Histopathologic parameters as predictors of response to endoscopic sinus surgery in nonallergic patients with chronic rhinosinusitis

OBJECTIVE: To estimate the predictable value of histopathologic parameters in chronic rhinosinusitis (CRS) for response to endoscopic sinus surgery (ESS). - - - - - STUDY DESIGN: Symptomatology was rated in 100 patients prior to as well as 12 and 24 months after surgery. Specimens taken during the procedure were examined and scored for goblet cells, subepithelial thickening, mast cells, and eosinophils. Multiple regression analysis was performed to predict the total score of subjective symptoms before treatment by histopathologic parameters. The correlation between histopathologic parameters and postoperative symptoms was then evaluated. - - - - - RESULTS: Goblet cells were the best predictor correlating with 5 symptoms. Subepithelial thickening correlated with 4 symptoms. Mast cell infiltration correlated with 3 symptoms. Eosinophilic infiltration correlated with only one symptom (P<0.05). - - - - - CONCLUSION: Certain histopathologic parameters in CRS are predictive of favorable response to ESS. - - - - - SIGNIFICANCE: Pathologic evaluation may help the ENT surgeon to predict the persistence of certain CRS symptoms after ESS, even in patients at low risk for surgical failure. - - - - - EBM rating: C-4

Thermochemical properties of different 1-(R-phenyl)-1H-imidazoles

© 2016 Elsevier B.V.Phenyl substituted imidazoles exhibit versatile biological activity. 1-(R-phenyl)-1H-imidazoles with different functional groups R provide a convenient suitcase of molecules with tunable physicochemical properties adjustable for many practical applications. In this work, the absolute vapor pressures of 1-(R-phenyl)-1H-imidazoles (with R = H, 2-methyl, 4-methyl, 2-methoxy, 4-methoxy, 2-fluoro, 4-fluoro, 2-bromo and 4-bromo) at different temperatures have been measured by the transpiration method for the first time. The standard enthalpies of vaporization of these compounds were derived from the temperature dependencies of the vapor pressures. An internal consistency of the standard vaporization enthalpies has been proven by comparison with vaporization enthalpies of parent species, as well as by a group contribution method. A system of group-additivity values is suggested for a quick assessment of vaporization enthalpies of different 1-(R-phenyl)-1H-imidazoles. Gas-phase standard molar enthalpies of formation of 1-(R-phenyl)-1H-imidazoles have been calculated using the high-level quantum-chemical method G3MP2. The combination of experimentally determined standard vaporization enthalpies with the G3MP2 results allows for the prediction of the liquid-phase standard enthalpies of formation for the studied compounds

Pathophysiological classification of chronic rhinosinusitis

BACKGROUND: Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic. METHOD: Statistical patterns of subjective and objective findings were assessed by retrospective chart review. RESULTS: CRS patients were readily divided into those with (50/99) and without (49/99) polyposis. Aspirin sensitivity was limited to 17/50 polyp subjects. They had peripheral blood eosinophilia and small airways obstruction. Allergy skin tests were positive in 71% of the remaining polyp subjects. IgE was<10 IU/ml in 8/38 polyp and 20/45 nonpolyp subjects (p = 0.015, Fisher's Exact test). CT scans of the CRS without polyp group showed sinus mucosal thickening (probable glandular hypertrophy) in 28/49, and nasal osteomeatal disease in 21/49. Immunoglobulin isotype deficiencies were more prevalent in nonpolyp than polyp subjects (p < 0.05). CONCLUSION: CRS subjects were retrospectively classified in to 4 categories using the algorithm of (1) polyp vs. nonpolyp disease, (2) aspirin sensitivity in polyposis, and (3) sinus mucosal thickening vs. nasal osteomeatal disease (CT scan extent of disease) for nonpolypoid subjects. We propose that the pathogenic mechanisms responsible for polyposis, aspirin sensitivity, humoral immunodeficiency, glandular hypertrophy, eosinophilia and atopy are primary mechanisms underlying these CRS phenotypes. The influence of microbial disease and other factors remain to be examined in this framework. We predict that future clinical studies and treatment decisions will be more logical when these interactive disease mechanisms are used to stratify CRS patients

Dual Hypocretin Receptor Antagonism Is More Effective for Sleep Promotion than Antagonism of Either Receptor Alone

The hypocretin (orexin) system is involved in sleep/wake regulation, and antagonists of both hypocretin receptor type 1 (HCRTR1) and/or HCRTR2 are considered to be potential hypnotic medications. It is currently unclear whether blockade of either or both receptors is more effective for promoting sleep with minimal side effects. Accordingly, we compared the properties of selective HCRTR1 (SB-408124 and SB-334867) and HCRTR2 (EMPA) antagonists with that of the dual HCRTR1/R2 antagonist almorexant in the rat. All 4 antagonists bound to their respective receptors with high affinity and selectivity in vitro. Since in vivo pharmacokinetic experiments revealed poor brain penetration for SB-408124, SB-334867 was selected for subsequent in vivo studies. When injected in the mid-active phase, SB-334867 produced small increases in rapid-eye-movement (REM) and non-REM (NR) sleep. EMPA produced a significant increase in NR only at the highest dose studied. In contrast, almorexant decreased NR latency and increased both NR and REM proportionally throughout the subsequent 6 h without rebound wakefulness. The increased NR was due to a greater number of NR bouts; NR bout duration was unchanged. At the highest dose tested (100 mg/kg), almorexant fragmented sleep architecture by increasing the number of waking and REM bouts. No evidence of cataplexy was observed. HCRTR1 occupancy by almorexant declined 4–6 h post-administration while HCRTR2 occupancy was still elevated after 12 h, revealing a complex relationship between occupancy of HCRT receptors and sleep promotion. We conclude that dual HCRTR1/R2 blockade is more effective in promoting sleep than blockade of either HCRTR alone. In contrast to GABA receptor agonists which induce sleep by generalized inhibition, HCRTR antagonists seem to facilitate sleep by reducing waking “drive”

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Brucellosis in Sub-Saharan Africa:Current challenges for management, diagnosis and control

Brucellosis is a highly contagious zoonosis caused by bacteria of the genus Brucella and affecting domestic and wild mammals. In this paper, the bacteriological and serological evidence of brucellosis in Sub-Saharan Africa (SSA) and its epidemiological characteristics are discussed. The tools available for the diagnosis and treatment of human brucellosis and for the diagnosis and control of animal brucellosis and their applicability in the context of SSA are presented and gaps identified. These gaps concern mostly the need for simpler and more affordable antimicrobial treatments against human brucellosis, the development of a B. melitensis vaccine that could circumvent the drawbacks of the currently available Rev 1 vaccine, and the investigation of serological diagnostic tests for camel brucellosis and wildlife. Strategies for the implementation of animal vaccination are also discussed.Publishe