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Biomedical subjects

M E De Broe

Publications and source records attributed to M E De Broe.

At least 19 recordsLinked to original sources
PubMed1995

New occupational risk factors for chronic renal failure.

Occupational pollutants may have a role in development of chronic renal failure (CRF). Most epidemiological studies have been cross-sectional, limited to certain renal diagnoses, or concentrated on early transient renal effects. In a case-control study, we examined the association between CRF and occupational exposure. Occupational histories of 272 men and women with CRF (of all types) were compared with those of 272 controls matched for age, sex, and region of residence. Exposures were assessed and degree and frequency were scored independently by three industrial hygienists unaware of case/control status. Significantly increased risks of CRF were found for exposure to lead (odds ratio 2.11 [95% CI 1.23-4.36]), copper (2.54 [1.16-5.53]), chromium (2.77 [1.21-6.33]), tin (3.72 [1.22-11.3]), mercury (5.13 [1.02-25.7]), welding fumes (2.06 [1.05-4.04]), silicon-containing compounds (2.51 [1.37-4.60]), grain dust (2.96 [1.24-7.04]), and oxygenated hydrocarbons (5.45 [1.84-16.2]). The frequencies of various occupational exposures were high among patients with diabetic nephropathy. This epidemiological study confirms previously identified risk factors and suggests that additional occupational exposures, for which there is some other experimental evidence, may be important in the development of CRF. The role of grain dust and the association between occupational exposure and diabetic nephropathy merit further investigation.

Adult↗
PubMed1995

Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium.

Urinary human intestinal alkaline phosphatase (IAP), beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cd-exposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between beta 2-MG and IAP or NAG. The beta 2-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and beta 2-MG is considered to be more useful.

Acetylglucosaminidase↗
PubMed1995

Wegener granulomatosis is associated to exposure to silicon compounds: a case-control study.

Wegener granulomatosis is a rare disease of unknown aetiology. In the majority of these patients the kidney is involved in the disease process. We performed a case-control study to evaluate the role of occupational exposure in the development of Wegener granulomatosis with renal involvement. The occupational histories of 16 cases with clearly established diagnosis of Wegener granulomatosis with renal involvement were compared with those of 32 age- and sex-matched controls. It was observed that inhalation of silicon-containing compounds such as silica and grain dust gave a nearly sevenfold risk for Wegener granulomatosis. Further epidemiological and experimental work needs to be performed in order to corroborate these findings.

Adult↗
PubMed1992

Laser microprobe mass spectrometric identification of cyclosporin-induced intrarenal microliths in rat.

Using laser microprobe mass analysis (LAMMA), the composition of 'micro-calcifications (dystrophic type)' or 'metastatic calcifications', previously described in rats given high doses of cyclosporin, have been identified. Female Wistar rats given 12.5, 25 or 50 mg kg-1 per day of cyclosporin in olive oil by gastric gavage developed intrarenal calcifications detected by silver nitrate staining (von Kossa) in the outer medulla after two weeks. The calcifications stained red with periodic acid-Schiff reagent and appeared to be intraluminal microliths with concentric laminations. They could be identified by LAMMA as calcium phosphate (hydroxyapatite), indistinguishable from undecalcified bone. These studies indicate that intraluminal obstruction by calcium phosphate microliths, similar to that seen with magnesium depletion or high phosphate diets, may contribute to renal damage in rats given high-dose cyclosporin. LAMMA appears to be an appropriate technique for identifying both the elemental and organic moieities of intrarenal calcium deposits.

Administration, Oral↗
PubMed1992

The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and guanidinosuccinic acid.

To better understand the biosynthesis of guanidinosuccinic acid, we determined urea, arginine, and guanidinosuccinic acid levels in nondialyzed uremic and hyperargininemic patients. These substances were also determined during several years of therapy in one hyperarginiemic patient. Interrelationships of guanidinosuccinic acid levels with their corresponding urea and arginine levels were assessed by linear correlation studies. In uremic patients, a significant positive linear correlation (r = .821, p less than .001) was found between serum urea and guanidinosuccinic acid levels A significant positive linear correlation was also found between serum urea levels and urinary guanidinosuccinic acid levels (r = .828, P less than .001), but not between serum arginine levels and urinary guanidinosuccinic acid levels in hyperargininemic patients. In the intrahyperargininemic patient study, a similar significant positive correlation was found between serum urea levels and the corresponding urinary guanidinosuccinic acid levels (r = .866, P less than .001); the correlation between serum arginine levels and the corresponding urinary guanidinosuccinic acid levels was smaller. The presented analytical findings in uremic and hyperargininemic patients clearly demonstrate a metabolic relationship between urea and guanidinosuccinic acid.

Adult↗
PubMed1992

Removal of aluminoxamine and ferrioxamine by charcoal hemoperfusion and hemodialysis.

We studied the removal of aluminoxamine (AlO) and ferrioxamine (FO) by (i) hemoperfusion/hemodialysis using an AluKart in combination with either a Cuprophan F-120 or a Hemophan FH-160 membrane, or (ii) hemodialysis with a high-flux F-60 polysulfone membrane. The same six dialysis patients underwent in a random order dialysis by the three set-ups after i.v. infusion of 30 mg/kg of desferrioxamine (DFO) during the last half an hour of the preceding dialysis session. The mean +/- SD plasma AlO and FO clearances of the AluKart combined with either a F-120 or FH-160 membrane were 194.3 +/- 25.8 ml/min (AlO) and 164.2 +/- 41.3 ml (FO) at the start of dialysis declining to respectively 76.6 +/- 27.3 and 68.5 +/- 42.6 ml/min at the end of dialysis. With a high-flux dialysis membrane the intra-dialytic plasma clearance remained constant at 81.5 +/- 6.8 ml/min for AlO and 60.0 +/- 2.8 ml/min for FO. In the presence of an AluKart combined with a FH-160 up to 84 +/- 27% and 84 +/- 19% of the available AlO and FO could be removed during a four-hour hemoperfusion/hemodialysis session. During the first hour of dialysis, respectively 59 and 58% of the total amount of AlO and FO extracted by the AluKart was removed compared to only 9 and 16% during the last hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pharmacokinetics of aluminoxamine and ferrioxamine and dose finding of desferrioxamine in haemodialysis patients.

We investigated the pharmacokinetics of desferrioxamine and its chelated compounds aluminoxamine and ferrioxamine in normal volunteers and haemodialysis patients with and without iron overload. Desferrioxamine was administered in a single dose of 30 mg per kg body-weight was a 30-min infusion to five healthy volunteers and to 20 haemodialysis patients (five patients without haemosiderosis and 15 patients with haemosiderosis). The interdialytic half-life of ferrioxamine was 2.2 h in normal volunteers, 13.3 h in dialysis patients without haemosiderosis, and 24.6 h in patients with haemosiderosis. There was no interdialytic elimination of aluminoxamine. In a second study, seven dialysis patients received 5, 10, and 20 mg per kg body-weight desferrioxamine in a random order with a time interval of 2 weeks. The peak serum concentrations after these doses were 4.1 +/- 2.9, 6.4 +/- 2.9, and 10.7 +/- 7.1 mumol/l for ferrioxamine and 2.8 +/- 1.5, 3.1 +/- 1.5, and 4.2 +/- 1.7 mumol/l for aluminoxamine. Thus, a 4-fold increase in desferrioxamine dosage resulted in a 2.7-fold increase in peak ferrioxamine levels and in only a 1.5-fold increase in peak aluminoxamine levels. We conclude that dialysis patients, especially those with haemosiderosis, are exposed to persistently elevated ferrioxamine levels. Weekly doses of 5-10 mg/kg of desferrioxamine would be sufficient for aluminium chelation therapy.

Adult↗
PubMed1992

Intestinal-type alkaline phosphatase in urine as an indicator of mercury induced effects on the S3 segment of the proximal tubule.

Intestinal-type alkaline phosphatase (IAP) is a specific and sensitive marker for alterations of the S3 segment of the human proximal tubule, the preferred part for several nephrotoxins. We studied IAP and other renal parameters in mercury-exposed workers and their controls. IAP excretion is clearly increased in the exposed workers, compared to other parameters, indicating that the determination of this enzyme can be a useful screening test of renal effects in occupational mercury exposure.

Acetylglucosaminidase↗
PubMed1992

A standardized surgical technique to obtain a stable and reproducible chronic renal failure model in dogs.

The remnant kidney, a model of chronic renal failure in animals, can be obtained by two techniques: either surgical removal of tissue of one kidney, combined with contralateral nephrectomy or inducing necrosis of kidney tissue by ligation of branches of the renal artery of one kidney combined with contralateral nephrectomy. In the literature, most reports concern the ligation technique. The technique is safe and simple but the results in dogs are unpredictable. In this paper, both techniques were compared. We could demonstrate that the unpredictable result of the ligation technique is due to the formation of collateral vessels bypassing the ligated branches and to the inconstant ramification pattern of the renal artery. In this study, a standardized technique consisting of the resection of 16-18 g of tissue of one beagle kidney and removal of the other one is described. This method results in a stable chronic renal failure until the dogs are sacrificed at 9-12 months.

Angiography↗
PubMed1992

Quantitative relationships between body weight, kidney weight and nephron size in mongrel dogs.

Mammalian species of large stature have larger kidneys with larger nephrons than smaller animals, although this relationship is not linear. In order to investigate whether in animals of different sizes within the same species similar differences exist, a study in mongrel dogs was undertaken. In animals weighing between 9 and 42 kg with kidney weights from 25 to 79 g the area and perimeter of the glomeruli and the cortical width were measured. The number of glomeruli per unit area was counted and corrected for the size of the glomeruli. The results show that larger dogs have larger kidneys and that this enlargement is due to the increase in size of the nephrons and not in their number.

Animals↗
PubMed1992

Magnetic beads in suspension enable a rapid and sensitive immunodetection of human placental alkaline phosphatase.

The kinetics and efficiency of the interaction between placental alkaline phosphatase and a monoclonal antibody (laboratory number 327) were determined by immunoassay using microtitre plates or magnetic beads. While only up to 45% of placental alkaline phosphatase was bound to microwells precoated with this antibody, even after prolonged incubation, no less than 60% and 100% binding were reached using magnetic beads after 1 and 3 h incubations, respectively. High-molecular-mass placental alkaline phosphatase and complexed placental alkaline phosphatase forms were also completely bound to magnetic beads in the presence of deoxycholate (up to 9 g/l for serum samples). The assay sensitivity was improved up to 4-fold. In addition, 100% binding of the antigen was achieved during simultaneous incubation of magnetic beads, monoclonal antibody (125 micrograms/l), and placental alkaline phosphatase. This one-step enzymatic assay, based on magnetic beads, is an attractive alternative to the classic assay performed in microtitre plates, enabling rapid, precise, and sensitive antigen detection, and only necessitating a minimum of laboratory equipment.

Alkaline Phosphatase↗
PubMed1992

Direct determination of zinc in serum by Zeeman atomic absorption spectrometry with a graphite furnace.

We developed a precise and accurate graphite furnace atomic absorption spectrometric method for the direct determination of zinc in serum. Serum samples are analyzed after 20-fold dilution with water of ultrapure analytical grade. No other reagent is used, from the moment of sampling until measurement. During atomization, the argon flow is kept at 150 mL/min instead of gas stop, to decrease the sensitivity and thus allow lower dilution ratios. Zinc concentrations are determined against a serum-matched calibration curve. Graphite tubes are uncoated and no L'vov platform is used. Between-run CVs were 5.9%, 3.5%, and 1.9% for serum zinc concentrations of 0.93, 1.15, and 1.43 mg/L, respectively. The characteristic mass was 9 pg, and the detection limit (meanblank + 3SDblank) was 0.060 mg/L.

Adult↗
PubMed1992

Differential release of human intestinal alkaline phosphatase in duodenal fluid and serum.

Human intestinal alkaline phosphatase (IAP) can be released by the enterocyte into duodenal fluid as a mixture of three isoforms. A proportion of the enzyme is associated with triple-layered membrane vesicles (vesicular IAP). Although, occasionally, free hydrophilic IAP dimers are present, the remaining enzyme usually consists of a mixture of hydrophobic IAP dimers and more complex hydrophobic IAP structures of larger size, both entities being identified as "intestinal variant" alkaline phosphatase (VAR IAP). The hydrophobicity of VAR IAP stems exclusively from its attached glycosyl-phosphatidylinositol (GPI) anchor. Both vesicular IAP and VAR IAP are converted to hydrophilic enzyme upon removal of the GPI tail by phospholipase D (PLD) present in duodenal fluid. The IAP released into the vascular bed consists mainly of VAR IAP; vesicular IAP is absent. The enzyme characteristics of VAR IAP partially purified from duodenal fluid and from serum are identical. In plasma, VAR IAP appears to associate with (lipo)protein complexes and is thus protected from further degradation by plasma PLD. Such complex formation may explain why, in the serum of a healthy reference population, VAR IAP was more abundant than hydrophilic dimeric IAP.

Alkaline Phosphatase↗
PubMed1992

Alkaline phosphatase isoenzyme patterns in malignant disease.

Early treatment of patients with malignant disease and liver or bone metastasis may increase their survival time. We have used the activity patterns of liver and bone isoenzymes of alkaline phosphatase (ALP), separated by agarose gel electrophoresis, to detect early metastasis. We studied ALP isoenzyme patterns in a background population of 101 patients with no evidence of any disease that might influence this pattern; a healthy reference population (n = 330); and the following three groups of patients: 143 with malignant disease, 47 with nonmalignant liver disease, and 22 with nonmalignant bone disease. Cutoff and predictive values of liver ALP, high-molecular-mass (high-M(r)) ALP, and bone ALP were established for detecting liver and bone metastasis. The positive predictive value of liver and high-M(r) ALP was higher than that of total ALP in detecting liver metastasis, but liver and high-M(r) ALP did not enable us to differentiate between malignant and nonmalignant liver disease. Total ALP activity was of slightly more value than liver and high-M(r) ALP in enabling us to rule out liver metastasis. From bone ALP activity we could not distinguish between nonmalignant bone disease and bone metastasis. The negative predictive value of bone ALP in the diagnosis of bone metastasis was low, but its positive predictive value was high and superior to that of total ALP.

Adult↗