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Biomedical subjects

M R First

Publications and source records attributed to M R First.

At least 181 records · Page 10Linked to original sources
PubMed1987

The effect of oral metoclopramide on the absorption of cyclosporine.

This study was performed to determine the effect of coadministered oral metoclopramide on the absorption of oral cyclosporine in 14 kidney transplant patients with stable renal function. The study was conducted on two consecutive days. Ten patients were studied twice and four patients once, giving 24 studies. The total dosage of metoclopramide was 20 mg. The day on which metoclopramide was administered was chosen randomly. Whole blood cyclosporine levels were analyzed by high performance liquid chromatography. Coadministration of cyclosporine with metoclopramide resulted in a significant increase in mean maximum blood concentration (567 ng/mL nu 388 ng/mL) and mean area under the blood concentration nu time curve (4120 ng X h/mL nu 3370 ng X h/mL), and a significant decrease in mean time to reach maximum concentration: The mean increase in area under the blood concentration versus time curve was 29%. No significant changes were observed in the elimination of cyclosporine when it was coadministered with metoclopramide. These observations suggest that coadministered metoclopramide increased the total absorption of cyclosporine. Metoclopramide has been shown to hasten gastric emptying; since cyclosporine is absorbed predominantly in the small intestine, coadministration of metoclopramide resulted in increased bioavailability of cyclosporine.

Administration, Oral↗
PubMed1986

Development and incidence of cancer following cyclosporine therapy.

Eighty-seven organ transplant recipients developed 88 tumors after immunosuppression with CsA. The neoplasms showed important differences from those seen following conventional immunosuppressive therapy (CIT). Malignancies appeared an average of 14 months (range, 1 to 82) after CsA and 59 months (range, 1.0 to 225.5) after CIT. Cancers were particularly common among recipients of extrarenal organs. NHLs were the most common neoplasms comprising 52%, compared with 12% in CIT patients. They appeared an average of 8.5 months after transplantation, compared with an average of 41 months after CIT. Unlike NHLs in CIT patients, they more often involved lymph nodes, were more widespread, more frequently involved the small intestine, rarely involved the brain, were more likely to regress, and had a better prognosis following reduction of immunosuppressive therapy. Skin cancers (13% of cancers) were less common than in CIT patients (40%). Kaposi's sarcomas were more common (10% v 3%). Some tumors commonly seen after CIT, including in situ uterine cervical carcinomas and carcinomas of the vulva/perineum, have not occurred in CsA patients. In this small series, there was a surprising frequency of endocrine-related malignancies (ovarian, testicular, breast, and thyroid) and renal cell carcinomas. Longer follow-up and study of larger numbers of patients will determine whether differences from CIT patients will persist. Only seven (8%) patients were treated only with CsA, the remainder received other immunosuppressive agents, mainly prednisone. The malignancies probably are not specific to CsA therapy but appear to be a complication of immunosuppression per se.

Adult↗
PubMed1986

Revaccination of renal transplant and hemodialysis recipients with pneumococcal vaccine.

Two years after pneumococcal vaccine was given to patients on a university renal transplant and hemodialysis service, vaccine failures began to occur. Serologic studies showed a threefold decrease in antibody levels during this period, from 913 ng of antibody nitrogen per milliliter to 315 ng/mL. The decrease was greater in patients undergoing hemodialysis than in renal transplant recipients (879 to 215 ng/mL vs 932 to 385 ng/mL). The lowest antibody levels were to types 4, 6A, and 19F. Patients were revaccinated, without serious reactions, and pneumococcal infections decreased as they had after the original vaccination program. After revaccination, there was a twofold increase in antibody levels (315 to 602 ng/mL), but the levels did not reach those seen after primary vaccination. The increase was greater in hemodialysis than in renal transplant recipients (215 to 757 ng/mL vs 385 to 536 ng/mL). This experience indicates that pneumococcal vaccines may be effective in patients undergoing hemodialysis and in asplenic renal transplant recipients, but these groups will require revaccination sooner than normal subjects to maintain immunity.

Antibodies, Bacterial↗
PubMed1985

Results of treatment in patients with end-stage renal disease: a multivariate analysis of risk factors and survival in 341 successive patients.

Factors that affect survival in patients with end-stage renal disease (ESRD) are still only partially understood. We report an analysis on a cohort of 341 successive patients who started ESRD treatment in one institution. Survival was calculated from the start of ESRD treatment, whether initial treatment was by dialysis (335 patients) or transplantation (6 patients). Analysis of factors affecting survival was done using the Cox multivariate hazard analysis. Relative risks were calculated for several demographic factors, the primary renal disease, the presence or absence of various high-risk co-morbid factors, and for a first transplant from a living-related or cadaver donor. Older patients, patients with no prior health insurance, those with diabetic nephropathy, and those with small kidneys of unknown cause had statistically significantly higher risks of dying. The risk of dying decreased by year of start of ESRD treatment. Living related donor transplantation was associated with a decreased hazard to age 45 years and older; whereas cadaver donor transplantation was associated with a hazard that increased with age and was significantly increased by age 45.

Actuarial Analysis↗
PubMed1985

Transplant glomerulopathy: evolution of morphologically distinct changes.

The study was undertaken to redefine morphological appearance and clinical implications of the diagnosis of transplant glomerulopathy (TGP). Fifty-seven renal transplant biopsy specimens from thirty patients with the diagnosis of TGP were evaluated. Multiple repeat biopsies in several cases enabled us to follow the pattern of the evolution of the changes. Transplant dysfunction manifested itself 8 days to 13 years post-transplantation by proteinuria and/or elevated creatinine level. The earliest recognizable morphological change was the swelling of endothelial and mesangial cells. This stage was called evolving TGP. The intermediate stage was characterized by enlarged glomeruli with lobular simplification, spongy matrix, and glomerular basement membrane (GBM) deformities. The advanced stage of TGP showed pronounced GBM changes (reduplication, interposition). These light microscopic changes were associated with vascular rejection. Immunofluorescence showed significant glomerular deposition of IgM (83% of biopsies) and fibrinogen (66%). Electron microscopy at an early stage showed subendothelial widening with cellular debris and focal endothelial damage with fibrin deposition. In the advanced stage, complex GBM changes developed as a reparative response to the capillary wall injury. Effacement of foot processes was a constant finding at all stages. In follow-up, twenty-three allografts failed (77%), five patients are stable, and two died due to other causes. TGP has specific morphology with an attendant poor long-term prognosis for the allograft.

Basement Membrane↗
PubMed1985

Renal transplantation in Alport's syndrome.

Nineteen patients (3 women and 16 men) with Alport's Syndrome and endstage renal failure received 23 allograft kidneys at two medical centers between 1972 and 1983. Ten patients had pretransplant splenectomies, and four patients had pretransplant thoracic duct drainage. After a mean follow-up time of 49 months, analysis revealed total allograft survival was 65 per cent at 1 year, 50 per cent at 2 years, and 57 per cent at 5 years. Pretransplant splenectomy resulted in 60 per cent allograft survival at 24 months mean follow-up. Pretransplant thoracic duct drainage resulted in 100 per cent allograft survival at 15.6 months mean follow-up. The overall allograft survival was greatest for three and four antigen-matched kidneys and for living related donor kidneys. Data indicated that 50 per cent of all allografts in men were functional at 50.8 months mean follow-up. All allografts in women were functional at 48.3 months mean follow-up. Three of four patients who expired had pretransplant splenectomies. From this study, the authors conclude that renal transplantation is the preferred method of treatment for patients with Alport's Syndrome.

Adolescent↗
PubMed1984

The late adverse effect of splenectomy on patient survival following cadaveric renal transplantation.

Kidney and patient survival of 351 consecutive patients undergoing first cadaveric renal transplants since 1968 were reviewed to determine the effects of splenectomy on outcome. Special emphasis was given to analysis of 106 splenectomized and 102 nonsplenectomized patients treated since 1975. During the first two years after transplant, kidney survival was better in the splenectomized patients, with no adverse effect on patient survival. However, after the first two years, patient survival became significantly worse in splenectomized patients (35.5% vs. 60.5% at 84 months). Of the deaths, infection was the cause in 26.7% of nonsplenectomized patients compared with 50% of splenectomized patients (P less than 0.07). Of patients alive at one year posttransplant, death rates were not different in patients splenectomized before 1975 or after 1975. Timing of splenectomy (prior vs. concurrent) had no effect on outcome. The adverse effect of splenectomy on mortality appeared to be more pronounced in younger (less than or equal to 45 year-old) than in older (greater than 45 year-old) patients. Splenectomy should not be performed routinely in preparation for a cadaveric transplant because of an unacceptably high late mortality that is primarily from sepsis.

Adult↗
PubMed1984

Membranous glomerulopathy following kidney transplantation. Association with renal vein thrombosis in two of nine cases.

The association of renal vein thrombosis and membranous glomerulopathy in native kidneys has been well documented. However, this association has only occasionally been described following renal transplantation. A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater than 2 g/24 hr) developed. Renal histology was available in all 77 patients. A diagnosis of membranous glomerulopathy was made in 7 patients. Two further cases were added on the basis of biopsy findings--1 patient had a protein excretion of 1.7 g/24 hr, the other had microscopic hematuria and red cell casts in the urine. Renal venography was performed in 4 cases. The decision to perform venography was based on clinical criteria (thrombophlebitis or marked edema of the leg on the side of the allograft), and/or histological criteria (associated interstitial edema and venous congestion). Renal vein thrombosis was present in 2 patients. Three of the 9 patients had membranous glomerulopathy as the cause of their end-stage renal disease; 2 of these patients had received kidneys from living-related donors. Four of the patients were classified as having de novo membranous glomerulopathy on the basis of having a different cause for their end-stage renal disease. Two patients were classified as having unspecified membranous glomerulopathy; both of these patients had had chronic glomerulonephritis, but there was lack of characterization of the original glomerular disease. Seven of the 9 patients continued to have stable allograft function 1-12 months after the diagnosis of membranous glomerulopathy was made in the renal allograft. The remaining 2 patients both had associated renal vein thrombosis; 1 had progressive deterioration of renal function and returned to dialysis 24 months after the diagnosis of membranous glomerulopathy had been made, while the other died of unrelated causes 27 months after the diagnosis had been made.

Adult↗
PubMed1984

Proteinuria following transplantation. Correlation with histopathology and outcome.

A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater than 2 g/24 hr) developed. Renal histology was available in all 77 patients. Twenty-one patients had received kidneys from living-related donors, the remaining 56 from cadaveric donors. The cause of proteinuria in these 77 patients was as follows: transplant glomerulopathy (30), allograft glomerulonephritis (22), chronic rejection (21), renal vein thrombosis (2), diabetic glomerulosclerosis (1), and hypertensive nephrosclerosis (1). Of the 22 patients who developed glomerulonephritis in the transplanted kidney, 6 had recurrent disease (3--membranous glomerulopathy, 2--focal sclerosis and hyalinosis, 1--membranoproliferative glomerulonephritis); 6 developed de novo glomerulonephritis; and in 10 the type of glomerulonephritis could not be classified as recurrent or as de novo because of lack of characterization of the original kidney disease. Renal vein thrombosis occurred in association with other lesions in an additional 5 cases (3--chronic rejection; 2--membranous glomerulopathy). In follow-up only 23.4% (18 of 77) of the patients maintained prolonged graft function; the majority of grafts being lost within one year of the development of persistent, heavy proteinuria. Of the 18 patients who retained their grafts, 8 had glomerulonephritis, 5 transplant glomerulopathy, and 5 chronic rejection. This study confirms the poor prognosis that has been reported with the development of nephrotic-range proteinuria in renal allograft recipients.

Graft Survival↗
PubMed1983

Polytetrafluoroethylene graft survival in hemodialysis.

Expanded polytetrafluoroethylene (PTFE) graft fistulas are widely used as secondary vascular access for patients receiving long-term hemodialysis treatment. Sixty-seven grafts were implanted in 48 patients and followed for 12 to 51 months. Cumulative patency for all grafts at 12 months was 67% +/- 6%, at 24 months 50% +/- 7%, and at 48 months 43% +/- 9%. Graft survival rates were different when considering graft configuration and location. Forearm straight graft survival at 12 months was 35% +/- 13%, upper arm curved grafts 60% +/- 19%, and forearm looped grafts 78% +/- 7%. Complications that decreased graft survival were related to thrombosis (21%), infection (25%), and intimal hyperplasia at the venous anastomosis (34%). After reviewing our experience, we believe that the challenge of secondary vascular access has not been solved by PTFE grafts. This should stimulate the search for better grafts and techniques.

Adult↗