Treatment of severe encephalopathy after porta-systemic anastomosis by suppression of the shunt

Encephalopathy is the most common complication after total portal by-pass operation. 5-15% of patients have severe and intractable encephalopathy. Many medical and surgical procedures were proposed to prevent and treat this complication but none of these were effective. Two cases of patients with severe encephalopathy after side to side portal by-pass are presented. They were treated with the procedure proposed by Bismuth; it consists of a gradual suppression of the anastomosis associated with esophagogastric devascularization. In the first case we obtained the regression of encephalopathy while the second patient died portal thrombosis (probably due to this procedure) two months after surgery. Validity and efficacy of this procedure must be evaluated with a higher number of patients. This surgical technique should lead to choose the type of portal by-pass: side to side portal by-pass operation allows according to Bismuth's procedure to reestablish an hepatopetal flow.     

Heterotopic mesenteric ossification. Description of a case

We describe a case of heterotopic mesenteric ossification presented in a 25 year-old male who underwent laparotomy for a fire-gun injury. Two weeks later he experienced small bowel obstruction and for this reason he has been operated five times with removal of segments of small bowel. Now, nine months later, he needs ileostomy to avoid another obstruction.     

Grasper trauma during laparoscopic cholecystectomy

BACKGROUND: The present study characterized the histopathological nature of laparoscopic grasper trauma during laparoscopic cholecystectomy in a prospective, blinded trial in order to establish a model for laparoscopic grasper trauma. The null hypothesis that graspers cause no histologically distinct tissue injury was tested. METHODS: The gall bladders of 19 patients undergoing laparoscopic cholecystectomy were examined. The area of gall bladder that had been grasped by Debakey laparoscopic forceps was excised (sample), along with an area of gall bladder that had not been grasped (control). Paired specimens were examined by a pathologist (blinded) to identify which was 'sample' and which was 'control' and to assess for histological markers of crushed tissue injury. The data were analysed by chi-squared or Fisher's exact tests. RESULTS: The pathologist was able to identify the sample (gripped) specimen in 13 of the 19 cases. In the remaining six cases the pathologist was unable to determine the specimen that had been gripped due to either absence of damage (four cases), or severe inflammation precluding assessment (two cases). The ability of the pathologist to distinguish the sample from the control specimen was significant (chi-squared test, P = 0.003). Of the histological markers of crushed tissue injury, focal thinning of the gall bladder wall and epithelial loss were present in significantly more sample (gripped) specimens than control specimens (chi-squared test, P = 0.0002 and P < 0.0001, respectively). CONCLUSIONS: Laparoscopic graspers cause tissue trauma that can be assessed histologically. The current study presents a relevant, reproducible, ethically acceptable human model for assessing the interaction between laparoscopic graspers and soft tissues.     

Synthesis and Antimuscarinic Activity of Derivatives of 2-Substituted-1,3-Dioxolanes

Geometric cis, trans isomers, derivatives of 2-substituted-1,3-dioxanes were designed and studied as antimuscarinic agents. The synthesized compounds were evaluated as perchlorides and methiodides by functional tests with rabbit vas deferens (putative M₁), guinea-pig heart (M₂) and guinea-pig ileum (M₃). The effect of the replacement of a trimethylammonium group with a dimethysulfonium in the two rings was also evaluated. Pharmacological results indicate that the 1,3-dioxane nucleus shows the highest stereoselective values on the studied receptors.     

O6-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications

O⁶-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age ≥18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval ≥3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27–67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.     

Growth-related oncogene alpha induction of apoptosis in osteoarthritis chondrocytes

OBJECTIVE: To evaluate the apoptotic effect of the chemokine growth-related oncogene alpha (GROalpha), which we recently reported to be up-regulated in osteoarthritis (OA) chondrocytes. Chondrocyte apoptosis is considered to be a major determinant of cartilage damage in OA, a disease resulting from the aberrant production of inflammatory mediators (cytokines and chemokines) and effectors (matrix metalloproteinases and reactive oxygen and nitrogen species) by chondrocytes. METHODS: We investigated the apoptotic effect of GROalpha on isolated human cells and on in vitro-cultured cartilage explants by conventional methods (morphology, detection of DNA fragmentation in situ and in solution, exposure of phosphatidylserine) and by analysis of "early" biochemical events (plasma membrane depolarization, activation of caspase 3, and phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase). RESULTS: We clearly demonstrated that GROalpha was able to initiate a series of morphologic, biochemical, and molecular changes that led to chondrocyte apoptosis. Moreover, we found that additional signals delivered from the extracellular matrix (ECM) were essential in the control of chondrocyte susceptibility to GROalpha-induced apoptosis, since cell death was detected only when cells were stimulated after reestablishment of their proper interactions with the ECM, or in cartilage explant samples with reduced ECM, as indicated by decreased Safranin O staining. CONCLUSION: GROalpha can induce apoptosis in articular chondrocytes, and the induction is dependent upon additional signals from the ECM. These findings are relevant to understanding the pathogenesis of OA, in view of the availability of the GROalpha chemokine in the joint space in the course of this rheumatic disease.     

Predictive factors for switching in patients with psoriatic arthritis undergoing anti-TNFα, anti-IL12/23, or anti-IL17 drugs: a 15-year monocentric real-life study

Clinical Rheumatology - We aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of...     

HMGB1 promotes CXCL12-dependent egress of murine B cells from Peyer's patches in homeostasis

High mobility group box-1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1–CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12-dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B-cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1–CXCL12 complex in PPs than in other lymphoid organs. HMGB1–CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1–CXCL12 complex in orchestrating B-cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.