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1.
Proc Natl Acad Sci U S A ; 116(52): 26474-26483, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31843883

RESUMO

Efforts to confront the challenges of environmental change and uncertainty include attempts to adaptively manage social-ecological systems. However, critical questions remain about whether adaptive management can lead to sustainable outcomes for both ecosystems and society. Here, we make a contribution to these efforts by presenting a 16-y analysis of ecological outcomes and perceived livelihood impacts from adaptive coral reef management in Papua New Guinea. The adaptive management system we studied was a customary rotational fisheries closure system (akin to fallow agriculture), which helped to increase the biomass of reef fish and make fish less wary (more catchable) relative to openly fished areas. However, over time the amount of fish in openly fished reefs slowly declined. We found that, overall, resource users tended to have positive perceptions about this system, but there were negative perceptions when fishing was being prohibited. We also highlight some of the key traits of this adaptive management system, including 1) strong social cohesion, whereby leaders played a critical role in knowledge exchange; 2) high levels of compliance, which was facilitated via a "carrot-and-stick" approach that publicly rewarded good behavior and punished deviant behavior; and 3) high levels of participation by community actors.

2.
Nat Sustain ; 2(7): 551-559, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35342825

RESUMO

Achieving effective, sustainable environmental governance requires a better understanding of the causes and consequences of the complex patterns of interdependencies connecting people and ecosystems within and across scales. Network approaches for conceptualizing and analyzing these interdependencies offer one promising solution. Here, we present two advances we argue are needed to further this area of research: (i) a typology of causal assumptions explicating the causal aims of any given network-centric study of social-ecological interdependencies; (ii) unifying research design considerations that facilitate conceptualizing exactly what is interdependent, through what types of relationships, and in relation to what kinds of environmental problems. The latter builds on the appreciation that many environmental problems draw from a set of core challenges that re-occur across contexts. We demonstrate how these advances combine into a comparative heuristic that facilitates leveraging case-specific findings of social-ecological interdependencies to generalizable, yet context-sensitive, theories based on explicit assumptions of causal relationships.

4.
J Laryngol Otol ; : 1-5, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24666920

RESUMO

Objectives: To investigate rates of septorhinoplasty and rhinoplasty in Scotland between 2006 and 2010, and to establish the impact of government legislation. Methods: Data on the rates of rhinoplasty and septorhinoplasty were collected and analysed according to specialty, region and year. Results: In 2006, 754 septorhinoplasty and rhinoplasty cases were recorded (147 per million population), rising to 893 (171 per million population) in 2010. Mean annual rates per million population were 152 (87 per cent of procedures) in ENT, 13.9 (8 per cent) in plastic surgery and 8.7 (8 per cent) in oromaxillofacial surgery. After 2009, there was a 43 per cent reduction in the rhinoplasty rate (p < 0.0001), although the oromaxillofacial surgery rate increased by 68 per cent (p < 0.05). Over the same period, the septorhinoplasty rate increased in ENT (46 per cent, p < 0.0001), and declined in plastic surgery (24 per cent, p = 0.49) and oromaxillofacial surgery (45 per cent, p = 0.05). Overall, the rate for rhinoplasty plus septorhinoplasty only declined by 1 per cent. There was significant regional variation. Conclusion: Overall, septorhinoplasty rates have increased and rhinoplasty rates have decreased. There was only a 1 per cent decrease in the overall rate following the 2009 legislation. Practice differs between regions.

5.
Perfusion ; 29(5): 443-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24534886

RESUMO

Cerebral embolization during pediatric cardiac surgery may be an underappreciated source of subsequent neurodevelopmental impairment. Transcranial Doppler ultrasound is a neuromonitoring tool that can provide intraoperative surveillance for cerebral embolization. We hypothesized that increased cerebral embolic signals detected during infant cardiac surgery would be associated with worse neurodevelopmental outcomes at follow-up. A study group of 24 children who underwent infant cardiac surgery with transcranial Doppler detection of cerebral embolic signals returned at intermediate follow-up for standardized neurodevelopmental assessment. The children were evaluated using two neurocognitive tests and the parents completed two questionnaires regarding observed behavior. Statistical analysis assessed for correlation between the number of cerebral embolic signals at surgery and the results of the neurodevelopmental assessment. Of the 67 test parameters analyzed, five showed a significant association with the number of embolic signals, yet, all in the contrary direction of the clinical hypothesis, likely representing a Type I error. Thus, in this small cohort of patients, the number of cerebral embolic signals detected during infant cardiac surgery was not shown to be associated with worse neurodevelopmental outcomes at intermediate follow-up. A larger study is probably necessary to ascertain the potential influence of cerebral embolic signals on eventual neurologic outcomes in children. The clinical relevance of cerebral embolic signals during pediatric cardiac surgery remains undetermined and deserves further investigation.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Circulação Cerebrovascular , Desenvolvimento Infantil , Embolização Terapêutica , Cardiopatias Congênitas , Ultrassonografia Doppler Transcraniana , Cognição , Seguimentos , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/terapia , Humanos , Lactente , Recém-Nascido , Masculino
8.
J Laryngol Otol ; 125(12): 1225-31, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21767430

RESUMO

OBJECTIVE: To present our experience of running a consultant-based otolaryngology emergency care service for more than five years. MATERIALS AND METHODS: In 2003, we developed a system of consultant-based emergency service: consultants spent a week on-call providing a dedicated emergency service, with routine commitments cancelled. RESULTS: Our new system had advantages over traditional working practices in terms of consultant involvement, trainee education, continuity and efficiency. It also reduced disruption to elective commitments for both consultants and registrars. This system was fundamental to the successful review of all urgent (and in future elective) cases within target periods. Only 31 per cent of new referrals to the consultant emergency clinics required a further appointment. Good teamwork and flexibility in working arrangements have been essential to the success of this service. CONCLUSION: Given that health service changes have reduced junior trainee working hours and numbers, and that patients increasingly expect to be treated by trained doctors, our new consultant-based emergency service has merit. Although implementation in other units may differ, we recommend this new service, for the above reasons.


Assuntos
Plantão Médico/organização & administração , Consultores , Serviço Hospitalar de Emergência/organização & administração , Corpo Clínico Hospitalar/organização & administração , Otolaringologia/organização & administração , Tolerância ao Trabalho Programado , Competência Clínica , Continuidade da Assistência ao Paciente/organização & administração , Educação Médica Continuada/organização & administração , Reforma dos Serviços de Saúde , Humanos , Corpo Clínico Hospitalar/educação , Inovação Organizacional , Otolaringologia/educação , Encaminhamento e Consulta/organização & administração , Escócia , Carga de Trabalho
9.
Eur Arch Otorhinolaryngol ; 268(7): 1005-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21327998

RESUMO

To establish the effect of tracheostomy on nasal function and quality of life. Teaching Hospital, Scotland, UK. Cross-sectional case-control study. Two groups of patients were selected; a group of ten patients who underwent surgical tracheostomy and a control group of ten patients with confirmed or suspected head and neck malignancy that did not require tracheostomy. Two questionnaires, the SNOT-22 quality of life instrument, and the Rhinogram nasal symptoms score were used to evaluate each group. For the Rhinogram questionnaire the median total score was 13.5 for the tracheostomy group and 2 for the control group (P = 0.02) whilst for the SNOT-22, the mean total scores were 39 and 29, respectively (P = 0.205). The tracheostomy group scored worse for all Rhinogram questions, and for the anosmia score this was independently statistically significant (5 vs. 0 units, P = 0.001). The tracheostomy group most commonly identified "loss of smell & taste" as their most important symptom, compared with only 2 subjects in the control group. Tracheostomy can give rise to nasal symptoms. This needs to be addressed in the routine follow up of these patients.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Cavidade Nasal/cirurgia , Transtornos do Olfato/etiologia , Distúrbios do Paladar/etiologia , Traqueostomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Escócia , Resultado do Tratamento
11.
Clin Exp Allergy ; 40(2): 242-50, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19895590

RESUMO

BACKGROUND: When presented with results from clinical measurements or research findings, clinicians must first make an interpretation of their importance, not only in statistical terms, but also the 'clinical importance' given the size of the change observed. To do this, they require an understanding of the relationship between their outcome measures, and the patient's perception of change. The minimal clinically important difference (MCID) illustrates this relationship by calculating the smallest change in a given outcome that is meaningful to a patient. There are few reports of calculated MCIDs in the Rhinology literature. OBJECTIVE: To calculate MCIDs for common subjective and objective outcome measures in allergic rhinitis (AR). METHODS: Nine randomized, blinded, placebo-controlled clinical trials in intermittent and persistent AR (pooled subjects, n=204) were analysed using anchor- and distribution-based approaches, applying regression and meta-analysis techniques. RESULTS: MCIDs were obtained for the Mini Rhinoconjunctivitis Quality of Life Questionnaire: 0.4 units, peak nasal inspiratory flow: 5 L/min and total nasal symptoms score: 0.55 units. Nasal NO measurement changes had no correlation with patient perceptions of benefit. CONCLUSION: Estimates of MCIDs were obtained for common subjective and objective rhinological outcomes. MCIDs can and should be applied by physicians interpreting research findings, as well as researchers reporting their findings. We can then be confident that our changes in practice will be of perceptible benefit to the patient.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/psicologia , Método Duplo-Cego , Humanos , Óxido Nítrico/análise , Qualidade de Vida , Análise de Regressão , Rinite Alérgica Perene/fisiopatologia , Sensibilidade e Especificidade , Inquéritos e Questionários , Resultado do Tratamento
12.
J Laryngol Otol ; 123(10): 1160-2, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19573257

RESUMO

OBJECTIVES: To establish the safety and effectiveness of nurse-led triage of otolaryngology out-patient referrals. METHOD: One hundred consecutive general practitioner referrals were reviewed by two consultants, two specialist registrars, two foundation year two senior house officers and two otolaryngology nurses. One of the nurses had received triage training. All referrals were triaged as 'urgent', 'soon' or 'routine' by each rater. RESULTS: The triage-trained nurse's results demonstrated good agreement with those of the senior consultant (80 per cent). This agreement was similar to that with the other consultant (77 per cent) and the specialist registrars (79 and 82 per cent). Weighted kappa statistics (correcting for chance agreement) showed that the triage-trained nurse had the second closest agreement to the senior consultant (0.66). After the actual out-patient appointments, retrospective review of the patients' case notes revealed that none had been triaged inappropriately by the trained nurse, and no urgent cases had been missed. CONCLUSIONS: Triage of out-patient referrals by trained ENT nurses is safe and effective, and is an acceptable alternative to traditional consultant vetting of referrals.


Assuntos
Otolaringologia/normas , Padrões de Prática em Enfermagem/normas , Triagem/normas , Humanos , Relações Interprofissionais , Otolaringologia/educação , Ambulatório Hospitalar , Estudos Prospectivos , Encaminhamento e Consulta/normas , Triagem/métodos
13.
Clin Exp Allergy ; 39(3): 409-16, 2009 03.
Artigo em Inglês | MEDLINE | ID: mdl-19187327

RESUMO

BACKGROUND: End-organ hyperreactivity is an important feature of the allergic airway. There are no data directly comparing the responsiveness to treatment of different nasal provocation tests (NPT). OBJECTIVE: We compared the effect of levocetirizine on nasal adenosine 5'-monophosphate (AMP) with specific allergen challenge in patients with intermittent and persistent allergic rhinitis (AR). METHODS: Patients with AR were randomized in double-blind cross-over fashion to receive single doses of levocetirizine 5 mg or identical placebo, with nasal challenge performed 12 h after dosing. Sixteen participants completed per protocol. Nasal AMP or allergen challenge was conducted on separate days with 1- and 2-week washout periods in between, respectively. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after each challenge. The primary end-point was the provocative concentration of AMP or allergen causing a 20% drop in the PNIF (PC(20)). RESULTS: The time-profile for PNIF recovery [area under the 60 min time-response curve as % PNIF change (min)] were significantly attenuated for AMP challenge, as mean difference [95% confidence interval (CI)]: 11.57 (3.87, 19.25), P=0.005 and for allergen challenge: 17.82 (0.11, 35.53), P=0.04. A highly significant correlation was shown between methods for the area under the curve: (R=0.86, P<0.001). A statistically significant correlation was also seen for the PC(20): (R=0.94, P<0.001). PC(20) improvement amounted to a 1.26 (95% CI 0.16, 2.35) and 0.16 (95% CI -0.41, 0.73) doubling-dilution shifts for allergen and AMP challenges, respectively. Bland-Altman plots confirmed good agreement between methods. CONCLUSION: A high correlation and statistical agreement has been demonstrated between AMP and allergen challenge for all outcome measures. In particular, the recovery profile after NPT is a sensitive and discriminatory measure of anti-allergic treatment.


Assuntos
Monofosfato de Adenosina/farmacologia , Alérgenos/farmacologia , Cetirizina/uso terapêutico , Testes de Provocação Nasal/métodos , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Adulto , Idoso , Alérgenos/imunologia , Área Sob a Curva , Cetirizina/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nariz/efeitos dos fármacos , Nariz/imunologia , Nariz/fisiopatologia , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/fisiopatologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Resultado do Tratamento , Adulto Jovem
14.
Clin Exp Allergy ; 37(5): 696-703, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17456217

RESUMO

INTRODUCTION: The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER). METHODS: Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 microg or 400 microg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios. RESULTS: Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 microg, and 12.9% (4.8-20.9, P=0.009) by FP 400 microg. The 400-100 microg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 microg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose. CONCLUSION: FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER.


Assuntos
Androstadienos/administração & dosagem , Glucocorticoides/administração & dosagem , Rinite Alérgica Perene/tratamento farmacológico , Monofosfato de Adenosina , Adolescente , Adulto , Idoso , Androstadienos/efeitos adversos , Androstadienos/uso terapêutico , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Feminino , Fluticasona , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Provocação Nasal/métodos , Qualidade de Vida , Resultado do Tratamento
15.
Allergy ; 62(1): 73-80, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17156345

RESUMO

BACKGROUND: Asthma and allergic rhinitis are manifestations of a single unified allergic airway, for which the best treatment is uncertain. OBJECTIVE: To compare the anti-inflammatory efficacy in the unified allergic airway of combined oral mediator antagonism and combined topical steroid. METHODS: Subjects with asthma and perennial allergic rhinitis entered a randomized double blind crossover study comparing montelukast 10 mg and cetirizine 10 mg to extra-fine inhaled beclomethasone 400 mcg/day and intranasal beclomethasone 200 mcg/day, each taken once daily for 2 months, after 2-week placebo washouts. Measurements were made after each washout and randomized treatment, comprising: methacholine PC20, exhaled and nasal nitric oxide, blood eosinophils and eosinophilic cationic protein, symptoms, lung and nasal function tests. RESULTS: Seventeen patients completed per protocol. For PC20 and exhaled nitric oxide, only combined topical steroid produced improvements (P < 0.005) from placebo baseline. Combined steroid was superior by a 0.93 (95% CI 0.14-0.93, P < 0.05) doubling dilution difference for PC20 and a 0.99 (95% CI 0.9-15.1, P < 0.01) doubling difference for exhaled nitric oxide. Both treatments attenuated eosinophils and eosinophilic cationic protein, and reduced nasal symptoms (P < 0.05). Only steroid improved nasal nitric oxide (P=0.05) and asthma symptoms (P < 0.05). Neither treatment affected lung or nasal function tests. CONCLUSION: Combined topical steroid and combined mediator antagonism both attenuated systemic inflammation in the unified allergic airway, but only the former reduced bronchial and nasal inflammatory markers. The relevance of this to exacerbations and airway remodelling needs to be defined.


Assuntos
Antialérgicos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Rinite Alérgica Perene/tratamento farmacológico , Acetatos/administração & dosagem , Administração Tópica , Adolescente , Adulto , Idoso , Beclometasona/administração & dosagem , Cetirizina/administração & dosagem , Estudos Cross-Over , Ciclopropanos , Método Duplo-Cego , Vias de Administração de Medicamentos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Sulfetos
16.
J Laryngol Otol ; 120(12): 1049-54, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17059620

RESUMO

In general, patients with malignant tumours of the skull base have a poor prognosis. Treatment may have a disfiguring physical and disabling mental effect on patients. To evaluate the effect of treatment on physical and mental quality of life in patients with skull base malignancy, we conducted a cross-sectional patient survey of 18 patients treated for such tumours, using the University of Washington (version 4) quality of life questionnaire and the hospital anxiety and depression scale. The total quality of life score (median value) was 980 (550-1125). Patients with anterior skull base malignancy scored lower than those with lateral skull base malignancy (p=0.003). In general, the worst individual domain scores were: mood (64 per cent); activity (69 per cent); and, specifically for patients with anterior skull base malignancy, taste (54 per cent, p=0.004) and anxiety (60 per cent, p=0.034). One-third of skull base cancer patients were at risk of suffering from mental distress and psychiatric morbidity (indicated as a score of more than seven on the hospital anxiety and depression scale).


Assuntos
Transtornos Mentais/etiologia , Qualidade de Vida , Neoplasias da Base do Crânio/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Neoplasias da Base do Crânio/patologia , Inquéritos e Questionários , Resultado do Tratamento
17.
Allergy ; 61(11): 1319-25, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17002709

RESUMO

BACKGROUND: Response to a single dose nasal adenosine monophosphate challenge has been used as a surrogate inflammatory marker for allergic rhinitis. Attenuation of response following intranasal corticosteroid would further validate the challenge. OBJECTIVE: To assess the effect of 4 weeks of 200 mcg once daily mometasone furoate nasal spray on a simplified (single 160 mg dose) nasal adenosine monophosphate challenge. METHODS: Twenty participants with persistent allergic rhinitis completed a double blind placebo-controlled crossover study. Outcome measures were the peak nasal inspiratory flow and total nasal symptoms score responses to nasal adenosine monophosphate challenge, as well as domiciliary peak nasal inspiratory flow and patient symptom diary cards. RESULTS: Mometasone significantly (P < 0.05) attenuated response time profiles vs. placebo for peak nasal inspiratory flow but not total nasal symptom scores. For the maximum percentage fall this amounted to a mean difference of 9.6% (95% confidence interval 1.3-17.9%). The coefficient of variation for repeatability was 48.7%. Improvements were seen in prechallenge and domiciliary measurements of peak nasal inspiratory flow (both P < 0.05) and total nasal symptom scores (both P < 0.01). CONCLUSIONS: Mometasone attenuates the peak nasal inspiratory flow response to a single 160 mg nasal adenosine monophosphate challenge. Such challenges have been shown to be sensitive to the effects of antihistamines, antileukotrienes and now nasal steroids. This further supports their application as surrogate inflammatory markers for therapeutic trials in allergic rhinitis, potentially as 20 min challenges which can be conducted in a non-hospital setting.


Assuntos
Monofosfato de Adenosina , Antialérgicos/administração & dosagem , Pregnadienodiois/administração & dosagem , Rinite Alérgica Perene/diagnóstico , Monofosfato de Adenosina/administração & dosagem , Administração Intranasal , Adolescente , Antialérgicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Furoato de Mometasona , Testes de Provocação Nasal , Pregnadienodiois/efeitos adversos , Rinite Alérgica Perene/tratamento farmacológico , Resultado do Tratamento
18.
Clin Exp Allergy ; 36(5): 676-84, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16650054

RESUMO

BACKGROUND: Addition of H(1) antagonists to intranasal corticosteroid treatment of allergic rhinitis (AR) is common in clinical practice and recommended by guidelines, despite some evidence that the additive benefits are negligible. OBJECTIVE: To assess additional benefits of 5 mg levocetirizine dihydrochloride in seasonal AR patients using 200 mcg fluticasone propionate nasal spray once daily. METHODS: In a double-blind placebo-controlled crossover study of 27 patients, following 2 weeks without treatment, subjects used fluticasone with levocetirizine or identical placebo for 2 weeks each. Assessments were the Juniper mini Rhinoconjunctivitis Quality-of-Life Questionnaire (mini-RQLQ), domiciliary peak nasal inspiratory flow (PNIF), total nasal symptoms (TNS) scores and nasal nitric oxide concentrations. Effects were interpreted and tested against minimal clinically important differences. RESULTS: Add-on effects for levocetirizine vs. placebo excluded any clinically significant benefits: mean effects (one sided 95% confidence intervals) were mini-RQLQ -0.11 (-0.34), PNIF +0.57 (+5.23), and TNS -0.11 (-0.60). Numbers needed to treat (95% confidence intervals) by outcome were mini-RQLQ 14 (5 to 49), PNIF 4 (3-7), and TNS 3 (2-6). No significant within or between treatment effects were seen for nasal nitric oxide. CONCLUSION: Contrary to current practice, the present results demonstrate that for the majority of patients, antihistamine add-on to effective nasal steroid treatment is inappropriate. Further work is required to confirm that this is also true in the most severe cases, and the available evidence needs to be put into guidelines and implemented.


Assuntos
Androstadienos/administração & dosagem , Antialérgicos/administração & dosagem , Cetirizina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Piperazinas/administração & dosagem , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Intranasal , Adolescente , Adulto , Idoso , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Eosinófilos/química , Feminino , Fluticasona , Humanos , Inalação/fisiologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análise , Nariz/fisiopatologia , Pólen/imunologia , Qualidade de Vida , Rinite Alérgica Sazonal/fisiopatologia , Resultado do Tratamento
20.
Bioorg Med Chem ; 7(12): 2823-33, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10658586

RESUMO

Solution and solid phase strategies for the synthesis of alpha-galactose based neoglycopeptide derivatives 2-13 were developed. Neoglycopeptides generated were tested for the inhibition of verotoxin binding to globotriosylceramide (Gb3) using ELISA. Among all of the compounds tested, only the lipid derivatives of neoglycopeptides, 11, 12 and 13 were found to be inhibitors, IC50 = 2.0 mM (11b and 12c) and 0.2 mM (11c and 13c). All of the inhibitors (11b, 11c, 12c and 13c) have a similar branching of the two alpha-galactosyl units at the N-terminal glycine residue of a short peptide and a lipid moiety attached at the C-terminal site. Both of these factors seem to be crucial for the inhibition. It is interesting to note that the inhibitors have only a portion of the natural trisaccharide ligand. The secondary groups either may contribute in sub-site oriented interactions with the protein receptors or may mimic the internal sugar units of the cell-surface ligand, Gb3.


Assuntos
Toxinas Bacterianas/antagonistas & inibidores , Toxinas Bacterianas/metabolismo , Galactose/química , Glicopeptídeos/química , Glicopeptídeos/farmacologia , Triexosilceramidas/metabolismo , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Sequência de Carboidratos , Desenho de Fármacos , Glicopeptídeos/síntese química , Humanos , Técnicas In Vitro , Ligantes , Espectroscopia de Ressonância Magnética , Modelos Biológicos , Dados de Sequência Molecular , Toxina Shiga I , Relação Estrutura-Atividade
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