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D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 235 records · Page 13Linked to original sources

Correlation of rejection of the duodenum with rejection of the pancreas in a pig model of pancreaticoduodenal transplantation.

To assess the correlation of rejection in the duodenum and the pancreas, we examined pancreatic and duodenal tissue from pancreaticoduodenal transplants in 32 outbred Yorkshire Landrace pigs. After streptozotocin-induced hyperglycemia, they were transplanted and treated with prednisone, AZA, and CsA. Immunosuppression was reduced by 50% weekly and discontinued at 3 weeks. The tissues were harvested at necropsy at various time points. Each organ was graded for interstitial rejection and vascular rejection separately as no, mild, moderate, and severe. All but 1 animal rejected their organs. Complete concordance of rejection between duodenum and pancreas considering both interstitial and vascular findings was found in 15/32 (47%) animals. In 11/17 (65%) of the remaining allografts, the pancreas had a higher rejection grade (3 interstitial, 5 vascular, 3 both) and in 6/17 (35%) the duodenum had higher rejection grades (2 interstitial, 4 vascular). Considering interstitial and vascular rejection separately, 23/32 (72%) and 20/32 (63%) showed concordance, respectively. Most cases (7/9, 78%) of discordant interstitial rejection showed higher interstitial rejection grades in the pancreas. Five cases (4 pancreas, 1 duodenum) showed interstitial discordance of 2 grades or more. Discordant cases with higher vascular rejection were 7 pancreas (58%) and 5 duodenum. Five cases (3 pancreas, 2 duodenum) showed vascular discordance of 2 grades or more. Interstitial rejection was seen alone (11 cases) and with vascular rejection (20 cases), but vascular rejection was never seen alone. We made the following conclusions. (1) Concordance of duodenal and pancreas rejection occurs in 47% of cases. (2) Discordant cases usually show higher grades of rejection in the pancreas (65%), but the opposite can also occur. (3) Therefore, if duodenal biopsies are positive, they are likely to be representative of pancreatic pathology, but when negative, they do not rule out rejection of the pancreas. (4) Interstitial rejection appears to precede vascular rejection, suggesting that factors released during interstitial rejection play a role in endothelial cell activation and vascular rejection.

Animals↗

Differences in rejection grading after simultaneous pancreas and kidney transplantation in pigs.

Clinical observations suggest that recipients of multiorgan transplants from the same donor can have disparate immunological reactions to each organ. We studied this phenomenon in 36 diabetic (streptozotocin-induced), bilaterally nephrectomized immunosuppressed (cyclosporine, azathioprine, prednisone) pig recipients of simultaneous (same donor) pancreas (bladder drained) and kidney allografts by grading the histological intensity of rejection in biopsies of each organ at defined intervals posttransplant. Graft function was monitored by plasma glucose (PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr) for the kidney. Interstitial rejection was graded as absent, mild, moderate, and severe in, respectively, 8%, 25%, 42%, and 5% of pancreas vs. 4%, 12%, 27%, and 50% of kidney biopsies at 1 week; and 0%, 43%, 29%, and 29% of pancreases vs. 10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of grades was similar in the two organs (P > 0.1), the grade of rejection for each pair at 1 week (n = 24) was discordant in 75% (41% differed by one and 35% by > or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2 grades). The inability to use the severity of interstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interstitial rejection at one week, the corresponding kidney showed moderate or severe rejection, and for the 1 kidney without rejection the corresponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution for the pancreas (57%, 30%, 9%, 4%) vs. kidney (56%, 30%, 0%, 13%) at 1 week, and at 2 weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11% for the kidney) (P > or = 0.64). However, the grading of vascular rejection in organ pairs was dyssynchronous in 51% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No vascular rejection in the pancreas with rejection in the kidney was seen in 5 pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%).(ABSTRACT TRUNCATED AT 400 WORDS)

Amylases↗

The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro.

The ability of fibroblasts to reproduce and attach to teeth is of paramount importance in re-establishing the lost connective tissue attachment after periodontal therapy. This study examined the effect of nicotine, a major component of the particulate phase of tobacco smoke, on human gingival fibroblast (HGF) reproduction and attachment to tissue culture surfaces. Pooled HGF cultures made from explants of gingival biopsies were utilized between passages 5 and 10 and plated in 96-well plates at 1.0 x 10(4) cells per well. Cell numbers were determined using 3-(4,5-dimethylthiazol-2-y)-2,5-diphenyl tetrazolium bromide (MTT), which is a reflection of mitochondrial dehydrogenase activity. The concentrations of nicotine used were 0.025, 0.05, 0.1, 0.2, and 0.4 microM, the average serum concentration for a smoker being approximately 0.1 microM. The effect of continuous nicotine exposure on HGF reproduction was determined by incubating cell cultures and media containing nicotine for up to 48 hours. Residual toxicity was determined by preincubating cells with nicotine for 1 or 6 hours. HGF suspensions and increasing concentrations of nicotine were added together to determine the effect on attachment. Results showed an enhanced effect of nicotine on HGF attachment, with increasing numbers of cells attaching with increasing nicotine concentrations, compared to the control. Low concentrations of nicotine had a stimulatory effect on cell replication, while higher concentrations of nicotine appear to have no significant effect on HGF reproduction. The responses of cells to some concentrations of nicotine may persist after its removal.

Analysis of Variance↗

Pancreas transplant results in United Network for Organ Sharing (UNOS) United States of America (USA) Registry with a comparison to non-USA data in the International Registry.

As of 1993, more than 5,000 pancreas transplants were reported to the International Pancreas Transplant Registry. More than 3,600 were performed in the USA, including 3,000 since the inception of the UNOS Registry in October, 1987. The BD technique was used for 96% of USA cases but for only 63% of non-USA cases. In the overall analysis of USA BD cadaveric pancreas transplants reported to the Registry by November 1993 (n = 2,464), patient survival and pancreas graft function survival rates at one year were 91% and 72%, respectively, 87% and 67% at 2 years, and 84% and 62% at 3 years. When the USA data for BD cases were analyzed according to the 3 major recipient categories (simultaneous pancreas/kidney transplants [SPK] [n = 2,112]; pancreas after kidney transplants [PAK] [n = 205]; and pancreas transplants alone [PTA] [n = 147]), patient survival rates were no different (91%, 92%, and 91% at one year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (76%, 47%, and 48%, at one year, respectively). In the SPK group, kidney graft survival rates at one year were 85%. Although the overall results were not as good for non-USA as for USA pancreas transplants, this was probably because the results with non-BD techniques were not as good as when BD was used, and in Europe more than one-third of the cases used techniques other than BD. The patient, pancreas, and kidney graft survival rates for BD SPK transplants in Europe (n = 522) and other non-USA locations (n = 64) were similar to those in the USA: in Europe 93%, 77%, and 84%, respectively, at one year. The graft survival rates for solitary pancreas transplants, however, were higher in the USA. Outcomes were also compared according to whether induction immunotherapy in USA recipients included ALG/ATG, OKT3, or neither. In the SPK category, there was no difference among the protocols: one-year graft survival rates were 76% with ALG/ATG (n = 1,141), 78% with OKT3 (n = 673), and 71% with neither (n = 249). In the PAK category, the use of OKT3 (n = 37) was associated with lower graft survival rates than when ALG/ATG (n = 133) or neither (n = 34) were given: 26%, 58%, and 53% at one year, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗