Biomedical subjects

B Smit

Publications and source records attributed to B Smit.

36 records · Page 2Linked to original sources

PubMed1988

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.

Animals↗

PubMed1988

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.

Animals↗

PubMed1988

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.

Animals↗

PubMed1988

Cytogenetic characterization of an established xenografted prostatic adenocarcinoma cell line (PC-82).

Detailed cytogenetic analysis was performed of a xenografted human prostatic adenocarcinoma cell line PC-82. A direct preparation method was developed that yielded metaphases of good quality. Flow cytometric data and banding analysis of metaphases showed a near-tetraploid karyotype with 18 consistent marker chromosomes. As a result of the rearrangements involved, parts of chromosomes 2, 3, 4, 7, 9, 10, 15, 18, and 21 were homozygous, while regions on 2p, 13q, and 17q were apparently completely lost. In contrast to this, some regions on #2, #5, and, especially, on #1 were present in three or even four times the normal copy number. Comparison of affected chromosomes in PC-82 with all data available on prostatic carcinoma showed chromosomes 1, 2, 3, 6, 7, 10, and 15 to be involved in rearrangements in over 50% of all prostatic carcinomas. When only data from primary prostatic adenocarcinomas (including PC-82) were taken into account it appeared that chromosomes 1, 7, and 10 were involved in all five primary tumors studied.

Adenocarcinoma↗

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

A cross-cultural study of the factorial dimensions of the NOSIE: a follow-up note.

The factor structure and its invariance of the Nurses' Observation Scale for Inpatient evaluation (NOSIE) were investigated in a Dutch psycho-geriatric population (N = 247) and compared with those of a short stay psychiatric population (N = 177). The previously found factor structure in the psychiatric population was replicated in this study and suggests, although not conclusively, a cross-cultural difference.

Cross-Cultural Comparison↗

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

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