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N Roche

Publications and source records attributed to N Roche.

At least 37 records · Page 2Linked to original sources

[The "COPD emergency 2003" study: a description of the hospital management of exacerbations of COPD].

CURRENT SITUATION: Despite its impact on public health and numerous recommendations COPD remains under-diagnosed and its care pathways are not well known. Exacerbations are common presentations of the illness and contribute greatly to its impact on the health of the individual and the community. Despite this the methods of their management in hospital have not been precisely described. The purpose of the prospective study "COPD emergency 2003" is to describe these different aspects of the management of COPD and to study their determining factors. MATERIALS AND METHODS: It is a prospective, multicentre observational study of all the exacerbations of COPD managed as emergencies in public and private hospitals during a two-month period. Enrolment takes place between October 2003 and January 2004. The analysis will begin when the last patient has been discharged from hospital. EXPECTED RESULTS: The data obtained will allow identification of those aspects of the management of COPD and its exacerbations that are heterogeneous or in conflict with the current guidelines as well as the patient care pathways. In the future this study should help target the approaches aimed at improving the outcomes of patients suffering from COPD.

Adult↗

[The therapeutic index in asthma: how should it be defined?].

INTRODUCTION: The therapeutic index (efficacy/tolerance or benefit/risk ratio) is a major determinant of treatment decisions in asthma. METHODS: For the numerator, the therapeutic index depends on efficacy (maximal effect) and not potency (dose-response relationship). With regard to the denominator, several pharmacological factors influence the occurrence of side-effects, the acceptability of which also has to be considered. RESULTS: In asthma, some strategies have a more favourable therapeutic index than others;e.g additional treatment (long acting beta2 agonists, leukotriene receptor antagonists, theophylline) to inhaled corticosteroids instead of doubling the dose of the latter. Conversely, it is extremely difficult to compare the therapeutic indices of different molecules of inhaled corticosteroids. CONCLUSIONS: The potential risk of systemic side effects with long-term administration of high doses of inhaled corticosteroids suggests the need to seek the minimal effective dose.

Administration, Inhalation↗

Incidence and prognostic value of respiratory events in acute leukemia.

Acute respiratory failure and infectious pneumonia are the major causes of death during induction chemotherapy of acute leukemia. However, the causes, incidence and prognostic value of all respiratory events (REs) occurring in this context have never been assessed prospectively. We recruited 65 consecutive patients with newly diagnosed acute leukemia into a 1-year prospective study (December 2000-November 2001) to evaluate the incidence and prognostic value of these events. REs were frequent: 38 were recorded in 30 patients. There was a significant relationship between REs and pre-existing respiratory disease and/or smoking. REs were caused by infection in 34% of cases, by an established cause other than infection in 42% and had an undetermined cause in 24%. Poor early outcome (death within 45 days of starting induction chemotherapy) in patients experiencing an RE was independently associated with a >25/min respiratory rate (P=0.003) and the nonachievement of complete remission (CR) (P<0.0001). Predictors of overall survival in the entire patient population were the absence of CR (P<0.0001), REs (P=0.02) and a > or =2 performance status (P=0.03). In conclusion, REs are frequent during induction chemotherapy of acute leukemia and represent an independent prognostic factor of poor outcome, regardless of their cause.

Acute Disease↗

Position of nuclear medicine modalities in the diagnostic work-up of breast cancer.

Breast tumors can be imaged by different modalities: mammography is the most widely used technique because of its diagnostic value, patient compliance and low costs. Some techniques such as ultrasound (US) are often indicated, while others, such as digital mammography and magnetic resonance imaging (MRI) are still under evaluation and seem to be very promising. Among the nuclear medicine techniques breast scintigraphy with (99m)Tc-labelled lipophilic cations (SestaMIBI or tetrofosmin), positron emission tomography (PET) with 18F-2-deoxy-2-fluoro-D-glucose (FDG) have been evaluated in many clinical trials. At present breast scintigraphy has limited applications due to its poor spatial resolution, which has a minimum of 8 mm. It is questionable whether single photon emission tomography (SPECT) can offer any substantially better information on the breast; however, SPECT is more accurate in detecting axillary lymph nodes. Recent approaches using breast dedicated collimators and cameras have greatly improved the SPECT resolution and sensitivity. The most interesting technique offered by nuclear medicine today are PET and lymphoscintigraphy with the intraoperative detection of handled gamma probe. The sentinel node detection has achieved a large consensus of reliability and at present it has an important place in the clinical management. In the same time many authors have acknowledged the value of PET in the differential diagnosis of breast lesions and in locoregional staging, since breast cancer is strongly avid for glucose. PET demonstrated also its efficacy in detecting axillary lymph node metastases. Even in some clinical trials its accuracy proved nearly comparable to that of lymphoscintigraphy with sentinel node biopsy, other studies showed that PET scanning does not currently have adequate spatial resolution to detect both micro- and small macrometastatic disease in axillary lymph nodes. The added value of PET in breast cancer staging is that with a single examination PET allows the characterisation of breast lesions, in addition to complete viewing of the entire body. Whole-body PET may substitute other diagnostic assessments by examining the various regions of potential tumour spread. The current diagnostic work-up for pre- and postoperative staging includes various examinations: chest X-rays, US of the abdomen, mammography of the contralateral breast. Bone scintigraphy with (99m)Tc-diphosphonates and laboratory tests can also be considered in women with large tumors or in symptomatic patients. Computed tomography (CT) and MRI may be used in order to resolve particular diagnostic problems. The current application of some of these modalities depends on the risk of the single patient of developing metastatic spread, which is revealed by a number of prognostic parameters of tumor aggressiveness and of course, clinical stage. Bone scintigraphy and PET may be useful in monitoring therapy response and in detecting tumour relapses during follow-up. In particular PET guided by tumor markers measurements shows to detect more lesions than other non nuclear medicine modalities.

Bone Neoplasms↗

Monitoring filamentous bulking in activated sludge systems fed by synthetic or municipal wastewater.

The stability with respect to filamentous bulking of two activated sludge fully-aerobic systems, one with a completely mixed tank and one with a channel reactor, fed either by a synthetic wastewater or by a primary-settled municipal wastewater, of variable composition and flow rate, has been investigated. The morphological characteristics of the biomass in terms of floc size and roughness and of filamentous bacteria abundance have been monitored by image analysis. Severe bulking was only observed in the well-mixed tank fed at a constant flow rate by synthetic substrate of constant concentration, when the channel reactor fed in a similar manner was fully stable. Variations of biomass characteristics as well as of settling properties were observed on both systems fed with the real wastewater, but these events were related to the characteristics of the wastewater, as similar changes were observed on the full-scale plant fed with the same substrate. In any case, automated image analysis was an efficient way to monitor in detail the fate of the activated sludge at pilot and full scale.

Journal Article↗

The effect of ultrasound-assisted liposuction and conventional liposuction on the perforator vessels in the lower abdominal wall.

Scientific reports of clinical in vivo research into the effects and side-effects of ultrasonic-assisted liposuction (UAL) are scarce. Advocates of UAL claim that the damage to vascular and nervous structures is limited and even less than with conventional and/or tumescent liposuction (CL). The effect of tumescent infiltration alone and combined with either CL or UAL was assessed by performing injection studies of the panniculus adiposus of the lower abdominal wall of 20 fresh cadavers and five abdominoplasty specimens. Besides the control and infiltration groups (n=5 in each), there was an additional group of ten cadaver flaps and five abdominoplasty flaps that underwent infiltration followed by UAL in the right half of the flap and infiltration followed by CL in the left half of the flap. Radiographs of these flaps were shown to a blinded panel of ten plastic surgeons, who were asked to evaluate and compare the damage on the basis of the number and magnitude of contrast-medium extravasations in the flap. Vascular damage to the perforating vessels was seen even after infiltration alone, although it was very limited. A variable amount of damage (ranging from little to extensive) was observed in the CL and UAL groups. Statistical analysis of the judgments of the observers could not show that either technique was less damaging than the other. UAL is, therefore, probably more beneficial to the surgeon than to the patient. The financial investment in the device is justified for surgeons with large liposuction practices, mainly, and probably solely, because of the reduced physical strain for the surgeon.

Abdominal Wall↗

Regulation of protease-activated receptor-1 in mononuclear cells by neutrophil proteases.

Neutrophils and mononuclear cells are implicated in the pathogenesis of several inflammatory conditions including chronic obstructive pulmonary disease (COPD). Neutrophil-derived serine proteases, such as cathepsin G (CG) and neutrophil elastase (NE), may interact with mononuclear cells via protease-activated receptors (PARs) which are seven-transmembrane G protein-coupled receptors activated by proteolytic cleavage of the extracellular N-terminus, and which, on activation, induce the release of several mediators and cytokines. We determined whether CG and NE could affect PAR-1 expression and function in mononuclear cells. Human blood mononuclear cells were isolated from 20 healthy donors. Surface and intracellular receptor expression and calcium mobilisation (using the calcium chelator, FLUO3-AM) were studied by fluorescence-assisted cell sorting (FACS analysis). Positive controls, i.e. thrombin (0.1-100 mU/ml) and the PAR-1-activating peptide SFLLRN (100 microM) induced a rapid and transient intemalisation of PAR-1 in monocytes and lymphocytes. CG but not NE had a similar effect. By contrast, in monocytes intracellular calcium mobilisation was induced by thrombin and SFLLRN but not by CG and NE. Thus, CG can induce intracellular PAR-1 sequestration without activation of the receptor, and may act as an antagonist and prevent subsequent activation of PAR-1 in mononuclear cells. These findings may be of relevance to the pathogenesis of COPD.

Calcium↗

Chronic bronchitis among French adults: high prevalence and underdiagnosis.

The aims of this survey were to determine the prevalence of symptoms indicative of chronic bronchitis (CB) in the French adult population, to identify the role of risk factors for CB, and to assess rates of CB diagnosis and pulmonary function testing (PFT) in the presence of CB. A representative sample of 14,076 individuals aged > or = 25 yrs completed a self-administered questionnaire on symptoms, comorbidities, smoking history, sociodemographical data, and diagnosis and care by physicians. The prevalence of CB was 4.1% and the prevalence of chronic cough and/or expectoration was 11.7%. In individuals with comorbidity, these figures were 10.4% and 24.4%, respectively. Smoking was associated with an increased frequency of CB. In subjects with CB, 44.6% had PFT (spirometry or peak expiratory flow measurement), 24% were diagnosed as having CB, and 7.2% received care. Rates of diagnosis, PFT, and follow-up were lower in young individuals and in those without comorbidity. PFT and follow-up were less common in current smokers. Prevalence of chronic bronchitis in French adults is high and similar in magnitude to that of other industrialised countries. Comorbidities and tobacco smoking increase the frequency of chronic bronchitis symptoms. Chronic bronchitis is too infrequently diagnosed, investigated and cared for.

Adult↗

Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability.

This study assessed whether the improper use of pressurized metered-dose inhalers (pMDIs) is associated with decreased asthma control in asthmatics treated by inhaled corticosteroids (ICS). General practitioners (GPs) included consecutive asthmatic outpatients treated by pMDI-administered ICS and on-demand, short-acting beta2-agonists. They measured an asthma instability score (AIS) based on daytime and nocturnal symptoms, exercise-induced dyspnoea, beta2-agonist usage, emergency-care visits and global perception of asthma control within the preceding month; the inhalation technique of the patient also was assessed. GPs (n=915) included 4,078 adult asthmatics; 3,955 questionnaires were evaluable. pMDI was misused by 71% of patients, of which 47% was due to poor coordination. Asthma was less stable in pMDI misusers than in good users (AIS: 3.93 versus 2.86, p<0.001). Among misusers, asthma was less stable in poor coordinators (AIS: 4.38 versus 3.56 in good coordinators, p<0.001). To conclude, misuse of pressurized metered-dose inhalers, which is mainly due to poor coordination, is frequent and associated with poorer asthma control in inhaled corticosteroid-treated asthmatics. This study highlights the importance of evaluating inhalation technique and providing appropriate education in all patients, especially before increasing inhaled corticosteroid dosage or adding other agents. The use of devices which alleviate coordination problems should be reinforced in pressurized metered-dose inhaler misusers.

Administration, Inhalation↗

Study of filamentous bacteria by image analysis and relation with settleability.

An automated procedure for the characterisation by image analysis of the morphology of activated sludge has been used to monitor the biomass in a pilot wastewater treatment plant during two runs inoculated with a different sludge and operated at two different temperatures. The bulking events were easily detected by image analysis. Correlations were found between settleability properties (Sludge Volume Index and settling velocity) and the morphological parameters (filament total length, filament number and floc size).

Bacteria↗

Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma.

BACKGROUND: Protease-activated receptors (PARs), which are G protein-coupled receptors that are activated after proteolytic cleavage of the amino terminus of the receptor, are likely to play a major role in airway inflammation. PARs are activated by endogenous proteases, including thrombin (PAR-1, -3, and -4) and tryptase (PAR-2 and -4), both of which are present in inflamed airways. OBJECTIVE: The purpose of this study was to compare the expression and distribution of PARs in biopsy specimens obtained from asthmatic and normal subjects and to examine the effect of inhaled corticosteroids on PAR expression. METHODS: Biopsy specimens were obtained from 10 normal and 20 asthmatic patients, and sections were stained for PAR-1, -2, -3, and -4 through use of specific antibodies. Staining was scored semiquantitatively for both intensity and distribution. RESULTS: Staining for all PARs was seen on the epithelium and smooth muscle in biopsy specimens from both normal and asthmatic subjects. In the epithelium, PAR-1 and -3 staining appeared to be apically concentrated, whereas PAR-2 and -4 staining was more diffuse. In normal subjects, epithelial staining intensity of PAR-1 and -3 was significantly greater than for PAR-4 (P < .05). Staining for PAR-1, -3, and -4 in biopsy specimens from asthmatic subjects was similar to that in specimens from normal subjects, irrespective of whether the former were using inhaled corticosteroids. However, PAR-2 staining in asthmatic epithelium was significantly increased in comparison with normal epithelium. Expression of PARs in airway smooth muscle did not differ between groups. CONCLUSION: Asthma per se is associated with increased PAR-2 expression in bronchial epithelium. Importantly, staining was not influenced by inhaled corticosteroids. These results suggest that PAR-2 might be involved in airway inflammation.

Administration, Inhalation↗