New Engl J Med 2000; July 27th.
Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-free Immunosuppressive Regimen.
James Shapiro AM, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, et al.
Surgical-Medical Research Institute. University of Alberta, Edmonton, Canada.
Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8% do not need insulin therapy after one year. The authors retrospectively studied 7 consecutive patients with type 1 diabetes and a history of severe hypoglycemia and metabolic instability who had undergone islet transplantation in conjunction with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab. All patients quickly attained sustained insulin independence after transplantation. All recipients required islets from two donor pancreases, and one required a third transplant from two donors to achieve sustained insulin independence. The mean glycosylated hemoglobin values were normal after transplantation in all recipients. The mean amplitude of glycemic excursions, which is a measure of fluctuations in blood glucose concentrations, significantly decreased after the attainment of insulin independence following the first transplantation. There were no further episodes of hypoglycemic coma. Complications were minor and there were no significant increases in lipid concentrations during follow-up.
These observations in patients with type 1 diabetes indicate that islet transplantation can result in insulin independence with good metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass.
Cancer Res 2000; 60:3117-22.
Pancreatic Duct Cell Carcinomas Express High Levels of High Mobility Group I(Y) Proteins
Abe N, Watanabe T, Masaki T, Mori T, Sugiyama M, Uchimura H, et al.
Kyorin University School of Medicine. Tokyo, Japan
The high mobility group I (HMGI) family of proteins in mammals belongs to a group of nonhistone nuclear proteins known as architectural transcriptional factors. They function in vivo both as structural components of chromatin and auxiliary gene transcription factors. Abe et al. (Cancer Res., 59: 1169-1174, 1999) demonstrated that the expression level of the HMGI(Y) gene/proteins was significantly increased in colorectal adenocarcinoma and colorectal adenoma with severe cellular atypia. In this study, the authors analyzed HMGI(Y) expression in several human pancreatic lesions to investigate whether HMGI(Y) overexpression is also observed in pancreatic carcinoma, and the role of HMGI(Y) in the diagnosis of pancreatic neoplasms.
HMGI(Y) expression was determined at the protein level by immunohistochemistry using a HMGI(Y)-specific antibody. The authors studied 6 surgically resected specimens of non-neoplastic tissue (4 normal pancreatic tissues and 2 chronic pancreatitis tissues), 8 pancreatic cystic neoplasms (5 intraductal papillary mucinous adenomas, 1 serous cystadenoma, and 2 solid pseudopapillary tumors), and 15 duct cell carcinomas of the pancreas. Immunohistochemical analysis revealed intense nuclear staining in the pancreatic carcinoma cells, whereas only very faint nuclear staining was seen in the non-neoplastic cells.
There was a strong correlation between HMGI(Y) protein overexpression and a diagnosis of carcinoma. An increased expression level of the HMGI(Y) proteins was clearly associated with the malignant phenotype in pancreatic tissue. In addition, a low level of protein expression was also apparent in two of the cystic neoplasms that exhibited cellular atypia, but not in those that did not exhibit cellular atypia. The authors conclude that HMGI(Y) proteins could be closely associated with tumorigenesis in the pancreas and that HMGI(Y) could serve as a potential diagnostic molecular marker for clearly distinguishing pancreatic malignancies from normal tissue or benign lesions.
Lancet 2000; 355:1955-60.
Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study
Neoptolemos JP, Kemppainen EA, Mayer JM, Fitzpatrick JM, Raraty MG, Slavin J, et al.
Royal Liverpool University Hospital. Liverpool, United Kingdom
The authors undertook a multicenter study in 246 patients: 172 with acute pancreatitis, 35 of whom had severe disease and 74 controls in order to assess the predictive value of urinary trypsinogen activation peptide (TAP) concentrations as measured by a validated competitive immunoassay. They compared the results of TAP with those for plasma C-reactive protein and three clinico-biochemical scoring systems. TAP and C-reactive protein concentrations were analyzed at set times after the onset of symptoms and compared with the clinico-biochemical systems scores at key times during the hospital stay. The sensitivity, specificity, positive and negative predictive values of the test in differentiating severe acute pancreatitis from mild acute pancreatitis at 24 h were as follows: TAP (>35 nmol/L), 58%, 73%, 39%, and 86%, respectively; C-reactive protein (>150 mg/L), 0%, 90%, 0%, and 75%. The values for the clinico-biochemical scoring systems 48 h after admission were: APACHE II (greater or equal to 8), 56%, 64%, 30%, and 85%; Ranson score (greater or equal to 3), 89%, 64%, 38%, and 96%; and Glasgow score (greater or equal to 3), 77%, 75%, 44%, and 93%. At 48 h, the values for TAP were 83%, 72%, 44%, and 94%, whereas those for C-reactive protein were 86%, 61%, 37%, and 94%. Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy.
The authors concluded that urinary TAP provided accurate severity prediction 24 h after the onset of symptoms and that this single marker of severity in acute pancreatitis merits routine clinical application.