Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.     

Irritable bowel syndrome and health-related quality of life: a population-based study in Calgary, Alberta.

BACKGROUND: Little is known about the health-related quality of life (HRQOL) of nonclinical samples of people with irritable bowel syndrome (IBS) in Canada. In a pilot survey, the impact of IBS on HRQOL using a population-based, urban sample was examined. METHODS: A random sample of Calgary residents (18 years of age or older), selected by random digit dialing (n=1521), completed a structured questionnaire including ROME II Criteria and Medical Outcomes Study Short-Form 12-Item Health Survey, version 2 (SF-12v2). The mean scale and summary scores of SF-12v2 for those who did and did not meet ROME II criteria and for those who met ROME II criteria with and without visiting a physician in past three months were determined and compared using multiple regression analyses. RESULTS: Of the 951 households successfully contacted, 590 (62%) were willing to participate, of which 437 (74%) individuals were recruited. One hundred ten IBS cases (81 of which were women) and 327 non-IBS controls (180 of which were women) were identified. All of the eight mean scale scores and the two mean summary scores were significantly lower in people with IBS than in those without, whether or not adjusting for demographics. Forty-four of the 110 IBS cases (40%) sought medical help. Significantly lower mean physical component score and three scale scores (general health, social functioning and role physical) were found in those who sought medical help than in those who did not. CONCLUSIONS: People with IBS experience significant impairment in HRQOL, including both physical and mental well-being. People with IBS who seek medical help report worse physical health than those who do not, but their mental health is no different.     

Potentiation of cholinergic activity with pyridino[1,2-a]imidazo[5,4-b]indole: in vitro studies

1. Effects of a novel imidazoindole derivative on cholinergic function were studied in isolated tissue preparations. 2. The compound demonstrated a dose-dependent (10(-11)-10(-9) potentiation (20-60%) of acetylcholine induced tension in guinea pig ileal tissue. 3. Increases in the size of end-plate potentials and nerve evoked muscle twitches were observed in frog nerve-skeletal muscle preparations. 4. Cholinesterase activity was not inhibited. 5. The results suggest that the compound has actions at the post-synaptic muscarinic receptor complex in smooth muscle and causes pre-synaptic increases in ACh release at the neuromuscular junction.     

Comparison of ThinPrep versus conventional smear cytopreparatory techniques for fine-needle aspiration specimens of head and neck masses.

OBJECTIVES: Diagnostic accuracy of the ThinPrep process (Cytyc, Boxborough, MA) was compared with that of conventional (smear) cytopreparation for fine-needle aspiration (FNA) of head and neck masses. METHODS: In a prospective, randomized, single-blinded study, 209 patients served as their own controls and underwent 236 FNAs using ThinPrep and conventional (smear) cytopreparatory techniques. RESULTS: ThinPrep produced less air-drying artifact and less mechanical distortion than the conventional method. The conventional technique was diagnostic in 63% of samples; the ThinPrep technique was diagnostic in 55% of samples. When all results were combined, pathologists subjectively preferred the conventional technique but accepted use of ThinPrep as the only cytopreparatory technique for most head and neck masses. CONCLUSIONS: For adequately experienced cytopathologists, ThinPrep is acceptable for FNA of salivary masses, neck cysts, metastatic lymph nodes, and thyroid lesions. Conventional smear technique should be used for FNA of nonmetastatic lymphoid lesions. Use of ThinPrep can complement use of the conventional (smear) cytopreparatory technique when aspirate is nondiagnostic or bloody, when the patient has a blood-borne infectious disease, when the clinician is inexperienced, or when aspirate has entered the syringe.     

Radium-226 dose to a boy from playing on mill tailings

Two boys born in September 1949 played on uranium mill tailings from about ages 8 to 12. One of these boys was diagnosed as having leukemia at age 15.5. The 226Ra body burden of the survivor was measured at age 38. The whole-body 226Ra content measured by counting in vivo was 0 +/- 17 Bq and independently by Rn breath analysis as 4.3 +/- 2.1 Bq. At the same time, a control subject with no known exposure to 226Ra, matched in age, height, and weight, was also measured. The whole-body content was estimated as 4 +/- 15 Bq and independently by Rn breath analysis as 5.5 +/- 3.7 Bq. The body burden of the control subject was not significantly different from that of the exposed person. The radiation dose to the marrow-free skeleton assuming a constant 226Ra:Ca ratio since birth was 0.49 and 1.33 mGy at ages 14 and 38, respectively. The radiation dose to the marrow-free skeleton assuming 226Ra intake only between ages 8 to 12 was 1.4 and 2.8 mGy at ages 14 and 38, respectively. The best estimate is the mean of these two estimates: 0.9 and 2.1 mGy at ages 14 and 38, respectively. The alpha-particle dose to the red marrow from 226Ra and its decay products was 0.05 mGy at age 14 and 0.10 mGy at age 38. Since no excess was found for the radium dial painters whose doses were much higher, the induction of leukemia by doses of this magnitude would seem quite unlikely.