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J J Heydenrych

Publications and source records attributed to J J Heydenrych.

At least 37 records · Page 2Linked to original sources
PubMed1987

Application of irradiation as an immunosuppressive agent.

The concept of using total lymphoid irradiation (TLI) for immunosuppression is based on the prolonged and profound immunosuppressive effects observed after TLI in the treatment of patients with Hodgkin's disease. Pre-operative TLI of allograft recipients has been shown to be immunosuppressive when used alone or together with chemical immunosuppression. Fractionated TLI and allogeneic bone marrow injections produce stable chimaerism without graft-versus-host disease in inbred mice, rats and mongrel dogs and transplantation tolerance of skin and cardiac grafts in rats. In the primate, TLI and bone marrow injection result in significant tolerance of liver and kidney allografts. In 1959 sublethal whole-body irradiation was used as an immunosuppressive agent for the first successful related-human renal allografts between non-identical twins. Despite the dangers of myelosuppression, recent clinical experience has shown TLI to be a useful immunosuppressant for organ transplantation, allowing decreased dosage of concomitant immunosuppressive drugs.

Animals↗
PubMed1987

The effect of ionizing radiation on the primate pancreas: an endocrine and morphologic study.

In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bonemarrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1,000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.

Animals↗
PubMed1987

Early postoperative pancreatic endocrine function after segmental and pancreaticoduodenal allotransplantation in nonimmunosuppressed primates.

In this study we evaluated the short-term hormonal effects of segmental and whole pancreatic allotransplantation on the glucose intolerance produced by hemipancreatectomy in the primate. In hemipancreatectomized animals without grafts the K-values were reduced to 0.6 +/- 0.05, plasma insulin increased from 27.5 +/- 2.5 to 63.5 +/- 6.3 microU/ml, and glucagon levels declined from 252 +/- 29.9 to 216.5 +/- 33.0 pg/ml. Hemipancreatectomized segmental allograft recipients rendered K-values of 0.79 +/- 0.05, plasma insulin increased from 19.98 +/- 3.43 to 66.0 +/- 17.03 microU/ml, and glucagon release declined from 395.6 +/- 63.0 to 226.2 +/- 37.6 pg/ml during IVGTT postoperatively. Hemipancreatectomized, pancreaticoduodenal allograft recipients rendered K-values of 0.82 +/- 0.1, results not significantly different from hemipancreatectomized or segmental allograft recipients. Plasma insulin increased from 29.5 +/- 4.0 to 186.0 +/- 25.0 microU/ml, and glucagon release declined from 1,087.0 +/- 31.6 to 656.0 +/- 12.7 pg/ml. In summary, segmental pancreatic allotransplantation could not, in the short-term, restore the reduced K-values and hypoinsulinaemia in hemipancreatectomized primates to that of normal, unstressed controls. Although K-values of hemipancreatectomized recipients were not significantly improved, whole pancreas transplantation resulted in improved insulin release and hyperglucagonaemia during IVGTT when compared to segmental allograft recipients. The unexpected findings of hypoinsulinaemia and hyperglucagonaemia in both transplant groups may only reflect a function of the stressed state of the animals in the immediate postoperative phase.

Animals↗
PubMed1987

Diabetes in pancreatectomized baboons: a model for pancreatic transplantation studies.

This study was designed to assess plasma glucose levels (PLG) and insulin release in totally pancreatectomized baboons when challenged with intravenous glucose administration (IVGTT). Ten animals (Papio ursinus) were used and duodenectomy was intentionally avoided. The PLG at death was 18.0 +/- mmol/L, and the mean K-value within 3 days after pancreatectomy was 0.4% +/- 0.2%, indicating a significant impairment of glucose disappearance from the blood when compared to the control animals (P less than 0.01). Plasma insulin levels before and after stimulation with glucose were below the lowest level of insulin assay sensitivity. We conclude that in the primate, as in the dog, surgical pancreatectomy produced a reliable diabetic model, which is uniformly lethal if left untreated.

Animals↗
PubMed1987

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.

Animals↗
PubMed1987

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.

Animals↗
PubMed1986

[Perspectives in the clinical application of pancreas transplantation in the diabetic].

Until June 1983 a total of 280 human pancreatic transplantations had been performed world-wide. Until July 1983, 57 were functioning (22%), 11% for more than 12 months. During the past 5 years a steady increase in the number of segmental transplants has been observed. In most cases simultaneous transplantation of pancreas and kidney was performed (144 cases), in 65 cases the pancreas was transplanted metachronously after kidney grafting, and in 64 cases pancreatic transplantation was performed alone. Currently, segmental or whole pancreatic transplantation is the favoured procedure. Islet transplantation has been disappointing because of the difficulty in procuring sufficient numbers of islets from an adult pancreas followed by immunological destruction of the transplanted islets. Most pancreas grafts have been procured from cadavers, but the favoured segmental technique allows living related donors to be used. After rejection the graft does not always have to be removed and exogenous insulin administration may be resumed, either permanently or until re-transplantation can be accomplished. Life-long immunosuppression is needed after transplantation and currently pancreatic allograft survival rates for cyclosporin (CSA) and azathioprine-treated patients have been similar. The longest survival of a living diabetic recipient with a functioning pancreas is 5 1/2 years. Some authors have recently claimed improvement and stabilization of impaired nerve conduction and diabetic retinopathy after pancreatic transplantation.

Diabetes Mellitus, Type 1↗
PubMed1986

Midazolam premedication in paediatric anaesthesia.

To investigate the efficacy of midazolam (Dormicum; Roche) as a paediatric premedication, 150 children, aged 6 months-5 years, were divided into three groups. All three groups spent time with the anaesthetist to allow rapport to be established. Group A received midazolam premedication, group B received oral trimeprazine, droperidol and methadone (TDM) and group C received no sedative medication. Midazolam gave the best behaviour patterns in the holding room. Behaviour at induction was the same in all three groups. The recovery times were similar in the midazolam and unsedated groups, but in the TDM group recovery was significantly delayed. Temperatures remained stable in the unsedated and midazolam groups, but decreased in the TDM group. It is concluded that midazolam is a satisfactory paediatric premedication agent.

Anesthesia Recovery Period↗
PubMed1986

The application, mechanism of action and side-effects of immunosuppressive agents in clinical transplantation.

The conventional agents (azathioprine and steroids) have been the mainstay or organ allograft immunosuppression for the past 20 years. The main drawback of the immunosuppressive agents at present in use is that they act nonspecifically with sequential general depression of the immune system. The introduction of cyclosporin, an undecapeptide of fungal origin, which selectively inhibits T-cell-dependent immuno-reaction has made a significant impact on organ allograft survival rates. Clinical application has been complicated because of renal or hepatotoxicity. Thoracic duct drainage is of historical interest but the use of antilymphocyte serum, despite its chequered history, has recently been shown to be safe and effective in cadaver kidney transplant recipients. There has also been a resurgence of interest in the use of total lymphoid irradiation as an immunosuppressive agent. The introduction of xenogenic monoclonal antibodies with anti-T-cell specificity opened a new era in clinical immunology and OKT3-PAN has emerged as a powerful major immunosuppressive agent with low toxicity.

Graft Rejection↗
PubMed1986

Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate.

The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

Animals↗
PubMed1985

Organ allotransplantation since the advent of cyclosporin.

Successful long-term organ transplantation has been made possible by the use of conventional immunosuppression. In contrast with transplantation of other organs, transplantation of the kidney has become an accepted successful form of therapy, 80% of patients being fully rehabilitated. However, complications of therapy are frequent and severe and include bone necrosis, cataract formation, infections and stunted growth in children. The discovery of the immunosuppressive properties of cyclosporin A (CYA) by Borel in 1976 offered new hope to recipients of hepatic, cardiac, pancreatic and heart-lung transplants, since rejection frequently resulted in death. Although the use of CYA has led to significant accomplishments, subsequent studies have documented deleterious side-effects including nephrotoxicity, hepatotoxicity, hirsutism, gingival hyperplasia, tremors and tumours. Yet despite the side-effects, CYA has proved to be a promising immunosuppressive agent for use in human organ transplantation and is at present being evaluated in transplant centres throughout the world.

Azathioprine↗
PubMed1985

Mycotic aneurysm--a rare complication of acute osteomyelitis in a child. A case report.

A case of mycotic aneurysm formation of the right iliac artery is described. This unusual complication developed as a result of acute osteitis of the left tibia which was initiated by a kick on the lower leg. One month after treatment for osteitis of the tibia, the patient was readmitted because of unequivocal evidence of ischaemia of the right leg and a large pulsatile mass in the right iliac fossa, confirming the clinical diagnosis of mycotic aneurysm. The aneurysm was excised but because the wall of the artery was extremely friable simultaneous revascularization was deferred for fear of uncontrollable haemorrhage from the anastomotic line.

Acute Disease↗
PubMed1985

Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report.

The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversible bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 X 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 X 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 X 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 X 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients. Some immunosuppressive regimens gave modest graft survival, none resulted in indefinite graft survival, and there was considerable toxicity with many of the regimens. Although CS administration alone or in combination with irradiation resulted in modest pancreatic allograft survival in this model, the place of CS combined with TBI or TLI or other chemical immunosuppressive agents remains to be defined.

Animals↗
PubMed1984

An unusual presentation of carcinoma of the colon in a child. A case report.

A patient with carcinoma of the large bowel who presented with a subphrenic abscess is reported. This case emphasizes two important facts relating to colonic cancer in childhood: (i) premalignant disease of the large bowel is no prerequisite for the development of colonic cancer; and (ii) in childhood this disease is characterized by a fulminating course and high mortality. In about 50% of cases the tumour is of the signet ring or mucin-producing type, which explains the grave prognosis.

Adenocarcinoma↗
PubMed1984

Prolongation of intraperitoneal segmental pancreatic allografts in primates receiving cyclosporin A.

In this study the efficacy of the new immunosuppressive agent, cyclosporin A (CYA), was examined in a model of segmental, intraperitoneal pancreatic allotransplantation with free duct drainage in totally pancreatectomized, outbred Chacma baboons. CYA, in doses of 25 to 50 mg/kg/day administered to recipients of heterotopic segmental (tail) allografts, produced a slight but significant prolongation of graft survival. CYA (25 to 85 mg/kg/day), administered orally after pancreatic transplantation gave daily serum trough levels of CYA that ranged from 300 to 600 ng/ml. Mean serum trough levels on the first postoperative day in recipients of 50 mg/kg/day were 121.1 +/- 61.6 ng/ml. There was a wide variation in daily serum trough levels exhibited between primates on the same daily oral dose, and there was no correlation between absolute serum trough levels of CYA and rejection. It is postulated that adequate serum CYA levels were not achieved by the oral administration of the drug to ensure allograft survival beyond 60 days in pancreatectomized recipients. Adverse effects occurred frequently and included anorexia, diarrhea, and tremors and were in direct proportion to the quantity of CYA required to prolong graft survival. Free duct drainage into the abdominal cavity frequently resulted in pancreatic ascites, which necessitated paracentesis, indicating that this method of duct drainage has limited clinical application. Although heterotopic autotransplantation or allotransplantation of the tail of the pancreas in the baboon was capable of maintaining normoglycemia in pancreatectomized baboons, glucose intolerance, reduced K values, and hypoinsulinemia were consistent findings during glucose tolerance tests, suggesting that an insufficient islet cell mass had been transplanted.

Animals↗