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Biomedical subjects

C G Groth

Publications and source records attributed to C G Groth.

At least 55 records · Page 3Linked to original sources
PubMed1998

Survival of fetal porcine pancreatic islet tissue transplanted to a diabetic patient: findings by ultrastructural immunocytochemistry.

Porcine fetal endocrine pancreatic tissue was placed under the kidney capsule in a diabetic renal transplant patient. In a core-needle kidney biopsy specimen obtained 3 weeks after transplantation, clusters of epithelial cells were identified in the subcapsular space. The ultrastructural and immunocytochemical features of these cells were typical of pancreatic islet cells. Some cells stained positively for insulin; others stained positively for glucagon, somatostatin or chromagranin A. There were well-defined cytoplastic storage and transport granulae that indicated hormone synthesis. The ultrastructural findings provide further evidence that porcine cells can survive after transplantation to humans.

Adult↗
PubMed1998

Urinary tract infections following renal transplantation.

The incidence of urinary tract infections (UTIs) in 363 adult renal transplant recipients transplanted during the period 1990-96 has been analysed. UTI occurred in 96 patients (26%), most frequently during the first year after transplantation. Female recipients had significantly more UTI than male recipients (49% vs. 14%, p < 0.0001). There was no difference in the incidence of UTI between recipients receiving pig-tail catheters as ureteral stents or not, the figures being 21% vs. 28%, respectively. Age had no influence on the incidence of UTI. In 341 patients treated with cyclosporine the incidence of UTI was 28%, while in 15 patients treated with FK-506 only 1 patient (7%) had a UTI (ns). The majority of organisms cultured were gram-negative (76%), with approximately 1/3 being Escherichia coli and 1/5 being Enterococcus and Klebsiella/Enterobacter. The bacterial spectrum was not influenced by the recipient's age. UTI had no effect on the number of rejections, or on graft and patient survival in living donor transplant recipients. No significant difference was found in graft and patient survival rates at 3 yr between patients who had UTI or no UTI.

Adolescent↗
PubMed1997

Kidney donors live longer.

BACKGROUND: A very important issue in living kidney donor transplantation is whether the donation is safe for the donor. The aim of this study was to examine survival and causes of death in kidney donors and to assess the renal function in those who had donated a kidney more than 20 years ago. METHODS: A total of 459 living donor nephrectomies were performed in Stockholm from 1964 until the end of 1994. By using national registers, all 430 donors living in Sweden were traced. Donor survival was analysed using the Kaplan-Meier method. Expected survival was computed using the Hakulinens method and was based on national mortality rates. RESULTS: Forty-one subjects had died between 15 months and 31 years after the donation. The mortality pattern was similar to that in the general population, the majority dying of cardiovascular diseases and malignancies. After 20 years of follow-up, 85% of the donors were alive, whereas the expected survival rate was 66%. Survival was thus 29% better in the donor group. One third of the donors (aged 46-91 years) who had donated >20 years ago had hypertension. There was a deterioration in the renal function with increasing age, similar to what is seen among normal healthy subjects. The average glomerular filtration rate in donors aged 75 years and over was 48 ml/min/1.73 m2. CONCLUSIONS: To donate a kidney does not seem to constitute any long-term risk. The better survival among donors is probably due to the fact that only healthy persons are accepted for living kidney donation.

Adult↗
PubMed1997

Efficacy of immunosuppressive drugs in islet xenotransplantation: leflunomide in combination with cyclosporine and mycophenolate mofetil prevents islet xenograft rejection in the pig-to-rat model.

BACKGROUND: Morphological characteristics of islet xenograft rejection differ from those of islet allograft rejection. Therefore, prevention of islet xenograft rejection probably requires a different type of immunosuppression from that used in allogeneic transplantation. METHODS: Fetal porcine islet-like cell clusters (ICC) were transplanted into the renal subcapsular space of rats treated with different immunosuppressive protocols. The existence of a cellular infiltrate or deposits of antibodies and complement in the grafts was evaluated at different times after transplantation using immunohistochemistry. RESULTS: Treatment with leflunomide (LEF), cyclosporine (CsA), mycophenolate mofetil (MMF), 15-deoxyspergualin, and rapamycin alone or in combination had an insufficient inhibitory effect on ICC xenograft rejection. However, in animals treated with LEF+CsA, the rejection process was markedly inhibited. However, some macrophages and T cells were still present, and at 24 days, the xenografts were destroyed. In LEF+CsA-treated animals that were given sera containing an excessive amount of rat anti-porcine xenoreactive antibodies, marked deposits of IgG, and to some extent C3 as well, were detected along the border between intact ICC, and the xenografts were surrounded by macrophages. However, almost no cells infiltrated the grafts, and there were many intact ICC. In animals treated with LEF+CsA+MMF, only occasional infiltrating cells were seen at 12 and 24 days after transplantation, and the endocrine tissue was completely intact. CONCLUSIONS: LEF+CsA+MMF prevented rejection of porcine ICC xenografts in the rat for up to 24 days after transplantation.

Animals↗
PubMed1997

Kinetics and dynamics of single oral doses of sirolimus in sixteen renal transplant recipients.

Sirolimus is a new immunosuppressive drug that has been evaluated in animal experiments. The current study was conducted on humans with reformulated sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients were included in this phase I study to determine the safety, tolerance, and preliminary pharmacokinetics of increasing single doses of orally administered sirolimus. All 16 patients had stable renal graft function after a renal transplant at least 6 months before the study. Basal immunosuppression consisted of cyclosporine and prednisolone (n = 10) or cyclosporine, azathioprine, and prednisolone (n = 6). Four groups (I, 3 mg/m2; II, 5 mg/m2; III, 10 mg/m2; IV, 15 mg/m2) of four patients were assigned randomly to receive sirolimus (n = 3) or placebo (n = 1). Among the 12 patients who received sirolimus, five had mild transient study events such as headache, nausea, mild dizziness, hypoglycemia, epistaxis, and decrease in platelets. No serious adverse events occurred and no nephrotoxic effects could be related to the single dose administration of sirolimus. The only study event that was judged as probably related to sirolimus was the single case of thrombocytopenia. The other events were evaluated as possibly related. Thrombocytopenia occurred at the highest dose level (15 mg/m2 sirolimus). In two of the patients in the placebo group, slight elevations of liver enzymes and serum amylase were seen. Blood and plasma sirolimus concentrations were analyzed by an electrospray-high performance liquid/mass spectrophotometric (ESP-HPLC/MS) method Sirolimus showed an extensive red blood cell distribution with a mean blood/ plasma ratio of 49.1. The elimination half-life ranged from 43.8 to 86.5 hours (mean 56.9 hours). The Cmax and the area under the concentration versus time curves (AUC) correlated reasonably with doses from 3 to 15 mg/m2. The oral dose clearance ranged from 42 to 339 ml/h.kg. No clinically significant differences were seen in the trough concentrations of cyclosporine or the AUCs before and after the administration of sirolimus. Administration of single oral doses of sirolimus from 3 to 15 mg/m2 was safe and well tolerated in stable renal transplant recipients. Thrombocytopenia may be the dose-limiting toxicity. Additional phase II and phase III clinical trials will define the immunosuppressive efficacy of sirolimus.

Administration, Oral↗
PubMed1996

Pancreatic endocrine function in recipients of segmental and whole pancreas transplantation.

To determine potential abnormalities in beta-cell function after pancreas transplantation, the secretory capacity of the pancreatic grafts was assessed by measuring the glucose-potentiating effect on arginine-induced insulin secretion in recipients of cadaveric segmental (SPx; n = 8) and whole organ pancreas grafts (WPx; n = 6) and compared to that in nondiabetic kidney transplant recipients (Kx; n = 6) and normal controls (Ns; n = 7). alpha-Cell adaptation to increasing hyperglycemia and the glucagon response to arginine stimulation were also studied. The secretory capacity of the beta-cell to arginine-induced (5 g L-arginine) insulin secretion was measured at fasting plasma glucose and 15 and 30 mmol/L glucose. Insulin secretion was evaluated by the calculation of insulin secretion rates. Insulin sensitivity was markedly reduced in all three transplanted groups compared to that in normal subjects (P < 0.05). The prestimulation insulin secretion rate and maximal insulin secretion rate in response to hyperglycemia and arginine were significantly lower in SPx than in WPx, Kx, or Ns (P < 0.05). The incremental amount of insulin secreted in response to arginine was reduced by 40-70% in SPx depending on glycemia compared to that in all other groups (P < 0.05), among which there were no statistical differences. Both SPx and WPx demonstrated suppression of glucagon release in response to graded hyperglycemia, but failure to adequately suppress arginine-induced glucagon release. In conclusion, recipients of cadaveric segmental pancreas grafts display a markedly reduced maximal insulin secretory reserve capacity. This impairment was primarily due to an insufficient beta-cell mass. Taking the concomitant insulin resistance into account, recipients of a cadaver whole organ pancreas graft had an impaired insulin secretory reserve capacity as well.

Adult↗