[Professional stressors and common mental health disorders: Causal links?] / Stresseurs professionnels et troubles mentaux courants : quels liens de causalité ?

According to the World Health Organization, depression has become the leading cause of disability in the world, contributing significantly to the burden of health issues especially in the industrialized countries. This is a major public health problem, with potential impact on work climates, productivity at work and the continued existence of the organizations. Some recent studies have examined potential links between professional factors and common mental health disorders, but none have demonstrated a direct causal link. OBJECTIVE: In the present study, we explored possible links between work-related stressors and common mental health disorders, with the objective of determining priority mental health prevention axes. METHOD: The study used a life trajectory method. We compared professional stressors and difficulties present in other spheres of life in the last five years between two groups: a group of 29 participants with common mental health disorders during the last five years (depression, anxiety disorders, eating disorders, substance use disorders, pathological gambling), and a group of 29 participants who have not experienced a mental health disorder in the last five years. Data were collected from semi-structured interviews with the participants using a life course analysis method. Each participant was interviewed during two or three meetings of two to three hour duration. Questions regarding difficulties in different spheres of life and mental health were asked. More precisely, data were collected with regards to the presence or absence of mental health disorders in the last five years and the nature of mental health disorders and difficulties. Moreover, we collected data pertaining to the most important positive and negative events in different spheres of life that were present in the last five years, including family life, romantic relationships, social life, academic difficulties, losses and separations, episodes of personal difficulties, financial difficulties as well as protective factors. Regarding professional difficulties present in the last five years, data were collected on different kinds of adversities such as difficulties in finding a job, periods of unemployment, frequent job changes, difficult working conditions, discrimination, difficult working relationships with colleagues and with employers, moral harassment and family-work conflicts. RESULTS: Participants with common mental health disorders are more concerned about having general professional difficulties at work and about having difficult working relationships with employers. However, difficulties related to other spheres of life do not differentiate the two groups. CONCLUSION: It is possible that the work environment is linked to common mental health disorders. In particular, having general professional stressors at the work place and having difficult relationships with employers can impact the occurrence of common mental health disorders. Inversely, these stressors at work can be the consequence of a common mental health disorder. Complementary studies are of interest. Professional stressors can constitute an essential part in the occurrence of common mental health disorders. Thus, the workplace seems a priority environment for deploying effective mental health prevention strategies. Moreover, this can be a strategy for organizations to improve the work climate and to increase productivity.

Enhanced isochoric heating from fast electrons produced by high-contrast, relativistic-intensity laser pulses.

Thin, mass-limited targets composed of V/Cu/Al layers with diameters ranging from 50 to 300 microm have been isochorically heated by a 300 fs laser pulse delivering up to 10 J at 2x10{19} W/cm{2} irradiance. Detailed spectral analysis of the Cu x-ray emission indicates that the highest temperatures, of the order of 100 eV, have been reached when irradiating the smallest targets with a high-contrast, frequency-doubled pulse despite a reduced laser energy. Collisional particle-in-cell simulations confirm the detrimental influence of the preformed plasma on the bulk target heating.

Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours.

PURPOSE: C-1311 is a member of the novel imidazoacridinone family of anticancer agents. This phase 1 trial was designed to investigate the safety, tolerability and preliminary anti-tumour activity of C-1311. PATIENTS AND METHODS: This was a phase 1, inter-subject dose escalating and pharmacokinetic study of intravenous (IV) C-1311, administered weekly during 3consecutive weeks followed by 1week rest (constituting 1 cycle) in subjects with advanced solid tumours. RESULTS: Twenty-two (22) patients were treated with C-1311, the highest dose given was 640mg/m(2). All subjects experienced one or more treatment-related adverse events (AEs). The most frequently observed treatment-related AEs were neutropaenia and nausea (50% each), followed by vomiting (27%), anaemia (23%), asthenia (23%) and diarrhoea (18%). Most treatment-related AEs were of Common Terminology Criteria for Adverse Events (CTCAE) grades 1-2, except for the blood and lymphatic system disorders, which were primarily of grades 3-4. The recommended dose (RD) of C-1311 administered as once weekly IV infusions for 3weeks every 4weeks is 480mg/m(2), with the dose limiting toxicity (DLT) being grade 4 neutropaenia lasting more than 7days. Treatment at this dose offers a predictable safety profile and excellent tolerability. CONCLUSION: The safety profile and preliminary anti-tumour efficacy of C-1311, observed in this broad-phase dose-finding study, warrants further evaluation of the compound.

c-Src tyrosine kinase co-associates with and phosphorylates signal transducer and activator of transcription 5b which mediates the proliferation of normal human B lymphocytes.

c-Src is the normal human cellular protein homologue of the viral oncogene v-src. c-Src activity was reported recently to increase in CD40-activated human B lymphocytes, suggesting its involvement in proliferation. To elucidate the exact role of c-Src in this process, we investigated the effects of c-Src over-expression on normal B lymphocyte growth. B lymphocytes purified from human peripheral blood were infected with Ad5/F35 vector encoding either a constitutively active c-Src (c-Src/dominant-positive) or a dominant-negative c-Src (c-Src/DN). Little variation of B lymphocytes expansion could be observed between control enhanced yellow fluorescent protein and c-Src/dominant-positive-infected cells. In contrast, over-expression of c-Src/DN results in a 40% inhibition of B lymphocyte expansion. These results suggest that DN c-Src may compete with endogenous c-Src, resulting in partial inhibition of a transcriptional pathway involved in B lymphocyte proliferation. We demonstrate further that c-Src can phosphorylate signal transducer and activator of transcription 5b (STAT5b) on tyrosine 699 and that c-Src and STAT5b co-associate during B lymphocyte proliferation. These results confirm an important role for c-Src in the expansion of normal human B lymphocytes in vitro, in which c-Src may regulate STAT5b in the intracellular signalling pathway important for the proliferation of normal human B lymphocytes.

[Review of the literature on the psychoemotional reality of women with vulvodynia: difficulties met and strategies developed]. / Une recension des écrits concernant la réalité psychoaffective des femmes ayant une vulvodynie: difficultes rencontrées et stratégies développées.

BACKGROUND: Within the past three decades, increased attention has been placed on the study of vulvodynia -- an unexplained chronic vulvular discomfort felt without any related pathology. In addition to its physical implications, vulvodynia has a psychosocial dimension. OBJECTIVE: The purpose of the current article is to present a review of the literature on the psychoemotional reality of women with vulvodynia. METHOD: A systematic literature review was conducted in the main social sciences databases, such as Dissertation Abstracts, Current Contents and PsycINFO. RESULTS: Although some discrepancies were found in study results, the review of the literature revealed that women with vulvodynia are often confronted with identity and psychological difficulties, which are, in turn, influenced by social standards regarding sexuality and femininity. To cope with these difficulties, women develop different strategies to decrease the stress related to pain and enhance their psychological well-being. CONCLUSION: The psychological and relational difficulties experienced by women with vulvodynia are not only due to the physical pain but also to the meaning they attribute to it, often influenced by social expectations related to heterosexuality and femininity. Hence, it is important to assist these women by increasing their knowledge on the psychosocial aspects of their experience while taking into account influences from the social context.

Bacillus licheniformis proteases as high value added products from fermentation of wastewater sludge: pre-treatment of sludge to increase the performance of the process.

Wastewater sludge is a complex raw material that can support growth and protease production by Bacillus licheniformis. In this study, sludge was treated by different thermo-alkaline pre-treatment methods and subjected to Bacillus licheniformis fermentation in bench scale fermentors under controlled conditions. Thermo-alkaline treatment was found to be an effective pre-treatment process in order to enhance the proteolytic activity. Among the different pre-treated sludges tested, a mixture of raw and hydrolysed sludge caused an increase of 15% in the protease activity, as compared to the untreated sludge. The benefit of hydrolysis has been attributed to a better oxygen transfer due to decrease in media viscosity and to an increase in nutrient availability. Foam formation was a major concern during fermentation with hydrolysed sludge. The studies showed that addition of a chemical anti-foaming agent (polypropylene glycol) during fermentation to control foam could negatively influence the protease production by increasing the viscosity of sludge.

[Bringing back scleral contact lenses]. / Vers une réhabilitation des verres scléraux?

PURPOSE: Although old generations of scleral contact lenses were totally replaced by soft and hard contact lenses, new designs and materials have recently allowed the successful use of nonfenestrated scleral contact lenses in patients who are intolerant to regular contact lenses. These new scleral contact lenses form a bridge over the cornea, which is thus permanently bathed in a saline reservoir. METHODS: Retrospective study in patients suffering from corneal diseases altering the vision and/or responsible for ocular discomfort, and who are intolerant to conventional contact lenses. RESULTS: Fifteen eyes (10 patients) were fitted with specially designed scleral contact lenses. The mean follow-up was 16 months (range, 1-31 months). The scleral lenses were indicated for optical and/or therapeutic reasons: keratoconus (3 eyes), corneal grafts (7 eyes), refractive surgery (2 eyes), corneal dysplasia (2 eyes), and Stevens-Johnson syndrome (1 eye). Optical results and tolerance were excellent except for one eye. CONCLUSION: New nonfenestrated scleral contact lenses provide a good alternative for patients who are intolerant to conventional contact lenses.

Female sex selection using clomiphene citrate and albumin separation of human sperm.

BACKGROUND: This study was undertaken to assess whether the use of clomiphene citrate in conjunction with albumin-separated sperm would alter the sex ratio (expressed as the proportion of males) towards females and, if so, whether this skewing was due solely to the induction of ovulation. METHODS: The sex ratios of 184 single and 42 twin births at five assisted reproduction biology clinics were determined. The normal approximation to the binomial distribution was used to determine significant differences between these sex ratios and the established sex ratios for single, twin and combined (single and twin) non- and ovulation-induced births. RESULTS: The non-ovulation-induced sex ratios for singletons (51.4%) and twins (50.2%) were greater than the treatment singleton (27.7%; P < 0.001) and twin (33.3%; P < 0.01) sex ratios respectively. Correspondingly, the non-induced sex ratio for combined births (51.4%) was greater than the treatment sex ratio (28.8%; P < 0.001). The previously established induced singleton and twin sex ratios (48.1%) were lower than the non-induced sex ratio (51.4%), but higher than the treatment singleton (27.7%; P < 0.001) or twin (33.3%; P < 0.03) sex ratios. The ovulation-induced combined ratio (48.1%) was less than the non-induced combined (51.4%) sex ratio, although greater than the treatment combined sex ratio (28.8%; P < 0.001). CONCLUSION: Clomiphene citrate in conjunction with albumin-separated sperm decreased the sex ratio; a reduction that was not exclusively due to induction of ovulation.

Preparation, characterization, and luminescence properties of gallium-metal face-to-face diporphyrins (M = H(2), GaL, Ru(CO)(OH), Co).

The preparation and characterization of a new series of mixed metal cofacial anthracene-bridged diporphyrins (DPA) containing a GaL fragment (L = OMe, OH) and another metallic center (M = GaL, Ru(CO)(OH), Co, and H(2) (i.e. free base)) are reported. The luminescence properties at 298 and 77 K, in degassed EtOH solution, are also reported, and are characterized by a weak pipi fluorescence (2 < tau(F) < 7 ns) arising from the low energy Q-bands (S(1)-->S(0)). In the mixed diporphyrin systems, a strong pipi fluorescence is detected from the free base, while the transition metalloporphyrins of Co(II) and Ru(II) do not emit. The homobimetallic di[Ga(OMe)] species exhibits an unprecedented double (pi)(pi) fluorescence arising from the two lowest energy absorption Q-bands. On the basis of a comparison with photophysical data on GaL monoporphyrins, the weak fluorescence and absence of phosphorescence for most cases indicate efficient intramolecular quenching. To define structural features, the X-ray structures of (DPA)[Ga(OMe)](2) (2), (DPA)[Ga-(OH)-Ru(CO)] (5a), and (DPA)[Ga(OMe)-Ru(MeOH)(CO)] (5b) have been obtained. The structures of 5a and 5b demonstrate an interesting aspect of the structural chemistry of these ligands related to the internal methoxide and methanolic ligands in 5b (resulting in a large interplanar separation and center-to-center distance) and the internal metal-bridging hydroxyl ligand in 5a (resulting in a small interplanar separation and center-to-center distance). These data support previously reported discussions on the ability of the DPA and the DPB analogue (diporphyrinylbiphenylenyl) ligands to open and close their "bite" around the binding pocket between the porphyrin macrocycles.

Successful planned pregnancy following endometrial ablation with the YAG laser.

In selected patients who previously have undergone YAG laser ablation of the endometrium and who have demonstrated normal intrauterine architecture, pregnancy as a planned event may be a reasonable and safe option.

Biochemical characterization of I-CmoeI reveals that this H-N-H homing endonuclease shares functional similarities with H-N-H colicins.

Endonuclease assays of the H-N-H proteins encoded by two group I introns in the Chlamydomonas moewusii chloroplast psbA gene revealed that the CmpsbA.1 intron specifies a site-specific DNA endonuclease, designated I-CMOE:I. Like most previously reported intron-encoded endonucleases, I-CMOE:I generates a double-strand break near the insertion site of its encoding intron, leaving 3' extensions of 4 nt. This enzyme was purified from Escherichia coli as a fusion protein with a His tag at its N-terminus. The recombinant protein (rI-CMOE:I) requires a divalent alkaline earth cation for DNA cleavage (Mg(2+) > Ca(2+) > Sr(2+) > Ba(2+)). It also requires a metal cofactor for DNA binding, a property shared with H-N-H colicins but not with the homing endonucleases characterized to date. rI-CMOE:I binds its recognition sequence as a monomer, as revealed by gel retardation assays. K:(m) and k(cat) values of 100 +/- 40 pM and 0.26 +/- 0.04 min(-1), respectively, were determined. Replacement of the first histidine of the H-N-H motif by an alanine residue abolishes both rI-CMOE:I activity and binding to its substrate. We propose that this conserved histidine residue plays a role in binding the metal cofactor and that such binding induces a structural modification of the enzyme which is required for DNA recognition.

Preparation and characterization of [[M(dmb)2]TCNQ.xTCNQo]n polymers (M=Cu,Ag; dmb = 1,8-diisocyano-p-menthane; x = 0, 0.5, 1.0, 1.5; TCNQ = 7,7,8,8-tetracyano-p-quinodimethane) and design of new semi- and photoconducting organometallic materials.

New thermoplastic organometallic materials of the type [[M(dmb)2]TCNQ.xTCNQo.y solvent], (M = Cu(I), Ag(I); dmb = 1,8-diisocyano-p-menthane; TCNQ = 7,7,8,8-tetracyano-p-quinodimethane, x = 0, 0.5, 1.0, 1.5; solvent = none, THF or toluene) have been prepared and characterized from X-ray powder diffraction patterns, X-ray crystallography (for some Ag polymers), DSC, and conductivity measurements. While the [[M(dmb)2]TCNQ.xTCNQo]n polymers (M = Cu,Ag; x = 0, 0.5) are insulating, the others (x = 1.0 and 1.5) are semiconducting, and the relative conductivity is found to be a function of the molecular weight and crystallinity. The [[Cu(dmb)2]TCNQ.1.5TCNQ]n material is also photoconducting, while the Ag analogue is not. Photochemical and luminescence quenching experiments in the solid-state established that the Cu+ center and TCNQo act as electron donor and acceptor, respectively, in this photoprocess. Finally photocells of the type glass/SnO2/[Cu(dmb)2]TCNQ.TCNQo]n + 0.5 acceptor/Al (acceptor = TCNQo, C60 and TCNN (13,13,14,14-tetracyano-5,12-naphthacenequinodimethane)) have been designed and characterized. The quantum yields (number of photoproduced electrons/number of photons) are as follows: TCNQ, 1.6 x 10(-4), C60, 5 x 10(-5), TCNN, 3.0 x 10(-4) at lambdaexc = 330 nm. X-ray data for [[Ag(dmb)2]TCNQ.2THF]n: space group P2(1/c), monoclinic, a = 13.5501(10), b = 9.9045(10), c = 32.564(2) A, beta = 91.130(10) degrees, Z = 4. X-ray data for [[Ag(dmb)2]TCNQ.0.5TCNQo.0.5 toluene]n: space group P2(1/c), monoclinic, a = 14.3669(19), b = 9.1659(3), c = 34.012(3) A, beta = 92.140(8) degrees, Z = 4. X-ray data for [[Ag(dmb)2]TCNQ.1.5TCNQo]n: space group C2/c, monoclinic, a = 25.830(11), b = 9.680(2), c = 42.183(19) A, beta = 104.87(4) degrees, Z = 8. X-ray data for [[Ag(dmb)2]DCTC]n: space group P2(1/a), monoclinic, a = 26.273(3), b = 9.730(3), c = 31.526(3) A, beta = 112.12(2)degrees, Z = 4.

Comparison of budesonide Turbuhaler with budesonide aqua in the treatment of seasonal allergic rhinitis. Rhinocort Study Group.

OBJECTIVE: To compare the effect of budesonide Turbuhaler 400 microg/day with budesonide aqua 256 microg/day in the treatment of seasonal allergic rhinitis (SAR). Secondarily to ascertain patients' preferences for the two nasal devices and to assess quality of life. DESIGN: Randomized, multicentre, double-blind, double- dummy, parallel groups study. SETTING: Private practices and hospital clinics in Ontario, Quebec and Manitoba. POPULATION: Two hundred and eighty-four out-patients with SAR, who were symptomatic during the ragweed season, volunteered for enrolment (243 randomized). RESULTS: Mean daily nasal symptom scores were significantly reduced with treatment. There were no statistically significant changes from baseline for eye symptoms. Most patients (more than 80%) achieved substantial control of their symptoms with budesonide. The most common nasal and non-nasal adverse events for both groups were epistaxis and headache. Turbuhaler was easier to use and more convenient to carry, had less of an unpleasant taste, and caused less nasal irritation than the aqua spray. More than twice as many patients preferred Turbuhaler to the aqua spray (69% versus 31%). Improvement in quality of life from baseline to clinic visits was statistically significant in both groups. CONCLUSION: Once daily use of 256 mg of budesonide aqua and 400 mg of budesonide Turbuhaler are equally safe and efficacious in the treatment of SAR. Patients preferred the budesonide powder formulation delivered via Turbuhaler two to one over the aqua formulation.

The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study.

BACKGROUND: Considerable debate swirls about the validity of symptoms described by many people after ingestion of monosodium glutamate (MSG), and the question has remained unresolved largely because of a paucity of well-designed challenge studies. METHODS: We conducted oral challenge studies in self-identified MSG-sensitive subjects to determine whether they had a statistically significant difference in the incidence of their specific symptoms after ingestion of MSG compared with placebo. First, 5 gm MSG or placebo was administered in random sequence in a double-blind fashion. Subjects who reacted only to a single test agent then underwent rechallenge in random sequence in a double-blind fashion with placebo and 1.25, 2.5, and 5 gm MSG. A positive response to challenge was defined as the reproduction of > of 2 of the specific symptoms in a subject ascertained on prechallenge interview. RESULTS: Sixty-one subjects entered the study. On initial challenge, 18 (29.5%) responded to neither MSG nor placebo, 6 (9.8%) to both, 15 (24.6%) to placebo, and 22 (36.1%) to MSG (p = 0.324). Total and average severity of symptoms after ingestion of MSG (374 and 80) were greater than respective values after placebo ingestion (232 and 56; p = 0.026 and 0.018, respectively). Rechallenge revealed an apparent threshold dose for reactivity of 2.5 gm MSG. Headache (p < 0.023), muscle tightness (p < 0.004), numbness/tingling (p < 0.007), general weakness (p < 0.040), and flushing (p < 0.016) occurred more frequently after MSG than placebo ingestion. CONCLUSIONS: Oral challenge with MSG reproduced symptoms in alleged sensitive persons. The mechanism of the reaction remains unknown, but symptom characteristics do not support an IgE-mediated mechanism. According to Food and Drug Administration recommendations, the symptoms, originally called the Chinese restaurant syndrome, are better referred to as the MSG symptom complex.

Budesonide aqueous nasal spray and pressurized metered dose inhaler in the treatment of adult patients with seasonal allergic rhinitis.

Budesonide, a topical corticosteroid used in the treatment of seasonal allergic rhinitis, can be administered to the nose as an aerosol via a pressurized metered dose inhaler (pMDI) or as a metered nasal pump spray. Studies have shown that about 64% (256 micrograms) of a nominal dose of 400 micrograms budesonide pMDI preparation is delivered to the patient compared with 100% of the nominal dose of the pump spray. The present study was undertaken to assess the efficacy and safety of budesonide delivered via a nasal pMDI twice daily (Rhinocort pMDI, at 400 micrograms/day) with an aqueous suspension of budesonide delivered via a metered nasal pump spray once daily (Rhinocort Aqua, at 256 micrograms/day or 400 micrograms/day). The multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in 318 patients (154 men, 164 women; aged 12-67 years) with ragweed-induced seasonal allergic rhinitis. A 1-week baseline period was followed by a 3-week treatment. Nasal symptoms were recorded by the patients, adverse events were noted, an overall evaluation of treatment efficacy was made, and urine cortisol and creatinine levels were measured. Substantial or total control of symptoms was achieved in 83.8% of patients treated with 256 micrograms of aqueous budesonide, 76.3% with 400 micrograms of aqueous budesonide, and 80.8% with 400 micrograms of budesonide pMDI; these were all significantly different (p < 0.001) compared with placebo (23.4% of patients). There were no significant differences in the 24-hour urine cortisol levels between the groups and there were few, infrequent adverse events, similar between the groups and resolved completely on discontinuation of treatment. It was concluded that budesonide, given once daily as 256 micrograms or 400 micrograms in an aqueous suspension or twice daily as 400 micrograms in a pMDI provides good alleviation of the symptoms of seasonal allergic rhinitis with no significant risk of suppression of urine cortisol.

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients.

BACKGROUND: Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. OBJECTIVE: To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. METHODS: This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS: Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSIONS: Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Intranasal fluticasone propionate versus loratadine in the treatment of adolescent patients with seasonal allergic rhinitis.

Fluticasone propionate (FP) is a topical corticosteroid with minimal systemic activity. We examined safety and compared the efficacy of FP aqueous nasal spray, 200 micrograms every day with loratadine tablets, 10 mg by mouth every day in 240 adolescents with ragweed pollen-induced seasonal allergic rhinitis for 4 weeks in a randomized, double-blind, parallel-group study. Nasal and eye symptoms were recorded daily on a 4-point (0 to 3) scale. A higher percentage of symptom-free days was observed for nasal blockage on waking during treatment with FP (p < 0.0001). Significant results were also obtained for all other nasal symptoms when analyzed for both symptom-free days and symptom scores. No differences were found for eye irritation symptoms (p = 0.14). Morning and evening nasal peak inspiratory flow (PIF) was recorded daily by 57 subjects. FP treatment was associated wit significantly higher PIF values than loratadine both morning (p = 0.0051) and evening (p = 0.0036). A greater improvement over 4 weeks was observed for PIF morning values in the FP group (p = 0.008) but not for evening values (p = 0.358). Statistically significant correlations were found for nasal blockage and PIF in the morning (r = -0.54, p = 0.0001) and in the evening (r = -0.46, p = 0.008).

Respiratory infections and the autumn increase in asthma morbidity.

Unexplained autumn increases in hospital admissions for asthma have been reported in many countries, including the United States, Canada, England and Wales. To investigate the role of infection, the association was tested between hospital admissions for asthma and respiratory infections among preschool children in Metropolitan Toronto, Canada during the period 1981 to 1989. The seasonal pattern in overall hospital utilization was assessed by admissions for nonrespiratory diseases. Time series analysis was used to remove potentially confounding temporal trends and the influence of correlated errors. A fourfold increase in asthma admissions occurred between July and October unaccompanied by similar increases in nonrespiratory admissions. Admissions began increasing during the third week of August, peaked during the third week in September, and slowly decreased during November and December. After adjusting for serial correlation, trends, climate, ambient air pollution and aeroallergens, the seasonal pattern of respiratory infection explained 14% of the variance in asthma admissions. Based on seasonal patterns, respiratory infection is the major identifiable risk factor for the large autumnal increase in asthma admissions.

Faster onset of action with topical levocabastine than with oral cetirizine.

This international multicentre, open-label, parallel-group trial was undertaken to compare the therapeutic efficacy and tolerability of topical levocabastine and oral cetirizine in patients with perennial allergic rhinoconjunctivitis, with particular reference to the comparative onset of action of the two drugs. A total of 207 patients were randomized to receive either levocabastine nasal spray (0.5 mg/ml, two sprays in each nostril twice daily) plus levocabastine eye drops as required (0.5 mg/ml, one drop in each eye twice daily p.r.n.) or cetirizine orally (10 mg once daily) with a treatment duration of 2 weeks. Onset of action was found to be significantly more rapid with levocabastine than with cetirizine for both nasal and ocular symptoms (p < 0.001). Within 15 min of study drug administration, 36% of levocabastine-treated patients reported relief from nasal symptoms and 32% relief from ocular symptoms compared with 10% and 17% of patients on cetirizine, respectively. At 1 h, the percentages of patients reporting relief were 76% and 38% for nasal symptoms, and 81% and 48% for ocular symptoms in the levocabastine and cetirizine treatment groups, respectively. At 8 h there were no differences between the two treatments. Overall therapeutic efficacy was found to be comparable in the two treatment groups over the 2-week study period with no significant intergroup differences in symptom severity or global therapeutic efficacy. Both drugs were well tolerated with no significant differences in the incidence or type of adverse reactions between the two groups. In conclusion, levocabastine eye drops and nasal spray are as effective and well tolerated as oral cetirizine for the treatment of perennial allergic rhinoconjunctivitis with the advantage of a significantly faster onset of action for both nasal and ocular symptoms.