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    Categorical and dimensional aspects of co-morbidity in obsessive-compulsive disorder (OCD).

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    OBJECTIVE: Obsessive-compulsive disorder (OCD) defined at the diagnostic level encompasses divergent symptoms and is often associated with other psychiatric problems. The present study examines OCD versus co-morbid symptom patterns in OCD in children and adolescents in order to investigate the presence of diagnostic heterogeneity. SUBJECTS AND METHODS: A total of 113 outpatients with primary OCD participated. The patients' and primary caretakers' responses on semi-structured interviews (child version of Schedule for Affective Disorders and Schizophrenia and the Children's Yale-Brown Obsessive Compulsive Scale) and parents' responses on the Child Behaviour Checklist were used in the study. Psychiatric diagnoses were related to CBCL syndrome scores and CBCL scores were compared with the Swedish normative data. RESULTS: Co-morbid diagnoses were very common and only one out of five patients had only OCD. The most common group was the neuropsychiatric disorders (47%) where tic disorders were most common (27%), especially among boys (40.8%; P = .006, Fisher's exact test). Also anxiety disorders were common (39.8%) as were affective disorders (24.8%) neither with any gender differences. Diagnoses of disruptive disorders were less common (8.8%), almost exclusively of the oppositional kind (ODD) (8.8%). From the dimensional point of view using the CBCL, patients with OCD scored higher than Swedish youngster generally do, and some gender differences were seen in that girls scored higher on anxiety and depression while both girls and boys had high scores on thought problems, attention problems and especially aggressive behaviour. Comorbidities explained from 25 to 50% scores of the CBCL sub-syndrome scales, often with both main effects and through complex patterns of interaction with gender, OCD-severity and other co-morbid problems. CONCLUSIONS: While co-morbid problems is an important facet of OCD, sub-syndromal levels of symptoms that can be assessed using a dimensional approach, is a large part of the total symptom burden in these youngsters. Our data indicate contributions of different pathways for girls and for boys for several comorbid problems together with OCD-severity

    Overexpression of the LexA-regulated tisAB RNA in E. coli inhibits SOS functions; implications for regulation of the SOS response.

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    The DNA damage induced SOS response in Escherichia coli is initiated by cleavage of the LexA repressor through activation of RecA. Here we demonstrate that overexpression of the SOS-inducible tisAB gene inhibits several SOS functions in vivo. Wild-type E. coli overexpressing tisAB showed the same UV sensitivity as a lexA mutant carrying a noncleavable version of the LexA protein unable to induce the SOS response. Immunoblotting confirmed that tisAB overexpression leads to higher levels of LexA repressor and northern experiments demonstrated delayed and reduced induction of recA mRNA. In addition, induction of prophage lambda and UV-induced filamentation was inhibited by tisAB overexpression. The tisAB gene contains antisense sequences to the SOS-inducible dinD gene (16 nt) and the uxaA gene (20 nt), the latter encoding a dehydratase essential for galacturonate catabolism. Cleavage of uxaA mRNA at the antisense sequence was dependent on tisAB RNA expression. We showed that overexpression of tisAB is less able to confer UV sensitivity to the uxaA dinD double mutant as compared to wild-type, indicating that the dinD and uxaA transcripts modulate the anti-SOS response of tisAB. These data shed new light on the complexity of SOS regulation in which the uxaA gene could link sugar metabolism to the SOS response via antisense regulation of the tisAB gene

    RAS signaling in colorectal carcinomas through alteration of RAS, RAF, NF1, and/or RASSF1A.

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    More than half of all colorectal carcinomas are known to exhibit an activated mitogen-activated protein kinase pathway. The NF1 gene, a negative regulator of KRAS, has not previously been examined in a series of colorectal cancer. In the present study, primary colorectal carcinomas stratified according to microsatellite instability status were analyzed. The whole coding region of NF1 was analyzed for mutations using denaturing high-performance liquid chromatography and sequencing, and the copy number alterations of NF1 were examined using multiple ligation-dependent probe amplification and real-time polymerase chain reaction. The mutational hot spots in KRAS and BRAF were sequenced, and promoter hypermethylation status of RASSF1A was assessed with a methylation-specific polymerase chain reaction. One sample had two missense mutations in NF1, whereas nine additional tumors had intronic mutations likely to affect exon splicing. Interestingly, 8 of these 10 tumors were microsatellite-unstable. Four other tumors showed a duplication of NF1. Mutations in KRAS and BRAF were mutually exclusive and were present at 40% and 22%, respectively. RASSF1A was hypermethylated in 31% of the samples. We show that the RAS signaling network is extensively dysregulated in colorectal carcinomas, because more than 70% of the tumors had an alteration in one or more of the four examined components

    Falciparum malaria and HIV-1 in hospitalized adults in Maputo, Mozambique: does HIV-infection obscure the malaria diagnosis?

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    BACKGROUND: The potential impact of HIV-1 on falciparum malaria has been difficult to determine because of diagnostic problems and insufficient epidemiological data. METHODS: In a prospective, cross-sectional study, clinical and laboratory data was registered consecutively for all adults admitted to a medical ward in the Central Hospital of Maputo, Mozambique, during two months from 28th October 2006. Risk factors for fatal outcome were analysed. The impact of HIV on the accuracy of malaria diagnosis was assessed, comparing "Presumptive malaria", a diagnosis assigned by the ward clinicians based on fever and symptoms suggestive of malaria in the absence of signs of other infections, and "Verified malaria", a malaria diagnosis that was not rejected during retrospective review of all available data. RESULTS: Among 333 included patients, fifteen percent (51/333) had "presumptive malaria", ten percent (28 of 285 tested persons) had positive malaria blood slides, while 69.1% (188/272) were HIV positive. Seven percent (n = 23) had "verified malaria", after the diagnosis was rejected in patients with neck stiffness or symptom duration longer than 2 weeks (n = 5) and persons with negative (n = 19) or unknown malaria blood slide (n = 4). Clinical stage of HIV infection (CDC), hypotension and hypoglycaemia was associated with fatal outcome. The "presumptive malaria" diagnosis was rejected more frequently in HIV positive (20/31) than in HIV negative patients (2/10, p = 0.023). CONCLUSION: The study suggests that the fraction of febrile illness attributable to malaria is lower in HIV positive adults. HIV testing should be considered early in evaluation of patients with suspected malaria

    Mechanical ventilation in the ICU- is there a gap between the time available and time used for nurse-led weaning?

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    ABSTRACT: BACKGROUND: Mechanical ventilation (MV) is a key component in the care of critically ill and injured patients. Weaning from MV constitutes a major challenge in intensive care units (ICUs). Any delay in weaning may increase the number of complications and leads to greater expense. Nurse-led, protocol-directed weaning has become popular, but it remains underused. The aim of this study was to identify and quantify discrepancies between the time available for weaning and time actually used for weaning. Further, we also wished to analyse patient and systemic factors associated with weaning activity. METHODS: This retrospective study was performed in a 12-bed general ICU at a university hospital. Weaning data were collected from 68 adult patients on MV and recorded in terms of ventilator-shifts. One ventilator-shift was defined as an 8-hour nursing shift for one MV patient. RESULTS: Of the 2000 ventilator-shifts analysed, 572 ventilator-shifts were available for weaning. We found that only 46% of the ventilator shifts available for weaning were actually used for weaning. While physician prescription of weaning was associated with increased weaning activity (p < 0.001), a large amount (22%) of weaning took place without physician prescription. Both increased nursing workload and night shifts were associated with reduced weaning activity. During the study period there was a significant increase in performed weaning, both when prescribed or not (p < 0.001). CONCLUSION: Our study identified a significant gap between the time available and time actually used for weaning. While various patient and systemic factors were linked to weaning activity, the most important factor in our study was whether the intensive care nurses made use of the time available for weaning

    Beregning av volum av et utvalg av kirurgiske prosedyrer i spesialisthelsetjenesten for nettstedet Fritt sykehusvalg Norge

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    Nasjonalt kunnskapssenter for helsetjenesten har utført en beregning av volum av utførte prosedyrer innen spesialisthelsetjenesten på oppdrag fra Helsedirektoratet. Datagrunnlaget er Norsk pasientregister (NPR), og datafiler for 2006 over alle innleggelser og polikliniske prosedyrer ble brukt. Valg av fagområder med tilhørende prosedyrer har vært i henhold til de fagområdene som nettstedet Fritt sykehusvalg Norge har.\ud \ud En intern prosjektgruppe ved Seksjon for kvalitetsmåling ved Kunnskapssenteret har gjennomgått alle de 22 fagområdene med tilhørende prosedyrer og undersøkelser som er oppgitt, for å operasjonalisere disse prosedyrene i NPRs datasett for 2006. Gruppen fant å måtte gjøre noen valg med hensyn på både fagområder og enkelte behandlinger og undersøkelser om hvilke av disse som egnet seg for utarbeiding av volumdata, og på grunnlag av denne gjennomgang gis det her resultater for 11 fagområder. Aktuelle prosedyrer innen fagområdet barn er revidert og presentert innen de forskjellige fagområder da informasjon om alder ikke var tilgjengelig for oss. Datafilen fra NPR var modifisert for å unngå bakover-identifikasjon av personer. For de andre fagområdene trengs en videre vurdering.\ud \ud Ved tolkning av disse resultatene gjøres det klart oppmerksom på at dette er rene driftsdata som viser et utvalg av utførte behandlinger/prosedyrer og hvordan de fordeler seg på de forskjellige sykehus. Volumtall oppfattes raskt som et uttrykk for kvalitet. Imidlertid er disse tall ikke en kvalitetsvurdering av spesialisthelsetjenesten. Det mangler mye relevant informasjon ved at vi for eksempel ikke vet om hvor mange operatører som har utført prosedyrer, da vi ikke vet om 50 operasjoner er utført av to eller ti leger. Vi vet ikke noe om sammensetningen av pasientpopulasjonen, og det er oppgitt tall for totalt antall utførte prosedyrer uavhengig om det er én prosedyre per pasient eller om noen pasienter har gjennomgått prosedyren flere ganger i løpet av 2006. Det er ukjent for oss om prosedyrene er planlagte eller mer tilfeldige av medisinske eller andre årsaker.\ud \ud Kunnskapssenteret har som en del av kvalitetssikringen av datauttrekket, kontaktet aktuelle fagmiljøer for å sikre at de foreslåtte koder for datauttrekk til volumberegning av de enkelte prosedyrer gir et klinisk relevant resultat. I den prosessen har man kunnet revidere hvilke prosedyrer/ behandlinger som er av mest interesse/relevante å legge ut på Fritt sykehusvalg Norge. Vi anbefaler at tall for prosedyre-volum ikke legges ut på Fritt sykehusvalg Norges nettsted før sykehusene er orientert om resultatene og metodene for uthenting av data

    Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up.

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    BACKGROUND: Obesity is one of the most important risk factors for osteoarthritis (OA) in knee(s). However, the relationship between obesity and OA in hand(s) and hip(s) remains controversial and needs further investigation. The purpose of this study was to investigate the impact of obesity on incident osteoarthritis (OA) in hip, knee, and hand in a general population followed in 10 years. METHODS: A total of 1854 people aged 24-76 years in 1994 participated in a Norwegian study on musculoskeletal pain in both 1994 and 2004. Participants with OA or rheumatoid arthritis in 1994 and those above 74 years in 1994 were excluded, leaving n = 1675 for the analyses. The main outcome measure was OA diagnosis at follow-up based on self-report. Obesity was defined by a body mass index (BMI) of 30 and above. RESULTS: At 10-years follow-up the incidence rates were 5.8% (CI 4.3-7.3) for hip OA, 7.3% (CI 5.7-9.0) for knee OA, and 5.6% (CI 4.2-7.1) for hand OA. When adjusting for age, gender, work status and leisure time activities, a high BMI (> 30) was significantly associated with knee OA (OR 2.81; 95%CI 1.32-5.96), and a dose-response relationship was found for this association. Obesity was also significantly associated with hand OA (OR 2.59; 1.08-6.19), but not with hip OA (OR 1.11; 0.41-2.97). There was no statistically significant interaction effect between BMI and gender, age or any of the other confounding variables. CONCLUSION: A high BMI was significantly associated with knee OA and hand OA, but not with hip OA

    Identification of differentially expressed genes in ileal Peyer's patch of scrapie-infected sheep using RNA arbitrarily primed PCR.

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    BACKGROUND: In scrapie and prion diseases, the knowledge concerning genes involved in host response during the early infection period in the lymphoid tissues, still remains limited. In the present study, we have examined differential gene expression in ileal Peyer's patches and in laser microdissected follicles of sheep infected with scrapie. METHODS: Ileal Peyer's patches and laser microdissected follicles were of scrapie and control lambs with susceptible genotypes for classical scrapie. Potential regulated genes were found using RNA arbitrarily primed polymerase chain reaction (RAP-PCR) and fingerprinting. The differentially expressed genes were confirmed using real-time RT-PCR. RESULTS: The expression of three genes (MAPRE3, LOC729073 and DNAJC3), were found to be significantly altered in scrapie infected lambs (P < 0.05). CONCLUSION: The three genes have not previously been associated with prion diseases and are interesting as they may reflect biological processes involved in the molecular pathogenesis of prion diseases

    Suspected retinopathies in Norwegian optometric practice with emphasis on patients with diabetes: a cross-sectional study.

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    BACKGROUND: The scope of optometry differs worldwide. In Norway the vast majority of optometrists perform ophthalmoscopy as part of their routine examinations. The aim of this study was to describe the frequency of suspected retinopathies in patients seen for routine optometric examination and to determine how optometrists deal with these patients. METHODS: 212 optometrists participated in a questionnaire survey and a practice registration during November 2004 - May 2005. In the practice registration, details for 20 consecutive patient encounters were recorded. Data were analysed by chi-square tests and multiple logistic regression. RESULTS: All optometrist stated that ocular history taking was an integrated part of their routine examination, while general health and diabetes history were routinely addressed by 59% and 42% of the optometrists, respectively. During the practice registration 4,052 patient encounters were recorded. Ophthalmoscopy was performed in 88% of the patients, of which 2% were dilated fundus examinations. Retinopathy was suspected in 106 patients, of whom 31 did not report a previous history of ocular or systemic disease. Old age (75+), hypertension and diabetes strongly predicted retinopathy with odds ratio (95% CI) of 6.4 (4.2 to 9.9), 3.8 (2.4 to 6.0) and 2.5 (1.4 to 4.7), respectively. Diabetic retinopathy was seen in 10% of diabetic patients and suspected in 0.2% of patients with no established history of diabetes. Retinopathy was not confirmed in 9 out 18 patients with a history of diabetic retinopathy; seven of these had undergone laser treatment. Out of the 106 patients with findings of retinopathy, 28 were referred to an ophthalmologist or a general practitioner (GP), written reports were sent to a GP in 16 cases, ten patients were urged to contact their GP for further follow up, while 52 were considered in need of routine optometric follow up only. CONCLUSION: Optometric practice provides a low threshold setting for detecting cases of ocular disease and retinal manifestations of systemic disease in the population. At present diagnosis of retinopathy in Norwegian optometric practice is unreliable. There are potentials for improving the optometrists' routine examination, their patient management patterns and collaboration routines with medical doctors

    Health-related quality of life after myocardial infarction is associated with level of left ventricular ejection fraction.

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    BACKGROUND: The objective was to explore the relationship between left ventricular ejection fraction (LVEF) assessed during hospitalization for acute myocardial infarction (MI) and later health-related quality of life (HRQoL). METHODS: We used multivariable linear regression to assess the relationship between LVEF and HRQoL in 256 MI patients who responded to the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D Index, and the EuroQol Visual Analogue Scale (EQ-VAS) 2.5 years after the index MI. RESULTS: 167 patients had normal LVEF (>50%), 56 intermediate (40%-50%), and 33 reduced (<40%). The mean (SD) KCCQ clinical summary scores were 85 (18), 75 (22), and 68 (21) (p <0.001) in the three groups, respectively. The corresponding EQ-5D Index scores were 0.83 (0.18), 0.72 (0.27), and 0.76 (0.14) (p = 0.005) and EQ-VAS scores were 72 (18), 65 (21), and 57 (20) (p = 0.001). In multivariable linear regression analysis age > or = 70 years, known chronic obstructive pulmonary disease (COPD), subsequent MI, intermediate LVEF, and reduced LVEF were independent determinants for reduced KCCQ clinical summary score. Female sex, medication for angina pectoris at discharge, and intermediate LVEF were independent determinants for reduced EQ-5D Index score. Age > or = 70 years, COPD, and reduced LVEF were associated with reduced EQ-VAS score. CONCLUSION: LVEF measured during hospitalization for MI was a determinant for HRQoL 2.5 years later

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