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Biomedical subjects

J S Cameron

Publications and source records attributed to J S Cameron.

At least 145 records · Page 8Linked to original sources

Diagnosis of rejection in renal allograft biopsies using the presence of activated and proliferating cells.

Forty cyclosporine-treated renal allograft biopsies were stained with anti-Tac, a monoclonal antibody (MoAb) against interleukin 2 receptor (CD25), anti-transferrin receptor MoAb, and Ki67 MoAb (a proliferating cell marker), using a method of gold enhancement of the diaminobenzidine reaction product, in order to study the utility of these markers to differentiate rejection from other causes of graft dysfunction. Biopsies were selected on the basis of availability of sufficient frozen material and optical microscopy diagnosis, and only biopsies that showed acute cellular rejection and biopsies that did not show any sign of rejection (cyclosporine toxicity or a stable graft) were studied. In addition biopsies were stained with a panel of monoclonal antibodies reacting with CD45, CD3, CD4, CD8, EBM11 (a monocyte-macrophage marker), HLA-DR, DP, and DQ, using the usual indirect immunoperoxidase method. The clinical diagnosis (rejection versus no rejection) was made in ignorance of the biopsy findings. In 17 of 18 (94%) episodes of rejection, anti-Tac and anti-transferrin receptor-positive cells, and in 15 of 18 rejection episodes (83%), proliferating cells, were found in the interstitium. Anti-Tac-positive cells were never found in the 11 biopsies diagnosed as no rejection, and only in two a few anti-transferrin receptor-positive cells were present. The proportion of activated and proliferating cells in rejection episodes, expressed as the percentage of CD45-positive cells were: anti-Tac MoAb 4.1 +/- 2.9%, anti-transferrin receptor MoAb 6.9 +/- 3.9%, and Ki-67 MoAb 6.3 +/- 4.8%. There was a positive correlation between the total number of infiltrating cells and the number of cells stained with anti-Tac (r = 0.75, P less than 0.005), anti-transferrin receptor MoAb (r = 0.84, P less than 0.0001), and Ki-67 (r = 0.50, P less than 0.05). The episodes of rejection that took place when cyclosporine levels were high had fewer 1L-2R-bearing cells in the interstitium than those that took place when cyclosporine levels were low (r = 0.47, P less than 0.05). We conclude that during rejection the presence of activated and proliferating cells is a consistent finding, and that these markers could be useful in differentiating between rejection and other causes of graft dysfunction as well as in grading the severity of rejection.

Adolescent↗

The relevance of induced class II HLA antigens and macrophage infiltration in early renal allograft biopsies.

Using a panel of monoclonal antibodies, immunohistological analysis was performed on frozen sections taken from 14 peritransplant renal biopsies and 42 biopsies taken 6 +/- 2 days posttransplantation. The following parameters were examined: tubular expression of HLA-DR, DP, and DQ and infiltration with T lymphocytes and macrophages. Of the 42 posttransplant biopsies, 26 were diagnosed as rejecting and 16 as nonrejecting according to clinical and histopathological criteria. HLA-DR antigens were strongly expressed on 8 of 14 peritransplant biopsies, 23 of 26 rejecting biopsies and 13 of 16 nonrejecting biopsies. Tubular expression of HLA-DP and DQ was weak or absent. In the rejecting biopsies there was a significantly increased infiltrate of T lymphocytes of all phenotypes and of macrophages when compared with the nonrejecting biopsies. Graft outcome was invariably favorable in the nonrejecting group, with no graft losses in the first posttransplant year. There were 4 graft losses in the rejecting group, all due to rejection, and further analysis revealed that all 4 had macrophage-dominated infiltrates in their early allograft biopsies. We conclude that immunohistological analysis of early allograft biopsies provides an accurate prognosis of subsequent graft acceptance or rejection and that early macrophage infiltration is a poor prognostic sign.

Antibodies, Monoclonal↗

Calcific stenosis of a mitral valve xenograft in a patient in chronic renal failure.

A 61 year old man presented with mitral regurgitation and glomerulonephritis caused by suspected infective endocarditis. His glomerulonephritis remitted on immunosuppression but mitral valve replacement with a Carpentier-Edwards porcine xenograft later proved necessary. The patient became dialysis dependent and cadaveric renal allografting was complicated by delayed graft function and refractory pulmonary oedema. Cardiac catheterisation showed severe calcification and stenosis of the xenograft with a transvalvar gradient of 23 mm Hg and despite emergency valve replacement the patient died. The valve had been in place less than five years. The rapid calcification and stenosis of a bioprosthetic heart valve calls into question the use of such prostheses in patients with chronic renal failure.

Bioprosthesis↗

Staphylococcus aureus nasal carriage, exit-site infection and catheter loss in patients treated with continuous ambulatory peritoneal dialysis (CAPD).

Over a three-year period, 217 episodes of bacterial peritonitis occurred in 183 patient years. Thirty-seven episodes were due to Staphylococcus aureus and 19 (51%) of these required removal of the catheter to eradicate infection. This compared with catheter loss in 4/63 (6.3%) coagulase negative staphylococci infections (p less than 0.001); 7/67 (9.5%) culture negative peritonitis (p less than 0.001); and 10/30 (33.3%) episodes due to gram-negative organisms (p less than 0.05). Over half (51.3%) the episodes due to S. aureus were associated with exit-site infections, and this rose to 100% (10/10) with recurrent peritonitis (p less than 0.01). A prospective analysis of nasal carriage and exit-site infections due to S. aureus was carried out in 87 patients. Exit-site infections were present in 21 (24%), almost entirely due to different strains as judged by sensitivity patterns and phage typing. Nasal carriage, defined as two positive swabs within the study period, was present in 20 (23%) patients. Fourteen (70%) of these had exit-site infections due to the same strain as that isolated from the nose, whereas no patient grew different strains from either site. Nasal carriage increased the risk of infection sixfold (p less than 0.001).

Catheters, Indwelling↗

Strain differences in the opsonisation of Staphylococcus epidermidis.

Ten isolates of coagulase-negative staphylococci, collected from patients receiving treatment with continuous ambulatory peritoneal dialysis (CAPD), exhibited marked differences in the degree of opsonisation when incubated in 10% and 1% pooled human serum, 10% and 1% heat-treated serum, Hanks' Balanced Salt Solution, and timed peritoneal dialysis (PD) effluent. The addition of exogenous IgG to PD effluent results in a greater increase in opsonisation in those fluids with the weakest inherent opsonic activity, but is ineffective against the majority of isolates in the absence of heat-labile opsonic activity. The results of this in vitro study suggest that host resistance to CAPD peritonitis due to coagulase-negative staphylococci may be determined as much by the characteristics of the contaminating strain, as by the opsonising activity of PD effluent.

Humans↗

Immunologically mediated interstitial nephritis: primary and secondary.

Tubulointerstitial disease has been reviewed twice in the past five years at the Necker Seminars in Nephrology; why is it necessary to return once again to this topic? Although the importance of the tubulointerstitial component of the kidney is self-evident, the literature on glomerular disease remains vastly greater than that on the tubules and interstitium. In this brief review I wish first to discuss the tubulointerstitial component of what are usually considered glomerular diseases--the glomerulonephritides and lupus, and then to discuss what appear to be primary tubulointerstitial nephritides (TIN), in which the glomeruli are usually spared and the primary attack appears to be on the tubules and interstitium.

Anti-Bacterial Agents↗

Genetics of classic Alport's syndrome.

41 families with classic Alport's syndrome (hereditary nephritis with sensorineural deafness) were studied. All their pedigrees were compatible with X-linked inheritance. DNA probes were used to investigate genetic linkage in these families. Linkage to probe S21 (DXS17) was confirmed (LOD score = 4.72 at 0 = 0.06), localising the gene for Alport's syndrome to the middle of Xq; thus the disorder is X-chromosomal in nature.

Adult↗

Poststreptococcal glomerulonephritis in children: clinicopathological correlations and long-term prognosis.

Between 1962 and 1970, 36 children with acute biopsy-proven poststreptococcal glomerulonephritis (PSGN) entered a prospective long-term follow-up study. The initial biopsies were scored into four histological grades using criteria based on endocapillary proliferation, leucocyte infiltration, epithelial "hump" and crescent formation; 5 patients had grade-1 (least severe), 14 grade-2, 15 grade-3 and 2 grade-4 biopsies. Two children died from rapidly progressive glomerulonephritis; both had grade-4 biopsies. Early repeat biopsy in 12 patients showed improvement in all but one patient who progressed from grade 2 to type 2 mesangiocapillary glomerulonephritis (MCGN). The initial biopsy grade correlated significantly with heavy proteinuria (chi2 = 9.73, P less than 0.01) but not with hypertension, haematuria or renal functional impairment. Follow-up observations were made after mean periods of 9.5 years (range 5.4-12.4 years; 32 subjects) and 19.0 years (range 14.6-22 years; 30 subjects). None of the survivors had an abnormal plasma creatinine. Only one patient (grade-3 biopsy), a female with a subsequent history of recurrent pyelonephritis, was hypertensive. Isolated microscopic haematuria persisted in 1 grade-2 and 2 grade-3 subjects. One grade-2 subject had proteinuria secondary to MCGN and one grade-3 subject had mild proteinuria and borderline hypertension. Although 20% of subjects had urinary abnormalities, we conclude that the long-term outcome of PSGN in children is excellent.

Adolescent↗

Renal disease and vasculitis.

Vasculitis is rare in childhood, apart from Henoch-Schönlein purpura, and paediatric nephrologists see few cases of Wegener's granuloma or microscopic polyarteritis. In contrast, this pattern is reversed in adults. Recently much information about the presentation and longer-term course of both these conditions has been described in adults, and more aggressive treatment of severe cases with renal failure has improved the outlook from a 5-year survival of about 5%-80% or more. In parallel, it has become evident that the abundant immune complexes in the circulation of patients with vasculitis may play little or no role in the pathogenesis of the vasculitic lesions. Current interest centres both on the possible role of cell-mediated immunity and the recent finding of antibodies which react with antigens in the cytoplasm of leucocytes. These antibodies seem to be of clinical use in defining patients with vasculitis, especially when only the kidney is involved at a clinical level. The nature of this leucocyte antigen (or antigens) and the possible role of antibodies directed against them in the pathogenesis of the disease are subjects of current work in many laboratories.

Antineoplastic Agents↗