Screening of tuberculosis before biologics.

Using anti-TNF has significantly improved the management of chronic inflammatory rheumatism. However, there is clear evidence that this treatment increases the risk of reactivating tuberculosis. The intradermal tuberculin skin test (ITT) and interferon-γ-release assays (IGRAs) are currently used to detect latent tuberculosis infection. The results of ITT are difficult to analyze in patients vaccinated with Bacille Calmette-Guérin (BCG) and because of variation in test administration and reading. Numerous authors have compared the sensitivity and specificity of IGRA and ITT, including in two recent meta-analyses and one literature review. These authors, however, compared different populations with different ITT positive thresholds (5, 10, and 15mm). We performed a meta-analysis of studies in which the threshold was 15mm, the recommended level in France. The sensitivity of QuantiFERON, T-spot, and ITT was 79% (IC 76%-83%), 84% (IC 75%-95%), and 69% (IC 65%-73%), respectively. In France, it is recommended to detect latent tuberculosis infection on the basis of history taking, physical examination, 5-unit ITT, and lung X-ray. This screening leads to treating 20%-30% of patients, with considerable adverse-effects. Because of the sensitivity and specificity of IGRAs, it is no longer justified to systematically perform TST for detection of tuberculosis before initiating anti-TNF treatment.

Optimal design of a microcavity organic laser device under electrical pumping.

The quality factor of microcavity organic lasers, designed for operation under electric pumping, has been numerically investigated. The microcavity structure consists of an organic light emitting diode set in between multilayer dielectric mirrors centered for an emission at 620 nm. In order to optimize the quality factor, different parameters have been studied: the impact of high and low index materials used for the multilayer mirrors, the role of a spacer inserted in between the mirrors to obtain an extended cavity, and the effect of an absorbing electrode made of metallic or transparent conductive oxide layer. The results of our different optimizations have shown a quality factor (Q) as high as 15,000.

Biotic and abiotic factors affecting the flight activity of Fopius arisanus, an egg-pupal parasitoid of fruit fly pests.

Climatic conditions and the physiological state of a parasitoid may alter its host selection behavior and thus its efficiency as a biological control agent. We studied the influence of these parameters on the behavior of Fopius arisanus (Sonan), an egg-pupal parasitoid of many Tephritidae. In the first experiment, we assessed in field cage assays the influence of temperature, humidity, light intensity, barometric pressure, and wind speed. Both flight and parasitism were mainly affected by temperature and humidity. However, because these two factors were strongly correlated in our experiments, the direct influence of each one cannot be specified. Flight activity was affected by variations in barometric pressure. In a second set of experiments, we conducted release and recapture assays with dyed insects to determine the influence of sex, mating status, egg load, age, and starvation on attraction toward infested fruit. Males were not attracted, suggesting that fruit are not a mating site. The egg load seemed to be a major parameter of foraging motivation. Finally, we showed that flight activity strongly decreased after 48 h of starvation. We observed a possible switch to food in the foraging motivation of starved females, but this result was impaired by poor recoveries: <10% of released females were recaptured after 96 h of starvation. We finally discuss the importance of these observations on the efficiency of F. arisanus as a biological control agent in tropical humid areas.

[Potential nosocomial disseminated infection due to Nocardia asteroides after a prosthesis insertion in an immunocompetent patient]. / Nocardiose disséminée nosocomiale probable après chirurgie prothétique ostéoarticulaire chez un patient immunocompétent.

Nocardia infections are rare and usually occurred in immunocompromised patients with systemic dissemination from a lung infection. We report a case of an immunocompetent patient in whom Nocardia asteroides had cause psoas and cerebral abcess without pulmonary infection, a short period after a hip prosthesis insertion. The clinical history is highly suggestive of a hospital-acquired infection.

[Kawasaki disease is also a disease of adults: report of six cases]. / La maladie de Kawasaki est aussi une maladie de l'adulte: a propos de six observations.

Kawasaki disease is an inflammatory arterial disease of unknown cause usually affecting young children, the principal complication of which is coronary artery aneurysm. Early treatment with immunoglobulins and aspirin prevents this complication. The diagnosis requires expert clinical criteria and, in atypical forms, a more recent decisional diagnostic tree has to be used. The authors report 6 cases of adult Kawasaki disease. As in the other sixty or so cases in the literature, hepatic forms were the commonest (5/6). Only three of the six cases met the classical clinical criteria and the diagnosis was made by the decisional tree or after coronary complications in the oldest subject. The five treated patients progressed favourably after a course of immunoglobulins. Echocardiography detected 100% of children with coronary disease but it was more difficult in adults in whom new non-invasive methods of coronary imaging (fast CT and MRI) and stress testing should complete the investigations. The association of prolonged pyrexia, clinical criteria and a biological inflammatory syndrome should, after exclusion of the differential diagnoses, suggest a diagnosis of Kawasaki disease in the adult as in the child. The possibility of coronary disease, even though extremely rare, should be recognised by the cardiologist and lead to diagnostic and therapeutic managements as aggressive as in children.

Safety and immunogenicity of subcutaneous or intramuscular administration of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae in healthy volunteers.

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.

[Non Hodgkin's and Hodgkin's lymphomas and HIV: frequency, outcome and immune response under HAART; Clermont-Ferrand University Hospital, 1991-2003]. / Lymphomes non hodgkiniens et hodgkiniens et infection VIH: fréquence, pronostic et reconstitution immune sous trithérapie antirétrovirale; CHU de Clermont-Ferrand, 1991-2003.

OBJECTIVES: The authors had for aim to identify cases of non Hodgkin's (NHL) and Hodgkin's (HL) lymphomas in HIV1-infected patients to assess 1) their incidence, before and after 1996, 2) the clinical features and outcome under treatment together with the survival rate of the patients, 3) the immune reconstitution of lymphoma-free patients under HAART. PATIENTS AND METHODS: A retrospective study was made of HIV1-infected patients managed at the Clermont-Ferrand University Hospital from 1991 to 2003 for the diagnosis and treatment of HIV1-related lymphomas. RESULTS: Forty-one patients were included: 35 NHL and 6 HL giving a cumulative incidence rate estimate from 2.4% between 1991 and 1996 to 3.4% between 1997 and 2003 while other opportunistic diseases were decreasing. A high proportion of aggressive and disseminated disease was observed among NHL cases. Complete remission was achieved in 17 (49%) and 5 (83%) NHL and HL cases respectively. The mean survival was 109+/-54 months and was correlated with CD4 cell count at lymphoma diagnosis (univariate analysis). Among responding patients, 5 died: 3 from opportunistic infections, 1 commited suicide, and 1 from hepatic carcinoma. For responding patients, the mean increase of CD4 cell count under HAART was 58/mm3 over a 2 year-period and 192/mm3 over a 5 year-period of follow-up. CONCLUSIONS: The incidence of lymphomas in HIV-infected patients has not decreased since the introduction of HAART. The immune status assessed by CD4 cell count on diagnosis is correlated with survival. Immune restoration in lymphoma-free patients under HAART is poor.

[Cryptococcal meningitis disclosed by visual loss in HIV negative patient with ventriculo-atrial shunting]. / Cryptococcose neuroméningée révélée par une baisse de l'acuité visuelle chez un patient atteint de neurosarcoïdose et porteur d'une dérivation ventriculoatriale.

INTRODUCTION: HIV infection is the main cause of cryptococcal neuromeningitis but other diseases may be associated with this infection. CASE REPORT: We report a case of cryptococcal neuromeningitis in a patient with sarcoidosis and ventriculoatrial shunting. The patient was successfully treated by effective therapy without device withdrawal. CONCLUSION: The relationship between cryptococcosis and sarcoïdosis has been already described and may be not fortuitous. However it remains a very rare complication of sarcoidosis. Because of its potential severity (mortality rate of 40%), the diagnosis of cryptococcosis should be evoked as a differential diagnosis of neuro-sarcoidosis.

[Infections associated to severe thrombotic events and antiphospholipid antibodies]. / Infections associées à des évènements thrombotiques sévères avec présence d'anticorps antiphospholipides.

The authors present 2 cases of infections in which the presence of antiphospholipid antibodies (APL), anticardiolipin and anti-beta2-GP1, was associated to the occurrence of significant thrombotic events: 1) a 55-year-old male patient whose serology (indirect immunofluorescence) revealed Coxiella burnetii infection (phase 2 antigens) with IgG at 1,600 and IgM at 50 (significant titer: IgG>or=200 and IgM>or=50); 2) and a 20-year-old male patient with a CMV infection confirmed by serology (IgG: 44 U/ml, significant threshold 6, IgM: 2.1 U/ml, significant threshold 0.9).

Randomized salvage therapy with saquinavir-ritonavir versus saquinavir-nelfinavir for highly protease inhibitor-experienced HIV-infected patients.

PURPOSE: To compare saquinavir + ritonavir and saquinavir + nelfinavir with nucleoside recycling in patients with multiple failures of highly active antiretroviral therapy (HAART). METHOD: This was a prospective, multicenter, randomized open trial. Inclusion criteria were the following: consent, age > 18, previous protease inhibitor (PI) exposure > 6 months, unchanged HAART > 3 months, and viral load > 3 log. The treatments compared were ritonavir 200 mg bid + saquinavir 600 mg bid (Rito-Saq), and nelfinavir 1,000 mg bid + saquinavir 600 mg bid (Nelf-Saq). Nucleoside analogues were recycled, and nonnucleoside inhibitors were not permitted. Trough levels of the three drugs were measured by high-performance liquid chromatography at the month 3 visit. After the study had been completed, genotyping analysis was done on the first serum at entry. RESULTS: The study was interrupted due to the availability of new anti-HIV drugs. A random sample of 31 (16 Rito-Saq and 15 Nelf-Saq) patients was divided into two groups, which were comparable in terms of demographic data and previous history of HIV infection. Mean CD4 cell count and plasma viral load (pVL) were 316 +/- 169 and 3.89 +/- 0.87 for Rito-Saq and 448 +/- 238 and 3.85 +/- 0.32 for Nelf-Saq. Previous duration of PI exposure was 31 months for both groups. The mean number of protease gene mutations was 3.8 (range, 2-7) and 4.4 (range, 2-9), respectively. On intention-to-treat (ITT) analysis at month 6, pVL stabilization or decrease >/= 0.5 log was observed in 18 patients (58%): 10 for Rito-Saq and 8 for Nelf-Saq. In a multivariate logistic regression analysis, virological success at month 3 was inversely correlated to baseline viral load (R = 0.14; 95% CI 0.03-2.9; p =.01); and at month 6, virological success was inversely associated to the number of mutations in the protease gene (R = 2.2; 95% CI 0.73-6.53; p =.06). CONCLUSION: Nelf-Saq and Rito-Saq combinations can be proposed in case of multiple HAART failures. The fact that the virological response was inversely correlated to baseline viral load makes the case for an early switch after a HAART failure.

Hospitalization decision for ambulatory patients with community-acquired pneumonia: a prospective study with general practitioners in France.

BACKGROUND: We designed a prospective study in the Puy-de-Djme region of France to identify factors associated with a hospitalization decision by general practitioners (GPs) for patients with community-acquired pneumonia (CAP). PATIENTS AND METHODS: 95 voluntary GPs were recruited to report over the period (February 1993 to March 1994) patients diagnosed with CAP defined as acute onset of fever associated with focal pulmonary crackles and/or radiological changes consistent with a pulmonary infection in patients over 3 years of age, living in the community. RESULTS: 37 of the 175 CAP patients (21.4%) were hospitalized. Univariate analysis showed that the hospitalization decision was related to age > 65 years, retirement, history of cardiovascular disease, other extrapulmonary chronic disease, chest auscultation findings, tachypnea at rest and altered mental status. Multivariate analysis identified four variables associated with hospitalization: living alone at home (OR = 3.75), history of cardiovascular disease (OR = 2.54), other chronic medical conditions excluding pulmonary diseases (OR = 4.28) and tachypnea at rest (OR = 3.33). The hospitalization decision by GPs for patients with CAP takes into account social conditions, co-morbid conditions of the patients and the seventy of CAP.

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

Human and animal epidemic of Yersinia enterocolitica O:9, 1989-1997, Auvergne, France.

Yersinia enterocolitica O:9 infections were reported in Auvergne in 1988 to 1989, while brucellosis due to Brucella abortus was almost eliminated. The serologic cross-reactions between the two bacteria complicated the diagnosis of brucellosis cases. In 1996, human cases of Yersinia enterocolitica O:9 infection were detected, with a peak incidence of 12 cases. Veterinary surveillance could have predicted the emergence of this disease in humans.

Threonine and methionine are limiting amino acids for protein synthesis in patients with AIDS.

This study was conducted to identify the most rate-limiting amino acids for whole-body protein synthesis in acquired immunodeficiency syndrome (AIDS) patients. We postulated that an essential amino acid that would be rate limiting in AIDS should have a low basal plasma concentration and should remain at a low level during amino acid infusion. Seven male AIDS patients (median age 37 y, CD4 cell count: 76 mm-3) without any clinically active opportunistic infection during the month before the experiment were infused intravenously with a complete amino acid-glucose mixture for 2.5 h. Eight healthy volunteers were used as controls. Before the infusion, the concentrations of most free essential amino acids (methionine, threonine, histidine, isoleucine, leucine and tryptophan) were significantly lower (P < 0.05) in AIDS patients than in controls. Most plasma free essential amino acids increased significantly during infusion. However, the absolute increase above basal levels for threonine, valine, lysine, (P < 0.05) and methionine (P < 0.073) was smaller in AIDS patients than in control subjects. Thus, threonine and possibly methionine may be rate limiting for whole-body protein synthesis in AIDS patients, suggesting that there are selective amino acid requirements in patients with AIDS.

Empirical therapy for nonhospitalized patients with community-acquired pneumonia. Study Group of General Practitioners.

A prospective survey involving a group of 95 general practitioners (GPs) in France was conducted to describe antibiotic therapy prescribed for out-patients with community-acquired pneumonia (CAP). A total of 173 cases of CAP, defined by the association of fever and pulmonary focal crackles and/or radiological changes consistent with a pulmonary infection, were reported between February 1993 and March 1994: 84 males and 89 females (mean age: 48 yrs) of whom 45% had no underlying disease. Nineteen (11%) were immediately hospitalized and the remaining 154 out-patients were treated without microbiological investigation. First-line antibiotic therapy was amoxicillin or amoxicillin-clavulanic acid combination (57%), a first or second generation cephalosporin (12%), ceftriaxone (8%), oral broad-spectrum cephalosporin (3%), a macrolide (16%), a tetracycline (1%) and a fluoroquinolone (2%). A total of 120 (78%) patients recovered with no change in treatment and 34 (22%) patients failed to improve: 18 were hospitalized and 16 had a second-line therapy, mainly a macrolide or a quinolone. Five patients died at hospital. The overall mortality was 3%, and 14% in hospitalized patients. Empirical therapy using a betalactam to target a presumed pneumococcal infection, in agreement with European guidelines, is appropriate for out-patients with mild lobar community-acquired pneumonia.

Responses of photosynthesis to irradiance and temperature in soybean, Glycine max (L.) Merr.

The response of photosynthesis to irradiance and temperature during growth was investigated in two soybean genotypes. Soybean is a species that can modify its structure and metabolism so as to adapt to differing light conditions; its responses to rapid changes in irradiance are characterized by their flexibility. However, the temperature during growth can change the response to irradiance: moreover, there may be a marked interaction with genotype.The response of photosynthesis to irradiance consists of changes in leaf thickness, which bring about variations in the mesophyll resistance to CO2 transfer. The increase in net photosynthesis per unit of leaf area is due to the increase in the amount of assimilating material beneath unit of area, as corroborated by the stability of the net photosynthesis per unit volume. Moreover, the response of photosynthesis to temperature is due to the mesophyll diffusion 'constant' which decreases with the growth temperature.