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Biomedical subjects

C Pusey

Publications and source records attributed to C Pusey.

11 recordsLinked to original sources
PubMed2001

Bone marrow contributes to renal parenchymal turnover and regeneration.

In order to establish whether extra-renal cells contribute to the turnover and repair of renal tissues, this study examined kidneys of female mice that had received a male bone marrow transplant and kidney biopsies from male patients who had received kidney transplants from female donors. By using in situ hybridization to detect Y-chromosomes it could be demonstrated that circulating stem cells frequently engraft into the kidney and differentiate into renal parenchymal cells. In the human renal grafts it was confirmed that some of the recipient-derived cells within the kidney exhibited a tubular epithelial phenotype, by combining in situ hybridization with immunostaining for the epithelial markers CAM 5.2 and the lectin Ulex europaeus. Female mouse recipients of male bone marrow grafts showed co-localization of Y-chromosomes and tubular epithelial markers Ricinus communis and Lens culinaris, and a specific cytochrome P450 enzyme (CYP1A2) indicating an appropriate functional capability of clustered newly formed marrow-derived tubular epithelial cells. Y-chromosome-containing cells were observed within glomeruli, with morphology and location appropriate for podocytes. Within the murine kidney, these Y-chromosome-positive cells were negative for the mouse macrophage marker F4/80 antigen and leukocyte common antigen, but were vimentin-positive. The presence of bone marrow-derived cells was noted in both histologically normal mouse kidneys and in human transplanted kidneys suffering damage from a variety of causes. These data indicate that bone marrow cells contribute to both normal turnover of renal epithelia and regeneration after damage, and it is suggested that this could be exploited therapeutically.

Animals↗
PubMed1999

Bullous dermatoses in end-stage renal failure: porphyria or pseudoporphyria?

Bullous dermatoses (BD) are well recognized in patients with end-stage renal disease (ESRD). It is important to distinguish pseudoporphyria (porphyrin accumulation due to decreased clearance) from true porphyrias, particularly those in which acute neurological attacks may occur. Investigation of the dialysis patient poses practical diagnostic difficulties because urinary porphyrin profiles are not available. We describe a patient on continuous ambulatory peritoneal dialysis (CAPD) with several recognized causative factors for porphyria cutanea tarda (PCT). The patient presented with a blistering photosensitive rash. We highlight the importance of investigating anuric patients with fractionation of both fecal and plasma porphyrins. Plasma porphyrins were grossly elevated (345 nmol/L; reference range, <13), whereas plasma porphyrins in a control group of CAPD patients without blistering rashes were only minimally elevated (mean, 23.9 nmol/L; SD, 11.0; n = 9). Fractionation of fecal porphyrins by high-performance liquid chromatography (HPLC) yielded a pattern typical of PCT. In addition to the contributory factors for PCT that were present, it is possible that porphyrin accumulation secondary to renal failure played a role in the expression of her disease. Patients with ESRD presenting with BD require careful evaluation, including fractionation of fecal porphyrins.

Diagnosis, Differential↗
PubMed1999

International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA)

Antineutrophil cytoplasmic antibody (ANCA) tests are used to diagnose and monitor inflammatory activity in the primary systemic small vessel vasculitides. ANCA is best demonstrated in these diseases by using a combination of indirect immunofluorescence (IIF) of normal peripheral blood neutrophils and enzyme-linked immunosorbent assays (ELISAs) that detect ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). For ANCA testing in "new" patients, IIF must be performed on all serum samples. Serum samples containing ANCA, any other cytoplasmic fluorescence, or an antinuclear antibody (ANA) that results in homogeneous or peripheral nuclear fluorescence then should be tested in ELISAs for PR3-ANCA and MPO-ANCA. Optimally, ELISAs for PR3-ANCA and MPO-ANCA should be performed on all serum samples. Inclusion of the most recent positive sample in the IIF or ELISA may help demonstrate a change in antibody level. Reports should use recommended terms. Any report of positive neutrophil fluorescence issued before the ELISA results are available should indicate that positive fluorescence alone is not specific for the diagnosis of Wegener granulomatosis or microscopic polyangiitis and that decisions about treatment should not be based solely on the ANCA results.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Outcome of renal replacement therapy in antineutrophil cytoplasmic antibody-associated systemic vasculitis.

Antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) frequently leads to end-stage renal disease (ESRD). Potentially fatal disease activity can continue after the onset of ESRD in both dialysis and transplant patients, despite the immunosuppressive effects of uremia and rejection prophylaxis, leading to concerns that such patients have greater morbidity and mortality. To assess the outcome of AASV patients receiving renal replacement therapy, a retrospective analysis of 59 patients from our unit who received chronic dialysis, renal transplantation, or both, was performed. The survival of AASV patients with ESRD was comparable to national registry controls, as were both graft and patient survival after renal transplantation. Ther is no evidence that standard immunosuppressive protocols should be altered for AASV patients receiving renal transplants. The rate of relapse of vasculitis for patients on chronic dialysis and after transplantation was 0.09 and 0.02 per patient per year, respectively. These rates are lower than those of other series and support the contention that continued immunosuppression after ESRD, as practiced in our unit, is warranted. Relapses usually responded to cyclophosphamide and high-dose prednisolone treatment. Significantly, vasculitic flare-ups in dialysis patients were sometimes initially misdiagnosed as dialysis complications, leading to fatal delays in effective treatment. Follow-up by physicians experienced in the diagnosis and treatment of vasculitis activity should continue in these patients.

Adolescent↗
PubMed1983

Essential mixed cryoglobulinaemia with false-positive serological tests for syphilis.

Analysis of serum from a patient with cutaneous leukocytoclastic vasculitis showed a mixed cryoglobulin with a monoclonal IgM kappa-antiglobulin component (6.5 mg/ml), strong rheumatoid factor activity (latex titre 1/5000), and positive serological tests for syphilis (fluorescent treponemal antibody-absorbed and Treponema pallidum haemagglutination assay). After removal of antiglobulin activity by immunoabsorption with heat-aggregated gammaglobulin all serological test results for treponemal infection became negative. Serological tests for syphilis and rheumatoid factor on the supernatant from whole serum (minus cryoglobulin) remained positive though at a lower titre (latex 1/1250). Cryoglobulin isolated from whole serum retained rheumatoid and TPHA reactivity but was negative in the FTA-ABS test. The IgM and IgG cryoglobulin components purified by gel filtration on Sepharose showed no antitreponemal reactivity even when tested individually. Reducing the concentration of cryoglobulin to 1.5 mg/ml by plasma exchange converted the test results for syphilis to doubtful-positive or negative. These results indicated that high concentrations of antiglobulin activity may be associated with falsely positive specific antitreponemal test results and that this phenomenon depends on the concentration of cryoglobulin in the test sample.

Cryoglobulinemia↗
PubMed1981

Subacute massive pulmonary embolism.

Twenty-four patients with subacute massive pulmonary embolism were studied both during their initial illness and up to nine years after it. The most common mode of presentation was progressive dyspnoea over a two to 12 week period, which in some, but not all, patients was accompanied by pleuritic chest pain and haemoptysis. Physical signs at diagnosis usually suggested right heart strain and ventilation/perfusion mismatch and in the five patients with the highest pulmonary artery pressures the pulmonary component of the second sound was accentuated. The chest x-ray and electrocardiogram provided useful diagnostic information in most patients though occasionally they were normal. Early response to thrombolytic treatment was poor when compared with patients with acute pulmonary embolism but was occasionally dramatically successful, and heparin alone provided satisfactory treatment in the eight patients receiving it. Pulmonary embolectomy provided poor results and four of the five patients undergoing this form of treatment died. Nine patients died during the initial illness and in seven death was directly related to embolic disease. One patient died from neoplastic disease during follow-up. Though the prolonged illness, poor initial response to treatment, and absence of predisposing factors suggest that recurrent embolic disease and late pulmonary hypertension might occur three was no evidence of this during a follow-up period of one to nine years (median five years).

Adult↗