Effect of the recipient's disease on the results of transplantation (other than diabetes mellitus).
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Biomedical subjects
Publications and source records attributed to J S Cameron.
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We report 17 patients who presented with either apparent idiopathic glomerulonephritis (16 patients) or post-streptococcal glomerulonephritis (one patient). Doubts arose about the nature of these patients' disease, either because their initial renal histology was suggestive of systemic lupus erythematosus (SLE) in the absence of its clinical or serological features, or because they developed with time the clinical or serological features of SLE. Three patients had a positive antinuclear antibody (ANA) test at the onset of their illness, but normal levels of serum binding of double-stranded DNA (dsDNAB). In another four patients the dsDNAB was slightly raised but with a negative ANA. On renal biopsy the predominant appearance was membranous glomerulonephritis (GN) in 10, subendothelial mesangiocapillary GN (MCGN) in three, and focal segmental glomerulosclerosis in two; one patient each had a focal proliferative GN and a diffuse endocapillary GN. On 1 micron renal sections stained with toluidine blue, 10 patients had immune deposits at multiple sites within the glomeruli. Over a period of one to 14 years, six patients developed extrarenal features suggestive of SLE, nine a positive ANA, and 12 increased serum levels of dsDNAB. Five patients became hypocomplementaemic. Cryoglobulins were isolated from the sera of 10 out of 12 patients; seven contained DNA. Separated cryoglobulin IgG from eight patients showed antibody activity directed against both ss and dsDNA in four, and against dsDNA only in three. On the basis of the clinical, histological and serological observation during follow-up five patients were reclassified as definite SLE, four as probable SLE and two as possible SLE. Rarely, SLE may present with nephritis as the sole disease manifestation, antedating other clinical features and even immunological markers of the disease by years. In addition, some patients with a glomerulonephritis may show clinical and immunological, or histological features of SLE, but do not fit accepted definitions of the disease.
Thirty-nine patients with severe crescentic glomerulonephritis and rapidly progressive renal failure were reviewed. Nineteen patients had a focal necrotizing glomerulonephritis, they usually presented with signs of multi-system disease, and eight had histologically-proven microscopic polyarteritis. A second group of 20 patients presented with an acute nephritic syndrome, often with nephrotic features, and had only minor prodromal symptoms. Renal biopsy material showed various forms of proliferative glomerulonephritis in addition to crescents. The most important prognostic feature at admission was renal function: only four of 21 patients who required dialysis recovered any renal function. The prognosis was worse for those with necrotizing glomerulonephritis, of whom two-thirds had oliguria on admission. All patients who were not oliguric, and some with oliguria, were treated with high doses of corticosteroids, usually accompanied by azathioprine and anticoagulants. Seventeen of 18 patients who were not oliguric initially retained or regained renal function, although three subsequently went into renal failure, and three others died of non-renal causes. At the most recent review, 25 of the 39 patients were either dead (16 patients) on dialysis or transplanted (nine patients). Ten were alive with diminished renal function, one had normal renal function but persisting proteinuria, and three were well. Prompt treatment may have contributed to these favourable results in a very severe disease.
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A survey of 138 patients with systemic lupus erythematosus (SLE) (113 with nephritis) was carried out following the finding of a patient with membranous nephropathy and IgA deficiency who later developed SLE. Two hundred random hospital patients and 143 patients with idiopathic glomerulonephritis were also studied. One patient with minimal change nephrotic syndrome had IgA deficiency, but the other 342 patients had normal IgA concentrations. In the SLE group, in contrast, 4 patients had IgA deficiency and another patient prolonged IgA deficiency following phenytoin treatment. These and other published data suggest that the association of IgA deficiency is about 20 times more common in patients with SLE and nephritis than in the general population. This association may be a manifestation of defective T-cell regulation, a failure to eliminate immune complexes in the absence of IgA, or both.
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The electrophysiologic effects of epinephrine on canine subendocardial Purkinje fibers were examined 24 hours after two-stage ligation of the left anterior descending coronary artery. Transmembrane action potential were monitored simultaneously in noninfarcted (NZ) and infarcted (IZ) zones during epinephrine superfusion at 37 degrees C. Epinephrine (10(-8) M to 10(-5) M) induced dose-dependent increases in maximum rate of phase O depolarization (Vmax), action potential amplitude (APA), and maximum diastolic potential (MDP) in both NZ and IZ. Epinephrine consistently shortened effective refractory period (ERP) in both regions No significant change in action potential duration (APD) was noted at either 50% or 90% repolarization. Impulse conduction through the NZ and into the IZ was significantly improved, as indicated by an increased maximum follow-rate in each region at 10(-6) and 10(-5) M epinephrine. The IZ fibers showed a marked hypersensitivity to this agent, in that responses were particularly pronounced in the IZ vs the NZ in terms of both absolute and percentage changes. The effects of epinephrine on Vmax, MDP, APA, and ERP were generally reversed by propranolol, while remaining relatively unaffected by phentolamine, suggesting a beta-adrenergic mechanism. Increased stimulation of ventricular beta-adrenoceptors in the period 16 to 72 hours after myocardial infarction may influence ventricular vulnerability to "late-phase" arrhythmias through nonuniform effects in Purkinje fibers.
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A cerebellar neuroaxonal dystrophy in working collie sheep dogs from two properties in New Zealand and one property in Australia is described. Clinical signs developed from 2-4 months of age and included hypermetria, wide-based stance, difficulty in maintaining balance, intention tremor and ataxia. Numerous spheroids, associated with mild Wallerian degeneration, were present in the central cerebellar, adjacent peduncular and folia white matter, and associated cerebellar roof and lateral vestibular nuclei. The history of several affected pups in litters from successive matings of the same sire and dam is suggestive of an autosomal recessive mode of inheritance.
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We examined renal biopsies from 121 patients with various forms of glomerulonephritis, using antisera against platelet membrane antigens, platelet factor 4, beta-thromboglobulin and fibrinogen using the indirect immunofluorescent technique. Eight biopsies were also studied by electron microscopy for recognizable platelets. Thirty-six of sixty-four (56%) biopsies from patients with severe forms of glomerulonephritis showed some intraglomerular platelet antigen, extensive fluorescence in seventeen (25%). Of forty-six patient with milder, usually non-progressive forms of nephritis, twenty (44%) were positive, but only four (9%) showed extensive fluorescence. Platelets were identified by electron microscopy within the capillary lumina equally in those with positive and negative results for platelet-related antigens. There was no correlation between the presence of fibrin and platelet-related material in the glomeruli, nor between the presence or extent of intraglomerular platelet antigen and simultaneous measurements of intraplatelet serotonin in circulating platelets. However, there was a strong correlation between presence, extent and distribution of platelet-related antigen and platelet factor 4 fluorescence. These studies provide further evidence for the involvement of platelets in some forms of glomerular disease.
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