Visual analogue scale in patients treated for allergic rhinitis: an observational prospective study in primary care: asthma and rhinitis.

BACKGROUND: Allergic rhinitis (AR) severity is evaluated using scores such as Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) and total symptom score (TSS). However, a simple assessment is needed to enable physicians to evaluate the severity of the AR and the efficacy of the treatment. OBJECTIVE: The main objective was to validate visual analogue scale (VAS) as a simple quantitative tool to assess the burden of AR in primary care. METHODS: The study was multi-centre prospective observational conducted in patients consulting general practitioners for symptomatic rhinitis. VAS, RQLQ and TSS6 were assessed at the consultation day and 14 days later, and changes were analysed using paired test. Correlations between VAS, RQLQ and TSS6 were assessed. Cut-off levels for VAS, which discriminate significant from insignificant changes, were established using Receiver Operating Characteristic curves. RESULTS: A total of 990 patients were included in the study. According to allergic rhinitis and its impact on asthma classification, mild intermittent rhinitis was diagnosed in 20% patients, mild persistent in 17%, moderate/severe intermittent in 15% and moderate/severe persistent in 48%, at the consultation day. At day-14, rhinitis symptoms and QoL improved significantly in almost all patients. Impairment incurred by AR and assessed with VAS improved also. The established cut-off variation of 23 mm for VAS was associated with a cut-off variation of 0.5 for RQLQ. Sensitivity analysis with RQLQ and TSS6 scales confirmed the aptitude of the cut-off value (23 mm) to discriminate changes in symptoms and QoL. CONCLUSION AND CLINICAL RELEVANCE: The VAS can detect with high sensitivity the variations of symptoms and QoL in patients with AR.

Presentation and treatment of acute maxillary sinusitis in general practice: a French observational study.

This survey-based study was conducted to determine the characteristics that influence the diagnosis and treatment patterns of acute maxillary sinusitis among general practitioners in France. Questionnaires were sent to 467 physicians and requested to be completed for the next 4 adult (≥ 15 years) patients diagnosed with acute maxillary sinusitis. A total of 397 physicians responded with eligible data on 1585 patients (57.5% female; mean age, 42.3 years). The most common presenting signs and symptoms were moderate-to-severe nasal obstruction (80.4%), pain on sinus palpitation (76.8%), facial pain (74.5%), rhinorrhea (70.4%), and headache (63.6%). Local treatments were prescribed in 93.2% of cases, including nasal lavage (52.1%), vasoconstrictors (42.2%), and intranasal corticosteroids (38.7%). Almost all patients (99%) were prescribed oral treatment including antibiotics (86.5%), analgesics (56.3%), antipyretics (53.7%), and expectorants/mucolytics (45.6%). Symptoms were indicated as having a moderate to very significant effect on quality of life areas including activities of daily living (71.6% of patients), leisure (63.1%), and professional/school activities (59.2%). The diagnosis and management patterns of acute maxillary sinusitis among general practitioners in France are generally consistent with the 2007 European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) guidelines.

Desloratadine relieves nasal congestion and improves quality-of-life in persistent allergic rhinitis.

BACKGROUND: Symptoms of allergic rhinitis (AR), particularly nasal congestion, can impair quality-of-life (QoL). However, only a modest correlation exists between these symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, suggesting that both be evaluated for a complete assessment of health. METHODS: Subjects with a > or =2-year history of moderate-to-severe AR to dust mite or cat dander were randomized to desloratadine 5 mg/day (n = 293) or placebo/day (n = 291) for 28 days. Primary endpoint was change from baseline in a.m./p.m. nasal congestion score. Secondary outcomes included change from baseline in total nasal symptom score, individual symptom scores and RQLQ scores (completed on days 1, 7, and 28). RESULTS: The Allergic Rhinitis and its Impact on Asthma criteria for persistent allergic rhinitis (PER) were fulfilled by 99% of subjects in the placebo arm. Between-treatment difference in a.m./p.m. nasal congestion score, observed from day 8 onward, significantly favored desloratadine (P = 0.0003). Desloratadine significantly improved a.m./p.m. nasal congestion and RQLQ scores after 1 week and at treatment end (P < 0.05). Improvements in 5 of 7 RQLQ domain scores exceeded the minimal important difference. On days 7 and 28, desloratadine was also significantly superior to placebo in mean change from baseline in a.m./p.m. total nasal symptom score and rhinorrhea score (both P < or = 0.01). Symptomatic benefit was primarily driven by improvement in nasal congestion and rhinorrhea. CONCLUSIONS: Desloratadine 5 mg/day significantly improved symptoms associated with PER, including nasal congestion, and provided significant improvement in QoL after 1 week of treatment.

[Patient preference survey on the lack of taste and odor of Nasonex nasal spray. Which impact on compliance to treatment?]. / Enquête de préférence patients sur l'absence de saveur et d'odeur du Nasonex en pulvérisation nasale. Quel impact sur l'observance du traitement ?

In order to assess the acceptability of a new scent-free formulation of mometasone furoate (Nasonex) among allergic rhinitis patients, who already have been treated by the scented formulation of Nasonex, a phone survey was performed with a sample of 216 patients recruited by Nasonex GP's prescribers and pharmacists. The aim of this survey is to assess the diagnosis modalities, the allergic rhinitis characteristics and associated symptoms in one hand and in the other hand, the main reasons which led them to prefer a new scent-free formulation, in comparison with the only commercialized scented mometasone furoate (Nasonex) at the time when this survey was conducted. The impact of unscented Nasonex on patient's compliance to treatment was also assessed. This survey confirms that the GP is the key actor who usually establish the allergy diagnosis and the interrogatory is the principle method used. The prick test was more often and significantly used in 35% of the perennial rhinitis instead of 19% in seasonal allergic rhinitis (p < or = 0.05). When the diagnosis of allergy was established by an allergologist, 89% of them used a prick test. In this survey, asthma was associated in 24% of the patients, particularly in who suffering from perennial allergic rhinitis. 85% of patients rate their smell as globally good. 75% of the treated patients were interested by the new unscented formulation of Nasonex, regardless of the type of their rhinitis, seasonal or perennial. About 60% of patients stated that the lack of odor will led them to be more compliant to their treatment.

Mutation in the Trapalpha/Ssr1 gene, encoding translocon-associated protein alpha, results in outflow tract morphogenetic defects.

Translocon-associated protein complex (TRAP) is thought to be required for efficient protein-specific translocation across the endoplasmic reticulum membrane. We created a mutation in the Trapalpha gene that leads to the synthesis of a truncated TRAPalpha protein fused to ShBle-beta-galactosidase. Analysis of Trapalpha cDNAs reveals that among three different messenger RNAs expressed in the mouse, one of them encodes a slightly larger protein that differs in its C-terminal end. This mRNA, specific for skeletal muscle and heart, is only expressed after birth. Homozygous Trapalpha mutant pups die at birth, likely as a result of severe cardiac defects. Indeed, the septation of the proximal part of the outflow tract is absent, resulting in a double-outlet right ventricle. Studies of protein secretion in transfected embryonic fibroblasts reveal that the TRAP complex does not function properly in homozygous mutant cells and confirm, in vivo, the involvement of TRAP in substrate-specific translocation. Our results provide the first in vivo demonstration that a member of the TRAP complex plays a crucial role in mammalian heart development and suggest that TRAPalpha could be involved in translocation of factors necessary for maturation of endocardial cushions.

Gene trap insertion reveals two open reading frames in the mouse SSeCKS gene: the form predominantly detected in the nervous system is suppressed by the insertion while the other, specific of the testis, remains expressed.

Scaffold proteins play an important role in regulating signal transduction by targeting kinases and phosphatases in close proximity to their relevant substrates. SSeCKS protein has been described as a protein kinase C and A (PKC/PKA) anchoring protein as well as a PKC substrate with a tumor suppressor activity. In this study, we report the generation, via gene trapping in embryonic stem cells of mice carrying an insertion in the mouse SSeCKS gene. Through the molecular analysis of the insertion site, we show that SSeCKS contains two alternative promoters directing the synthesis of mRNAs (P1- and P2-mRNA), encoding two different proteins, one of which would be a truncated form of the other. Interestingly, these RNAs are differentially expressed, P2 being found exclusively in the male germ line, while P1 exhibits a dynamic and wider pattern of expression during embryonic development and in the adult; its expression is predominant in the nervous system. Finally, we show that P1- but not P2-mRNA expression is abolished by the insertion and furthermore that mice homozygous for the mutation lack SSeCKS in all tissues except the male germ cells. Nevertheless and surprisingly, these mice do not exhibit any obvious phenotype. The functional implications of these observations are discussed.

Alkaloids from Aspidosperma species from Bolivia.

Two Bolivian Aspidosperma species were investigated. The seed and stem bark of Aspidosperma macrocarpon Mart. contain six known alkaloids: (-)-vincadifformine, ervinceine, kopsanone, kopsinine, kopsanol in the seed, and kopsanone, kopsinine, kopsanol, 18-epikopsanol in the stem bark. The stem bark of Aspidosperma pyrifolium Mart. contains eleven known alkaloids: (-)-vincadifformine, O-demethylpalosine, haplocine, N-formylaspidospermidine, vallesine, demethoxyaspidospermine, palosine, (-)-aspidospermine, aspidospermidine, akuammicine, tubotaiwine, beside the two new bases dehydroxyhaplocidine and 10-methoxyaspidospermidine.

Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality.

Targeted disruption of the insulin receptor gene (Insr) in the mouse was achieved using the homologous recombination approach. Insr+/- mice were normal as shown by glucose tolerance tests. Normal Insr-/- pups were born at expected rates, indicating that Insr can be dispensable for intrauterine development, growth and metabolism. However, they rapidly developed diabetic ketoacidosis accompanied by a marked post-natal growth retardation (up to 30-40% of littermate size), skeletal muscle hypotrophy and fatty infiltration of the liver and they died within 7 days after birth. Total absence of the insulin receptor (IR), demonstrated in the homozygous mutant mice, also resulted in other metabolic disorders: plasma triglyceride level could increase 6-fold and hepatic glycogen content could be five times less as compared with normal littermates. The very pronounced hyperglycemia in Insr-/- mice could result in an increased plasma insulin level of up to approximately 300 microU/ml, as compared with approximately 25 microU/ml for normal littermates. However, this plasma level was still unexpectedly low when compared with human infants with leprechaunism, who lack IR but who could have extremely high insulinemia (up to > 4000 microU/ml). The pathogenesis resulting from a null mutation in Insr is discussed.

Alkaloids from leaves and stems of Vallesia glabra.

Eleven known indole alkaloids: vallesine, aspidospermine, 11-methoxydichotine, apparicine, tubotaïwine, vincadifformine, condylocarpine, (-)-rhazinilam, aspidospermatine, haplocidine, and 18-oxohaplocidine, have been isolated from leaves and stems of Vallesia glabra (Cav.) Link. (Apocynaceae) from Bolivia. Analysis of 2 D NMR spectra complete previous 1H and 13C data for vallesine, aspidospermine, and 11-methoxydichotine.