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Biomedical subjects

S R Smith

Publications and source records attributed to S R Smith.

At least 145 records · Page 8Linked to original sources
PubMed1996

Clinical, biochemical and pathological predictors of poor response to intravenous cyclophosphamide in patients with proliferative lupus nephritis.

BACKGROUND: Reports in the literature on the outcome of lupus nephritis (LN) treated with intravenous (i.v.) cyclophosphamide have varied considerably. Previous studies have suggested that less than 25% of patients with LN will progress to end stage renal failure (ESRD) after 5 years. In addition it has been reported that serum creatinine and chronic histologic changes on kidney biopsy are useful markers of renal prognosis. Whether treatment with cyclophosphamide alters the predictive value of these markers in LN patients is not clear. The aim of this study was to review our experience of treating a large cohort of patients with LN treated with i.v. cyclophosphamide and to identify biochemical and histological features at the time renal biopsy which predict outcome in these patients. DESIGN: We retrospectively reviewed our experience with 43 consecutive patients who met criteria for either World Health Organization (WHO) classification III (focal proliferative) or IV (diffuse proliferative) LN and were treated with monthly i.v. cyclophosphamide. Biochemical indices of renal function and lupus disease activity were recorded. Renal biopsies, performed within two months of commencing therapy, were reviewed by two experienced pathologists and classified according to WHO classification as well as activity and chronicity index. The primary outcome variable for the analysis was the development of ESRD. RESULTS: Patients were followed for a mean of 2 years after renal biopsy. The mean dose of cyclophosphamide received by patients was 8.3 g. One patient died during follow up and 22 (51%) progressed to ESRD. A higher serum creatinine (p = 0.003) and higher score for interstitial fibrosis (p = 0.001) were associated with shorter renal survival. There was no significant association between activity index or its components or in the total chronicity score and survival free from the need for dialysis. CONCLUSION: In our experience more than half of patients treated with i.v. cyclophosphamide for LN progress to ESRD and a high serum Cr and a high degree of interstitial fibrosis on renal biopsy before treatment are associated with a worse renal prognosis.

Adult↗
PubMed1996

Renal transplantation in adults with thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome.

BACKGROUND: Thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome (TTP/HUS) is a rare cause of renal failure in adults. There is little data concerning the outcome of adult patients who receive a renal transplant for TTP/HUS: METHODS: We have carried out a survey of 22 transplant centres in the USA to determine the outcome of patients who developed ESRD from TTP/HUS and latter received a renal transplant. RESULTS: Twelve of the 22 centres responded to our inquiry. Seven centres had not transplanted any patients with TTP/HUS, and five centres had transplanted a total of 24 grafts in 17 patients with TTP/HUS: Thirty-three per cent of patients demonstrated definite clinical and pathological evidence of recurrence of TTP/HUS: An additional 16% of patients demonstrated pathological evidence of possible recurrence of TTP/HUS in the absence of clinical manifestations. The overall 1-year graft survival rate was 42% and the 2-year graft survival rate was 35%. In our experience recurrence TTP/HUS was associated with universal graft failure. Although cyclosporin A does occasionally cause a thrombotic angiopathy in patients with no history of TTP/HUS, we found no evidence that it should be avoided in patients with a previous history of ESRD from TTP/HUS who subsequently receive a renal transplant. CONCLUSIONS: TTP/HUS frequently recurres in adults who receive a renal transplant, with a 2-year graft survival rate of 35%.

Adult↗
PubMed1995

Inhibitory effects of recombinant human interleukin 10 on disease manifestations in a P-->F1 model of acute graft versus host disease.

Interleukin 10 (IL-10) is a cytokine with both antiinflammatory and immunosuppressive properties. In the present study, we have examined the effects of recombinant human IL-10 (rHuIL-10) on the development of acute graft-vs.-host disease (GVHD) in unirradiated (C57B1/6JxA/J) F1 recipients of parental A/J lymphocytes. rHuIL-10 (2.5 to 100 micrograms/mouse administered subcutaneously) caused a significant reduction in splenomegaly in GVH mice. GVH splenocytes exhibited an augmented capacity to produce IFN-gamma when stimulated in culture with Con A or LPS. The IFN gamma produced in response to LPS stimulation was found to be derived from CD4+ and CD8+ T cells with little or no contribution from the NK1.1+ subpopulation of the GVH spleen. Treatment with IL-10 in vivo was found to diminish the capacity of splenocytes to produce IFN gamma when stimulated with LPS but not with Con A. IL-10 did not protect GVH mice from a lethal dose of LPS but caused a marked reduction in the serum TNF alpha response triggered by the LPS challenge. We conclude that IL-10 may be useful in controlling those clinical manifestations of acute GVHD that arise as a result of the activities of proinflammatory cytokines such as IFN gamma and TNF alpha.

Animals↗
PubMed1995

Staphylococcal enterotoxin B and tumor-necrosis factor-alpha-induced relapses of experimental allergic encephalomyelitis: protection by transforming growth factor-beta and interleukin-10.

A study was made of the ability of the superantigen staphylococcal enterotoxin B (SEB) to induce relapses of experimental allergic encephalomyelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.v. induces mild relapses in 50% of such mice. In addition, tumor necrosis factor (TNF)-alpha (0.2 micrograms, i.p.) also induces EAE relapses in 43% of SJL mice when injected 1-2 months after recovery. SEB does not induce a second relapse if reinjected when V beta 17a+T cells are still partially deleted. In these mice, however, TNF-alpha is equally effective in inducing relapses as in mice that did not receive SEB previously. We showed earlier that transforming growth factor (TGF)-beta and TNF-alpha have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF-beta and anti-TNF were protective, while anti-TGF-beta caused disease exacerbation. Interleukin (IL)-10 is also known to counteract certain TNF effects. We now find that both human IL-10 and TGF-beta 2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF-alpha. The protective effect of TGF-beta is significant only against relapses induced by SEB (reduced to 9%), and that of IL-10 only against relapses induced by TNF (reduced to 0%) with the treatment regimens employed. Neutralizing anti-TGF-beta does not increase the incidence of SEB-induced EAE relapses. In contrast, anti-IL-10 increases both the incidence and the severity of such relapses. We conclude that TNF production is probably important in causing EAE relapses, but that other aspects of the SEB-induced reactivation of myelin-specific T cells also contribute. Furthermore, endogenous IL-10 rather than TGF-beta production appears to limit the susceptibility to induction of EAE relapses in this model.

Animals↗
PubMed1995

T cells are necessary for Th2 cytokine production and eosinophil accumulation in airways of antigen-challenged allergic mice.

In a murine model of pulmonary inflammation, aerosolized antigen challenge of sensitized B6D2F1 mice leads to eosinophil accumulation within the lungs. Little is known of the role of T cells and their cytokine products in these allergic animals. In this study, we show that T cells migrate into the lungs in response to antigen challenge and are necessary for local production of cytokines (IL-4 and IL-5) important in B and T cell development as well as eosinophil activation and differentiation. Flow cytometry revealed an increase in the percentage of Thy1+ T cells but not in B220+ B cells in bronchoalveolar lavage fluid after challenge when compared to unchallenged mice. Although there was an increase in both T cell subsets, there were twice as many CD4+ cells as CD8+ cells at 24 hr and after 48 hr the CD4+ subset predominated. The CD4+ T lymphocytes were CD44+ CD45RBlo indicating an activated/memory phenotype and tracheobroncheal lymph node cells obtained from challenged mice proliferated in a dose-dependent manner in response to antigen stimulation in vitro. Reverse transcriptase-polymerase chain reaction analysis of lung tissue-derived RNA indicated an increase in Th2-like cytokines. IL-4 and IL-5 steady-state mRNAs were at peak levels 6 hr after challenge, while no consistent increase was found for IFN-gamma mRNA levels. Treatment with the glucocorticoid betamethasone just prior to challenge reduced the levels of cytokine mRNA as well as the eosinophil influx. In vivo depletion of T cells from sensitized mice reduced pulmonary eosinophilia as well as the expression of IL-4, IL-5, and IFN-gamma steady-state mRNAs in the lungs of sensitized and challenged mice. These results indicate that T cells migrating into the lungs of mice after antigen challenge play an important role in the production of Th2-like cytokines and the accumulation of eosinophils in bronchial fluids.

Animals↗
PubMed1995

Late withdrawal of cyclosporine in stable renal transplant recipients.

The use of cyclosporine (CsA) in renal transplantation has been associated with an improvement in 1-year graft survival, but has not changed the rate of late graft loss. We sought to determine whether the intent to withdraw CsA late after renal transplantation affects renal transplant survival and whether there is a racial difference in the effect of CsA withdrawal. This retrospective study included 384 consecutive patients receiving a renal transplant during the 1984 to 1991 period who were treated with CsA/azathioprine/prednisone and who had a functioning allograft 6 months following transplantation. Of these, 97 were electively withdrawn from CsA at a median of 22 months following transplantation. Factors significantly associated with the decision to withdraw CsA included white race, older age, and lower serum creatinine. Acute rejection within 6 months of stopping CsA occurred in 12 patients (12.4%), including nine of 78 (11.5%) white patients and three of 19 (15.8%) black patients. For the group of 287 patients who were not withdrawn from CsA, the 6-year graft survival rate was 59% (95% confidence interval, 52%, 66%). For the group of patients taken off of CsA, the 6-year graft survival rate was 84% (95% confidence interval, 76%, 92%). Cox proportional hazard survival analysis indicated that the intent to discontinue CsA was associated with better graft survival, with a hazard ratio of 0.37 (95% confidence interval, 0.20, 0.70), independent of other variables that may affect graft survival. A separate analysis controlling for waiting time bias also favored the CsA withdrawal group. There was no detectable racial difference in the effect of CsA withdrawal on graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Spinal stabilisation in plasma cell disorders.

Five patients with plasma cell disorders and vertebral body lesions who presented with severe localised back pain associated with spinal instability are described. They underwent a total of six surgical spinal stabilisation procedures with excellent symptomatic relief. Spinal stabilisation was performed at presentation in 1 patient with a cervical spine lesion, and at sites of previously irradiated disease or recurrent disease in the other 4 patients. Stabilisation was achieved using various internal fixation techniques, and in 2 cases external fixation was obtained with a halo brace. The procedures were performed with minimal operative morbidity, and resulted in good symptom control. Spinal instability should be considered as a cause of severe localised back pain exacerbated by movement in patients with plasma cell disorders and vertebral body lesions. Operative spinal stabilisation should be considered as part of their management.

Aged↗
PubMed1995

Longstanding proliferation of CD3 negative large granular lymphocytes preceding the development of high grade non-Hodgkin's lymphoma.

A patient with a persistent CD3 negative large granular lymphocyte (LGL) proliferation with immunophenotypic and functional characteristics of natural killer cells is described. The LGL proliferation persisted and six years after diagnosis the patient developed a high grade B cell non-Hodgkin's lymphoma. Molecular studies demonstrated clonal B cell populations in the peripheral blood, distinct from that identified in the lymphoma, both at presentation with non-Hodgkin's lymphoma and at complete remission following combination chemotherapy. It is postulated that T cell dysregulation associated with the CD3 negative LGL proliferation may have led to B cell dysfunction and loss of normal B cell control, with the subsequent development of a clonal B cell lymphoproliferative disorder.

Adult↗
PubMed1995

Transmission of cancer with cadaveric donor organs.

A case is presented in which each of the recipients of a pair of cadaveric kidneys developed metastatic carcinoma. One of the recipients died, and the other demonstrated involution of metastatic deposits after graft nephrectomy and withdrawal of immunosuppression. By the use of polymerase chain reaction of minisatellite regions of donor and recipient DNA, the donor origin of the tumor was conclusively demonstrated. Although a relatively uncommon complication of cadaveric renal transplantation, the transmission of cancer with cadaveric organs may become more frequent as older donors are accepted for organ donation.

Adult↗
PubMed1995

The renal manifestations and outcome of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in adults.

Thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome (TTP/HUS) is generally regarded to be a rare disease. The present study was undertaken to identify presenting features, prognostic variables, pathological features and outcome associated with TTP/HUS. The present study is a retrospective chart review of 68 patients treated with plasmapheresis for TTP/HUS at a single tertiary referral medical institution from 1980-1992. The annual number of patients with TTP/HUS treated with plasmapheresis increased from an average of one case per year in 1980 to nine cases per a year in 1992. The in-hospital mortality for patients presenting with TTP/HUS was 25%. Forty four percent of patients presented with an elevated serum creatinine, and 16% required hemodialysis support. Of the seven patients who survived and required hemodialysis support only two patients continued on dialysis. None of the patients presenting with a normal serum creatinine required dialysis at any time in their course. Patient age, sex, presenting platelet count, white blood cell count, hemoglobin level and presence of neurological disease were not significantly associated with death or need for dialysis. The histopathological features of TTP/HUS (fibrin/platelet thrombi in renal vessels and glomeruli, fibrinoid necrosis of vessel walls) were found in all five cases autopsied. The incidence of TTP/HUS may be increasing. Alternative possibilities for the increased frequency of cases seen include greater diagnostic suspicion and referral bias. Despite the use of plasmapheresis, mortality during the initial hospital admission was almost 25%. In retrospect prognosis could not be predicted based on admission biochemical or clinical variables. The majority of patients who developed acute renal failure and survived to hospital discharge recovered renal function and became independent of dialysis.

Adult↗
PubMed1995

The Occupational Health Partnership Program: a new paradigm for occupational health services.

For a variety of reasons, occupational health services at Army Material Command installations became severely strained during the 1980s. The Occupational Health Partnership Program, developed to improve this support, describes control, responsibility, and cost sharing between Army Materiel Command and Army Medical Command. This innovative approach is finding new solutions to challenging problems. The authors describe the history, principles, status, and possible future of the partnership program.

Health Plan Implementation↗