The impact of lung ultrasound assessment during a whole lung lavage: A paediatric case of pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is the first-line treatment for pulmonary alveolar proteinosis. We hypothesized that lung ultrasound (LUS) would guide flooding during treatment in a 15-year-old boy. WLL of each lung consisted of instillation of saline followed by kinesiotherapy and fluid drainage. In the first WLL, the lung was repeatedly flooded until the lavage fluid was clear on macroscopic examination. During this process, LUS was used to visualise lung aeration. In the second WLL, we used LUS signs to guide the lavage volume. The appearance of the fluid bronchogram sign showed that saline infusion could be stopped earlier than in the first lavage. In conclusion, LUS helped monitor the different stages of controlled lung de-aeration during WLL and reduce the total amount of saline used. This technique will also reduce the risk of WLL-related complications.

The year's new drugs and biologics 2019.

Highlights of our annual review of new approvals and launches on global drug markets include the approval and launch of Trikafta, the most widely applicable treatment to date for cystic fibrosis; approval of the first Ebola vaccine for general (rather than emergency) use; the pilot rollout in three African countries of the world's first malaria vaccine; approval of a new treatment option for multidrug-resistant bacterial infections; and the approval and launch in China of the first new drug to treat Alzheimer's disease in more than a decade. Several new immune checkpoint inhibitors and antibody-drug conjugates were approved for cancer indications, confirming continued industry enthusiasm for cancer immunotherapy. The most notable trend of 2019 was the granting by the Food and Drug Administration (FDA) of a record number of accelerated approvals, many of which were issued several months ahead of the expected action date.

The year's new drugs and biologics 2018: Part I.

Sixty-four new drugs and biologics reached their first global markets in 2018, the greatest number in at least a decade. In addition, 19 important new line extensions (new indications, new combinations or new formulations of previously marketed drugs) were introduced over the course of 2018. Twenty-three other new products and new line extensions were approved but not launched before December 31. As has been the trend in recent years, oncology was the most active therapeutic area in terms of new launches, with cancer drugs accounting for 25% of all novel drugs and biologics introduced worldwide last year. Eight first-in-class agents were launched for the first time in 2018, including the first RNA interference agent as well as the photo-finish approval and rollout of the first three members of a radically different class of non-vasoconstricting antimigraine agents, the anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies. Twenty-nine of the drugs launched last year were designated orphan drugs, reflecting the continued upswing in investment in the area of neglected diseases. This is especially true in the U.S., which welcomed 25 of the newly launched orphan drugs. Overall, the U.S. was the most active market for new drugs and biologics, accounting for two-thirds of all new launches in 2018.

The year's new drugs and biologics 2018: Part II - News that shaped the industry in 2018.

This eagle's-eye overview of the drug industry in 2018 provides insight into some of last year's top stories, including a large and still growing outbreak of Ebola in the Democratic Republic of the Congo, as well as the potential uses (and abuses) of CRISPR technology. As in previous years, we also review orphan drug development, new regulatory agency-supported programs such as Priority Medicines Scheme (PRIME) and Sakigake, pipeline attrition, and pharma/biotech mergers and acquisitions of note. Finally, we take a glimpse into the crystal ball to anticipate the new drugs that will be approved in 2019.

[Acceptance of influenza vaccination by caregivers in a geriatric and long-term care institution]. / Acceptation de la vaccination antigrippale par les soignants au sein d'une institution gériatrique et médicosociale.

INTRODUCTION: Seasonal influenza is a viral transmissible infectious disease causing increased morbidity or mortality in frail subjects, especially those living in institutions. Measures to prevent the impact of infectious diseases were proposed based on the use of influenza vaccination among health-care professionals. We wanted to evaluate the acceptance of our institutional vaccination procedure initiated in 2005 and possible improvement. METHODS: A questionnaire was sent in May 2007 to all health-care professionals (n=730) to identify their current vaccine status in 2006 and their opinion concerning vaccination against influenza in 2007. RESULTS: Subsequently, 369 (50.2%) responses were obtained. Amongst those responding, 31.7% were vaccinated in 2006, 77.8% using the institutional procedure. Also, 221 (87.7%) nonvaccinated health-care professionals indicated their position concerning influenza vaccination: 37% of them would accept the vaccination in 2007 (on the condition that our current institutional procedure be improved), 63% of them would refuse influenza vaccines in spite of any improvement. CONCLUSION: Our study emphasizes that the use of an adapted procedure for influenza vaccination among health-care professionals could improve vaccine coverage. It also emphasizes that a margin of those professionals are still reluctant to vaccination.

The year's new drugs and biologics 2017: Part I.

This review presents the 113 new drugs and biologics that were approved or launched for the first time globally in 2017. Fifty-two new drugs and biologics reached their first markets worldwide in 2017. Seven of the new launches were first-in-class agents, meaning the first drug with a novel mechanism of action to be approved and launched anywhere in the world. In addition, 36 notable line extensions (i.e., new indications, new combinations and new formulations of previously marketed products) were introduced last year. The remaining 25 products discussed in this article were approved for the first time during the year just passed, but had not yet been launched as of December 31, 2017. The United States was the most active market for new drugs, and oncology was the most active therapeutic group. Information on these new arrivals is covered in depth in part I of our annual review of the pharma and biotech industry.

The year's new drugs & biologics, 2017, part II - News that shaped the industry in 2017.

This eagle's-eye overview of the drug industry in 2017 provides insight into some of last year's top stories, including the growing opioid crisis affecting the U.S. and other developed countries and the 2017-2018 influenza epidemic, with a spotlight on the need for a universal flu vaccine. As in previous years, we also review orphan drug development, new agency-supported programs such as PRIME and RMAT, pipeline attrition and drug pricing, as well as pharma/biotech mergers and acquisitions of note. Finally, we take a glimpse into the crystal ball to anticipate the new drugs that will be approved in 2018.

The year's new drugs & biologics 2016: Part I.

Nearly 90 new drugs and biologics, including important new line extensions, were approved or launched for the first time globally in 2016, a comparatively lower number with respect to previous years. Forty-four new drugs and biologics reached their first markets worldwide in 2016, nearly 10% fewer than the previous year. Seven of the new launches were first-in-class agents, meaning the first drug with a novel mechanism of action to be approved and launched anywhere in the world. In addition, 23 novel line extensions (i.e., new formulations, new combinations and new indications) were introduced last year. The remaining 21 products discussed in this article were approved for the first time during the year just passed, but had not yet been launched as of December 15, 2016. Information on these new arrivals is covered in depth in part I of our annual review of the pharma and biotech industry.

Association between sleep stages and hunger scores in 36 children.

BACKGROUND: Childhood obesity is a growing health challenge. Recent studies show that children with late bedtime and late awakening are more obese independent of total sleep time. In adolescents and adults, a delayed sleep phase has been associated with higher caloric intake. Furthermore, an adult study showed a positive correlation between REM sleep and energy balance. This relationship has not been demonstrated in children. However, it may be important as a delayed sleep phase would increase the proportion of REM sleep. OBJECTIVES: This study investigated the relationship between hunger score and sleep physiology in a paediatric population. METHODS: Thirty-six patients referred for a polysomnogram for suspected obstructive sleep apnoea were enrolled in the study. Sleep stages were recorded as part of the polysomnogram. Hunger scores were obtained using a visual analogue scale. Mean age was 9.6 ± 3.5 years. RESULTS: Mean hunger scores were 2.07 ± 2.78. Hunger scores were positively correlated with percentage of total rapid eye movement (REM) sleep (r = 0.438, P < 0.01) and REM sleep duration in minutes (r = 0.471, P < 0.05). Percentage slow wave sleep (SWS) was negatively correlated with hunger score (r = -0.360, P < 0.05). There were no correlations between age, sex, body mass index percentiles, apnoea-hypopnoea index, total sleep time, sleep efficiency, sleep onset latency, stage 2 sleep duration and hunger scores. CONCLUSIONS: These findings suggest that delayed bedtime, which increases the proportion of REM sleep and decreases the proportion of SWS, results in higher hunger levels in children.

[Surveillance of antimicrobial resistance of bacteria isolated from bloodstream infections: data of the French National Observatory for Epidemiology of Bacterial Resistance to Antibiotics (ONERBA), 1998-2003]. / Surveillance de la résistance bactérienne aux antibiotiques dans les bactériémies: données de l'observatoire national de l'épidémiologie de la résistance bactérienne aux antibiotiques (ONERBA) 1998-2003.

UNLABELLED: The French national observatory for epidemiology of bacterial resistance to antibiotics (ONERBA) includes numerous networks for the surveillance of bacterial resistance to antibiotics. OBJECTIVE: The aim of this study was to update antimicrobial resistance data of bacterial pathogens isolated from blood cultures. METHOD: Data was collected from several surveillance surveys reviewed by the ONERBA scientific committee during 2003. RESULTS: Gram positive cocci and Gram negative bacilli accounted respectively for 45 and 49% of all bacteria isolated from blood cultures (N=19 882). The frequency of MRSA among S. aureus was 35%. The frequencies of resistance to penicillin, amoxicillin and cefotaxime of S. pneumoniae were 10, 2, and 0.2%, respectively. In 2002, 70% of coagulase negative staphylococci were resistant to methicillin. Only 50 and 60% of E. coli isolates were susceptible to aminopenicillin and a combination amoxicillin-clavulanic acid, respectively. Since 2001, the susceptibility of E. coli isolates to ciprofloxacin has been regularly decreasing. Imipenem and ceftazidime were the most active antimicrobial agents against P. aeruginosa with a susceptibility rates below 90%. CONCLUSION: Data provided by the ONERBA should allow to improve the quality of empiric antimicrobial treatments.

Intravenous administration of the natriuretic peptide urodilatin at low doses during coronary reperfusion limits infarct size in anesthetized pigs.

OBJECTIVE: It has been shown that cGMP content is reduced in post-ischemic myocardium, and that stimulation of cGMP synthesis prevents cardiomyocyte hypercontracture and cell death in vitro. This study was aimed at determining whether administration of the natriuretic peptide urodilatin (URO) at the time of reperfusion could limit myocardial cell death secondary to transient coronary occlusion. METHODS: The relation between cGMP content in reperfused myocardium and the extent of cell death was investigated in isolated rat hearts (n=62) receiving different URO concentrations during initial reperfusion. The dose of intravenous URO necessary to obtain the targeted increase in cGMP in reperfused myocardium was investigated in ten pigs submitted to transient coronary occlusion (CO), and the effect of two selected doses of URO on infarct size was investigated in 22 pigs. RESULTS: cGMP was severely reduced in post-ischemic rat hearts. Addition of 0.01 microM URO during the first 15 min of reperfusion had no effect on myocardial cGMP content, functional recovery or LDH release in hearts submitted to 40 or 60 min of ischemia. At 0.05 microM, URO increased myocardial cGMP to 111% of values in normoxic hearts, improved functional recovery (P=0.01) and reduced peak LDH released by 40% (P=0.02). The beneficial effect of urodilatin was abolished by ANP receptor inhibition. At 1 microM, URO increased cGMP in reperfused myocardium to 363% of normoxic controls and had no beneficial effect. In pigs allocated to 47 min of CO and 5 min of reperfusion, cGMP was markedly reduced in reperfused myocardium. Intravenous URO at 10 ng/kg per min during the first 25 min of reperfusion normalized myocardial cGMP after 5 min of reflow (95% of control myocardium), and reduced infarct size by 40% (P=0.04). At 50 ng/kg per min, urodilatin increased myocardial cGMP in reperfused myocardium to 335% of control myocardium and failed to significantly reduce infarct size (46 vs. 66%, P=0.125). None of these doses had detectable hemodynamic effects. CONCLUSIONS: Intravenous low-dose URO at the time of reperfusion normalizes myocardial cGMP and limits necrosis. Large doses of URO increasing myocardial cGMP well over normal values may lack this beneficial effect.

ATR-FTIR spectroscopic investigation of E. coli transconjugants beta-lactams-resistance phenotype.

Hyphenation of attenuated total reflection Fourier transform infrared spectroscopy and cluster analysis has been used to characterise a susceptible Escherichia coli K12 strain and the transconjugants TEM-1, TEM-2, TEM-3, SHV-2, SHV-3, SHV-4. A good discrimination of the susceptible strain from the transconjugants was obtained. Although a limited success was achieved in the differentiation of SHV and TEM phenotypes in general, results obtained with TEM-2 and SHV-3 were convincing. Spectral differences observed are ascribed to the global effects of the conjugation process, particularly their repercussions in the nucleic acids and carbohydrate absorbing regions, rather than to beta-lactamase point-mutations.

Regulation of tyrosine-containing activation motif-dependent cell signalling by Fc gamma RII.

Crosslinking of the B-cell receptor (BCR) for antigen to low-affinity receptors for IgG (Fc gamma RII) inhibits B-cell activation induced by BCR aggregation. The cell-triggering properties of the BCR depend on tyrosine-containing activation motifs (TAM), in the intracytoplasmic domain of its Ig alpha and Ig beta subunits. TAMs also account for the cell-triggering capabilities of the T-cell receptor (TCR) for antigen, in T lymphocytes, and of the high-affinity receptor for IgE (Fc epsilon RI), in mast cells. Using as a model, rat basophilic leukemia cells (RBL-2H3) stably transfected with cDNA encoding wild-type or mutated murine or human Fc gamma RIIB and chimeric molecules having the intracytoplasmic domain of the FcR gamma subunit or of TCR-CD3 zeta subunit, we found that the inhibitory properties of Fc gamma RII are neither restricted to B cells nor to BCR-dependent cell activation, but can be extended to other cells and, as a general rule, to TAM-dependent cell activation.

A simple method for the construction of small format tissue arrays.

Tissue arrays can evaluate molecular targets in high numbers of samples in parallel. Array construction presents technical difficulties and tissue arrayers are expensive, particularly for small and medium sized laboratories. This report describes a method for the construction of 36 sample arrays using widely available materials. A blunted 16 gauge needle for bone marrow aspiration was used to extract paraffin wax cylinders and manually define a 6 x 6 matrix on a blank paraffin wax block. Tissue cores from 36 paraffin wax embedded premalignant lesions and invasive cervical carcinomas were injected into the matrix using a 14 gauge needle. This tissue array was sectioned using a standard microtome and used for the immunodetection of CD44 variant 9 and interleukin 18 with satisfactory results. This method can be applied in any laboratory, without the need of specialised equipment, offering a good alternative for the wider application of tissue arrays.

Nitrogen budget in Scenedesmus obliquus cultures with artificial wastewater.

Semicontinuous cultures of Scenedesmus obliquus in artificial wastewater, recycled into proteins about 33% and 25% of the dissolved nitrogen missing from the medium 24 h after harvesting 50% and 70% of the culture, and replacing the volume harvested with fresh medium. The residual dissolved nitrogen concentrations were 25% and 43% of the initial, respectively, with an imbalance in the mass budget close to 17 and 20 mg N l(-1) d-1. Most or all the nitrogen missing was found in an ammonia trap located at the air vent of the closed cultures, showing that an important role of microalgae in wastewater treatment is that of favouring NH3 stripping due to the photosynthesis-induced pH increases.

[Phenotype and genotype analysis of Torulopsis glabrata isolated from nosocomial infections]. / Analyse phénotypique et génotypique de souches de Torulopsis glabrata isolées lors d'infections nosocomiales.

Twenty-one strains of Torulopsis glabrata have been isolated in the hospital of Versailles during a three months period, in eight patients, and related to nosocomial infections. In order to know if they have been cross infected, a genotypic analysis (pulsed field electrophoresis) has been performed. The strains from four patients had the same karyotype, suggesting they had probably crossed infections. Since this kind of analysis is expensive and time consuming, we have tried a more practical approach. The susceptibility of the strains has been tested by Etest for five antifungal agents: amphotericin B, 5-fluorocytosine, ketoconazole, fluconazole et itraconazole. Statistical analysis of these results has not given the same classification of the strains of T. glabrata. Karyotyping by pulsed field electrophoresis of strains seems to be a better method to confirm strain clonality.

[Detection of circulating Candida albicans mannan and antimannan antibodies: useful for diagnosis of deep seated candidiasis]. / Intérêt de l'antigénémie mannane, du dosage des anticorps totaux par Elisa Platelia dans le diagnostic des infections profondes à Candida.

In deep seated candidiasis, only 40% of blood cultures are positive. The aim of the study was to investigate circulating Candida albicans mannan and anti-mannan antibodies as a possible help for the diagnosis of deep seated candidiasis. We have compared the results to the detection of IgM by Elisa and antibodies by immunoflourescence. The best tests, in accord to their sensitivity and specificity, are the mannan antigenemia (43% and 100%) and IgM (86% and 100%) and have to be used together.

[Nosocomial rotavirus infections in a general pediatric ward: epidemiology, molecular typing and risk factors]. / Infections nosocomiales à rotavirus dans un service de pédiatrie générale: épidémiologie, typage moléculaire et facteurs de risque.

OBJECTIVES: Nosocomial rotavirus infections induce difficult problems for pediatric wards during winter epidemics. This prospective study was carried out to measure their incidence in a general pediatric ward by using epidemiological tools, clinical and molecular methods, and to examine the main factors increasing the risk of cross contamination. MATERIAL AND METHODS: The study was carried out on children, younger than three years old, hospitalized between 15 November 1996 and 1 March 1997. We examined the feces of all children for rotavirus on admission and during their hospital stay if they had developed diarrhea. The strains were typed by RNA electrophoresis. A cohort study was done to identify the factors of exposure to risk. RESULTS: Three hundred twenty-six of the 415 hospitalized infants were studied. One hundred and five were hospitalized for gastroenteritis, including 39 (37.1%) with rotavirus infection. Among 221 infants admitted without diarrhea, 11 (5.0%) had an asymptomatic community infection and nine (4.3%) developed nosocomial gastroenteritis. The only significant predisposing factor (P = 0.003) for nosocomial infection was the distance between the hospital rooms and the nurses station. Despite the low level of typing (51%), the molecular study suggested a wide diversity of nosocomial and community strains. CONCLUSION: The relatively low incidence of nosocomial infections found may be due to routine assignment to individual rooms, the isolation of infants admitted with acute diarrhea, and the policy of routine detection of asymptomatic carriers with the use of similar isolation measures for these children.