N-2-butyl-cyanoacrylate for bleeding gastric varices: a United States pilot study and cost analysis

OBJECTIVES: N-butyl-2-cyanoacrylate has been reported to be effective for bleeding varices but is not available in the United States. We report the initial US experience with cyanoacrylate in this prospective trial and evaluate its safety, efficacy, and relative costs. METHODS: Patients with active or recent gastric variceal bleeding were eligible. Cyanoacrylate therapy was performed until variceal occlusion was achieved. Rebleeding was assessed at 72 h (acute phase), 6 wk (subacute phase), and 1 yr (chronic phase). Survival was assessed at 3 months and 1 yr. Cost analysis was performed comparing the first 17 patients to historical control patients not treated with cyanoacrylate. RESULTS: A total of 44 patients were enrolled, 37 with cirrhosis and seven with noncirrhotic portal hypertension (NCPH). In cirrhotic patients, rebleeding was seen in two of 37 (5%) at 72 h, one of 30 (3%) at 6 wk, and five of 28 (18%) at 1 yr. Survival without shunt at 3 months was 30 of 34 (88%) and at 1 yr was 24 of 31 (77%). In NCPH patients, rebleeding was seen in two of seven (29%) at 72 h. These patients received definitive therapy for NCPH after diagnosis. Mortality and costs were substantially higher in the non-cyanoacrylate group. The odds of death were greater by 7-fold in the non-cyanoacrylate group than within the cyanoacrylate group (95% CI = 1.18-41.36, p = 0.0318). At 3 months, there was a 3.18-fold difference (95% CI = 1.05-9.64, p = 0.0411) in accrued costs; at 1 yr, the difference was 2.55-fold (95% CI = 0.96-6.94, p = 0.0585). The cost-effective ratio was estimated as 108,237 US dollars/death averted, reflecting marked cost reduction with improved survival in the cyanoacrylate-treated group. This is believed to result largely from avoidance of shunt interventions. CONCLUSIONS: Cyanoacrylate treatment of gastric varices is safe, clinically effective, and cost effective.     

Preoperative Prediction of Small Bowel Length Using CT Scan and Tridimensional Reconstructions: a New Tool in Bariatric Surgery?

Purpose

During Roux-en-Y-gastric Bypass, the limb lengths are preoperatively determined regardless of individual small bowel length (SBL), which presents a great variability. Few studies highlighted anthropometric factors associated with SBL, and none attempted to predict SBL preoperatively.

Objective

The aim of this study is to evaluate factors correlated to SBL (anthropometric and radiologic) and to establish a preoperative SBL prediction.

Material and Methods

In this single-center prospective study, 30 adult patients who underwent laparotomy with a preoperative CT scan were included. Intraoperative SBL measurement was performed with an umbilical tape. Anthropometric parameters were age, gender, height, and BMI. 2D radiological measurements consisted of subcutaneous thickness, abdominal diameters, waist circumference, and mesenteric root length. 3D radiological volumetric reconstructions consisted of whole small bowel and mesentery (WSBM), lean small bowel and mesentery (LSBM), and fat small bowel and mesentery (FSBM).

Results

Mean intraoperative measurement of SBL was 531 ±?105 cm. Among the clinical and radiological measurements, the FSBM volume presented the greatest dispersion. Height (p?<?0.02) and LSBM volume (p?<?0.01) were significantly correlated to the SBL in univariate analysis. LSBM volume was the only measurement significantly associated with SBL in multivariate analysis (p?<?0.006). From the multivariate model, a formula was created to predict SBL. The mean percentage difference between predicted and intraoperative SBL measurements for all patients was 13.7%, and 8.4% for obese patients.

Conclusion

LSBM volume is significantly correlated to the SBL. A preoperative SBL prediction with low percentage error could be performed with LSBM volume.

     

Comparison of measured resting energy expenditure versus predictive equations in pediatric burn patients

Many equations have been developed to estimate resting energy expenditure (REE) in thermally injured patients. A consensus has not been reached on the accuracy of these equations in children. The purpose of our study was to compare three predictive equations: Harris Benedict x 2 multiplier (HB x 2), Mayes (MG), and the WorId Health Organization x 2 multiplier (WHO x 2) with measured resting energy expenditure x I.3 multiplier (MREE x 1.3) in pediatric burn patients. MREE was measured by open-circuit indirect calorimetry in 10 burned children (6 boys, 4 girls) aged 2 to 10 years with TBSA burn ranges from 35% to 97%. MREE x 1.3 was compared with values obtained by HB x 2, MG, and WHO x 2 predictive equations. When comparing MREE x 1.3 with all three equations, significant differences were found when compared with HB x 2 and MG, but there were no significant difference between MREE x 1.3 vs WHO x 2. The HB x 2 and MG equations overpredicted MREE x 1.3 by 29% and 19%, respectively. Many predictive equations have been developed to predict energy expenditure in burns, but their accuracy in predicting MREE x 1.3 is variable. A larger study comparing/contrasting predictive equations and resting energy expenditure measured by indirect calorimetry is needed to improve the prediction of energy needs in burned children.     

Serum Mannose-Binding Lectin Levels are Linked with Respiratory Syncytial Virus (RSV) Disease

The innate immune response facilitates the quality of the adaptive immune response and is critical to an individual’s susceptibility to infection and disease. Mannose-binding lectin (MBL) is a plasma protein with anti-microbial properties that binds a wide range of pathogens to flag them for immune destruction independent of antibodies. In this study, serum MBL levels were measured in 81 children <5 years old experiencing acute respiratory syncytial virus infection and in 40 control children to determine the association with disease severity. Almost 70% of all RSV-infected children had low to intermediate MBL levels (<500 ng/ml) compared to controls, and most of the <6 months old RSV interned patients had low to intermediate levels. No differences were detected in MBL levels between case and control children <1 month old. Analysis of the T-cell compartment in peripheral blood mononuclear cells (PBMC) from acute RSV-infected and control children showed that the percent CD4⁺ T cells was statistically lower in RSV-infected children ≥6 months old compared to controls, while the percent CD8⁺ T cells in RSV-infected and control PBMC was generally similar. These results suggest that low serum MBL levels may be a marker of RSV disease severity in children and that MBL may be important in limiting RSV disease pathogenesis.     

Long term alterations in neuroimmune responses of female rats after neonatal exposure to lipopolysaccharide

Male and female rats display significant gender-associated differences in their responses to an immune challenge, and gender-specific alterations in many aspects of physiology are seen after a variety of interventions during the neonatal period. It is well-established that neonatal exposure to an immune challenge can alter centrally mediated inflammatory responses in adult male rats and yet little is known about female responses after a similar challenge. We therefore asked if neonatal exposure to lipopolysaccharide (LPS) would alter febrile and hypothalamic cyclooxygenase (COX)-2 responses to an adult immune challenge in female rats. Female Sprague-Dawley rats were administered a single injection of the bacterial endotoxin LPS at postnatal day 14 and were examined as adults for febrile, COX-2 and activity changes to LPS, as well as responses to interleukin (IL)-1beta. Adult female rat responses were similar to those we have seen previously for the males in that febrile and hypothalamic COX-2 responses to adult LPS were attenuated in neonatally LPS-treated animals. Responses to adult IL-1beta were unaffected. Interestingly, females did not display the elevated basal hypothalamic COX-2 that was previously seen in males. Thus we demonstrate that, like in the males, neonatal exposure to LPS has a powerful effect on adult responses to further LPS challenge in the female rats.     

Induction of apoptosis in renal tubular cells by histone deacetylase inhibitors, a family of anticancer agents

Inhibitors of histone deacetylases, including suberoylanilide hydroxamic acid (SAHA) and Trichostatin A, are a new class of anticancer agents. With potent chemotherapy effects in cancers, these agents are not obviously toxic in normal nonmalignant cells or tissues. However, their toxicity in kidney cells has not been carefully evaluated. Here, we demonstrate a potent apoptosis-inducing activity of SAHA in cultured renal proximal tubular cells. SAHA induces apoptosis at low micromolar concentrations. At 5 muM, SAHA induces 30 to approximately 40% apoptosis in 18 h. The apoptosis is accompanied by notable caspase activation; however, the general caspase inhibitor VAD can only partially suppress SAHA-induced apoptosis, suggesting the involvement of both caspase-dependent and -independent mechanisms. SAHA treatment leads to cytochrome c release from mitochondria, which is suppressed by Bcl-2 but not by VAD. Bcl-2 consistently blocks SAHA-induced apoptosis. During SAHA treatment, Bcl-2 and Bcl-XL decrease, and Bid is proteolytically cleaved, whereas Bax and Bak expression remains constant. Bid cleavage, but not Bcl-2/Bcl-XL decrease, is completely suppressed by VAD. SAHA does not activate p53, and pifithrin-alpha (a pharmacological p53 inhibitor) does not attenuate SAHA-induced apoptosis, negating a role of p53 in SAHA-induced apoptosis. SAHA induces histone acetylation, which is not affected by VAD, Bcl-2, or pifithrin-alpha. Trichostatin A can also induce apoptosis and histone acetylation in renal tubular cells. Together, the results have shown evidence for renal toxicity of histone deacetylase inhibitors. The toxicity may be related to protein acetylation and decrease of antiapoptotic proteins including Bcl-2 and Bcl-XL.     

Design and implementation of occupational health programs in the workplace: the Québec approach

This paper describes the Québec experience in the design and implementation of occupational health programs in the workplace. To begin with, a brief overview of the historical context and organisational framework of occupational health are presented. Next, each of the phases involved in the design of occupational health programs is described: identification of workers' health and safety problems, selection of action priorities, and program design, implementation and evaluation.... In the end, the roles and responsibilities of the doctors, nurses and industrial hygienists generally involved in these multidisciplinary teams are presented.     

Insect antifeedant sesquiterpene acetals from the liverwort Lepidolaena clavigera. 2. structures, artifacts, and activity

Clavigerin A ( 1) was isolated from the New Zealand liverwort Lepidolaena clavigera and shown to be a polyoxygenated bergamotane sesquiterpene with an unusual ring system. L. clavigera shows infraspecific variation, since 1 was the only clavigerin detected in a North Island collection, whereas the previously reported clavigerins B ( 2) and C ( 3) were found in South Island collections with no sign of 1. Three new clavigerins, 4- 6, were identified, but these are artifacts formed by alcoholysis of the acetoxy acetal group of the clavigerins 2 and 3, with either the extraction solvent ethanol or the RP column eluent methanol. The insect antifeedant and cytotoxic activities of these compounds are reported, and it is proposed that they act as hidden 1,4-dicarbonyl compounds.