Case of the month. A hearing problem with a difference.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
J Hill
Publications and source records attributed to J Hill.
Localized whole eye radiotherapy for retinoblastoma using a (125)I applicator, "claws".
PURPOSE: To treat children with retinoblastoma, who require whole eye radiotherapy, with a specially designed (125)I applicator that irradiates the eye while sparing the surrounding tissues. METHODS AND MATERIALS: Under general anesthesia, a pericorneal ring is attached to the 4 extraocular muscles, and 4 appendages, each loaded with (125)I seeds, are inserted beneath the conjunctiva in-between each pair of muscles and attached anteriorly to the ring. Twenty-nine eyes were treated. Eighteen received a median dose of 28 Gy during 91 hours and 11 received 40 Gy during 122 hours, when the relative biologic effectiveness was taken as 1 instead of 1.5. Six had received prior chemotherapy. RESULTS: Twenty-four eyes were followed up for 2-157 months (median 29). Although 22 eyes responded, local control was achieved in 13 patients, 3 of whom required additional treatment for new tumors; a further 3 required additional treatment for tumor recurrence as well as new tumors. One of these eyes was enucleated for neovascular glaucoma. All 6 Group I-III eyes and 6 of 18 Group V eyes were retained for 2-157 months (median 39), with good vision in 10 eyes. Three developed cataracts 7, 8, and 12 years later, 1 of which has been removed. CONCLUSIONS: This is a new way of irradiating the whole eye with a minimal dose to the surrounding tissues. The treatment time is only 5 days. It is effective in Groups I-III, but only 33% of Group V eyes retained vision. No late cosmetic defects occurred.
Antineoplastic Combined Chemotherapy Protocols↗
Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.
Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.
Journal Article↗
Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.
We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.
Journal Article↗
Molecular cloning and functional characterization of MCH2, a novel human MCH receptor.
Melanin-concentrating hormone (MCH) is involved in the regulation of feeding and energy homeostasis. Recently, a 353-amino acid splice variant form of the human orphan receptor SLC-1 () (hereafter referred to as MCH(1)) was identified as an MCH receptor. This report describes the cloning and functional characterization of a novel second human MCH receptor, which we designate MCH(2), initially identified in a genomic survey sequence as being homologous to MCH(1) receptors. Using this sequence, a full-length cDNA was generated with an open reading frame of 1023 base pairs, encoding a polypeptide of 340 amino acids, with 38% identity to MCH(1) and with many of the structural features conserved in G protein-coupled receptors. This newly discovered receptor belongs to class 1 (rhodopsin-like) of the G protein-coupled receptor superfamily. HEK293 cells transfected with MCH(2) receptors responded to nanomolar concentrations of MCH with an increase in intracellular Ca(2+) levels and increased cellular extrusion of protons. In addition, fluorescently labeled MCH bound with nanomolar affinity to these cells. The tissue localization of MCH(2) receptor mRNA, as determined by quantitative reverse transcription-polymerase chain reaction, was similar to that of MCH(1) in that both receptors are expressed predominantly in the brain. The discovery of a novel MCH receptor represents a new potential drug target and will allow the further elucidation of MCH-mediated responses.
Amino Acid Sequence↗
Obtaining consent for epidural analgesia for women in labour.
Explore the source record for details and available documents.
Analgesia, Epidural↗
Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle.
Nuclear reprogramming requires the removal of epigenetic modifications imposed on the chromatin during cellular differentiation and division. The mammalian oocyte can reverse these alterations to a state of totipotency, allowing the production of viable cloned offspring from somatic cell nuclei. To determine whether nuclear reprogramming is complete in cloned animals, we assessed the telomerase activity and telomere length status in cloned embryos, fetuses, and newborn offspring derived from somatic cell nuclear transfer. In this report, we show that telomerase activity was significantly (P < 0.05) diminished in bovine fibroblast donor cells compared with embryonic stem-like cells, and surprisingly was 16-fold higher in fetal fibroblasts compared with adult fibroblasts (P < 0.05). Cell passaging and culture periods under serum starvation conditions significantly decreased telomerase activity by approximately 30-50% compared with nontreated early passage cells (P < 0.05). Telomere shortening was observed during in vitro culture of bovine fetal fibroblasts and in very late passages of embryonic stem-like cells. Reprogramming of telomerase activity was apparent by the blastocyst stage of postcloning embryonic development, and telomere lengths were longer (15-23 kb) in cloned fetuses and offspring than the relatively short mean terminal restriction fragment lengths (14-18 kb) observed in adult donor cells. Overall, telomere lengths of cloned fetuses and newborn calves ( approximately 20 kb) were not significantly different from those of age-matched control animals (P > 0.05). These results demonstrate that cloned embryos inherit genomic modifications acquired during the donor nuclei's in vivo and in vitro period but are subsequently reversed during development of the cloned animal.
Animals↗
Fabry disease: 20 novel GLA mutations in 35 families.
Thirty two mutations have been found in 35 unrelated patients of European origin with Fabry disease, including 8 females. Twenty of the mutations are novel and comprise of 13 missense: H46Y, W47G, R49P, C94S, F113S, G258R, P259R, Q279H, Q280H, R363H, A377D, P409A, P409T; 1 nonsense: L294X; 5 small deletions: 154delT, 520delT, 909-918del10, 1152-1153delCA, 1235-1236delCT and 1 splice site mutation: IVS5+2t-->c. The remaining 12 mutations have all been reported previously. All patients with deletions had the classic form of the disease but it was not possible to predict the phenotype from the missense mutations.
DNA Mutational Analysis↗
DNA hypomethylation of karyoplasts for bovine nuclear transplantation.
The objective of this research was to evaluate if DNA hypomethylation in cells used as karyoplasts would improve development of bovine nuclear transplantation (NT) embryos. DNA from serum-fed (SF), serum-starved (SS), and 1, or 5 microM 5-azacytidine (5-aza-CR) treated cells was digested with a methylation sensitive enzyme, and evaluated for DNA methylation. A significant reduction in DNA methylation was observed in cells cultured for 48 or 72 hr in SS medium as well as in cells cultured for 48 hr in the presence of 5 microM 5-aza-CR when compared to cells cultured in SF medium. All other comparisons contained no significant differences when compared to controls. When donor cells were cultured in 5-aza-CR, SF, or SS treatment media for 48 hr, no significant difference was observed (P = 0.06) in blastocyst development rates after NT. One embryo produced by donor cells treated with 5-aza-CR established a pregnancy. Four pregnancies resulted from embryos produced by SS donor cell NT and 3 resulted from embryos produced by SF donor cell NT. Supplementation of the donor cell culture medium with 5-aza-CR was not beneficial for increasing blastocyst rate or establishing pregnancy after NT.
Animals↗
Constitutive tyrosine phosphorylation of the GABA(A) receptor gamma 2 subunit in rat brain.
GABA(A) receptors are the major sites of fast synaptic inhibition in the brain, where they are predominantly composed of alpha, beta and gamma2 subunits. A role for direct tyrosine phosphorylation of residues 365 and 367 (Y365/367) within the intracellular domain of the gamma2 subunit has been suggested to be important in modulating GABA(A) receptor function, based on the study of recombinant receptors. To address the relevance of these observations for neuronal GABA(A) receptors we have studied the phosphorylation of the gamma2 subunit in the brain. In adult rat brain the gamma2 subunit is phosphorylated on tyrosine residues, including Y365/367 as defined using a phosphospecific antisera. In cultured cortical neurones, phosphorylation of Y365/367 is highly regulated and was only evident upon inhibition of tyrosine phosphatases. We also establish that the tyrosine kinase Src is capable of specifically interacting with the intracellular domains of receptor beta and gamma2 subunits. This may specifically localise tyrosine kinase activity to GABA(A) receptors, facilitating rapid receptor tyrosine phosphorylation upon kinase activation. Together our results suggests that tyrosine phosphorylation of the gamma2 subunit, possibly by closely associated Src, may be a dynamic mechanism for regulating GABA(A) receptor function in the brain.
Amino Acid Sequence↗
The effect of NKISK on tendon in an in vivo model.
The mechanism through which ligaments and tendons change length during growth and contracture is unclear. It has been hypothesized that there is a reversible "interfibrillar bond" that, when broken, allows the sliding of collagen fibrils past one another during length changes. The pentapeptide NKISK has been reported to inhibit the binding of decorin to fibronectin. This study was designed to evaluate the effect of NKISK in an in vivo model. Male Sprague-Dawley rats were divided into three groups (n = 9, 9 and 14, respectively). The left patellar tendon was injected with 1.0 ml of NKISK (Group 1 = 1.0 mM, Groups 2 and 3 = 5.0 mM). The contralateral/control limb was injected with carrier. Group 1 was sacrificed after three, Group 2 after four and Group 3 after seven daily injections. The patellar tendon lengths were measured in all groups with comparisons made to the contralateral control limb. NKISK injection resulted in a significant increase in length in Group 2 (3.14% +/- 2.04, P = 0.002) and in Group 3 (6.12% +/- 3.84, P < 0.001). Biomechanical testing of Group 3 showed no differences in maximum load, ultimate strength, structural stiffness, or elastic modulus of the treated tendons but did demonstrate a statistically significant decrease in the displacement and strain at maximum load in the NKISK-treated tendons. This study demonstrates that inhibition of decorin/fibronectin binding by NKISK results in tendon lengthening in an in vivo setting as noted by a progressive increase in the length of the patellar tendon.
Animals↗
Screening of patients at high risk of colorectal cancer.
OBJECTIVE: To determine the present state of colonoscopic screening practice for patients at a high risk of developing colorectal cancer. METHODS: We assessed colonoscopic screening practice in nine colorectal surgery or gastroenterology units referring patients to the regional genetics centre in the North-west of England. The validity of the pedigree was confirmed by inspection of Hospital records, use of cancer registries and records of general practitioners across the United Kingdom. The screening activity at the participating centres was investigated by means of a questionnaire, site visit and study of case notes. RESULTS: One hundred and eight high risk families were identified. Outside the genetics unit, family history was not taken in a structured manner and family pedigree was not confirmed. In four units screening was offered directly by the consultant surgeon. Differing protocols for screening were in place in six units, but were frequently not adhered to. Colonoscopy completion rates were known in only four units (range 83-97%). Frequency of screening varied from 2 to 5 years. Recording of information was minimal outside the patients' records and there were no dedicated databases. Facilities for families to be screened together existed in three units and the psychological effect of screening was not determined outside the genetics centre. CONCLUSIONS: Screening practice should be standardized and specific criteria met before regular screening is initiated. A dedicated database should be established to record information from units screening patients at high risk of colorectal cancer.
Journal Article↗
Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans.
Apolipoprotein E (apo E) deficiency (or its abnormalities in humans) is associated with a series of pathological conditions including dyslipidemia, atherosclerosis, Alzheimer's disease, and shorter life span. The purpose of this study was to characterize these conditions in apo E-deficient C57BL/6J mice and relate them to human disorders. Deletion of apo E gene in mice is associated with changes in lipoprotein metabolism [plasma total cholesterol (TC) (>+400%), HDL cholesterol (-80%), HDL/TC, and HDL/LDL ratios (-93% and -96%, respectively), esterification rate in apo B-depleted plasma (+100%), plasma triglyceride (+200%), hepatic HMG-CoA reductase activity (-50%), hepatic cholesterol content (+30%)], decreased plasma homocyst(e)ine and glucose levels, and severe atherosclerosis and cutaneous xanthomatosis. Hepatic and lipoprotein lipase activities, hepatic LDL receptor function, and organ antioxidant capacity remain unchanged. Several histological/immunohistological stainings failed to detect potential markers for neurodegenerative disease in the brain of 37-wk-old male apo E-KO mice. Apo E-KO mice may have normal growth and development, but advanced atherosclerosis and xanthomatosis may indirectly reduce their life span. Apo E plays a crucial role in regulation of lipid metabolism and atherogenesis without affecting lipase activities, endogenous antioxidant capacity, or appearance of neurodegenerative markers in 37-wk-old male mice.
Animals↗
Population-based study of rotavirus vaccination and intussusception.
BACKGROUND: During the first year that the rhesus rotavirus tetravalent vaccine (RRV-TV) was licensed, the Vaccine Adverse Event Reporting System received several reports of intussusception after vaccination. To evaluate the risk of intussusception, we conducted a retrospective cohort study in ten managed care organizations. METHODS: Cases of intussusception were identified by searching electronic databases for diagnoses of intussusception (ICD-9 Code 560.0) in infants 1 to 11 months of age and confirmed by medical chart review. Vaccination and enrollment data were obtained from administrative databases. Incidence rate ratios (RR) of intussusception were computed by dividing incidence rates in prespecified risk intervals after vaccination by the background rate of intussusception and adjusted for age by Poisson regression. Cox proportional hazard regression was used to evaluate risk by vaccine dose. RESULTS: Of 463,277 children 56,253 had been vaccinated with a total of 91 371 doses of RRV-TV. The incidence rate of intussusception was 25/100,000 person years among unexposed infants and 340/100,000 person years 3 to 7 days postvaccination. In the interval 3 to 7 days after vaccination, the age-adjusted RR was 16.0 (95% confidence interval, 5.5 to 46.7) for all doses combined and 30.4 (95% confidence interval, 8.8 to 104.9) after the first dose. RRs for the 8- to 14- and 15- to 21-day risk intervals were >1.0, but the confidence intervals substantially overlapped 1.0. The attributable risk was one case of intussusception per 11 073 children vaccinated. CONCLUSIONS: RRV-TV is associated with an increased risk of intussusception. The risk is greatest 3 to 7 days after the first vaccination dose.
Humans↗
Individual predictors of posttraumatic distress: a structural equation model.
OBJECTIVE: Recent research has called into question the "dose-effect" model of understanding response to trauma and has turned attention to the contribution of personality and environmental factors. This research seeks to model the interrelation of relational capacity (a component of personality), perceptions of social support, and posttraumatic distress. METHOD: A group of firefighters (n = 164) completed questionnaires that addressed exposure to traumatic events, social support, current level of distress, and relational capacity. Structural equation modelling was used to develop a framework for understanding traumatic reactions. RESULTS: The overall fit of the hypothesized model was excellent. Relational capacity had a significant negative effect on support, indicating that perceived social support decreased as disturbances in relational capacity increased. Perceived social support had a significant negative effect on level of distress. CONCLUSION: While some emotional response to disturbing events may be normal, the severity of symptoms covaries with the ability of the individual to develop and sustain supportive relationships to buffer the impact of events.
Adolescent↗
Child sexual abuse, poor parental care and adult depression: evidence for different mechanisms.
BACKGROUND: Child sexual abuse (CSA) and poor parental care (neglect and institutional care) are associated with depression in adult life. Little is known about possible mechanisms underlying these associations. AIMS: To examine the role of adult intimate-love relationships as differential mediators or moderators of the associations between CSA, poor parental care and adult depression. METHOD: Sampling was carried out in two phases. In the first, questionnaires were sent to women aged 25-36 years in five primary care practices. Second-phase subjects for interview (n=198) were drawn from three strata defined on the basis of childhood adversities. Recalled childhood experiences and recent adult relationships and depression were assessed and rated independently. Frequencies of predictor and response variables, effect estimates and their confidence intervals were weighted back to the general population questionnaire sample. RESULTS: The risk for depression associated with CSA was unaffected by quality of adult relationships, while the risk associated with poor parental care was substantially altered. CONCLUSIONS: There may be different pathways linking CSA and poor parental care to adult depression.
Adult↗
The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism.
In 1997 in this Journal we published the "Reading the Mind in the Eyes" Test, as a measure of adult "mentalising". Whilst that test succeeded in discriminating a group of adults with Asperger syndrome (AS) or high-functioning autism (HFA) from controls, it suffered from several psychometric problems. In this paper these limitations are rectified by revising the test. The Revised Eyes Test was administered to a group of adults with AS or HFA (N = 15) and again discriminated these from a large number of normal controls (N = 239) drawn from different samples. In both the clinical and control groups the Eyes Test was inversely correlated with the Autism Spectrum Quotient (the AQ), a measure of autistic traits in adults of normal intelligence. The Revised Eyes Test has improved power to detect subtle individual differences in social sensitivity.
Adult↗
Differential response to targeted recruitment strategies to fitness promotion research by African-American women of varying body mass index.
OBJECTIVE: To assess patterns of recruitment into a community-based NCI-funded physical activity and dietary lifestyle change program targeting African-American women. DESIGN: Acquisition of a convenience sample to be screened for participation in a randomized, controlled prevention intervention. SETTING: African-American-owned and -operated health club located in an area of Los Angeles in which African Americans are concentrated. PARTICIPANTS: 893 African-American women. RECRUITMENT STRATEGIES: Social networking/word-of-mouth, staff presentations, mass and targeted media, and physician referral. MAIN OUTCOME MEASURE: Completion of screening questionnaire indicating a desire to enroll in the study. Screening questionnaire domains included self-reported height and weight, recent participation in organized weight loss programs, ability to walk one mile unassisted, current medication use, smoking status, personal medical history of cancer, sociodemographic variables, and recruitment source. RESULTS: Sociodemographic and anthropometric characteristics distinguished between respondents obtained through different recruitment strategies. In particular, women with a higher body mass index (BMI) were more likely than those with lower BMIs (P = .014) to be recruited through more personalized methods (eg, social networking). CONCLUSIONS: Culturally tailored recruitment strategies are critical in securing the participation of members of "hard-to-reach" populations, who are both under-represented in health promotion research and at high risk for chronic diseases.
Adult↗