Loss of heterozygosity at chromosome 11 in breast cancer: association of prognostic factors with genetic alterations.

We examined DNA from 116 female and four male breast cancer patients for loss of heterozygosity (LOH). DNA was analysed by polymerase chain reaction using ten microsatellite markers on chromosome 11. Three distinct regions of LOH were identified: 11p15.5, 11q13 and 11q22-qter with a LOH frequency of 19, 23 and 37-43% respectively. The marker D11S969 showing the highest frequency of LOH (43%) is located at the 11q24.1-q25 region. No previous molecular genetic studies have shown frequent LOH at the region telomeric to q23 on chromosome 11. Southern analysis revealed that LOH at 11q13 was due to amplification, whereas LOH at 11q22qter was due to deletion. LOH at 11p15.5 was associated with paucity of hormone receptor proteins, high S-phase and positive node status. An association was found between LOH at 11q13 and positive node status. LOH at the 11q22-qter region correlated with a high S-phase fraction. A significant association was found between LOH at 11p15 and chromosome regions 17q21 (the BRCA1 region) and 3p

BRIKKER TIL EN EVOLUTIONÆR NEUROSOCIAL TEORI OM STRESS

De seneste 20 års forskning i stress har peget på en lang række problemer i forbindelse med den klassiske stressteori, udformet af Cannon og Selye. I artiklen argumenteres for, at et lovende bud på et svar på disse udfordringer kan bestå i udformningen af en stressteori, der også inddrager andre og parallelt udviklede psykofysiologiske systemer. Dette indebærer (i) en sondring mellem det evolutionært ældre GAS (Selye) og (ii) det nyere system, der er baseret på HPA (Cannon), og (iii) at stresssystemets regulering anskues ud fra den nyere allostatiske model (Sterling, McEwen), som derved erstatter den oprindelige homeostase-model. Denne fornyede forståelse bør også omfatte (iv) den poly-vagale teori. Teorien åbner for inddragelsen af stress som kommunikation og social regulering. Dette åbner for en bedre forståelse af, hvordan stress påvirker sociale relationer og interaktioner. Sidst, men ikke mindst (v), argumenteres for inddragelse af teorier om social smerte. Denne synsvinkel peger på, at stress medfører, regulerer og skærper oplevelse af social smerte ved trussel. Et sådant moderniseret og flerstrenget system vil kunne åbne nye perspektiver, både i forhold til diagnostik og behandling af stress og afledte syndromer

A population-based study of stimulant drug treatment of ADHD and academic progress in children.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.We evaluated the hypothesis that later start of stimulant treatment of attention-deficit/hyperactivity disorder adversely affects academic progress in mathematics and language arts among 9- to 12-year-old children. We linked nationwide data from the Icelandic Medicines Registry and the Database of National Scholastic Examinations. The study population comprised 11,872 children born in 1994-1996 who took standardized tests in both fourth and seventh grade. We estimated the probability of academic decline (drop of ≥ 5.0 percentile points) according to drug exposure and timing of treatment start between examinations. To limit confounding by indication, we concentrated on children who started treatment either early or later, but at some point between fourth-grade and seventh-grade standardized tests. In contrast with nonmedicated children, children starting stimulant treatment between their fourth- and seventh-grade tests were more likely to decline in test performance. The crude probability of academic decline was 72.9% in mathematics and 42.9% in language arts for children with a treatment start 25 to 36 months after the fourth-grade test. Compared with those starting treatment earlier (≤ 12 months after tests), the multivariable adjusted risk ratio (RR) for decline was 1.7 (95% confidence interval [CI]: 1.2-2.4) in mathematics and 1.1 (95% CI: 0.7-1.8) in language arts. The adjusted RR of mathematics decline with later treatment was higher among girls (RR, 2.7; 95% CI: 1.2-6.0) than boys (RR, 1.4; 95% CI: 0.9-2.0). Later start of stimulant drug treatment of attention-deficit/hyperactivity disorder is associated with academic decline in mathematicsPfizer Novartis University of Iceland Icelandic Centre for Research (RANNIS

Electroencephalography as a clinical tool for diagnosing and monitoring attention deficit hyperactivity disorder: a cross-sectional study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The aim of this study was to develop and test, for the first time, a multivariate diagnostic classifier of attention deficit hyperactivity disorder (ADHD) based on EEG coherence measures and chronological age.The participants were recruited in two specialised centres and three schools in Reykjavik.The data are from a large cross-sectional cohort of 310 patients with ADHD and 351 controls, covering an age range from 5.8 to 14 years. ADHD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria using the K-SADS-PL semistructured interview. Participants in the control group were reported to be free of any mental or developmental disorders by their parents and had a score of less than 1.5 SDs above the age-appropriate norm on the ADHD Rating Scale-IV. Other than moderate or severe intellectual disability, no additional exclusion criteria were applied in order that the cohort reflected the typical cross section of patients with ADHD.Diagnostic classifiers were developed using statistical pattern recognition for the entire age range and for specific age ranges and were tested using cross-validation and by application to a separate cohort of recordings not used in the development process. The age-specific classification approach was more accurate (76% accuracy in the independent test cohort; 81% cross-validation accuracy) than the age-independent version (76%; 73%). Chronological age was found to be an important classification feature.The novel application of EEG-based classification methods presented here can offer significant benefit to the clinician by improving both the accuracy of initial diagnosis and ongoing monitoring of children and adolescents with ADHD. The most accurate possible diagnosis at a single point in time can be obtained by the age-specific classifiers, but the age-independent classifiers are also useful as they enable longitudinal monitoring of brain function.Icelandic Technology Development Fund 071201007 Landspitali University Hospital Research Fun

Cognitive-behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology:a randomized controlled trial using multi-level analysis

Background. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by high rates of co-morbid psychopathology. Randomized controlled trials of multimodal interventions, combining pharmacological and psychological treatments, have shown a robust treatment effect for ADHD symptoms but outcomes for co-morbid symptoms have been mixed. This may be accounted for by the type of intervention selected and/or by methodological problems including lack of follow-up and low power. The current study addressed these limitations in a parallel-group randomized controlled trial conducted in Iceland.  Method. A total of 95 adult ADHD patients who were already being treated with medication (MED) were randomly assigned to receive treatment as usual (TAU/MED) or 15 sessions of cognitive-behavioural therapy (CBT/MED) using the R&R2ADHD intervention which employs both group and individual modalities. Primary measures of ADHD symptoms and severity of illness, and secondary measures of anxiety, depression and quality of life were given at baseline, end of treatment and 3-month follow-up. Primary outcomes were rated by clinicians blind to treatment condition assignment.  Results. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater reduction in primary outcomes for clinician-rated and self-rated ADHD symptoms. Treatment effect of primary outcomes was maintained at follow-up, which suggests robust and lasting findings. In contrast to the primary outcomes, the secondary outcomes showed significant improvement over time.  Conclusions. The study provides evidence for the effectiveness of R&R2ADHD and demonstrates that there are differential effects over time for ADHD symptoms versus co-morbid problems, the latter taking longer to show positive effects

Fish skin grafts compared to human amnion/chorion membrane allografts: A double-blind, prospective, randomized clinical trial of acute wound healing.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadChronic, nonhealing wounds consume a great deal of healthcare resources and are a major public health problem, associated with high morbidity and significant economic costs. Skin grafts are commonly used to facilitate wound closure. The grafts can come from the patient's own skin (autograft), a human donor (allograft), or from a different species (xenograft). A fish skin xenograft from cold-water fish (Atlantic cod, Gadus morhua) is a relatively recent option that shows promising preclinical and clinical results in wound healing. Chronic wounds vary greatly in etiology and nature, requiring large cohorts for effective comparison between therapeutic alternatives. In this study, we attempted to imitate the status of a freshly debrided chronic wound by creating acute full-thickness wounds, 4 mm in diameter, on healthy volunteers to compare two materials frequently used to treat chronic wounds: fish skin and dHACM. The purpose is to give an indication of the efficacy of the two therapeutic alternatives in the treatment of chronic wounds in a simple, standardized, randomized, controlled, double-blind study. All volunteers were given two identical punch biopsy wounds, one of which was treated with a fish skin graft and the other with dehydrated human amnion/chorion membrane allograft (dHACM). In the study, 170 wounds were treated (85 wounds per group). The primary endpoint was defined as time to heal (full epithelialization) by blinded assessment at days 14, 18, 21, 25, and 28. The superiority hypothesis was that the fish skin grafts would heal the wounds faster than the dHACM. To evaluate the superiority hypothesis, a mixed Cox proportional hazard model was used. Wounds treated with fish skin healed significantly faster (hazard ratio 2.37; 95% confidence interval: (1.75-3.22; p = 0.0014) compared with wounds treated with dHACM. The results show that acute biopsy wounds treated with fish skin grafts heal faster than wounds treated with dHACM.Icelandic Technology Development Fun

A randomized controlled trial reporting functional outcomes of cognitive-behavioural therapy in medication‑treated adults with ADHD and comorbid psychopathology

Studies assessing psychological treatment of attention deficit hyperactivity disorder (ADHD) in adults are increasingly reported. However, functional outcomes are often neglected in favour of symptom outcomes. We investigated functional outcomes in 95 adults with ADHD who were already treated with medication and randomized to receive treatment as usual (TAU/MED) or psychological treatment (CBT/MED) using a cognitive–behavioural programme, R&R2ADHD, which employs both group and individual modalities. RATE-S functional outcomes associated with ADHD symptoms, social functioning, emotional control and antisocial behaviour were given at baseline, end of treatment and three-month follow-up. The Total composite score of these scales is associated with life satisfaction. In addition, independent evaluator ratings of clinicians who were blind to treatment arm were obtained on the Clinical Global Impression scale at each time point. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater functional improvement on all scales. Post-group treatment effects were maintained at follow-up with the exception of emotional control and the Total composite scales, which continued to improve. The largest treatment effect was for the RATE-S Total composite scale, associated with life satisfaction. CGI significantly correlated with all outcomes except for social functioning scale at follow-up. The study provides further evidence for the effectiveness of R&R2ADHD and demonstrates the importance of measuring functional outcomes. The key mechanism associated with improved functional outcomes is likely to be behavioural control

Women's experiences of sexual health when living with Rheumatoid Arthritis - an explorative qualitative study

<p>Abstract</p> <p>Background</p> <p>The ICF core sets for patients with Rheumatoid Arthritis (RA) acknowledge sexual function and intimate relationships as important since the patients' sexual health can be affected by the disease. About 36-70% of all RA-patients experience a reduced sexual health, and their perceived problems are directly or indirectly caused by their disease. Physiotherapy is often used as non-pharmacological treatment for RA. Mobility treatment, pain reduction, and physical activities are often included in physiotherapy for patients with RA. The aim of the study was to explore sexual health in relation to physiotherapy in women living with RA.</p> <p>Method</p> <p>An explorative qualitative interview study with a phenomenological approach was performed. The study consisted of ten interviews with women with RA. The analysis was performed according to Giorgi.</p> <p>Results</p> <p>The main theme that emerged in the material was that the body and the total life situation affected sexual health. Three categories were included in the theme: 1) sexual health - physical and psychological dimensions, 2) Impacts of RA, and 3) Possibilities to increase sexual health - does physiotherapy make a difference?</p> <p>Conclusions</p> <p>Sexual health was affected by RA in different ways for the informants. Possibilities to improve sexual health were improved partner communication and physiotherapy. Physiotherapy can play an active role in improving sexual health for patients with RA.</p

Marjolin's ulcers at a university teaching hospital in Northwestern Tanzania: a retrospective review of 56 cases

Marjolin's ulcer is a rare but highly aggressive squamous cell cancer that is most often associated with chronic burn wounds. Although many individual case reports exist, no comprehensive evaluation of Marjolin's ulcer patients has been conducted in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our local setting and to identify predictors of outcome. This was a retrospective study of histologically confirmed cases of Marjolin's ulcer seen at Bugando Medical Centre over a period of 10-years between January 2001 and December 2010. Data were retrieved from patients' files and analyzed using SPSS computer software version 15.0 A total of 56 patients were studied. Male to female ratio was 2.1:1. Burn scars (89.3%) were the most common causative lesions of Marjolin's ulcer. The mean latent period between original injury and diagnosis of Marjolin's ulcer was 11.34 ± 6.14 years. Only 12.0% of the reported cases were grafted at the time of injury (P < 0.00). Most patients (48.2%) presented between one and five years of onset of illness. The lower limb (42.9%) was the most frequent site for Marjolin's ulcers. The median tumor size at presentation was 8 cm and the vast majority of patients (85.7%) presented with large tumors of ≥ 5 cm in diameter. Lymph node metastasis at the time of diagnosis was recorded in 32.1% of cases and distant metastasis accounted for 26.9% of cases. Squamous cell carcinoma (91.1%) was the most common histopathological type. Wide local excision was the most common surgical procedure performed in 80.8% of cases. Post-operative complication rate was 32.1% of which surgical site infection was the most common complication in 38.9% of patients. Local recurrence was noted in 33.3% of cases who were treated surgically. The mean length of hospital stay for in-patients was 7.9 ± 2.3 days. Mortality rate was 7.1%. According to multivariate logistic regression analysis, stage and grade of the tumor and presence of local recurrence were the main predictors of death (P < 0.001). Marjolin's ulcers are not rare in our environment and commonly occur in burn scars that were not skin grafted and were left to heal secondarily. A high index of suspicion is required in the management of chronic non-healing ulcers and all suspected lesions should be biopsed. Early recognition and aggressive treatment of Marjolin's ulcers and close follow-up are urgently needed to improve outcomes in our environment