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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
PubMed2001

Bismuth overdosing-induced reversible nephropathy in rats.

Overdosing of colloidal bismuth subcitrate (CBS), used to treat peptic ulcers and Helicobacter pylori infections, has been reported to result in serious, though reversible, nephrotoxicity in humans. However, little is known about the nature of the renal damage induced by bismuth (Bi), and no well-described experimental model exists. Single large oral CBS doses (0.75, 1.5, and 3.0 mmol Bi/kg) were administered to three groups of 20 female Wistar rats. A control group (n = 20) received only the vehicle. Standard kidney function parameters, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and the Bi content were monitored in blood, urine, liver, and kidneys for 14 days. A dose of 3.0 mmol Bi/kg, 100 times the daily therapeutic dose, caused kidney damage within 6 h as detected by proteinuria, glucosuria, and elevated plasma urea and plasma creatinine levels. The kidneys of all animals, except two that died, recovered functionally within 10 days. At a dose of 1.5 mmol Bi/kg, clinical parameters changed less and normalized within 48 h, whereas a dose of 0.75 mmol Bi/kg induced no changes. Histological evaluation revealed that the S3 tubular segment necrotized first with additional necrotization of the S1/S2 segment when more Bi was absorbed. The lesions were accompanied by interstitial infiltrates of CD45+ leukocytes. In summary, we developed a rat model for Bi-induced reversible nephropathy. A large single oral overdose of CBS administered to Wistar rats led to damage to the proximal tubule, especially in the last segment.

Acetylglucosaminidase↗
PubMed1998

Al and Si: their speciation, distribution, and toxicity.

OBJECTIVES: In dialysis patients both aluminum (AI) and silicon (Si) may accumulate. Whereas the toxic effects of AI within this population are clearly established, little is known on the role of Si in the development/protection of particular dialysis-related diseases. A clear insight in the protein binding and speciation of trace elements is important to better understand the mechanisms underlying their toxicity/essentiality. Research in this field however is complex and often prone to analytical difficulties and inaccuracies. DESIGN AND METHODS: In the first part of this review techniques used for speciation studies of AI and Si in biological fluids are discussed. Notwithstanding recent technical advances (a) extraneous metal contamination, (b) unrecognized aspecific binding of metals to proteins, and (c) unwanted interactions with separation equipment such as chromatography columns and ultrafiltration membranes remain important pitfalls and often lead to erroneous conclusions. The factors that determine the speciation of AI and Si and their ultimate tissue distribution and toxicity are dealt with in the second part. Here, experimental data obtained with various speciation techniques are linked to in vivo data on the tissue distribution, localization/toxicity of both elements. CONCLUSIONS: A model in which the AI tissue distribution/toxicity is mediated by either its citrate or transferrin bound form is proposed.

Aluminum↗
PubMed1997

Prevalence and clinical expression of HCV-genotypes in haemodialysis-patients of two geographically remote countries: Belgium and Saudi-Arabia.

Hepatitis C virus is the leading cause of acute and chronic liver disease in hemodialysis patients. There are at least six major HCV-genotypes, with a well documented geographical distribution in the general population. Moreover, HCV-genotype is one of the major determinants of the therapeutic response to Interferon Alpha in affected patients. Since the therapeutic outcome in HCV-positive hemodialysis patients, especially with regard to the different HCV-genotypes, is of interest, a multicentre epidemiologic study was performed in HCV-antibody positive hemodialysis patients of two geographically remote countries, i.e. in Flanders (Belgium) and in Saudi-Arabia. 184 chronic hemodialysis patients, with a positive second or third generation Elisa assay for HCV, were tested for HCV-viremia and HCV-genotype, using a 5' untranslated region (UR) nested PCR for the detection of HCV-RNA and subsequently type-specific probes to hybridize with HCV-RNA (Inno-Lipa). Additionally, clinical data were collected by means of a standardized questionnaire, thoroughly completed by the nephrologist in charge of each respective patient. Viremia was present in 79% of the patients (146 out of 184). The prevalence of HCV-genotypes differed significantly between Belgian and Saudi-Arabian dialysis-patients. In Belgian dialysis patients HCV-genotype 1b was most prevalent (i.e. 62%), while in Saudi-Arabian patients HCV-genotypes 4, 1b, and la were present in respectively 36,4%, 31,7%, and 25,8% of the HCV-PCR positive patients. Although there were significant differences between Belgian and Saudi-Arabian dialysis patients, no clinical data showed any significant correlation with the HCV-genotype. Transaminases, determined over a six months period, showed normal average values. Doubling of the transaminases, in at least one out of six measurements over a six monthly period, occurred only in 14% (alanine aminotransferase, ALT) and 10% (aspartate aminotransferase, AST) of the patients. In Belgian dialysis patients, HCV-genotype 4 (or HCV-genotype 5) significantly correlated with a more recent start of dialysis treatment. We conclude that there is a significant different geographical prevalence of HCV-genotypes in HCV-affected hemodialysis patients. None of the different HCV-genotypes shows any particular clinical expression. Transaminases are not a sensitive marker for ongoing HCV-replication in hemodialysis patients. In Belgian dialysis patients, a changing pattern of HCV-infection is suggested, with an increasing prevalence of HCV-genotype 4 (or HCV-genotype 5) in more recent years. These data suggest possible implications for the therapeutic strategy in dialysis patients.

Adult↗
PubMed1996

Occupational renal diseases.

There is no doubt that particular occupational exposures may induce acute renal effects. The role of occupational exposure in the development or progression of chronic renal failure, however, is still not clear. Recent epidemiological studies point towards a contributive role of particular occupational exposures in the progression of renal disease. Furthermore, some observations in the 1994-1995 literature suggest a primary or secondary role, or both, of new substances such as silicon-containing compounds in the development of anti-neutrophil cytoplasmic antibody-positive rapidly progressive glomerulonephritis and Wegener's granulomatosis. Finally, studies suggesting a particular sensitivity of the diabetic kidney towards the damaging effects of certain occupational exposures deserve confirmation.

Humans↗
PubMed1995

An in vitro study on the binding of Al(III) to human serum transferrin with the isoelectric focusing technique.

Transferrin saturated with Al3+ subjected to isoelectric focusing (IEF) in a pH gradient can be separated into four fractions, representing the apotransferrin, transferrin with aluminum at the metal binding site in the C- or N-terminal lobe, or both. The electrophoretic mobilities of these four fractions are identical to those of the iron-transferrin counterparts. Simultaneous binding of aluminum and iron to transferrin can also be demonstrated. The decreased saturation after IEF indicates that the affinity of transferrin for aluminum is low compared with its affinity for iron. This effect is particularly evident when bicarbonate is used as the synergistic anion in the loading procedure. In contrast, loading of transferrin with aluminum in the presence of oxalate produces a di-aluminum-transferrin complex that is stable during IEF.

Aluminum↗
PubMed1995

Impact of legislative measures on the sales of analgesics and the subsequent prevalence of analgesic nephropathy: a comparative study in France, Sweden and Belgium.

In a number of European countries (e.g. Belgium), analgesic nephropathy continues to be a highly prevalent renal disease, whereas in other countries (e.g. Sweden) the problem has been resolved after legislative measures were taken. In still other countries, e.g. France, the official prevalence of analgesic nephropathy has always been low. The aim of the present study is to detect whether specific legislation in particular countries has played a role in the prevalence of analgesic nephropathy. Hence, we compared analgesic legislation in Belgium, France and Sweden, and then compared it with the respective sales data of non-narcotic analgesics and with the prevalence data of analgesic nephropathy in the dialysis population. Each investigated country represents a different evolution pattern in the prevalence of analgesic nephropathy. This study indicates that legislation restricting the over-the-counter availability of the majority of analgesic components and resulting in the absence of analgesic mixtures--containing two analgesic substances and one potentially addictive substance--on the market, has effectively resulted in a substantially lower prevalence of analgesic nephropathy. Moreover, it shows that permissive legislation could be associated with very different sales data, depending on the marketing strategy of the pharmaceutical industry and the subsequent purchasing behaviour of the population. These findings indicate that, in order to eradicate analgesic nephropathy, there is a need to elaborate legislation that prohibits the availability of analgesic mixtures containing two analgesic components and at least one potentially addictive substance.

Analgesics↗
PubMed1991

Legionella pneumophila peritonitis in a kidney transplant patient.

Legionella pneumophila serotype 6 was isolated from the peritoneal fluid of a 59-year-old immunosuppressed patient who developed peritonitis shortly after kidney transplantation. Clinical and radiological examination did not show pulmonary abnormalities until shortly before his death when multiple organ failure developed with adult respiratory distress syndrome (ARDS). Post mortem examination showed L. pneumophila in the peritoneum and in a small pulmonary infiltrate, confirmed by positive cultures. A primary peritoneal inoculation via an indwelling Tenckoff catheter seems to have been the most likely route of infection. Positive L. pneumophila type 6 cultures were obtained from the shower and hot water tap in the room of the patient. L. pneumophila must be considered as a potential cause of peritonitis in which routine microbiological cultures remain negative.

Ascitic Fluid↗
PubMed1989

Segment-specific localization of intestinal-type alkaline phosphatase in human kidney.

Specific monoclonal antibodies raised against human intestinal and human tissue-unspecific alkaline phosphatase (AP) were developed and were used to study the expression of these two isoenzymes in human renal tissue and their release into urine. Approximately 25% of the total AP content of renal tissue at the transition between cortex and medulla was of the intestinal type; the remainder was of the tissue-unspecific type (liver, bone, kidney AP). Immunoperoxidase staining using specific monoclonal antibodies against liver and intestinal AP revealed that the tissue-unspecific AP isoenzyme is present through-out the different segments of the proximal tubule, whereas intestinal-type AP is found exclusively in tubuloepithelial cells of the S3-segment of the proximal tubule. The intestinal-type enzyme obtained from the kidney had a similar heat stability and Km value, and similar immunologic and inhibitory (L-p-bromotetramisole; L-phenylalanine) characteristics compared to adult intestinal and fetal intestinal AP. Its electrophoretic mobility in agarose gel was intermediate between that of adult intestinal and fetal intestinal AP; after neuraminidase treatment it became indistinguishable from the adult intestinal isoenzyme. The intestinal-type AP found in the urine was not sensitive to neuraminidase and had a molecular weight significantly lower than the urinary tissue-unspecific AP isoenzyme. In conclusion, intestinal AP in the kidney is a specific marker for the brush border of the S3 segment of the proximal tubule, and this finding opens new perspectives in the cell biology of this particular part of the nephron.

Alkaline Phosphatase↗
PubMed1988

Acquired immunodeficiency syndrome mimicking Sjögren's syndrome and systemic lupus erythematosus.

We describe a patient in whom the diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was delayed because her clinical symptoms were similar to those of systemic lupus erythematosus and Sjögren's syndrome and because of a false-negative result on a Western blot test for human immunodeficiency virus. The importance of using different diagnostic tests for AIDS and the pitfalls in diagnosing AIDS in patients who appear to have connective tissue disease are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Aluminum accumulation in children on chronic dialysis: predictive value of serum aluminum levels and desferrioxamine infusion test.

In 7 children on chronic dialysis the correlation between serum aluminum, aluminum after desferrioxamine (DFO) challenge and bone aluminum was studied. In children the DFO challenge test is not superior to the serum aluminum level for the estimation of aluminum body burden. A significant correlation between serum aluminum and bone aluminum content was found. In all children, except one, aluminum bone content was markedly elevated.

Adolescent↗
PubMed1986

Laser microprobe mass analysis (LAMMA) to verify the aluminon staining of bone.

Triammonium aurin tricarboxylate (aluminon) has been used to localize aluminum in 2 micron sections of undecalcified, methyl methacrylate embedded bone obtained from patients with terminal chronic renal failure. Aluminum appeared in four cases as bright red lines at the mineralized-bone boundary. In two cases, however, purplish lines were found and one patient showed red as well as purplish lines. Laser microprobe mass analysis (LAMMA) identified aluminum at the location of the red lines and both aluminum and iron at the purplish lines. Furthermore, both iron and aluminum were found in histiocytic bone marrow cells, which showed brownish aluminon staining. It appears that when aluminum and iron occur together, aluminon staining may yield aberrant results. This study shows that LAMMA can be used for the identification of elements sought by histochemical methods and thus permits the evaluation of their staining effects.

Aluminum↗
PubMed1985

Screening of sera and tumor extracts of cancer patients using a monoclonal antibody directed against human placental alkaline phosphatase.

A sensitive endogenous enzyme immunoassay involving an anti-human placental alkaline phosphatase (PLAP) monoclonal antibody was used in the screening of sera and tumor extracts of patients with various types of cancer. In sera of breast cancer patients an incidence of 5.2% was recorded. This value rose to 43% when tumor extracts were analyzed. For lung and bronchial cancers we found 11.2% seropositive patients. On several occasions a good correlation was observed between the PLAP determinations and the histopathological staging of tumor tissue.

Adult↗
PubMed1982

Early toxic events in kidney of rat and man following administration of gentamicin at low doses.

Kidney cortex of rats and humans treated with low doses of Gentamicin have been examined both morphologically and biochemically. Specific alterations of the lysosomes (loss of activity of phospholipases; accumulation of phospholipid-like material) was detected as early as from 2-4 days of treatment. This finding is consistent with the concept that Gentamicin exerts its toxic action on kidney through lysosomal dysfunction.

Animals↗
PubMed1981

Occurrence of enzyme-immunoglobulin complexes in chronic inflammatory bowel disease.

The presence of circulating enzyme-immunoglobulin complexes was investigated in serum samples of patients with inflammatory bowel disease. In a series of 20 patients with ulcerative colitis AP-Ig complexes were demonstrated in three and LDH-Ig complexes were observed in two others. No AP-Ig or LDH-Ig complexes were found in the sera of 25 patients with Crohn's disease. These findings suggest a relationship between enzyme-immunoglobulin complex formation and ulcerative colitis.

Adult↗