[Acute exacerbations of COPD admitted to hospital: predictive factors of 3 year mortality]. / Exacerbations aiguës de BPCO hospitalisées: facteurs prédictifs de mortalité à trois ans.

INTRODUCTION: COPD is a disease whose gravity is underestimated by doctors and patients. The development of acute exacerbations (AE) accelerates the progression of the disease and leads to increased financial costs, notably on account of hospitalisation. MATERIALS AND METHODS: An observational prospective study will be undertaken based on a cohort of consecutive patients hospitalised in departments of respiratory medicine in general hospitals. The main objective is to study the factors predictive of mortality at 3 years after one admission for AE. The secondary objectives are to describe the characteristics of the AE on arrival and 3 months after discharge from hospital. A register will be set up and a questionnaire will be completed for each patient, consisting of items concerning COPD, the AE and the condition of the patient and his treatments 3 months after discharge. The level of mortality at 3 years and the predictive factors will be calculated from the data in the register. EXPECTED RESULTS: Identification the characteristics of the AE and determination of a predictive score for mortality should allow optimisation of the management of patients suffering from COPD.

[Caffeine citrate utilization for treatment of apnea in French neonatal units]. / Utilisation du citrate de caféine pour le traitement des apnées idiopathiques du prématuré dans les équipes Françaises de médecine néonatale.

UNLABELLED: Caffeine citrate is commonly used for prophylaxis and treatment of apnea in preterm babies. OBJECTIVE: To evaluate the use of caffeine citrate in french neonatal units. MATERIALS AND METHODS: Postal survey in 100 neonatal units. RESULTS: Answers were obtained from 81 units. Sixty-three units use systematic prophylactic treatment and the threshold of gestationnal age (weeks gestation) for this systematic treatment is 32 weeks. Caffeine citrate is administered as a loading dose of 20 mg/kg followed by a maintenance dose of 5 mg/kg in 95% of the units. Discontinuing the treatment occurs between 33 and 35 weeks in 37% of the units and between 35 and 37 weeks in 53%. Two third of neonatologits describe recurrent apnea beyond 37 weeks, with the need to continue treatment. Fourteen units sometimes discharge babies at home with ambulatory caffeine citrate treatment and discontinue treatment by 42 to 46 weeks'gestation. A mean duration of 5 days without apnea is required before discharge. CONCLUSION: French teams respect "recommendations" concerning doses and duration without apnea before discharge. Indication of treatment, threshold for systematic treatment, duration of treatment and ambulatory treatment differ among teams.

[Apnea of prematurity: risk factors and ambulatory treatment with caffeine citrate]. / Apnées tardives du prématuré: facteurs de risque, traitement ambulatoire par citrate de caféine.

INTRODUCTION: Apnea of prematurity develop during the first days of life and usually resolve by the time the infant reaches 36-37 weeks postmenstrual age. In a few cases, they persist beyond term, especially in infants delivered at the youngest gestational ages (24-28 GA), and require specific care. In our unit, those preterm babies are discharged home with caffeine citrate treatment. Discontinuing the treatment is performed in hospital when they achieve a postmenstrual age of at least 42 weeks. OBJECTIVE: To identify predictive factors of persistent apnea in preterm babies. MATERIAL AND METHODS: Retrospective study comparing a population of 41 preterm infants discharged with treatment to 123 preterm babies discharged without treatment to identify predictors of persistent apnea. RESULTS: Factors significantly associated were: birth weight<1500 g, initial hypotension, gastroesophageal reflux, need for continuous positive airway pressure and multiparity. At home, no infant died and no adverse effect was reported by parents. CONCLUSION: Persistent apnea can be responsible for prolonged hospitalization. Risk factors can be identified in some children. Discharging with treatment can be an alternative to their hospitalization.

[Cohort KBP-2000-CPHG: Evaluation of factors influencing survival in lung cancer]. / Cohorte KBP-2000-CPHG: évaluation des facteurs pronostiques de la survie du cancer bronchique primitif à 2 et 5 ans.

INTRODUCTION: Lung cancer continues to have a poor prognosis despite some therapeutic advances. BACKGROUND: The last fifteen years has seen a dramatic increase in the incidence of lung cancer in women and an increased proportion of adenocarcinomas in both sexes. A study of overall survival as a function of gender and other prognostic factors has been established using the cohort of patients from the study KBP-2000-CPHG. METHODS: KBP-2000-CPHG is an epidemiological study carried out throughout the year 2000 looking at histologically confirmed primary lung cancers managed in general hospitals. 5,667 patients have been included. The study of survival looks at 2 and 5-year outcomes. The date and cause of death are recorded for each patient. In the absence of these data the date of the last contact is noted. If this is less than 4 months the patient is considered to be alive. If more than four months have elapsed a graduated strategy for establishing vital status is pursued which involves reviewing records from various different sources. RESULTS AWAITED: A preliminary review of the data was undertaken between September 2004 and March 2005 which obtained data on 5 567 patients. The analysis of survival according to sex and other forecast prognostic factors is underway.

[Oxidatif-stress and COPD. Role of infection. Prevention]. / Stress oxydatif et BPCO. Rôle des infections. Prévention.

For the next decade, COPD will become the third cause of mortality in the world. COPD is mainly due to cigarette smoking and presents different levels of severity according to people, probably linked to environmental and genetic factors, which are not well documented. Recent publications pointed out bacterial bronchial colonization and exacerbations of infectious origin as worsening factors through a pro-inflammatory effect and oxidative stress. This should lead to a comprehensive review of anti-infectious prevention tools and to discuss the role of prophylactic antibiotherapy and antioxidants.

[Oxidative stress in bronchopulmonary disease: contribution of N-acetylcysteine (NAC)]. / Le stress oxydatif en pathologie broncho-pulmonaire: apport de la N-acétyl-cystéine (NAC).

Oxidative stress is a frequent mechanism involved in the pathogenesis of bronchopulmonary disease. The cause can be exogenous, in particular related to to atmospheric pollution and tobacco smoke, or endogenous, related to mobilization of inflammatory cells (macrophages and polymorphonuclear neutrophils). In this general review, we present work demonstrating this oxidative stress and activation of inflammatory cells. We discuss the effect of oxidative stress on the bronchial tree and the need to maintain an adequate balance between oxidants and anti-oxidants. This reviews focuses on experimental studies proving the anti-oxidant effect of NAC on glutathione synthesis and on different pharmacological models. We then discuss human trials, initially experimental then in different bronchopulmonary pathologies related to oxidative stress. Acetaminophen intoxication and pulmonary fibrosis are models for use of NAC. Recent work on COPD appears to show a decrease in exacerbations, improvement in symptoms and quality-of-life, and perhaps a reduction in the alteration of ventilatory function.

Influence of rifampin on the pharmacokinetics of pefloxacin.

Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections. The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers. Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period. During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d. oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day. The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12-hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05). The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05). The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A. This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable.

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

Fluticasone propionate 50 micrograms BID versus 100 micrograms BID in the treatment of children with persistent asthma. Fluticasone Propionate Study Group.

The aim of this multicenter, double-masked study was to compare the efficacy and safety of two different doses of inhaled fluticasone propionate dry powder--50 micrograms and 100 micrograms--administered BID via a multidose powder inhaler with those of placebo in the treatment of children with persistent asthma. After a 2-week run-in period, 263 patients were randomized to treatment with twice-daily placebo (n = 92), fluticasone 50 micrograms (n = 85), or fluticasone 100 micrograms (n = 86) for 12 weeks. One hundred sixty-six (63%) patients were male, and 224 (85%) were white, with a mean age of 8 years. Two hundred twenty-one (84%) patients were atopic, and 167 (63%) had been asthmatic for 1 to 5 years. Baseline mean morning peak expiratory flow (PEF) values were 207 L/min, 199 L/min, and 194 L/min, and baseline percentages of predicted normal values were 86%, 80%, and 81% for the groups receiving placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. At the end of the first week of treatment, patients in both fluticasone groups had significantly greater improvements in morning PEF than did those receiving placebo. Patients experienced mean increases of 4 L/min, 22 L/min, and 26 L/min with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. At the end point (the last evaluable visit), patients in both fluticasone groups continued to have significantly greater improvements in morning PEF than did patients receiving placebo. Patients experienced mean increases of 17 L/min, 50 L/min, and 57 L/min with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. Changes in the percentage of predicted values by end point were 8%, 20%, and 26% with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. The probability of remaining in the study, according to predefined withdrawal criteria, indicated a significant treatment difference in favor of fluticasone. Withdrawal criteria were met by 63%, 42%, and 29% of patients receiving placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. This study clearly demonstrates the superiority of fluticasone 50 and 100 micrograms BID over placebo in the treatment of persistent asthma in children.

Effects of ketoprofen (NSAID) on the pharmacokinetics of pefloxacin and ofloxacin in healthy volunteers.

The influence of ketoprofen (K), a non steroidal antiinflammatory drug (NSAID) on the pharmacokinetics of two fluoroquinolone derivatives: ofloxacin (O) and pefloxacin (P) was studied in ten healthy adult male volunteers. All subjects orally received every 12 h the fluoroquinolone derivative (either O or P) for three days and the combination of the quinolone and ketoprofen (once a day) during the three following days. Two pharmacokinetic studies were performed for each quinolone, on days four and eight of the treatment. Blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after dosing. Urine was collected during 4 time-periods: 0-4 h, 4-8 h, 8-12 h and 12-24 h. Plasma and urine concentrations of the active drug of O and P were measured by microbiological assay. Ketoprofen did not significantly modify the pharmacokinetic parameters of the two fluoroquinolones studied in terms of peak plasma levels, time to peak, area under the curve, elimination half-life, volume of distribution and total and renal clearances.

Cisplatin and vindesine for disseminated non-small cell lung cancer. Results of a prospective trial with 81 patients.

Eighty-one patients with disseminated non-small cell lung cancer (stage IV) were treated with 2 monthly cycles of initial chemotherapy combining cisplatin with vindesine. The initial chemotherapy-responding patients (CR, PR, MR) were randomized to 2 cycles or 4 cycles of maintenance chemotherapy. After initial chemotherapy, the response rate was 33% (CR, PR, MR) with 18.5% objective responses. The overall 1-year survival rate was 15% with 37% for responders as opposed to 2% for non-responders. Maintenance chemotherapy did not improve the response rate obtained after initial cycles. The small number of patients does not allow us to reach a definite conclusion on the optimum duration of maintenance chemotherapy. In the absence of large placebo versus chemotherapy randomized trials, no definite conclusion can be made on the benefit of chemotherapy in disseminated non-small cell lung cancer. This study suggests, however, that chemotherapy is associated with a significantly longer survival in responding patients.

Effects of lactation on fetal survival and development in rabbit does mated shortly after parturition.

Primiparous rabbit does were mated within 12 h after parturition (d 0). They were immediately weaned (Group W; n = 31) or allowed to suckle 10 young rabbits (Group L; n = 32). Blood samples were collected at d 0, 7, 17, and 28. Feed intake and live weight were measured weekly and pregnant does (Group W, n = 24; Group L = 25) were slaughtered at d 28. Feed intake was 78% higher in L than in W females throughout gestation (P < .001). However, L females lost weight during the second half of gestation (-243 +/- 25 g) compared with W females, which gained weight (246 +/- 20 g). The weights of carcass, skin, and adipose tissues were severely reduced at d 28 in the L group (P < .01). Ovulation rate (11.0 +/- .3 corpora lutea) and early embryonic mortality (< d 15) were similar in both groups (12.3 +/- 2%), whereas late embryonic mortality (> or = d 15) was higher in L than in W does (13.9 +/- 3 vs 3.9 +/- 1%; P < .01). Fetal weight was reduced by nearly 20% in L compared with W females (P < .01). Plasma concentrations of progesterone were lower in L than in W females at d 7 and 17 (P < .001), whereas concentrations of estradiol were similar in both groups throughout gestation. These results indicate that fetal survival and development can be impaired in lactating females.

Effect of cooking temperature and cooking time on Warner-Bratzler tenderness measurement and collagen content in rabbit meat.

The effects of cooking temperature (50-90 °C) and time (10-120 min) on Warner-Bratzler (WB) tenderness measurement of longissimus lumborum (LL) muscle in 70-day-old rabbits were investigated. Cooking losses, total collagen content and collagen solubility of LL muscle were measured in parallel. Increasing cooking temperature caused a four-phase effect on WB measurement. Stress and total energy were significantly increased between raw meat and cooked meat at 50 °C, then they dramatically decreased to a minimum observed at 60-65 °C, and increased again to reach a maximum at 80-90 °C. Cooking losses exhibited an 83% increase between 50 and 80 °C. At 80 °C, stress and total energy values remained constant after 20 and 40 min respectively. LL muscle collagen content was 16.4±2.3 mg/g of dried muscle. Collagen solubility at 77 °C for 1 h was high: 75.3±8.1%.

[Analgesic effects of Emla cream and saccharose solution for subcutaneous injections in preterm newborns: a prospective study of 265 injections]. / Effet analgésique de la crème Emla, du saccharose et de leur association pour les injections sous-cutanées chez le nouveau-né prématuré: étude prospective de 265 injections.

OBJECTIVE: To compare the analgesic effects of non nutritive pacifier sucking, oral administration of a 30% saccharose solution, local application of Emla and their association for subcutaneous injection of erythropoietin (EPO) in preterm infants. METHODS: Our study was a randomised, prospective study conducted over 5 months. Neonates with a gestational age below 33 weeks of gestation and older than 8 days of life were included if they were treated with EPO (three subcutaneous injections per week during 6 weeks). For each consecutive EPO injection, patients were randomised between four groups of intervention: non nutritive pacifier sucking (T), oral administration of 0.2-0.5 ml of a 30% saccharose solution with non nutritive pacifier sucking (S), local application of Emla with non nutritive pacifier sucking (E), and oral administration of 0.2-0.5 ml of a 30% saccharose solution with local application of Emla and with non nutritive pacifier sucking (S + E). Each child was its own control. Pain was assessed with the Newborn Acute Pain scale (DAN) and with the Neonatal Facial Coding System (NFCS). RESULTS: Thirty-three neonates were included, representing 265 injections. Distribution was: 41 in group T, 71 in group E, 86 in group S and 67 in group E + S. Mean DAN and NFCS scores were statistically different between groups T, E and S. Analgesic effect of saccharose (-1.05) was greater than Emla (-0.56). Used together, effects were adding up without potentialisation. CONCLUSION: This study shows that the association of non nutritive pacifier sucking with oral administration of saccharose and local application of Emla has a better analgesic effect than each of these three interventions alone for subcutaneous injection of EPO.

[Congenital toxoplasmosis: a new case of infection during pregnancy in an previously immunized and immunocompetent woman]. / Toxoplasmose congénitale: un nouveau cas d'infection pendant la grossesse chez une femme antérieurement immunisée et immunocompétente.

UNLABELLED: Congenital toxoplasmosis is a potentially serious infection which usually affects infants born to non immune women. CASE REPORT: Our case report focuses on a baby born to a normally immunocompetent woman previously immunized against toxoplasmosis. To our knowledge only three similar cases have been published until now. CONCLUSION: We conclude that in front of a patient neonatal congenital infection picture, toxoplasmosis cannot be excluded on the ground of maternal immunity status and must be quickly investigated, given the emergency of appropriate treatment.

[Use of diazepam in the treatment of opioid neonatal abstinence syndrome]. / Traitement par le diazépam du syndrome de sevrage néonatal aux opiacés (23 cas).

INTRODUCTION: The fetal opiate exposure presents many risks for the newborn. One of the most important is the neonatal abstinence syndrome that associates neurological and digestive signs. In some cases the vital prognosis can be involved. The evaluation of the syndrome's severity is based on certificated scales. The mortality has been reduced by the improved management of these neonates. Diamorphine, phenobarbital, chlorpromazine and diazepam are the most currently used. However, there is no consensus on the treatment. The data concerning the treatment are controversial, especially for the use of diazepam. The aim of our study was to describe the effects of diazepam obtained in three different centers and to compare our results to those of the literature. POPULATION AND METHODS: Twenty-three neonates were included. They were all hospitalized for abstinence syndrome and treated by diazepam. The Finnegan scale was used to evaluate the symptom's severity and the effects of the diazepam. The principal evaluation criteria were the duration of treatment and hospitalization, the timing in recovery of birth weight and the percentage of birth weight loss. RESULTS: The average treatment duration was 7 days, the average hospitalization duration was 18 days, the birth weight was recovered at 10 days of life and the percentage of loss of birth weight was 6.5%. Diazepam treatment failed in only one case. No case of intense dehydration occurred. CONCLUSION: Due to the retrospective design of the study, the diazepam could not be compared to other drugs. Nevertheless, it argues against the "anti-diazepam" attitude. A controlled randomised prospective study is needed to evaluated the optimal therapeutic strategy.

[Efficacy of rituximab in lymphomatoid granulomatosis]. / Efficacité du Rituximab au cours d'une granulomatose lymphomatoïde.

INTRODUCTION: Lymphomatoid Granulomatosis is a rare and serious disease, now considered to be a B-cell lymphoma, which is frequently associated with Epstein-Barr virus infection. There is no consensus on treatment, which is usually based on steroid therapy, either alone or combined with cyclophosphamide and combination chemotherapy. CASE REPORT: We report the case of an asymptomatic patient diagnosed after the incidental discovery of bilateral nodular opacities on their chest x-ray. Physical examination and bronchoscopy were normal. The diagnosis of Lymphomatoid Granulomatosis was made on the basis of surgical lung biopsy. Immunohistochemical studies confirmed the B phenotype of the lymphoma with the identification of atypical large CD 20 positive cells. In situ hybridisation confirmed the presence of EBV. In this case the course of the disease was slow. Treatment with anti CD 20 monoclonal antibodies (rituximab) led initially to a reduction in parenchymal abnormalities and mediastinal adenopathy. CONCLUSION: This treatment, recently used in Lymphomatoid Granulomatosis with pulmonary involvement, has shown promising results. Rituximab can be used in combination chemotherapy as standard treatment for aggressive B-cell lymphoma.

[Primary bronchogenic and pharyngo-laryngeal carcinomas (author's transl)]. / Cancers bronchiques primitifs et cancers pharyngo-laryngés.

The study of 112 case histories of lung cancers, both primary and secondary, has allowed the authors to determine as being of 5% the incidence of primary bronchogenic carcinoma associated with treated pharyngo-laryngeal cancer. One out of three such primaries was a solitary lung opacity. Bronchogenic primaries appeared be almost as frequent as lung, pleura and mediastine secondarie. They can be diagnosed at any moment of the treatment or follow-up of pharyngo-laryngeal cancer, and appear to occur later than pulmonary metastases. Their symptoms are more "bronchopulmonary" in nature. They are more frequently associated with endolarynx and chorda carcinomas. They are possibly more frequent in cases of smaller primaries without lymph-node involvement. Solitary lung opacities should be considered as independent primaries and constitute the best candidates for efficient pulmonary treatment. Treated pharyngo-laryngeal patients should undergo regularly spaced lung roentgenograms and frequent tracheal sputum cytology.

[Pulmonary malacoplakia caused by Rhodococcus equi in AIDS: a case report]. / Malacoplasie pulmonaire à Rhodococcus equi au cours du SIDA: à propos d'un cas.

We describe the observation of a right upper lobe consolidation with cavitation produced by Rhodococcus equi in a patient suffering from AIDS. The inefficacy of a prolonged antimicrobial therapy adapted against R. equi led to a right upper lobectomy. The histopathology showed a pseudotumoral mass, with dense infiltration of macrophages containing Michaelis-Gutmann bodies, which was positive for the culture of R. equi. Pulmonary malacoplakia with Rhodococcus equi was diagnosed. This pathology should be evoked when a R. equi pneumonia persists despite a right management of treatment for several months. The features of pneumonia with Rhodococcus equi and of pulmonary malacoplakia are taken from a literature review.

[Drug-induced pneumonitis due to sirolimus: an interaction with atorvastatin?]. / Pneumopathie médicamenteuse sous sirolimus: interaction avec l'atorvastatine?

INTRODUCTION: Sirolimus is an immunosupressant used in renal transplantation because of its lack of nephrotoxicity. We report four cases of pneumonitis due to sirolimus, possibly revealing an interaction with atorvastatin. CASE REPORT: Four patients (previously on long-term treatment with atorvastatin) presented with respiratory symptoms between 3 and 56 months after starting treatment with sirolimus following renal transplantation. Thoracic CT scans showed bilateral areas of peripheral alveolar consolidation. Bronchial lavage showed a lymphocytic alveolitis. Open-lung biopsy showed organizing pneumonia associated with diffuse alveolar damage and caseating granulomata. We attributed the pneumonitis to sirolimus on account of clinical and radiological resolution within 1 to 6 months of stopping treatment. We raise the possibility of an association between sirolimus and atorvastatin by competition for their hepatic degradation pathway via cytochrome P450 3A4. CONCLUSION: Sirolimus causes drug-induced pneumonitis that is predominantly an organizing pneumonia. Atorvastatin may encourage its development by competition with sirolimus in the liver.