Experimental study of the efficacy of the endoluminal prosthesis in colonic anastomoses

Colorectal surgery is still associated with a significant morbidity and mortality rate, mostly related to suture failure. We have carried out a randomized experimental study in dogs on colonic anastomoses exposed to a number of anastomotic risk situations. A total of 42 dogs was used. They were divided into three study groups (control, occlusion and diverticulitis), with and without an endoluminal tube. The aim was to assess the efficacy of the endoluminal prosthesis using clinical and radiological assessment of anastomotic healing. Pre- and post-anastomotic intraluminal pressures were also measured to determine whether these might be a factor in suture failure. There were significant differences in suture failure in animals in which the endoluminal tube was used. Mean duration of placement was 10.5 days. In the colon healing study, no significant differences were found between the groups in the pathological examination or in the assay of hydroxyproline content. The presence of the endoluminal tube may increase the maximum pressure applied on the colon wall. No significant differences were found in the intracolonic pressure differentials between the different groups or after the inclusion of the endoluminal prosthesis. The results obtained establish the efficacy of the endoluminal prosthesis in protecting the colonic anastomosis, and could be a valuable technique in colonic anastomoses with a high risk of suture dehiscence.     

S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat

S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/- 8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine's antidepressant effect.     

A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.     

Treatment of oesophageal cancer with preoperative chemoradiotherapy may increase operative mortality

AIMS: This phase II multicentric study evaluates a modified preoperative chemoradiotherapy schedule. METHODS: Patients <75 years with potentially resectable neoplasm were eligible. Treatment included an initial course of CDDP 100 mg/m2 (Day 1) and 5-FU CI 5000 mg/m2 (Days 1-5) followed by 45 Gy (Days 28-63) and 5-FU CI 5000 mg/m2 (Days 28-33), CDDP 75 mg/m2 (Day 56) and 5-FU CI 3750 mg/m2 (Days 56-61). Regional lymph nodes were irradiated. RESULTS: Nineteen patients were studied. Oesophagectomy was performed in 17. Clear margins were achieved in 16 of these. Eight patients showed a pathologic complete response (pCR). One patient died of infection during the preoperative treatment and four died due to acute surgical complications. The study was closed prematurely because of excessive mortality. Median follow-up was 19 months. Local and regional relapse occurred in one and three patients, respectively. Median time and actuarial 3-year of overall survival and progression free rates were 18.6 months and 28%, and 12.7 months and 10.4%, respectively. CONCLUSIONS: This schedule showed a high pCR, resectability and local control rate. Treatment-related mortality limits its clinical applicability, but further investigations are warranted.     

MMR vaccine effectiveness in an outbreak that involved day-care and primary schools

Objective

In 2006, a large measles outbreak occurred in Catalonia (Spain), where the immunization schedule included two doses of MMR vaccine at 15 months and 4 years. The aim of this study was to investigate the vaccine effectiveness (VE) of MMR in children attending day-care and pre-school centres and to estimate the number of cases that would have been avoided by administering the first dose of MMR at 12 months.

Methods

A retrospective cohort study was carried out between October 2006 and January 2007 in day-care and pre-school centres with confirmed measles cases. VE was calculated in children aged ≥15 months without previous measles infection. Cases avoided by advancing the first dose of MMR to 12 months were estimated by calculating the basic and effective reproduction number in centres where transmission outside the class was observed.

Results

Fifteen centres and 1394 children were included. There were 77 confirmed cases (attack rate = 5.5%). Vaccination coverage of the 1121 children aged ≥15 months was 91.6% and VE was 96% (95%CI 89-98%).There were 33 (41%) cases in the 81 children aged 12-14 months. Advancing the first dose to 12 months would have prevented 74 cases (91.5%) and lowered the attack rate from 41% to 8.6%.

Conclusions

Over 90% of cases in children aged 12-14 months would have been avoided by MMR administration at 12 rather than 15 months. We strongly recommend advancing the first dose of MMR to 12 months in order to reduce the risk of measles outbreaks.     

Automatic Methods for Carotid Contrast-Enhanced Ultrasound Imaging Quantification of Adventitial Vasa Vasorum

Adventitial vasa vasorum are physiologic microvessels that nourish artery walls. In the presence of cardiovascular risk factors, these microvessels proliferate abnormally. Studies have reported that they are the first stage of atheromatous disease. Contrast-enhanced ultrasound (CEUS) of the carotid allows direct, quantitative and non-invasive visualization of the adventitial vasa vasorum. Hence, the development of computer-assisted methods that speed image analysis and eliminate user subjectivity is important. We developed methods for automatic analyses and quantification of vasa vasorum neovascularization in CEUS and tested these methods in a cohort of 186 individuals, 63 of whom were healthy volunteers. We implemented alternative automatic strategies for using the images to stratify patients according to their risk group and compare the strategies with respect to diagnostic performance. An automatic single-parameter strategy performs less effectively than the corresponding Arcidiacono method based on manual interpretation of the images (68 < area under the receiver operating characteristic curve [AUROC] for the manual Arcidiacono method < 82; 60 < AUROC for the automatic single-parameter strategy < 63). However, by use of additional image parameters, an automatic multiparameter strategy has significantly improved performance with respect to the manual Arcidiacono method (78 < AUROC < 90). The automatic multiparameter strategy is a valuable alternative to the manual Arcidiacono method, improving both diagnostic speed and diagnostic accuracy.     

Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane

The liver is the major source of reduced glutathione (GSH) in blood plasma. The transport protein mediating the efflux of GSH across the basolateral membrane of human hepatocytes has not been identified so far. In this study we have localized the multidrug resistance protein 4 (MRP4; ABCC4) to the basolateral membrane of human, rat, and mouse hepatocytes and human hepatoma HepG2 cells. Recombinant human MRP4, expressed in V79 hamster fibroblasts and studied in membrane vesicles, mediated ATP-dependent cotransport of GSH or S-methyl-glutathione together with cholyltaurine, cholylglycine, or cholate. Several monoanionic bile salts and the quinoline derivative MK571 were potent inhibitors of this unidirectional transport. The K(m) values were 2.7 mmol/L for GSH and 1.2 mmol/L for the nonreducing S-methyl-glutathione in the presence of 5 micromol/L cholyltaurine, and 3.8 micromol/L for cholyltaurine in the presence of 5 mmol/L S-methyl-glutathione. Transport of bile salts by MRP4 was negligible in the absence of ATP or without S-methyl-glutathione. These findings identify a novel pathway for the efflux of GSH across the basolateral hepatocyte membrane into blood where it may serve as an antioxidant and as a source of cysteine for other organs. Moreover, MRP4-mediated bile salt transport across the basolateral membrane may function as an overflow pathway during impaired bile salt secretion across the canalicular membrane into bile. In conclusion, MRP4 can mediate the efflux of GSH from hepatocytes into blood by cotransport with monoanionic bile salts.