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Biomedical subjects

R C Atkins

Publications and source records attributed to R C Atkins.

At least 235 records · Page 13Linked to original sources

The effect of maintenance dialysis on lymphocyte function. II. Peritoneal dialysis.

Lymphocyte function, as assessed by PHA-stimulated DNA synthesis, was studied in chronic renal failure patients maintained by peritoneal dialysis. In contrast to patients on haemodialysis, peritoneal dialysis patients had normal lymphocyte responsiveness pre-dialysis. There was no deterioration in the post-peritoneal dialysis plasma's ability to support control lymphocyte responsiveness as occurred after haemodialysis. Plasma dilution and reconstitution studies indicated that haemodialysis depleted the patients' plasma of nutrients and also added toxins, but peritoneal dialysis had neither effect.

Adult↗

The effect of maintenance dialysis on lymphocyte function. I. Haemodialysis.

The effect of haemodialysis on mitogen-stimulated lymphocyte DNA synthesis was determined in twenty-four uraemic patients. Lymphocytes pre-haemodialysis were significantly less responsive to phytohaemagglutinin (PHA) than were control lymphocytes and showed the same degree of impairment as uraemic lymphocytes. Intrinsic lymphocyte responsiveness improved immediately after each haemodialysis. Pre-haemodialysis plasma inhibited control lymphocyte responsiveness and this inhibition was even greater in post-haemodialysis plasma. This effect of haemodialysis on plasma lasted for 4--8 hr. Similar alterations of response were noted, despite the use of different dialysers and also when two other mitogens were substituted for PHA. This deleterious effect of haemodialysis on lymphocyte function is important for its possible immune consequences, and may indicate a deficiency in current haemodialysis technique.

Adult↗

Reversible acute renal failure in the nephrotic syndrome with minimal glomerular pathology.

A case of minimal change glomerulonephritis, associated with the nephrotic syndrome and prolonged acute renal failure requiring two months of dialysis, is reported. Complete recovery of renal function occurred, but proteinuria recurred, responding to a course of steroids. Normal renal function without proteinuria has been observed for two years subsequently. The full return of renal function without specific therapy demonstrates that spontaneous recovery is possible in this rare complication of minimal change glomerulonephritis.

Acute Disease↗

Preservation of cadaver of renal allografts: comparison of ice storage and machine perfusion.

Preservation of cadaveric renal allografts by ice storage and by machine perfusion after a preliminary flush with a hypertonic citrate solution has been compared in a prospective clinical trial between matched pairs of kidneys from the same cadaver donor. Over a two-year period, ice storage after flushing with the new solution gave results comparable with machine perfusion. Times of warm ischaemia and total times of storage were similar in ice-stored and machine-perfused kidneys and averaged about 16 hours. In each group of recipients, more than half of the kidneys had good early function and one-year survival times were also similar.

Cadaver↗

The pituitary-testicular axis in men with chronic renal failure.

We studied the effects of uremia on the pituitary-testicular axis in 35 men with creatinine clearances less than 4 ml per minute per 1.7m(2). We found significant elevation (p less than 0.001) of plasma luteinizing hormone and follicle-stimulating hormone (p less than 0.005) and subnormal levels of testosterone (p less than 0.005). Testicular histology revealed severe spermatogenic damage. Human chorionic gonadotropin produced a subnormal testosterone response. The initial response of plasma luteinizing hormone and follicle-stimulating hormone to luteinizing-hormone-releasing hormone was normal, but their subsequent decline was prolonged. The suppression of plasma luteinizing hormone levels by testosterone propionate was normal, but the nadir occurred late; the elevated plasma luteinizing hormone level was due to reduced metabolic clearnace and increased production. Chronic renal failure interferes with testicular steroid production and spermatogenesis.

Adolescent↗

Preservation of cadaveric renal allografts-comparison of flushing and pumping techniques.

A prospective clinical trial comparing flushing and ice storage using a new hypertonic citrate solution, with machine preservation by continuous perfusion showed early graft function was similar with each method, and preservation times were comparable. Good early function occurred in half the grafts with preservation times up to 24 hours. Graft survival at three and 12 months was similar with each method of preservation. Graft survival at 12 months was worsened by poor early graft function, whereas patient survival at 12 months was unaffected by early function or by the method of preservation.

Cadaver↗

Prolonged antibiotic peritoneal lavage in the management of gross generalized peritonitis.

Since there is a high mortality and morbidity with conventional therapy in generalized peritonitis, a treatment regime of prolonged continuous peritoneal lavage (two to 10 days) with the lavage solution containing kanamycin (40 mug/ml) and cephalothin (100 mug/ml) was undertaken in 14 cases of gross, well established, diffuse peritonitis. Antibiotics were also given systemically. In 11 cases, in which the causative lesion was definitively repaired, no intraperitoneal complications developed and convalescence was rapid. Three patients, in whom causative lesion was not definitively repaired at operation, subsequently died. Prolonged antibiotic peritoneal lavage appears to be beneficial for patients with gross and diffuse peritoneal soiling, after the causative lesion has been repaired.

Adolescent↗

Radioimmunoassay as an improved method for measurement of serum levels of gentamicin.

A radioimmunoassay is described for the measurement of serum concentrations of gentamicin. This radioimmunoassay is more rapid, more specific and more accurate than microbiological assays. Knowledge of serum levels of gentamicin assists the clinician in regulating drug dosage to obtain an optimal therapeutic effect, and yet avoid toxic serum levels.

Animals↗

The macrophagen in human rapidly progressive glomerulonephritis.

Glomeruli from 18 "normal" patients and from 35 patients with glomerulonephritis have been maintained in tissue-culture and examined by time-lapse cinemicroscopy and electron microscopy. At least two distinct cell types with features of epithelial and mesangial cells emerge in the outgrowths from normal and non-crescentic glomeruli. 4 patients with rapidly progressive glomerulonephritis formed a distinct subgroup. Glomerular culture revealed that their crescents contained large numbers of macrophages. This suggests that, contrary to belief, the crescents in rapidly progressive glomerulonephritis consist of accumulated macrophages rather than proliferated epithelial cells.

Culture Techniques↗

Renal transplantation.

Kidney transplantation is now a very acceptable form of treatment of end-stage renal failure. About 50% of kidney grafts are still functioning after five years. If the kidney graft fails, and failure is usually due to rejection, patients are returned to dialysis for definitive treatment or to await another transplant. Although kidneys from living related donors offer the best chance of success, most kidneys in Australia are transplanted from cadavers. A shortage of cadaver kidneys necessitates a wait of 6 to 12 months for a transplant.

Adolescent↗

Systemic herpes simplex infection with fulminant hepatitis post-transplantation.

Immunosuppression for renal transplantation is associated with the risk of severe overwhelming infection with ubiquitous but normally relatively harmless micro-organisms. In recent years a number of adult cases of fatal hepatitis due to herpes simplex virus (HSV) infection have been reported. Nearly always immune deficiency was a significant factor. A case of fatal HSV infection with hepatitis following transplantation is reported. The case failed to respond to infusion with the antiviral agent cytosine arabinoside. The presentation, diagnosis and treatment of HSV fulminant hepatitis is discussed.

Adolescent↗

Immune and phagocytic function in patients on maintenance dialysis and post-transplantation.

Immune, phagocytic and opsonic function was assessed in stabilized hemodialysis patients and compared with patients on maintenance immunosuppression following successful renal transplantation. Dialysis patients had a lymphopenia and a qualitative defect in lymphocyte function but opsonic and neutrophil metabolic function was normal. Post-transplant patients had normal intrinsic lymphocyte function but overall immunosuppression due to lymphopenia, selective T cell depletion, and drug inhibition. Neutrophil metabolic function was normal though there was a defect in opsonization.

B-Lymphocytes↗

Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes.

A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a "third party" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex.

Animals↗

Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex.

A graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain (AO) lymphocytes into irradiated (AO times HO)F1 or (AO times DA)F1 hybrids. The proportion of donor T cells which had responded to the F1 hybrid antigens within 24 h was estimated by two methods. (a) Donor lymphocytes were labeled with [3H]uridine in vitro before injection. The proportion of labeled cells which had morphologically transformed in the recipient's spleen was 17-19%. In both series of experiments syngeneic transfers were performed in which case the proportion of transformed cells was 1-2.4%. A similar low proportion was found after parental to F1 transfer in a non-Ag-B strain combination. These figures were used to calculate the frequency of responding cells in the injected population given three additional pieces of information: (a) the extent of selection in the spleen which transformed the estimate to 4.5%-6.0% responders; (b) division of donor cells was shown to be negligible under the conditions of the experiment; and (c) the nonspecific recruitment of lymphocytes was shown to be negligible. A speculative model of antigen recognition by T cells which accounts for the high proportion of responders is outlined.

Animals↗

Management of Candida peritonitis by prolonged peritoneal lavage containing 5-fluorocytosine.

A 55 year old woman on chronic maintenance peritoneal dialysis developed Candida albicans peritonitis. This was successfully treated by continous five day peritoneal lavage containing 5-fluorocytosine. By this technique stable serum levels of the drug (58 mug/ml +/- 3.2 SEM) could be maintained. The peritoneal clearance of 5-fluorocytosine was found to be 7.5 ml/min (for peritoneal dialysis flow rate 1.2 1/hr) and the serum half-life 34 hours. The use of this drug in renal failure and its kinetics are reviewed.

Candidiasis↗

Ice storage versus perfusion for preservation of kidneys before transplantation.

The results of simple ice storage and prolonged perfusion storage of kidneys were compared in two series, each of 100 cadaver kidney transplants. There was a similar warm ischaemia time for both groups, but the average total storage time was 17 hours for the perfused kidneys as compared to three and a half hours for those stored in ice. The results of transplantation (as shown by transplant function at three and 12 months) were the same for both groups. There was no evidence of damage due to prolonged perfusion. The extra time, however, enabled a more convenient operation time to be chosen and more extensive tissue matching to be undertaken.

Dialysis↗