Evaluation of the efficacy and safety of olopatadine and fexofenadine compared with placebo in Japanese cedar pollinosis using an environmental exposure unit.

BACKGROUND: Second-generation oral H1-antihistamines have become a mainstay of treatment for the symptoms of seasonal allergic rhinitis; however, the effect of olopatadine has not been widely reported to date. OBJECTIVES: To evaluate the efficacy of 2 oral H1-antihistamines, olopatadine and fexofenadine, in the treatment of the nasal symptoms of Japanese cedar pollinosis and their possible side effects. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study conducted in an environmental exposure unit (EEU). Twenty volunteers suffering from Japanese cedar pollinosis were randomly divided into 3 groups and exposed to cedar pollen in the EEU with oral administration of olopatadine hydrochloride (5 mg), fexofenadine hydrochloride (60 mg), or placebo 1 hour prior to pollen exposure. Nasal symptoms, activity impairment, and subjective sleepiness were self-assessed during the study period. Attention was measured using the digit cancellation test. The trial was repeated after 4 and 7 weeks. RESULTS: Compared with placebo, olopatadine significantly improved nasal symptoms and activity impairment during pollen exposure (P < .05). There was no significant relief of nasal discharge or nasal congestion with fexofenadine throughout the 5-hour exposure to cedar pollen. Furthermore, olopatadine significantly reduced nasal congestion during the first 2 hours, as well as sneezing and nasal discharge 4 hours after admission to the EEU compared with fexofenadine (P < .05). There was no significant difference in the effect on subjective sleepiness among the 3 groups, and all 3 agents had little effect on attention. CONCLUSIONS: These findings suggest that olopatadine is more effective than placebo and fexofenadine in improving nasal symptoms of Japanese cedar pollinosis.

Clinical effects of apple polyphenols on persistent allergic rhinitis: A randomized double-blind placebo-controlled parallel arm study.

BACKGROUND: We often encounter persistent allergic rhinitis due to house dust mites in the practice of otolaryngology, and its prevalence in Japan is high (18.7%). Persistent allergic rhinitis is usually treated with antihistamines and local steroids, but they often cause adverse effects such as sedation and drowsiness. Polyphenols derived from apples have been reported to suppress histamine release from rat cells, reduce auricular swelling in allergic mice, and alleviate skin inflammation in atopic patients. These effects suggest that apple polyphenols are effective for the treatment of various allergic disorders, but the results of their clinical use have not been reported. OBJECTIVE: To assess the effect of drinks containing apple polyphenols on clinical symptoms of persistent allergic rhinitis. METHODS: Thirty-three patients aged 15 to 65 years with moderate or severe persistent allergic rhinitis in whom the symptoms persisted for 3 years or longer were treated without apple polyphenols (control group), with a low dose of apple polyphenols, or with a high dose of apple polyphenols, and changes in the clinical symptoms were examined. RESULTS: Significant improvements were observed in sneezing attacks (P<.05) and nasal discharge (P<.01) in the high-dose group and in sneezing attacks (P<.05) in the low-dose group. Compared with the control group, an improvement was observed in sneezing attacks and nasal discharge in many patients of the polyphenol-treated groups. In terms of intranasal findings, a significant improvement was observed in swelling of the nasal turbinate in the low-dose group (P<.05). The percentage of patients who showed an improvement in swelling of the nasal turbinate was higher in the polyphenol-treated groups. CONCLUSIONS: We conclude that apple polyphenols are effective in alleviating symptoms of persistent allergic rhinitis.

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen.

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.

Improved nonpenetrating trabeculectomy with trabeculotomy.

PURPOSE: To examine surgical effects and complications of improved nonpenetrating trabeculectomy with trabeculotomy in glaucoma patients. METHODS: Glaucoma patients in two medical institutions underwent nonpenetrating trabeculectomy with sinusotomy with or without trabeculotomy, and the results were compared retrospectively in the two groups by evaluation of final intraocular pressure, drug score, and occurrence of postsurgical complications. RESULTS: Of the 63 eyes of 51 patients in this study, 31 were treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy and 32 eyes were treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy. The mean follow-up period was 17.0 months. The clinical features in both groups were similar in terms of age, presurgical intraocular pressure (P = 0.96), and presurgical drug score. The eyes treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy had significantly reduced intraocular pressures from 21.0 +/- 4.3 (mean +/- SD) to 15.8 +/- 6.3 mm Hg (P = 0.0003) and drug scores from 2.4 +/- 1.2 to 1.6 +/- 1.1 without postsurgical complications. The eyes treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy had significantly reduced intraocular pressures from 22.3 +/- 7.5 to 12.5 +/- 2.3 mm Hg (P < 0.0001) and drug scores from 2.5 +/- 1.9 to 0.9 +/- 1.3 without postsurgical complications. Thus, the eyes treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy had significantly lower intraocular pressures (P = 0.016) and drug scores than did those treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy. CONCLUSION: The authors obtained satisfactory results in reducing intraocular pressure by the combination of nonpenetrating trabeculectomy, sinusotomy, and trabeculotomy.

Terson syndrome: a case report suggesting the mechanism of vitreous hemorrhage.

OBJECTIVE: To present a patient with Terson syndrome and to propose a mechanism for vitreous hemorrhage. DESIGN: Observational case report. PARTICIPANT: A 50-year-old woman with subarachnoid hemorrhage and unilateral vitreous hemorrhage. METHODS: Detailed examination with fluorescein angiography and funduscopy. MAIN OUTCOME MEASURES: Site of dye leakage on fluorescein angiography in the eye with vitreous hemorrhage. RESULTS: Fluorescein angiography showed the leakage site at the margin of the disc in the eye with vitreous hemorrhage after the vitreous hemorrhage had been removed. CONCLUSIONS: The damage to peripapillary tissues demonstrated by fluorescein leakage suggests that intracranial hypertension affects peripapillary structures through the intervaginal space of the optic nerve sheath.

XAFS analysis of corroded metal surfaces with molten salts by conversion-electron-yield method.

We have measured XAFS spectra of metal surfaces corroded with melting salt (NaCl, KCl, and Na2SO4). Steel samples used were S45C, SCM435, SUS310S, and SUS304. We measured the Fe K-edge XAFS spectra for all samples and the Ni K-edge for SUS310S and SUS304 samples before and after the corrosion. The XANES spectra of samples before the corrosion show metallic structure because surface oxide thickness is thinner than probing depth with a conversion yield XAFS method. Each result of these XAFS spectra gives good agreements with the FEFF calculation in the assumption of bcc and/or fcc structure. The Fe K-edge spectra of steel samples except SUS310S after corroded treatment show existence bonding between Fe and another light element although the spectra of SUS310S samples before and after corroded treatment are much the same.

[Japanese cedar pollen in house dust].

Caring for oneself against Japanese cedar pollinosis is important as well as receiving medical-care. Although the importance of avoiding pollen is described in the guideline for nasal allergy medical treatment, however, there is no information for effective dust cleaning for the home. This study examined how many cedar pollens were included in indoor dust in order to obtain basic data whether dust removal for cedar pollen is available for pollinosis suffers. As a result, the study found that there were many Japanese cedar pollens in indoor dust even before the pollen season. Cedar pollen increased with the increasing number of airborne pollen. The highest number of pollen found in one week was approximately 450 pollens in a square meter of a living room floor. The study concluded that cleaning is one of the best way to remove Japanese cedar pollens found in indoor dust.

Immunohistochemical study of p53, p21 and PCNA in pterygium.

Since mutated p53 is one of the most frequent gene abnormalities in human cancer, we hypothesized that mutation of p53 may play an important role in growth and recurrence of pterygia, a dysplasia of the conjunctiva. Therefore, we compared pterygia of Japanese and Tunisian patients using antibodies against p53, p21 and proliferating cell nuclear antigen (PCNA). In Nagasaki, 21 pterygia of Japanese individuals were removed and in Gabes, 19 primary pterygia of Tunisian individuals. Positive staining of wild type p53 was not found in the Japanese pterygia, whereas 38.1% were positive for mutant p53, none were positive for p21 and 76.2% were positive for PCNA. The incidence of mutant p53-positive staining was 50.0% in males and 22.2% in females, which was statistically significant. In the 19 Tunisian patients, positive staining of wild type p53 was not found, whereas 36.8% were positive for mutant p53, 0% for p21 and 63.1% for PCNA. Differences between Japanese patients and Tunisian patients were not significant. There were 2 types of pterygium. One type did not show mutant p53 and the other showed mutant p53 caused by ultraviolet light. However, damage caused by p53-dependent programmed cell death of pterygium cells may lead to mutations in other genes which may allow the progressive multistep development of limbal tumors. It is possible that mutant p53-positive pterygia can develop into limbal tumors.

Month of birth, atopic disease, and atopic sensitization.

BACKGROUND: Japanese cedar (Cryptmeria japonica; CJ) pollen and house dust mites are the two important aeroallergens in Japan. However, no epidemiological survey has been performed in Japan to investigate the relationship between month of birth and manifestations of allergic disease and sensitization. OBJECTIVE: This study evaluates the correlation between month of birth and sensitization to aeroallergens or the occurrence of allergic disease on 755 Japanese school children aged 12-13 years. METHODS: The personal history of atopic disease (bronchial asthma, allergic rhinitis, eczema, and allergic conjunctivitis) as recorded by questionnaires was investigated in relation to total serum IgE and specific IgE toward house dust mites and CJ pollen. RESULTS: Positive specific IgE toward house dust mites was significantly less prevalent in the children born between January and March than those born during the rest of the year (p < 0.01). Positive specific IgE toward CJ pollen was significantly more prevalent in the children born between December and January than those born during the rest of the year (p < 0.05). High total IgE was less prevalent in the children born between February and April than in children born during the rest of the year (p = 0.05). The prevalence of bronchial asthma was 26.2% among children born between November and December, compared with a ratio of 17.3% among children born during the rest of the year (p < 0.05). A significantly higher proportion of the children with allergic rhinitis was born between August and October than during the rest of the year (p < 0.05). The prevalence of allergic conjunctivitis was 15.8% among the children who were born between December and January, compared with 9.1% among children born during the rest of the year (p < 0.01). No relationship between prevalence of eczema and season of birth was found. CONCLUSION: Month of birth appears to influence the risk in the development of allergic sensitization and atopic diseases. The findings concerning higher CJ pollen sensitization in children born in the months that proceed the CJ pollen seasons are as evident as the house-dust-mite-related findings.

Imbalance production between interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1Ra) in bronchial asthma.

Genes of the IL-1 family encode three different peptides, IL-1alpha, IL-1beta, and IL-1Ra, respectively. IL-1 operates through IL-1RI, and is involved in airway inflammation in asthmatic subjects, whereas IL-1Ra appears to be a specific competitive inhibitor of IL-1. All genes are on chromosome 2q12-21 where genomewide searches have identified linkage for asthma. To test whether variants of IL-1 relate to asthma, we conducted a genetic association study in a Japanese population. We show that the A2 allele of IL1RN (encoding IL-1Ra) associates with nonatopic asthma [OR = 5.71, 95% CI: 1.63-19. 8, Pc = 0.007]. Both atopic and nonatopic asthmatics with the A2 allele had significantly lower serum IL-1Ra levels in both types of asthmatics. Peripheral blood cells from asthmatics with A2 alleles, however, produced as much IL-1 as did those with A1 homozygotes. Since Th1 and Th2 cytokines differentially regulate the ratio between IL-1beta and IL-1Ra, these findings suggest that dysregulation of IL-1beta/IL-1Ra, probably due to interaction between epithelium and immuno-competent cells in the airway, is important in asthma inflammation.

[An office technique for myringoplasty without the use of fibrin glue].

A simple method for office closure of eardrum perforation using an atero-collagen graft used for dermal defects (Terdermis) without fibrin glue was developed. Eardrum perforations were successfully closed in 71.4% of all cases (63 ears) after the initial treatment. Neither skin incision nor the use of temporal fascial grafts was necessary in this method. The merit of the method is that there is no possibility of blood infection because no blood materials are used.

Genetic variants of IL-13 signalling and human asthma and atopy.

Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Ralpha and either gammac or IL-13Ralpha1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ralpha and IL-13Ralpha1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13Ralpha1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13Ralpha1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3. 38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.

Nonpathogenic common variants of IFNGR1 and IFNGR2 in association with total serum IgE levels.

Atopy is an immune disorder in which a Th2 dominant mechanism leads to high IgE levels and the clinical disorder asthma. It has been postulated that the Th1 cytokine IFNgamma, acting through its heterodimeric receptors, IFNgammaR1 and IFNgammaR2, in the induction/proliferation of Th1 cells, might suppress the Th2 responses that may underlie atopic asthma. However, neither murine nor human variants of IFNgamma associate with atopy. Several dysfunctional mutations have been identified in IFNgamma receptor genes (IFNGR1 and IFNGR2) in relation to severe and selective infections with poorly pathogenic organisms. However, little is known about common polymorphisms and their functional role in atopy. To test whether such variants of IFNGR1 and IFNGR2 relate to atopic asthma, we conducted a genetic association study in both British (n = 300) and Japanese (n = 200) populations. An intronic variant of IFNGR1 showed marginal association with total serum IgE levels in the British population compared with those with total IgE levels <30 IU/ml and those with >120-500 IU/ml [odds ratio = 2.00 (95% CI 1. 00-4.07), P = 0.048]. A coding variant, Gln64Arg of the IFNGR2, also associated with total serum IgE levels in the British population [chi(2) = 5.08, P = 0.024]. Further genetic and functional analyses are needed to clarify the role of variants of IFNgamma receptor genes in atopic immune disorder among different ethnic groups.

Variants of endothelin-1 and its receptors in atopic asthma.

Endothelin-1 (ET-1) is a 21 amino acid peptide released from several types of bronchial cells. It operates through two types of receptors, type A(ET-RA) and type B(ET-RB) and has various activities in the pathophysiology of atopic asthma. These genes are localised on different chromosomes where genome-wide searches have identified linkage for atopic asthma, thus supporting the candidacy of ET-1 and its receptors for atopic asthma. A genetic association study was performed with variants of these three genes in both British (n = 300) and Japanese populations (n = 200). No significant association was found between variants of EDN1 and EDNRB genes, and atopic asthma in either population. However, variants of EDNRA gene showed a marginal association with atopy [odds = 0.39(95% CI: 0.17-0.89), p = 0.022, Pc = 0.066], especially with antigen specific IgE levels [odds = 0.31 (95% CI: 0.20-0.77), p = 0.006, Pc = 0.018] in the British population. These findings suggest that EDNRA is a major candidate locus for atopy on chromosome 4.

[Environmental control for allergic diseases--avoiding and killing effect on housedust-mite by eastern red cedar].

Housedust-mite has been a trigger factor for allergic diseases such as asthma, rhinitis and eczema. Therefore, it is important to remove housedust-mite from the environment of an allergic patient. Eastern red cedar is one kind of cypress tree which grows naturally in Northern America. It is used for the material of pencils, and the essence of soap. Its oil is used for oily substance for microscope lens. Using original system, we examined eastern red cedar and its oil, and found that it is effective for killing and preventing housedust-mites. The result was very effective. In conclusion the eastern red cedar and its oil seems to be useful for controlling mites in the home environment of allergic patients.

Pterygium with bulbar conjunctival hemorrhages.

BACKGROUND: This study was carried out to describe the clinical features and electron-microscopic characteristics of the capillaries in pterygium with conjunctival hemorrhage. METHODS: We compared the clinical findings in Japanese and Tunisian primary pterygia and in pterygium with and without bulbar conjunctival hemorrhages. The capillary fine structures of pterygium with bulbar conjunctival hemorrhages were studied by electron microscopy and compared with those without bulbar conjunctival hemorrhages. RESULTS: Conjunctival hemorrhages were noted in 16.4% of Tunisian patients but not in any Japanese patients. The former pterygia were significantly larger, more vascular and more frequently hyperemic than the latter. Pterygia with bulbar conjunctival hemorrhages were more hyperemic than without hemorrhages. Electron microscopy revealed interruptions of the endothelial cells and basement membrane of the capillaries in the pterygia with bulbar conjunctival hemorrhages, with blood cells escaping through the endothelial interruptions. CONCLUSION: Conjunctival hemorrhage in pterygia may be caused by fragility of the endothelial cells and basement membrane in the capillaries, which easily induces hemorrhage when the eyes are irritated by rubbing or by conjunctival foreign bodies. Pterygium with conjunctival hemorrhage is more frequently found in Tunisians than in Japanese.

[The positivity rate of specific IgE antibody to Japanese cedar pollen in Wakayama Prefecture].

The incidence of Japanese cedar pollinosis has been increasing each year in Japan. Japanese cedar pollinosis is a state of allergic response, mediated by IgE. So, it is important to know the state of sensitization against Japanese cedar pollen. The subjects were 1321 nonselective cases who were more than 16 years of age and who live in Wakayama Prefecture. Specific IgE antibodies to Japanese cedar pollen were measured by Lumiward immunoassay system. The results showed that positivity for sera class 2 or higher was 30.9%. Furthermore, the positivity in 1995 was higher than the positivity in either 1985 (13.9%) or 1990 (18.3%). The incidence of specific IgE antibody positivity was higher in males. Also the age distribution of the positivity was highest in the 20-29 years old group, and the positivity was decreased with age. We examined the kinds of factors influencing the positivity of specific IgE antibodies. However, the relation between the positivity of specific IgE antibodies and the various environmental factors was unclear.

[Epidemiologic study of Chlamydia pneumoniae with ELISA].

Chlamydia Pneumoniae (C. pneumoniae) is a bacterium involved in infections of the upper airway as well as in lower respiratory diseases. It has been reported that infections from this bacterium are prevalent worldwide and that the proportion of the population having the antibody is high. It is, however, difficult to identify the pathogen by routine bacterial examination because it is an obligate cytozoic bacterium. In addition, the examination has been feasible in only a limited number of laboratories because the determination of the serum antibody titer has required preparation of the antigen as well as sophisticated skill. We conducted an epidemiological survey of 320 healthy males and females in their 20s living in the three cities of Osaka, Kobe and Oita using "HITAZYME C. Pneumoniae", which is a recently developed kit for determination of anti-C. pneumoniae specific antibody. The statistical method used was the chi square test for the comparison of proportions. Mean proportion of the population showing positive antibody test was 58.1%. IgA antibody was positive in 42.8% and IgG in 46.5% of the above population. There were no statistically significant differences between districts of between genders in the percentages of cases positive for these antibodies. The results were comparable to those previously reported suggesting that C. pneumoniae is prevalent all over Japan. This kit was found to be an easy way to use the ELISA method and therefore to be clinically useful.