[Is it worth delivering Direct-Current Counter shock to critically ill patients with supra-ventricular tachyarrhythmia?] / Vaut-il la peine de délivrer un choc électrique aux patients de réanimation avec tachycardie supra-ventriculaire ?

Supra-ventricular tachyarrhythmia and its treatment have been poorly investigated in ICU patients. AIMS: To evaluate efficacy and safety of cardioversion for supra-ventricular tachyarrhythmia in the intensive care unit (ICU). PATIENTS AND METHODS: Prospective inclusion of all patients who presented supra-ventricular tachyarrhythmias lasting≥30seconds in a single medico-surgical ICU, except cardiac surgery. Anti-arrhythmic drugs and/or direct-current cardioversion were administered on a liberal basis. RESULTS: During the 15-month study period, 108/846 patients (12.8%) experienced supra-ventricular tachyarrhythmias. Anti-arrhythmic drugs were administered in 78 patients (72%); mostly amiodarone (92%), and/or magnesium (23%), resulting in an overall conversion rate of 68%. Direct-current cardioversion was used in 26 patients (24%), (24 patients received drug enhancement by anti-arrhythmic drugs) with an immediate 80.8%-success rate. CONCLUSION: Direct-current cardioversion was associated with sustained conversion to sinus rhythm in 80.8% of ICU patients with supra-ventricular tachyarrhythmias, although most of them had already received drug enhancement.

[Management of cardiogenic shock: Results from a survey in France and Belgium]. / Prise en charge d'un patient en état de choc cardiogénique : résultats de l'enquête de pratique franco-belge.

PURPOSE: Physician survey on cardiogenic shock management; recommendations for the management of patients with cardiogenic shock are based mostly on experts' opinion. METHODS: Overall 1585 emails were sent to "senior" intensive care physicians from France and Belgium from September 2014 to march 2015. Response rate was 10% (157 respondents). Agreement was assessed based on RAND/UCLA methodology. RESULTS: Continuous monitoring of cardiac output, vascular filling, noninvasive ventilation were deemed appropriate. The use of systematic diuretics and dopamine seemed inappropriate. There was a strong agreement to use dobutamine as inotropic drug in first intention. The use of noradrenaline and adrenaline was considered appropriate. There was a strong agreement to use mechanical circulatory support, in particular extracorporeal life support, in refractory cardiogenic shock. Only 25% of responders felt that there are criteria of refractory cardiogenic shock. Concerning the objectives of systolic, diastolic and mean blood pressure, 95% of the responses were in the range between 70 to 100, 30 to 50, and 55 to 65mmHg, respectively. The target of SvO2 was between 55% and 75%, and cardiac index between 1.5 and 3L/min/m2 for 95% of responders. There was a strong agreement to maintain hemoglobin between 7 and 9.9g/dL. CONCLUSION: Based on our physician survey, we found an agreement in vascular filling and early enteral nutrition. Dobutamine and noradrenaline should be the preferred drugs, but not dopamine. Mechanical circulatory support (preferably with extracorporeal support) should be restricted to refractory cardiogenic shock. Those responses differed slightly from experts' opinion, available in terms of recommendations.

Comparison of porcine thorax to gelatine blocks for wound ballistics studies.

Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 × 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 × 45 Federal Premium® Tactical® Bonded®) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations, though greater debris was produced in the thoraxes.

Demonstrating the effect of forensic firearm countermeasures: Bullet characteristics generated due to barrel modifications.

Forensic awareness and the declining availability of firearms have resulted in an increase in the use of modified and re-activated firearms in crime. Although some modifications are undertaken to simply acquire a functioning firearm, others are perpetrated as a direct forensic countermeasure to prevent the association between a firearm and a crime. This article describes the effects of these modifications on bullet striation patterns imparted from the barrel to a fired bullet. The key results indicated that the investigated modifications display assessable characteristics. The use of an oversized barrel imparted striations consistent with firing with the absence of typical rifling. Subsequent or consecutively fired bullets possessed striation variations, with the first showing the least evidence of striations. The application of a choke resulted in more obvious bullet elongation compared to a smoothbore barrel. The restriction caused merging of lands and groves of the imparted rifling and obscured their usual definition. Effects of breech adaption were also characterised by observing the buckling and enlargement of the cartridge case. This deformity of the cartridge case was most evident when the barrel pressure increased due to the presence of the choke. From this study it was evident that unique characteristic impressions associated with different modifications most commonly found in criminal investigations can be utilised by a forensic expert and impart significant intelligence to an investigation.

Activation of the NF κ B Pathway Enhances AhR Expression in Intestinal Caco-2 Cells.

Recent data suggest that apart from its well-known role in the regulation of xenobiotic metabolizing enzymes, AhR is also involved in inflammation. However, the influence of inflammation on AhR expression remains unknown. Here, we demonstrated that proinflammatory conditions induced by either PMA or IL-1 ß enhance AhR expression in Caco-2 cells. This was associated with an increase in AhR promoter activity. By means of directed mutagenesis experiments and the use of proteasome inhibitors, we demonstrated that inflammation-induced AhR expression involved the NF κ B pathway but not AP-1. Moreover, conditioned media from PMA-treated Caco-2 cells were also able to induce AhR expression, and this induction was repressed by anti-IL-1 ß blocking antibodies. Similar results were obtained with conditioned media from PMA-treated THP-1 cells. Taken together, these data suggest that AhR could be involved in vivo in an inflammatory loop. AhR was recently suspected to be implicated in inflammatory bowel disease. Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.

[Cardiac impairment after hanging attempt: a preliminary descriptive study]. / Anomalies cardiaques après tentative de pendaison : étude descriptive préliminaire.

PURPOSE OF THE STUDY: Cardiomyopathy has sometimes been reported after suicide attempts by hanging. The objective of this retrospective observational study was to describe cardiac dysfunction occurring after hanging and its consequences on prognosis. PATIENTS AND METHODS: Fifteen patients admitted to the intensive care unit for hanging from 1997 to 2011 were included and divided into two groups according to presence or absence of cardiac arrest at initial presentation. Cardiac dysfunction was defined by the presence of clinical, biological, electrocardiographic or echocardiographic abnormalities. RESULTS: Cardiac impairment was diagnosed in nine patients over 15 (60%). Of the six patients with initial cardiac arrest, only one survived without severe neurological sequellae. Among the nine patients without cardiac arrest, eight survived and five patients (56%) had cardiac impairment, including two cases of echocardiographic aspect of Takotsubo complicated by pulmonary edema. Mortality in intensive care was significantly related to the severity of the initial neurological state assessed by the Glasgow Coma Score (OR=1.7; P=0.02), and the occurrence of cardiac arrest (OR=40; P=0.016). The presence of cardiac involvement, reversible after the acute phase in all surviving patients was not associated with increased mortality. CONCLUSION: In the aftermath of hanging, predictors of mortality are the presence of impaired consciousness or initial cardiac arrest, but not the occurrence of cardiac disease.

Parental work schedules and child overweight and obesity.

OBJECTIVE: Studies in school-age children have consistently shown a positive association between maternal paid work hours and child obesity. However, there is conflicting evidence about the impact of maternal work hours scheduled at nonstandard times (for example, evenings, nights or weekends), and no previous examination of paternal work schedules and child weight. We examined the associations between maternal, paternal and combined parental paid work schedules and overweight/obesity in children at age 9 years. METHODS: Data were analysed from the most recent follow-up of 9-year-old children (n=434) in an Australian birth cohort study. Children were measured and classified as overweight/obese using the International Obesity Taskforce body mass index cutoff points. Current working conditions of parents were obtained from a structured interview with the primary caregiver. Logistic regression analyses were used to investigate the effect of parental work schedules on child overweight/obesity with adjustment for a range of sociodemographic and household factors associated with parental employment and child weight. RESULTS: At 9 years of age, 99 children (22.8%) were overweight or obese. When parental work schedules were examined separately, child overweight/obesity was significantly associated with paternal nonstandard work schedules (adjusted odds ratio (OR) 1.97, 95% confidence interval (CI) 1.08-3.61). There was no association with any type of maternal work schedule. We also found an association between child overweight/obesity and circumstances in which both parents worked nonstandard schedules; however, this was of borderline statistical significance in the adjusted models (adjusted OR 2.26, 95% CI 0.99-5.16). CONCLUSION: Work hours scheduled at nonstandard times, when worked by the father or both parents, were associated with child overweight and obesity. These findings indicate the potential importance of fathers' paid work arrangements for child overweight/obesity, which until recently has largely been ignored.

[One case of nosocomial A(H1N1)v2009 influenza in Réunion Island]. / Un cas de grippe A(H1N1)v2009 nosocomiale à la Réunion.

A 19-year-old patient admitted in an oncology unit for an autograft (Hodgkin disease), developed on day 20 a fatal acute respiratory failure and multiple organ failure due to an infection of the A(H1N1)v2009 virus, which was acquired in the hospital, despite partial preventive measures. At that time, the specific vaccine was not available in Réunion. We discuss the nosocomial origin of the infection. Following the epidemic wave, the vaccination rate of the general population and the hospital employees remains very low.

[Severe cases of A(H1N1)v2009 infection in Réunion Island in 2009 and 2010]. / Formes graves d'infection par le virus A(H1N1)v2009 à La Réunion en 2009 et en 2010.

In the Southern hemisphere, Réunion Island acts as a sentinel for infections preferentially occurring during the austral winter that are likely to reach the Northern hemisphere a few months later. We relate the main features concerning patients that were admitted during years 2009 and 2010 in our intensive care unit with an A(H1N1)v2009 infection, mainly for acute respiratory distress. Demographic, clinical, and biological data as well as given medications and outcome were prospectively collected among all PCR-confirmed influenza-infected patients. In 2009 and 2010, 25 patients met the criteria. Patients' median age was 40.4 (±17.4) years. Most of them (22/25) had comorbidities such as: chronic diseases, overweight, obesity, pregnancy, and Down syndrome. Maximum bed-occupation rate was 10 days per million inhabitants. Main diagnosis for ICU admission was virus-related pneumonia. Twenty-two out of 25 patients needed mechanical ventilation, some required rescue therapies such as extracorporeal membranous oxygenation (ECMO) or hi-frequency oscillation ventilation (HFOV), both only available in few French hospitals. Within the study period, 12 patients died (48%) mainly of multi-organ failure. Through 2009 and 2010 autumn and winter periods, for several weeks, the A(H1N1)v2009 virus infection resulted in a significant increase of workload in Réunion Island ICUs. In 2010, the failure of the mass immunization campaign, particularly among the at-risk groups, led to severe cases of A(H1N1)v2009 infections, particularly among patients with comorbidities. Our data may contribute toward better management of influenza virus pandemics in the future.

Oxidative stress pathways highlighted in tumor cell immortalization: association with breast cancer outcome.

An improved understanding of cell immortalization and its manifestation in clinical tumors could facilitate novel therapeutic approaches. However, only rare tumor cells, which maintain telomerase expression in vitro, immortalize spontaneously. By expression-profiling analyses of limited-life primary breast tumor cultures pre- and post-hTERT transduction, and spontaneously immortalized breast cancer cell lines, we identified a common signature characteristic of tumor cell immortalization. A predominant feature of this immortalization signature (ImmSig) was the significant overexpression of oxidoreductase genes. In contrast to epithelial cells derived from low histologic grade primary tumors, which required hTERT transduction for the acquisition of ImmSig, spontaneously immortalizing high-grade tumor cultures displayed similar molecular changes independent of exogenous hTERT. Silencing the hTERT gene reversed ImmSig expression, increased cellular reactive oxygen species levels, altered mitochondrial membrane potential and induced apoptotic and proliferation changes in immortalized cells. In clinical breast cancer samples, cell-proliferation-pathway genes were significantly associated with ImmSig. In these cases, ImmSig expression itself was inversely correlated with patient survival (P=0), and was particularly relevant to the outcome of estrogen receptor-positive tumors. Our data support the notion that ImmSig assists in surmounting normal barriers related to oxidative and replicative stress response. Targeting a subset of aggressive breast cancers by reversing ImmSig components could be a practical therapeutic strategy.

Implantable gastric stimulation to achieve weight loss in patients with a low body mass index: early clinical trial results.

This report describes the authors' early outcomes with implantable gastric stimulation (IGS) used to achieve weight loss in patients with a low body mass index (BMI). After prescreening of potential candidates with a selection algorithm, 24 patients (21 women and 3 men) with a low BMI (30-34.9) underwent IGS implantation at two centers. The patients had a mean age of 43 years (range, 32-60 years), a mean BMI of 33 (range, 30-36), and a mean weight of 92 kg (range, 80-117 kg). At this writing, 6 months postoperatively, there have been no serious adverse events related to the device. The mean percentage of excess weight loss (EWL) was 5.9%, with three patients explanted because of noncompliance. The mean waist circumference decreased 5.8%, which was significant (p = 0.009). A subset of nine patients (37.5%) had an EWL exceeding 10% (mean, 20.1%). A subset of low BMI patients lost a clinically significant amount of weight with IGS within 6 months. Further study is required for better identification of potential candidates for this novel approach.

The development of a quantitative flexibility test for body armour and comparison with wearer trials.

In this paper a mechanical flexibility test is developed which can be used to assess multi layer body armour systems. This is compared with a subjective manual test, and then with the results of wearer trials conducted using the recently approved ISO body armour standard ISO 14876-1 (2002). A series of trials was conducted on six different ballistic and/or stab resistant body armour types with a variety of protection levels and constructions. These were tested using the mechanical test system in which the armour was forced through a 200 mm hole by a 100 mm hemispherical plunger. The results of this test were then compared to a second set of trials in which flexibility of the same armour was assessed by manual handling and flexing of the armour. Finally an ergonomic wearer trial was conducted with four armours according to ISO 14876-1 (2002) each armour being assessed by four volunteers and the results compared to flexibility data collected in the first two trials. It was shown that the mechanical flexibility test produced results which were in good agreement with a purely subjective flexibility assessment. These results in turn showed reasonable but not exact correlation with the wearer trials. The ISO wearer trials addressed other factors such as overall comfort and fit of the systems and so the results were not purely a function of flexibility.

Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites.

BACKGROUND AND AIMS: Cytochrome P450 1A1 catalyzes the degradation of endobiotics (estradiol, fatty acids, and so on) and the bioactivation of numerous environmental procarcinogens, such as arylamines and polycyclic aromatic hydrocarbons, that are found in food. Several peroxisome proliferators and arachidonic acid derivatives enhance cytochrome P450 1A1 activity, but the mechanisms involved remain unknown. The aim of this work was to study the role of peroxisome proliferator-activated receptors in cytochrome P450 1A1 gene induction. METHODS: The role of peroxisome proliferator-activated receptor transcription factors in cytochrome P450 1A1 induction was assessed by means of enzymatic activities, quantitative real-time polymerase chain reaction, gene reporter assays, mutagenesis, and electrophoretic mobility shift assay. RESULTS: We show that peroxisome proliferator-activated receptor-alpha agonists (WY-14643, bezafibrate, clofibrate, and phthalate) induce human cytochrome P450 1A1 gene expression, whereas 2,4-thiazolidinedione, a specific peroxisome proliferator-activated receptor-gamma agonist, represses it. The induction of cytochrome P450 1A1 transcripts by WY-14643 was associated with a marked increase of ethoxyresorufin O -deethylase activity (10-fold at 200 mumol/L). Transfection of peroxisome proliferator-activated receptor-alpha complementary DNA enhanced cytochrome P450 1A1 messenger RNA induction by WY-14643, although WY-14643 failed to activate xenobiotic responsive element sequences. Two peroxisome proliferator response element sites were located at positions -931/-919 and -531/-519 of the cytochrome P450 1A1 promoter. Their inactivation by directed mutagenesis suppressed the inductive effect of WY-14643 on cytochrome P450 1A1 promoter activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay experiments showed that the 2 cytochrome P450 1A1 peroxisome proliferator response element sites bind the peroxisome proliferator-activated receptor-alpha/retinoid X receptor-alpha heterodimer. CONCLUSIONS: We describe here a new cytochrome P450 1A1 induction pathway involving peroxisome proliferator-activated receptor-alpha and 2 peroxisome proliferator response element sites, indicating that peroxisome proliferator-activated receptor-alpha ligands, which are common environmental compounds, may be involved in carcinogenesis.

Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial.

OBJECTIVE: To compare the effect of a Serenoa repens extract with placebo for symptoms of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In a double-blind placebo-controlled randomized trial between January 1999 and March 2000, 100 men with symptoms of BPH, aged < 80 years, with a maximum urinary flow rate of 5-15 mL/s for a voiding volume of 150 mL, were randomly and equally allocated to 320 mg S. repens extract or placebo (paraffin oil). The main outcome measures were the International Prostate Symptom Score (IPSS), peak urinary flow rate, and the Rosen International Index of Erectile Function (IIEF) questionnaire. RESULTS: There was no significant difference between the treatments over the 12 weeks of the study in the IPSS, peak urinary flow rate or for the IIEF questionnaire. CONCLUSIONS: During the trial all participants had some improvement in their symptoms of BPH but there was no significant beneficial effect of this S. repens extract over placebo in this 12-week trial.

Wounding patterns and human performance in knife attacks: optimising the protection provided by knife-resistant body armour.

BACKGROUND: Stab attacks generate high loads, and to defeat them, armour needs to be of a certain thickness and stiffness. Slash attacks produce much lower loads and armour designed to defeat them can be far lighter and more flexible. METHODS AND SUBJECTS: Phase 1: Human performance in slash attacks: 87 randomly selected students at the Royal Military College of Science were asked to make one slash attack with an instrumented blade on a vertically mounted target. No instructions on how to slash the target were given. The direction, contact forces and velocity of each attack were recorded. Phase 2: Clinical experience with edged weapon attacks: The location and severity of all penetrating injuries in patients attending the Glasgow Royal Infirmary between 1993 and 1996 were charted on anatomical figures. RESULTS: Phase 1: Two types of human slash behaviour were evident: a 'chop and drag' blow and a 'sweep motion' type of attack. 'Chop and drag' attacks had higher peak forces and velocities than sweep attacks. Shoulder to waist blows (diagonal) accounted for 82% of attacks, 71% of attackers used a long diagonal slash with an average cut length of 34 cm and 11% used short diagonal attacks with an average cut length of 25 cm. Only 18% of attackers slashed across the body (short horizontal); the average measured cut length of this type was 28 cm. The maximum peak force for the total sample population was 212 N; the maximum velocity was 14.88 m s(-1). The 95 percentile force for the total sample population was 181 N and the velocity was 9.89 m s(-1). Phase 2: 431 of the 500 patients had been wounded with edged weapons. The average number of wounds sustained by victims in knife assaults was 2.4. The distribution of wounds by frequency and severity are presented. CONCLUSIONS: Anti-slash protection is required for the arms, neck, shoulders, and thighs. The clinical experience of knife-attack victims provides information on the relative vulnerabilities of different regions of the body. It is anticipated that designing a tunic-type of Police uniform that is inherently stab and slash resistant will eventually replace the current obvious and often bulky extra protective vest. Attempts at making a combined garment will need to be guided by ergonomic considerations and field testing. A similar anatomical regional risk model might also be appropriate in the design of anti-ballistic armour and combined anti-ballistic and knife-resistant armour.

Involvement of nuclear factor kappaB in c-Myc induction by tubulin polymerization inhibitors.

We showed previously that microtubule disassembly by vinblastine induces the proto-oncogene c-myc in epithelial mammary HBL100 cells. In this study, we demonstrate that vinblastine treatment in these cells, in contrast to what was observed with the colon adenocarcinoma cell line HT29-D4, activated the transcription factor NFkappaB, which has been involved in c-myc regulation. The microtubule disassembly also induced IkappaB degradation. Using transient transfection analysis, we show that the trans-activation of c-myc by vinblastine was decreased when NFkappaB binding sites on c-myc promoter were mutated. Additionally, we demonstrate that microtubule dissolution trans-activated a thymidine kinase-CAT construct containing an NFkappaB binding site at -1180 to -1080 bp relative to the P1 promoter. Thus, vinblastine up-regulates the enhancer activity of the NFkappaB binding site. These results suggest that microtubule disassembly induced by vinblastine can trans-activate the c-myc oncogene through NFkappaB. Taking into consideration the paradoxical roles of both c-myc and NFkappaB in proliferation or apoptosis, this data reveals the complex action mechanism of this microtubule interfering agent.

Rehabilitation of a quadruple amputee subsequent to electrical burns sustained whilst hang gliding.

PURPOSE: The purpose of this article is to describe the management, difficulties encountered and level of independence achieved during the initial stage of a quadruple amputee's rehabilitation. METHOD: This is a case study of the rehabilitation of the first known person losing all four limbs due to electrocution whilst hang gliding. RESULTS: The patient became a successful upper limb prosthetic user and returned to work six hours a day. Full independence in activities of daily living was not achieved nor considered practical. Independent walking was accomplished in physiotherapy. however an electric wheelchair remains the only functional means of mobility. CONCLUSION: The rehabilitation is described in detail to assist those managing such a rare and complex case.

Ribavirin-induced resistance to heat shock, inhibition of the Ras-Raf-1 pathway and arrest in G(1).

Ribavirin [1-(beta-D-ribofuranosyl)1,2,4-triazole-3-carboxamide (virazole)], a specific inhibitor of inositide 5'-monophosphate dehydrogenase (IMPDH), induces a strong depletion of GTP pools in IGR39 cells. After a 3-day treatment, the cell cycle was reversibly arrested in G(0)/G(1), suggesting the involvement of GTP in the cell cycle process. The reduction of the GTP cell content modified the appearance of the microtubule network, as examined using immunofluorescence. However, the dynamics of repolymerisation were not altered. When arrested in G(0)/G(1), cells displayed a surprising resistance to a 3-h period of heat shock at 45 degrees C. Considering the lack of coimmunoprecipitation of p21ras with Raf-1, the reduction of the level of GTP-associated p21ras and the decrease of the activation of the extracellular signal-regulated protein kinases (ERK), also known as mitogen-activated protein (MAP) kinase, in ribavirin-treated cells, we suggest a possible relationship between the expression of heat-shock proteins and the change, in GTP-depleted cells, of the regulation of Raf kinase by ras protein.