Effect of epidural anesthesia on colorectal anastomosis

PURPOSE: Epidural anesthesia is believed to benefit colorectal anastomotic blood flow because of the sympathetic blockade it produces. Our purpose is to measure with tonometry the effect of epidural anesthesia on colorectal anastomotic oxygenation. PATIENTS AND METHODS: Fifteen patients operated on for rectal cancer (radical anterior resection) were monitored postoperatively using tonometers placed in the stomach (celiac trunk), transverse colon (superior mesenteric artery), and the anastomotic area during the operation. An epidural catheter was placed at L1-2, and on the first postoperative day, 8 ml of bupivacaine (0.25 percent) was administered. The anesthetic effect extended up to T-4. Intramucosal pH (pHi) at the three locations was measured before, during, and after the epidural blockade. RESULTS: Gastric and transverse colon pHi increased during the epidural blockade from 7.35±0.01 to 7.41±0.01 and from 7.34±0.02 to 7.40±0.02, respectively. The anastomotic pHi decreased from 7.3±0.02 to 7.24±0.03 under the epidural and increased up to 7.34±0.02 after withdrawal of the effect on the following day. All pHi variations were statistically significant (P<0.05, paired Student'st-test and Wilcoxon's test), because it was the comparison between gastric and transverse colon pHi with the anastomotic pHi during the epidural (P<0.05, one-way analysis of variance and Kruskal-Wallis tests). None of the patients developed anastomotic or other complications. CONCLUSIONS: Epidural anesthesia with bupivacaine causes a significant decrease in the oxygenation-perfusion state of colorectal anastomosis in comparison with the increase in other areas of the digestive tract. Further studies need to be done to see if other epidural anesthetic-analgesic protocols also worsen colorectal anastomotic blood flow.Supported in part by a grant from the Spanish Society of Digestive Diseases, Madrid, Spain. All tonometric catheters and drugs were donated by the Clinic University Hospital of Valencia, Spain.Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms

LIG4 syndrome patients have hypomorphic mutations in DNA ligase IV. Although four of the five identified patients display immunodeficiency and developmental delay, one patient was developmentally normal. The developmentally normal patient had the same homozygous mutation (R278H) in DNA ligase IV as one of the more severely affected patients, who additionally had two linked polymorphisms. Here, we examine the impact of the mutations and polymorphisms identified in the LIG4 syndrome patients. Examination of recombinant mutant proteins shows that the severity of the clinical features correlates with the level of residual ligase activity. The polymorphisms decrease the activity of DNA ligase IV by approximately 2-fold. When combined with the otherwise mild R278H mutation, the activity is reduced to a level similar to other LIG4 patients who display immunodeficiency and developmental delay. This demonstrates how coupling of a mutation and polymorphism can have a marked impact on protein function and provides an example where a polymorphism may have influenced clinical outcome. Analysis of additional mutational changes in LIG4 syndrome (R580X, R814X and G469E) have led to the identification of a nuclear localization signal in DNA ligase IV and sites impacting upon DNA ligase IV adenylation.     

Are HLA-DR or TAP Genes Genetic Markers of Severity in Ulcerative Colitis?

The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n=91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n=200) were included. HLA-DRB103 was less frequent in UC patients than in healthy controls (8% vs 28%,PC<0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively (PC<0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.     

Prospective study of morphologic and functional changes with time in the mucosa of the ileoanal pouch

PURPOSE: This study was undertaken to investigate the morphologic and functional changes with time in the mucosa of the ileoanal pouch. METHODS: A morphologic study by histopathologic analysis, mucosal morphometry, and mucin histochemistry and a functional study by analysis of transmucosal potential difference were performed in 27 patients with an ileoanal J-pouch after restorative proctocolectomy for ulcerative colitis. In 19 patients with a normal ileoanal pouch, two prospective follow-up analyses were performed after median functional pouch times of 14 and 39 months. We also evaluated eight patients with the diagnosis of pouchitis (median follow-up, 52.5 months). RESULTS: In the normal ileoanal pouch group, some degree of chronic and acute inflammatory infiltration was identified in 100 percent and 63.2 percent of cases, respectively, with no significant differences being observed between the two follow-up analyses. The mean villous atrophy index at the first and second follow-up was 0.54 and 0.52, respectively, significantly lower (P<0.001; an indication of a greater degree of villous atrophy) than the value obtained from the control group with a healthy terminal ileum (0.77). The group of patients with pouchitis exhibited statistically significant differences in the degree of acute and chronic inflammatory infiltration, the extent of ulceration, the crypt depth, and the villous atrophy index, compared with patients without pouchitis. In the normal ileoanal pouch group, the median percentage of sulfomucin with each degree of atrophy (1=mild; 2=moderate; and 3=severe) was 2.6, 4.5, and 20.9 percent, respectively. In patients with pouchitis, the median percentage of sulfomucin was 5.9 percent. The mean transmucosal potential difference at the first follow-up (–25.3 mV) was significantly lower (P=0.001) than at the second (–30.4 mV). Significant differences were apparent with respect to both the normal ileum (–8.9 mV) and the normal rectum (–40.2 mV). CONCLUSION: These results suggest that the ileal pouch behaves as a neorectum, with different degrees of colonic metaplasia from a morphologic and a functional perspective.Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997. Dr. Garcia-Granero is an International Scholarship recipient.     

Apoptosis of naive CD4+ T-cells from HIV-infected patients with poor immune response to HAART is enhanced in vitro by steroid

OBJECTIVE: Because the absence of immune restoration in HIV-infected patients efficiently treated by highly active antiretroviral therapy (HAART) may be due to excessive immune activation, we prospectively studied the effect of hydrocortisone on T-cell apoptosis in a cohort of patients with satisfactory virologic response. METHODS: Apoptosis of T-cell subsets including na?ve CD45RA(+)CD4+ T-cells was determined at baseline and at months 1 and 3 after initiation of HAART. A satisfactory immune response was defined as an increase >100/microL CD4+ T-cells at month 3 compared to baseline. RESULTS: Twenty out of 63 patients showed undetectable viral load at month 3, among whom eight exhibited a satisfactory immune response. Down-regulation spontaneous CD4+T-cell apoptosis was significant in the group of patients with a satisfactory immune response compared to the other patients. However, hydrocortisone up-regulated apoptosis of na?ve CD4+ CD45RA+ T-cells, specifically in group of patients with poor immune response, whatever the time point considered: percentage of apoptotic CD4 T-cells was 16+/-16% without hydrocortisone and 22+/-22% with hydrocortisone at month 1, and respectively, 10+/-9 and 17+/-15% at month 3 (P < 0.05) Hydrocortisone had no impact on CD8+ T-cell apoptosis, whatever the considered group. CONCLUSION: Our results suggest to not use steroid therapy as adjuvant immunotherapy in patients with less than optimal immunologic response to HAART.