Inhaled corticosteroid for persistent cough following upper respiratory tract infection

OBJECTIVE: The aim of this study was to determine the clinical effect of inhaled corticosteroid treatment for persistent cough, post upper respiratory tract infection (URTI) in previously healthy individuals, and on bronchial hyperresponsiveness (BHR). METHODOLOGY: This was a prospective, randomized, double-blinded, placebo-controlled study conducted at a university hospital. A total of 30 non-asthmatic, non-smoking patients who were >15 years old and who had persistent post-URTI cough for >3 weeks were assessed by a physical examination, CXR and spirometry, and were allocated to receive inhaled budesonide (400 microg/puff, twice daily) or placebo for 4 weeks. If a patient suffered from sinusitis, it was a requirement that it had been well treated. A symptom score (frequency of cough, frequency of coughing bouts, symptoms associated with cough, night-time cough, frequency of taking medications to relieve cough, and number of medications) was recorded at entry, and after 2 and 4 weeks of treatment. A methacholine challenge test was performed at entry and after 4 weeks of treatment. RESULTS: The mean symptom scores for the treatment group (9.4) and the placebo group (9.8) at baseline were not significantly different (P=0.79), and no differences were found between the groups after week 2 and week 4 of treatment (3.93 and 4.27 vs 2.26 and 2.66, P=0.29). The mean change in symptom scores from baseline to week 2 and to week 4 of treatment were also not different between groups (5.93 and 5.6 vs 7.00 and 7.58, P=0.23). No difference between groups was found in the mean changes in FEV(1), FVC, and FEF(25--75%) after 4 weeks of treatment. A positive bronchial provocation test occurred in three patients (10%) but these were borderline. CONCLUSION: Inhaled corticosteroid is ineffective in treating persistent post-URTI cough in previously healthy individuals.     

Dual signaling by innate and adaptive immune receptors is required for TLR7-induced B-cell–mediated autoimmunity

Toll-like receptor 7 (Tlr7) has been linked to systemic lupus disease incidence in humans and mice, but how TLR7 potentiates autoimmunity is unclear. We used a Tlr7 transgenic (tg) mouse model to investigate the cellular and molecular events required to induce spontaneous autoimmunity through increased TLR7 activity. We determined that Tlr7 exerts B-cell–intrinsic effects in promoting spontaneous germinal center (GC) and plasmablast B-cell development, and that these B-cell subsets are dependent on T-cell–derived signals through CD40L and SLAM-associated protein (SAP), but not IL-17. Antigen specificity also factored into TLR7-induced disease, as both a restricted T cell receptor (TCR) specificity and MHC haplotype H2^k/k protected Tlr7tg mice from spontaneous lymphocyte activation and autoantibody production. Inflammatory myeloid cell expansion and autoimmunity did not develop in Tlr7tgIgH^−/− mice, suggesting either that spontaneous TLR7 activation does not occur in dendritic cells, or, if it does occur, cannot drive these events in the absence of B-cell aid. These data indicate that autoimmune disease in Tlr7tg mice is contingent upon B cells receiving stimulation both through innate pathways and T-cell–derived signals and suggest a codependent relationship between B cells and T cells in the development of autoimmunity.     

Routine prophylactic application of Monsel's solution after loop electrosurgical excision procedure of the cervix: is it necessary?

AIM: To determine the benefit of an immediate application of Monsel's solution after loop electrosurgical excision procedure (LEEP) of the cervix for preventing postoperative bleeding. METHODS: This randomized controlled trial was conducted at Chiang Mai University Hospital, Chang Mai, Thailand. Women who were scheduled for LEEP were approached for participation in the study. The primary endpoint was the duration of uncomplicated vaginal bleeding. Secondary endpoints were the incidence of persistent vaginal bleeding, and postoperative complications including severe early bleeding, severe delayed bleeding and infection. RESULTS: Between October 2004 and May 2006, 285 women with an abnormal Pap-smear, who had undergone LEEP, were randomly allocated to the Monsel's group (n = 140) or control group (n = 145). The baseline outcomes were similar between the two groups. In the Monsel's group, the duration of uncomplicated vaginal bleeding was significantly shorter (P < 0.001) and the occurrence of persistent vaginal bleeding was significantly lower (P = 0.014) than in the control group. The occurrence of severe complications that required treatment, including bleeding and infection, was not significantly different between the two groups (P = 0.379). CONCLUSION: An application of Monsel's solution after LEEP appears to reduce the duration of postoperative vaginal bleeding, but does not significantly prevent severe complications. Such practice may not be necessary if adequate hemostasis is achieved using electrical cauterization.     

Alteration of pregnancy related hormones and fetal survival in F-344 rats exposed by inhalation to benzo(a)pyrene

The objective of this study was to evaluate the effect of subacute exposure to inhaled benzo(a)pyrene (BaP) on fetal survival and luteal maintenance using timed-pregnant Fisher 344 rats. Prior to assignment of pregnant rats to treatment and control groups, numbers of implantation sites were determined on gestation day (GD) 8 via midventral laparotomy. Subsequently, animals were assigned randomly to three treatment groups and two control groups. Treatment consisted of subacute exposure of rats via inhalation to BaP 25, 75, and 100 μg/m³, 4 h daily for 10 days (GD-11–20). Control animals were either sham exposed to carbon black (CB) to control for inert BaP carrier or remained unexposed (UNC). Blood samples were collected on days 15 and 17 of gestation via sinus orbital veini-puncture for plasma. Number of pups per litter was determined postpartum and fetal survival rate was expressed as a percentage of the corresponding implantation sites. Radioimmunoassays were used to determine plasma progesterone, estrogen, and prolactin (indirect measurement of decidual luteotropin) concentrations. Fetal survival among BaP-treated rats declined in a dose-dependent manner (25 μg/m³, 78.3% per litter; 75 μg/m³, 38.0% per litter; 100 μg/m³, 33.8% per litter; P<0.05) compared with CB (96.7% per litter) and UNC (98.9% per litter). Plasma progesterone, estrogen, and prolactin concentrations also declined as a result of subacute exposure of rats to BaP compared to controls. These data suggest that inhaled BaP compromised fetal survival and consequently luteotropic activity in the exposed animals.     

Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation

Nucleic acid-binding innate immune receptors such as Toll-like receptor 7 (TLR7) and TLR9 have been implicated in the development of some autoimmune pathologies. The Y chromosome-linked genomic modifier Yaa, which correlates with a duplication of Tlr7 and 16 other genes, exacerbates lupus-like syndromes in several mouse strains. Here we demonstrated that duplication of the Tlr7 gene was the sole requirement for this accelerated autoimmunity, because reduction of Tlr7 gene dosage abolished the Yaa phenotype. Further, we described new transgenic lines that overexpressed TLR7 alone and found that spontaneous autoimmunity developed beyond a 2-fold increase in TLR7 expression. Whereas a modest increase in Tlr7 gene dosage promoted autoreactive lymphocytes with RNA specificities and myeloid cell proliferation, a substantial increase in TLR7 expression caused fatal acute inflammatory pathology and profound dendritic cell dysregulation. These results underscore the importance of tightly regulating expression of TLR7 to prevent spontaneous triggering of harmful autoreactive and inflammatory responses.     

Coinheritance of Hb A2-Melbourne (HBD: c.130G>A) and Hb E (HBB: c.79G>A) in Laos and Simultaneous High Resolution Melt Detection of Hb A2-Melbourne and Hb A2-Lampang (HBD: c.142G>A) in a Single Tube

Abstract

We report the molecular and hematological identifications of a Hb A₂ variant [coinheritance of Hb A₂-Melbourne (HBD: c.130G>A) and Hb E (HBB: c.79G>A)] found for the first time in the Lao People’s Democratic Republic (PDR). The subject was a 29-year-old pregnant Laotian woman who was a foreign worker in Thailand and was diagnosed with thalassemia and hemoglobinopathies. Capillary electrophoresis (CE) demonstrated 1.6% of Hb A₂, with a minor unknown peak at the initial Z1 zone (1.7%). Identification of abnormal hemoglobin (Hb) using direct DNA sequencing showed a genetic defect causing a δ-globin gene missense mutation at codon 43 (GAG>AAG) causing a glutamic acid to lysine substitution corresponding to Hb A₂-Melbourne. The origin of Hb A₂-Melbourne in Lao PDR may be similar to a case found in Thailand with the [+ –?– –?– + +] haplotype. We developed a method that could clearly detect Hb A₂-Melbourne and Hb A₂-Lampang (HBD: c.142G>A) mutations in a single tube using high resolution melt (HRM) analysis. The HRM analysis is a more effective method for rapid detection than conventional polymerase chain reaction (PCR), as there is no need for a post-PCR step, and no exposure to ethidium bromide. This new method would be a useful addition for the first investigation of a suspected Hb A₂ variant in the routine molecular setting.     

Pseudomembranous aspergillus tracheobronchitis superimposed on post-tuberculosis tracheal stenosis

Pseudomembranous aspergillus tracheobronchitis superimposed on post-tuberculosis tracheal stenosis has not been previously reported. In the patient described in this case report, the airway obstruction was worsened by aspergillus infection which responded to antifungal therapy and debridement of pseudomembranous tissues by rigid bronchoscopic procedures. A silicone stent was successfully placed in the trachea to restore airway patency when there was no more evidence of tracheobronchial aspergillosis. This case raises the questions of whether, how and when to restore airway patency in patients with tracheal stenosis and concurrent aspergillus tracheobronchitis.     

Differences in levels of platelet-derived microparticles in platelet components prepared using the platelet rich plasma,buffy coat,and apheresis procedures

Background

There has been an increased interest in platelet-derived microparticles (PMPs) in transfusion medicine. Little is known about PMP status during the preparation of platelet concentrates for transfusion.

Aerosol OT microemulsions as carriers for transdermal delivery of hydrophobic and hydrophilic local anesthetics

The skin permeation enhancement of many kinds of drugs and cosmetic substances by microemulsions has been widely known; however, the correlations between microemulsion microstructures and the efficiency of skin permeation are not fully elucidated. Therefore, the aim of our study was to investigate the influence of microemulsion types on in vitro skin permeation of model hydrophobic drugs and their hydrophilic salts. The microemulsion systems were composed of isopropyl palmitate (IPP), water, a 2:1 w/w mixture of Aerosol OT (AOT) and 1-butanol, and a model drug. The concentrations of surfactant mixture and model drug were maintained at 45% and 1% w/w, respectively. The concentrations of IPP and water were 15% and 39% w/w, respectively, for oil-in-water (o/w) type and vice versa for water-in-oil (w/o) type. The samples were prepared by simple mixing and characterized by visual appearance, pH, refractive index, electrical conductivity, viscosity, and determination of the state of water and IPP in the formulations using differential scanning calorimetry. Transdermal flux of lidocaine, tetracaine, dibucaine, and their respective hydrochloride salts from the drug-loaded AOT-based microemulsions through heat-separated human epidermis was investigated in vitro using modified Franz diffusion cells. The o/w microemulsions resulted in the highest fluxes of the model drugs in base form as compared with the other formulations within the same group of drugs. Moreover, the skin permeation of drug from microemulsions depended on drug molecular structure and interaction between drug and surfactant.