Surgical treatment of intestinal obstruction

The etiology of intestinal obstruction (I.O.) has changed markedly since the beginning of this century. In this series, the authors studied 121 cases of I.O. treated surgically; adhesions were the commonest cause of high intestinal obstruction, accounting for 43.03 percent in a total of 79 patients, with hernia being the obstruction lesion in 16.45 percent. Colo-rectal cancer were the commonest cause of low intestinal obstruction accounted for 73.81 percent, with volvulus of the sigmoid colon in 14.28 percent. Complications occurred in 15.7 percent of patients following operative intervention; wound infection was the most common postoperative complication. The overall operative mortality was 9.09 percent.     

Management of infarction with ST elevation in the acute phase: the current guidelines

The 2002 and 2005 recommendations of the European Society of Cardiology for the management of ST-elevation myocardial infarction at the acute stage are reviewed. Primary angioplasty should, whenever possible, constitute the default strategy, but intravenous thrombolysis still has an important role, particularly in the first few hours following symptom onset.     

Biliary tract reconstruction: comparison of different techniques after 187 paediatric liver transplantations

Biliary complications after liver transplantation are common and cause significant morbidity and mortality. In order to evaluate the complications related to differents sort of biliary reconstruction, from January 1984 to July 1992 we retrospectively analysed 187 consecutive liver transplants in 136 paediatric patients at Addenbrooke's Hospital, Cambridge. There were 51 (27.2%) retransplantations. Biliary reconstruction consisted of: type 1 —common bile duct — Roux loop (CBD-RL); n=90 (48.1%); type 2 —gallbladder conduit — Roux loop (GC-RL), n=51 (27.2%); type 3 —gallbladder conduit — common bile duct (GC-CBD), n=20 (10.6%); type 4 — common bile duct — common bile duct (CBD-CBD), n=18 (9.6%); and type 5 — common bile duct — common bile duct+gallbladder drainage (CBD-CBD+GB), n=8 (4.2%). There were, in all 26 biliary complications (14%). Of these 26 complications, biliary stricture was the most common (17/26; 65.3%) and 6 out of these 17 (35.2%) were associated with chronic rejection. Hepatic artery thrombosis was directly related to biliary leakage in 6 out of 26 (23.1%) biliary tract complications. This series demonstrated that type 1 and type 4 reconstructions were related to fewer biliary complications (9/90, 10% and 2/18; 11%, respectively) than the other techniques: 8/51 (16%) for GC-RL 5/20 (25%) for GC-CBD and 2/8 (25%) for CBD-CBD+GB (P=0.09).     

Correlation of mycophenolic acid pharmacokinetic parameters with side effects in kidney transplant patients treated with mycophenolate mofetil

BACKGROUND: Mycophenolate mofetil (MMF) is widely used in organ transplantation to prevent acute rejection. Because MMF can produce hematologic and/or gastrointestinal toxicity, therapeutic monitoring is becoming mandatory. This study was designed to investigate the relationship between the clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult renal transplantation. METHODS: Thirty-one adult kidney recipients were prospectively included in the study. MPA pharmacokinetic profiles (blood sampling at 0, 0.5, 1, 2, 4, 6, and 12 h after MMF oral dose) were obtained after transplantation (desired creatinine clearance, 40 mL/min), at 3 months after grafting, and at every clinical event (e.g., side effect or rejection). All patients received a 10-day course of anti-thymocyte globulin, cyclosporine, MMF (1 g twice daily), and steroids. RESULTS: We divided the 31 patients into two groups (groups 1 and 2). Ten patients (32%; group 1) had uneventful outcomes, and 21 patients (68%; group 2) presented with MPA-related side effects. For groups 1 and 2, the MPA trough concentrations (C(min)) were 1.63 +/- 1.07 and 2.29 +/- 1.16 mg/L, respectively (P = 0.06), and the areas under the curve (AUCs) for MPA from t(0) to t(12 h) (MPA-AUC(0-12h)) were 39.80 +/- 15.29 and 62.10 +/- 21.07 mg. h/L, respectively (P = 0.0005, two-sample t-test). Three patients experienced acute graft rejection after the oral MMF dose was reduced because of side effects. In this group, the MPA-C(min) and MPA-AUC were significantly lower by the time acute rejection occurred (1.00 +/- 0.45 mg/L and 25.00 +/- 6.20 mg. h/L, respectively). At a fixed dose (1 g twice per day), we compared the pharmacokinetic parameters of MPA [C(min), the MPA concentration 30 min after the oral dose of MMF (C(30)), and AUC] according to the presence or absence of side effects in the two groups. C:(min) and AUC did not differ between the two groups [C(min) = 2.22 +/- 1.13 vs 2.17 +/- 1.13 mg/L (P = 0.9); AUC = 66.82 +/- 29.87 vs 55.70 +/- 11.74 mg. h/L (P = 0.11)]; and C(30) was significantly higher in group 2 than in group 1 (C(30) = 32.99 +/- 12.59 vs 7.45 +/- 5.40 mg/L; P <0.0001). CONCLUSIONS: Our results demonstrate a pharmacokinetic/pharmacodynamic relationship between MPA and clinical events. At a fixed dose of 2 g/day, a high C(30) is associated with increased risk for side effects. This study suggests that dividing the MMF daily oral dose into more than two divided doses might prevent early MPA toxicity.     

DNA repair pathways to regulate response to chemoradiotherapy in patients with locally advanced head and neck cancer

Platinum-based chemoradiotherapy (CRT) is a preferred standard of care for locally advanced head and neck cancer (HNC). However, survival benefit is small, with substantial toxicity and biomarkers of CRT resistance that could guide treatment selection and spare morbidity. Increased DNA repair in solid tumors may contribute to cancer cells’ ability to survive in genotoxic stress environments afforded by therapy. We assessed mRNA expression levels of DNA repair-related genes BRCA1, RAP80, 53 binding protein 1 (53BP1), mediator of DNA damage checkpoint 1 (MDC1), and RNF8. We correlated our findings with response and overall survival in 72 head and neck patients treated with weekly carboplatin AUC 2 and radiotherapy. Complete response (CR) to CRT was 50 % in patients with low levels of 53BP1 compared to 6.3 % in patients with high levels (p = 0.0059). Of high BRCA1 mRNA expressors, 41.2 % had CR compared to 29.4 % of low expressors (p = 0.72). For a small group of patients with low 53BP1 and either high BRCA1 or RAP80, CRs were 66.7 and 71.4 %, respectively. A trend for better overall survival (OS) was found for patients with low 53BP1 (15 vs 8 m; p = 0.056). Our findings highlight the potential usefulness of 53BP1 mRNA as a predictive biomarker of response and overall survival in HNC patients treated with chemoradiotherapy. Those with high 53BP1 expression could derive only a meager benefit from treatment. Analysis of BRCA1 and RAP80 could further reinforce the predictive value of 53BP1. Although this was a retrospective study with small sample size, it could inform larger translational studies in HNC.

     

Bromoenol lactone enhances the permeabilization of rat submandibular acinar cells by P2X7 agonists

The permeabilizing effect of P2X(7) agonists was tested in rat submandibular acinar cells using the uptake of ethidium bromide as an index. The uptake of ethidium bromide by acini incubated at 37 degrees C in the presence of 1 mM ATP increased with time and reached after 5 min about 10% of maximal uptake measured in the presence of digitonin. The response to ATP was dose-dependent (half-maximal concentration around 40 microM) and it was decreased when the temperature was lowered to 25 degrees C. Benzoyl-ATP reproduced the response to ATP (half-maximal concentration around 10 microM). UTP or 2-methylthioATP had no effect. The permeabilization in response to ATP was blocked by oxidized ATP and by magnesium and inhibited by Coomassie blue. ATP increased the activity of a calcium-insensitive phospholipase A(2) (iPLA(2)). Bromoenol lactone (BEL) inhibited the iPLA(2) stimulated by ATP but potentiated the uptake of ethidium bromide in response to the purinergic agonist. From these results it is concluded that the activation of P2X(7) receptors permeabilizes rat submandibular acinar cells. The pore-forming activity of the receptor might be negatively regulated by the concomitant activation of the iPLA(2) by the receptor.