Engraftment and growth of transplanted pancreatic islets

Transplantation of pancreatic islets may provide a cure for type 1 diabetes. However, this treatment can currently be offered only to very few patients. To improve transplantation success we need to understand better the mechanisms of how the implanted islets survive, grow and/or maintain adequate function. We herein report on our studies to evaluate the factors responsible for the engraftment, i.e. revascularization, reinnervation etc., of transplanted islets and relate these factors to the metabolism and growth of the islets. Graft metabolism can be monitored by microdialysis probes that allow for the measurement of minute amounts of islet metabolites and hormonal products. Growth of the endocrine cells can be stimulated both in vitro before implantation and in vivo post-transplantation. Another problem is rejection of transplanted islets, which may be overcome by the microencapsulation of islets. The knowledge gained by the present studies will enable us to elucidate the optimal treatment of islets to ensure a maximal survival of the transplanted islets, and may be applied also to clinical islet transplantation.     

Reported use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors was not associated with reduced recurrence of colorectal adenomas.

We did a secondary analysis of data from three large colorectal adenoma chemoprevention trials to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor use and reduced risk of recurrent colorectal adenomas. Reported use of HMG-CoA reductase inhibitors was not associated with a reduced recurrence of colorectal adenomas, multiple adenomas, or advanced adenomas. Lack of statistical power from limited exposure to HMG-CoA reductase inhibitors might be responsible for the lack of association.     

Long-term outcomes among localized prostate cancer survivors: health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy.

PURPOSE: We sought to elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a well-characterized cohort of prostate cancer (PC) survivors 4 to 8 years after primary treatment. PATIENTS AND METHODS: Patients who had been evaluated previously at a median of 2.6 years after radical prostatectomy (RP), external radiation (three-dimensional conformal radiation therapy [3-D CRT]), or brachytherapy (BT) were recontacted at a median of 6.2 years after treatment. The clinical relevance of long-term HRQOL impairment among survivors was established by comparison with controls of similar age. Factors associated with HRQOL changes during this interval were evaluated. RESULTS: Of the 964 eligible men, 709 (73.5%) completed measurable questionnaires. In four domains (urinary irritative-obstructive, urinary incontinence, bowel, and sexual), significant HRQOL differences were detected for at least one of the therapy groups, compared with controls (all P < .05). During the 4-year interval, significant improvement was observed for the urinary irritative-obstructive (P < .0001) and bowel (P < .0001) domains among BT patients, whereas urinary incontinence HRQOL worsened for both the BT (P = .0017) and 3-D CRT (P = .0008) treatment groups. Overall sexual HRQOL deteriorated for the 3-D CRT cohort (P = .0017), as well as for controls (P = .0136). Among RP patients, significant HRQOL changes were not observed. CONCLUSION: During a 4-year interval from earlier to longer-term phases of PC treatment survivorship, sexual, urinary, and bowel dysfunction remain significant concerns among early-stage PC treatment survivors, compared with control men. Although postprostatectomy HRQOL remains relatively stable during this interval, disease-specific HRQOL continues to evolve among men treated with BT and 3-D CRT.     

Unsuccessful air-enema reduction of intussusception: is a second attempt worthwhile?

Pneumatic reduction of idiopathic intussusception is successful in about 80% of cases, while 60% of the failures are reduced at surgery without resection. To determine whether delayed, repeated attempts at enema reduction of failures would reduce the need for operation in selected cases, over a 2-year period (1994-1996 inclusive), 17 infants with idiopathic intussusception underwent delayed repeat enemas 2-19 h following the first failed attempt at reduction. Clinical parameters and radiologic findings were evaluated with respect to outcome. Ten intussusceptions were successfully reduced after the second attempt in 9 and after the fourth attempt in 1. Seven children underwent a laparotomy, 5 because of failure of progressive reduction at air enema (AE). Two were taken to surgery early in the series, 1 because of perforation during a second attempt and 1 while awaiting a third reduction attempt. The 10 successful reductions all showed progressive movement of the intussusceptum on each AE; the 2 who perforated failed to show progressive reduction on their second AE. Because of these cases, the remaining 5 were referred to surgery because of failure of progressive reduction of the intussusceptum on the second attempt. At laparotomy, of the 7 unsuccessful reductions, 4 required resection and 3 had difficult manual reduction. The presence of vomiting, a mass, and/or bloody stools were not predictors of outcome. Failures had higher body temperatures (38.1 +/- 0.3 vs 37.4 +/- 0.1 degrees C, P = 0.07), heart rates (153.7 +/- 8 vs 136.9 +/- 2.1 min, P = 0.03), and longer duration of symptoms (36.8 +/- 4 vs 21.3 +/- 3.6 h; P = 0.01) than successes. Delayed repeat AEs may be safe and effective in selected cases of idiopathic intussusception, but should be considered only if significant movement of the intussusceptum is noted at each attempt. The ideal time for repeat AE reduction prior to surgery is not established, but 2-4 h appears appropriate. Pyrexia, tachycardia, and duration of symptoms greater than 36 h are relative contraindications to this course of management.     

Chronic pancreatitis: ultrasonic features

A retrospective analysis of 84 ultrasound examinations (in 77 patients) was performed to assess the frequency of sonographic findings in chronic pancreatitis. The findings included: inhomogeneously increased echogenicity in 53% of these examinations, focal or diffuse enlargement in 41%, focal dense echoes in 40%, pseudocyst formation in 21%, and a hypoechoic head mass in 7%. Thirteen per cent of our patients had a normal sonogram. Several presentations of chronic pancreatitis not previously described in the sonographic literature included: pancreatic or common bile duct enlargement or pseudocyst formation with otherwise normal-appearing glands. There was no direct relationship between the presence of focal high-intensity echoes within the pancreatic parenchyma and the presence of radiographic calcification. There was no difference in the frequency of ultrasonic abnormalities between patients with and without clinical evidence of pancreatic insufficiency. These results indicate that the sonographic findings in chronic pancreatitis are significantly more varied than previous reports would indicate.     

Childhood infections and the risk of inflammatory bowel disease

Adults with inflammatory bowel disease from North Carolina were questioned during 1986 and 1987 to assess risk due to a variety of childhood infections and treatments with antibiotics. Responses were compared with those of neighbor controls. Persons with Crohn's disease were more likely to report an increased frequency of childhood infections in general (odds ratio 4.67, 95% CI 2.65–8.23) and pharyngitis specifically (odds ratio 2.14, 95% CI 1.30–3.51). This was validated by an increased frequency of tonsillectomy (odds ratio 1.53, 95% CI 1.07–2.20). Crohn's cases were more likely to report frequent treatment with antibiotics for both otitis (odds ratio 2.07, 95% CI 1.03–4.14) and pharyngitis (odds ratio 2.14, 95% CI 1.20–3.84). Although Crohn's cases were more likely to report frequent exposure to penicillin (odds ratio 1.81, 95% CI 0.98–3.31), there did not appear to be excess risk conferred by penicillin after controlling for frequency of infections. Persons with ulcerative colitis also reported an excess of infections generally (odds ratio 2.37, 95% CI 1.19–4.71), but not an excess of specific infections or treatments with antibiotics. Persons who reported an increased frequency of infections tended to have an earlier onset of Crohn's disease (P<0.0001) and ulcerative colitis (P=0.04). Finally, it was noted that urban living in childhood increased the risk for Crohn's disease. We conclude that childhood infections may be a risk factor for Crohn's disease and may presage the early onset of disease.This research was supported in part by grants from the Crohn's and Colitis Foundation of America and the National Irstitutes of Health (P30 DK34987, T32 DK07364 and RR00046).