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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
PubMed1997

Clinical and economic outcomes of expanded criteria donors in renal transplantation.

Although graft and patient survival rates were similar between recipients of kidneys from ECDs and non-ECDs, transplantation with organs from ECDs was significantly more expensive. Multivariate analysis using stepwise linear regression demonstrated length of stay to be a strong proxy for total hospital costs. Inherent tensions between the overall good clinical outcomes associated with the use of ECDs in terms of graft survival and the markedly increased costs seen with these organs are evident.

Age Factors↗
PubMed1997

The donor supply.

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Age Factors↗
PubMed1997

An update on new immunosuppressive drugs undergoing preclinical and clinical trials: potential applications in organ transplantation.

Recent advances in immunobiology and immunopharmacology have led to a better understanding of the actions of immunosuppressive drugs. Over the past 2 years, a number of new agents have been approved for use in solid organ transplant recipients. In addition, new immunosuppressive agents are being tested in preclinical and clinical trials, leading to the promise of an exciting future in organ transplantation. This report reviews the mechanisms of action and the potential future role of these agents in clinical transplantation.

Humans↗
PubMed1997

Impact of ganciclovir prophylaxis on cytomegalovirus infection in recipients of cadaveric renal allografts.

Cytomegalovirus (CMV) infection is a major cause of morbidity and occasionally of mortality in immunosuppressed allograft recipients. At the University of Cincinnati Medical Center, ganciclovir has been administered for the prevention of CMV infection since July 1992. Forty-six recipients of cadaveric renal allografts (Group I) received ganciclovir at a dose of 2.5 or 5 mg/kg/day (adjusted for renal function) for 14-21 days, during induction treatment and during antirejection treatment with monoclonal or polyclonal antilymphocyte preparations. In this retrospective study, these 46 patients were compared with 77 recipients of cadaveric renal allografts transplanted prior to July 1992 (Group II) for the prevalence, severity and time of CMV occurrence after transplantation. CMV diagnosis was based on clinical evaluation and was confirmed by blood cultures, CMV antigen immunofluorescence assay and/or histology. Patients were stratified according to CMV serology (+) or (-) in donor and recipient. CMV infection developed in 16 of 46 (35%) patients in Group I vs. 27 of 77 (35%) patients in Group II (p = 0.97). A total of 25 episodes of CMV infection occurred in Group I compared to 44 in Group II (p = 0.76). CMV infection was diagnosed an average of 97.4 days after transplant in Group I compared to 48.3 days in Group II (p = 0.0003). Tissue-invasive CMV infection occurred in 3 patients in Group I (19%) vs. 12 in Group II (44%) (p = 0.5). In conclusion, ganciclovir prophylaxis resulted in a delayed onset of clinical CMV infection with a trend towards less severe infection in patients treated with antilymphocyte antibody preparations.

Adult↗
PubMed1997

Causes of renal allograft loss in black vs. white transplant recipients in the cyclosporine era.

Black renal transplant recipients have a higher rate of allograft loss than white recipients. From 1 January 1984 to 1 January 1995, 463 transplants were performed at a single center and followed for a mean duration of 71 months. The causes of graft loss for white and black recipients, their age, gender, retransplantation rate, organ source, and HLA matching were compared. In the 150 black and 313 white recipients, graft loss rates in the first year were 20% in both groups, while after 1 yr there were 42 (28%) graft losses in blacks vs. 62 (20%) in whites (log-rank test p = 0.04). All diagnoses deemed causative of allograft loss were confirmed by biopsy. Chronic rejection resulting in graft loss occurred in 15% (n = 23) of black recipients compared to only 7% (n = 22) of white recipients (p = 0.002). There were no significant differences in the rate of death with a functioning kidney or other causes of graft loss between the two groups. A significant increase in HLA mismatches was noted in black recipients of cadaveric grafts compared to whites, but there was no difference between races in the rate of graft loss due to acute rejection. While the rate of graft survival remains lower in black recipients in the cyclosporine era, this is due entirely to late graft loss after 1-yr post-transplant due to chronic rejection.

Acute Disease↗
PubMed1997

Expanding the donor pool.

Advances in techniques and the development of new immunosuppressive drugs have made it possible to transplant a large number of patients throughout the world. However, the shortage of cadaveric organ donors remains the major obstacle for the full development of organ transplantation, imposing a severe limit to the number of patients who could benefit from this therapy. Although transplants save thousands of lives and transform the quality of life of thousands more, many people will die or remain on renal replacement therapy because the organ supply falls drastically short of actual demand. In the US, the number of organ donors has increased approximately 20% over the past 5 years, but this increase has been brought about largely by the use of older donors and other donors considered by some to be marginal. In the 6 years from 1988 to 1994, the waiting list for kidneys grew by 76% in the US. By the end of August 1996, there were 33,339 patients registered for kidneys on the national transplant waiting list. This report examines the issue of the elderly donor, the role of living-unrelated kidney transplantation, and proposes various strategies to enhance procurement of cadaver kidneys.

Adolescent↗
PubMed1997

Combined kidney-pancreas and parathyroid transplantation: a case report.

We report the first successful multiorgan kidney-pancreas and parathyroid tissue transplant in a patient with autoimmune polyglandular syndrome and medullary cystic disease. Successful transplantation included quadruple drug induction therapy consisting of antithymocyte globulin, azathioprine, cyclosporine and prednisone. All three grafts are functioning 2 yr after transplantation.

Adult↗
PubMed1996

Diabetic nephropathy after renal transplantation. Clinical and pathologic features.

The histologic diagnosis of diabetic glomerulosclerosis was made in 14 renal transplant recipients. All 14 had insulin-dependent diabetes mellitus, which was the original cause of end-stage renal disease in 12; one patient had membranoproliferative glomerulonephritis and another patient had membranous nephropathy as the cause of end-stage renal disease. Insulin-dependent diabetes mellitus was diagnosed at an average age of 18.5 years (range, 8-41 years), and the mean duration of diabetes prior to transplantation was 15 years (range, 2-25 years). All patients were recipients of first kidney transplants (six living related donors and eight cadavers). The histologic diagnosis of diabetic glomerulosclerosis was made on average, 97 months after transplantation (range 41-154 months). All 14 patients had proteinuria (mean 5.3 g/24 hr; range 1.1-12 g/24 hr) and renal dysfunction (mean serum creatinine level, 2.8 mg/dl). Patient and graft survival rates at 1 year, 5 years, and 10 years after transplantation were 100%, 92%, and 59%, and 100%, 92%, and 34%, respectively. Graft failure was due to diabetic nephropathy in seven patients, diabetic nephropathy and membranous nephropathy in one patient, and death due to a cerebrovascular accident in one patient. A total of five patients are alive with a functioning kidney. Of the eight patients who returned to dialysis, four are alive, three remain on dialysis, and 1 had a combined kidney and pancreas transplant. Histologic findings were as follows: 9/14 had moderate or severe diffuse glomerular basement membrane thickening and 2/14 had nodular glomerulosclerosis. Arteriolar lesions were prominent in all cases and was graded moderate or severe in 11 cases. The development of allograft diabetic nephropathy is associated with a high rate of allograft failure.

Adult↗
PubMed1996

Rescue therapy with tacrolimus after combined kidney/pancreas and isolated pancreas transplantation in patients with severe cyclosporine nephrotoxicity.

This study details 11 pancreas transplant recipients (10 combined kidney and pancreas and 1 pancreas after kidney) who were converted to tacrolimus (FK506) due to acute severe cyclosporine nephrotoxicity in 8 cases and persistent rejection with cyclosporine toxicity in three cases. Arteriolopathy was documented by renal histology in all cases. Cyclosporine was discontinued for 24 hr immediately prior to initiation of tacrolimus. Tacrolimus was started orally at 0.1 mg/kg twice daily with dose adjustments to maintain whole blood trough levels of 8-15 ng/mL by IMx. Tacrolimus was initiated a mean of 14.5 months (range 1-81) after pancreas transplantation. The mean serum creatinine level had increased to 2.9 mg/dl from 1.0 mg/dl at the diagnosis of cyclosporine arteriolopathy (P=0.003). The mean serum creatinine and blood glucose levels at the time of initiation of tacrolimus were 2.1 mg/dl and 104 mg/dl, respectively. Serum creatinine was 1.7 mg/dl, 1.9 mg/dl, 1.8 mg/dl, and 1.7 mg/dl after 1, 2, 3, and 6 months of tacrolimus therapy, respectively; ANOVA (P = 0.02). The corresponding blood glucose levels were 117 mg/dl, 112 mg/dl, 109 mg/dl, and 116 mg/dl, respectively (P=NS). Normal C-peptide levels were present before (5.9 ng/ml) and after (6.2 ng/ml), the initiation of tacrolimus therapy (P=NS), and mean HbA1C was 6.1% before and 6.3% after tacrolimus therapy, (P=NS). There were 4 episodes of acute rejection, 3 responded to intravenous methylprednisolone, and 1 required OKT3 during tacrolimus therapy. Reversible tacrolimus nephrotoxicity was noted in three patients without any evidence of progressive vasculopathy. All 11 patients are alive, and 10/11 kidney and pancreas grafts are functioning with a mean follow-up of 7.7 months (range 5-10). In this study, conversion from cyclosporine to tacrolimus in kidney and pancreas recipients resulted in improvement and stabilization of renal function while maintaining stable blood glucose, C peptide, and HbA1C levels.

Administration, Oral↗
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↗