PubMed HealthSearch

Biomedical subjects

C S Ogg

Publications and source records attributed to C S Ogg.

At least 19 recordsLinked to original sources

Peritoneal drainage: an important element in host defence against staphylococcal peritonitis in patients on CAPD.

The growth of Staphylococcus aureus and coagulase-negative staphylococci were studied in fresh and effluent peritoneal dialysate from patients on continuous ambulatory peritoneal dialysis (CAPD). Peritoneal drainage during CAPD removes bacterial contaminants from the peritoneal cavity with an efficiency that depends upon the volume of peritoneal fluid remaining after drainage (residual volume). Combination of our data on the growth of coagulase-negative staphylococci in dialysate with a mathematical model of peritoneal drainage during CAPD shows that a residual volume of less than 800 ml (normal = approximately 400 ml) will prevent survival in the peritoneal fluid. A residual volume of less than 200 ml is required to eliminate S. aureus because of its faster rate of growth in dialysate. Previous work has shown that numbers of macrophages are too few to influence bacterial growth in the peritoneal dialysate. Coagulase-negative staphylococci adhere poorly to mesothelial cells in culture. Survival within the peritoneal cavity during CAPD probably depends on colonization of the PD catheter. Coagulase-negative staphylococcal peritonitis is likely to be localized to areas of the peritoneal membrane in close contact with the PD catheter. S. aureus is able to multiply in the peritoneal dialysate during CAPD and thereby causes generalized peritonitis.

Drainage

Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease.

This paper reports investigations in a young woman with renal disease and six other seemingly healthy young members of a new kindred (four male:two female) with familial juvenile gouty nephropathy (McKusick 16200). The family had previously been known to have a "familial" renal disease, but came to attention through an isolated episode of gout in the propositus when renal function was already impaired. A reduced GFR was found in three of the other six subjects. Hyperuricemia associated with a grossly reduced fractional uric acid clearance (Cur/Ccr x 100) was present in the propositus and five kindred members, three of whom were children. The finding of this abnormality in two subjects with normal GFR suggests that this apparent hallmark of the disease precedes the onset of renal damage. The results confirm the dominant nature of the disorder, and highlight the need to investigate all kindred members of patients with juvenile gout and renal failure. Early recognition is important, since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion.

Adolescent

Peritoneal defence mechanisms and Staphylococcus aureus in patients treated with continuous ambulatory peritoneal dialysis (CAPD).

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients due to S. aureus is associated with an adverse clinical outcome, suggesting impaired clearance of this organism by the host. The ability of peritoneal macrophages (PM0) derived from CAPD patients to take up S. aureus and mount a respiratory burst was investigated. Whilst significant activity was observed in the absence of opsonin, both parameters of phagocytosis were augmented by addition of 20% pooled human serum (PHS), complement-depleted PHS, and fibronectin. When used as sole opsonin, fibronectin resulted in a dose-related increase in chemiluminescent response by both blood neutrophils and PM0. The opsonic activity of dialysis effluent, as judged by neutrophil chemiluminescence, correlated with IgG and fibronectin content, but not with complement as assessed by C3 levels. The addition of urokinase to dialysate improved its opsonic properties whilst having no effect on the activity of PHS-20%; this would suggest that the formation of fibrin in dialysate, promoted by S. aureus, interferes with phagocytosis. This and the low IgG, complement and fibronectin levels in dialysate may explain in part the relatively poor clearance of this organism from the peritoneum.

Dialysis Solutions

Activation of immunocompetent cells in the peritoneum of patients treated with CAPD.

Chemiluminescence and flow cytometry, employing a number of monoclonal antibodies, was used to investigate activation of immunocompetent cells in the blood and peritoneum of patients treated with CAPD. Increased expression of HLA-DR and RFD7, both markers of macrophage maturation, was observed on peritoneal macrophages, 78% and 33.5% cells positive, when compared to blood monocytes, which were 46% and 5.3%, respectively (P less than 0.001). Macrophage chemiluminescent response to opsonized zymosan was greater than that of circulating blood monocytes in CAPD patients, whereas the inverse was true for normal controls. Enhanced expression of IL-2 receptor and surface IgG by peritoneal macrophages were 24.9% and 65.3% cells positive compared with monocytes, 5.7% and 12.3% (P less than 0.01), and also suggests their activation. There was a marked increase in the HLA-DR expression by peritoneal lymphocytes from CAPD patients (32% cells positive) compared with those from CAPD blood (13.8%), normal blood (11.3%) and normal peritoneal fluid (14.5%), P less than 0.001. This was partially accounted for by increased numbers of B cells (18%) and activated T cells bearing HLA-DR. TFR and IL-2 receptor expression by CAPD peritoneal lymphocytes was similar to that of blood lymphocytes, implying the lack of an organized immune response within the peritoneum. Taken together, these results suggest that peritoneal macrophages from CAPD treated patients have features of maturation and activation, while changes in the lymphocyte populations are compatable with the actions of IL-1, indicating activity of the cellular immune system within the peritoneum.

B-Lymphocytes

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

Improved prognosis of renal microscopic polyarteritis in recent years.

To determine if the short- and long-term prognosis of renal micropolyarteritis (including Wegener's granulomatosis) had improved in our Unit in the last 5 years compared to our previous series from 1965 to 1980, we examined data from 26 recent patients, 1981-1986. Twenty were admitted during acute phase and six after a mean of 7.1 months of disease. The acute phase showed mild to severe impairment of renal function, and renal biopsies showed necrotising glomerulitis in all acute patients with extensive crescents in 67%. Acute patients (20) were treated with 'aggressive' immunosuppression including i.v. methylprednisolone (15), plasmapheresis (seven) and cyclophosphamide (ten). Chronic immunosuppressive treatment was continued in most patients. In the 20 acute-onset patients, life survival at 2 and 5 years was 77%; four of five deaths occurred during the acute phase in aged patients with severe renal failure. The notable improvement in life and kidney survival (only one patient underwent chronic dialysis) probably resulted from greater awareness of vasculitis in general practice with early referral of patients to specialised units, and to more aggressive treatment.

Acute Disease

Diabetogenic effect of cyclosporin.

A young woman given a renal allograft for polycystic kidney disease developed insulin dependent diabetes mellitus 25 days after transplantation. There was no family history of diabetes, plasma glucose concentrations had been normal at presentation and on five subsequent occasions, and at no time were islet cell antibodies detectable. Plasma C peptide concentrations, however, were greatly suppressed after transplantation and remained so for up to six months. The immunosuppressive regimen had included cyclosporin A, which had been difficult to regulate and caused definite signs of toxicity in the patient. By virtue of its reported toxicity for beta cells and the reversal of the diabetes several months after the dose was reduced cyclosporin was incriminated as the probable causative agent. Dose related beta cell toxicity of cyclosporin A may be a risk in recipients of this drug and warrants careful monitoring of drug and glucose concentrations.

Adolescent

Histopathological changes in cyclosporin-treated renal allografts biopsied at one and twelve months.

Forty-four renal allograft recipients were biopsied routinely one month and one year after transplantation. All patients received cyclosporin and prednisolone. Fifteen patients had at least one rejection episode, while 29 patients never underwent rejection. At one year there were no specific histological features that enabled these two groups to be distinguished. Between one month and one year, interstitial cellular infiltrate and vascular pathology regressed, and renal function steadily improved. Interstitial fibrosis, however, was either unchanged or mildly increased in all patients. There was no correlation between the amount of interstitial fibrosis at one year and either the total dose of cyclosporin or the mean concentration during the first 3 months. Our results suggest that trough, whole blood cyclosporin concentrations, at the upper level of the therapeutic range (800-200 ng/ml), may be safely tolerated during the first 3 months, with little evidence of chronic damage at one year. At one year maintenance doses of cyclosporin can be achieved that are associated with almost normal plasma creatinine concentrations and minimal tubular atrophy and interstitial fibrosis. We expect that such doses may be continued indefinitely.

Adolescent

Clinical and immunological evolution of oligoanuric anti-GBM nephritis treated by haemodialysis.

Eight patients with oligoanuric anti-glomerular-basement-membrane (GBM), antibody-mediated glomerulonephritis without lung haemorrhage who were not treated with plasma exchange therapy were reviewed. All had severe crescentic nephritis and required dialysis. Circulating anti-GBM antibodies disappeared gradually and spontaneously in all patients. The autoantibodies became undetectable in five patients after an average of 11 months. No patient recovered renal function. Two patients have been successfully transplanted and anti-GBM nephritis has not recurred. One of these needed a pre-transplant course of plasma exchange and immunosuppression to reduce a slightly raised anti-GBM antibody titre. Of five patients who remain on dialysis, only two cannot be transplanted due to the persistence of circulating autoantibodies. One patient died from causes unrelated to renal disease. Oligoanuric patients with anti-GBM nephritis who need dialysis rarely benefit from aggressive therapy unless lung haemorrhage is present.

Acute Disease