PubMed Health⌕ Search

Biomedical subjects

G Basadonna

Publications and source records attributed to G Basadonna.

At least 19 recordsLinked to original sources
PubMed2000

Posttransplant bone disease: evidence for a high bone resorption state.

Loss of bone is a significant problem after renal transplant. Although bone loss in the first post transplant year has been well documented, conflicting data exist concerning bone loss after this time. It is equally unclear whether bone loss in long-term renal transplant recipients correlates with bone turnover as it does in postmenapausal osteoporosis. To examine these issues, we conducted a cross-sectional study to define the prevalence of osteoporosis in long-term (> 1 year) renal transplant recipients with preserved renal function (mean creatinine clearance 73 +/- 23 ml/min). Bone mineral density (BMD) was measured at the hip, spine and wrist by DEXA in 69 patients. Markers for bone formation (serum osteocalcin) and bone resorption [urinary levels of pyridinoline (PYD) and deoxypyridinoline (DPD)] were also measured as well as parameters of calcium metabolism. Correlations were made between these parameters and BMD at the various sites. The mean age of the patients was 45 +/- 11 years. Eighty eight percent of patients were on cyclosporine (12% on tacrolimus) and all but 2 were on prednisone [mean dose 9 +/- 2 mg/day)]. Osteoporosis (BMD more than 2.5 SD below peak adult BMD) at the spine or hip was diagnosed in 44% of patients and osteopenia was present in an additional 44%. Elevated levels of intact parathyroid hormone (i PTH) were observed in 81% of patients. Elevated urinary levels of PYD or DPD were present in 73% of patients and 38% had elevated serum levels of osteocalcin. Levels of calcium, and of 25(OH) and 1,25(OH)2 vitamin D were normal. In a stepwise multiple regression model that included osteocalcin, PYD, DPD, intact PTH, age, years posttransplant, duration of dialysis, cumulative prednisone dose, smoking, and diabetes: urinary PYD was the strongest predictor of bone mass. These results demonstrate that osteoporosis is common in long-term renal transplant recipients. The data also suggest that elevated rates of bone resorption contribute importantly to this process.

Adult↗
PubMed1998

Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Acute Disease↗
PubMed1992

Kidney transplantation in patients with type I diabetes: 26-year experience at the University of Minnesota.

With current immunosuppressive protocols, 1- and 6-year graft survival is similar in diabetic and nondiabetic kidney transplant recipients. Living-donor transplant recipients have significantly better outcome. Death with function and chronic rejection remain the 2 predominant causes of graft loss for diabetic recipients. Compared with national statistics on diabetic patient survival on dialysis, our data suggest that transplantation is the treatment of choice for diabetic patients with end-stage renal disease.

Adolescent↗
PubMed1988

Cyclosporin A and islet function.

Long-term cyclosporin A (CsA) administration in dogs was studied with respect to function of the islets of Langerhans. After 3 weeks of immunosuppression with therapeutic doses, the islets were isolated and assessed in vitro for insulin release in response to glucose challenge. Islet tissue retrieved from the CsA-treated animals showed a total insulin output significantly lower than that of the control animals (p less than 0.01). The first and second phases of insulin release were both impaired in animals treated with CsA compared with controls (p less than 0.001 and p less than 0.05, respectively). The negative impact of CsA on the beta cells was easily demonstrated in this in vitro study. Similar results are more difficult to achieve with purely in vivo models, probably due to the great redundancy of the islet mass in intact animals. The mechanism of this CsA toxicity remains to be defined.

Animals↗
PubMed1988

Cyclosporine absorption in apancreatic dogs.

The plasma concentration time course of orally administered cyclosporine was studied in apancreatic dogs with established islet autografts and compared with that in normal control dogs. After oral administration of cyclosporine (20 mg/kg), blood samples were collected at 0, 1, 2, 3, 4, 6, 8, and 24 hours, and the plasma cyclosporine concentrations were measured by radioimmunoassay. The plasma level of cyclosporine increased promptly in both groups after dosing. Peak plasma concentrations ranged from 435 to 1,542 ng/ml and were attained at between 2 and 6 hours in the apancreatic dogs, and concentrations from 602 to 4,414 ng/ml were attained at between 1 and 6 hours in the control dogs. Even though there was substantial variation among animals, the plasma concentration curve of the apancreatic group was quite comparable with that of the control group. The Student's test for unpaired data failed to show any significant differences over the time course. Area under the concentration-time curves, maximum concentration, and times of peak concentration were calculated. These data demonstrated the capacity of apancreatic dogs with islet autografts to absorb cyclosporine when they are stable, nutritionally normal, and have full endocrine reconstitution.

Absorption↗
PubMed1987

Donor-specific antigen and cyclosporine in rat islet allografts.

Combination therapy with one dose of 3 M KCl extracted donor-soluble antigen (Ag) and a short course of cyclosporine (CsA) has proven to prolong the survival of kidney allografts by enhancing specific T-suppressor populations. This regimen is tested in rat islet allografts in this study (Lewis to ACI). A 3-day perioperative course of 10 mg/kg/day CsA on Days -1, 0, and 1 did not prolong graft survival (MST = 10.7 +/- 2.5 days vs 9.4 +/- 1.2 days in controls). When this course of CsA therapy was combined with a single dose of donor antigen on Day -1, the survival time was prolonged slightly but significantly (MST = 14.0 +/- 5.8 days). Three cycles of a 3-day course of CsA therapy at 7-day intervals, a total of nine doses of 10 mg/kg/day CsA, were effective in delaying rejection of islet allografts (MST = 26.4 +/- 30.3). Moreover, combined therapy with donor antigen and three cycles of a 3-day course of CsA prolonged the survival of islet allografts (MST = 57.7 +/- 51.4 days) with 50% of recipients still normoglycemic at 60 days after transplantation. These findings indicate that the combination therapy of donor antigen with a short course of CsA has a powerful effect to prevent the rejection of islet allografts, as shown in kidney allografts, in rats.

Animals↗
PubMed1987

Allotransplantation of islet endocrine aggregates.

Dissociated pancreatic islets form endocrine aggregates from single-cell suspension by rotation culture. Islet cell aggregates, or neoislets, can provide endocrine reconstitution for diabetic rats and enjoy prolonged graft survival when neoislets are transplanted across a major histocompatibility barrier (Lewis to ACI). Long-term survival of grafted neoislets was obtained in 71% of recipients without any immunosuppression and in 100% of recipients with minimal immunosuppression. As predicted by cell-cell recognition in rotation-mediated aggregation, neoislets apparently exclude mesenchymal cells that bear la antigens. Therefore, reduced immunogenicity is accomplished.

Animals↗
PubMed1986

Effect of cyclosporine on established islet autografts.

Cyclosporine (CyA) is toxic to the function of isolated islets and this toxicity may, in part, explain the failure of islet allografts as well as autografts with CyA immunosuppression. Not only do canine allografts fail despite CyA immunosuppression, but control autografts given CyA from the day prior to transplantation have a very high failure rate. In this study, we investigated CyA effects on established islet autografts. Twenty mongrel dogs underwent total pancreatectomy and successful intrasplenic islet autotransplantation. Ten served as control autografts (Group 1); five were started on oral CyA on the 5th postoperative day (Group 2) and 5 dogs were given CyA from the 10th day after grafting (Group 3). Intravenous glucose tolerance tests were performed before operation, before starting CyA and after 3 weeks. Plasma insulin was determined by radioimmunoassay. Control dogs remained normoglycemic throughout the study as did Group 3 animals. In Group 2, 2 of 5 dogs failed, both on the 4th day of CyA, while the other 3 were normoglycemic throughout the study. No significant difference was shown among the K values, fasting blood glucose and peak plasma insulin values following IVGTT before and after treatment with CyA. CyA begun the day before autografting gravely compromises graft success. However, after the graft is well established, an adverse effect of CyA on islet cell function is not evident.

Administration, Oral↗
PubMed1986

Neural regulation of heterotopic islets of Langerhans.

The possibility of vagal reinnervation to intrasplenic islet grafts was examined by measuring portal insulin response to electric stimulation of the dorsal vagus nerve in autografted dogs. Grafted islets responded appropriately to an exogenous cholinergic agent given intravenously. However, no insulin secretory response could be observed in grafted dogs after vagal stimulation, which markedly increased portal insulin levels in control dogs. Therefore, intrasplenic islets are not under direct vagal control. At the basal state, normal oscillatory release of insulin was observed in the animals with grafts, suggesting that the mechanism of rhythmic basal insulin release is intrinsic to the islet of Langerhans with no regulatory input from the vagus nerve or any element of pancreatic structure.

Animals↗
PubMed1985

Canine islets in an ultrafiltered environment.

Molecular sieve membranes can protect pancreatic islets against immune recognition in diabetic patients treated by endocrine tissue replacement. These biocompatible membranes permit the passage of small peptides such as insulin, and preclude the diffusion of immunoglobulins and immunogenic molecules. However, the tissue must function indefinitely in an ultrafiltered environment determined by the sequestering membranes. The chronic perifusion of canine islet tissue was compared in ultrafiltered and microfiltered chambers. The biphasic pattern of insulin release by similar numbers of islets from the same pancrease preparation was not significantly different when tissue was cultured in a micro- or an ultrafiltered environment. The cumulative insulin output of the two systems was quite similar over 3 days of culture. Canine islet tissue can be sustained in an ultrafiltered environment with maintenance of insulin release to glucose stimulation, which is quantitatively similar to islet tissue maintained in chronic perifusion without ultrafiltration.

Animals↗