[Bilateral vestibulopathy and sensorineural hearing loss in necrobiotic xanthogranuloma, multiple myeloma and amiloidosis]. / Dvustoronnyaya vestibulopatiya i sensonevral'naya tugoukhost' u patsienta s nekroticheskoi ksantogranulemoi, mnozhestvennoi mielomoi i amiloidozom.

This article describes a rare case of necrotic xanthogranuloma in a 46-year-old patient who presented with the development of periorbital xanthelasms, progressive bilateral sensorineural hearing loss and bilateral vestibulopathy, followed by multiple myeloma and amyloidosis. For several years, the patient underwent standard rehabilitation for chronic sensorineural hearing loss and was fitted with a hearing aid. During hospitalisation for exacerbation of chronic bronchitis, monoclonal gammopathy was identified, and later, after careful examination and repeated biopsies, necrotic xanthogranuloma, multiple myeloma and AL-amyloidosis were confirmed. Targeted immunochemotherapy resulted in improvement of hearing and significant recovery of the vestibuloocular reflex bilaterally.

Smoke-free environment policy in Vietnam: what did people see and how did they react when they visited various public places?

INTRODUCTION: Since Vietnam has signed WHO framework on tobacco control (FCTC) in 2003 and has issued tobacco control law in 2013, there has been little research concerning about what impacts smoke-free regulations have had on public compliance. The objective of this study was to assess public exposure to secondhand smoke and reaction toward smoke-free policy regulations in Vietnam and the associated factor. METHODS: Using the design of GATS (Global Adult Tobacco Survey), a nationally representative sample of 8,996 adults were approached for data collection. Logistic regression was used to examine the associated factor. RESULTS: The study revealed that the prevalence of respondents exposed to secondhand smoke was much higher in bars/café/tea shops (90.07%) and restaurants (81.81%) than in any other public places, universities (36.70%), government buildings (31.12%), public transport (20.04%), healthcare facilities (17.85%) and schools (15.84%). 13.23% of respondents saw smokers violate smoke-free regulations. Among those who saw them violate smoke-free regulations, just one-third cautioned them to stop smoking. Strikingly, a higher rate of cautioning smokers to stop smoking was observed among the older, married, and better educated respondents. Respondents who were married, better educated and in lower economic status were more likely to remind smokers to stop smoking. CONCLUSIONS: The study has called for strengthening two of the six MPOWER (Monitor, Protect, Offer, Warn, Enforce and Raise) components of the tobacco free initiative introduced by WHO, Monitoring tobacco use and prevention policies and Protecting people from tobacco smoke.

Assessing the costs of disposable and reusable supplies wasted during surgeries.

BACKGROUND: The management of disposable and reusable supplies might have an impact on the cost efficiency of the Operating Room (OR). This study aimed to evaluate the cost and reasons for wasted supplies in the OR during surgical procedures. METHODS: We conducted an observational and prospective study in a French university hospital. We assessed the cost of wasted supplies in the OR (defined by opened unused devices), the reasons for the wastage, and the circulator retrievals. At the end, we assessed the perception of surgeons and nurses relative to the supply wastage. RESULTS: Fifty routine procedures and five non-scheduled procedures were observed in digestive (n = 20), urologic (n = 20) and gynecologic surgery (n = 15). The median cost [IQR] of open unused devices was €4.1 [0.5; 10.5] per procedure. Wasted supplies represented up to 20.1% of the total cost allocated to surgical supplies. Considering the 8000 surgical procedures performed in these three surgery departments, the potential annual cost savings were 100 000€. The most common reason of wastage was an anticipation of the surgeon's needs. The circulating nurse spent up to 26.3% of operative time outside of the OR, mainly attending to an additional demand from the surgeon (30%). Most of the survey respondents (68%) agreed that knowing supply prices would change their behavior. CONCLUSIONS: This study showed the OR is a major source of wasted hospital expenditure and an area wherein an intervention would have a significant impact. Reducing wasted supplies could improve the cost efficiency of the OR and also decrease its ecological impact.

Microwaves Probe Dipole Blockade and van der Waals Forces in a Cold Rydberg Gas.

We show that microwave spectroscopy of a dense Rydberg gas trapped on a superconducting atom chip in the dipole blockade regime reveals directly the dipole-dipole many-body interaction energy spectrum. We use this method to investigate the expansion of the Rydberg cloud under the effect of repulsive van der Waals forces and the breakdown of the frozen gas approximation. This study opens a promising route for quantum simulation of many-body systems and quantum information transport in chains of strongly interacting Rydberg atoms.

Mesenteric lymphatic vessels adapt to mesenteric venous hypertension by becoming weaker pumps.

Lymphangions, the segments of lymphatic vessels between two adjacent lymphatic valves, actively pump lymph. Acute changes in transmural pressure and lymph flow have profound effects on lymphatic pump function in vitro. Chronic changes in pressure and flow in vivo have also been reported to lead to significant changes in lymphangion function. Because changes in pressure and flow are both cause and effect of adaptive processes, characterizing adaptation requires a more fundamental analysis of lymphatic muscle properties. Therefore, the purpose of the present work was to use an intact lymphangion isovolumetric preparation to evaluate changes in mesenteric lymphatic muscle mechanical properties and the intracellular Ca(2+) in response to sustained mesenteric venous hypertension. Bovine mesenteric veins were surgically occluded to create mesenteric venous hypertension. Postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 6) and sham surgery (Sham; n = 6) animals were isolated and evaluated 3 days after the surgery. Spontaneously contracting MVH vessels generated end-systolic active tension and end-diastolic active tension lower than the Sham vessels. Furthermore, steady-state active tension and intracellular Ca(2+) concentration levels in response to KCl stimulation were also significantly lower in MVH vessels compared with those of the Sham vessels. There was no significant difference in passive tension in lymphatic vessels from the two groups. Taken together, these results suggest that following 3 days of mesenteric venous hypertension, postnodal mesenteric lymphatic vessels adapt to become weaker pumps with decreased cytosolic Ca(2+) concentration.

Effects of capsazepine, a transient receptor potential vanilloid type 1 antagonist, on morphine-induced antinociception, tolerance, and dependence in mice.

BACKGROUND: Repeated morphine treatment has been shown to induce transient receptor potential vanilloid type 1 (TRPV1) expression in the spinal cord, dorsal root ganglion (DRG), and sciatic nerve of a rat model. Increased TRPV1 expression may therefore play a role in morphine tolerance. In this study, we evaluated the hypothesis that blockage of TRPV1 may be useful as an adjunctive pain management therapy. We investigated whether blockage of TRPV1 by capsazepine, a TRPV1 antagonist, affected antinociception, development of tolerance, and physical dependence on morphine in mice. METHODS: Institute of Cancer Research mice were pretreated with capsazepine and post-treated with morphine acutely and repeatedly. Antinociception and its tolerance were assessed using the hot-plate test. Morphine dependence was examined through the manifestation of withdrawal symptoms induced by naloxone in morphine-dependent mice. RESULTS: Acute capsazepine treatment (5 mg kg⁻¹, i.p.) potentiated the antinociceptive effects of morphine, as measured by the hot-plate test. Repeated co-treatment of capsazepine (2.5 mg kg⁻¹ i.p.) with morphine attenuated the development of tolerance to the antinociceptive effect of morphine. The development of morphine dependence was also reduced by capsazepine (1.25 or 2.5 mg kg⁻¹ i.p.). CONCLUSIONS: Our results suggest that TRPV1 antagonists can be used adjunctively to morphine treatment because they strengthen morphine antinociception and prevent the development of tolerance, and also physical dependence, on morphine.

Macromolecular cobalt carbonyl complexes encapsulated in a click-cross-linked micelle structure as a nanoparticle to deliver cobalt pharmaceuticals.

Block copolymers poly(trimethylsilyl propargyl methacrylate)-block-poly(poly(ethylene glycol) methyl ether methacrylate) (P(TMS-PAMA)-b-P(PEGMA)) were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequent removal of the trimethylsilyl protective groups on the P(TMS-PAMA)(24)-b-P(PEGMA)(40) polymer with tetra-n-butylammonium fluoride hydrate lead to the polymer P(PAMA)(24)-b-P(PEGMA)(40) with pendant alkyne groups, which self-assembled in aqueous solution into micelles with hydrodynamic diameters of less than 20 nm. The alkyne groups in the core took on two functions, acting as a ligand for Co(2)(CO)(8) to generate a derivative of the antitumor agents based on (alkyne)Co(2)(CO)(6) as well as an anchor point for the cross-linking of micelles via click chemistry. The click process was shown to be highly efficient with the two types of cross-linker employed: 1,2-bis-(2-azidoethoxy)ethane and bis-(azidoethyl)disulfide, with almost all of the cross-linker reacting with the micelle at room temperature. The cross-linking density was influenced by the amount of added cross-linker leaving a well-defined amount of alkyne groups that were utilized in the formation of the cobalt complexes. The successful complexation was confirmed via UV/vis and FT-IR spectroscopy. With the formation of (alkyne)Co(2)(CO)(6) moieties in the core, the un-cross-linked and cross-linked micelles were found to almost double in size. The resulting Co-loaded un-cross-linked micelles were observed to be highly toxic to L929 fibroblast cells, while the cross-linking of the micelle was shown to reduce the toxicity.

Theoretical study of the gas-phase ozonolysis of beta-pinene (C10H16).

The O3-initiated oxidation of beta-pinene, a monoterpene emitted in forested areas, was theoretically characterized using DFT, CBS-QB3 and CASPT2 quantum chemical calculations combined with statistical kinetic RRKM/master equation analysis and transition state theory. The first-principles based rate coefficient of the initial 03 attack on the exocyclic double bond shows a slight positive temperature dependence, k(tot)T = 1.27 x 10(-22) x T2.64 x exp(-714 K/T) cm3 molecule(-1) s(-1) and is in close agreement with experiment. The resulting primary ozonides are found to give rise to two distinct, non-interconvertible conformers of the predominant Criegee intermediate (CI-1 and CI-2), with subsequent chemistries that are shown to be very different; this crucial aspect of beta-pinene ozonolysis was not taken into account in earlier studies. One of the conformers CI-2--carrying nearly half the total reaction flux--cannot undergo the usual "hydroperoxide channel", thus rationalizing why the OH yield from beta-pinene is barely half of that from alpha-pinene. The predicted first-generation product distribution for atmospheric conditions is consistent with the available experimental data on the overall products. Our final results predict 5% of nopinone formation, 28% OH radicals with 2-oxo-alkyl radical coproducts, 37% of stabilized Criegee intermediates (SCI), 17% lactones, 10% CO2 formed after an intersystem crossing, and 3% of a newly proposed biradical formed from prompt ring opening in the CI. In atmospheric conditions, additional OH production is expected from the stabilized CI-1 conformer via the thermal unimolecular "hydroperoxide channel", whereas the stabilized CI-2 can react with H2O and its dimer, to produce additional nopinone. The expected subsequent chemistries of the large coproduct radicals formed from reactions of the two CI are also addressed in extenso.

The gas-phase ozonolysis of beta-caryophyllene (C(15)H(24)). Part II: A theoretical study.

The O(3)-initiated oxidation of beta-caryophyllene, a sesquiterpene emitted in forested areas, was theoretically characterized for the first time using DFT quantum chemical calculations combined with statistical kinetic RRKM/master equation analysis and variational transition state theory. O(3)-Addition occurs primarily, >95%, on the endocyclic double bond without a barrier, leading to a total rate coefficient of 8.3 x 10(-24) T(3.05) exp(1028 K/T) cm(3) molecule(-1) s(-1), with a slight negative T-dependence. Thermal and chemically activated unimolecular reactions following this addition, including the so-called ester and hydroperoxide channels, and internal formation of the secondary ozonide, where characterized and quantified; a newly discovered reaction pathway through intersystem crossing from a dioxirane to a triplet bis(oxy) biradical intermediate is incorporated in the mechanism. The first generation product distribution at 298 K is predicted as 74% stabilized Criegee intermediates (CI), 8% OH radicals together with vinoxy-type 2-oxo alkyl radical co-products, 8% acids, 0.3% esters, and 9% CO(2) with two alkyl radical co-products. The thermalized CI can convert to the secondary ozonide in many reaction conditions, in particular the atmosphere; secondary ozonides are thus expected as dominant products of the beta-caryophyllene ozonolysis. These results are consistent with the experimental data presented in the accompanying paper (Part I). The temperature dependence and uncertainties of the product distribution are discussed. The high molecular weight oxygenated products, including beta-caryophyllonic acid and secondary ozonides, are expected to contribute to secondary organic aerosol formation.

Manipulation of the nuclear factor-kappaB pathway and the innate immune response by viruses.

Viral and microbial constituents contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). In addition, intracellular viral double-stranded RNA is detected by two recently characterized DExD/H box RNA helicases, RIG-I and Mda-5. Both TLR-dependent and -independent pathways engage the IkappaB kinase (IKK) complex and related kinases TBK-1 and IKKvarepsilon. Activation of the nuclear factor kappaB (NF-kappaB) and interferon regulatory factor (IRF) transcription factor pathways are essential immediate early steps of immune activation; as a result, both pathways represent prime candidates for viral interference. Many viruses have developed strategies to manipulate NF-kappaB signaling through the use of multifunctional viral proteins that target the host innate immune response pathways. This review discusses three rapidly evolving areas of research on viral pathogenesis: the recognition and signaling in response to virus infection through TLR-dependent and -independent mechanisms, the involvement of NF-kappaB in the host innate immune response and the multitude of strategies used by different viruses to short circuit the NF-kappaB pathway.

Photodissociation of benzene under collision-free conditions: an ab initio/Rice-Ramsperger-Kassel-Marcus study.

The ab initio/Rice-Ramsperger-Kassel-Marcus (RRKM) approach has been applied to investigate the photodissociation mechanism of benzene at various wavelengths upon absorption of one or two UV photons followed by internal conversion into the ground electronic state. Reaction pathways leading to various decomposition products have been mapped out at the G2M level and then the RRKM and microcanonical variational transition state theories have been applied to compute rate constants for individual reaction steps. Relative product yields (branching ratios) for C(6)H(5)+H, C(6)H(4)+H(2), C(4)H(4)+C(2)H(2), C(4)H(2)+C(2)H(4), C(3)H(3)+C(3)H(3), C(5)H(3)+CH(3), and C(4)H(3)+C(2)H(3) have been calculated subsequently using both numerical integration of kinetic master equations and the steady-state approach. The results show that upon absorption of a 248 nm photon dissociation is too slow to be observable in molecular beam experiments. In photodissociation at 193 nm, the dominant dissociation channel is H atom elimination (99.6%) and the minor reaction channel is H(2) elimination, with the branching ratio of only 0.4%. The calculated lifetime of benzene at 193 nm is about 11 micros, in excellent agreement with the experimental value of 10 micros. At 157 nm, the H loss remains the dominant channel but its branching ratio decreases to 97.5%, while that for H(2) elimination increases to 2.1%. The other channels leading to C(3)H(3)+C(3)H(3), C(5)H(3)+CH(3), C(4)H(4)+C(2)H(2), and C(4)H(3)+C(2)H(3) play insignificant role but might be observed. For photodissociation upon absorption of two UV photons occurring through the neutral "hot" benzene mechanism excluding dissociative ionization, we predict that the C(6)H(5)+H channel should be less dominant, while the contribution of C(6)H(4)+H(2) and the C(3)H(3)+C(3)H(3), CH(3)+C(5)H(3), and C(4)H(3)+C(2)H(3) radical channels should significantly increase.

Severe hypoxia specifically downregulates hepatocyte nuclear factor-4 gene expression in HepG2 human hepatoma cells.

The liver is one of the organs in which hypoxia helps to regulate gene expression under normal physiological conditions and in diseases such as cirrhosis and cancer. We postulated that the expression/activity of some of the 'liver-enriched' transcription factors, which control liver-specific genes, was sensitive to hypoxia. We tested hepatocyte nuclear factor-1 (HNF-1), HNF-3 and HNF-4, which play key roles in differentiation, development and hepatic gene expression, using HepG2 human hepatoma cells cultured under hypoxic conditions. Severe hypoxia/anoxia downregulated HNF-4 DNA-binding activity while DNA-binding activity of HNF-1 and HNF-3 remained unaffected. These hypoxic conditions also strongly and specifically decreased cell contents of HNF-4 protein, indicating that the decrease in HNF-4 DNA-binding activity was due to the lower amount of protein and not to decreased DNA-binding affinity. Northern analysis indicated that the expression of the hnf-4 gene was also downregulated in HepG2 cells cultured under hypoxic conditions. These results provide evidence that hypoxic stress triggers a cascade of events that inhibits the transactivation potential of HNF-4 in HepG2 cells. This step may be crucial in modulating the expression of a subset of liver genes that are targets for this nuclear receptor. This relationship provides a new route for the investigation of the effects of hypoxia on the liver cell.

Tumor necrosis factor alpha levels in plasma and whole-blood culture in dengue-infected patients: relationship between virus detection and pre-existing specific antibodies.

The pathogenesis of dengue hemorrhagic fever (DHF) is not well known, but the role of host factors has been suggested. The level of immunoreactive circulating and cell-generated tumor necrosis factor alpha (TNF alpha) was studied in 35 patients with DHF; its relationship with virus isolation and/or genome detection by reverse transcription polymerase chain reaction (RT-PCR) and specific antibodies were detected by hemagglutination inhibition (HI). Large variation of TNF alpha plasma levels was obtained in dengue-infected patients at the same stage of the disease and at the same day after infection. Most of the patients (14 out of 17 patients) who displayed augmented spontaneous in vitro production of TNF alpha by heparinized whole-blood culture compared with controls also had elevated levels of TNF alpha in the plasma. The TNF alpha values in lipopolysaccharide and phytohemagglutinin heparinized whole-blood cultures were not higher in patients than in controls, but low TNF alpha levels were obtained in three out of 30 patients. An inverse correlation was observed between spontaneous in vitro TNF alpha production and viral replication, which raises the issue of the antiviral effect of TNF alpha in dengue infection. The results do not support the hypothesis of the role of antibody-dependent enhancement giving rise to increased viremic titers and production of TNF alpha in patients. The present study demonstrates the activation of the TNF alpha-producing cells in dengue-infected patients and suggests further investigation to define the mechanism and the role of TNF alpha in the pathogenesis of dengue virus infection.

[Congenital dilatation of the common bile duct in children. Study of a series of 52 cases]. / Dilatation congénitale de la voie biliaire principale chez l'enfant. Etude d'une série de 52 cas.

OBJECTIVE: The aim of this study was to evaluate results at long-term follow-up of patients suffering from congenital dilatation of the bile duct according to the type of operative procedure. METHOD: A retrospective study of 52 patients who were operated on during a 25-year period was carried out. Of 52 patients, 43 (83%) were female and 9 (17%) were male, with a ratio of 4.8/1. In six cases, the diagnosis was made antenatally by ultrasonography. Transhepatic cholangiography showed an extrahepatic dilatation in 25 cases (48%) and a combined extra and intrahepatic dilatation in 27 cases (52%). A common bilio-pancreatic channel was found in 25 patients. Mean age at the time of operation was 4.2 years. Operative procedures included: cyst excision and hepaticojejunostomy in 47 cases, cystojejunostomy or cystoduodenostomy in 4 cases and cystostomy in one case. There were two postoperative deaths. RESULTS: Long-term follow-up was established in 43 of 50 survivors (80%). One patient was reoperated because of portal hypertension. Cholangitis developed in 11 patients: 2/2 patients who had undergone in internal drainage and 9/41 patients who had undergone a cyst excision with hepaticojejunostomy. In patients with cyst excision, cholangitis developed twice as frequently in those with associated intrahepatic dilatation. Two of 11 children with recurrent cholangitis died following sepsis, and three others were reoperated because of intrahepatic bile duct stones, one of these 15 years later. CONCLUSION: A total excision of the extrahepatic biliary tract, followed by hepaticojejunostomy is considered as a treatment of choice. The site of the biliary anastomosis should be adapted to the type of dilatation of intrahepatic bile duct in the case of a combined extra and intrahepatic dilatation.

Synthesis and photodynamic activities of silicon 2,3-naphthalocyanine derivatives.

Bis(tert-butyldimethylsiloxy)- (7), bis(dimethylthexylsiloxy)- (8), bis(tri-n-hexylsiloxy)- (9), and bis(dimethyloctadecylsiloxy)silicon 2,3-naphthalocyanines (10) were prepared via substitution of the bis(hydroxy) precursor with the corresponding chlorosilane ligands and characterized by spectroscopic and combustion analyses. They show strong absorption around 780 nm where tissues exhibit optimal transparency. Compounds 7-10 are capable of producing singlet oxygen. They are relatively photostable although less stable than the analogous phthalocyanine, i.e., the bis-(dimethylthexylsiloxy)silicon phthalocyanine (12). They were evaluated as potential photosensitizers for the photodynamic therapy (PDT) of cancer in vitro against V-79 cells and in vivo against the EMT-6 tumor in Balb/c mice. In vitro all four dyes showed limited phototoxicity combined with substantial dark toxicity. Surprisingly, in vivo (i.v., 0.1 mumol/kg, 24 h prior to the photoirradiation of the tumor with 780-nm light, 190 mW/cm2, 400 J/cm2) all dyes induced tumor regression in at least 50% of mice whereas compound 8 gave a complete tumor response in 80% of mice without apparent systemic toxicity at doses as high as 10 mumol/kg. At 24 h postinjection, compound 8 showed a favorable tumor to muscle ratio of 7, assuring minimal damage to the healthy tissue surrounding the tumor during PDT. Our data confirm the potential of silicon naphthalocyanines as far-red-shifted photosensitizers for the PDT of cancer and indicate the importance of the selection of the two axial silicon ligands for optimal photodynamic efficacy.

Surgical treatment of congenital cystic dilation of the biliary tract.

Cystic dilation of the biliary tract in 38 Vietnamese children is reported. Most had symptoms and signs of cholangitis and biliary obstruction. The surgical management is discussed, and for choledochal cyst resection of the cyst with hepaticojejunostomy Roux-en-Y is recommended. Postoperative cholangitis occurred in 16% of the children. The overall mortality was 18% after a median follow-up time of 28 months. Cystic dilation of the biliary tract is suggested to be a congenital entity, resulting from two pathogenetic factors--an unexplained structural anomaly of the biliary duct wall and an abnormality of the choledochopancreatic junction. A new classification is proposed, based on previous reports and the present study: A1) choledochal cyst, A2) choledochal diverticulum, A3) choledochocele, B) biliary cyst of the main hepatic ducts, C) intrahepatic and extrahepatic cyst, and D) Caroli's disease (intrahepatic biliary cysts).

Determination of chlorpromazine and its major metabolites by gas chromatography/mass spectrometry: application to biological fluids.

A method for the quantitative determination of chlorpromazine and five of its major metabolites in a single sample of biological fluid in the ng/ml range has been developed utilizing gas chromatography/mass spectrometry with selected ion recording. The assay is highly specific and quantification is accomplished by an inverse stable isotope dilution technique, using deuterium-labeled variants of the compounds as internal standards. In this way the concentrations of chlorpromazine and five of its major metabolites (the sulfoxide, the N-oxide, the monodemethylated, the didemethylated, and the 7-hydroxylated compounds) can be determined in biological fluids. Levels in humans have been measured both in plasma and in red blood cells and are compared to those found in related in vitro studies.

Metabolic oxidation of nicotine to chemically reactive intermediates.

Studies on the metabolism of nicotine by rabbit liver microsomal fractions in the presence of 0.01 M sodium cyanide have led to the characterization of two isomeric cyanonicotine compounds. The locations of the cyano groups were established by GC--EIMS analyses of the deuterium-labeled products obtained from the specifically deuterium-labeled substrates (S)-nicotine-5',5'-d2, (R,S)-nicotine-2',5',5'-d3, and (R,S)-nicotine-N-methyl-d3. One cyano adduct was shown to be 5'-cyanonicotine, a product previously isolated from similar microsomal preparations. The second cyano adduct was shown to be N-cyanomethyl)nornicotine; this structure assignment was confirmed by synthesis. Formation of N-cyanomethyl)nornicotine appears to occur, at least in part, without prior nitrogen--carbon bond cleavage, implicating the in situ generation of the N-methyleniminium species during the course of metabolic oxidative N-demethylation of nicotine.