Immunological properties of subcellular rat lymphocyte preparations. Primary allogeneic stimulation in vitro by fractions containing Ia (RT1-B), but not RT1-A antigens.

Rat thymocyte membrane fractions have been prepared which exhibit strain-specific primary mixed-lymphocyte reaction (MLR)-stimulating and Ia (RT1-B) antigenic properties. These preparations lack the antigenicity of classical, serologically-defined RT1-A (Ag-B) antigens, as defined by in vitro serologic assays. Furthermore, after immunization of allogeneic hosts, specific anti-Ia and MLR-blocking antibodies, but not anti-AgB, alloantibodies are elaborated. Thymidine suicide experiments show that the same clones respond to whole cells and the fragments made from those cells, and the response segregates appropriately in F2 progeny as a major histocompatibility complex (RT1)-linked phenomenon. Hence, it is possible to generate Ia-related allogeneic helper signals in primary, as well as secondary, in vitro responses, using subcellular membrane fragments that have restricted expression of RT1-B-, but not RT1-A-, encoded antigens.

Cyclosporin A spares selectively lymphocytes with donor-specific suppressor characteristics.

The effect of cyclosporin A (Cy A) on the host responses to heart allografts have been examined in rats following administration of the drug for 7 days after grafting. All grafts functioned greater than 100 days without rejection episodes in animals of major histocompatibility differences. Thymic or splenic lymphocytes (1 X 10(8) from LEW recipients of (LEW X BN)F1 hearts were transferred at varying periods into untreated LEW rats transplanted with (LEW X BN)F1 test hearts 24 hr later. Test grafts survived 12 to 16 days significantly (P less than 0.001) longer than in untreated animals (MST +/- SD = 7 +/- 0.3 days). Cells from normal LEW animals, Cy A-treated but ungrafted, and grafted but not treated animals, all failed to prolong test graft survival. Specificity of the effect was tested in vivo, using hearts from donor and third-party rats, and in vitro, using the mixed lymphocyte response (MLR). In vivo, thymocytes from treated LEW recipients of (LEW X WF)F1 grafts failed to prolong (LEW X BN)F1 test grafts; conversely, transferred thymocytes from LEW recipients of LEW X BN)F1 grafts failed to prolong (LEW X WF)F1 grafts. The MLR of lymphocytes from Cy A-treated rats was significantly decreased against donor lymphocytes but not against third-party lymphocytes. Additionally, both cellular and humoral immunity mounted by Cy A-treated recipients was depressed throughout the entire follow-up period. Prolonged heart graft survival after 7 days of Cy A treatment suggests emergence of cells with specific suppressor activity, which in turn may cause profound abrogation of host effector responses against vascularized organ allografts.

Percutaneous subclavian vein catheter hemodialysis--impact on vascular access surgery.

The problem of the immediate need for access to the circulation for hemodialysis arises because of an acute renal failure (ARF), the failure of an established access route, or the acute presentation of end-stage renal disease. Prior to 1976 emergent hemodialysis at our center necessitated either surgical placement of an external shunt or intermittent femoral vein cannulization, Since 1976 indwelling percutaneous subclavian vein catheterization (SVC) has been used on a routine basis for emergency hemodialysis. We have evaluated retrospectively the clinical courses of 50 patients with ARF and 48 patients with chronic renal failure (CRF) who underwent SVC dialysis in comparison with the clinical courses of 50 patients with ARF and 35 patients with CRF who had external shunt dialysis. In the ARF group, SVC dialysis resulted in lower incidences of serious infection, hemorrhage, and access thrombosis and reduced the number of replacement access procedures needed. In the CRF group, SVC permitted creation of more autogenous fistulas, rarely failed because of infection or thrombosis, and could therefore be used for extended periods, allowing primary autogenous fistula placement and maturation. Future access sites were also saved. SVC dialysis has become our primary interval angioaccess procedure for acute hemodialysis.

Acute abdominal events and their impact on morbidity and mortality in a CAPD program.

A retrospective analysis was done to explore the impact of acute abdominal events other than peritonitis, on morbidity and mortality in a CAPD program over a span of 6 years. Subtlety of clinical manifestations and low yield from investigational attempts (except microbiologic) made decision-making as to whether or not to continue CAPD, hard. An increased prevalence of septicemic shock with its inevitable high risk of morbidity and mortality was striking. Timely termination of CAPD and change over to hemodialysis may help to prevent dissemination of infection in these patients. Among the vascular causes of death in CAPD patients, bowel infarction seemed to be the most common.

A comparison of continuous ambulatory peritoneal dialysis in diabetic and nondiabetic patients.

Between May of 1978 and December of 1980 we have treated 33 patients with continuous ambulatory peritoneal dialysis (CAPD) for a total of 1209 patient weeks. Thirteen patients were diabetic, 14 nondiabetic but with complications that made CAPD the treatment of choice, and six were nondiabetic without complications. Good control of plasma glucose was obtained n diabetics by the use of intraperitoneal insulin. Overall plasma glucose control, as estimated by glycohemoglobin and fasting plasma glucose levels was the same in both groups. Plasma triglyceride levels were normal in most of the diabetic patients and elevated in most of te nondiabetic patients. Visual difficulties did not prevent self-dialysis in seven diabetic patients who were legally blind, and these patients spent the least time in hospital and had the least peritonitis. Diabetic patients seem at least as able to cope with CAPD as nondiabetic patients and may derive some special advantages from the technique.

Mechanism of D-cycloserine action: transport systems for D-alanine, D-cycloserine, L-alanine, and glycine.

The accumulation of d-alanine, l-alanine, glycine, and d-cycloserine in Escherichia coli was found to be mediated by at least two transport systems. The systems for d-alanine and glycine are related, and are separate from that involved in the accumulation of l-alanine. d-Cycloserine appears to be primarily transported by the d-alanine-glycine system. The accumulation of d-alanine, glycine, and d-cycloserine was characterized by two line segments in the Lineweaver-Burk analysis, whereas the accumulation of l-alanine was characterized by a single line segment. d-Cycloserine was an effective inhibitor of glycine and d-alanine accumulation, and l-cycloserine was an effective inhibitor of l-alanine transport. The systems were further differentiated by effects of azide, enhancement under various growth conditions, and additional inhibitor studies. Since the primary access of d-cycloserine in E. coli is via the d-alanine-glycine system, glycine might be expected to be a better antagonist of d-cycloserine inhibition than l-alanine. Glycine and d-alanine at 10(-5)m antagonized the effect of d-cycloserine in E. coli, whereas this concentration of l-alanine had no effect.

Fatal cytomegalovirus infection and coronary arterial thromboses after heart transplantation: a case report.

A 36-year-old woman died because of disseminated cytomegalovirus infection after a heart allograft transplantation was performed. Autopsy revealed that widespread coronary arterial thromboses were associated with cytomegalovirus infection of endothelial cells. Its possible pathogenetic mechanism and significance were discussed.

Bridging circulatory support before heart transplant without invasion of the mediastinum.

Heart transplantation is becoming a useful tool in the clinical treatment of patients with end-stage cardiac decompensation. Donor organs are not always available at a critical time for a patient waiting for a transplant. Bridging techniques have been described that use mechanical support systems. This article describes the use of femoral-venous to femoral-arterial bypass over a period of 50 hours in a 38-year-old woman waiting for a donor heart. Because the patient sustained cardiopulmonary arrest before organ availability, mechanical circulatory support that used femoral-venous to femoral-arterial bypass was instituted. The patient's own lungs were used as an oxygenator. Pump flow levels were determined by the level of central aortic oxygen saturation. Successful transplant was performed, and bridging, therefore, was done without invasion of the mediastinum.

Effects of recombinant human erythropoietin on renal function in chronic renal failure predialysis patients.

A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.