Immunosuppression in composite tissue allografts.
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Biomedical subjects
Publications and source records attributed to M Da Silva.
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BACKGROUND: Patients on dialysis are less physically active than sedentary persons with normal kidney function. To assess the consequences of inactivity and the results of efforts to increase activity in the end-stage renal disease (ESRD) population, valid instruments to measure physical activity and physical functioning in this group are needed. METHODS: We performed a cross-sectional study to establish the validity in ESRD of several questionnaires designed to measure physical activity or physical functioning in the general population. Questionnaires studied included the Stanford 7-day Physical Activity Recall questionnaire (PAR), the Physical Activity Scale for the Elderly (PASE), the Human Activity Profile (HAP), and the Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Physical activity was measured using three-dimensional activity monitors (accelerometers) over a seven-day period (the "gold standard"). Patients also underwent physical performance tests, including measurement of gait speed, stair climbing time, and chair rising time. Study questionnaires were administered, and questionnaire results were compared with each other and with activity monitor and physical performance test results. RESULTS: Thirty-nine maintenance hemodialysis patients participated in the study. Dialysis patients scored worse than previously published healthy norms on all tests. All questionnaires correlated with seven-day accelerometry and with at least one measure of physical performance. The HAP correlated best with accelerometry (r = 0.78, P < 0.0001). Seventy-five percent of the variability in physical activity measured by accelerometry could be explained by a model that combined information from the HAP and the PASE. The HAP and the physical functioning scale of the SF-36 were about equally well correlated with physical performance measures. CONCLUSIONS: These questionnaires are valid in patients on hemodialysis and should be used to study the physical activity and rehabilitation efforts in this population further.
PURPOSE: We established a primate model to investigate the effects of the antileukocyte function associated antigen 1 (CD 11a) mAb odulimomab (Imtix-Sangstad, Lyon, France) for preventing renal ischemia-reperfusion injury. MATERIALS AND METHODS: We randomly divided 34 Macaca cynomolgus monkeys into groups 1 and 2, which received a renal autograft after 2 hours of cold ischemia, and groups 3 and 4, which received the autograft after 24 hours of cold ischemia. Before cold ischemia all harvested kidneys were subjected to 30 to 45 minutes of warm ischemia. Groups 1 and 3 monkeys were treated with an antileukocyte function associated antigen 1 mAb before cold ischemia and then for 3 days, while groups 2 and 4 monkeys received an IgG1 isotype control. In all groups renal function was investigated before warm ischemia and 72 hours after reperfusion. Serum creatinine and the leukocyte count were determined daily. Histological studies were done and lactoferrin was measured in the autotransplanted kidney 72 hours after reperfusion. RESULTS: A decrease in renal function was shown after 2 hours of cold ischemia with tubular necrosis and mild cell infiltration, while after 24 hours of cold ischemia there was severe renal failure with tubular and glomerular necrosis, and leukocyte infiltration. A significant improvement in renal function and decrease in kidney lactoferrin content was evident in group 1 compared to group 2 at 72 hours, while no significant difference was noted in groups 3 and 4. No difference in histological patterns was evident in treated and untreated animals. CONCLUSIONS: This study provides evidence for the validity of this ischemia-reperfusion injury model in primates. The protective effects of antileukocyte function associated antigen 1 mAb on renal injury was not as dramatic as in rodent models but a significant improvement in renal function was observed in treated animals after 2 hours of cold ischemia.
A randomized study of combined kidney-pancreas transplantation was performed on 30 insulin-dependent diabetic patients with end-stage renal disease to compare the consequences of pancreas transplantation with portal venous (PV) and systemic venous (SV) drainage. Fourteen patients (SV) group) received systemically drained and sixteen (PV group) portally drained pancreas allografts. Enteric drainage was performed in both groups. The routine follow-up included documentation of the clinical course and detailed endocrine studies. At 1 year after transplantation, the patient survival rate was 92% for the SV group and 96% for the PV group; the graft survival rate was 78% and 82%, respectively. Endocrine studies indicated no difference in fasting and stimulated glucose or in glycosylated hemoglobin between the two groups. In addition, no hyperinsulinemia and lipidic abnormalities were evidenced in either group Long-term studies are required to conclude whether PV and SV drainage in pancreas transplantation are equivalent in terms of patient and graft survival as well as metabolic consequences.
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Simultaneous pancreas-kidney (SPK) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end-stage diabetic nephropathy. This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function. From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were randomly assigned to two groups: the first group (SV group = 17) received SPK transplantation with systemic venous drainage, and the second group (PV group = 17) received pancreas allograft with portal drainage. A Roux-en-Y loop was performed in all the patients. Patient follow-up included clinical course and metabolic studies. At 1 yr, patient survival rates were 88.2% in the SV group and 94.1% in the PV group while graft survival rate was 76.4% in both groups. Several surgical complications were attributed to the enteric drainage without any graft failure in both groups. One venous thrombosis occurred in each group. No significant differences have been evidenced in kidney and pancreas function. The preliminary results of this randomized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft.
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It has been recently proposed that haemodialysis membrane choice may influence the maintenance of residual renal function. The aim of the present study was to prospectively analyse the effect of membrane choice on the outcome of renal function in patients entering a chronic haemodialysis programme. Twenty-two patients from four hospitals have been randomly assigned to be dialysed with either polysulphone (PSF)/polyacrylonitrile (PAN) (group A; n = 9), or cuprophane membranes (group B; n = 13). Basal and monthly serum biochemistry, residual creatinine clearance (Ccr) and urine volume (Vu), pharmacological and dialytic treatment, diet, and haemodialysis-related complications were recorded. A significant decrease was observed in the two most relevant variables, i.e. remnant Ccr and Vu, within 3 months of starting haemodialysis, with stabilization during the further follow-up. Such decrease was similar (P NS) for both groups A and B throughout the 9-month observation period. In conclusion, our results suggest that the choice of haemodialysis membrane does not influence the outcome of the residual renal function. Renal function decreased significantly within 3 months on haemodialysis, independently of the type of dialyser membrane.
The metabolic changes in neonatal hydrocephalus that lead to permanent brain injury are not clearly defined, nor is the extent to which these changes can be prevented by a cerebrospinal fluid shunt. To clarify these processes, cerebral glucose utilization was examined using [14C]2-deoxyglucose autoradiography in 1-month-old kittens, kaolin-induced hydrocephalic littermates, and hydrocephalic kittens in which a ventriculoperitoneal shunt had been inserted 10 days after kaolin injection. The hydrocephalic kittens showed thinning of the cerebral mantle and an anterior-to-posterior gradient of enlargement of the ventricular system, with a ventricle:brain ratio of 24% for the frontal and 35% for the occipital horns compared with control (< 0.5%) and shunted (< 5%) animals. White matter in hydrocephalic animals was edematous. Myelination was delayed in the periventricular region and in the cores of the cerebral gyri. Glucose utilization in hydrocephalic and shunted animals was unchanged from control animals in all gray-matter regions examined. However, in hydrocephalic animals, the frontal white matter exhibited a significant increase in glucose utilization (25 mumol.100 gm-1.min-1) in the cores of gyri compared with normal surrounding white-matter values (14.8 mumol.100 gm-1.min-1). Very low values (mean 4 mumol.100 gm-1.min-1) were found in areas corresponding to severe white-matter edema, and these areas were surrounded by a halo of increased activity (24 mumol.100 gm-1.min-1). In contrast, cytochrome oxidase activity in white matter was homogeneous. Shunting resulted in restoration of the cerebral mantle thickness, a return to normal levels of glucose utilization in the white matter, and an improvement in myelination. It is suggested that the areas of increased glucose utilization seen in the white matter represent anaerobic glycolysis which, if untreated, progresses to infarction. The pattern of this increased glucose utilization matches that of expected myelination and, during this period of high energy demand, white matter may be susceptible to the hypoperfusion associated with hydrocephalus.
A pineal germinoma in a 9-month-old boy is described. After surgical resection and cerebrospinal fluid diversionary shunting, the child developed hematogenous metastases which showed marked increased uptake on radionuclide gallium-67 scans.
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