Evaluation of a flexible bronchoscope prototype designed for bronchoscopy during mechanical ventilation: a proof-of-concept study.

Bronchoscopy during mechanical ventilation of patients' lungs significantly affects ventilation because of partial obstruction of the tracheal tube, and may thus be omitted in the most severely ill patients. It has not previously been possible to reduce the external diameter of the bronchoscope without reducing the diameter of the suction channel, thus reducing the suctioning capacity of the device. We believed that a better-designed bronchoscope could improve the safety of bronchoscopy in patients whose lungs were ventilated. We designed a flexible bronchoscope prototype with a drumstick-shaped head consisting of a long, thin proximal portion; a short and large distal portion for camera docking; and a large suction channel throughout the length of the device. The aims of our study were to test the impact of our prototype on mechanical ventilation when inserted into the tracheal tube, and to assess suctioning capacity. We first tested the efficiency of the suction channel, and demonstrated that the suction flow of the prototype was similar to that of conventional adult bronchoscopes. We next evaluated the consequences of bronchoscopy when using the prototype on minute ventilation and intrathoracic pressures during mechanical ventilation: firstly, in vitro using a breathing simulator; and secondly, in vivo using a porcine model of pulmonary ventilation. The insertion of adult bronchoscopes into the tracheal tube immediately impaired the protective ventilation strategy employed, whereas the prototype preserved it. For the first time, we have developed an innovative flexible bronchoscope designed for bronchoscopy during invasive mechanical ventilation, that both preserved the protective ventilation strategy, and enabled efficient suction flow.

Somatic tinnitus prevalence and treatment with tinnitus retraining therapy.

OBJECTIVES: Somatic tinnitus originates from increased activity of the dorsal cochlear nucleus, a cross-point between the somatic and auditory systems. Its activity can be modified by auditory stimulation or somatic system manipulation. Thus, sound enrichment and white noise stimulation might decrease tinnitus and associated somatic symptoms. The present uncontrolled study sought to determine somatic tinnitus prevalence among tinnitus sufferers, and to investigate whether sound therapy with counselling (tinnitus retraining therapy; TRT) may decrease tinnitus-associated somatic symptoms. METHODS: To determine somatic tinnitus prevalence, 70 patients following the TRT protocol completed the Jastreboff Structured Interview (JSI) with additional questions regarding the presence and type of somatic symptoms. Among 21 somatic tinnitus patients, we further investigated the effects of TRT on tinnitus-associated facial dysesthesia. Before and after three months of TRT, tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI), and facial dysesthesia was assessed with an extended JSI-based questionnaire. RESULTS: Among the evaluated tinnitus patients, 56% presented somatic tinnitus-including 51% with facial dysesthesia, 36% who could modulate tinnitus by head and neck movements, and 13% with both conditions. Self-evaluation indicated that TRT significantly improved tinnitus and facial dysesthesia in 76% of patients. Three months of TRT led to a 50% decrease in mean THI and JSI scores regarding facial dysesthesia. CONCLUSIONS: Somatic tinnitus is a frequent and underestimated condition. We suggest an extension of the JSI, including specific questions regarding somatic tinnitus. TRT significantly improved tinnitus and accompanying facial dysesthesia, and could be a useful somatic tinnitus treatment.

Fate of inhaled monoclonal antibodies after the deposition of aerosolized particles in the respiratory system.

Monoclonal antibodies (mAbs) are usually delivered systemically, but only a small proportion of the drug reaches the lung after intravenous injection. The inhalation route is an attractive alternative for the local delivery of mAbs to treat lung diseases, potentially improving tissue concentration and exposure to the drug while limiting passage into the bloodstream and adverse effects. Several studies have shown that the delivery of mAbs or mAb-derived biopharmaceuticals via the airways is feasible and efficient, but little is known about the fate of inhaled mAbs after the deposition of aerosolized particles in the respiratory system. We used cetuximab, an anti-EGFR antibody, as our study model and showed that, after its delivery via the airways, this mAb accumulated rapidly in normal and cancerous tissues in the lung, at concentrations twice those achieved after intravenous delivery, for early time points. The spatial distribution of cetuximab within the tumor was heterogeneous, as reported after i.v. injection. Pharmacokinetic (PK) analyses were carried out in both mice and macaques and showed aerosolized cetuximab bioavailability to be lower and elimination times shorter in macaques than in mice. Using transgenic mice, we showed that FcRn, a key receptor involved in mAb distribution and PK, was likely to make a greater contribution to cetuximab recycling than to the transcytosis of this mAb in the airways. Our results indicate that the inhalation route is potentially useful for the treatment of both acute and chronic lung diseases, to boost and ensure the sustained accumulation of mAbs within the lungs, while limiting their passage into the bloodstream.

[Epidemiology of the resistance of Mycobacterium tuberculosis to antituberculosis drugs at the main hospital in Dakar, Senegal. A 4-year retrospective study (2000-2003)]. / Épidémiologie de la résistance de Mycobacterium tuberculosis aux antituberculeux à l'hôpital principal de Dakar. Étude rétrospective sur quatre ans (2000-2003).

A retrospective study was carried out from January 2000 to December 2003 to assess the resistance of Mycobacterium tuberculosis to antituberculosis drugs and the impact of this on the treatment result. Two hundred and two patients' files were studied (average age: 36 years; sex-ratio: 1.7). Pulmonary localisation (85.7%) or extrapulmonary localisation (14.3%). HIV status is negative (71.3%), positive (10.8%) or unknown (17.9%). The overall recovery rate is 60.7% (61.4% in HIV-; 46.1% in HIV+), the rate of treatment failure is 2.7% (1.1% in HIV-; 15.4% in HIV+), the death rate due to tuberculosis is 6.3% (2.3% in HIV-; 23.1% in HIV+), and the rate of patients who disappeared from the system is 30.3% (35.2% in HIV-; 14.2% in HIV+). Hepatotoxicity that occurred during treatment is observed in 14.3% of cases (recovery: 56.2%; failure: 6.2%; lost from the system: 18.8%). Eighty-four percent of patients never received antituberculosis treatment (group A) versus 15.8% of patients who had already received one or more antituberculosis drugs (group B). The rates of resistance to isoniazid are 6.4% (A) and 12.5% (B), to rifampicin 1.7% (A) and 12.5% (B), to ethambutol 0.5% (A) and 0% (B), to streptomycin 24.1% (A) and 46.8% (B). The percentage of multiresistant strains is 1% in patients not treated previously and 11% in those who had already received antituberculosis treatment. When the patients are carriers of a strain that is responsive to the treatment administered, the recovery rate is 64.2% versus 46.7% in patients whose strain is resistant to at least one of the treatments administered.

[Assessment of the Patho-TB kit for diagnosis of tuberculosis]. / Evaluation du kit Patho-TB dans le cadre du diagnostic de la tuberculose.

Where tuberculosis is concerned, early diagnosis, especially for active pulmonary cases, allows to quickly start therapy. We evaluated the Patho-TB kit (Anda Biologicals, France) as an alternative for the fastidious search for acid-fast bacilli by the Ziehl-Neelsen method. Three hundred and ten samples from 189 patients were collected between July 2005 and March 2006, these were divide between 301 pulmonary and 9 extrapulmonary samples. The Patho-TB tests consists of a filtration step on a cassette followed by an immuno-chromatographic revelation. Samples were decontaminated by the Kubica method; after neutralization, an aliquot of the centrifuged pellet was saparated for evaluation of the Patho-TB test. The rest was used for direct microscopic examination and cultures on solid and liquid medium. Positive results with auramine were always confirmed by the ZN staining. Analysis of the results per sample gave the follows results: 91.1% sensitivity and 85.5% specificity compared to 91.8% and 100% respectively or microscopy. Sensitivity of the Patho-TB test rose to 93.7% when only the MTB complex was considered. Per patient, the Patho-TB was found to be 96.4% sensitive and 86% specific. By comparison the sensitivity of microscopy was 94.5% and its specificity 100%. Positive and negative values were respectively 90.6% and 94.4% for the Patho-TB while they were 100% and 92.9% for microscopy. It is concluded that the Patho-TB test gives good performances; it is easy to use and very easy to determine the results. For direct observation, we recommend this test to laboratories that do not perform microscopy with auramine, which is the case in tuberculosis endemic areas.

[Staphylococcus aureus infections carrying Panton-Valentine leukocidin genes in hospitals: which statute should be given to these strains?]. / Infections à Staphylococcus aureus porteurs du gène codant la leucocidine de Panton-Valentine à l'hôpital: quel statut donner à ces souches?

OBJECTIVES: The aim of the present study was to investigate the prevalence Staphylococcus aureus infections carrying Panton-Valentine leukocidin (LPV) genes in our hospital by screening patients that are hospitalised or admitted for consultation, as well as to study the characteristics of these strains and the respectively infected patients. METHODS: A descriptive and retrospective study over the course of a 14 month period was conducted. The isolates of S. aureus were tested for antimicrobial resistance, in which detection of the virulence gene was performed by way of PCR, such as is the case for gene luk-PV which encoding the LPV. The genetic diversity of the strains carrying gene, luk-PV, was determined by way of pulsed-field gel electrophoresis and by the MLVA (Multiple Loci VNTR Analysis; VNTR, Variable Number of Tandem Repeats) method. RESULTS: 7.14% of the S. aureus isolates carried genes for LPV, which are primarily sourced from surgery, emergency, and outpatient consultation services. The nature of the reported infections is often surface, immediately collected, and more rarely deep. Genotyping revealed three principal clones that were gathering 55% of the strains, which in turn highlighted transmission to the nursing staff. COMMENTS: These strains of S. aureus LPV+ have the capacity for diffusion and pathogenicity, which leads to the need to take some specific measures at hospitals: the tracking of the LPV during repeat or deep infections with S. aureus, possibly the search for conveyance and individual measures for the eradication of the strain. Lastly, it is necessary to increase the nursing staff's awareness of the appropriate hygiene measures when they come into contact with these patients.

[Performances of the "Amplified Mycobacterium tuberculosis Direct Test" in respiratory and non-respiratory specimens]. / Performances du test "Amplified Mycobacterium tuberculosis Direct Test" sur les échantillons respiratoires et extrarespiratoires.

From March 1998 to December 2004, 3641 specimens (2427 respiratory samples and 1214 non-respiratory samples) collected from 2079 patients, were tested using the "Gen-Probe Amplified Mycobacterium tuberculosis Direct Test" (AMTD). After decontamination procedure every sample was testing by AMTD and by culture on solid and liquid media. The "Gold-standard" was considered by the combination of culture results and clinical diagnosis. Respiratory tuberculosis was present in 9.7% (127 patients), and non-respiratory tuberculosis was present in 18.9% (170 patients, mostly originated from Africa). Among the 2427 respiratory samples (197 culture positive samples, 211 AMTD positive) 225 corresponded to tuberculosis; for the 1214 non-respiratory samples (184 culture positive samples, 213 AMTD positive) 231 corresponded to tuberculosis. After resolving the discordant results, the sensitivity, specificity, positive and negative predictive values were 93.8, 100, 100, 99.4% respectively for respiratory samples and 92.2, 99.9, 99.5, 98% for non respiratory samples.

[Hepatosplenic and kidneys candidasis complicating an acute myeloblastic leukemia. A case treated with voriconazole and caspofungin]. / Candidose hépato-spléno-rénale compliquant une leucémie aiguë myéloblastique. A propos d'un cas traité par l'association voriconazole et caspofungine.

We report the observation of hepato-splenic and kidneys candidiasis complicating the chemotherapy of a myeloblastic leukemia (LAM5b). Following the lack of effectiveness of a first line treatement, using amphotericine B liposomale and 5-fluorocytosine, implementation of an association of new molecules, a triazole of second generation (voriconazole) and an echinocandine (caspofungine) has allowed a successful result.

[Severe hypofibrinegenemia after rattlesnake envenomation in France]. / Hypofibrinogénémie sévère après morsure de crotale en France.

A 22-year-old man, who maintains illegally numerous exotic snakes at home (suburbs of Paris), was bitten by one of his Bresilian rattlesnakes, the lance-headed viper Bothrops moojeni, with grade III envenomation. The fibrinogen was less than 0,5 g/L, the prothombin time was 22%, the activated partial thromboplastin time was 94 seconds. The authors discuss the biological and clinical management of this defibrination, due to defibrinogenating proteases (thrombin-like enzymes), present in Bothrops moojeni venom. The patient received 7 vials of an antivenom directed to another crotal, Bothrops lanceolatus. Despite the importance of defibrinogenation, there was only a few clinical evidence of bleeding, according to the literature. The normalization of coagulation studies occured only after day 11. This case-report outlines the danger of the increase of exotic snakes maintained as pet in France and the difficulties to obtain specific antivenoms.

[A 7-year survey of strains identified in blood cultures in a clinical hematology unit]. / Etude sur sept ans des isolats d'hémocultures dans un service d'hématologie clinique.

GOAL: This study had for aim to analyze the epidemiology of strains identified in blood cultures (hôpital d'instruction des armées Percy, Clamart, France, hematology unit) to compare the rate of identified micro-organisms with literature data, and to search for a possible correlation between antibiotherapy management and evolution of resistance profiles. MATERIAL AND METHODS: All the micro-organisms (N = 690) collected over seven years (January 1996 to December 2002), from blood cultures of hospitalized patients in conventional and sterile sector were studied. RESULTS: Gram positive cocci rate (GPC) was 62.6% and Gram negative bacilli (GNB) 31.3%. Evolution in time showed a decrease of GPC and an increase of GNB, notably the non fermenting Gram negative bacilli, leading to an equal rate by 2001-2002. The most frequently identified species were Staphylococcus epidermidis (36.4%), Escherichia coli (8.7%), Pseudomonas aeruginosa (6.8%), and Staphylococcus aureus (4.9%). The rate of methicillin-resistant staphylococci was 63.6%. Fifty-five percent of E. coli strains had a penicillinase phenotype. Pseudomonas aeruginosa resistance was 8.5, 8.5, 6.4 and 8.5%, respectively for ceftazidime, piperacillin-tazobactam, imipenem, and amikacin. CONCLUSION: This study showed a tendency to inversion of former bacteremia epidemiology with increasing negative Gram bacilli. It justifies the antibiotherapy protocols adopted in the hematology unit.

Clinical evaluation of the gen-probe amplified mycobacterium tuberculosis direct test for rapid diagnosis of tuberculosis lymphadenitis.

This prospective study evaluated the performance of the Amplified Mycobacterium Tuberculosis Direct Test (MTD) for the diagnosis of lymph node tuberculosis in Djibouti, Republic of Djibouti. Of 197 specimens sampled from 153 patients, 123 were from 95 tuberculous patients. The sensitivity and specificity of MTD were 93 and 100%, respectively. The sensitivity of culture was 89%.

[Immune response to equine Chorionic Gonadotropin used for the induction of ovulation in goats and ewes]. / Réponse immunitaire à la eCG utilisée dans le traitement de l'induction d'ovulation chez la chèvre et la brebis.

In dairy goats and ewes the use of equine Chorionic Gonadotropin (eCG) as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination (AI). Treatment for induction and synchronization of ovulation consists of a progestagen delivered by vaginal sponge, followed by an eCG injection. In some females, the first injection of eCG induces a humoral response with high concentrations of anti-eCG antibodies in contrast to other females displaying a very low concentration of anti-eCG antibodies. Females eliciting a low response were also poor responders after the following treatments. Conversely, high responders at the first treatment systematically yielded high immune responses upon the following treatment. By a molecular genetic approach using microsatellites we showed that the anti-eCG immune response phenotypes were associated with MHC class II polymorphism. Females with high residual antibody concentrations at the time of eCG injection exhibited a much lower kidding rate than other females did. Lower fertility of these females, inseminated at a fixed time after eCG treatment (43H for goats and 55H for ewes), might be due to the delay in estrus occurrence and the pre ovulatory LH surge. Consequently, under field conditions old females selected for AI are only those with low residual anti-eCG antibody concentrations and old females with high residual antibody concentration are culled from AI breeding because of their low fertility during the previous year. So we have undertaken comparative studies to establish if the anti-eCG immune response is correlated with the global immunity in animals.

Use of equivocal zone in interpretation of results of the amplified mycobacterium tuberculosis direct test for diagnosis of tuberculosis.

The sensitivity and specificity of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test, evaluated with 1,363 respiratory samples (128 from tuberculous patients), were 92.97 and 98.7%, respectively. When an equivocal zone (30,000 to 1,000,000 relative light units [RLU]) was used instead of a 30,000-RLU cutoff, the sensitivity and specificity of the AMTD test were 92.97 and 100%, respectively.

[Antibiotic sensitivity of Salmonella isolated in army hospitals between 1998-1999]. / Sensibilité aux antibiotiques des salmonelles isolées dans les hôpitaux des armées en 1998-1999.

OBJECTIVES: Monitor the evolution in France of antibiotic sensitivity of non-typhoid salmonella isolated in fecal cultures conducted in army hospital laboratories. METHODS: A prospective study was performed from January 1998 to December 1999 in all the biology departments of the 11 army hospitals in France. All the non-repetitive strains were sent to an official center for serotyping and determination of the minimum inhibiting concentrations, by dilution in Mueller Hinton's gelose. The antibiotics currently used in treatment were tested and interpretation endpoints followed the recent recommendations of the Antibiogram committee of the French society of microbiology. Identification of beta-lactamase was conducted by iso-electric focalization and polymerization by chain reaction (PCR). For Salmonella Typhimurium, research for the specific resistance locus of the DT104 clone was made using PCR. RESULTS: Two hundred and twenty-two non-repetitive salmonella strains were isolated. The principle serotypes found were: Salmonella Enterididis (23.9%), S. Typhimurium (21.2%) and S. Hadar (10.8%). All the strains were sensitive to ciprofloxacin and cefotaxim, whereas one third exhibited reduced sensitivity to aminopenicillin. Depending on the serotype, Typhimurium and Hadar serotypes exhibited significantly lesser sensitivity to aminopenicillin, nalidixic acid and tetracycline. For S. Typhimurium, resistance is related to the diffusion of the multiresistant DT104 clone, which involves half of the strains of this serotype. For S. Hadar, 18 out of 24 strains (75%) were resistance to nalidixic acid, and 5 of them exhibited reduced resistance to ciprofloxacin. There was no difference in sensitivity to antibiotics between the strains responsible for diarrhea and those isolated in systematic examinations for capacity to work in the food trade (respectively 54 and 46% of strains). CONCLUSION: Non-typhoid salmonella are frequently isolated in diarrhea of infectious origin. The increasing resistance to antibiotics is primarily related to the diffusion of the DT104 clone, regarding S. Typhimurium and to the increase in resistance to quinolone, regarding S. Hadar.

[Epidemiology of resistance to antituberculosis drugs in Mycobacterium tuberculosis complex strains isolated from adenopathies in Djibouti. Prospective study carried out in 1999]. / Epidemiologie de la resistance aux antituberculeux des souches du complexe Mycobacterium tuberculosis isolees d'adenopathies a Djibouti. Etude prospective realisee en 1999.

Tuberculosis is a major cause of death in the Republic of Djibouti. Tuberculous lymphadenitis represents about 25% of the clinical forms of tuberculosis in this country. Between January 1999 and April 1999, 196 lymph node specimens were consecutively collected from 153 patients living in Djibouti. Testing of susceptibility to the major anti-tuberculosis drugs was performed by the proportion method. Growth of Mycobacterium tuberculosis complex strains was obtained from specimens of 85 patients including 9 with prior treatment. Strains were identified as Mycobacterium tuberculosis in 78 cases, Mycobacterium canetti in 3, Mycobacterium africanum in 3, and Mycobacterium bovis in 1. Prevalence of HIV infection was 15%. Assessment of primary resistance demonstrated that the overall resistance rate, i.e., resistance to 1 or more drugs, was 18 (21.2%). Results showed resistance to isoniazid (H) in 6 cases (7.1%), rifampicin (R) in 3 (3.5%), ethambutol (E) in 1 (1.2%), streptomycin (S) in 13 (15.3%) and pyrazinamide (Z) in 1 (1.2%). Multidrug resistance (MDR) was found in 2 cases (2.4%). Assessment of acquired resistance demonstrated resistance to H in 4 cases (44%), R in 2 (22%), S in 2 (22%), E in 0, Z in 0 and MDR in 1 (11%). These findings were not significantly different from data obtained from sputum samples analysed between 1997 and 2000 or from those described in a study conducted in 1985.

[Tinea capitis: sample surveys among school doctors and dermatologists in the Paris suburbs]. / Prise en charge des teignes: enquête auprès de médecins scolaires et de dermatologues franciliens.

BACKGROUND: Subsequent to detection of several cases of anthropophilic tinea capitis, we wanted to know whether the legal decree requiring eviction from school and an epidemiology survey in the children community or the family is implemented properly. METHODS: Two sample surveys were carried out among 50 school doctors from the Hauts-de-Seine department and 110 dermatologists working the Paris suburbs. RESULTS: Eviction from school was rare and not based on the type of dermatophytes (anthropophilic or zoophilic agent). Likewise, epidemiology survey was neglected, often being solely clinical for other family members. Systematic sampling in the children community or in the family was very exceptional. DISCUSSION: Despite the rise in the number of cases of anthropophilic tinea capitis in Paris suburbs, the decree is not often implemented. Dermatologists would appear to be responsible for this situation, especially in case of M. langeronii, which is very contagious in nursery school.

[Thoracic nocardiasis associated with macrophage activation syndrome]. / Nocardiose thoracique associée à un syndrome d'activation macrophagique.

Nocardiasis is an uncommon bacterial disease often observed in immunodepressed patients. Its interactions with the immune system remain poorly known. We report a case of Nocardia asteroides thoracic nocaridiasis in an African subject who also had macrophage activation syndrome. We recall the classic data on nocardiasis in Africa and emphasize the importance of emergence in HIV-infected subjects. The association between nocardiasis and macrophage activation syndrome suggest a possible pathogenic mechanism involving the immune system (lymphocytes and macrophages) and Nocardia asteroides.