[The VR, the Russian version of the nerve agent VX]. / Le VR, version russe du neurotoxique organophosphoré VX.

A product of the arms race during the Cold War, the Russian VX, or VR, is an organophosphorus compound that is a structural isomer of the western VX compound (or A4), with which it shares a very high toxicity. It is much less studied and known than VX because the knowledge of its existence is relatively recent. A very low volatility and high resistance in the environment make it a persistent agent. Poisoning occurs mainly following penetration through skin and mucosa but vapour inhalation is a credible risk in some circumstances. The clinical presentation may be differed by several hours and despite the absence of signs and symptoms, the casualty should not be considered as contamination or intoxication-free. This agent has a long residence time in blood, a characteristics that clearly differentiates it from other compounds such as sarin. The protocols for antidote administration may thus have to be changed accordingly. The fact that VR poisoned individuals will less respond to the current oxime therapy used in France, the 2-PAM and that VR represents a higher threat than VX, being probably possessed by some proliferating states, justify the interest for this toxic product.

Hereditary neuropathy with liability to pressure palsies occurring during military training.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant peripheral neuropathy characterized by recurrent isolated nerve palsies, which are precipitated by trivial compression and trauma. Although HNPP has been well-described in literature, it often goes unrecognized. We report a case of HNPP occurring during military training to promote recognition and proper management of this entity.

[Arsine: an unknown industrial chemical toxic]. / L'arsine : un toxique chimique industriel peu connu.

Arsines family includes many compounds with various toxicities. Arsenic trihydride or arsine is the most toxic form of arsenic. Powerful haemolytic gas, it has never been used as a chemical weapon because its toxicity is not immediate and it is non persistent. However, cases of industrial poisoning with arsine are still identified in spite of a strict regulation at work. It is also identified as a potential toxic of chemical terrorism. This agent, of which the mechanism of action is still not well defined, is badly recognized because of intoxications rarity. However, fast detection means are available. Health professionals and especially those who are involved in piratox plan need to learn to recognize arsine intoxication (hematuria, oliguria, haemolytic anemia) in order to provide early, specific treatment and avoid damages.

[Value of assaying adenosine deaminase level in patients with neuromeningeal tuberculosis]. / Intérêt du dosage de l'adénosine désaminase dans les infections tuberculeuses neuro-méningées.

Neuromeningeal tuberculosis is a rare extrapulmonary location in France. Delayed diagnosis can lead to therapeutic failure and severe sequels. However early diagnosis is a major challenge that requires the proper epidemiological, clinical, radiological and biological resources. Problems related to diagnosis of mycobacteria infection and to shortcomings in certain healthcare systems can hinder early diagnosis. The purpose of this review was to describe the diagnostic value of assaying adenosine deaminase activity in cerebrospinal fluid from patients with neuromeningeal tuberculosis. Evidence from studies published over the last 25 years indicate that the sensitivity and specificity of measuring adenosine deaminase activity range from 36 to 92% and 71 to 100% respectively depending of cutoff values used. Before performing this assay, it is necessary to rule out obvious or frequent etiologies such as purulent bacterial meningitis or cryptococcosis in HIV patients. Taken together these studies show that this simple, inexpensive technique is a valuable tool for early diagnosis and management of tuberculosis patients and that it can be easily implemented in hospital labs regardless of technical or financial resources.

Influence of protein- versus carbohydrate-enriched feedings on physiological responses during an ultraendurance climbing race.

This study investigated effects of a high protein (PROT) versus a high carbohydrate (CHO) diet on performance and physiological responses during an ultraendurance climbing race at moderate altitude. On two different periods, in a randomised crossover design, ten climbers (30.0+/-0.9 years) participated in the race (duration 29 h approximately, energy expenditure 43.6+/-1.2 MJ.day (-1)) and were fed either with the PROT (30% protein content) or the CHO diet (68% carbohydrate) each providing 16.74 MJ. Mental performance was assessed by the Stroop test and we estimated maximal voluntary strength of quadriceps muscle. We quantified metabolic and hormonal circulating concentrations. Mental performance was unaffected after the two races, while muscular performance and body weight were decreased (both p<0.01) with no diet effects. Decreases were measured for IGF-I concentration and its binding protein IGFBP-3 (p<0.001), and increases for cortisol and norepinephrine (p<0.01) with no diet effects. Glucose concentration decreased (p<0.05) without diet effects, while amino acids (leucine, isoleucine, valine, and tyrosine) decreased in CHO group (p<0.001). Leptin concentration decreased (p<0.001) without diet effects, whereas total ghrelin increased in CHO group (p<0.01). Our results showed that a high PROT or high CHO intake during physical exertion at moderate altitude maintained mental performance, but did not limit muscle force reduction and body weight loss. There was decreased glucose availability, and hormonal responses indicated both catabolism and extreme energy deficiency induced by exercise with opposite responses of ghrelin and leptin. The ghrelin response was additionally indicative of macronutrient intake during the race.

[Pharmacological and pharmacogenetic study of two immunomodulators: azathioprine and 6-mercaptopurine. Strategies for preventing complications]. / Etude pharmacologique et pharmacogénétique de deux immunomodulateurs: l'azathioprine et la 6-mercaptopurine. Stratégies de prévention des complications.

Thiopurines are frequently used in gastroenterology for Crohn's disease or hemorrhagic rectocolitis. Their metabolism is regulated by a particular enzyme, thiopurine S-methyltransferase or TPMT. There are three ways to evaluate the effectiveness and the risk of side effects associated with this treatment. TPMT activity measurement or genotyping are recommended to decide for treatment, while metabolites determination is a used as marker of monitoring. Phenotypic approach (TPMT activity measurement or metabolites determination) requires delicate techniques and interindividual variations make the interpretation difficult. Genotyping is easier to interpret but cannot exclude some risk of side effects.

Sweet little Gabonese palm wine: a neglected alcohol.

BACKGROUND: During the last ten years, consumption of palm wine, a popular traditional alcoholic beverage, seriously increases in Gabon. This sweet beverage seems to be the main alcohol and the most drunken in low socioeconomic population. OBJECTIVE: To have an idea of its composition and toxicity, 21 samples of palm wine were collected in the country and analysed. METHODS: Twenty-one palm wine samples were randomly selected from all over Gabon. Methanol and ethanol concentrations in the samples were measured by gas chromatography. Aromatic hydrocarbons were measured by selected ion monitoring mode in mass spectrometry. Delection of heavy metals was by standard techniques. RESULTS: Gabonese palm wine contained ethanol at a mean concentration of about 60 g*L-1, i.e. 7.5 degrees (volume %), volatile components such as alcohols, aldehydes, carboxylic acids and esters and trace metals. Trace metals were present at low concentrations below internationally recognized maximal limits for alcoholic beverages with less than 2 microg*L-1 for cadmium, less than 10 microg*L-1 for arsenic and for lead 15 samples with concentrations under 10 microg*L-1 and the last six samples with concentrations between 11 and 61 microg*L-1. None of the searched aromatic or chlorinated solvents, indicative of refined fuel or industrial contamination, was detected. CONCLUSION: For the parameters analyzed here, there seems to be no significant difference in constitution between Gabonese wine palm and others kind of palm wine produced in West Africa. This alcohol needs to be more considered by public health authorities and medical teams because of its health and economic consequences.

[Automation and consolidation of clinical biology: the HIA Begin experiment]. / Automatisation et consolidation en biologie clinique: l'expérience de l'hôpital d'instruction des armées Bégin.

Reorganization of hospital or private sector labs is a strong trend. Such process implies consolidation of tests on a minimum of analyzers, harmonization of equipment (limitation of number of suppliers), posts number reduction, and development of powerful software. Increase of productivity needs set up of automation systems, specially at the level of pre-analytical phase, in a way to limit manual steps. At the same moment, quality improvement generates a decreasing TAT (Turn-Around-Time), a strong reduction of errors, a better protection against biological hazards, and standardization of sample management and validation process. After giving some notions about consolidation and integration, our choices for a brand new and innovative solution are explained.

[Obligate running and anorexia]. / Addiction au sport et anorexie.

The relationship between athletic participation and eating disorders is complex. We describe the case of a sportive man and examine the overall relationship between athletic participation and eating problems.

[Role of pharmacogenetics in chemotherapy of colorectal cancers]. / Implication de la pharmacogénétique dans les traitements des cancers colorectaux.

SCOPE: Clinical implications associated with polymorphisms in drug-metabolizing genes involved in the chemotherapy of colorectal cancers (5-flurorouracil, oxaliplatin and irinotecan) are reviewed. CURRENT SITUATION AND SALIENT POINTS: Treatments of colorectal cancers have been greatly improved last years but patients respond differently to identical medication. Genetic polymorphisms are one of the major causes of these individual responses to drugs associated with sometimes severe adverse effects. Pharmacogenetics is based on all polymorphisms that determine genetic human diversity associated with variable response to anticancer drugs. PERSPECTIVES: Morbidity and mortality related to toxicity or inefficacy of these drugs could be reduced by analyzing the pharmacogenetic profile of patients before treatment. Results should be integrated in protocols for monitoring and assessment the dosage of drugs.

Should we have more definitions of metabolic syndrome or simply take waist measurement?

The disorder now known as metabolic syndrome has been recognized for 50 years, but its multiple definitions have led to some confusion and even doubt about its very nature. Metabolic syndrome is directly linked to the presence of android obesity, which indicates insulin resistance and lies at the root of all risk factors and early indications of type 2 diabetes. It is diagnosed by systematic measurements of waist size and its direct interpretation taking ethnic origin into account. This pragmatic approach avoids the uncertainties generated by differing definitions and is subtler than the presence or absence of metabolic syndrome in a given patient. Drug-free treatment of an android obese patient is inexpensive and effective, but this apparently simple approach masks difficulties of application. However, these are sociological problems.

[Inappropriate ADH secretion-induced hyponatremia and associated with paroxetine use]. / Hyponatrémie par sécrétion inappropriée d'ADH associée à la prise de paroxétine.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressants prescribed for elderly people. Although they are generally better tolerated than other antidepressant treatment classes, they can be responsible for potentially life-threatening hyponatremia, related to syndrome of inappropriate antidiuretic hormone secretion (SIADH). OBSERVATION: A 64 years-old woman was hospitalized for cognitive function alteration and vomiting after introduction of paroxetine for depressive symptoms. Serum investigations revealed hyponatremia (121 mmol/l) with low plasma osmolarity and normal natriuria consistent with diagnosis of SIADH. Hyponatremia was reversible after paroxetine withdrawal. DISCUSSION: Hyponatremia induced by SIADH is a serious but underestimated complication of SSRI treatment. This complication occurs in the elderly people within the first month of treatment. Monitoring of the serum sodium concentration during the first month of treatment is recommended for older patients.

[Adenosine deaminase is useful for the diagnosis of peritoneal tuberculosis in patients with end-stage renal failure]. / Le dosage d'adénosine déaminase est utile pour le diagnostic de tuberculose péritonéale chez le patient dialysé

INTRODUCTION: End-stage renal failure patients are particularly at risk for tuberculosis, especially for peritoneal tuberculosis. Microbiological diagnosis remains hazardous in many cases. CASE REPORT: We report on a case of peritoneal tuberculosis in an end-stage renal failure patient. The diagnosis was suspected on the basis of adenosine deaminase dosage in peritoneal fluid, allowing an early presumptive treatment and a favourable outcome with a 3 years follow-up. DISCUSSION: The measurement of adenosine deaminase activity in ascites represents a diagnostic advance in tuberculous peritonitis among end-stage renal failure patients.

[The usefulness of adenosine deaminase determination in biological fluids for tuberculosis diagnosis]. / L'intérêt du dosage de l'adénosine désaminase dans les liquides biologiques au cours d'une tuberculose.

Tuberculosis may affect several organs and its prevalence is continuously increasing. Laboratory diagnosis still remains difficult. Adenosine deaminase (Ada) is an enzyme which contributes to purine metabolism and its presence in lymphocyte, monocyte and macrophage cells is associated with T cells mediated immunity. Many studies have shown the usefulness of Ada determination in various biological fluids for the diagnosis of tuberculosis. In pleural fluid, cutoff vary from 33 to 48 U/L, with sensitivity higher than 80% and specificity near 100%. In peritoneal fluid the cutoff value is 30 U/L. In cerebrospinal fluid, the value of 7 U/L can make discriminate negative and positive cases with a good sensitivity and specificity. The data from the literature show that 50 U/L in pericardic fluid is a reliable threshold for tuberculosis diagnosis. Ada determination in serum is not as relevant as in others fluids because of its low specificity. Ada measurement in biological fluids, easy and not expensive, may be add to other biological tests for tuberculosis diagnosis.

Epidemiology of the metabolic syndrome in 2045 French military personnel (EPIMIL study).

CONTEXT: The Metabolic syndrome is considered to be an important public health problem, but few epidemiological studies have defined the present situation in France. EPIMIL is a prospective epidemiological study that began on February 1, 2003. SUBJECTS AND METHODS: This study was designed to identify the clinical and laboratory parameters of metabolic syndrome and cardiovascular risk factors in a population of 2045 male military personnel based in the Paris region. The initial 1-year cross-sectional study will be followed by a 10-year follow-up and patient care. RESULTS: The 2045 subjects included 185 (9%) presented at least 3 of the 5 NCEP ATP III criteria defining metabolic syndrome. They were significantly older (42.2 +/- 8.5 yrs) than the other subjects (37.3 +/- 8.7 yrs, P<0.001), had a higher BMI (29.5 +/- 3.4 vs 24.8 +/- 2.9 kg/m2, P<0.001) and a greater body weight at age 20 (75.4 +/- 11 vs 70.4 +/- 8.5 kg, P<0.01). Smoking, little physical activity and family histories of diabetes and arterial hypertension were more frequent in these men. While levels of the cholesterol and CRP us were higher, Lp(a) and homocysteine concentrations were normal. Plasma insulin and BMI (r = 0.456 P<0.0001) and plasma insulin and waist circumference (r = 0.446 P<0.0001) were well correlated. Lastly, plasma insulin, free fatty acids and cardiovascular risk increased steadily with the increase in the number of metabolic syndrome criteria. CONCLUSIONS: These results in a large and particularly uniform population of men show the prevalence of metabolic syndrome in adult men, and demonstrate its link with insulin resistance. Men with several risk factors require specific care, particularly for hypertension and dyslipidemia; the effectiveness of this care will be evaluated during the follow-up period.

[Is mild hyperhomocysteinemia an additional risk factor of the metabolic syndrome?]. / L'hyperhomocystéinémie est-elle un facteur de risque supplémentaire du syndrome métabolique?

INTRODUCTION: Metabolic syndrome is a cardiovascular risk factors cluster and hyperhomocysteinemia an obvious independant risk factor. OBJECTIVE: To ascertain if hyperhomocysteinemia is associated with the metabolic syndrome. METHODS: "Epimil" is a prospective epidemiologic survey, which began by a cross-sectionnal study of cardiovascular risk factors in a French population, which then will be followed for ten years for supervision and intervention. Initial data collection, blood pressure measurement, ECG and blood samples (biology and DNA) have been performed. For the metabolic syndrome, we used the criterias of the third report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (NCEP ATP III). RESULTS: Out of 2045 men aged from 20 to 58 years (37.7+/-8.7 years), 185 (9%) have metabolic syndrome (at least three criterias), 587 (29%) a blood homocysteine>or=12 micromol/L and 202 (10%)>or=15 micromol/L. Homocysteinemia is 10.97+/-5.01 micromol/L for the whole population and doesn't differ with (11.4+/-6 micromol/L) or without (10.9+/-5 micromol/L) the metabolic syndrome, as does its values distribution. It's not correlate with the body mass index, waist and hip measurements, nor with glycemia, HbA1c, insulin resistance and cardiovascular risk markers (CRPus, microalbuminuria). It weakly correlates with systolic and diastolic blood pressure, creatinine clearance, tobacco use, cholesterolemia, triglycerides and free fatty acids but not with HDL and LDL fractions, nor lipoprotein (a). Among this population, it slightly contributes to the ten years vascular risk evaluated according to Framingham equations or Score system. CONCLUSIONS: Homocysteinemia and the prevalence of hyperhomocysteinemia don't differ with or without the metabolic syndrome and doesn't correlate its main criterias.

[Prolonged succinylcholine-induced apnoea associated with cholinesterase silent plasma variant]. / Curarisation prolongée à la succinylcholine liée à un variant silencieux de la cholinestérase plasmatique.

Mivacurium and succinylcholine are short-acting neuromuscular blocking drugs. The duration of their action depends on their rapid hydrolysis by plasma cholinesterase or butyrylcholinesterase. More than thirty genetic variants of this enzyme have been described but the atypical variant is the most frequently involved in prolonged apnoea following the administration of these two myorelaxants. We present one case of patient who presented a five hours long apnoea associated with null cholinesterase activity and detection of a butyrylcholinesterase silent variant (Sil-1, 1 for 100,000 persons in population) after sequencing.

Living high-training low altitude training: effects on mucosal immunity.

Secretory immunoglobulin A (sIgA) is the major immunoglobulin of the mucosal immune system. Whereas the suppressive effect of heavy training on mucosal immunity is well documented, little is known regarding the influence of hypoxia exposure on sIgA during altitude training. This investigation examined the impact of an 18-day Living high-training low (LHTL) training camp on sIgA levels in 11 (six females and five males) elite cross-country skiers. Subjects from the control group (n=5) trained and lived at 1,200 m of altitude, whereas, subjects from the LHTL group (n=6) trained at 1,200 m, but lived at a simulated altitude of 2,500, 3,000 and 3,500 m (3x6-day, 11 h day(-1)) in hypoxic rooms. Saliva samples were collected before, after each 6-day phases and 2 weeks thereafter (POST). Salivary sIgA, protein and cortisol were measured. There was a downward trend in sIgA concentrations over the study, which reached significance in LHTL (P<0.01), but not in control (P=0.08). Salivary IgA concentrations were still lower baseline at POST (P<0.05). Protein concentration increased in LHTL (P<0.05) and was negatively correlated with sIgA concentration after the 3,000 and 3,500 m-phase and at POST (P<0.05 all). Cortisol concentrations were unchanged over the study and no relationship was found between cortisol and sIgA. In summary, data were strongly suggestive of a cumulative negative effect of physical exercise and hypoxia on sIgA levels during LHTL training. Two weeks of active recovery did not allow for proper sIgA recovery. The mechanism underlying this depression of sIgA could be mediated by neural factors.

Intense training: mucosal immunity and incidence of respiratory infections.

This investigation examined the impact of a multistressor situation on salivary immunoglobulin A (sIgA) levels, and incidence of upper respiratory tract infection (URTI) during the French commando training (3 weeks of training followed by a 5-day combat course). For the URTI, the types of symptoms were classified according to the anatomical location of the infection. Saliva samples were collected (8 a.m.) from 21 males [21 (2) years] before entry into the commando training, the morning following the 3 weeks of training, after the 5-day combat course, and after 1 week of recovery. sIgA, protein and cortisol concentrations were measured. Symptoms of URTI were recorded during the study from health logs and medical examinations. After the 3 weeks of training, the sIgA concentration was not changed, although it was reduced after the 5-day course [from 120 (14) mg l(-1) to 71 (9) mg l(-1), P<0.01]. It returned to pre-training levels within a week of recovery. The incidence of URTI increased during the trial (chi(2)=53.48; P<0.01), but was not related to sIgA. Among the 30 episodes of URTI reported, there were 12 rhino-pharyngitis, 6 bronchitis, 5 tonsillitis, 4 sinusitis and 3 otitis. Cortisol levels were raised after the 3-week training (P<0.01), dropping below baseline after the combat course (P<0.01). Stressful situations have an adverse effect on mucosal immunity and incidence of URTI. However, the relationship between sIgA and illness remained unclear. The large proportion of rhino-pharyngitis indicated that the nasopharyngeal cavity is at a higher risk of infection.