Elevated reticulocyte count--a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report.
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In adults, the haemolytic-uraemic syndrome (HUS) is associated with probable causative factors in the minority of all cases. Cytotoxic drugs are one of these potential causative agents. Although metastatic cancer by itself is a recognized risk-factor for the development of HUS, therapy with mitomycin-C, with cis-platinum, and with bleomycin carries a significant, albeit extremely small, risk for the development of HUS, compared with all other cytotoxic drugs. Gemcitabine is a novel cytotoxic drug with promising activity against pancreatic adenocarcinoma. We are reporting on one patient with metastatic duodenal papillary carcinoma developing HUS while on weekly gemcitabine therapy. The presenting features in this patient were non-cardiac pulmonary oedema, renal failure, thrombocytopenia and haemolytic anaemia. The diagnosis of HUS was made on the day of admission of the patient to this institution. Upon aggressive therapy, including one single haemodialysis and five plasmaphereses, the patient recovered uneventfully, with modestly elevated creatinine-values as a remnant of the acute illness. Re-exposure to gemcitabine 6 months after the episode of HUS instituted for progressive carcinoma, thus far has not caused another episode of HUS. (+info)
A large outbreak of hemolytic uremic syndrome caused by an unusual sorbitol-fermenting strain of Escherichia coli O157:H-.
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Escherichia coli O157:H7 does not ferment sorbitol, a factor used to differentiate it from other E. coli. From December 1995 to March 1996, 28 children with hemolytic uremic syndrome in Bavaria, Germany, were identified; many had a sorbitol-fermenting (sf) E. coli O157:H- cultured. A case-control study showed a dose-response relationship between sausage consumption and illness. A second case-control study showed a relationship between mortadella and teewurst consumption and illness, particularly during December (mortadella odds ratio [OR], 10.5, P=.004; teewurst OR, 6.2, P=.02). Twelve sf O157:H- were characterized to determine clonality and virulence traits. The strains possessed the Stx2, eae, and EHEC-hlyA genes but were nonhemolytic on blood agar plates. The O157:H- isolates belonged to phage type 88 and had identical pulsed-field gel electrophoresis patterns. This outbreak was caused by sf E. coli O157:H-, which is not detectable by culture on sorbitol MacConkey's agar. Consumption of two sausages, including a raw beef-containing sausage, was statistically related to illness. (+info)
A laboratory model of toxin-induced hemolytic uremic syndrome.
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BACKGROUND: Verocytotoxin-producing (Shiga-like toxin-producing) Escherichia coli infection is the principal cause of hemolytic uremic syndrome (HUS). The pathogenesis is unclear, and there is a need for animal models. These are impeded by the different distribution of verocytotoxin receptors between species. We have circumvented this restriction using ricin, which gains entry into cells via various galactose receptors. Like verocytotoxin, ricin specifically cleaves a single adenine from ribosomal RNA. METHODS: Rats were given ricin at a dose of 6.7 micrograms/100 g body wt, with or without lipopolysaccharide at 10 micrograms/100 g body wt. Lipopolysaccharide alone or saline were used as controls. Changes in glomerular filtration rate, hematological parameters, histology, and plasma cytokine concentrations were measured. RESULTS: Extensive glomerular thrombosis, pyknotic nuclei, and an infiltration of ED1-positive cells into glomeruli were observed eight hours after an injection of ricin. Other vascular beds were unaffected. Histologic changes were preceded by oliguric renal failure, hemolysis, and thrombocytopenia. Ricin produced a rise in plasma concentrations of monocyte chemotactic protein-1, > tumor necrosis factor-alpha, > interleukin-1 beta, > interleukin-6. Interferon-gamma showed a small increase at the end of the experiment. CONCLUSIONS: Ricin induces glomerular thrombotic microangiopathy, closely resembling that which occurs in verocytotoxin-producing E. coli-induced HUS. As in HUS, high concentrations of proinflammatory cytokines are present, which are probably a result of cytokine superinduction by the toxin. (+info)
Up-regulation of Duffy antigen receptor expression in children with renal disease.
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BACKGROUND: The Duffy antigen chemokine receptor (DARC) is a promiscuous chemokine receptor that binds chemokines from the C-X-C and C-C families. DARC was initially described on red blood cells, but subsequent studies have demonstrated DARC protein expression on renal endothelial and epithelial cells, even in Duffy-negative individuals whose red cells lack DARC. Because approximately 68% of African Americans lack the Duffy/DARC on their red cells, we carried out experiments to identify the specific renal cells expressing DARC protein and mRNA in African American children and to define whether DARC expression was altered in renal inflammatory processes. METHODS: Immunohistochemistry and in situ hybridization studies were done in 28 renal sections from children with each of the following diagnoses: HIV nephropathy (HIVAN), HIV-associated hemolytic uremic syndrome (HIV-HUS), HIV infection without renal disease, HIV-negative children without renal disease, and Argentinean children with classic HUS. RESULTS: The predominant localization of DARC mRNA and protein was found in endothelial cells underlying postcapillary renal venules in all patients studied. However, DARC mRNA and protein were significantly up-regulated in peritubular and glomerular capillaries, collecting duct epithelial cells, and interstitial inflammatory cells in children with HIVAN, HIV-HUS, and classic HUS. CONCLUSION: These findings support the notion that the renal DARC is linked to the inflammatory cascade and that African American children may be at risk of accumulating chemokines in renal tissues. (+info)
Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura.
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Familial hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) carry a very poor outcome and have been reported in association with decreased serum levels of the third complement component (C3). Uncontrolled consumption in the microcirculation, possibly related to genetically determined deficiency in factor H--a modulator of the alternative pathway of complement activation--may account for decreased C3 serum levels even during disease remission and may predispose to intravascular thrombosis. In a case-control study by multivariate analysis, we correlated putative predisposing conditions, including low C3 serum levels, with history of disease in 15 cases reporting one or more episodes of familial HUS and TTP, in 25 age- and gender-matched healthy controls and in 63 case-relatives and 56 control-relatives, respectively. The relationship between history of disease, low C3, and factor H abnormalities was investigated in all affected families and in 17 controls. Seventy-three percent of cases compared with 16% of controls (P < 0.001), and 24% of case-relatives compared with 5% of control-relatives (P = 0.005) had decreased C3 serum levels. At multivariate analysis, C3 serum level was the only parameter associated with the disease within affected families (P = 0.02) and in the overall study population (P = 0.01). Thus, subjects with decreased C3 serum levels had a relative risk of HUS or TTP of 16.56 (95% confidence interval [CI], 1.66 to 162.39) within families and of 27.77 (95% CI, 2.44 to 314.19) in the overall population, compared to subjects with normal serum levels. Factor H abnormalities were found in four of the cases, compared with three of the healthy family members (P = 0.02) and none of the controls (P = 0.04) and, within families, factor H abnormalities were correlated with C3 reduction (P < 0.05). Reduced C3 clusters in familial HUS and TTP is likely related to a genetically determined deficiency in factor H and may predispose to the disease. Its demonstration may help identify subjects at risk in affected families. (+info)
Characterization of the baboon responses to Shiga-like toxin: descriptive study of a new primate model of toxic responses to Stx-1.
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The baboon response to intravenous infusion of Shiga toxin 1 (Stx-1) varied from acute renal failure, proteinuria, hyperkalemia, and melena with minimal perturbation of host inflammatory and hemostatic systems (high-dose group, 2.0 microg/kg; n = 5) to renal failure with hematuria, proteinuria, thrombocytopenia, schistocytosis, anemia, and melena (low-dose group, 0.05 to 0.2 microg/kg; n = 8). Both groups exhibited renal shutdown and died in 57 hours or less. Both groups produced urine that was positive for tumor necrosis factor and interleukin-6 although neither of these cytokines was detectable (+info)
Neuropsychological sequelae of haemolytic uraemic syndrome. Investigators of the HUS Cognitive Study.
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BACKGROUND: Severe haemolytic uraemic syndrome (HUS) in childhood can cause stroke, hemiplegia, cortical blindness, and psychomotor retardation. These outcomes are evident at the time of discharge immediately after the acute illness. Less is known about the neuropsychological outcomes of less severely affected children who recover from acute HUS. AIMS: This multicentre case control study investigated the hypothesis that children who survive an acute episode of HUS without recognizable neurological injuries have greater impairment of cognitive, academic, and behavioural functions than controls. DESIGN: Children with HUS were eligible if they had no evidence of severe neurological dysfunction when discharged from one of six Canadian hospitals. Controls had been admitted to hospital for a non-HUS illness and were matched by age, sex, first language, and socioeconomic status. All subjects underwent evaluation of behaviour, academic achievement, cognitive function, and verbal abilities using standardised tests administered by a psychometrist blinded to the case or control status. RESULTS: Ninety-one case control pairs were enrolled. No important differences between patients with HUS and paired controls were evident on tests of IQ, behaviour, verbal abilities, or academic achievement. There was no increased risk of attention deficit disorder among patients with HUS. There was no correlation between the severity of acute renal failure and neuropsychological measures, although scores on some verbal ability tests were lower in those with the highest serum creatinine concentrations during illness. CONCLUSIONS: Children discharged from hospital without apparent neurological injury after an episode of acute HUS do not have an increased risk of subclinical problems with learning, behaviour, or attention. (+info)
Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency.
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BACKGROUND: In a recent study of three families we have found that inherited haemolytic uraemic syndrome (HUS) maps to a region of chromosome 1q containing the gene for complement factor H. In one of these families and also in a case of sporadic D-HUS, we have identified mutations in the factor H gene. A further family with inherited HUS has therefore been investigated. METHODS: DNA extracted from the family members and DNA extracted from archival post-mortem material from a deceased family member, was studied. Review of renal biopsies and study of complement components was also undertaken. RESULTS: This family demonstrates an inherited deficiency of complement factor H. Non-diarrhoeal HUS has affected at least two family members with half normal levels of factor H. CONCLUSION: These findings represent further evidence of the association between factor H dysfunction and HUS. (+info)