Induced pluripotent stem cells for disease modeling,cell therapy and drug discovery in genetic autonomic disorders: a review

Clinical Autonomic Research - The autonomic nervous system (ANS) regulates all organs in the body independent of consciousness, and is thus essential for maintaining homeostasis of the entire...     

Validation of a simplified technique for using the POPQ pelvic organ prolapse classification system

Our objective was to determine the inter-examiner agreement of a simplified pelvic organ prolapse quantification (POPQ) exam and to assess its correlation with the standard POPQ exam. This study consists of two parts; both were preformed in a prospective, randomized, blinded fashion on women presenting with complaints attributed to pelvic organ support defects. The first study was done to determine the inter-examiner reliability of a simplified POPQ exam. The simplified POPQ exam is based on the POPQ with similar ordinal staging but with only four points measured instead of nine. Forty-eight women underwent exams by five different investigators. The order of exams was randomized and the examiners were blinded to the results of each other’s findings. The results of these two exams were compared using weighted kappa statistics. The second part of the study was done to determine the inter-system agreement between the simplified vs standard POPQ exam. A group of 49 women were examined by four different investigators: one using the simplified and the other using standard POPQ exams. The order of the exams was randomized and the examiners were blinded to the results of each other’s exam. Kendall’s tau-b statistics were used to determine the inter-system agreement. For the inter-examiner reliability of the POPQ exam, the average age was 60±13 years. The weighted kappa statistics for the inter-examiner reliability of the simplified prolapse classification system were 0.86 for the overall stage, 0.89 and 0.86 for the anterior and posterior vaginal walls, respectively, 0.82 for the apex/cuff, and 0.72 for the cervix. All demonstrate significant agreement. For the inter-system association between the simplified POPQ and standard POPQ, the average age was 61±15 year. The Kendall’s tau-b value for overall stage was 0.90, 0.83, and 0.87 for the anterior and posterior walls respectively, and 0.78 for the cuff/apex and 0.98 for the cervix. There is good inter-examiner agreement of a simplified POPQ classification system and it appears to have good inter-system association with the POPQ.IUGA Standardization of Terminology Committee members: Robert Freeman MD (chairman), Steven Swift, Eckhard Petri MD, Richard J. Scotti MD, and Peter Dwyer MD.     

Oligonucleotide fingerprint analyses of influenza C virion RNA recovered from five different isolates

Summary Five different isolates of influenza C virus which were isolated over a period of 32 years and from four different continents were compared by RNA genome oligonucleotide fingerprinting analyses. The earliest isolate of influenza C virus was reported in 1949 byTaylor (19) and served as a reference strain for this study.The results obtained using this technique of comparing relatedness between viruses clearly showed that all strains are distinct. However, the similarities in the pattern of the oligonucleotide fingerprints are marked for the more recent virus isolates (1966–1979), whereas the reference strain C/Taylor shows more pronounced differences.The results are consistant with the high degree of serological crossreaction amongst influenza C viruses isolated over a long period of time, a property which sets this group of viruses apart from type A and B members of the orthomyxoviridae.With 3 Figures     

First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model.

The aim of this study in pigs was to investigate the local pharmacokinetics of fexofenadine in the intestine and liver by using the pig as a model for drug transport in the entero-hepatobiliary system. A parallel group design included seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a jejunal single-pass perfusion combined with sampling from the bile duct and the portal, hepatic, and superior caval veins was performed. Fexofenadine was perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000 mg/l, total dose 200 mg). The animals were fully anesthetized and monitored throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/- S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/- 0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or biliary clearance. The E(H) for verapamil and antipyrine agreed well with human in vivo data. Verapamil did not increase the intestinal absorption of fexofenadine, even though the jejunal permeability of fexofenadine, verapamil, and antipyrine showed a tendency to increase in G2. This combined perfusion and hepatobiliary sampling method showed that verapamil did not affect the transport of fexofenadine in the intestine or liver. In this model the E(H) values for both verapamil and antipyrine were similar to the corresponding values in vivo in humans.     

Incidence and survival in patients with pharyngeal cancer in northern Finland

A population-based survey was conducted in northern Finland in order to study the incidence rate and survival in patients with pharyngeal cancer diagnosed between 1986 to 1996. A total of 95 new patients with hypopharyngeal, oropharyngeal or nasopharyngeal cancers were identified. The overall age-adjusted incidence rates (per 100,000 years) were 1.28 in men and 0.60 in women, giving an overall incidence rate of 0.89. Most of the tumours were diagnosed at stage IV, and the median disease-specific survival times were 27.6 months for the patients with oropharyngeal cancer, 13.5 months for nasopharyngeal cancer and 17.7 for hypopharyngeal cancer. The most important factors that were associated with a poor prognosis were stage IV in oropharyngeal [Hazard ratio (HR) 3.68, 95% confidence interval (CI) 0.97-13.92] and hypopharyngeal cancer (HR 3.99, CI 1.51-10.67) and age over 65 years in nasopharyngeal cancer (HR 9.28, CI 1.79-47.99).