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Biomedical subjects

N Roche

Publications and source records attributed to N Roche.

15 recordsLinked to original sources

Ambulatory inhalation therapy in obstructive lung diseases.

The inhalation route is widely used for the treatment of obstructive lung diseases, because administered drugs have a high therapeutic index as they reach their target directly; this requires that they be of adequate size to penetrate the conducting airways, i.e. 2-5 microns. Pressurized inhalers were the first reliable metered-dose devices available, and are still the most frequently used. However, metered-dose inhaler (MDI) suspensions will have to be reformulated: they contain chlorofluorocarbons (CFCs), whose production has to be stopped within a few years, as they affect the stratosphere. Another limitation of MDI usage is paradoxical bronchospasm; this phenomenon, however, occurs in a low number of patients and is rarely clinically relevant. The main cause of concern with MDIs is their misuse by more than 50% of patients, which leads to a reduced lung deposition and clinical efficacy. Therefore, other inhalation devices have been developed: spacers, dry-powder inhalers (DPIs), and breath-actuated MDIs have been shown to increase lung deposition of drugs in poor coordinators. However, all have limitations which may have varying consequences on clinical efficacy: cumbersome dimensions of spacers, effect of inspiratory flow rate and humidity on lung deposition of dry powders, need for reformulation with CFC-free gases for breath-actuated pressurized inhalers. Reformulation of MDI aerosols is a complex procedure, which may not be feasible for all drugs. The new products need extensive toxicological and clinical testing, as some of their characteristics may differ from those of their predecessors.

Aerosols

Allergic and nonallergic interactions between house dust mite allergens and airway mucosa.

Asthma and allergy are extremely frequent diseases, affecting 5-10% and 30% of the population, respectively. The prevalence of asthma has increased in many developed countries, which may be due to several factors, including increased exposure to house dust mite (HDM) allergens. HDM to which humans are most frequently sensitized are Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei. These mites multiply in carpets, bedding and upholstered furniture in a hot and humid atmosphere. The allergens are digestive enzymes of the mites. Several epidemiological studies have shown that an increase in exposure to HDMs is associated with an increase in the prevalence of sensitization and asthma, whereas mite avoidance leads to a decrease in respiratory symptoms of sensitized asthmatic subjects. Sensitized subjects have specific immunoglobulin G and E (IgG and IgE) humoral responses, as well as proliferative T-cell responses to HDM allergens. Experimental exposure to HDM allergens induces bronchoalveolar inflammatory responses, that are characterized by the recruitment and activation of eosinophils, mastocytes, neutrophils, monocytes and lymphocytes. The cysteine protease activity of Der p 1 (a major allergen of D. pteronyssinus) has been shown to increase airway mucosal permeability, and may thereby contribute to the pathogenesis of airway inflammation and hyperresponsiveness by nonimmunological mechanisms. These epidemiological and experimental data support the recommendations for mite avoidance, especially in persons at high risk of developing asthma.

Allergens

Respiratory symptoms and peak expiratory flow in survivors of the Nyos disaster.

In August 1986, gases from the Nyos volcanic lake killed 1,746 persons in northwestern Cameroun, but 1,500 others living in the affected area survived. Gas emanations contained carbon dioxide, sulfur dioxide, and hydrogen sulfide. The objective of this study was to evaluate the delayed respiratory consequences of the inhalation of such volcanic gases. Two groups of subjects living in the same area, exposed (Nyos group; n = 381) or not exposed (control group; n = 128) to Nyos gases, were evaluated with a short questionnaire and by measurement of peak expiratory flow (PEF, percent predicted) in March 1991. Eleven percent of the subjects smoked, more often men than women (23% vs 4%; p < 0.001). In the whole population (exposed and unexposed), smoking was associated with a 3.6-fold increase in the frequency of cough (p < 0.001) and with a 6-fold increase in the frequency of sputum production (p < 0.005), but not with a decrease in PEF. There was no difference in the frequency of dyspnea, cough, sputum production, and PEF between Nyos and control groups. We conclude that 55 months after the emanation of gases from Nyos volcanic lake, there was no difference in respiratory symptoms, and PEF between survivors who inhaled volcanic gases and control subjects, whereas smoking was associated with cough and sputum production.

Adolescent

[Treatment of obstructive sleep apnea syndrome].

Obstructive sleep apnea syndrome (OSAS) is a chronic disorder in which the subject experiences an abnormally large number of episodes of more or less complete and prolonged ventilatory arrest due to pharyngeal obstruction leading to fragmented sleep pattern and reduced arterial oxygen saturation. OSAS produces invalidating daytime symptoms and appears to be associated with cardiovascular complications and overmortality. Diagnosis is based on an exploration of the sleeping pattern with recording of ventilation function, arterial oxygen saturation, heart rate, and electrophysiological characteristics (polysomnography). Prevalence of a high apnea index (more than 5 per hour of sleep) associated with day-time somnolence may be as high as 3% of the population in the 30 to 60 year age range. Current treatment is mainly based on nasal continuous positive airway pressure given via the nasal route during sleep and pharyngeal surgery (uvulopalatopharyngoplasty). Surgery is reserved for subgroups of patients with anatomic abnormalities and free of contraindications for anesthesia. Continuous positive pressure is always effective in case of symptomatic apnea and has a favorable effect on several associated complications. It can be proposed for any patient with OSAS but its use is limited due to incomplete compliance (approximately 70%). It appears that patients with particularly severe disease benefit most. Thus the ANDEM experts recommend treatment for all symptomatic patients with 30 or more episodes of apnea or hypopnea per hour of sleep during night-time exploration. Below this threshold, electrophysiological recordings are required to eliminate another cause of fragmented sleep which could explain the symptomatology despite a moderately elevated apnea index. Once the treatment has been started, regular surveillance is recommended. In addition, general health and nutritional counselling (weight reduction, smoking cessation, interruption of alcohol consumption and use of sedatives) should be proposed but usually have minimal and transitory effect.

Databases, Bibliographic

Nasal response to capsaicin in patients with allergic rhinitis and in healthy volunteers: effect of colchicine.

We studied the effect of nasal administration of capsaicin in eight patients with allergic rhinitis and eight healthy subjects. We also studied the effect of colchicine, a drug known to inhibit microtubular axonal transport of peptides, on nasal response to capsaicin in these subjects. Colchicine or placebo was administered orally in a double-blind, randomized, crossover manner with a 35 day wash-out interval. Nasal challenge was performed on the last day of each period of treatment, using increasing doses of capsaicin (10(-9) to 3 x 10(-5) mmol). Capsaicin induced a dose-dependent decrease in nasal airflow conductance (active posterior rhinomanometry) (p < 0.002) that was greater in patients with allergic rhinitis (0.40 +/- 0.02 to 0.20 +/- 0.03) than in healthy subjects (0.44 +/- 0.01 to 0.35 +/- 0.02) (p = 0.0001). Capsaicin provoked a greater number of sneezes in patients with allergic rhinitis than in healthy subjects (p < 0.001), but the amount of nasal secretions was similar in these two groups of subjects. In nasal lavage fluid, capsaicin induced an increase in total, epithelial, and neutrophil cell counts in patients with allergic rhinitis (each comparison, p < 0.05), but not in healthy subjects. Capsaicin induced a slight, although not significant, increase in the concentration of elastase in nasal lavage fluid in patients with allergic rhinitis (p = 0.07), but not in healthy subjects. Albumin concentration decreased in nasal lavage fluid in both groups of subjects (p < 0.05). The tendency of capsaicin to increase neutrophil elastase in nasal lavage fluid of patients with allergic rhinitis was not observed after treatment with colchicine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Physiological roles of the respiratory epithelium].

The epithelium of the airways plays a complex role in the organism's defence system against aggressive inhaled agents. Classically, the continuous cell layer of the epithelial mucosa acts as a protective barrier, but physiological role is much more complex and varied. The airway epithelium transports secretions by a collaborative effect of the ciliary movements and the rheological properties of the mucosa resulting from hydro-electrolytic movements occurring transepithelially. The epithelium participates in bronchial inflammatory response by interactions with inflammatory cells in the mucosal itself and by its capacity to produce free radicals and inflammatory mediators. Its membrane enzymes also participate in regulating neurogenic inflammation. A further role involves repairing damage which could compromise mucosal integrity. The airway epithelium participates in the immune defence system by interacting with lymphocytes and probably also by its capacity to express class II HLA molecules responsible for antigen presentation. Finally, the epithelium participates in anti-infectious mechanisms via its micro-organism receptors, its relationship with immune cells and inflammatory cells, its participation in mucociliary clearance and finally by the secretion of antiinfectious molecules (lysozymes, free radicals) by the mucosa.

Bronchi

Clinical practice guidelines: from methodological to practical issues.

The main goal of clinical practice guidelines is to help clinical decision by practitioners, who can not integrate in their daily practice all the published data concerning new technologies and knowledge. Guidelines also have growing applications in the ethical, legal, socio-economic, public policy and health care funding fields. This article describes the various methodologies that have been proposed to develop guidelines. These methods rely to varying degrees on formal methods of analysis of scientific evidence and expert opinions. Then a step by step process is described, that should ensure a rigorous, feasible and explicit guideline development and lead to valid and applicable recommendations. In order for guidelines to be used, they have to be efficiently implemented. Respective efficiency and justification of educational and coercive methods of implementation are discussed.

Clinical Competence

Transforming growth factor-beta in human aqueous humor.

The transforming growth factor-beta s are peptide growth factors known to play a central role in wound healing. Using a specific, in vitro assay of cell growth inhibition, we have detected transforming growth factor-beta (TGF-beta) in 24/24 aqueous humor specimens from eyes undergoing cataract extraction with intraocular lens implantation. The amount of TGF-beta ranged from 2.3 to 8.1 ng/ml (mean +/- SD = 4.5 +/- 1.7 ng/ml), with 61% present in the active form. Subtyping of TGF-beta was performed by addition of antibodies specific for the beta 1 and beta 2 isoforms to the growth inhibition assay, and confirmed with a sandwich enzyme-linked immunosorbent assay. None of the TGF-beta detected was of the beta 1 isoform; in contrast, the beta 2 isoform was present in every sample, implying that it might have originated from ocular tissues. The presence of this potent modulator of tissue repair in aqueous humor suggests a role in the healing processes following intraocular surgery, including glaucoma filtration surgery.

Aged

Cone adaptation in age-related maculopathy.

Cone adaptation was measured in patients with age-related maculopathy (ARM) and age-matched controls. A red stimulus was used to selectively bias responses toward cone function and adaptation was measured 5, 10, 20, and 40 degrees eccentric to fixation. The ARM patients' thresholds were elevated by 1 log unit at 5 and 10 degrees, with the threshold difference reducing to 0.5 log units at 40 degrees. Curves of the form log (threshold luminance) = ae-bt + c (where t is time and a, b, and c are constants) were fitted to each adaptation curve; a procedure involving differentiation of the above equation was used to estimate the constant parameters. Time constants of cone recovery (1/b) were derived for each fitted curve. No significant difference was found between the time constants of the two test groups. Our data suggest that cone adaptation is significantly affected in patients with ARM, with raised cone thresholds occurring for areas well into the peripheral retina. We suggest that the effect is mediated by a reduction in the number of functional cones, which elevates the final cone thresholds without altering the adaptation time constant. Our findings imply that age-related "maculopathy" may not be confined to the macular area, and that early signs of the degeneration may be present in the peripheral retina even when central acuity is normal.

Adaptation, Physiological

Life stress and risk of precancerous cervical lesions: a pretest directed by the life stress model.

PURPOSE/OBJECTIVES: To present the results of a pilot study to pretest instruments designed to measure selected variables named in the Life Stress Model, a model of health outcomes. Additional aims were to determine the effect of completing personal risk assessments for precancerous squamous-cell intraepithelial lesions of the cervic (SIL) on receptivity to cervical cancer prevention information and to extend knowledge of stressful life events experienced by inner-city women attending high-risk health clinics. DESIGN: Cross-sectional. SAMPLE: 20 adult women attending high-risk prenatal or human immunodeficiency virus (HIV) outpatient clinics in one of two New York City hospitals. Most were recovering drugs abusers; half were diagnosed with HIV infections. METHODS: Data were collected by self-report using standard measures. Demographics, medical histories of immunosuppressive states, and investigator-developed screening inventories of behavioral and dietary risk factors associated with SIL also were administered. MAIN RESEARCH VARIABLES: Life event stressors, psychological state, social support, symptom distress, and SIL diagnosis. FINDINGS: Instruments met acceptable psychometric standards for internal consistency, but the standard measure of stressful life events did not capture the full range of stressors experienced by this group of patients: hovering relatives, abusive spouses, HIV diagnosis, changes in welfare benefits, the HIV status of the unborn, and mandatory foster care. Although unable to recall cancer histories of family members, about half of the women who completed study instruments were interested in receiving more information cervical cancer. Exploratory analyses suggest that women diagnosed with SIL experience more psychological distress and family disfunction than women without SIL. CONCLUSIONS: Completing personal SIL risk assessments may stimulate patients' receptivity to cancer risk factor information. Health outcomes studies guided by the Life Stress Model may prove fruitful. IMPLICATIONS FOR NURSING PRACTICE: Cancer risk factor assessments may be an important method for promoting receptivity to cancer prevention information.

Adult