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61.
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63.
Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population 总被引:8,自引:0,他引:8
Jacquemont S Hagerman RJ Leehey MA Hall DA Levine RA Brunberg JA Zhang L Jardini T Gane LW Harris SW Herman K Grigsby J Greco CM Berry-Kravis E Tassone F Hagerman PJ 《JAMA》2004,291(4):460-469
Context Premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are frequent in the general population, with estimated prevalences of 1 per 259 females and 1 per 813 males. Several articles have recently described the presence of late-onset neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified syndrome are cerebellar ataxia and intention tremor. Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction. Objective To study the penetrance of the fragile Xassociated tremor/ataxia syndrome (FXTAS) among premutation carriers. Design, Setting, and Participants Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through a survey and a standardized neurological examination, which was videotaped and subsequently scored in a blinded fashion. Main Outcome Measures Penetrance of intention tremor and ataxia among adult carriers (aged =" BORDER="0">50 years) of premutation expansions of the FMR1 gene. Results Data from the survey of 192 individuals demonstrated an age-related penetrance of the combination of reported intention tremor and gait ataxia in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants aged 50-59, 60-69, 70-79, and =" BORDER="0">80 years, respectively). The male carrier group had an age-adjusted 13-fold increased risk (95% confidence interval, 3.9-25.4; P = .003) of combined intention tremor and gait ataxia when compared with male controls. The clinical examination data from 93 individuals demonstrated that male carriers experienced more difficulties on each of 3 standardized neurological rating scales compared with controls (P<.05). Female carrier scores were also higher than those of female controls (P<.05) on 2 of the 3 neurological rating scales, but no participant was identified with probable or definite FXTAS. Conclusions The study demonstrates that older male carriers of premutation alleles of the FMR1 gene are at high risk of developing FXTAS. Since male premutation carriers are relatively common in the general population, older men with ataxia and intention tremor should be screened for the FMR1 mutation, especially if these signs are accompanied by parkinsonism, autonomic dysfunction, or cognitive decline, regardless of family history. 相似文献
64.
In this study, we present a new method to derive a single-number measure of the directivity of hearing aids. The method is an extension of the conventional directivity index (DI), and is called overall directivity index (ODI). The directivities of five different hearing aid styles were compared with that of the open ear. The behind-the-ear (BTE) style showed the lowest directionality compared to the other hearing aid styles and the open ear. There were only minor differences in directivity between any of the four different hearing aid styles placed in the ear and of the open ear canal. The conventional measure of DI is less suitable for hearing aids, because it ignores sound coming from other than the frontal direction. To quantify directionality of a hearing aid in a real-life situation, we suggest the single-number ODI, weighted with the articulation index and related to a listening segment of 0-30 degrees. An application of the data is shown for a BTE with a directional microphone. 相似文献
65.
Loesch DZ Huggins RM Bui QM Epstein JL Taylor AK Hagerman RJ 《Journal of developmental and behavioral pediatrics : JDBP》2002,23(6):416-423
The effect of the fragile X mental retardation 1 (FMR1) gene product (fragile X mental retardation protein [FMRP]) deficits on Full-Scale IQ (FSIQ) and FSIQ-adjusted Wechsler subtests and index scores in fragile X disorder were assessed using a robust modification of the maximum likelihood estimators for pedigree data. The results from 144 extended families have demonstrated a linear effect of progressively reduced levels of FMRP on the FSIQ and all subtest and summary scores in either gender. The effect of FMRP in decreasing FSIQ-adjusted subtest scores was highly significant for Digit Span, Symbol Search, Object Assembly, and Picture Arrangement, with a consistent trend in both genders. Heritability for FSIQ and unadjusted subtest scores estimated from the covariance model did not exceed 50% and varied widely from the highest for Verbal score to the lowest for Picture Completion score. Possible mechanisms by which FMRP deficit impacts on specific weaknesses in fragile X are considered on the basis of present data. 相似文献
66.
Fragile X syndrome: a model of gene-brain-behavior relationships 总被引:5,自引:0,他引:5
67.
Gould EL Loesch DZ Martin MJ Hagerman RJ Armstrong SM Huggins RM 《American journal of medical genetics》2000,95(4):307-315
Sleep patterns and endogenous melatonin profiles in 13 fragile X boys between the age of 4.7 and 11.0 years were compared to those of 8 age-matched, normal control boys. Parents recorded sleep patterns on a Sleep Diary Chart for 14 consecutive days. Twelve saliva samples were obtained from 8 fragile X participants and all of the controls over 48 hours for the assessment of salivary melatonin profiles. The results showed greater variability in total sleep time and difficulty in sleep maintenance in fragile X boys compared with the control participants. Nocturnal melatonin production, expressed as both peak level and area under the concentration-time curve between 20:00 h and 08:00 h, were found to be significantly larger in fragile X boys than in controls. Additionally, the mean of the minimum daytime melatonin levels recorded was significantly higher for the fragile X group. Elevated levels in some fragile X boys relative to the range seen in controls, occurring either during the day or at night, or in both segments of the secretory profile for some individuals, may be due in part to overactivity of the sympathetic nervous system. Alternative molecular mechanisms leading to changes in melatonin profiles in fragile X are also discussed. 相似文献
68.
Understanding diet and energy balance as risk factors for breast, colon,
and other cancers requires information on the contribution of each factor
and of interactions among factors to cancer risk. Rodent models for breast
cancer provide extensive data on effects of dietary fat and calories,
energy balance, body weight gain, and physical activity on tumor
development. Analyses of the combined data from many studies have shown
clearly that quality and quantity of dietary fat and energy balance
contribute independently to increased mammary gland tumorigenesis. These
findings were seen in female rats fed diets high in fat (35-40% of
calories) compared to rats fed control diets, with approximately 10% of
calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46,
215-223). The methods used permit comparison of experimental and
epidemiological data, and they may be useful in extrapolating between
species and developing public health recommendations. In addition to the
contributions of lifetime-diet composition, intake, energy balance, and
physical activity to cancer risk, there are questions about the timing and
duration of alterations in these factors and about the "dose-response"
characteristics of cancer risk to the factors. Endocrine mechanisms may be
significant in mammary gland tumor risk, but experimental and
epidemiological data indicate that cancers at other sites, such as colon
and liver, also are influenced by the factors listed. Other diet and
lifestyle factors that influence energy, or specifically fat, metabolism
may also affect risk for cancers that are promoted by increased intake of
fat and calories. Studies of separate and interactive effects of dietary
fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et
al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using
adjustment of carcinogenesis endpoints for body weight, tumor burden, and
latency, they were found to be related to weight gain within treatment
groups in 2 of 3 experiments.
相似文献
69.
Background
Postal questionnaires are an economical and simple method of data collection for research purposes but are subject to non-response bias. Several studies have explored the effect of monetary and non-monetary incentives on response. Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates. However, large surveys rarely have the resources to reward individual participants. Three previous papers report on the effectiveness of lottery incentives with contradictory results. This study aimed to determine the effect of including a lottery-style incentive on response rates to a postal health survey.Methods
Randomised controlled trial. Setting: North and West Birmingham. 8,645 patients aged 18 or over randomly selected from registers of eight general practices (family physician practices). Intervention: Inclusion of a flyer and letter with a health questionnaire informing patients that returned questionnaires would be entered into a lottery-style draw for £100 of gift vouchers. Control: Health questionnaire accompanied only by standard letter of explanation. Main outcome measures: Response rate and completion rate to questionnaire.Results
5,209 individuals responded with identical rates in both groups (62.1%). Practice, patient age, sex and Townsend score (a postcode based deprivation measure) were identified as predictive of response, with higher response related to older age, being female and living in an area with a lower Townsend score (less deprived).Conclusion
This RCT, using a large community based sample, found that the offer of entry into a lottery style draw for £100 of High Street vouchers has no effect on response rates to a postal health questionnaire. 相似文献70.