Zensei Matsuzaki

Fosfomycin nebulizer therapy to chronic sinusitis

OBJECTIVEneffects of Fosfomycin (FOM) nebulizer therapy were studied in patients with chronic sinusitis.nnnMETHODSnabout 28 patients with chronic sinusitis were administered 2 ml of FOM sodium (3% w/v) by nebulizer three times per week for 4 weeks. Levels of IL-1 beta, IL-6, IL-8, and TNF-alpha in nasal lavage were also measured before and at the end of treatment.nnnRESULTSnthe overall efficacy of this treatment on the basis of both subjective and objective symptoms, was excellent for 28.6%, good for 10.7%, fair for 39.4%, and yield no change for 21.4% of the patients. Both IL-1 beta and IL-6 concentrations were significantly decreased after treatment. Although the IL-8 level did not significantly decrease, it seems to be related to the overall efficacy. TNF-alpha was not detected in all of the samples.nnnCONCLUSIONnFOM nebulization therapy is highly effective in treatment for chronic sinusitis, and efficacy may be due to an immunomodulatory mechanism, as well as its bactericidal effect.

Carotid artery resection: preoperative temporary occlusion is not always an accurate predictor of collateral blood flow.

Conclusion The morbidity predicted by means of preoperative PET studies does not always correlate with the morbidity experienced after permanent carotid artery occlusion. A pre-resection extracranial–intracranial bypass may be necessary to reduce the risk of neurologic morbidity, in particular when carotid artery resection is planned for tumors involving the skull base. Objectives Carotid artery resection is generally considered the only curative treatment for patients with advanced head and neck carcinoma involving the carotid artery. PET can be used during temporary occlusion of the internal carotid artery to assess the safety of the procedure. The aims of this paper were to clarify the risk of carotid artery resection and the benefit of extracranial–intracranial bypass. Material and methods Twelve patients diagnosed with head and neck cancer adherent to the carotid artery and in proximity to the skull base who had shown good hemispheric collateral blood flow by means of PET underwent carotid artery resection without preoperative bypass. Results Of the 12 patients who underwent carotid artery resection without reconstruction, 10 suffered no serious neurologic complications; however, 2 suffered cerebral infarctions intraoperatively.

Suppressive effect of locally produced interleukin‐10 on respiratory syncytial virus infection

Interleukin (IL)‐10 is known to be a multifunctional cytokine. This study was designed to evaluate the role of IL‐10 during respiratory syncytial virus (RSV) infection using a C57BL/6 transgenic (TG) mouse model in which the expression of murine IL‐10 cDNA was regulated by a human salivary amylase promoter (IL‐10 TG mice). These mice expressed a large amount of IL‐10 in the nasal mucosa and in salivary glands. Viral replication in the respiratory tract after intranasal infection with RSV was suppressed significantly in IL‐10 TG mice compared to non‐transgenic controls. This suppression was IL‐10 specific, because it was prevented by treating mice with neutralizing anti‐IL‐10 antibodies. We also found that IL‐10‐stimulated T cells displayed cytotoxic activity against infected murine nasal epithelial cells. Previous data indicated that IL‐10 induces Fas ligand (L) expression on mouse T cells. Taken together, these data suggest that Fas/Fas L mediated cytotoxicity is involved in the suppression of RSV replication observed in IL‐10 TG mice after intranasal infection.

Cetirizine decreases interleukin-4, interleukin-5, and interferon-γ gene expressions in nasal-associated lymphoid tissue of sensitized mice

Although the action of cetirizine dihydrochloride (cetirizine), a potent histamine H1 receptor antagonist, has been well known, its effect on the cytokine profiles in the nasal immune inductive site has not been elucidated yet. We studied the effect of cetirizine on the cytokine profiles in the nasal-associated lymphoid tissue (NALT), which is a principal mucosal lymphoid tissue of the respiratory tract in rodents. Two different doses of cetirizine were given intraorally for 5 days before the nasal challenge of ovalbumin in sensitized mice. The sensitized group was given normal saline instead of cetirizine, and the nonsensitized group had no sensitization or medication. The cytokine gene expressions in the NALT taken from the mice were investigated with real-time quantitative reverse-transcription polymerase chain reaction. The effect of cetirizine on the allergic symptom score, histamine threshold, and the eosinophil count in the nasal septal mucosa were examined also. Compared with the normal mice, the sensitized mice showed significantly increased levels of interleukin (IL)-4 and IL-5 gene expression although the increase of interferon (INF)-γ gene expression was not significant. In the cetirizine groups, the levels of expression of IL-4, IL-5, and INF-γ in the NALT were significantly decreased compared with the sensitized group. The cetirizine groups also showed decreased allergic symptom score, histamine threshold, and eosinophil count in the nasal septal mucosa compared with the sensitized group. In conclusion, cetirizine reduced the levels of expression of IL-4, IL-5, and INF-γ in the NALT of ovalbumin-sensitized mice. Cetirizine also reduced the acute allergic symptom, histamine sensitivity, and eosinophil count in the nasal septal mucosa.

Patterns of drug prescription for Japanese cedar pollinosis using a clinical vignette questionnaire.

BACKGROUNDnAlthough prescribed drugs directly affect patient outcome, the variation in physicians attitudes towards drug therapy for cedar pollinosis has not been quantitatively assessed. This research investigated the prescription patterns of drugs for cedar pollinosis by ear, nose, and throat specialists (ENTs), general physicians (GPs) and internal medicine doctors (IMs) in Yamanashi Prefecture, Japan.nnnMETHODSnA cross-sectional study was conducted by mailing questionnaires to 532 physicians in autumn 2006. The main part of the questionnaire constituted clinical vignettes of pollinosis cases with nasal and ocular symptoms ranging from mild to severe. We requested that the physicians fill out prescription medications they considered appropriate for each vignette.nnnRESULTSnResponses from 172 physicians (32%) for six clinical vignettes were analyzed. The number of drugs prescribed by ENTs was significantly higher than that by GPs and IMs for vignettes representing moderate to severe cases (p < 0.004). The percentage of physicians who said they would prescribe nasal corticosteroid and eye drops was higher in the ENT group compared to the other two groups in these vignettes. In terms of second-generation antihistamines, no differences were observed between the three groups for all vignettes.nnnCONCLUSIONSnOur investigation suggested that, compared to ENTs, GPs and IMs have a lower tendency to concomitantly prescribe drugs for localized treatment such as nasal corticosteroids and eye drops with oral medication. There may be differences in prescription patterns of drugs for pollinosis between ENTs and non-specialist physicians.

A Randomized Control Trail of Stepwise Treatment with Fluticasone Propionate Nasal Spray and Fexofenadine Hydrochloride Tablet for Seasonal Allergic Rhinitis

BACKGROUNDnIn Japan, oral antihistamines are frequently used as the initial treatment for seasonal allergic rhinitis (SAR), and intranasal steroids are added when nasal symptoms worsen. This study aimed to evaluate whether starting treatment with fluticasone propionate nasal spray (FP) from the beginning of pollinosis symptoms and adding fexofenadine hydrochloride tablet (FEX) when SAR is aggravated could achieve improved amelioration of nasal symptoms throughout the pollen season in comparison with a treatment that involves starting with FEX and later adding FP.nnnMETHODSnIn this pragmatic, randomized, open-label, parallel-group trial, 51 Japanese cedar pollinosis patients (age, 16-85 years) were randomly divided and administered FP 100 mcg twice daily as an initial drug with FEX 60 mg twice daily as an additional drug and the same treatment in the reverse order. Nasal symptoms were evaluated in a daily dairy using a 4-point scale. The primary outcome was area under curve of the line representing the daily total nasal symptom score in the pollen season on a graph.nnnRESULTSnInitial treatment with FP was significantly (P = 0.0015) more effective than initial treatment with FEX in improving the primary outcome. The average daily total nasal symptom score in the initial treatment with FP group was better than that in the initial treatment with FEX group throughout the pollen season.nnnCONCLUSIONSnInitiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order.

Analysis of T-helper Responses and FOXP3 Gene Expression in Patients with Japanese Cedar Pollinosis:

Background Evidence has been accumulated indicating that regulatory T (T-reg) cells play a crucial role in the maintenance of peripheral T-cell tolerance to allergens. To explore the role of FOXP3, which is required for the development of T-reg cells, in allergen-specific immune responses, we examined the relationship between the alteration of FOXP3 gene expression and in vitro immune responses against allergens. Methods Peripheral blood mononuclear cells obtained from 19 human histocompatibility leukocyte antigens (HLA)-DPB1*0501 donors, including patients with Japanese cedar pollinosis and nonallergic healthy donors, were stimulated with Cry j 1 p61-75 peptide. On day 7, T cells were tested for peptide-specific reactivity in IFN-γ and interleukin (IL)-5 enzyme-linked immunospot (ELISPOT) assays. Real-time quantitative RT-PCR was performed to assess relative change of FOXP3 gene expression before and after in vitro stimulation. Neutralization assays using anti-glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) and anti-IL-10 monoclonal antibody were also performed. Results Of 14 patients with allergic pollinosis tested, 10 responders displayed T-helper type 2 (Th2)-polarized reactivity to Cry j 1 p61-75, and 2 donors showed Th0 responses. Notably, the change of FOXP3 gene expression in donors showing peptide-specific T-helper responses was significantly lower than that in nonresponders, regardless of allergic pollinosis. Conclusion Our data indicate that FOXP3 is functional in nonallergic healthy donors as well as allergic patients, and FOXP3-expressing T cells may be responsible for the down-regulation of allergen-specific T-helper responses in individuals. A better understanding of the nature and specificity of FOXP3-expressing T cells in a suppressive mechanism is necessary to develop new immunotherapies against allergic rhinitis.