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BACKGROUND: Systemic antibiotics are routinely prescribed for severe acute malnutrition (SAM). However, there is no consensus regarding the most suitable regimen. In a therapeutic feeding centre in Khartoum, Sudan, a randomised, unblinded, superiority-controlled trial was conducted, comparing once daily intramuscular injection with ceftriaxone for 2 days with oral amoxicillin twice daily for 5 days in children aged 6-59 months with SAM. METHODS: Commencing with the first measured weight gain (WG) following admission, the risk difference and 95% confidence interval (95% CI) for children with a WG > or = 10 g/kg/day were calculated over a 14-day period. The recovery rate and case fatality ratio (CFR) between the two groups were also calculated. RESULTS: In an intention-to-treat analysis of 458 children, 53.5% (123/230) in the amoxicillin group and 55.7% (127/228, difference 2.2%, 95% CI -6.9-11.3) in the ceftriaxone group had a WG > or = 10 g/kg/day during a 14-day period. Recovery rate was 70% (161/230) in the amoxicillin group and 74.6% (170/228) in the ceftriaxone group (p=0.27). CFR was 3.9% (9/230) and 3.1% (7/228), respectively (p=0.67). Most deaths occurred within the 1st 2 weeks of admission. CONCLUSION: In the absence of severe complications, either ceftriaxone or amoxicillin is appropriate for malnourished children. However, in ambulatory programmes, especially where there are large numbers of admissions, ceftriaxone should facilitate the work of medical personnel., Epicentre

Background: This randomized, double blind trial determined the short and long-term clinical and hemodynamic vasodilator effects induced by percutaneous applications of natural CO2 gas in patients with moderate Fontaine stage II. Patients and methods: 62 patients with intermittent claudication (100-500 meters) were randomized to 18 consecutive days of CO2 treatment or placebo (air). The gas fluids were applied at a constant temperature of 30°C on pre-humidified skin. The effects of the treatment were evaluated by total distance walked (primary criterion) and hemodynamic and microcirculatory findings. Patients also answered a quality of life questionnaire. Results: The Strandness test showed a significant increase in total distance walked (+ 131 meters, 66%; p = 0.001) and pain-free distance (+ 81 meters, 73%; p = 0.02) after 18 days of CO2 treatment. The improvement was maintained 3 and 12 months later. The systolic pressure index (ABI) increased by 37% (p = 0.001) 1 minute after treadmill walking and ABI recovery time decreased significantly by 38% (p = 0.002). Microcirculatory findings showed an increase in systolic pressure of the great toe (13%; p

Les cliniciens rencontrent de nombreuses difficultes pour mettre en evidence et quantifier l’effet analgesique des nouvelles molecules. Une des principales explications a ces echecs est le decalage entre le developpement de molecules agissant sur des cibles pharmacologiques tres specifiques et l’heterogeneite des mecanismes physiopathologiques impliques dans la douleur. Les methodes visant a attenuer les facteurs de variabilite dans les reponses aux traitements peuvent ameliorer la puissance des essais cliniques. Une autre piste consiste a selectionner les patients sur des criteres qui ont une reelle pertinence pharmacologique. Cette approche peut avoir des retombees positives dans l’individualisation des traitements.

The safety and immunogenicity of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae was evaluated in 84 volunteers according to the route of administration, i.e., subcutaneous (SC) or intramuscular (IM), in a double-blind randomised trial. The volunteers were randomised into four groups: SC vaccine; IM vaccine; SC placebo; and IM placebo. Primary vaccination comprised two injections on day 0 and day 14, with a booster after 6 months. A second booster was given 30 months after primary vaccination. Local reactions within 1 h of injections were rare, with no difference between vaccine groups. Local reactions within 3 h were more frequent after the second, third and fourth SC injections than after IM injections. Systemic reactions never occurred within 1 h of vaccination and were rare within 3 days; the rates were comparable for the different vaccine groups. Evolution of the antibody responses, as assessed by microscopic agglutination tests and specific IgG and IgM ELISAs, were similar for both injection routes. IgG seroconversion rates after the first booster were 97% (95% CI 80–100%) for the SC vaccine group, and 96% (95% CI 80–100%) for the IM vaccine group, and both reached 100% for IgG after the second booster. The safety and immunogenicity of the anti-leptospiral vaccine were both good. Monitoring of antibody levels established that a booster dose triggered a strong antibody response in fully vaccinated subjects at 30 months after primary vaccination.

The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day(-1)).A three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24-h period.In all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, Cmax was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for Cmax and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 micro g ml(-1) (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 microg ml(-1) (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10-14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 micro g ml(-1). Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets.These data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects.

Jusqu’a une date recente, aucun antalgique de palier II ne pouvait etre prescrit en France chez l’enfant de moins de 15 ans, si l’on voulait respecter les conditions d’Autorisation de Mise sur le Marche. Pour certains de ces antalgiques tels que le dextropropoxyphene ou le tramadol, on dispose aujourd’hui de trop peu de recul clinique et d’un manque d’etudes realisees chez l’enfant avec une methodologie rigoureuse, pour en recommander l’usage pediatrique. Ce n’est pas le cas de la codeine, qui est assez largement prescrite en pediatrie dans de nombreux pays, notamment les pays anglo-saxons, a des posologies de 0,5 a 1 mg/kg toutes les 4 a 6 heures, si necessaire et ceci a partir de l’âge de 30 mois. Actuellement les medecins attendent avec impatience la mise a disposition de formes galeniques de codeine adaptees a un usage pediatrique. La nalbuphine, qui peut etre prescrite a partir de l’âge de 18 mois, occupe une place particuliere, dans la mesure ou elle est utilisable par voie parenterale, en principe reservee a un usage hospitalier.

Chronic postsurgical pain (CPSP) is a common clinical situation which is still poorly assessed and often treated too late. An understanding of the neuropathic or inflammatory nature of CPSP will lead to an appropriate therapeutic approach. In everyday practice and in the majority of treatment studies, pain assessment is based on validated scales or questionnaires and simple clinical examination tools. Sophisticated investigations (electrophysiology, psychophysical techniques, or functional cerebral imaging) are reserved for pathophysiological studies or for clinical trials seeking to understand the mechanism of action of analgesic drugs. Postsurgical neuropathic pain (PSNP), due to its frequency, its relative homogeneity and its rather stereotyped time of onset, offers an excellent model for clinical research into neuropathic pain, which has been little used until now.

Plasma norepinephrine (NE) concentration increases with altitude exposure while maximal heart rate (HR) and chronotropic response to isoproterenol (IP) are blunted. Downregulation of cardiac beta-adrenergic receptors (beta-AR) has been evoked to explain this phenomenon. Chronotropic response was studied at extreme altitude in 10 subjects (4 women, 6 men; aged 35 +/- 6 yr). Observations were made in normoxia (N) and after 1 (H1) and 3 (H3) wk at 6,542 m. Acclimatization was accomplished by gradual climbing from 4,000 to 6,542 m over 10 days. Plasma NE was obtained at rest and during submaximal exercise. Successive doses of IP (0.02, 0.04, and 0.06 microgram/kg-1.min-1) were infused for 5 min each. Density and affinity of lymphocyte beta 2-AR were also measured. Increase in HR for maximal dose of IP decreased from 57 +/- 12 to 34 +/- 7 and 37 +/- 10 min-1 in H1 and H3, respectively (P < 0.001 for both). IP dose for which HR rises by 25 min-1 (I25) increased from 27 +/- 5 in N to 42 +/- 10 and 43 +/- 17 ng.kg-1.min-1 in H1 and H3, respectively (P < 0.001 for both). Arterial O2 saturation at rest was 98 +/- 2% in N, 72 +/- 6% in H1 (P < 0.001), and 79 +/- 5% in H3 (P < 0.001). The chronotropic response was neither restored nor further attenuated after 3 wk at 6,542 m. Plasma NE levels at rest and during exercise were higher at 6,542 m than values obtained in previous studies at 4,350 and 4,800 m.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality-reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). Methods and Findings: We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. Conclusions: Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality-reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy. © 2007 Grais et al.

Low measles vaccination coverage (VC) leads to recurrent epidemics in many African countries. We describe VC before and after late reinforcement of vaccination activities during a measles epidemic in Niamey, Niger (2003-2004) assessed by Lot Quality Assurance Sampling (LQAS). Neighborhoods of Niamey were grouped into 46 lots based on geographic proximity and population homogeneity. Before reinforcement activities, 96% of lots had a VC below 70%. After reinforcement, this proportion fell to 78%. During the intervention 50% of children who had no previous record of measles vaccination received their first dose (vaccination card or parental recall). Our results highlight the benefits and limitations of vaccine reinforcement activities performed late in the epidemic.

The relationships between inflammation and pain were known for a long time, even by antique civilizations. However most of the fundamental knowledge about biological mechanisms explaining some of the links between inflammation and nociception processes have been discovered over the last three decades. Peripheral infection or injury can induce an inflammation and related pain but also some nerves, especially C fibers which are mainly involved in nociception transmission, can generate a so called “neurogenic inflammation”. New findings rise some questions about the role of magnesium (Mg) in these two phenomena.

Extension to the unanesthetized dog with chronic A-V block of the method of determination of the atrial effective refractory period described in vitro by Dawes provides a useful model for the study in atria of potential antiarrhythmic agents. This model, which comes fairly close to physiological conditions, is capable of furnishing reproducible results which correlate well with those obtained by other techniques, as shown by a study of quinidine chosen as reference. It also makes possible long-term studies of the effects of prolonged administration of antiarrhythmic agents on atrial effective refractory period, under conditions close to those of therapeutic practice, and so is likely to have predictive value.

The renin-aldosterone system may be depressed in subjects exercising at high altitude, thereby preventing excessive angiotensin I (ANG I) and aldosterone levels, which could favor the onset of acute mountain sickness. The role of beta-adrenoceptors in hormonal responses to hypoxia was investigated in 12 subjects treated with a nonselective beta-blocker, pindolol. The subjects performed a standardized maximal bicycle ergometer exercise with (P) and without (C) acute pindolol treatment (15 mg/day) at sea level, as well as during a 5-day period at high altitude (4,350 m, barometric pressure 450 mmHg). During sea-level exercise, pindolol caused a reduction in plasma renin activity (PRA, 2.83 +/- 0.35 vs. 5.13 +/- 0.7 ng ANG I.ml-1.h-1, P less than 0.01), an increase in plasma alpha-atrial natriuretic factor (alpha-ANF) level (23.1 +/- 2.9 (P) vs. 10.4 +/- 1.5 (C) pmol/1, P less than 0.01), and no change in plasma aldosterone concentration [0.50 +/- 0.04 (P) vs. 0.53 +/- 0.03 (C) nmol/1]. Compared with sea-level values, PRA (3.45 +/- 0.7 ng ANG I.ml-1.h-1) and PA (0.39 +/- 0.03 nmol/1) were significantly lower (P less than 0.05) during exercise at high altitude. alpha-ANF was not affected by hypoxia. When beta-blockade was achieved at high altitude, exercise-induced elevation in PRA was completely abolished, but no additional decline in PA occurred. Plasma norepinephrine and epinephrine concentrations tended to be lower during maximal exercise at altitude; however, these differences were not statistically significant. Our results provide further evidence that hypoxia has a suppressive effect on the renin-aldosterone system. However, beta-adrenergic mechanisms do not appear to be responsible for inhibition of renin secretion at high altitude.

A three-year-old girl who had for two months suffered bruising after minimal injury was admitted because of diffuse ecchymoses and a large haematoma hindering elbow movement. These symptoms were attributable to the development of antifactor VIII inhibitor. No definite etiology was evident despite repeated immunological investigation. Although the inhibitor still persisted at high levels after two years, no further haemorrhage occurred, excepted haematomas three months after the onset of symptoms, in association with mumps.

Three brothers with isolated thyroid-stimulating hormone (TSH) deficiency were observed at ages 17, 15, and 10 years. They suffered from severely retarded growth, with a marked retardation in bone maturation. Their serum T4, T3, and TSH levels were low. Serum thyrotropin-releasing hormone (TRH) concentration was normal. No increases in TSH levels were elicited during the TRH test. The other pituitary hormones, adrenocorticotropic hormone, growth hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin hormone, responded normally to stimulation. Thyroxin treatment triggered a growth acceleration. Genetic investigation revealed several instances of small stature on the father's side.