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Biomedical subjects

M R First

Publications and source records attributed to M R First.

At least 73 records · Page 4Linked to original sources
PubMed1996

Successful pregnancy after combined renal-pancreas transplantation: a case report and literature review.

A long-standing history of insulin-dependent diabetes mellitus can result in multiple organ damage. We present a case of successful pregnancy in a patient who underwent combined renal-pancreas transplantation for end-stage renal disease due to diabetic nephropathy. A 29-year-old white gravida 7, para 2 female was diagnosed with diabetes mellitus at age 7. She was well controlled with insulin until age 21. She developed complications of diabetes mellitus which included retinopathy resulting in legal blindness, nephropathy resulting in end-stage renal disease, and chronic hypertension. Following nine months of dialysis she underwent a combined renal-pancreas transplant. She subsequently became pregnant 21 months after transplantation and delivered a healthy male at 35 1/2 weeks gestation. Renal-pancreas transplant recipients who become pregnant may be at an increased risk for adverse outcome. We present a successful pregnancy outcome in a combined transplant recipient who had a prior poor obstetrical history.

Adult↗
PubMed1996

Role of granulocyte colony stimulating factor (G-CSF) in reversing neutropenia in renal allograft recipients.

Neutropenia in solid organ transplant recipients may be caused by immunosuppressive therapy, antimicrobial therapy, as well as bacterial and viral infections. Filgrastim, a human granulocyte colony stimulating factor (G-CSF) is used for the reversal of neutropenia. Although its influence is principally restricted to neutrophil progenitors, the safety of G-CSF in terms of percipitating or aggravating allograft rejection and its efficacy in reversing neutropenia in kidney and combined kidney and pancreas transplant patients has not been studied or reported. In this study we retrospectively analyzed the use of G-CSF between March 1992 and May 1994 at the University of Cincinnati Medical Center, in patients who received either a kidney or a combined kidney and pancreas transplant. A total of 25 patients developed 35 episodes of neutropenia and received an average of 2.9 doses of G-CSF per episode. The mean WBC nadir was 2.6 x 10(3)/cu mm with an average peak WBC count of 15.5 x 10(3)/cu mm following treatment (p = < 0.00001). The average number of days to peak WBC after initiation of treatment was 4.6 days. The mean pre-treatment serum creatinine level was 2.3 mg/dl and the peak serum creatinine in the week following treatment remained the same. We conclude that G-CSF is an effective treatment in reversing neutropenia in renal transplant recipients and does not precipitate or aggravate allograft rejection.

Creatinine↗
PubMed1996

Serial monitoring of soluble interleukin-2 receptor as a rapid marker of cytomegalovirus infection and response to antiviral therapy.

Serial sIL-2R serum levels were evaluated as an indicator of cytomegalovirus infection and response to antiviral therapy. All cases of post-transplant CMV infection or disease were studied over a 2.5-year period with serial sIL-2R serum levels monitored daily post-transplant until discharge, during each inpatient admission and with each outpatient laboratory analysis. Mean sIL-2 levels +/- S.E.M. rose from a baseline level of 3662 +/- 321 U/ml to 11657 +/- 3311 U/ml at the time of diagnosis. Serum sIL-2R concentrations were significantly elevated from baseline as early as 14 days prior to diagnosis of CMV. Mean peak sIL-2R levels occurred an average of 4 days after the initiation of ganciclovir therapy and remained significantly elevated for an average of 20 days of treatment. Serum sIL-2R levels in patients with resolved CMV returned to within 20% of baseline after 20 days of therapy. These data support the idea that serial monitoring of sIL-2R serum levels may be useful adjunctively in the diagnosis of CMV as well as determining the response to and duration of antiviral therapy.

Adult↗
PubMed1996

Cyclosporine bioavailability: dosing implications and impact on clinical outcomes in select transplantation subpopulations.

Reports in the literature indicate that clinical outcomes in select patient subpopulations have been inferior to those in the general transplantation population. Of potential interest in this regard is the finding that lower cyclosporine bioavailability correlates with a higher incidence of acute rejection and graft loss. To gain insights into these issues, we examined data from renal transplant recipients at our own centers and in one large data base. Our experience revealed that cyclosporine bioavailability was markedly lower in patients who developed acute or chronic rejection than in those with stable graft function. An analysis by demographic or clinical factors showed that cyclosporine bioavailability was lower in diabetics and black patients. In one study, diabetics required much higher daily doses of cyclosporine to achieve outcomes comparable to those in non-diabetics; even then, diabetics attained lower cyclosporine blood levels. Other work found that long-term graft survival rates were poorer in blacks, even though cyclosporine dosages and blood levels were comparable to those in whites. A case-controlled study from the pregnancy registry found that cyclosporine dosages were consistently higher in pregnant patients who maintained good graft function than in those who experienced graft dysfunction. These results suggest that the subpopulations examined should receive immunosuppression with higher cyclosporine dosages than those used in the general transplantation population. These subpopulations may also benefit from a cyclosporine formulation that provides better absorption, resulting in more consistent and predictable cyclosporine bioavailability.

Biological Availability↗
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↗