Induction of cell proliferation and differentiation in the pancreas of the adult Vervet monkey (Cercopithecus aethiops): preliminary results.

Cellophane wrapping of the adult Syrian golden hamster pancreas has been found to result in ductular cell proliferation leading to islet regeneration. Injection of cytosol from a cellophane-wrapped pancreas into normal or diabetic hamsters evoked a similar response. In view of the therapeutic potential of the active substance in this cytosol, it was decided to investigate whether a similar response could be achieved in a primate. In normal adult Vervet monkey (Cercopithecus aethiops) pancreas, proliferation is seen only rarely in islet cells and occasionally in duct and acinar cells. Immunohistochemical investigation of normal Vervet monkey pancreas (n = 4) and 14 days (n = 2) and 56 days (n = 1) after cellophane wrapping of the Vervet monkey pancreas revealed a slight increase in proliferation of islet and acinar cells and a larger increase in proliferation of duct cells and in total endocrine cell volume. The results suggest that there is a latent developmental capability in the adult primate pancreas.

Behavioural changes in children following minor surgery--is premedication beneficial?

One hundred and twenty-three male children, aged one to ten years, were studied to determine the influence of premedication on changes in patterns of behaviour following hospitalization for repair of inguinal hernias. Four comparable groups were selected for premedication regimen: (1) A control group without premedication; (2) oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg and droperidol 0.15 mg/kg; (3) oral midazolam 0.45 mg/kg; (4) intramuscular midazolam 0.15 mg/kg. Standard inhalational anesthesia was used and caudal blocks employed for analgesia. The parents returned a questionnaire at two weeks. Changes in behaviour were reported in 78% of the children and overall, premedication showed little benefit. However, midazolam premedication was associated with a significantly lower incidence of night-time crying and awakening, compared with no premedication. Only for night-time crying and day-time toilet training did age below five years prove to be a significant contributing factor.

Solitary gumma in a neonate. A case report.

An unusual case of congenital syphilis is reported. A week-old baby presented with abdominal distension, small-bowel obstruction, bilious vomiting and a large left upper quadrant mass. Histopathological examination of a specimen of the mass confirmed the clinical diagnosis of gumma formation. Primary resection with end-to-end anastomosis was carried out. The baby made an uneventful recovery.

Significant prolongation of segmental pancreatic allograft survival in two species.

A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

Pancreatic transplantation in a patient with severe insulin resistance. A case report.

A 22-year-old white woman with insulin-dependent diabetes mellitus of 20 years' duration and advanced secondary complications underwent pancreatic transplantation for severe insulin resistance and rapidly progressive nephropathy. Resistance to all forms and strengths of subcutaneously administered insulin had necessitated almost permanent hospitalisation for the previous 10 years. Short-term improvement of the endocrine and metabolic status was achieved by initial segmental and subsequent whole pancreatic transplantation.

Islet cell function in long-term surviving primates after segmental pancreatic allotransplantation.

Islet cell function was studied in pancreatectomized primates with functioning segmental pancreatic allografts more than 100 days after transplantation. Segmental allograft recipients were immunosuppressed with total lymphoid irradiation (TL1) and cyclosporine (CSA). After 100 days, islet function was assessed, at which stage immunosuppression was terminated. Glucose, insulin, glucagon, and C-peptide response was assessed during intravenous glucose tolerance test (IVGTT) and during arginine and tolbutamide stimulation. In eight normoglycaemic primates in which immunosuppressive treatment had been stopped and with mean graft survival of 145 days, islet stimulation was associated with moderate glucose intolerance, reduced K-values, hypoinsulinaemia, and low C-peptide values. Postmortem findings in all animals intentionally killed revealed severe graft atrophy in the absence of significant rejection. Severe graft atrophy in normoglycaemic primates, together with significantly impaired graft function after segmental pancreatic transplantation compared to normal animals, suggest that transplantation of the whole pancreas may be mandatory if normal or near-normal function is to be achieved.

Endocrine function after hetero- and ortho-topic segmental pancreatic transplantation in primates.

This study assessed the early postoperative pancreatic endocrine function after intraperitoneal segmental hetero- and ortho-topic pancreatic allotransplantation in hemipancreatectomized, nonimmunesuppressed chacma baboons. Hemipancreatectomized animals remained normoglycaemic but rendered significantly reduced K values and insulin release during IVGTT, findings consistent with major pancreatic resection. Segmental hetero- or ortho-topic pancreatic transplantation did not improve reduced K values and hypoinsulinaemia following hemipancreatectomy although orthotopically sited grafts rendered the best glucose tolerance test curves. Glucagon output during IVGTT remained the same in both transplant models. It is concluded that the postoperative hormonal response was similar in both orthotopic and heterotopic transplant recipients, which indicates that drainage of graft venous effluent into the portal circulation has no advantage over systemic insulin drainage as reflected in this "diabetic" model.

Effect of cyclosporine and irradiation on experimental pancreatic allografts in the primate.

The present study assessed the effectiveness of cyclosporine (CSA) and subtotal marrow irradiation (TL1) alone, and CSA in combination with TL1 in a primate segmental pancreatic allotransplantation model. Continuous administration of CSA 25 mg/kg/day and 50 mg/kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. Administration of fractionated TL1 800 rad (8 Gy) and 1,000 rad (10 Gy) alone resulted in mean graft survival of 13.3 days and 14.5 days, respectively. Of 20 animals that received TL1 1,000 rad (10 Gy) and CSA 25 mg/kg/day orally for 5 days then 10 mg/kg/day intramuscularly indefinitely, 3 had graft survival of greater than 100 days. Likewise, of a group of 15 animals that received TL1 800 rad (8 Gy) and combined indefinite administration of CSA, 6 had graft survival of greater than 100 days. Although CSA and TL1 administration alone produced modest pancreatic allograft survival, a combination of IL1 (800 or 1,000 rad) and CSA resulted in highly significant segmental pancreatic allograft survival in the primate.

Caudal block for analgesia after paediatric inguinal surgery.

Two hundred and eleven children aged 1-5 years were studied after undergoing herniorrhaphy or orchiopexy. In 111 cases a caudal block was used for postoperative analgesia. This was administered immediately after induction of anaesthesia, using bupivacaine 0.25% plain (0.7 ml/kg lean body mass), and was successful in 100 patients. A mean analgesic level (+/- SE) of T9.9 +/- 0.47 was achieved (range L2-T6). In 5 cases no block occurred and in 6 the level was below T12. The other 100 children acted as controls. Behaviour patterns were more restful in the caudal block group on awakening and less opiate was required during the first 5 postoperative hours. No complications resulted.

Primate endocrine function after pancreatico-duodenal-splenic allotransplantation.

In this study the endocrine function following intraperitoneal hetero- and orthotopic pancreatico-duodenal-splenic allotransplantation (PDS) in hemipancreatectomized, non-immune-suppressed chacma baboons was assessed. Significantly reduced K-values and insulin release together with glucose intolerance during IVGTT were observed in hemipancreatectomized recipients (HPS) without grafts. Orthotopic and heterotopic PDS transplantation improved the glucose intolerance of HPS recipients; orthotopically sited grafts rendering the best curves. Normal glucose tolerance was not achieved. Both orthotopic and heterotopic PDS transplantation rendered suboptimal insulin release during IVGTT; heterotopically draining grafts released significantly more insulin than orthotopic grafts. Hyperglucagonaemia during IVGTT was a constant feature in both groups, heterotopic grafts releasing the most glucagon during stimulation. C-peptide release was significantly lower in orthotopic grafts compared to normal animals or heterotopically drained insulin. It is concluded that glucose tolerance was not directly related to insulin or glucagon release in this study as orthotopic grafts rendered near-normal IVGTT curves in the presence of hypoinsulinaemia, hyperglucagonaemia, and reduced C-peptide values. The hormonal response after PDS transplantation was variable and the advantages of portal vs systemic insulin drainage remain to be defined.

Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine.

The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum.