Biomedical subjects
Publications and source records attributed to J M Barry.
Ongoing research will no doubt change the way we diagnose and manage cystic kidney diseases in the not-too-distant future (probably before the turn of the century). The immediate clinical benefits are the more modest: Genetic tests have not replaced imaging techniques for the diagnosis of ADPKD, and clinical management of all cystic kidney diseases is still largely empiric.
Between May 10, 1982 and September 1, 1990, 1,000 kidney transplant recipients underwent parallel incision extravesical ureteroneocystostomy for urinary tract reconstruction. Complications attributed to this surgical technique that required reoperation occurred in 2.1% of the recipients. These complications included urinary extravasation in 9 patients, ureteral necrosis in 3, ureteral obstruction in 3, ureteral bleeding in 3, ureteral implantation into thickened folds of peritoneum in 2 on chronic ambulatory peritoneal dialysis and ureteral implantation into an ovarian cyst in 1. Vesicoureteral reflux occurred in 0.4% of the ureteroneocystostomies, none of which was revised. No allografts were lost as a result of these complications. The principles of the technique are sound. One should be careful if the patient has a small, defunctionalized or scarred bladder, has undergone multiple pelvic operations or has had pelvic inflammatory disease.
99mTechnetium-mercaptoacetyltriglycine (99mTc-MAG-3) has rapidly become the best isotope for transplant renal scintigraphy because of the excellent anatomical resolution. Because 99mTc-MAG-3 is also sequestered by the liver and excreted into the biliary system, images of the gallbladder and intestinal tract will appear in normal 99mTc-MAG-3 scans, especially on delayed scintigraphs. We describe the clinical interpretation of normal bowel images as urinary extravasation in a renal transplant recipient with a sudden decrease in renal function.
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A prospective study was undertaken to evaluate the efficacy of surgical cyst decompression for retarding the progression of renal failure and for the management of chronic pain associated with autosomal dominant polycystic kidney disease (ADPKD). Thirty patients with ADPKD and pain (14 patients), renal insufficiency (4 patients), or both (12 patients) underwent unilateral (19 patients) or bilateral (11 patients) cyst reduction surgery. The patients were monitored for 21 +/- 2 months postoperatively. The probability of being painfree was 80% at 1 yr and 62% at 2 yr. Preoperative and 1-to 3-month postoperative serum creatinine levels and GFR (clearance of insulin or (125I) iothalamate) were not significantly different (2.2 +/- 0.3 versus 2.2 +/- 0.3 mg/dL and 49 +/- 8 versus 54 +/- 9 mL/min/1.73 m2, respectively). One-year serum creatinine levels remained unchanged in patients with normal preoperative renal function (1.0 +/- 0.07 versus 1.0 +/- 0.05 mg/dL), whereas those with preoperative progressive renal insufficiency had no difference in the mean slope of reciprocal serum creatinine plots preceding and after surgery (-0.008 +/- 0.001 versus -0.009 +/- 0.002 dL/mg/month). In patients who underwent unilateral surgery, split function isotope scans showed no change in function of the operated kidney when compared with the nonoperated kidney. Surgical cyst decompression provides effective relief of chronic pain without compromising renal function. However, the data in this article do not support the use of this procedure to slow progression of renal insufficiency in ADPKD.
Currently, expected 10-year first graft survival rates for kidneys from HLA-identical sibling, 1-haplotype-matched relative, and cadaver donors are 74, 51, and 40%, respectively. Histocompatibility, immunological conditioning with blood products, and immunosuppression with glucocorticoids, azathioprine, cyclosporin, and the antithymocyte (antilymphocyte) antibody preparations have been significant factors in the gradual improvement of kidney graft survival rates. Nearly all immunosuppression regimens are cyclosporin-based. Antithymocyte antibody induction therapy with delayed administration of cyclosporin is widely practised to avoid cyclosporin nephrotoxicity while the kidney graft is recovering from preservation injury. Late cyclosporin withdrawal results in inferior cadaver kidney transplant survival rates. Rejection crises usually respond to high dose glucocorticoid therapy. Glucocorticoid-resistant rejection usually responds to treatment with antithymocyte antibody. FK-506 is a promising new immunosuppressant that has properties similar to cyclosporin. Prophylaxis against viral, bacterial and fungal infections is necessary to reduce the morbidity of immunosuppression. The incidence of malignant conditions associated with viral infections is significantly increased with immunosuppression. New immunopharmacological agents and advances in genetic procedures may allow the induction of specific transplantation tolerance and successful xenotransplantation within the next decade.
OBJECTIVE: To identify clinical characteristics of diabetic end-stage renal disease patients that place individual transplant candidates at high risk for arterial morbidity and mortality after transplantation. RESEARCH DESIGN AND METHODS: We studied the course of 101 sequential renal allograft recipients with insulin-dependent diabetes mellitus, transplanted between 10 November 1980 and 1 April 1986. Arterial disorders were tabulated from medical records and interviews with individual patients, their families, and their private physicians. Documentation of discrete arterial events included recorded physical examinations, radiographic studies, laboratory data, electrocardiograms, peripheral vascular flow studies, and operative reports. The prevalence of preoperative arterial disease was compared with the occurrence of new arterial events after kidney transplantation. RESULTS: Within a mean follow-up period of 47 mo, a 30% absolute mortality rate was observed. Of these deaths, 57% resulted from arterial disorders. Clinical manifestations of arterial disease were recognized in 41% of recipients before transplantation, and 78% of these patients suffered new vascular events after transplantation. Of the entire sample, 57% developed at least one new complication of arterial disease after transplantation, whereas only 34% had no vascular diagnosis before or after transplantation. Cerebral, coronary, and peripheral arterial complications after transplantation occurred in 14, 28, and 36% of the patients, respectively. The corresponding incidences of stroke, myocardial infarction, and amputation were 12, 14, and 25%. Pretransplant coronary artery disease predisposed to new coronary events after transplantation, but only peripheral arterial complications occurred more often after transplantation compared with the preoperative period. The probability of arterial complications or death correlated with patient age at first transplant and duration of diabetes but not with sex or smoking history. CONCLUSIONS: Intrinsic arterial disease in diabetic renal allograft recipients contributes heavily to the long-term morbidity and mortality after transplantation and poses the major threat to survival. Diabetic transplant candidates greater than 35 yr of age or with clinical evidence of arterial disease should undergo an extensive vascular assessment, including stress thallium myocardial imaging and/or coronary arteriography. Such recipients should receive careful preoperative counseling about their excess risk for subsequent arterial disorders.
1. Graft survival increased over the 4 periods between 1982 and 1990 (82-84, 85-86, 87-88, 89-90). The largest increase was in the 89-90 period. 2. Immunosuppression was the key to improved outcome. Cadaveric graft recipients given OKT3 induction plus triple therapy with cyclosporine, azathioprine, and prednisone had significantly better graft survival compared with all other drug combinations. Other factors were improved patient selection, donor management, and outpatient care. 3. Mean serum creatinine levels did not change after cyclosporine was introduced for immunosuppression. The mean serum creatinine level was approximately 1.7 mg/dl at 3 months, 6 months, and 12 months post-transplantation in all 4 periods. 4. Living-related donor outcome was significantly better than cadaveric donor outcome. Half-life for 2-haplotype-matched kidneys was 37 years compared with 12 years for 1-haplotype matches and 6.5 years for cadaveric kidneys. 5. Immediate function and a rejection-free first month were both associated with significantly improved graft survival. 6. Neither peak PRA nor graft number (1st vs regraft) correlated with graft survival. Highly sensitized (PRA greater than 50%) patients and regrafted patients fared as well as less sensitized (PRA less than or equal to 50%) and first graft recipients. This outcome was attributed to a sensitive crossmatch. Because of the crossmatch, highly sensitized patients received much better HLA matches. 7. The incidence of early rejection and delayed function declined significantly between the earliest and latest periods. Improved immunosuppression, donor management, and renal preservation were cited as contributing factors.
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Thirty-one pediatric patients with acute renal allograft rejection were treated with the monoclonal antibody OKT3. In 24 cases, increased doses of steroids followed by a polyclonal antithymocyte globulin were ineffective in reversing the rejection episode. Twenty-eight patients completed the prescribed minimum 10-day treatment course, with effective rejection reversal in 22. Three patients failed to complete the course of therapy: one because of leukopenia that developed after the first dose, one because of a clotted graft, and another because of symptomatic cytomegalovirus infection. The overall success rate of OKT3 for rejection reversal was 74%; however, 55% of recipients had rebound rejection, and 85% of patients had detectable anti-OKT3 antibodies after completion of the course of therapy. Ten patients were treated with a second course of OKT3, and in eight of these patients, rejection was at least temporarily reversed. The starting dose of OKT3 for second-course therapy was the same as that used during first-course therapy, but in five cases the dose was increased during the course because of inadequate therapeutic response. Seven of these patients lost their grafts a mean of 6.5 months after completion of second-course therapy. We looked for anti-OKT3 antibody in nine recipients after completion of a second treatment course and found it in all nine. Our observations regarding a second treatment course with this monoclonal antibody preparation suggest that although rejection reversal may be observed, ultimate graft survival is poor and anti-OKT3 antibody formation is enhanced.
We analyzed the results obtained with protocols for immunosuppression of pediatric recipients of haploidentical living-related renal transplants. In the donor-specific transfusion group transfusion of blood products obtained from the prospective organ donor was performed before transplantation, and at transplantation maintenance immunosuppression of azathioprine and prednisone was begun. In the cyclosporine group donor-specific transfusion was not used, and maintenance immuno-suppression of cyclosporine and azathioprine was begun 1 week before transplantation, with the addition of prednisone at transplantation. Of 24 donor-specific transfusion recipients 3 had circulating cytotoxic antibodies to the prospective donor for an incidence of 12%. There was no significant difference between groups with respect to 1-year actual patient and graft survival (100 and 89 versus 100 and 86%, respectively), 1-year mean serum creatinine level (1.1 versus 1.2 mg./dl.), rejection treatments per patient (2.5 versus 2.6) and total days hospitalized during year 1 after transplantation (27 versus 18), with donor-specific transfusion data presented first. Initial hospitalization was significantly shorter (10 versus 16 days, p less than 0.05) and the incidence of rejection crises within 3 months was significantly less (68 versus 94%, p less than 0.05) in the cyclosporine group. We believe that cyclosporine and azathioprine pre-treatment of pediatric recipients of haploidentical living-related renal transplants with the addition of prednisone at transplantation is preferable to a donor-specific transfusion protocol because there is no risk of recipient sensitization to the prospective donor, and patient and graft survival is not adversely affected.
Immunocompetence has been postulated as an important defense against the progression of urothelial carcinoma. Three cases of de novo lower urinary tract carcinoma in renal transplant recipients demonstrated the potential for unusually rapid urothelial extension and invasion in chronically immunosuppressed patients. Two patients had a history of perineal condyloma acuminata; tumors from 1 of these harbored the genetic sequences of human papillomavirus type 6. One patient had multiple manifestations of cyclophosphamide-related urothelial injury, including bladder carcinoma. Treatment of 2 patients culminated in a radical operation during which the remaining native urinary system was resected completely, with sacrifice of the allograft kidney in 1 and diversion into an ileal conduit in 1. The remaining patient underwent urethrectomy and partial cystectomy with a sigmoid conduit.
Renal transplantation is an accepted treatment for patients with end stage renal disease from insulin-dependent diabetes mellitus. Acute lumbosacral plexopathy developed following renal transplantation in 4 female patients with insulin-dependent diabetes mellitus between January 1, 1981 and June 30, 1988. In all 4 patients the internal iliac artery was used for revascularization of the renal allograft with ligation of the anterior and posterior divisions. Within 24 hours of surgery they complained of ipsilateral buttock pain, numbness in the leg and weakness below the knee. This complication has not been observed in nondiabetic patients at our institution, nor in diabetic patients when the internal iliac artery was not used. However, lumbosacral plexopathy occurred in 4 of 27 (14.8%) female patients with insulin-dependent diabetes mellitus when the internal iliac artery was used (p less than 0.001). Age, duration of insulin-dependent diabetes mellitus, hypertension, cigarette smoking history and kidney donor were not significant predictors of this complication. This unusual and newly recognized complication appears to result from ischemia of the lumbosacral plexus following ligation of the internal iliac artery in patients with severe small vessel disease.
We trained 82 community hospital cadaver kidney retrieval teams during a 10-year period ending June 30, 1987. During the last 5 years of that period the concept of multiple organ retrieval was introduced into the training sessions and 429 cadaver kidney grafts were retrieved. Of those kidneys 292 were transplanted at our hospital, and the function of 220 cadaver kidney grafts retrieved by the community hospital teams was compared to that of 72 retrieved by the transplant center retrieval team. Of the cadaver kidney transplants 114 were from multiple organ donors. There was no significant difference in 1-month serum creatinine nadir of surviving grafts (2.1 +/- 1.8 versus 1.9 +/- 1.7 mg. per dl.), 6-month serum creatinine level (1.7 +/- 0.8 versus 1.6 +/- 0.6 mg. per dl.), 12-month serum creatinine level (1.8 +/- 0.9 versus 1.6 +/- 0.6 mg. per dl.) and 5-year actuarial graft survival (44.8 +/- 4.1 versus 52.4 +/- 7.5%), with the community hospital data presented first. The delayed graft function rate was significantly higher in the recipients of cadaver kidney grafts retrieved by community hospital teams (54 versus 35%), which was reduced by the in situ flush technique. There was no significant difference in delayed graft function rate (48 versus 40%) for the 114 cadaver kidney transplants retrieved from multiple organ donors by either community hospital or transplant center teams. With continuing education and quality control, community hospital retrieval teams can provide kidneys satisfactory for transplantation, even when working with multiple organ retrieval teams.
The role of staging transurethral resection of the prostate in the management of stage A prostate cancer is controversial. The accuracy of staging transurethral resection, A1/A2 substaging and probability of progression tables for predicting cancer progression was evaluated in untreated patients with stage A adenocarcinoma of the prostate who were followed for at least 5 years. Survival free of disease was predicted correctly in 93% of 52 patients who underwent staging transurethral resection of the prostate, 92% of 96 with the probability tables and in 85% of 96 using a common criteria for A1 and A2 substaging. Staging transurethral resection of the prostate upgraded patient risk in 7% of the low risk patients predicted by the probability tables and 14% of the stage A1 cancer patients. Staging transurethral prostatectomy and the probability of progression tables were more accurate in predicting survival free of disease than the A1/A2 substaging system. Comparison of the predictive accuracy of staging transurethral prostatectomy to that of the probability of progression tables showed no significant difference. There was no additional benefit from combining the 2 methods. When the probability of progression tables are used to predict cancer progression it may be unnecessary to use staging transurethral resection of the prostate in the patient with stage A prostate cancer.
Described herein are renal transplant techniques which have been successfully applied to general urology patients. These include surface and core cooling of the kidney, autotransplantation, renal vein translocation, the use of a transcutaneous stent for upper urinary tract repairs, and an unstented, parallel incision, extravesical ureteroneocystostomy.
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