67 research outputs found
Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer.
PURPOSE:
Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. PATIENTS AND METHODS:
Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls. RESULTS:
Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to \u3c .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P \u3c .001). Cumulative cisplatin doses \u3e 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P \u3c .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. CONCLUSION:
Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing
Communicating population health statistics through graphs: a randomised controlled trial of graph design interventions
BACKGROUND: Australian epidemiologists have recognised that lay readers have difficulty understanding statistical graphs in reports on population health. This study aimed to provide evidence for graph design improvements that increase comprehension by non-experts. METHODS: This was a double-blind, randomised, controlled trial of graph-design interventions, conducted as a postal survey. Control and intervention participants were randomly selected from telephone directories of health system employees. Eligible participants were on duty at the listed location during the study period. Controls received a booklet of 12 graphs from original publications, and intervention participants received a booklet of the same graphs with design modifications. A questionnaire with 39 interpretation tasks was included with the booklet. Interventions were assessed using the ratio of the prevalence of correct responses given by the intervention group to those given by the control group for each task. RESULTS: The response rate from 543 eligible participants (261 intervention and 282 control) was 67%. The prevalence of correct answers in the control group ranged from 13% for a task requiring knowledge of an acronym to 97% for a task identifying the largest category in a pie chart. Interventions producing the greatest improvement in comprehension were: changing a pie chart to a bar graph (3.6-fold increase in correct point reading), changing the y axis of a graph so that the upward direction represented an increase (2.9-fold increase in correct judgement of trend direction), a footnote to explain an acronym (2.5-fold increase in knowledge of the acronym), and matching the y axis range of two adjacent graphs (two-fold increase in correct comparison of the relative difference in prevalence between two population subgroups). CONCLUSION: Profound population health messages can be lost through use of overly technical language and unfamiliar statistical measures. In our study, most participants did not understand age standardisation and confidence intervals. Inventive approaches are required to address this problem
Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas
The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/ brachyury for proliferation
Water quality changes in floodplain lakes due to the Amazon River flood pulse: Lago Grande de Curuaí (Pará)
Qualidade pós-colheita de frutos de tomateiro submetidos a preparados em altas diluições
A model to explain specific cellular communications and cellular harmony:- a hypothesis of coupled cells and interactive coupling molecules
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In vitro generation of human cytotoxic lymphocytes by virus. Viral glycoproteins induce nonspecific cell-mediated cytotoxicity without release of interferon.
Purified hemagglutinin and fusion glycoproteins of measles virus either in soluble form or inserted in artifical membranes bind to human peripheral blood lymphocytes and induce cell-mediated cytotoxicity (CMC) in a dose-response fashion. Both autologous and heterologous noninfected target cells are lysed in vitro. The expression of CMC is not inhibited by anti-measles virus antibody added to lymphocytes previously exposed to viral glycoproteins. THe killer lymphocytes are Fc receptor positive, both erythrocyte-rosetting and non-erythrocyte-rosetting, as assessed by both positive and negative selection experiments. The induction of nonspecific CMC by viral glycoproteins either in the soluble state or inserted into artificial membranes could be segregated from the CMC associated with whole virions. First, on kinetics studies, purified viral glycoproteins induced CMC more rapidly than did whole virus. Second, viral glycoprotein-produced response occurred in the absence of detectable release of interferon into the culture medium, whereas CMC activity due to whole virions was associated with interferon release. The fact that purified measles virus glycoproteins integrated into artificial membrane bilayers were as efficient as their soluble counterparts in inducing CMC suggests that the hydrophobic portion of the glycoproteins was not involved in the induction and expression of the lytic activity. Purified glycoproteins from lymphocytic choriomeningitis virus behave similarly, although this virus is unrelated to measles virus. It is inferred that interferon-independent CMC induced by viral glycoproteins might account for some of the biological reactions occurring early in the control of a viral infection
Protecting the hearing-impaired worker: speech understanding with electronic hearing protection devices
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