the permeability characteristics of the peritoneal membrane.

Adult↗

Circadian rhythm of glomerular filtration rate in normal individuals.

1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles. 2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (SD 22) in the daytime, a minimum of 86 ml/min (SD 12) at night and with a relative amplitude of 33% (SD 15). 3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well. 4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion. 5. Urinary albumin and beta 2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm. 6. The highest quantity of sodium, water and beta 2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.

Adult↗

Influence of gastric emptying on the PABA test.

Serum and urine PABA curves monitored in 13 healthy volunteers were analysed and compared with curves from 11 healthy volunteers after administration of the gastrokinetic agent domperidone. Both in serum and in urine less variation in the PABA curves was observed after domperidone. Results without domperidone were subdivided in a group with normal gastric emptying (I) and a group with slow gastric emptying (II), based upon the time at which the serum PABA peak was found. Maximal serum PABA concentration, serum PABA at t = 60 min, lagphase and t1/2 for urinary excretion, and % PABA excretion from 0-3 h, 3-6 h and 0-6 h differed significantly between the two groups. Instead, no differences were found between subgroup I and volunteers after concomitant domperidone administration. In summary, PABA test results in serum and urine are influenced by variations in gastric emptying. Domperidone corrects for delayed gastric emptying and thereby narrows the range of normal PABA excretion values.

4-Aminobenzoic Acid↗

Quantification of cholesterol nucleation promoting activity in human gallbladder bile.

We have developed a simple method to quantitate cholesterol nucleation promoting activity in bile. The method makes use of the fact that gallbladder bile of cholesterol gallstone patients contains potent nucleation promoting activity. Gallbladder bile samples were serially diluted, routinely from 1/25 to 1/6,400. The diluted samples were mixed with a supersaturated model bile and the nucleation time (NT) of the mixtures was determined. The greatest dilution that resulted in a significant shortening of the NT was called the nucleation promoting activity titre (NPAT). The determination is independent of the original lipid content of the bile sample. The NPAT was measured in 14 gallbladder bile samples derived from patients with cholesterol gallstones and 9 controls. In all samples promoting activity was found. In the samples from the stone patients the NPAT was significantly elevated as compared to the patients without cholesterol stones (p = 0.01). Our results suggest that the cholesterol saturation index and the activity of cholesterol nucleation promoting factors are the most important factors in the pathogenesis of cholesterol gallstone disease. Assessment of the NPAT allows the differentiation of groups of patients with a normal cholesterol saturation index who are at risk for gallstone formation due to a high NPAT.

Bile↗

Characterization of the content of occluded biliary endoprostheses.

In an attempt to establish why biliary endoprostheses clog we analysed the contents of 21 occluded endoprostheses. The major components of the endoprosthesis sludge were protein (25%) and an insoluble residue (20%) which consisted mainly of plant fibers. Compared with bile the material was also rich in unconjugated bilirubin, while the major components of bile--bile acids and lecithin--accounted for only 15%. Although the sludge often contained some cholesterol crystals, no cholesterol gallstones or pigment or mixed stones were found. The material contained bacteria, but not in abundance. Scanning electron microscopy of the walls of clogged endoprostheses revealed adherence of amorphous material, probably protein. SDS-polyacrylamide gel electrophoresis of the protein fraction of the material from different endoprostheses showed a characteristic pattern. The material always contained two major bands of approximately 16 and 13 kDalton, which were not observed in corresponding bile samples. The 16 and 13 kDalton proteins bound most avidly to the endoprosthesis wall. We postulate that the initial phase in the clogging process is adsorption of proteins, after which other materials such as bacteria, fibers from food and unconjugated bilirubin bind to the wall of the endoprosthesis.

Bile Acids and Salts↗

Improved specificity of the PABA test with p-aminosalicylic acid (PAS).

Until now use of the PABA test together with [14C] PABA to calculate the PABA excretion index has probably been the best adaptation suggested to enhance the specificity of this non-invasive pancreatic function test. Drawbacks of the method are the application of radioactivity, the fact that children, pregnant women, and patients with renal insufficiency have to be excluded from the test, and the possible interference of drugs and isotopes. We propose simultaneous administration of p-aminosalicylic acid (PAS) in the PABA test and quantification of the urinary PABA and PAS excretion with liquid chromatography. Urinary PABA and PAS excretion in six hours are comparable (69.5 +/- 8.4% and 65.6 +/- 18.4% respectively in five healthy volunteers). Application of the PABA/PAS ratio was compared with the urinary PABA excretion in 21 normal controls, 38 patients with pancreatic disease, and 42 patients without pancreatic pathology. The PABA/PAS ratio and the per cent PABA excretion correlated very well in pancreatic patients: (PABA/PAS ratio) = 0.0149 (% PABA) + 0.052 (r = 0.902). Use of the PABA/PAS ratio enhanced the specificity of the test from 76 to 89%.

4-Aminobenzoic Acid↗

Red blood cell electrolytes for monitoring digoxin therapy in adults.

Red blood cell (RBC) electrolyte concentrations were determined, with a method that can be applied easily in any clinical chemistry laboratory, in 18 patients not on digoxin therapy and 37 patients on maintenance digoxin therapy for various diagnoses. Of the digoxin-treated patients, 11 had electrocardiographic changes and other clinical evidence of digoxin toxicity. Mean RBC sodium was higher and mean RBC potassium was lower in patients on prolonged digoxin therapy than in controls, and these changes were more pronounced in patients with toxic symptoms. In the group of 11 patients with toxicity, a positive correlation was found between the ratio of RBC sodium to potassium and plasma digoxin levels (r = 0.8234, p less than 0.05). Plasma digoxin concentrations did not clearly distinguish between toxic and nontoxic patients. The RBC sodium/potassium ratio, however, identified 35 of 37 patients correctly, with two patients from the toxic and two patients from the nontoxic group giving the same results. Changes in intracellular erythrocyte electrolytes in adults appear to correlate closely with clinical signs of digoxin toxicity.

Adult↗

Further evidence for the influence of intraduodenal pH on the PABA test.

The effect of prior administration of 400 mg of cimetidine on the outcome of the PABA test was investigated. In 8 patients the PABA test result rose with on average 27.5% after the administration of cimetidine. Four of them were selected for these investigations, because a much lower PABA test result had been obtained than was expected from the Lundh test result. In one patient, the low PABA test result was in conflict with faecal fat excretion and the clinical condition. Three patients were selected with severe pancreatic dysfunction, as demonstrated by the PABA test, Lundh test and faecal fat excretion. The change effected by cimetidine was shown to be significantly related to duodenal pH and mean trypsin activity as measured in the Lundh test. In a control group of four patients with a PABA test result in the normal range, no significant effect of cimetidine administration was seen. The beneficial effect of cimetidine can be explained by its known inhibiting influence on gastric acid production, resulting in higher intraduodenal pH with subsequent enhanced enzymatic activity. The importance of intraduodenal pH for the PABA test result is further stressed by these results.

4-Aminobenzoic Acid↗