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Biomedical subjects

M R First

Publications and source records attributed to M R First.

At least 91 records · Page 5Linked to original sources
PubMed1996

Disseminated histoplasmosis in renal allograft recipients.

Histoplasmosis, an opportunistic fungal infection endemic in the Ohio and Mississippi river valleys, is caused by a dimorphic fungus Histoplasma capsulatum. Most infections are asymptomatic or self-limited febrile illness. Immunosuppressed renal transplant recipients are susceptible to a disseminated disease. We report 5 cases of disseminated histoplasmosis seen in our institute over a period of 25 years amongst 1074 renal transplant recipients. The duration of immunosuppression prior to the diagnosis of infection ranged from 84 days to 14 years. All patients had pulmonary involvement. Three patients received an antilymphocyte preparation and 1 patent received intravenous pulse steroids in the 3 months prior to the onset of infection. Histopathologic examination of the involved organ(s) provided rapid diagnostic information allowing early treatment with amphotericin B. All infections resolved with no relapses to date. In conclusion immunosuppressed patients are more prone to disseminated histoplasmosis. Early recognition and prompt treatment with amphotericin B resolved the infection without relapse.

Adult↗
PubMed1996

Outcome of cadaveric renal transplantation by induction treatment in the cyclosporine era.

A total of 358 cadaveric renal transplantations performed between 1984 and 1993 received induction therapy with Minnesota antilymphoblast globulin (MALG) 95, muromonab-CD3 (OKT3) 58, antithymocyte globulin--Upjohn (ATGAM) 104, rabbit antithymocyte serum (RATS) 37, or cyclosporine (CyA) 64. There were no differences in age, gender, HLA mismatches and maintenance immunosuppression between these groups of recipients. A significantly higher proportion of OKT3 induction patients were retransplants (50%, p < 0.0001). There were fewer diabetic recipients in the group that received RATS (8%) compared to the other groups (p = 0.0009). There was no significant difference in overall graft survival with the various forms of induction treatment (log rank test, p = 0.48). Similarly, primary cadaveric graft outcome was not different with various forms of induction treatment (p = 0.62). Acute rejection was higher with ATGAM, occurring in 65% of patients, compared to MALG (52%), OKT3 (55%), RATS (43%) and CyA (55%). A significantly lower number of patients were rejection-free with ATGAM (35%) compared to MALG (48%) (p = 0.04). Patients who received ATGAM induction also had a higher rate of rebound rejection. Patients receiving ATGAM induction had a significantly higher serum creatinine level at 1 and 6 months post-transplantation (p < 0.005) compared to other induction treatments. In conclusion, the prevalence of acute rejection was higher with ATGAM, which was also reflected by higher serum creatinine levels. However, the long-term graft function and survival were not different with the various induction treatments.

Adult↗
PubMed1996

Gastric bypass in morbidly obese kidney transplant recipients.

Severe post-transplant obesity has previously been shown to have a negative impact on graft survival following kidney transplantation. It also contributes to late patient mortality and is associated with hypertension, diabetes and hyperlipidemia. We undertook Roux-en-Y gastric bypass (GBP) in three morbidly obese (200-260% ideal body weight) (IBW) patients 6-8 yr following kidney transplantation. Roux-en-Y gastrojejunostomy to a 30 ml stapled gastric pouch was created with the jejunojejunostomy (both loops) 80-120 cm from the ligament of Treitz. By 12 months post-GBP, weight loss plateaued at 100-150% IBW. Both patients that had developed post-transplant diabetes mellitus (PTDM) had complete resolution within 9 months following GBP. On average the patients required 3 less hypertension (HTN) medications after GBP; 2 of the 3 patients are now normotensive off medication. Improvements in hyperlipidemia were also shown. The absolute cyclosporine (CsA) requirement (mg/d) increased by approximately 33% (p = NS), and there was also a significant increase in the weight adjusted CsA requirement from 1.8 to 3.5 mg/kg/d (p = 0.02, ANOVA) following GBP in order to maintain similar TDX trough CsA levels. GBP offers significant reduction in weight, HTN, PTDM and hyperlipidemia in morbidly obese kidney transplant recipients. However, CsA dose requirements may increase after GBP as a consequence of the defunctionalized intestine.

Adult↗
PubMed1996

Impact of first acute rejection episode and severity of rejection on cadaveric renal allograft survival.

A total of 504 renal transplants were performed between 1984 and 1993; 408 (81%) were cadaver grafts. This study evaluated the impact of a first acute rejection episode and the severity of the rejection on cadaveric allograft survival. Acute allograft rejection was based on clinical evaluation and confirmed by renal biopsy. Ten patients were excluded from this study due to early patient or graft loss. Patients were divided into Group I (n = 179), who never experienced acute rejection, and Group II (n = 219), who had an acute rejection episode. Group II patients were divided into IIA (n = 140), who had a mild first acute rejection episode treated with methylprednisolone, and IIB (n = 79), who had moderate or severe acute rejection treated with OKT3. The overall 1-, 2-, 3-, and 5-yr actuarial cadaveric renal allograft survival for Group I was 80%, 76%, 74%, and 68%. The corresponding graft survival for Groups IIA and IIB were 75%, 63%, 58%, and 50%; and 79% 71%, 65%, and 53% [p = 0.03 (I vs IIA), p = NS (I vs. IIB and IIA vs IIB)]. A similar pattern of survival was seen in primary kidney allograft recipients. In conclusion, long-term graft survival was superior in patients who never experienced acute rejection compared to those with rejection. Improvements in long-term graft survival can be accomplished in patients with severe rejection with OKT3 treatment resulting in comparable survival to those with mild rejection.

Actuarial Analysis↗
PubMed1995

Lack of effect of pregnancy on renal allograft survival or function.

To determine whether pregnancy had a long-term influence on the survival or function of renal allografts, a case-control study was conducted. Patients were selected from a pool of 915 patients transplanted at the University of Cincinnati from 1967 to 1990. The pregnancy group consisted of 18 women who became pregnant 3 months to 17 years after transplantation and who elected to continue pregnancy. There were 26 nonpregnant female controls, and 23 male control renal transplant recipients. Matching criteria were cause of end-stage renal disease (ESRD), donor source, age at transplantation, calendar year of transplantation, time from transplantation to pregnancy, and serum creatinine concentration at the time corresponding to conception. Matching was performed by one investigator, who had no knowledge of long-term outcome in any of the patients. The three groups were well-matched with regard to these criteria. Male controls had higher baseline creatinine clearances than pregnancy cases or female controls. During pregnancy, serum creatinine levels fell by 20%, and creatinine clearance rose by 53%. Immediately after pregnancy, these values returned to baseline. Graft survival, with a mean posttransplant follow-up of 11-12 years, was 77.8% in the pregnancy cases, 69.2% in the female controls, and 69.6% in the male controls. By life-table analysis, none of these differences was significant. Among surviving grafts, serum creatinine levels and creatinine clearances remained stable throughout the follow-up period. In this study, using well-matched male and nonpregnant female cohorts for comparison, pregnancy did not have an adverse long-term effect on renal allograft function or survival.

Adult↗
PubMed1995

Living-related donor transplants should be performed with caution in patients with focal segmental glomerulosclerosis.

The success rates of living-related donor (LRD) transplants are clearly superior to those obtained with cadaver donors. However, caution should be exercised when considering LRD transplantation for a condition which has an increased chance of recurring after transplantation and causing ultimate graft failure. The recurrence rate of focal segmental glomerulosclerosis (FSGS) in the allograft is 20%-40%, with graft failure resulting in 40%-50% of these cases. However, these figures may be an underestimation of the true rate of recurrence of FSGS. Once a first transplant fails due to recurrent disease, the risk of recurrence in the second transplant approaches 80%. Subgroups of patients at high risk for recurrence have been identified. In patients not at high risk for recurrent FSGS, the use of a LRD should be considered, provided that the donor and recipient and their families have been informed that the disease may recur and lead to graft failure. In patients at high risk for recurrence, a LRD transplant should be avoided. Hopefully, future development of a simple and reliable test to predict the likelihood of recurrence will enable us to counsel and advise our patients with FSGS about the wisdom or dangers of proceeding with a LRD transplant.

Child↗
PubMed1995

Optimizing the use of cyclosporine in renal transplantation.

OBJECTIVE: To review the existing data on the use of cyclosporine (CsA) in kidney transplantation, particularly with respect to therapeutic drug monitoring. DATA SOURCES: A literature search was conducted of applicable articles related to therapeutic drug monitoring of cyclosporine in renal transplantation. Previous consensus guidelines were examined. Discussions on issues related to this topic convened in Toronto, ON, on June 15-16, 1994. DATA SYNTHESIS: The literature was analyzed to examine patient factors and drug interactions affecting CsA concentrations, the effect of CsA concentrations on patient outcome, current methods of analysis, pharmacodynamic monitoring, and new immunosuppressants. CONCLUSIONS: CsA has improved the success of kidney transplantation, reducing the incidence and severity of acute rejection and improving short-term patient and graft survival. The rate of graft loss after the first year (primarily due to chronic rejection) has remained largely unchanged. Sandimmune Neoral offers promise due to its better bioavailability and limited dependence on bile flow for absorption. Long-term studies are underway to determine its effectiveness and safety. Indications for therapeutic drug monitoring for CsA are provided.

Cyclosporine↗
PubMed1995

Pregnancy in a combined liver and kidney transplant recipient with type 1 primary hyperoxaluria.

BACKGROUND: Little is known about pregnancy outcomes in multiple organ transplant recipients. We present a case of pregnancy in a patient after liver and kidney transplantation for the genetic disorder of type 1 primary hyperoxaluria. CASE: A 14-year-old Hispanic teenager presented with end-stage renal disease and had a kidney biopsy that revealed hyperoxaluria. A liver biopsy revealed type 1 primary hyperoxaluria. After a year of dialysis and worsening renal status, she underwent a combined orthotopic liver and kidney transplant. The patient subsequently became pregnant, but she required no antihypertensive therapy throughout the prenatal or postpartum period and showed no signs of renal or liver graft rejection. She delivered by cesarean at 38 weeks. CONCLUSION: Combined liver and kidney transplant recipients who become pregnant can have a successful outcome.

Adolescent↗
PubMed1994

Variations in serum OKT3 concentration based upon age, sex, transplanted organ, treatment regimen, and anti-OKT3 antibody status.

An essential parameter of the efficacy of OKT3 therapy is serial determinations of serum OKT3 levels. We hypothesized that precise monitoring of these levels would optimize treatment protocols. Therefore, enzyme-linked immunosorbent assay (ELISA) technology was utilized to measure OKT3 serum concentrations daily during 263 OKT3 treatment courses in recipients of solid organ grafts. Patient characteristics were: mean age 33 years (0.1-71), 147 male/116 female, 134 kidney/82 liver/47 heart, 122 prophylaxis/141 rejection, and 213 conventional dosing/50 increased dosing. Mean OKT3 levels were higher in women than in men at all time points from day 1 to day 14, reaching the greatest difference between groups on day 7 (849 versus 598 ng/ml, p = 0.004). Patients receiving OKT3 as a component of a prophylactic protocol had higher levels than those receiving the drug for treatment of rejection from day 1 to day 6, with the greatest difference between groups occurring on day 1 (678 versus 333 ng/ml, p < 0.00001). However, from day 7 to day 14 patients receiving OKT3 prophylactically had lower mean OKT3 levels than did those receiving OKT3 for rejection, with the greatest difference between groups occurring on day 11 (555 versus 784 ng/ml, p < 0.05). Liver transplant recipients had significantly higher OKT3 levels than did kidney or heart transplants at all time points. However, more liver patients required increased OKT3 doses to modulate peripheral blood CD3+ cells to < 25/mm3. Kidney recipients had higher levels than did heart recipients. Children < 10 years of age had higher OKT3 levels than did older patients at all time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Steroid-free immunosuppression after renal transplantation.

Concerns about the side effects of chronic steroid therapy have prompted increasing interest in steroid-free immunosuppression for renal transplant recipients who are maintained on cyclosporine-based regimens. Studies to date suggest that at least 50% of cyclosporine-treated patients can be managed without steroid therapy. Reported benefits of avoiding or withdrawing steroid therapy have included improvements in hyperlipidemia, hypertension, and glucose intolerance and accelerated growth in children. Whether these effects will increase patient or allograft survival remains to be proved. Furthermore, the benefits of steroid-free immunosuppression must be weighed against the risk of precipitating allograft rejection. Although the elimination of steroids clearly increases the short-term risk of acute rejection, further studies are needed to determine the effects of steroid-free immunosuppression on long-term allograft function and to identify clinical or immunologic factors that can predict a successful outcome after the elimination of steroids.

Adrenal Cortex Hormones↗
PubMed1994

Hypertension after renal transplantation.

Hypertension is a frequent complication after organ transplantation in both children and adults and is a significant risk factor for the development of cardiovascular disease and graft dysfunction. There are multiple mechanisms responsible for the development of posttransplant hypertension. In the precyclosporine era, chronic rejection was the most common cause. The introduction of cyclosporine A has increased the prevalence of hypertension in solid organ transplant recipients. Cyclosporine increases renal vascular resistance by causing vasoconstriction of the afferent arteriole. From a pathophysiologic point of view, a calcium channel blocker should be used as the initial therapy in patients with cyclosporine-associated hypertension. Hypertension needs to be treated aggressively in all transplant recipients in an attempt to minimize allograft and cardiovascular damage.

Adult↗