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D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 145 records · Page 8Linked to original sources
PubMed1995

Retransplantation after renal allograft loss due to noncompliance. Indications, outcome, and ethical concerns.

Noncompliance is increasingly recognized as a major cause of renal allograft loss, but the results of retransplantation of such patients have never been described. At our center, 52 of 3525 kidney recipients between June 1, 1963 and December 31, 1993 lost their graft due to overt noncompliance. Of these, 14 (27%) underwent retransplantation after thorough interdisciplinary evaluation. All but 1 patient had returned to dialysis before retransplantation. Of the retransplanted grafts, 2 were lost (1 technical failure, 1 chronic rejection in a compliant patient); both recipients were retransplanted once again. Currently, all retransplanted patients are alive and have a functioning graft. We conclude that for selected patients with graft loss due to noncompliance excellent results can be achieved with retransplantation. However, the issue of retransplanting previously noncompliant patients in the face of a significant donor organ shortage requires public debate.

Adolescent↗
PubMed1995

Correlation between cystoscopic biopsy results and hypoamylasuria in bladder-drained pancreas transplants.

BACKGROUND: Urinary amylase (UA) remains the most common biochemical parameter to detect rejection in bladder-drained pancreas allografts. With the development of the cystoscopic transduodenal pancreas transplant biopsy technique, tissue samples of the pancreas graft are now frequently obtained. A definitive correlative analysis between UA activity and biopsy results has not been done in the three different pancreas transplant categories (simultaneous pancreas-kidney, pancreas transplant alone, and pancreas after kidney). METHODS: We studied 66 pancreaticoduodenal biopsy specimens obtained for hypoamylasuria. Rejection was defined as a greater than 25% decrease from stable posttransplantation baseline on two consecutive measurements at least 12 hours apart. To perform biopsies we used our newly developed 14- and 16-gauge core-cut needles (50 cm long). Biopsy specimens were considered positive if either pancreatic or duodenal rejection was found. To assess the quality of UA activity we studied 13 biopsy specimens from patients with stable UA levels; these 13 specimens were negative for rejection. RESULTS: Acute rejection was diagnosed in 36 biopsy specimens (55%). The mean decrease in UA levels was 67% +/- 8% (range, 28% to 99%) for the positive biopsy results, and 57% +/- 16% (range, 22% to 92%) for the negative biopsy results (p = 0.147). Within 1 month, UA levels returned to baseline in 19% of our patients with positive biopsy results versus 97% with negative results; postbiopsy 1-year graft survival was 64% versus 97% (p < or = 0.05). In assessing the test quality of our biopsy specimens (including 13 obtained for reasons other than hypoamylasuria), we found a sensitivity of 100% (stable UA levels mean no rejection) and a specificity of 30%. The predictive value of a positive test was 53%; of a negative test it was 100%. By performing biopsies we avoided antirejection treatment in 47% of the patients studied. We found no biopsy-related complications. CONCLUSIONS: Stable UA levels reliably rule out rejection; a decrease is a marker for acute rejection but is unspecific. Performing biopsy is currently the only way to reliably diagnose rejection in solitary pancreas recipients (pancreas transplant alone and pancreas after kidney) and in simultaneous pancreas-kidney recipients with isolated hypoamylasuria. The procedure is safe and should always be attempted to avoid unnecessary rejection treatment.

Adult↗
PubMed1995

Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant recipients.

Five years of normoglycemia following pancreas transplantation (PT) does not ameliorate glomerular lesions in patients with their own kidneys and with long-term insulin-dependent diabetes (IDDM) (Lancet 342:1193, 1993). All these patients received cyclosporine (CsA) as part of their immunosuppression. Here we examined the relationship of CsA dose and blood levels to the presence and severity of CsA-associated renal lesions and changes in renal function in these PT patients. Renal biopsies were taken before (0) and two and five years after PT from 13 non-uremic IDDM patients and were compared with baseline and five year biopsies from 10 IDDM controls (C). CsA dose was reduced from 10 +/- 3 mg/kg/day in the first month to 5 +/- 2 in the fifth year post-PT. Creatinine clearance (CCr) decreased by 34% at one year post-PT and was stable thereafter, and did not change in C. The decline in CCr from 0 to one year was related to CsA blood levels and dose (P < 0.005) at one year. Cortical interstitial volume fraction [Vv(Int/Cortex)], the index of tubular atrophy, and % sclerotic glomeruli increased significantly from 0 to five years post-PT (P < 0.005, 0.01 and 0.001, respectively), but did not change in C. There was no significant change from 0 to two years post-PT in these lesions, while there was a clear progression from two to five years. Mean CsA dose and blood levels in the first year post-PT correlated with the increase (delta) in Vv(Int/Cortex) at five years (P < 0.05 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Sequential renal biopsies in insulin-dependent diabetic patients: structural factors associated with clinical progression.

Quantitative structural studies in native kidneys of IDDM patients have almost all been cross sectional, and little is known regarding the dynamics of progression of structural lesions in relation to clinical progression. It has been suggested that interstitial may be more important than glomerular changes in determining functional outcome. This study evaluated renal structure in sequential biopsies from IDDM patients with established renal lesions to determine whether glomerular, arteriolar and interstitial changes progress together and in concordance with measures of renal function. Eleven long-term IDDM patients [age 29 +/- 10 years, duration 17 +/- 7 years (mean +/- SD)] had renal function studies and kidney biopsies performed at two occasions 5.6 +/- 1.6 years apart. HbA1 as well as creatinine clearance (CCr) did not change over this time; albumin excretion rate (AER) increased from 12 (6 to 280) to 19 (5 to 2462) [median (range)] mg/24 hr (P < 0.03). AER increased in the three patients with abnormal albuminuria at first observation, and two normoalbuminuric patients became microalbuminuric. Blood pressure (BP) did not change; however, the number of patients on antihypertensive therapy increased from 1 to 5. All structural parameters were abnormal at first evaluation. Mesangial fractional volume [Vv(mes/glom)] and mean glomerular volume increased and the surface density of the peripheral glomerular basement membrane (GBM) decreased, while GBM width did not change over the five years of the study. Also, arteriolar hyalinosis lesions progressed, while the fractional volume of cortical interstitium [Vv(interstitium/cortex)] and the percent of globally sclerosed glomeruli did not change. The only structural change that correlated with the increasing AER was the change in Vv(mes/glom). Changes in structural parameters, AER or CCr did not significantly correlate with baseline BP or change in BP over the five years. Although based on a small number of patients, this study suggests that at the stage of disease where renal lesions are established and where some IDDM patients are in transition to microalbuminuria or early clinical nephropathy, continuing mesangial expansion is the central variable. Interstitial changes were not occurring over this time. Progressive interstitial expansion at the later stages of diabetic nephropathy may thus be consequent to advanced diabetic glomerular injury.

Adult↗
PubMed1995

Short- and long-term outcomes of kidney transplants with multiple renal arteries.

OBJECTIVE: The authors determined whether the use of kidney allografts with multiple renal arteries adversely effects post-transplant graft and patient outcome or increases the incidence of vascular and urologic complications. BACKGROUND: Kidney grafts with multiple renal arteries have been associated with an increased incidence of early vascular and urologic complications. Kidney transplants with single versus multiple renal arteries have not been compared in regard to long-term graft and patient outcome or post-transplant incidence of hypertension, acute tubular necrosis, rejection, and late vascular and urologic complications. METHODS: We analyzed 998 adult kidney transplants done from December 1, 1985 through June 30, 1993, in which only the recipient's external or internal iliac artery was used for anastomosis. We divided the study population into 3 groups: Group A-1 renal artery, 1 arterial anastomosis (n = 835), Group B-->1 renal artery, 1 arterial anastomosis (n = 112), Group C-->1 renal artery, > 1 arterial anastomosis (n = 51). We compared the incidence of post-transplant hypertension, acute tubular necrosis, acute rejection, and vascular and urologic complications; mean creatinine levels at 1, 3, and 5 years post-transplant; and patient and graft survival. Univariate and multivariate analyses were done to identify risk factors for vascular complications. RESULTS: We found no significant differences among the three groups for the following variables: post-transplant hypertension, acute tubular necrosis, acute rejection, creatinine levels, early vascular and urologic complications, and graft and patient survival. In kidneys with single arteries, the presence (vs. absence) of an aortic patch and the type of the arterial anastomosis (end-to-end to the hypogastric vs. end-to-side to the external iliac artery) did not have an impact on the incidence of early or late vascular complications. In kidneys with multiple arteries, only the rate of late renal artery stenosis was higher, the rate of early vascular and urologic complications was not different. Our multivariate analysis identified acute tubular necrosis as a risk factor for renal artery and vein thrombosis; graft placement on the left side for arterial thrombosis; and preservation time > or = 24 hours and multiple renal arteries for renal artery stenosis. CONCLUSIONS: Results of kidney transplants using allografts with multiple versus single arteries are similar.

Adolescent↗
PubMed1995

Autologous islet transplantation to prevent diabetes after pancreatic resection.

BACKGROUND: Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. OBJECTIVE: Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. PATIENTS AND METHODS: Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. RESULTS: One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005). CONCLUSION: Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

Adolescent↗
PubMed1995

Effect of bisphosphonates and gallium on dentin resorption in vitro.

Replacement resorption may follow the replantation of an avulsed tooth. Currently there is no effective treatment for replacement resorption. The purpose of this study was to investigate the effect of bisphosphonates and gallium nitrate, which have been shown to reduce bone resorption, on cells which resorb dentin. Osteoclast-like cells were obtained by culturing cells from prenatal chick tibeas. These cells were seeded onto slices of human dentin which had been soaked in either saline (control), or solutions of 10(-5) M 1-hydroxyethylidene-1, 1-bisphosphonic acid (EHBP), 10(-6) M dichloromethylene bisphosphonic acid (Cl2MBP), or 10(-6) M gallium nitrate. Resorption was measured by counting the number of resorptive lacunae produced by the cells. Results indicated that the experimental groups did not differ significantly from each other, but each exhibited significantly reduced resorption compared with saline controls (p < 0.01). These results suggested that the experimental treatment reduced dentinal resorption by the osteoclast-like cells, and that these agents might be useful to prevent or at least postpone replacement resorption in avulsed teeth.

Animals↗
PubMed1995

Neuropathy profile of diabetic patients in a pancreas transplantation program.

We describe the results of extensive neurologic evaluation of 290 patients with insulin-dependent diabetes mellitus who came to our institution as potential recipients of a pancreas transplant. Large nerve fibers were evaluated by motor and sensory nerve conduction, small sensory fibers by thermal sensation thresholds, vagal and vasomotor functions by cardiovascular reflexes, and sympathetic sudomotor fibers by silicone imprints and evaporimetry. A scored anamnesis revealed symptoms of neuropathy in 86% of patients; 94% had an abnormal neurologic examination. The most frequently abnormal measurements of motor conduction were the amplitude of the extensor digitorum brevis muscle action potential to peroneal nerve stimulation and the conduction velocity of peroneal and tibial nerves in more than 80% of patients. Sensory nerve action potentials were abnormal in 76% and the distal latency of the sural nerve in 91%. Heart rate variability with deep breathing and during a Valsalva's maneuver was abnormal in 90% and 88%. Sudomotor function was reduced in 59% on the foot. Thermal sensitivity limen was above normal limits in 95% in the foot and 77% in the hand. Composite indexes of the degree of abnormality found for each type of function tested were correlated one with another, but were not predictive of results for any other test. The neuropathy of most patients was symmetric, involving to a similar degree motor, sensory, and autonomic nerves. Thus, diabetic neuropathy is very common and severe among patients who decide to be candidates for pancreas transplantation.

Adult↗
PubMed1995

Expression of intrahepatic inducible nitric oxide synthetase mRNA correlates with production of nitric oxide during intraportal isogeneic and allogeneic rat islet transplantation.

Intrahepatic NO production is related to the islet mass transplanted. Nitric oxide production is higher in recipients of allogeneic rather than syngeneic islets. In addition, in allogeneic recipients a possible second peak of NO production was observed at 120 hours corresponding to the time of cellular rejection of the islet grafts (P = .22 vs 96 hours). Finally, the time to rejection of Wistar rat donor islets transplanted into Lewis rat diabetic recipients treated with NMA was not affected. However, inhibiting NO production in the minimal islet transplant model decreased the time to islet function, it does not affect the time to clinical rejection in recipients of a high number of allogeneic islet, which functions immediately. High-level NO has been shown to inhibit T-cell activation in vitro, and thus decreasing the levels by administrating NMA may accentuate the rejection response, canceling out the beneficial effect that might otherwise have occurred on islet function. Further experiments are required to clarify these issues.

Amino Acid Oxidoreductases↗