Low incisional hernia incidence using a large-bite, low-tension technique for celiotomy closure.

Background: Incisional herniae (IH) are reported in 5->20 % of patients undergoing open celiotomy, and can be linked to closure technique. The STITCH randomized trial favors a small bite technique for midline celiotomy closure with a 1-year IH rate of 13 % over larger bites (23 %). Methods: A continuous musculofascial mass closure with absorbable looped #1 PDS suture with 2-cm bite size was used for all open celiotomies. IH frequency and associated clinicopathologic factors were retrospectively analyzed from prospective data in 336 consecutive patients undergoing visceral resections by a single surgeon. Results: The study population included 192 men and 144 women, 81 % of whom had a cancer diagnosis, who underwent hepatobiliary, pancreatic, gastroesophageal, and colorectal resections, or a combination. The majority of patients (84 %) had subcostal incisions, and 10 % received a midline incision. At a median follow-up of 19.5 months, the overall IH rate was 3.3 %. Hernia rates were 2.5 % for subcostal margin, 2.9 % for midline, and 5.5 % for other incisions (p = 0.006). Median time to hernia detection was 492 days. Factors associated with IH were increased weight, abdominal depth/girth, male sex, spleen size, visceral fat, and body height (p ≤ 0.04 for all), but not type of resection, prior operations, underlying diagnosis, weight loss, adjuvant chemotherapy or radiation, incision length or suture to incision ratio. Conclusions: The described technique leads to a low IH rate of <3 % in subcostal or midline incisions, and can be recommended for routine use. The observed results appear superior to those of the STITCH trial, even for the smaller midline incision cohort.

The Geras Solutions Cognitive Test for Assessing Cognitive Impairment: Normative Data from a Population-Based Cohort.

BACKGROUND: There is a need for the development of accurate, accessible and efficient screening instruments, focused on early-stage detection of neurocognitive disorders. The Geras Solutions cognitive test (GSCT) has showed potential as a digital screening tool for cognitive impairment but normative data are needed. OBJECTIVE: The aim of this study was to obtain normative data for the GSCT in cognitively healthy patients, investigate the effects of gender and education on test scores as well as examine test-retest reliability. METHODS: The population in this study consisted of 144 cognitively healthy subjects (MMSE>26) all at the age of 70 who were earlier included in the Healthy Aging Initiative Study conducted in Umeå, Sweden. All patients conducted the GSCT and a subset of patients (n=32) completed the test twice in order to establish test-retest reliability. RESULTS: The mean GSCT score was 46.0 (±4.5) points. High level of education (>12 years) was associated with a high GSCT score (p = 0.02) while gender was not associated with GSCT outcomes (p = 0.5). GSCT displayed a high correlation between test and retest (r(30) = 0.8, p <0.01). CONCLUSION: This study provides valuable information regarding normative test-scores on the GSCT for cognitively healthy individuals and indicates education level as the most important predictor of test outcome. Additionally, the GSCT appears to display a good test-retest reliability further strengthening the validity of the test.

Imatinib: Major photocatalytic degradation pathways in aqueous media and the relative toxicity of its transformation products.

Imatinib (IMA) is a highly potent tyrosine kinase inhibitor used as first-line anti-cancer drug in the treatment of chronic myeloid leukemia. Due to its universal mechanism of action, IMA also has endocrine and mutagenic disrupting effects in vivo and in vitro, which raises the question of its environmental impact. However, to date, very little information is available on its environmental fate and the potential role of its transformation products (TPs) on aquatic organisms. Given the IMA resistance to hydrolysis and direct photolysis according to the literature, we sought to generate TPs through oxidative and radical conditions using the AOPs pathway. Thus, the reactivity of the cytotoxic drug IMA in water in the presence of OH and h+ was investigated for the first time in the present work. In this regard, a non-targeted screening approach was applied in order to reveal its potential TPs. The tentative structural elucidation of the detected TPs was performed by LC-HRMSn. The proposed approach allowed detecting a total of twelve TPs, among which eleven are being described for the first time in this work. Although the structures of these TPs could not be positively confirmed due to lack of standards, their chemical formulas and product ions can be added to databases, which will allow their screening in future monitoring studies. Using the quantitative structure-activity relationship (QSAR) approach and rule-based software, we have shown that the detected TPs possess, like their parent molecule, comparable acute toxicity as well as mutagenic and estrogenic potential. In addition to the in silico studies, we also found that the samples obtained at different exposure times to oxidative conditions, including those where IMA is no longer detected, retained toxicity in vitro. Such results suggest further studies are needed to increase our knowledge of the impact of imatinib on the environment.

Managing the Unmanageable: A Two-Staged Palliative Resection to Control Life-Threatening Duodenal Bleeding Due to Recurrent Paraganglioma.

BACKGROUND This report presents therapeutic decision-making and management of refractory, life-threatening duodenal bleeding in a young man with recurrent metastatic retroperitoneal paraganglioma. CASE REPORT The patient had been symptom free for 8 years after radioactive MIBG (metaiodobenzylguanidine) therapy. Failure of endoscopic or angiographic bleeding control led to urgent need to evaluate possible endocrine functional status, tumor curability, safety of incomplete resection, intra- and postoperative support needs, and anticipated recovery potential and postoperative function. Aside from these considerations, impact of tumor biology, alternative therapeutic options, current management guidelines, and ethical challenges of resource utilization for such complex palliative operative intervention were reviewed. CONCLUSIONS Based on the observed outcomes after an urgent presentation of an unusual tumor-related complication, palliation-intent therapy was justifiable even if significant treatment-related risks were expected and complex resources were required.

Prevalence and diversity of Chlamydiales and other amoeba-resisting bacteria in domestic drinking water systems.

A growing number of human infections incriminate environmental bacteria that have evolved virulent mechanisms to resist amoebae and use them as a replicative niche. These bacteria are designated amoeba-resisting bacteria (ARB). Despite the isolation of these ARB in various human clinical samples, the possible source of infection remains undetermined in most cases. However, it is known that the ARB Legionella pneumophila, for instance, causes a respiratory infection in susceptible hosts after inhalation of contaminated water aerosols from various sources. The Chlamydiales order contains many ARB, such as Parachlamydia acanthamoebae or Simkania negevensis, previously implicated in human respiratory infections with no identified contamination sources. We thus investigated whether domestic water systems are a potential source of transmission of these Chlamydiales to humans by using amoebal culture and molecular methods. Other important ARB such as mycobacteria and Legionella were also investigated, as were their possible amoebal hosts. This work reports for the first time a very high prevalence and diversity of Chlamydiales in drinking water, being detected in 35 (72.9%) of 48 investigated domestic water systems, with members of the Parachlamydiaceae family being dominantly detected. Furthermore, various Legionella and mycobacteria species were also recovered, some species of which are known to be causal agents of human infections.

Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study.

OBJECTIVE: Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). METHODS: A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. RESULTS: At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. CONCLUSIONS: Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.

Modeling of hospital wastewater pollution by pharmaceuticals: first results of Mediflux study carried out in three French hospitals.

A study has been carried out in three French hospitals in order to assess and model the pharmaceutical load in hospital wastewater and its impact in WWTP. This study, called Mediflux, consisted of three successive steps: first, an original prioritization procedure developed in our laboratory enabled us to select a list of relevant molecules from different Anatomical Therapeutic Chemical (ATC) classes containing pharmaceuticals for specific hospital use such as anesthetics or antineoplastic agents and pharmaceuticals dispensed in the community. Then, analytical quantification procedures were developed and validated according to 2002/657/EC European directive. Sampling campaigns were performed in three different hospitals, two located in the Paris area and one in a medium-sized city 150 km from Paris. Sampling was also carried out in wastewater treatment plants. At the same time, in order to model the pharmaceutical loads from hospitals, predicted concentrations were calculated as a first approach assuming it would be a single-box model, i.e. hospitals have no effect on drug loads and only human metabolism is taken into account to evaluate the fraction of drugs eliminated in hospital effluent. In the last step, the comparison of measured and calculated concentrations showed a satisfactory correlation for some pharmaceuticals, mainly those with short elimination half-lifes and weak human metabolism. For others, it appeared that modeling should take into account various factors such as out patient use, pharmacokinetic data and molecule stability in wastewater.

The case for re-evaluating the upper limit value for selenium in drinking water in Europe.

Selenium is an essential trace element for life, which can be toxic for humans when intakes reach a certain amount. Therefore, since the margin between healthy intake and toxic intake is narrow, the selenium concentration of tap water is a parameter that must be monitored because of its potential for increased intake. The present work gives an overview of the different approaches used to calculate safe limits for selenium. As recommended by WHO, the guidelines for drinking water form the basis of national legislated standards for drinking water. Before setting a maximum acceptable level in drinking water, it is necessary to take into account the total intake of selenium in both food and beverage. The limit value of 10 microg l(-1) for drinking water laid down in the European regulations for all countries should be adapted depending on geographic area, as previously recommended by WHO.

In vitro assessment of thyroid and estrogenic endocrine disruptors in wastewater treatment plants, rivers and drinking water supplies in the greater Paris area (France).

The presence of estrogenomimetic compounds in the environment, and particularly in water resources, is well known. In contrast, little data is available about the disruption of the thyroid system, even though thyroid hormones are strongly involved in regulating metabolism, growth and development. The aim of this study was to carry out a parallel evaluation of the disruptions of thyroid and estrogenic hormone receptor transcriptional activities, induced by water samples from two wastewater treatment plants (WWTPs), in the river Seine, and from four drinking treatment plants located in the Paris area. Two in vitro bioassays were used for the evaluation of thyroid (PC-DR-LUC) and estrogenic (MELN) disruption. Our observations of thyroidal activity show that a disruption potential was only present in the WWTPs influents, whereas estrogenicity was systematically detected in both influents and effluents. The great majority of endocrine activity was removed during the biological process. In the river Seine, only estrogenicity was detected, and no activity was observed in drinking water supplies. Fractionation of the influents revealed that most of the thyroidal effect was associated with compounds with low polarity, and could be partly attributable to 4-nonylphenol.

A new bioluminescent cellular assay to measure the transcriptional effects of chemicals that modulate the alpha-1 thyroid hormone receptor.

Interactions of environmental pollutants with the thyroid endocrine axis have received much attention especially because thyroid hormones (THs) play a major role in mammalian brain development. In order to screen for compounds that act on the triiodothyronine (T3) signaling pathway, we developed a new reporter gene assay expressing luciferase under the control of the TH receptor (TR). PC12 cells expressing the alpha1-isoform of TR of avian origin were stably transfected with a luciferase gene controlled by the SV40 promoter, and enhanced by a four-spaced direct repeat (DR4) thyroid response element (TRE). The resulting PC-DR-LUC cells were used to optimize a T3 assay in multiwell microplates. This assay was highly sensitive (30 pM T3) and reproducible, and responded as expected to TH analogues. Several halogenated phenolic (3,3',5,5'-tetrabromobisphenol A, 3,3',5,5'-tetrachlorobisphenol A, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl) and phenol (pentachlorophenol, 2,4,6-triiodophenol) compounds suspected of being thyroid-disrupting environmental chemicals induced partial agonistic and/or complex competitive/uncompetitive antagonistic responses in PC-DR-LUC cells at micromolar concentrations. A cell viability test indicated that these effects were not related to cytotoxicity of the chemicals. These results suggest that the PC-DR-LUC assay could be a valuable tool for the large-scale screening for thyroid receptor agonists and antagonists in vitro, and for detecting thyroid disruptors in the environment.

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

The prevalence of obesity and associated morbidity among 17-year-old Israeli conscripts.

BACKGROUND: There has been a significant increase in the prevalence of obesity among children and adolescents over the last few decades. Obesity is associated with significant psychosocial and physical morbidity. OBJECTIVE: The aim of this study was to define the prevalence of obesity and associated morbidity, including type 2 diabetes and hypertension, among 17-year-old adolescents. A comparison between the morbidity patterns of females and males was also performed. DESIGN: All 17-year-old Israeli nationals are obliged by law to present at the Israel Defence Forces recruiting office for a medical examination, with the exception of orthodox religious and Arabic adolescents. Height and weight are measured and classified, and a trained specialist evaluates those with suspected associated diseases. The level of education is also recorded. RESULTS: Our survey included 76,732 adolescents, 32,402(42.2%) females and 44,330(57.8%) males. The prevalence of obesity and morbid obesity among 17-year-old Israeli conscripts was 4.1% in males and 3.3% in females. The prevalence of borderline overweight was 12.4% in males and 11.4% in females. The prevalence of hypertension and type 2 diabetes was significantly higher among conscripts with BMI>30 kg/m2 in both genders. There was also a significantly higher prevalence of hypertension and type 2 diabetes in males compared with females(P<0.001, 0.015). A significantly higher prevalence of conscripts without high-school education(<10 years of education) was found among females with BMI>30 kg/m2. There was no significant difference among the male conscripts. CONCLUSIONS: This study found a relatively low prevalence of obesity among 17-year-old Israeli conscripts, but an alarmingly high prevalence of borderline overweight. Obesity was correlated with a higher prevalence of hypertension and type 2 diabetes, and a lower level of education. There was a significant difference between genders in the prevalence of hypertension and type 2 diabetes, and this should be further investigated. These data call for the creation of new education programmes on the prevention of overweight among children and adolescents.

Comparison of disinfectants for biofilm, protozoa and Legionella control.

The aim of this study was to compare the efficiency of different disinfectants applicable to Legionella control in domestic water systems. A domestic water supply simulation unit that allowed simulation of real-world conditions was developed for this purpose. The system, consisting of seven identical rigs, was used to compare treatment efficiency under equivalent conditions of system design, materials, hydraulics, water quality, temperature and initial contamination. During the study, each of six loops received continuous application of one of the following disinfectants: chlorine, electro-chlorination, chlorine dioxide, monochloramine, ozone, or copper/silver. The seventh loop was used as a control and remained untreated. Performance evaluation of these disinfectants was based on their ability to reduce not only Legionella, but also protozoa and biofilms, which contribute to the establishment and dissemination of these bacteria in water systems, and their resistance to treatments. Regarding these criteria, chlorine dioxide and chlorine (as bleach or obtained by electro-chlorination) were the most effective treatments in this study. However, in comparison with chlorine, chlorine dioxide showed a longer residual activity in the system, which constituted an advantage in the perspective of an application to extensive pipework systems.

Amoebae in domestic water systems: resistance to disinfection treatments and implication in Legionella persistence.

AIMS: Monitoring of microbial changes during and after application of various disinfection treatments in a model domestic water system. METHODS AND RESULTS: A pilot-scale domestic water system consisting of seven galvanized steel re-circulation loops and copper dead legs was constructed. Culture techniques, confocal laser scanning microscopy after fluorescent in situ hybridization and viability staining with the BacLight LIVE/DEAD kit were used for planktonic and biofilm flora monitoring. Before starting the treatments, the system was highly contaminated with Legionella pneumophila and biofilm populations mainly consisted of beta-proteobacteria. In the water and the biofilm of the loops, continuous application of chlorine dioxide (0.5 mg l(-1)), or chlorine (2.5 mg l(-1)) were very effective in reducing the microbial flora, including L. pneumophila. Heterotrophic bacteria, although strongly reduced, were still detectable after ozone application (0.5 mg l(-1)), whereas with monochloramine (0.5 mg l(-1)) and copper-silver ionization (0.8/0.02 mg l(-1)), the contamination remained significantly higher. Monochloramine and copper-silver did not remove the biofilm. During copper-silver application, Legionella re-growth was observed. Only chlorine dioxide led to detectable effects in the dead leg. Amoebae could not be eliminated, and after interrupting the treatments, L. pneumophila quickly recovered their initial levels, in all cases. CONCLUSIONS: Chlorine dioxide, applied as a continuous treatment, was identified in this study as the most efficient for controlling L. pneumophila in a domestic water system. Chlorine dioxide showed a longer residual activity, leading to improved performance in the dead leg. Amoebae resisted to all the treatments applied and probably acted as reservoirs for L. pneumophila, allowing a quick re-colonization of the system once the treatments were interrupted. SIGNIFICANCE AND IMPACT OF THE STUDY: Control of microbial contamination requires maintenance of a constant disinfectant residual throughout the water system. Treatment strategies targeting free-living amoebae should lead to improved control of L. pneumophila. Such treatment strategies still have to be investigated.

Monitoring genotoxicity during the photocatalytic degradation of p-nitrophenol.

p-Nitrophenol is a common structural unit of many pesticides and was chosen as a model compound to monitor genotoxicity during photocatalytic degradation. The genotoxicity of p-nitrophenol (PNP) and its breakdown products was measured using a bioluminescent bacterial bioassay, Vitotox. The genotoxic potential decreased with the concomitant photocatalytic degradation of the parent PNP concentration. The rate of genotoxicity reduction was slower than the rate of removal of the parent PNP, due to the formation of genotoxic by-products. After 6 h of photocatalytic treatment the total genotoxicity was removed. These results indicate that bioassays can be used as a simple and highly sensitive method for monitoring the general toxicity of chemical pollutants before, during and after photocatalytic treatment or other destructive processes.

[Molecules used for therapeutic or diagnostic purposes are micro water polluants]. / Des molécules à usages thérapeutiques et de diagnostic sont des micropolluants des milieux aquatiques.

Molecules used for therapeutic or diagnostic purposes have been identified and quantified in Europe and North America in surface and ground waters used for production of drinking water. When mixed with other organic compounds such as pesticides, hydrocarbons, or plasticizers which may present endocrine-disturbing or genotoxic effects, such molecules may, even in low concentrations, present an ecotoxicological or public health hazard. For this reason, healthcare professionals involved in drug production as well as drug users must take care to limit release of such molecules into the environment. Work on environmental behavior of marketed products and on health hazard assessment must be favored in order to acquire appropriate knowledge of the environmental and health risks.

An ATP-based method for monitoring the microbiological drinking water quality in a distribution network.

The titration of adenosine triphosphate (ATP) by bioluminescence permits rapid evaluation of the quantity of viable micro-organisms present in a water sample. During two sampling campaigns, Société Anonyme de Gestion des Eaux de Paris (SAGEP) tested a new extraction and titration system of bacterial ATP in the Paris drinking water distribution network. As far as the entire set of results of analyses of water in the network is concerned there is a linear relationship between log [ATP] and log(HPC-R2A/ml). Furthermore, as regards the drinking water originating from treatment of surface waters, some of the results obtained indicate a slight change as regards the Paris network in the microbiological quality. This is certainly linked to the distance travelled from the production location as well as to a reservoir effect observed on a site. Conversely, no change is apparent with regard to waters of underground origin. Lastly, despite changes in temperature and chlorine residual, no significant influence has been observed, essentially because of the very low density of culturable bacteria.

A colorimetric and fluorometric microplate assay for the detection of microcystin-LR in drinking water without preconcentration.

Protein phosphatase inhibition assays currently used for the detection of cyanobacterial peptide hepatotoxins in drinking water require an enrichment step using C18 cartridges to achieve lower the detection limit. This paper describes a colorimetric and fluorometric protein phosphatase inhibition method for the direct detection of microcystin-LR (MCYST-LR) in drinking water without complex clean-up steps and preconcentration procedures. In this assay three different substrates, p-nitrophenyl phosphate (p-NPP) and two fluorogenic compounds, 4-methylumbelliferyl phosphate (MUP) and 6,8-difluoro-4-methylumbelliferyl phosphate DiFMUP), were tested. The detection limits of the assay are 0.25 and 0.1 microg/l using colorimetric and fluorometric methods, respectively. These levels are well below the provisional guideline value for MCYST-LR of 1 microg/l of drinking water. The detection limit of the fluorometric method is comparable to that of the classical ELISA test. Although both the latter tests allow the detection of MCYST-LR in drinking water directly without pretreatment, the protein phosphatase inhibition assay remain less expensive and therefore more attractive for use in the routine assessment of drinking water contamination by microcystins.

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Use of the SpaceMaker balloon in sternal wound closure: comparison with other techniques.

Sternal wound infection is surgically treated by debridement of the infected sternum and closure of the defect with a muscular flap. These operations tend to be long, stressful, and time-consuming and to involve heavy blood loss. To facilitate wound closure, the SpaceMaker balloon was applied intraoperatively to expand the pectoralis major muscles and enable tensionless closure with musculocutaneous flaps. The aim of the present study was to compare the effectiveness and feasibility of this technique with a variety of others described in the literature. The study population consisted of 40 consecutive patients with sternal wound infection following median sternotomy who were treated with the advancement flap, turnover flap, transposition flap, or SpaceMaker balloon-assisted advancement flap technique (n = 10 each). The balloon-assisted technique was associated with a shorter length of operation and fewer blood transfusions than the other methods. Furthermore, there was no need for reoperation and there were no cases of skin necrosis. In conclusion, closure with the SpaceMaker balloon-assisted bilateral pectoralis major musculocutaneous flap may serve as an adjunctive measure in the treatment of sternal wound infection. This technique seems to have advantages over simple pectoralis major musculocutaneous advancement, particularly for midsternal wounds.