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| Type of Article | | Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT
| | | Humans or Animals | | Humans Animals
| | | Ages | | All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined
| | | Language | | English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French
| | | Intervention | | Patient education Communication and counselling Patient involvement through self-monitoring Reminders Reinforcement or rewards Other (e.g. combined education and reminders) Unknown Educational Materials Group threrapy Couples threrapy Individual threrapy Healthy eating Increased physical activity Not Diet or Exercise Welfare-to-work program
| | | Patient Demograhics | | Welfare recipients Unknown Not on welfare Mean Age Percent high school diploma Percent GED or high school diploma Mean number of years of education
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Kirsten D Mertz,Francesca Demichelis,Andrea Sboner,Michelle S Hirsch,Paola Dal Cin,Kirsten Struckmann,Martina Storz,Simone Scherrer,Daniel M Schmid,Räto T Strebel,Nicole M Probst-Hensch,Mark Gerstein,Holger Moch,Mark A Rubin The purpose of our study was to demonstrate that distinct cytogenetic alterations in the most common subtype of renal cell cancer, clear cell renal cell carcinoma (ccRCC), are reflected in protein expression profiles. We performed conventional cytogenetics and immunohistochemical analysis for cytok... ( view more )eratins (CKs) on 126 ccRCCs. Protein expression was evaluated in situ using a semiautomated quantitative system. The results were validated using an independent cohort of 209 ccRCCs with long-term follow-up. Cytogenetic alterations were identified in 96 of 126 ccRCCs, most of them involving chromosome 3 through loss, deletion or translocation. Expression of CKs and E-cadherin in ccRCC was associated with lack of cytogenetic alterations and low nuclear grade. In the validation set, CK7 and CK19 protein expression was associated with better clinical outcome. At the multivariate level, the best model included metastatic status and CK19 expression. Expression microarray analysis on 21 primary ccRCCs and 14 ccRCC metastases identified genes significantly associated with CK7 and CK19 expressing ccRCCs. Two novel ccRCC biomarkers associated with the CK7 positive ccRCC phenotype, PMS2 and MT1-MMP (MMP14), were further validated. We conclude that the variability observed for CK expression in ccRCC can be explained by genetic heterogeneity. Distinct molecular subtypes of ccRCC with prognostic relevance were identified, and the CK7/CK19 expressing subtype is associated with better outcome. ( view less ) Bronwyn Hall,Kirsten Howard,Kirsten McCaffery OBJECTIVE: New human papillomavirus (HPV) DNA technologies for the detection and prevention of cervical cancer have led to exciting changes in cervical cancer screening worldwide. Their introduction, however, has left many women with unanswered medical and psychosocial HPV questions. This study con... ( view more )sidered the degree to which women's own HPV questions were addressed in Australian cervical cancer screening patient information leaflets. METHODS: Based on previous qualitative research that asked women to identify their own HPV information needs, categories of interest were identified and a coding framework was developed. Manifest content analysis was conducted by counting the number of times a category of interest was stated in the text of the patient information leaflets (n=75). Latent content analysis methodology was employed to assess the underlying and embedded meaning within the leaflets. RESULTS: Women's medical questions were addressed more frequently than psychosocial ones. Leaflets were designed for specific target audiences (Aboriginal, lesbian, older women, women with disabilities, HPV-specific, cervical cancer-specific and general Pap screening) and the type and amount of HPV information varied by group. Merging the manifest and latent results, we identified three broad themes for discussion: the medicalisation of women's cervical screening experience, the purpose and target audience of cervical screening leaflets and HPV as a community versus women's health issue. CONCLUSIONS: Women's questions on HPV were inconsistently and often inadequately answered. PRACTICE IMPLICATIONS: In order that women's information needs are met, more accurate and balanced representations of medical and psychosocial HPV information should be provided in patient information leaflets. ( view less ) Kirsten F Condry,Elizabeth S Spelke Reports an error in "The development of language and abstract concepts: The case of natural number" by Kirsten F. Condry and Elizabeth S. Spelke (Journal of Experimental Psychology: General, 2008[Feb], Vol 137[1], 22-38). The DOI for the supplemental materials was printed incorrectly. The correct D... ( view more )OI is as follows: http://dx.doi.org/10.1037/0096-3445.137.1.22.supp (The following abstract of the original article appeared in record 2008-01081-003.) What are the origins of abstract concepts such as "seven," and what role does language play in their development? These experiments probed the natural number words and concepts of 3-year-old children who can recite number words to ten but who can comprehend only one or two. Children correctly judged that a set labeled eight retains this label if it is unchanged, that it is not also four, and that eight is more than two. In contrast, children failed to judge that a set of 8 objects is better labeled by eight than by four, that eight is more than four, that eight continues to apply to a set whose members are rearranged, or that eight ceases to apply if the set is increased by 1, doubled, or halved. The latter errors contrast with children's correct application of words for the smallest numbers. These findings suggest that children interpret number words by relating them to 2 distinct preverbal systems that capture only limited numerical information. Children construct the system of abstract, natural number concepts from these foundations. (PsycINFO Database Record (c) 2008 APA, all rights reserved). ( view less ) Kirsten Howard,Glenn Salkeld,Kirsten McCaffery,Les Irwig A two-stage standard gamble was used to evaluate women's preferences for alternative managements of atypical squamous cells of undermined significance (ASCUS) on Pap smear (repeat Pap smear compared with immediate HPV test), and to test for the evidence of process utility. Women's utilities for the... ( view more ) health state scenarios were clustered towards the upper end of the 0-1 scale with considerable variability in women's preferences. There was evidence of process utility, with immediate human papillomavirus (HPV) testing strategies having lower valuations than repeat Pap smear, where the clinical outcome was the same. Mean (95% CI) utilities for HPV testing (negative test) followed by resolution were 0.9967 (0.9957-0.9978) compared with repeat Pap smear followed by resolution: 0.9972 (0.9964-0.9980). Mean (95% CI) utilities for immediate HPV testing (positive test), followed by colposcopy, biopsy and treatment were 0.9354 (0.8544-1.0) compared with repeat Pap smear followed by colposcopy, biopsy and treatment: 0.9656 (0.9081-1.0). Our results add to the existing evidence that the impact of healthcare interventions on well-being is not limited to the effect of the intervention on the health outcomes expected from the intervention; process of care can have quality of life implications for the individual. A modelled application of trial-based data will allow characterisation of the true population costs, benefits, risks and harms of alternative triage strategies and subsequent policy implications thereof. ( view less ) Poul Holm-Pedersen,Kirsten Schultz-Larsen,Niels Christiansen,Kirsten Avlund OBJECTIVES: To examine whether tooth loss at age 70 is associated with onset of disability at 5-, 10-, 15-, and 20-year follow-up and to mortality at 21-year follow-up. SETTING: Community-based population in Copenhagen. DESIGN: A baseline study of a random sample of 70-year-old people born in 1914 ... ( view more )and follow-up 5, 10, 15, and 20 years later. PARTICIPANTS: A total of 573 nondisabled individuals participated in the study of 70-year-olds in 1984, 460 participated in the 5-year follow-up, 292 in the 10-year follow-up, 150 in the 15-year follow-up, and 78 in the 20-year follow-up. MEASUREMENTS: Data from interviews and a medical and oral examination. Oral health was measured according to number of teeth (0, 1-9, 10-19, > or = 20). Disability was measured using the Avlund Mob-H scale at age 75, 80, 85, and 90. Mortality data were obtained from the National Death Register. RESULTS: Being edentulous or having one to nine teeth was associated with onset of disability at age 75 and 80. Health-related variables and education attenuated the associations between edentulism and onset of disability, although they remained marginally significant, whereas the association between having one to nine teeth and onset of disability remained unchanged and statistically significant at 10-year follow-up (odds ratio=3.02, 95% confidence interval (CI)=1.26-7.24). Persons who were edentulous at age 70 were at significantly higher risk of mortality 21 years later, also in the adjusted analysis (hazard ratio=1.26, 95% CI=1.03-1.55). CONCLUSION: Tooth loss is independently associated with onset of disability and mortality in old age. The findings indicate that tooth loss may be an early indicator of accelerated aging. ( view less ) Anette Bendixen,Thorkild I A Sørensen,Kirsten Hørder,Anders J Svendsen,Charlotte Leboeuf-Yde,Ida E Steffensen,Kirsten Ohm Kyvik INTRODUCTION: Body satisfaction has mostly been investigated among patients with psychiatric diseases. A few studies have found an association between physical activity, obesity and body satisfaction in the healthy population, but the focus has mostly been on the risk of developing diseases. The ai... ( view more )m of the present study has been to study the association between body satisfaction, BMI, physical activity and chronic diseases. MATERIALS AND METHODS: A total of 15,252 women and 14,181 men born between 1953 and 1982 (both years included) and registered with The Danish Twin Registry answered a questionnaire which they were sent in 1994. We used the questions on chronic diseases, height and weight, physical activity and body satisfaction. Univariat analysis of body satisfaction and the other variables was carried out using chi2-tests and t-tests. Multivariat analysis was carried out with logistic regression. RESULTS: More men than women are satisfied with their bodies; BMI confers a negative association, while physical activity confers a positive association with body satisfaction. This satisfaction appears to some degree mediated by BMI. The presence of asthma and other lung symptoms and lower-back pain was negatively associated with body satisfaction. DISCUSSION: Thinness tends to be the ideal body image today and this may explain why more obese people are dissatisfied with their body. This ideal is more important for women s perception of their bodies. Physical activity and being healthy adds to body satisfaction. ( view less ) Jim I Mann,David C Tipene-Leach,Helen L R Pahau,Nathan R Joseph,Sally Abel,Kirsten A McAuley,Kirsten J Coppell,Chris S Booker,Sheila M Williams We sought to identify lifestyle behaviours which influence risk of impaired glucose metabolism, IGM (newly diagnosed type 2 diabetes, impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) or insulin resistance (IR) in a predominantly Maori community, and applied the McAuley formula t... ( view more )o determine whether it predicts high risk individuals amongst this community. Three hundred and seventy one participants completed a lifestyle and dietary behaviour questionnaire and oral glucose tolerance test. Clinical variables, microalbuminuria, fasting glucose, insulin and lipids were measured. Diabetes, IFG and IGT were defined according to WHO criteria. IR was defined using the McAuley formula. Those with IGM and those with IR showed similar risk factor attributes. Odds ratios (95% CI) for development of IGM and IR were 0.43 (0.21-0.88) and 0.51 (0.33-0.80), respectively, for regular physical activity, and 0.55 (0.26-1.15) and 0.59 (0.37-0.96), respectively, for two or more dietary behaviours characterized by a high intake of fibre. Regular physical activity and a diet characterized by a high intake of dietary fibre were found to reduce risk of newly diagnosed IGM or IR. The McAuley formula appears to predict high-risk individuals in a predominantly Maori population as it does in European populations. ( view less ) Elvira Schettler,Falko Steinbach,Iris Eschenbacher-Kaps,Kirsten Gerst,Franz Muessdoerffer,Kirsten Risch,Wolf Jürgen Streich,Kai FrölichAn active survey on transmissible spongiform encephalopathies was performed from 2002 to 2005 on 4,255 roe deer, 1,445 red deer, and 1,604 fallow deer in Germany. All cervids tested negative. This survey has been the largest in European wildlife and provides no evidence of prion diseases in free-li... ( view more )ving German cervids. ( view less ) Peter la Cour,Kirsten Avlund,Kirsten Schultz-Larsen The aim of the study was to analyse associations of religiosity and mortality in a secular region. The sample consisted of 734 Danish, community dwelling elderly persons, living in a secular culture, and all aged 70 when primary data were collected. Secondary data consisted of a 20 year follow-up o... ( view more )n vital status or exact age of death. The study was designed to be highly comparable to studies conducted in more religious environments in order to compare results. Three variables of religion were investigated in relation to survival: importance of affiliation, church attendance and listening to religious media. Relative hazards (RH) of dying were controlled in models including gender, education, medical and mental health, social relations, help given and received, and health behaviour. The results showed significant and positive associations between claiming religious affiliation important and survival (relative hazard of dying=RH .70; 95% CI .58-.85) and church attendance and survival (RH .73; 95% CI .64-.87). Results decreased and only stayed significant regarding church attendance when controlled for covariates. Nearly all significant effects were seen in women, but not in men. The effect size of the full sample is less than in more religious environments in United States samples. Although the positive overall RHs are comparable to those of other studies, the mediating variables and pathways of effects seem dissimilar in this sample from a secular environment. Receiving and especially giving help to others are suggested as variables of explanatory value. ( view less ) Nikolas Offenhauser,Kirsten Thomsen,Kirsten Caesar,Martin Lauritzen Functional neuroimaging relies on the robust coupling between neuronal activity, metabolism and cerebral blood flow (CBF), but the physiological basis of the neuroimaging signals is still poorly understood. We examined the mechanisms of activity-dependent changes in tissue oxygenation in relation t... ( view more )o variations in CBF responses and postsynaptic activity in rat cerebellar cortex. To increase synaptic activity we stimulated the monosynaptic, glutamatergic climbing fibres that excite Purkinje cells via AMPA receptors. We used local field potentials to indicate synaptic activity, and recorded tissue oxygen partial pressure (P(tiss,O2)) by polarographic microelectrodes, and CBF using laser-Doppler flowmetry. The disappearance rate of oxygen in the tissue increased linearly with synaptic activity. This indicated that, without a threshold, oxygen consumption increased as a linear function of synaptic activity. The reduction in P(tiss,O2) preceded the rise in CBF. The time integral (area) of the negative P(tiss,O2) response increased non-linearly showing saturation at high levels of synaptic activity, concomitant with a steep rise in CBF. This was accompanied by a positive change in P(tiss,O2). Neuronal nitric oxide synthase inhibition enhanced the initial negative P(tiss,O2) response ('dip'), while attenuating the evoked CBF increase and positive P(tiss,O2) response equally. This indicates that increases in CBF counteract activity-induced reductions in P(tiss,O2), and suggests the presence of a tissue oxygen reserve. The changes in P(tiss,O2) and CBF were strongly attenuated by AMPA receptor blockade. Our findings suggest an inverse relationship between negative P(tiss,O2) and CBF responses, and provide direct in vivo evidence for a tight coupling between activity in postsynaptic AMPA receptors and cerebellar oxygen consumption. ( view less ) Kirsten Gehlhar,Marcus Peters,Kirsten Brockmann,Hans van Schijndel,Albrecht Bufe BACKGROUND: To date, there is no well-established test available that can be used to measure functional properties of modified allergens (allergoids). Due to the cross-linking process, the IgE-binding capacity of the allergens, normally necessary for their characterization, is lost. The aim of this... ( view more ) study was to test whether the rat basophilic leukaemia (RBL) cell assay (beta-hexosaminidase release by rat basophils upon allergen stimulation) can be adopted to characterize allergoids and to evaluate the assay for testing allergoids and native allergens as well. METHODS: Mice were immunized with native and modified Phleumpratense extracts in the presence of alum. Their sera were used to sensitize RBL-2H3 cells and measure basophil stimulation induced by different allergen extracts in the presence or absence of various additives. RESULTS: Sera containing specific IgE against both extract formulations were obtained. Native as well as modified extracts induced dose-dependent beta-hexosaminidase release from RBL cells. Both extracts were used to evaluate the characteristics of the assay, which showed high precision. Storage conditions were chosen to enhance extract degradation, which could be read directly from the altered stimulatory capacity of the extracts. Additives turned out to have diverse effects on the assay, whereas phenol had no measurable effect, alum had an inhibitory effect and glycerol elevated basophil activation. CONCLUSIONS: For the first time, a reliable, precise in vitro assay is available that is able to directly measure the properties of modified allergen extracts after their production process. The test is well evaluated and its advantages and limitations are discussed in this report. ( view less ) Mark T Ross,Darren V Grafham,Alison J Coffey,Steven Scherer,Kirsten McLay,Donna Muzny,Matthias Platzer,Gareth R Howell,Christine Burrows,Christine P Bird,Adam Frankish,Frances L Lovell,Kevin L Howe,Jennifer L Ashurst,Robert S Fulton,Ralf Sudbrak,Gaiping Wen,Matthew C Jones,Matthew E Hurles,T Daniel Andrews,Carol E Scott,Stephen Searle,Juliane Ramser,Adam Whittaker,Rebecca Deadman,Nigel P Carter,Sarah E Hunt,Rui Chen,Andrew Cree,Preethi Gunaratne,Paul Havlak,Anne Hodgson,Michael L Metzker,Stephen Richards,Graham Scott,David Steffen,Erica Sodergren,David A Wheeler,Kim C Worley,Rachael Ainscough,Kerrie D Ambrose,M Ali Ansari-Lari,Swaroop Aradhya,Robert I S Ashwell,Anne K Babbage,Claire L Bagguley,Andrea Ballabio,Ruby Banerjee,Gary E Barker,Karen F Barlow,Ian P Barrett,Karen N Bates,David M Beare,Helen Beasley,Oliver Beasley,Alfred Beck,Graeme Bethel,Karin Blechschmidt,Nicola Brady,Sarah Bray-Allen,Anne M Bridgeman,Andrew J Brown,Mary J Brown,David Bonnin,Elspeth A Bruford,Christian Buhay,Paula Burch,Deborah Burford,Joanne Burgess,Wayne Burrill,John Burton,Jackie M Bye,Carol Carder,Laura Carrel,Joseph Chako,Joanne C Chapman,Dean Chavez,Ellson Chen,Guan Chen,Yuan Chen,Zhijian Chen,Craig Chinault,Alfredo Ciccodicola,Sue Y Clark,Graham Clarke,Chris M Clee,Sheila Clegg,Kerstin Clerc-Blankenburg,Karen Clifford,Vicky Cobley,Charlotte G Cole,Jen S Conquer,Nicole Corby,Richard E Connor,Robert David,Joy Davies,Clay Davis,John Davis,Oliver Delgado,Denise Deshazo,Pawandeep Dhami,Yan Ding,Huyen Dinh,Steve Dodsworth,Heather Draper,Shannon Dugan-Rocha,Andrew Dunham,Matthew Dunn,K James Durbin,Ireena Dutta,Tamsin Eades,Matthew Ellwood,Alexandra Emery-Cohen,Helen Errington,Kathryn L Evans,Louisa Faulkner,Fiona Francis,John Frankland,Audrey E Fraser,Petra Galgoczy,James Gilbert,Rachel Gill,Gernot Glöckner,Simon G Gregory,Susan Gribble,Coline Griffiths,Russell Grocock,Yanghong Gu,Rhian Gwilliam,Cerissa Hamilton,Elizabeth A Hart,Alicia Hawes,Paul D Heath,Katja Heitmann,Steffen Hennig,Judith Hernandez,Bernd Hinzmann,Sarah Ho,Michael Hoffs,Phillip J Howden,Elizabeth J Huckle,Jennifer Hume,Paul J Hunt,Adrienne R Hunt,Judith Isherwood,Leni Jacob,David Johnson,Sally Jones,Pieter J de Jong,Shirin S Joseph,Stephen Keenan,Susan Kelly,Joanne K Kershaw,Ziad Khan,Petra Kioschis,Sven Klages,Andrew J Knights,Anna Kosiura,Christie Kovar-Smith,Gavin K Laird,Cordelia Langford,Stephanie Lawlor,Margaret Leversha,Lora Lewis,Wen Liu,Christine Lloyd,David M Lloyd,Hermela Loulseged,Jane E Loveland,Jamieson D Lovell,Ryan Lozado,Jing Lu,Rachael Lyne,Jie Ma,Manjula Maheshwari,Lucy H Matthews,Jennifer McDowall,Stuart McLaren,Amanda McMurray,Patrick Meidl,Thomas Meitinger,Sarah Milne,George Miner,Shailesh L Mistry,Margaret Morgan,Sidney Morris,Ines Müller,James C Mullikin,Ngoc Nguyen,Gabriele Nordsiek,Gerald Nyakatura,Christopher N O'Dell,Geoffery Okwuonu,Sophie Palmer,Richard Pandian,David Parker,Julia Parrish,Shiran Pasternak,Dina Patel,Alex V Pearce,Danita M Pearson,Sarah E Pelan,Lesette Perez,Keith M Porter,Yvonne Ramsey,Kathrin Reichwald,Susan Rhodes,Kerry A Ridler,David Schlessinger,Mary G Schueler,Harminder K Sehra,Charles Shaw-Smith,Hua Shen,Elizabeth M Sheridan,Ratna Shownkeen,Carl D Skuce,Michelle L Smith,Elizabeth C Sotheran,Helen E Steingruber,Charles A Steward,Roy Storey,R Mark Swann,David Swarbreck,Paul E Tabor,Stefan Taudien,Tineace Taylor,Brian Teague,Karen Thomas,Andrea Thorpe,Kirsten Timms,Alan Tracey,Steve Trevanion,Anthony C Tromans,Michele d'Urso,Daniel Verduzco,Donna Villasana,Lenee Waldron,Melanie Wall,Qiaoyan Wang,James Warren,Georgina L Warry,Xuehong Wei,Anthony West,Siobhan L Whitehead,Mathew N Whiteley,Jane E Wilkinson,David L Willey,Gabrielle Williams,Leanne Williams,Angela Williamson,Helen Williamson,Laurens Wilming,Rebecca L Woodmansey,Paul W Wray,Jennifer Yen,Jingkun Zhang,Jianling Zhou,Huda Zoghbi,Sara Zorilla,David Buck,Richard Reinhardt,Annemarie Poustka,André Rosenthal,Hans Lehrach,Alfons Meindl,Patrick J Minx,Ladeana W Hillier,Huntington F Willard,Richard K Wilson,Robert H Waterston,Catherine M Rice,Mark Vaudin,Alan Coulson,David L Nelson,George Weinstock,John E Sulston,Richard Durbin,Tim Hubbard,Richard A Gibbs,Stephan Beck,Jane Rogers,David R Bentley The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise proc... ( view more )ess that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. ( view less ) David Tipene-Leach,Helen Pahau,Nathan Joseph,Kirsten Coppell,Kirsten McAuley,Chris Booker,Sheila Williams,Jim Mann AIM: To determine the prevalence of insulin resistance, impaired fasting glycaemia, impaired glucose tolerance, and diabetes mellitus in a rural Maori community, and to compare different methods for identifying individuals with insulin resistance. METHODS: 589 randomly selected individuals from the... ( view more ) Ngati Porou Hauora Register aged 25 years and over and resident on New Zealand's East Coast north of Gisborne were invited to participate in the study. A questionnaire was administered, anthropometric measures made, and blood samples taken for an oral glucose tolerance test and biochemical analysis. Impaired fasting glycaemia, impaired glucose tolerance, and diabetes mellitus were defined according to World Health Organization (WHO) diagnostic criteria, and among those persons with normal glucose tolerance, insulin resistance was calculated according to the McAuley formula and three other recognised methods for calculating insulin sensitivity. RESULTS: The overall age-standardised prevalence of diabetes (both known and newly diagnosed) was 10.6% and the age-standardised prevalence of insulin resistance was 37.0%. Age-specific diabetes rates were high among the older age groups, peaking at 34.1% for 60-69 year olds, whereas age-specific insulin resistance rates were high among the young age groups with the highest rate (44.3%) occurring among 30-39 year olds. Persons identifying as insulin-resistant reported higher rates of gout and family history of diabetes--and were found to have a higher waist circumference, blood pressure, and lower high-density lipoprotein (HDL) cholesterol than those without a glucose metabolism disorder. CONCLUSION: Diabetes is a common disorder among this population, but insulin resistance is even more prevalent, especially among young age groups. This is considerable cause for concern given that insulin resistance is believed to be the underlying cause of most cases of type 2 diabetes mellitus, and is confirmed by these data to be associated with a high degree of cardiovascular risk. ( view less ) Iben Bache,Elvire Van Assche,Sultan Cingoz,Merete Bugge,Zeynep Tümer,Mads Hjorth,Claes Lundsteen,James Lespinasse,Kirsten Winther,Anita Niebuhr,Vera Kalscheuer,Inge Liebaers,Maryse Bonduelle,Herman Tournaye,Carmen Ayuso,Gotthold Barbi,Elisabeth Blennow,Georges Bourrouillou,Karen Brondum-Nielsen,Gert Bruun-Petersen,Marie-Francoise Croquette,Sophie Dahoun,Bruno Dallapiccola,Val Davison,Bruno Delobel,Hans-Christoph Duba,Laurence Duprez,Malcolm Ferguson-Smith,David R Fitzpatrick,Elizabeth Grace,Ingo Hansmann,Maj Hultén,Peter Ka Jensen,Philippe Jonveaux,Ulf Kristoffersson,Isidora Lopez-Pajares,Jean McGowan-Jordan,Jan Murken,Maria Orera,Tony Parkin,Eberhard Passarge,Carmen Ramos,Kirsten Rasmussen,Werner Schempp,Regine Schubert,Eberhard Schwinger,Fiorella Shabtai,Kim Smith,Raymond Stallings,Margarita Stefanova,Lisbeth Tranebjerg,Catherine Turleau,Carl Birger van der Hagen,Michel Vekemans,Nadja Kokalj Vokac,Klaus Wagner,Jan Wahlstroem,Leopoldo Zelante,Niels Tommerup In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. W... ( view more )e excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility. ( view less ) Nina Støvring,Kirsten Avlund,Kirsten Schultz-Larsen,Marianne Schroll AIMS: As elderly people form a steadily growing part of the population in most parts of the world we are in need of knowledge of the influence of modifiable lifestyle factors on functional ability late in life. This study aims to examine the cumulative impact of smoking from age 50 to 70 on functio... ( view more )nal ability at age 75. METHODS: 387 men and women born in 1914 and living in seven municipalities in the western part of the County of Copenhagen were followed for 25 years with examinations in 1964, 1974, 1984, and 1989. Associations between smoking and functional ability were examined using multiple logistic regression analyses with cumulative smoking as determinant and physical activity, sex, basic school education, and household composition as possible confounders. RESULTS: There is an adverse relation between smoking and functional ability regardless of the time of examination or the ways of accumulating the smoking habits over the examinations. Cumulated former smokers have a larger risk of having reduced functional ability at age 75 (OR: 1.35 (1.13-1.61)) compared with never smokers. The odds ratios of reduced functional ability were 2.46 (1.44-4.17) among cumulated smokers of 1-14 grams of tobacco/day and 3.32 (1.63-6.72) among smokers of more than 14 grams of tobacco/day. CONCLUSIONS: The findings in this study stress the importance of continuing and strengthening efforts to reduce the prevalence of smokers in the population. Furthermore the results indicate that even after the 50th birthday it is possible to gain a healthier old age by abstaining from smoking. ( view less ) Kirsten Caesar,Kirsten Thomsen,Martin Lauritzen Functional neuroimaging relies on the robust coupling between neuronal activity, metabolism and cerebral blood flow (CBF) to map the brain, but the physiological basis of the neuroimaging signals is still not well understood. Here we applied a pharmacological approach to separate spiking activity, ... ( view more )synaptic activity, and the accompanying changes in CBF in rat cerebellar cortex. We report that tonic synaptic inhibition achieved by topical application of gamma-aminobutyric acid type A (GABAA) (muscimol) or GABAB (baclofen) receptor agonists abolished or reduced spontaneous Purkinje cell spiking activity without affecting basal CBF. The magnitude of CBF responses evoked by climbing fiber stimulation decreased gradually over time after exposure to muscimol, being more pronounced in the superficial than in the deep cortical layers. We provide direct evidence in favor of a laminar-specific regulation of CBF in deep cortical layers, independent of dilatation of surface vessels. With prolonged exposure to muscimol, activity-dependent CBF increments disappeared, despite preserved cerebrovascular reactivity to adenosine and preserved local field potentials (LFP). This dissociation of CBF and LFPs suggests that CBF responses are independent of extracellular synaptic currents that generate LFPs. Our work implies that neuronal and vascular signals evoked by glutamatergic pathways are sensitive to synaptic inhibition, and that local mechanisms independent of transmembrane synaptic currents adjust flow to synaptic activity in distinct cortical layers. Our results provide fundamental insights into the functional regulation of blood flow, showing important interference of GABAA receptors in translating excitatory input into blood flow responses. ( view less ) Merete Osler,Kirsten Todsen,Kirsten Nørmark,Birgit Viskum INTRODUCTION: We investigated whether the health visitor at an examination of children aged 18 months could identify those with an increased risk of morbidity and use of health services. METHODS: From 1992 to 1997, 233 children aged 18 months were examined by the health visitor from the district of... ( view more ) Sundeved, Denmark. At each examination, the visitor filled in a questionnaire concerning the child's health, living conditions, and development. RESULTS: Forty-one per cent of the children had been breast-fed for less than nine weeks. This percentage was highest in working class families and families outside the labour market. Nearly one third had a mother who smoked. Children whose mother smoked had a lower mean birth-weight than those with a non-smoking mother. The mother's smoking habits and age were also related to the duration of breast-feeding. Non-smoking mothers and mothers above 30 years of age had breast-fed more weeks than mothers who smoked or were younger. Diseases such as ordinary colds, inflammation of the middle ear, and bronchitis were common. Seventy-two per cent of the children had been treated with antibiotics once or more, 28% had visited a specialist, and 26% had been to hospital once or more. DISCUSSION: Social factors are of great importance for the health of young children. ( view less ) R Kirsten,K Nelson,D Kirsten,B Heintz Stimulating cardiac beta 1-adrenoceptors with oxyfedrine causes dilatation of coronary vessels and positive inotropic effects on the myocardium. beta 1-adrenergic agonists increase coronary blood flow in nonstenotic and stenotic vessels. The main indication for the use of the phosphodiesterase inhi... ( view more )bitors pamrinone, mirinone, enoximone and piroximone is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmonary disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be beneficially affected by elcosanoids. These drugs must be administered parenterally and have a half-life of only a few minutes. Sublingual or buccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsules. The short half-life (about 2.5 min) of nitroglycerin (glyceryl trinitrate) makes long term therapy impossible. Tolerance is a problem encountered with longer-acting nitric oxide donors. Knowledge of the pharmacokinetic properties of vasodilating drugs can prevent a too sudden and severe blood pressure decrease in patients with chronic hypertension. In considering the administration of a second dose, or another drug, the time necessary for the initially administered drug to reach maximal efficacy should be taken into account. In hypertensive emergencies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phentolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood hypertension is most often treated with angiotensin-converting enzyme (ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propagation of health benefits to breast-fed infants, combined with more women delaying pregnancy until their fourth decade, has entailed an increase in the need for hypertension management during lactation. Low dose hydrochlorothiazide, propranolol, nifedipine and enalapril or captopril do not pose enough of a risk of preclude breastfeeding in this group. The most frequently used antihypertensive agents during pregnancy are methyldopa, labetalol and calcium channel antagonists. Methyldopa and beta-blockers are the drugs of choice for treating mild to moderate hypertension. Prazosin and hydralazine are used to treat moderate to severe hypertension and hydralazine, urapidil or labetalol are used to treat hypertensive emergencies. The use of overly aggressive antihypertensive therapy during pregnancy should be avoided so that adequate uteroplacental blood flow is maintained. Methyldopa is the only drug accepted for use during the first trimester of pregnancy. ( view less ) R Kirsten,K Nelson,D Kirsten,B Heintz Understanding the mechanism of action and the pharmacokinetic properties of vasodilatory drugs facilitates optimal use in clinical practice. It should be kept in mind that a drug belongs to a class but is a distinct entity, sometimes derived from a prototype to achieve a specific effect. The most c... ( view more )ommon pharmacokinetic drug improvement is the development of a drug with a half-life sufficiently long to allow an adequate once-daily dosage. Developing a controlled release preparation can increase the apparent half-life of a drug. Altering the molecular structure may also increase the half-life of a prototype drug. Another desirable improvement is increasing the specificity of a drug, which may result in fewer adverse effects, or more efficacy at the target site. This is especially important for vasodilatory drugs which may be administered over decades for the treatment of hypertension, which usually does not interfere with subjective well-being. Compliance is greatly increased with once-daily dosing. Vasodilatory agents cause relaxation by either a decrease in cytoplasmic calcium, an increase in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors, angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids and NO donors. Despite chemical differences, the pharmacokinetic properties of calcium antagonists are similar. Absorption from the gastrointestinal tract is high, with all substances undergoing considerable first-pass metabolism by the liver, resulting in low bioavailability and pronounced individual variation in pharmacokinetics. Renal impairment has little effect on pharmacokinetics since renal elimination of these agents is minimal. Except for the newer drugs of the dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine, nisoldipine and nitrendipine, the half-life of calcium antagonists is short. Maintaining an effective drug concentration for the remainder of these agents requires multiple daily dosing, in some cases even with controlled release formulations. However, a coat-core preparation of nifedipine has been developed to allow once-daily administration. Adverse effects are directly correlated to the potency of the individual calcium antagonists. Treatment with the potassium channel opener minoxidil is reserved for patients with moderately severe to severe hypertension which is refractory to other treatment. Diazoxide and hydralazine are chiefly used to treat severe hypertensive emergencies, primary pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors prevent conversion of angiotensin-I to angiotensin-II and are most effective when renin production is increased. Since ACE is identical to kininase-II, which inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and cardioreparative effects by preventing and reversing cardiac fibrosis and ventricular hypertrophy in animal models. The predominant elimination pathway of most ACE inhibitors is via renal excretion. Therefore, renal impairment is associated with reduced elimination and a dosage reduction of 25 to 50% is recommended in patients with moderate to severe renal impairment. Separating angiotensin-II inhibition from bradykinin potentiation has been the goal in developing angiotensin-II receptor antagonists. The incidence of adverse effects of such an agent, losartan, is comparable to that encountered with placebo treatment, and the troublesome cough associated with ACE inhibitors is absent. ( view less ) A M Kirsten,R A Jörres,D Kirsten,H Magnussen Inhalation of swine confinement dust containing endotoxin causes an inflammatory response in the nose as reflected by an influx of neutrophils 3 hrs after exposure (Am J Respir Crit Care Med 149: A401(1994)). As there is evidence that nitric oxide (NO) in exhaled air indicates cellular activation, ... ( view more )we studied whether endotoxin causes an increase in nasal NO production in human subjects. Seven healthy subjects underwent a nasal challenge in which 50 mg swine confinement dust was given into each nostril (endotoxin concentration, 23.6 microg . g-1). Exhaled NO was measured before and during 3 hrs after the challenge and was compared to control values measured over the same period of time. Endotoxin produced a slight but statistically significant (p = 0.017) increase in nasal NO concentrations, mean (+/-SEM) values over 3 hrs being 367.5 +/- 7.5 ppb after endotoxin and 342.1 +/- 7.2 ppb under control conditions. The difference was most pronounced during the first hour after the challenge. We conclude that nasal administration of endotoxin causes a short-term increase in NO production which must precede cell influx or upregulation of transcription. ( view less ) A M Kirsten,R A Jörres,D Kirsten,H Magnussen Nitric oxide (NO) appears to play an important role in the pathophysiology of airway diseases as suggested from measurements of NO in exhaled air, animal and in vitro experiments. As NO is produced in variable amounts within the bronchial system and the nose, we studied the relationship between nas... ( view more )al and bronchial production of NO in patients with asthma and determined to which extent these productions were increased compared to healthy subjects. The nasal and bronchial production rates of NO as a function of breathholding time were assessed in 10 healthy subjects, 7 patients with asthma without inhaled corticosteroids, and 5 patients with asthma and a therapy of inhaled corticosteroids. After a breathhold of 10 s bronchial NO concentrations were elevated in the patients with asthma without steroids by the factor 3.5 (p < 0.005) and nasal concentrations by the factor 1.2 (n.s.) compared to healthy subjects. NO concentrations increased with time. Correspondingly, bronchial production rates were increased by factor 2.7 (p < 0.01) and nasal production rates by factor 1.1 (n.s.) in asthmatic compared to healthy subjects. The asthmatic patients with steroids showed lower production rates than those without steroids. We conclude from these data that in patients with asthma as compared to normal subjects bronchial production of NO is markedly increased, whereas the corresponding relative increase in nasal production is lower. ( view less ) G F Kirsten,C L Kirsten,M Faber,C Collett,C A Mitchell,A R Bird OBJECTIVE: To conduct an audit of the frequency of red cell concentrate transfusions (RCCTs) in infants of different weight categories, the donor exposure rate (DER), in these transfused infants and the volume of blood wasted during each transfusion, and to identify from this baseline information s... ( view more )pecific categories of infants who would benefit from the introduction of a limited donor exposure programme (LDEP). STUDY SETTING: Neonatal wards and neonatal intensive care unit (NICU), Tygerberg Hospital, Western Cape. STUDY DESIGN: A prospective descriptive study and comparison with a historic control group. SUBJECTS: Information on the birth weight, age at the time of each RCCT and number of blood donors to whom an infant was exposed were collected post factum for all infants admitted to the neonatal wards and NICU between May 1993 and May 1994. During this time, the red blood cell concentrate was supplied as single paediatric bags (180 ml) transfused within 14 days of donation. An LDEP was introduced in February 1995. With this system, red blood cells were supplied as triple packs: a main unit of 250 ml with three empty satellite packs allowing up to three separate transfusions. These were assigned to a specific infant and were to be transfused within 21 days of donation. A second system where one adult blood bag was divided into two 180 ml bags and assigned to one infant to be transfused within 35 days of donation was also assessed. RESULTS: Of the 7854 infants admitted during the first 12-month audit period, 387 (4.9%) received 977 RCCTs. Of these, 183 (47.3%) received one transfusion, 72 (18.6%) two transfusions, 51 (13.2%) three transfusions, 27 (7.0%) four transfusions and 54 (13.9%) five or more transfusions. Infants (N = 188) with a birth weight below 1500 g admitted to the NICU were identified as the group with the highest prevalence of RCCTs (68.6%), and it was therefore decided that in the prospective study such infants would qualify for the LDEP. A total of 81 infants was transfused with either the double (N = 47) or the triple bags (N = 34) over a 5-month period. The decrease in the mean DER (+/-SD) was clinically significant when the triple (1.9 +/- 0.8) (P = 0.0001) and the double bags (1.6 +/- 0.8) (P = 0.0001) were compared with the previous single-bag system (4.4 +/- 3.5). Of concern was the large mean volume of concentrated red cells (118.5 +/- 12.5 ml) wasted per transfusion with the single-bag system. CONCLUSIONS: This survey confirmed a high RCCT rate as well as a very high DER in very-low-birth-weight (VLBW) infants treated at a tertiary centre. By assigning a triple or double bag of red cells from one blood donor and extending the storage of blood for small-volume RCCTs in infants from 14 days to 35 days, donor exposure was reduced significantly. We urge the introduction of the multibag blood transfusion system and extended storage period of blood for small-volume RCCT for VLBW infants in South Africa. ( view less ) A Sóoki-Tóth,G Bánfalvi,J Szöllösi,E Kirsten,M Staub,F Antoni,E Kun Thymic cells were isolated at intervals of between 0 and 144 h from mice that received one intraperitoneal injection of emetine (33 mg/kg), and thymus weight, incorporation of [14C]leucine into proteins and [3H]thymidine into DNA in intact thymic cells, as well as initial rates of protein ADP-ribos... ( view more )ylation in permeabilized cells [A. Sóoki-Tóth, F. Asghari, E. Kirsten, and E. Kun (1987) Exp. Cell Res. 170, 93] were simultaneously monitored. The effect of emetine as an inhibitor of protein synthesis [F. Antoni, N. G. Luat, I. Csuka, I. Oláh, A. Sóoki-Tóth, and G. Bánfalvi (1987) Int. J. Immunopharmacol. 9, 333] corresponds to the induction of sequential cellular events, such as cell exit and remigration, by other antimitotic agents [C. Penit and F. Vasseur (1988) J. Immunol. 140, 3315] and produces an activation of proliferation of cells reentering into this organ. Proliferation, as demonstrated by a large increase in DNA synthesis and entrance into S phase, was kinetically related to an apparent increase in poly(ADP-ribose) polymerase activity in thymic cells and a highly significant in vitro ADP-ribosylation of histone H3. Since no DNA fragmentation occurred in thymic cells, as tested by a fluorometric technique [C. Birnboim and J. J. Jevac (1981) Cancer Res. 41, 1889], it is probable that a selective activation of poly(ADP-ribose) polymerase may have been induced in cells that undergo differentiation and proliferation while repopulating the thymus. ( view less ) R Kirsten,K Nelson,U Rüschendorf,W Seger,T Scholz,E Kirsten The plasma level of free fatty acids (FFA) in adrenalectomized rats increases by 50% after treatment with aldosterone (2 microng/100 g rat). Lipolytic activity in peripheral fat tissue is lowered after adrenalectomy and doubles after in vivo administration of aldosterone to adrenalectomized rats (m... ( view more )easured as free fatty acid release in vitro from epididymal fat tissue). Lypolysis of adipose tissue stimulated by the in vitro presence of ACTH also increases after in vivo administration of aldosterone. Incorporation of intravenously administered label from U-14C-palmitate into total extractable lipid of renal tissue is augmented 3 h after aldosterone administration to adrenalectomized rats, while no increase of the radioactivity is observed in total lipid from liver tissue. Treatment with aldosterone does not affect the total lipid content of kidney or liver in adrenalectomized rats. The oxygen consumption rate of kidney cortex slices with lactate, beta-hydroxybuterate or acetoacetate as substrates is lowered after in vivo administration of aldosterone to adrenalectomized rats. With slccinate, however, the respiratory rate of kidney slices increases after aldosterone treatment of adrenalectomized rats, the ouabain-sensitive respiration being more affected than the ouabain-insensitive respiration. An interpretation of the O2 consumption data implicating competition of lipid metabolism for CoA-SH is discussed. ( view less ) E Kirsten,W Seger,K Nelson,R Kirsten Mitochondria of rat kidney red medulla form a single band (rho = 1.163) on a sucrose gradient, while mitochondria of the cortex form bands in 2 density regions, namely ca. 66% (M1) at rho = 1.173 and ca. 33% (M2) at rho = 1.163. The mitochondria of the red medulla contain more cytochrome a, more cy... ( view more )tochrome b, and less cytochrome c, compared to the M1 population which predominates in cortex. Mitochondria from the red medulla show higher rates of Pi incorporation into total organically bound phosphorus in the presence of ADP, Pi, and oxidizable substrate than do mitochondria from cortex. However, in absence of added oxidizable substrate the reverse is observed, indicating that isolated cortex mitochondria contain more endogenous substrate. The superiority of the red medulla organelles in phosphorylation in the presence of substrate persists in preparations made according to LOWENSTEINS [3] procedure (shortened isolation time, removal of lysosomal enzymes by digitonin treatment). This shows that the observed differences are not artifacts due to different degrees of damage to the organelles by lysosomal attack. ( view less )
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