Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers

Montelukast, a cysteinyl leukotriene receptor antagonist, is being developed for the treatment of asthma and related diseases. This study was designed to evaluate whether montelukast at clinically used dosage levels would interfere with the anticoagulant effect of warfarin. In a two-period, double-blind, randomized crossover study, 12 healthy male subjects received a single oral dose of 30 mg warfarin on the 7th day of a 12-day treatment with montelukast, 10 mg daily by mouth, or a placebo. Montelukast had no significant effect on the area under the plasma concentration-time curves and peak plasma concentrations of either R- or S-warfarin. However, slight but statistically significant decreases in time to peak concentration of both warfarin enantiomers and in elimination half-life of the less potent R-warfarin were observed in the presence of montelukast. These changes were not considered as clinically relevant. Montelukast had no significant effect on the anticoagulant effect of warfarin, as assessed by the international normalized ratio (INR) for prothrombin time (AUC0-144 and INR maximum). The results of this study suggest that a clinically important interaction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.     

Use of Antibiotic Prophylaxis in Ear Surgery

A prospective, double-blind, randomized, placebo-controlled study was performed to evaluate the effect of antibiotic prophylaxis in ear surgery. The present study reports on the results of 750 patients, half of whom received cefuroxime for 1 day, the other half, placebo. All postoperative infections occurring within 2 weeks after the intervention were recorded, together with several preoperative and perioperative parameters. It is concluded that exploratory tympanoplasties (including stapedotomy) and “dry perforation” tympanoplasties should be considered “clean” operations according to the American National Research Council and do not benefit from antibiotic prophylaxis. On the other hand, tympanoplasties performed on draining ears and on ears with cholesteatoma should be considered “dirty” operations for which antibiotic prophylaxis may decrease the postoperative infection rate by factor 3. All postoperative infections healed without sequels under proper treatment, except for three that resulted in graft necrosis-one in the placebo group and two in the cefuroxime group. In consequence, prophylaxis may not be mandatory in the dirty group, although the authors advocate its use for the sake of patient and surgeon comfort.     

Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction

A significant proportion of hemophilia A patients receiving transfusions of factor VIII (FVIII) develop a specific antibody response towards FVIII. These antibodies are usually detected by assays in which they inhibit the function of the molecule, such as the Bethesda clotting test. We have prepared anti-FVIII antibodies by specific immunoadsorption from the plasma of four hemophiliacs with stable inhibitor levels. The isotypic distribution of such antibodies was determined and their capacity to bind to insolubilized FVIII was compared with their inhibitory activity in two functional assays, namely, the Bethesda assay and a chromogenic assay. In addition, the FVIII epitope specificity was determined by competition with monoclonal antibodies for the binding to insolubilized FVIII. We show here that (1) anti-FVIII antibodies are not isotypically restricted; thus, a significant proportion of specific IgG2 was found; (2) antibodies are frequently directed towards epitopes of FVIII that are not directly involved in the function of the molecule and therefore escape detection in the Bethesda method or chromogenic assay; and (3) each patient shows a unique pattern of FVIII epitope recognition. We conclude that evaluation of anti-FVIII antibodies by a functional method does not provide an accurate evaluation of the specific antibody response. These findings have important implications for the comparison of the immunogenicity of FVIII molecules produced by different technologies and for the development of methods to control anti-FVIII antibody production.     

Comparative Study of IS6110 Restriction Fragment Length Polymorphism and Variable-Number Tandem-Repeat Typing of Mycobacterium tuberculosis Isolates in the Netherlands,Based on a 5-Year Nationwide Survey

In order to switch from IS6110 and polymorphic GC-rich repetitive sequence (PGRS) restriction fragment length polymorphism (RFLP) to 24-locus variable-number tandem-repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates in the national tuberculosis control program in The Netherlands, a detailed evaluation on discriminatory power and agreement with findings in a cluster investigation was performed on 3,975 tuberculosis cases during the period of 2004 to 2008. The level of discrimination of the two typing methods did not differ substantially: RFLP typing yielded 2,733 distinct patterns compared to 2,607 in VNTR typing. The global concordance, defined as isolates labeled unique or identically distributed in clusters by both methods, amounted to 78.5% (n = 3,123). Of the remaining 855 cases, 12% (n = 479) of the cases were clustered only by VNTR, 7.7% (n = 305) only by RFLP typing, and 1.8% (n = 71) revealed different cluster compositions in the two approaches. A cluster investigation was performed for 87% (n = 1,462) of the cases clustered by RFLP. For the 740 cases with confirmed or presumed epidemiological links, 92% were concordant with VNTR typing. In contrast, only 64% of the 722 cases without an epidemiological link but clustered by RFLP typing were also clustered by VNTR typing. We conclude that VNTR typing has a discriminatory power equal to IS6110 RFLP typing but is in better agreement with findings in a cluster investigation performed on an RFLP-clustering-based cluster investigation. Both aspects make VNTR typing a suitable method for tuberculosis surveillance systems.     

Estrogen Activation of G-Protein–Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes

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Radiographic assessment of impacted teeth and associated pathosis prevalence: Pattern of occurrence at different ages in Saudi male in Western Saudi Arabia

Objectives:

To assess the prevalence of both impaction and associated pathosis in a Saudi population in Al-Madinah, Saudi Arabia based on digital panoramic radiographs.

Methods:

This study was carried out from December 2013 to February 2015. Panoramic radiographs of 359 male patients attending the Oral Diagnosis Clinics, Faculty of Dentistry, Taibah University, Al-Madinah, Saudi Arabia were reviewed. All images were evaluated to determine the prevalence and pattern of impacted third molars and canines, and associated pathosis.

Results:

Among 359 panoramic radiographs examined, 124 patients had impacted teeth. The impacted mandibular third molars were the most prevalent impacted teeth, 77.6% had class II pattern of impaction. Among the impacted maxillary canines, 75% were mesioangular and among 66 impacted maxillary third molars, 63.6% had class C. Our study showed that 5.8% of Saudi patients had 3 or more impacted teeth, 13.1% had 2 impacted teeth, and 15.6% had one impacted tooth. Associated pathosis was found in 18.2% among impacted maxillary third molars, and 31.5% among impacted mandibular third molars. The incidence of impaction decreases with age.

Conclusion:

The prevalence and pattern of impacted third molars among Saudis are almost similar to other racial populations. The number of missing wisdom increases with age. Although the percentage of pathosis associated with impaction was considerably low, it is essential to carry you regular oral examinations to preserve asymptomatic impacted teeth in good health.As eruption is a complex process, therefore tooth retardation or failure of eruption may arise, so failure of permanent teeth eruption and subsequent impaction is a common dental anomaly.1 Previous literature reported that teeth impaction is a usual incident and many factors affect its prevalence including aging and eruption time.2 Genetic and environmental factors play a role in developmental disturbances. The incidence of impacted teeth is contradictory in different populations and ethnic groups.3 Complications associated with impaction may range from simple problems to serious life threatening problems. Hyperplastic follicular space, subsequent dentigerous cyst or odontogenic keratocyst are the most common simple problems with impaction.4,5 Serious complications involve malignant transformation of cystic wall into squamous cell carcinoma or mucoepidermoid carcinoma. Consequently, life threatening conditions maybe a chain of simple problem such as impaction, which if solved from the beginning would cost less, and would be simple to solve.6 Panoramic radiography is a simple tomographic technique that introduces the panoramic view of the maxillofacial region.7 Radiographic examinations are either digital imaging or conventional. Digital imaging has many advantages versus conventional, such as reduction of radiation exposure, feasibility of image manipulation and analysis, which improves sensitivity and diminishes errors.8 The United States guidelines state that the panoramic radiograph is one of the screening images for Adolescent with Permanent Dentition and Adult, Dentate or Partially Edentulous.9 During our daily oral examinations, we notice poor patient awareness of oral health and its implications in Saudi Arabia. Additionally, there is no present data on the prevalence of impacted teeth, and associated pathologies in the Saudi population in Al-Madinah, Saudi Arabia. The aim of the present study was to determine the prevalence and pattern of occurrence of impacted teeth at different ages based on digital panoramic radiograph. In addition, to report the radiographic features of associated pathologies in a Saudi male population, in order to correlate between impaction and associated pathosis     

Optimization of Standard In-House 24-Locus Variable-Number Tandem-Repeat Typing for Mycobacterium tuberculosis and Its Direct Application to Clinical Material

Variable-number tandem-repeat (VNTR) typing with a panel of 24 loci is the current gold standard in the molecular typing of Mycobacterium tuberculosis complex isolates. However, because of technical problems, a part of the loci often cannot be amplified by multiplex PCRs. Therefore, a considerable number of single-locus PCRs have to be performed for the loci with missing results, which impairs the laboratory work flow. Therefore, the original in-house method described by Supply et al. in 2006 was reevaluated. We modified seven primers and the PCR master mixture and obtained a strongly optimized in-house 24-locus VNTR typing method. The percentage of instantly complete 24-locus VNTR patterns detected in the routine flow of typing activities increased to 84.7% from the 72.3% obtained with the typing conducted with the commercially available Genoscreen MIRU-VNTR typing kit. The analytical sensitivity of the optimized in-house method was assessed by serial dilutions of M. tuberculosis in bronchoalveolar lavage fluid. A 1:10 dilution of the different strains tested was the lowest dilution for the detection of a complete 24-locus VNTR pattern. The optimized in-house 24-locus VNTR typing method will reduce the turnaround time of typing significantly and also the financial burden of these activities.