A. J. Matas

INCREASED INCIDENCE OF MALIGNANCY DURING CHRONIC RENAL FAILURE

The incidence of cancer in 646 dialysis/transplant patients before uraemia developed, during the period of progressive uraemia, and post-transplantation was compared. 10 tumours (3 breast, 2 kidney, 1 leukaemia, 1 lung, 1 insulinoma, 1 thyroid, 1 cervix in situ) developed in 9 patients during the period of progressive uraemia, a significant increase over the expected number in the age-matched general population. 6 of these patients have received transplants and have no evidence of recurrent disease 6 months to 4 years post-transplantation. 11 de-novo tumours have developed in 530 transplant recipients (4 cervix in situ, 2 skin, 2 reticulum-cell sarcoma, 1 lip, 1 dysgerminoma, 1 colon)--a significant increase over the age-matched general population. The cancers in the uraemic patients are relatively common types of mesenchymal tumours while the cancers in the transplant recipients are epithelial and lymphoproliferative. This difference may reflect the presence of the graft in the transplant patient or may be due to different patterns of immunosuppression in these two populations.

Effects of Pancreatic Islet Transplantation on the Increased Urinary Albumin Excretion Rates in Intact and Uninephrectomized Rats with Diabetes Mellitus

The effects of reduced renal mass and of islet transplantation on urinary albumin excretion (UAE) rates in diabetic rats were examined. Increased UAE rates were noted two months after the induction of streptozotocin diabetes in 100-gm. inbred Lewis rats. Over the subsequent seven months, UAE rates remained constant in controls but were increasing in diabetic rats at the end of this time. Uninephrectomized nondiabetic rats had increasing UAE with time as compared with intact controls. Uninephrectomized diabetic rats had greater UAE than their respective controls, and the magnitude of this difference increased over the nine-month period of these studies. Uninephrectomized and intact rats, diabetic for seven months, were cured of the diabetic state by neonatal pancreatic tissue administered via the portal vein. Within one month of transplantation, UAE values decreased in these animals as compared with their pretransplant values and, within two months, were no longer different from values in their respective nondiabetic controls. In contrast, untreated uninephrectomized and intact diabetic rats increased their UAE over these same two months. At two months posttransplant, glomerular mesangial thickening was decreased in transplanted uninephrectomized and intact diabetic rats when compared with their respective untreated diabetic littermates. Thus, the albuminuria of diabetes in rats is reversed by pancreatic islet transplantation. It is unclear whether this reversal is primarily due to improvement in functional or structural abnormalities in glomeruli of diabetic rats.

The dispersed pancreas: Transplantation without islet purification in totally pancreatectomized dogs

SummaryForty-eight mongrel dogs were made diabetic by total pancreatectomy. Fifteen untreated pancreatectomized animals survived for a mean of 7±1 (SEM) days. Thirty-three dogs were divided into five groups and received autotransplants to the spleen of pancreatic fragments dispersed by collagenase digestion for 0, 10, 15, 20 or 25 minutes. Animals transplanted with tissue digested for 0 minutes or for 10 minutes remained hyperglycaemic (mean survival 22±12 days and 28±9 days). Normoglycaemia occurred in all but one of 21 dogs transplanted with tissue digested for 15–25 minutes. Two weeks after transplantation tolbutamide and glucose tolerance curves in the group receiving tissue digested for 20 minutes most closely resembled those of normal animals. Glucose tolerance test K values in dogs receiving tissue digested for 15, 20 and 25 minutes were 1.20±0.19 percent, 1.60±0.25 percent and 0.78±0.08 percent, respectively. The K values of the transplanted animals were significantly different from the K value of 0.35±0.05 percent in the apancreatic control dogs (p < 0.001). The mean K value of the dogs transplanted with tissue digested for 20 minutes was significantly better than the value in the dogs transplanted with tissue digested for 25 minutes (p < 0.02), but was significantly less than the K value (3.30±0.27 percent) obtained in 22 normal control dogs (p < 0.005). Hyperglycaemia recurred immediately following splenectomy in 12 normoglycaemic dogs 10 weeks after transplantation and all animals died. The remaining normoglycaemic transplanted dogs survived for at least six months. Histological examination of spleens from the transplanted animals showed the presence of islet and exocrine tissue within the splenic pulp with no apparent destructive effect on surrounding splenic parenchyma.

Uremic pericardial effusion. Treatment by catheter drainage and local nonabsorbable steroid administration

Pericardial drainage via percutaneous catheter placement and local nonabsorbable steroid instillation was employed as definitive therapy for uremic patients who had intractable pericardial effusions. Twelve patients are reported. Prior daily dialysis, and in one case systemic steroids, were not curative. 11 of 12 cases suffered severe tamponade requiring pericardiocentesis. One patient had an organized pericardial effusion, making pericardiocentesis impossible. He required pericardiectomy with prolonged hospitalization (2 weeks) due to postoperative complications. There were no complications in the 11 patients where catheter drainage and local steroid instillation were employed. No patient had recurrence of his pericardial effusion (followed from 2 weeks to 32 months). Instillation of a relatively nonabsorbable steroid through an indwelling pericardial catheter provides immediate and lasting relief without either the inconvenience or postoperative complications and prolonged hospitalization associated with the surgical procedure of pericardial fenestration. This report offers initial evidence that the percutaneous approach may be a safe and effective alternative to pericardial fenestration in most uremic patients with pericardial effusion.

Pre-discharge, post-transplant kidney biopsy does not predict rejection

Abstract The value of allograft biopsy 2 to 3 weeks after renal transplantation as a predictor of rejection was studied. Fifty non-HLA identical recipients had pre-discharge biopsy without complication. Biopsies were studied under light microscopy and with immunofluorescent stains; interpretation was done without knowledge of the clinical course and the biopsy was not used in patient management. Based on light microscopic findings, the patients were divided into three groups: normal (n = 33); acute interstitial infiltrate (n = 12), and acute tubular necrosis (n = 5). Subsequent course was determined. There was no difference between groups in percent patients having a subsequent acute rejection episode, timing of the first rejection, percent having more than one rejection, and percent kidneys currently functioning. Immunofluorescent studies did not help in predicting subsequent rejection. We conclude that pre-discharge biopsy does not predict subsequent course.

Successful long-term cryopreservation of neonatal rat islet tissue☆

Neonatal rat pancreatic tissue was frozen to -196 degrees C using Me2SO as a cryoprotectant and a slow freezing rate to -70 degrees C followed by immersion in liquid nitrogen. Rapid thawing was used. Viability was demonstrated by successful transplantation to streptozotocin-induced diabetic recipients. Long-term preservation, up to 4 weeks, did not demonstrably affect viability. Cryopreservation techniques may afford a method for providing a diabetic recipient the opportunity to receive a large quantity of pooled islet tissue from well-matched donors.

Autotransplantation von Pankreasfragmenten an total pankreatektomierten Hunden unter Verzicht auf Trennung von exo- und endokrinem Gewebe

Es wurde wiederholt nachgewiesen, das ein experimentell induzierter Diabetes mellitus bei Laboratoriumsnagetieren durch Autooder Allotransplantation isolierter Langerhans’scher Inseln gebessert werden kann — Literaturubersicht bei (5). Nur sporadische Berichte existieren uber erfolgreiche Inseltransplantationen an groseren Tieren, wohl weil die an Nagetieren so erfolgreichen Methoden der Inselgewinnung bei hoheren Spezies problematisch anzuwenden sind.

Cellular immunity in species with variable rejection of vascularized grafts

We studied the in vitro and in vivo cellular response in three distinctly different xenograft models, using C57BL/6 mice as responders and Lewis rats (LR), Golden Syrian hamsters (GSH), and Strain 2 guinea pigs (GP) as stimulators. Previous work has shown that cardiac grafts from rats, hamsters, and guinea pigs are rejected by C57BL/6 mice in 7 days, 4 days, and 10 min., respectively. In xenogeneic mixed lymphocyte culture, response was in general greatest to GSH splenocytes: stimulation index (S.I.) = 11.4 +/- 3.6 followed by the response to LR cells, S.I. = 3.5 +/- .09, which was less than that of an allogeneic control C57BL/6 anti-DBA, S.I. = 8.4 +/- 1.7. GP stimulator splenocytes produced inhibition of response (S.I. = 0.23 +/- .07) with all counts being below baseline and remaining low despite addition of IL-1, IL-2, or both. In fact, these cells were inhibitory to other allo or xeno mixed lymphocyte cultures in a dose-dependent manner. Cytotoxicity studies revealed maximal killing of ConA blasts in the allogeneic control followed by killing of GSH blasts and LR blasts and no killing of GP blasts. There was also a moderate degree of nonspecific killing between allo and xeno systems. In vivo analysis of cell-mediated cytotoxicity was done using a sponge matrix allograft model. The sponge was injected with donor cells and implanted into C57BL/6 mice. The response to donor cells was tested using cells accumulating in the sponge. There was maximal response to GSH cells greater than DBA greater than LR greater than GP.(ABSTRACT TRUNCATED AT 250 WORDS)