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Biomedical subjects

G Philip

Publications and source records attributed to G Philip.

At least 19 recordsLinked to original sources
PubMed2006

Effect of montelukast on lung function in asthma patients with allergic rhinitis: analysis from the COMPACT trial.

BACKGROUND: The Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) trial demonstrated that montelukast added to budesonide (MNT + BD) was as efficacious as double the dose of budesonide (dBD) in improving morning peak expiratory flow (AM PEF) in adult asthmatics. Recent studies have demonstrated that montelukast is also effective in treating daytime and nighttime allergic rhinitis (AR) symptoms in asthmatic patients. This analysis was designed to examine whether asthmatic patients with comorbid AR respond differently than patients without comorbid AR in terms of asthma control (lung function). METHODS: There were 216 asthmatic patients in the MNT+BD group and 184 patients in the dBD group with AR. Treatment differences in the change from baseline in AM PEF were compared. Least square (LS) mean and 95% confidence interval (CI) were derived from an anova model adjusting for baseline and study site. RESULTS: There was a 9.2% increase in AM PEF from baseline in the MNT+BD group compared with a 6% increase in the dBD group. The LS mean difference [(MNT+BD)-dBD] was 14.2 l/min (P=0.028). Other secondary endpoints were similar between groups. CONCLUSION: In the subgroup of asthmatic patients with AR, a combined treatment approach that included montelukast and budesonide provided significantly greater efficacy in reducing airflow obstruction compared with doubling the dose of budesonide. These results support recommendations by the Allergic Rhinitis and its Impact on Asthma initiative that suggest a unified approach aimed at treating the airway inflammation common to both diseases is beneficial for the large proportion of asthmatics who also suffer from AR.

Acetates↗
PubMed2003

Expression of cysteinyl leukotriene synthetic and signalling proteins in inflammatory cells in active seasonal allergic rhinitis.

BACKGROUND: Cysteinyl leukotrienes (CysLTs) are bioactive lipids that have been shown to contribute to allergic and inflammatory diseases. Eosinophils and mast cells have the capacity to produce large amounts of CysLTs after allergic or non-allergic stimulation. Molecular identification of both the synthetic and signalling proteins in the CysLT pathway allows the investigation of expression of the CysLT enzymes and receptors in active allergic rhinitis. OBJECTIVE: We examined the expression of the proteins involved in the synthesis of CysLTs and the cysteinyl leukotriene-1 (CysLT1) and cysteinyl leukotriene-2 (CysLT2) receptors in inflammatory cells from patients with active seasonal allergic rhinitis. METHODS: Nasal lavage samples were obtained from patients during active seasonal allergic rhinitis. Specific cellular immunocytochemical techniques were used to detect the cysteinyl leukotriene synthetic proteins, namely 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and leukotriene C4 synthase (LTC4S). In situ hybridization and immunocytochemical techniques were used to identify the mRNA and proteins for the CysLT1 and CysLT2 receptors. RESULTS: 5-LO, FLAP and LTC4S, and the CysLT1 and CysLT2 receptors were expressed in the majority of eosinophils and in subsets of mast cells and mononuclear cells. 5-LO, FLAP and the CysLT1 receptor, but not LTC4S or the CysLT2 receptor, were expressed in a subset of nasal neutrophils. CONCLUSIONS: Our study demonstrates the presence of CysLT pathway proteins in key allergic and inflammatory cells from the upper airway of patients with active seasonal allergic rhinitis. Our expression data highlight the potential of CysLT-modifying agents to treat both upper and lower airway symptoms in patients suffering from allergic rhinitis and asthma.

5-Lipoxygenase-Activating Proteins↗
PubMed2003

Montelukast improves symptoms of seasonal allergic rhinitis over a 4-week treatment period.

BACKGROUND: Proinflammatory mediators such as the cysteinyl leukotrienes are important in the pathophysiology of allergic rhinitis. This study evaluated the efficacy and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, given once daily in the morning for treatment of seasonal (fall) allergic rhinitis for 4 weeks. METHODS: This was a randomized, double-blind trial with a placebo run-in and a 4-week treatment period. Patients (n = 1079) with a history of allergic rhinitis and a positive skin test to seasonal pollen allergens were assigned to placebo, montelukast 10 mg, or loratadine 10 mg. Symptoms were assessed with a daily diary. RESULTS: Montelukast was more effective than placebo in improving scores for the primary endpoint of daytime nasal symptoms (P = 0.003) and the secondary endpoints of night-time, composite, and daytime eye symptoms, patient's and physician's global evaluations of allergic rhinitis, and rhinoconjunctivitis quality-of-life (P </= 0.006). The positive control loratadine also improved scores for the primary endpoint (P </= 0.001) and the majority of the secondary endpoints (P < 0.03). When analyzed by week, the treatment effect of montelukast was more persistent than loratadine over all 4 weeks of treatment. CONCLUSION: Montelukast provided effective relief of seasonal allergic rhinitis symptoms when given once daily in the morning, showed significant and sustained improvement in symptoms of allergic rhinitis over 4 weeks of treatment, and was well-tolerated.

Acetates↗
PubMed2002

Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring.

BACKGROUND: Cysteinyl leukotrienes are important proinflammatory mediators believed to have a role in allergic rhinitis. OBJECTIVE: This multicentre, randomized, double-blind, placebo- and active-controlled trial evaluated the effectiveness and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, for treating patients with seasonal allergic rhinitis. METHODS: After a 3- to 5-day, single-blind placebo run-in period, 1302 male and female patients (aged 15-81 years) with active allergic rhinitis symptoms were randomly assigned to receive montelukast 10 mg (n = 348), loratadine 10 mg (n = 602), or placebo (n = 352) administered once daily at bedtime for 2 weeks during the spring allergy season. RESULTS: Mean patient characteristics and symptom scores at baseline were similar for the three treatment groups. The primary end-point, daytime nasal symptoms score (mean of nasal congestion, rhinorrhea, nasal pruritus, and sneezing scores; 0-3 scale), improved from baseline during treatment by (least squares mean, 95% confidence interval) - 0.37 (- 0.43, - 0.31), - 0.47 (- 0.52, - 0.43), and - 0.24 (- 0.29, - 0.18) in the montelukast, loratadine, and placebo groups, respectively (P < or = 0.001 comparing each active treatment with placebo). Mean changes from baseline in all other diary-based scores, including night-time and eye symptom scores, were significantly greater for each active treatment than for placebo. The rhinoconjunctivitis quality of life overall score improved significantly with montelukast and with loratadine as compared with placebo. Montelukast and loratadine showed a safety profile comparable to that of placebo. CONCLUSION: Montelukast is well tolerated and provides improvements in daytime and night-time symptoms, as well as quality of life parameters, for patients with seasonal allergic rhinitis.

Acetates↗
PubMed2001

Right and left atrial activation during external direct-current cardioversion shocks delivered for termination of atrial fibrillation in humans.

We examined the regional electrophysiologic effects of successful and unsuccessful direct-current cardioversion shocks on different right and left atrial regions in patients with sustained atrial fibrillation (AF). Patients with sustained AF undergoing external cardioversion underwent simultaneous mapping of the right and left atria. Electrogram changes after shock delivery, regional atrial activation, and effects of shock intensity were analyzed. Twenty-two patients with sustained AF received 52 shocks (mean 2.4/patient, 22 successful and 30 unsuccessful). The efficacy of 50, 100, 200, and 300 J was 18%, 39%, 100%, and 100%, respectively. In all 22 successful shocks, there was virtually simultaneous termination of electrical activity in all right and left atrial regions mapped. Unsuccessful shocks resulted in a significant increase in mean atrial cycle length at lateral right atrium, superior left atrium, and proximal, mid, and distal coronary sinus (p = 0.01), but not at the interatrial septum (p >0.2), which often disappeared before the next shock. This cycle length prolongation was accompanied by reduction in fragmented and chaotic electrograms (p <0.03) and emergence of discrete electrograms at all right and left atrial regions that persisted until the next shock. The changes in electrogram morphology failed to alter the surface electrocardiographic appearance of AF. There was no correlation between the shock intensity and the magnitude of these effects. We conclude that termination of AF with external cardioversion shocks is associated with the widespread extinction of regional atrial wave fronts. Unsuccessful shocks are associated with a temporary slowing of atrial activation at all regions except at the interatrial septum and emergence of organized and/or rapidly propagating wave fronts.

Adult↗
PubMed2000

Evaluation of the information and support services in the voluntary sector using a new P-C-P (pivotal-core-peripheral) attributes model.

This paper describes the development and use of a modified SERVQUAL research instrument for measuring the service quality of voluntary organizations from the perspective of their 'customers'. A series of focus group meetings were run with providers and users of the services to identify the appropriate dimensions of service quality. These were structured meetings led by the researchers addressing set questions in a group setting. The meeting enabled the identification of six different dimensions of service quality which neatly mapped on to the pivotal-core-peripheral (P-C-P attributes model [Philip and Hazlett, 1997]), which was developed after extensive research of existing models such as SERVQUAL. These dimensions were used to develop a questionnaire to assess service quality within the voluntary sector. The questionnaire was distributed to 2005 service users, representing eight voluntary organizations from across Northern Ireland. The research resulted in the development of a methodology and research instrument suitable for measuring service quality in the voluntary sector.

Community Mental Health Centers↗
PubMed1999

Is involvement of the surgical margins of large loop excision of the cervical transformation zone specimens for cervical intraepithelial neoplasia III a risk factor for persistent cervical intraepithelial neoplasia?

We aimed to test the hypothesis that patients with cervical intraepithelial neoplasia (CIN) III treated by large loop excision of the cervical transformation zone (LLETZ) are more likely to suffer recurrence of cervical abnormalities if the CIN reaches the margins of the index specimen. Three hundred and forty-five women treated by LLETZ in 1991, and 1992, and in whom the histological diagnosis was CIN III, were studied. The reports were reviewed and the cases were categorised as completely excised, incompletely excised, or undetermined. Cytological follow-up, or in some cases histological follow-up in the same year and in each of the 5 following years was tabulated. Follow-up data were recorded from the same and also surrounding institutions. The chi-squared test was used to compare the differences in recurrence rates between the three groups at the various points in time. A small advantage was demonstrated for those cases where excision was complete. This was statistically significant in the third following year (P=0.022). The resection margin status of LLETZ specimens for CIN III has only a minor effect on the likelihood of recurrence. Nevertheless, recording the status may be important in case of unexpected invasion. The relative reassurance the information will provide when the lesion has been excised may also be seen as worthwhile.

Journal Article↗
PubMed1999

Hyperosmolar saline induces reflex nasal secretions, evincing neural hyperresponsiveness in allergic rhinitis.

We investigated whether hyperosmolar saline (HS), applied via paper disk onto the septum of one nostril, induces a nasal secretory response. Furthermore, we examined whether this response is accentuated in patients with active allergic rhinitis (AR) compared with healthy volunteers. Unilateral HS produced significant nasal secretions both ipsilateral and contralateral to the site of challenge in the AR group and only ipsilaterally in the healthy group. The HS-induced nasal secretions were significantly greater in the AR vs. the healthy subjects. In a separate study, we ascertained that the nasal response to HS is neurally mediated and found that ipsilateral nerve blockade with lidocaine significantly attenuates the HS-induced secretions bilaterally. In another group of AR subjects, we determined whether nociceptive fibers were involved in this response and found that sensory nerve desensitization with repeated application of capsaicin attenuated the HS-induced nasal secretions. Finally, we determined whether the secretory hyperresponsiveness in AR is attributable to increased reactivity of submucosal glands rather than of nerves. We found that the dose response to methacholine, which directly stimulates the glands, was identical among AR and healthy subjects. We conclude that, in AR, nasal challenge with HS induces significantly greater reflex secretions involving capsaicin-sensitive nerve fibers, consistent with the notion of neural hyperresponsiveness in this disease.

Adolescent↗
PubMed1998

Comparison of nasal mucosal responsiveness to neuronal stimulation in non-allergic and allergic rhinitis: effects of capsaicin nasal challenge.

BACKGROUND: Neuronal involvement has been implicated in the pathophysiology of non-allergic and allergic rhinitis, contributing to the typical exacerbation of these conditions upon exposure to non-specific environmental irritants. OBJECTIVES: To determine if non-allergic and allergic rhinitis are characterized by increased responsiveness of the nasal mucosa to sensorineural stimulation. METHODS: Nasal challenges with capsaicin and its vehicle were performed in three groups of subjects -- non-allergic rhinitics, perennial allergic rhinitics, and healthy controls -- and resultant symptom scores, glandular secretion reflected by lactoferrin levels, and plasma extravasation reflected by albumin levels in nasal lavage fluid were compared. RESULTS: Capsaicin-sensitive nerve stimulation produced increases in symptom scores and lactoferrin levels which were similar among the three groups of subjects. On the other hand, only the group of subjects with allergic rhinitis demonstrated a significant capsaicin-induced increase in albumin levels and a trend in total protein levels. CONCLUSIONS: We conclude that non-allergic rhinitis is not characterized by increased responsiveness of capsaicin-sensitive nerve fibres; while allergic rhinitis is marked by hyperresponsiveness manifested as increased albumin leakage in nasal fluids. This may reflect the activity of an axonal reflex to sensorineural stimulation.

Administration, Intranasal↗
PubMed1998

A double blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics.

The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient. Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were randomised to receive either zuclopenthixol acetate or haloperidol. They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the same medication, no other anti-psychotic was given for the duration of the study. 50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating (p < 0.001). There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study. Both groups had minimal side effects. Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic.

Adult↗
PubMed1997

The effects of contact frequency and transport on the efficacy of the boar effect.

Ninety six Large White/Landrace cross-bred gilts were used in this study, sixteen gilts being allocated to each of six treatments. The treatments compared the effects on puberty attainment of exposing gilts to boar contact either 0, 1 or 3 times daily (C, D and 3D), with or without the addition of transport "stress" (T). Treatments began at a mean gilt age of 160 days and continued for 40 days. The duration of each period of boar contact was 20 min. Those gilts receiving transport "stress" were placed on a trailer daily for the first ten days of the study and driven at a constant speed for 20 min. There was no significant effect of transport alone on the timing of gilt puberty attainment. Boar exposure significantly increased the proportion of gilts attaining puberty within 40 days of the commencement of treatments (P < 0.05) compared with gilts not receiving boar contact. Boar exposure three times daily significantly reduced mean gilt age at puberty relative to no boar exposure (190.2 vs. 202.3 days of age respectively, P < 0.01) while once-daily boar exposure gave an intermediate value (196.7 days). In addition, a significant (P < 0.01) interaction occurred between boar contact frequency and transport in this study. It is concluded that (a) transport alone does not provide a significant stimulus for early puberty attainment in the gilt, (b) the pubertal response of the gilt to the boar effect is enhanced when boar contact occurs several times each day compared with a single boar contact period, and (c) a combination of frequent boar contact and transport may result in a greater degree of gilt puberty stimulation than frequent boar contact alone.

Adaptation, Physiological↗
PubMed1996

Hairy polyp of the oropharynx: an unusual cause of intermittent neonatal airway obstruction.

Oropharyngeal hairy polyps are rare benign congenital tumours that usually present at birth or shortly afterwards with acute upper airway obstruction or feeding difficulties. We describe a case of intermittent airway obstruction in a neonate caused by a mobile hairy polyp of the tonsil. This rare benign lesion proved difficult to diagnose because of its tendency to prolapse into the nasopharynx.

Airway Obstruction↗
PubMed1996

Inflammatory cellular influx follows capsaicin nasal challenge.

Capsaicin is a specific activator of sensory nerve endings. In rodents, mucosal application of capsaicin causes cells to infiltrate the tissue. To examine whether inflammatory-cell influx follows sensory-nerve activation in human airways, we delivered capsaicin (200 microM) nasal spray into the nares of 20 subjects (10 with allergic rhinitis and 10 normal), and measured the total leukocyte content of nasal lavage fluid obtained from 10 min to 4 h after the capsaicin challenge. Vehicle spray (1% EtOH in 0.9% saline) served as a control. Capsaicin challenge caused significant increases from prechallenge leukocyte counts at 10 min (p<0.03), 30 min (p<0.01), and 4 h (p<0.03) after challenge, but not at 1 h after challenge (p = 0.68). Vehicle challenge did not increase leukocyte counts. Differential counts (performed on the 13 of 20 subjects from whom adequate specimens for differential counts were obtained) showed that neutrophils, eosinophils, and mononuclear cells increased at 10 min, 30 min, and 4 h (all p < 0.04), but not at 1 h after capsaicin challenge. Comparing the rhinitic to the normal subjects, we found no significant differences in the cellular response to capsaicin. These data support a nonspecific inflammatory effect of sensory nerve activation in the human nose. Consequently, this work provides evidence that neurogenic inflammation can be induced in the human airway in vivo.

Adult↗
PubMed1996

Psychiatric presentation of Huntington's disease in a Malaysian family.

A 32-year-old Chinese lady presented to the Psychiatric Clinic with a history of change in personality for 2 years and abnormal movements for a year. After thorough investigations and observation a diagnosis of Huntington's Disease was made. Her elder brother was traced and found to have Huntington's Disease as well. He had a long standing history of antisocial behaviour and substance abuse long before the onset of the choreiform movements. Her younger brother also has choreiform movements for the last 2 years and had recent change in personality. Their mother also had abnormal movements and was recorded to be depressed and attempted suicide. The maternal grandfather had a mental illness and was warded at a mental institution till his death in 1942. Psychiatric presentation of Huntington's Disease in this Malaysian family is prominent and preceded the characteristic movements in the present generation.

Adult↗