<Emphasis Type="Italic">TP53</Emphasis>mutation status and gene expression profiles are powerful prognostic markers of breast cancer

Introduction  

Gene expression profiling of breast carcinomas has increased our understanding of the heterogeneous biology of this disease and promises to impact clinical care. The aim of this study was to evaluate the prognostic value of gene expression-based classification along with established prognostic markers and mutation status of the TP53 gene (tumour protein p53) in a group of breast cancer patients with long-term (12 to 16 years) follow-up.     

Birth order pattern in the inheritance of chronic lymphocytic leukaemia and related lymphoproliferative disease

Rank order of affected offspring in a sibship can inform on epigenetic factors in disease susceptibility. Here we report an analysis of birth order in 32 families segregating chronic lymphocytic leukaemia (CLL) and other B-cell lymphoproliferative disorders. A paternal-offspring, but not a maternal-offspring birth rank order was observed. Cox regression analysis provided relative risks (RR) for paternal and maternal transmission of 3.60 (CI 95%: 1.54 - 8.42; P = 0.0005) and 1.64 (CI 95%: 0.90 - 3.01; P = 0.096), respectively. The significance of paternal and maternal transmission of CLL-CLL pairs employing Haldane and Smith's test were 0.006 and 0.63, respectively. There was no evidence of a relationship between parental age and birth order. The genetic mechanism behind the birth order effect observed is discussed in the light of non-Mendelian imprinting and pregnancy related microchimerism.     

Psychiatric and behavioural symptoms and the use of psychotropic medication in Special Care Units and Regular Units in Norwegian nursing homes

Background: In a number of countries Special Care Units (SCUs) have been established to meet the particular needs of patients with dementia. The criteria for SCUs are poorly defined and often not met. Aim: To assess the frequency distributions of dementia, psychiatric and behavioural symptoms and the use of psychotropic medication in SCUs and Regular Units (RUs) across different regions. Methods and material: By means of a structured interview, comprising the Neuropsychiatric Inventory, the Clinical Dementia Rating Scale and Lawton’s Physical Self‐maintenance scale, a representative sample of 1163 nonselected nursing home patients was assessed. In addition, information was collected from the patients’ records. Results: Overall SCU patients were significantly more likely to be younger, to have higher level of functioning, to have dementia, to exhibit clinically significant psychiatric and behavioural symptoms and to receive psychotropic medication. There were significant differences across regions in terms of psychiatric and behavioural symptoms and the use of psychotropic medication. The ratio of accommodation in SCUs to that in RUs varied across the regions. Conclusion: Patients in SCUs and patients in RUs are distinct nursing home populations. Regional differences, which might be due to diverse ratios of SCUs, are evident.     

Freehand real-time elastography: impact of scanning parameters on image quality and in vitro intra- and interobserver validations

Real-time elastography is a method for visualization of the elastic properties of soft tissue and may potentially enable differentiation between malignant and benign pathologic lesions. Our aim was to validate the method on a tissue-mimicking (TM) phantom and to evaluate the influence of different scanning parameters and investigator variability. A TM-phantom containing eight spherical inclusions with known storage modulus was examined using two different transducers on an ultrasound (US) scanner equipped with software for real-time elasticity imaging. The ultrasound transducers were moved vertically in a repetitive manner to induce strain. Two investigators performed series of standardized elastography scans applying a 0-4 categorical quality scale to evaluate the influence of seven parameters: dynamic range of elasticity, region-of-interest, frequency of transducer movement, rejection of elastogram noise, frame rate, persistence and smoothing. Subsequently, repeated examinations of four selected inclusions were performed using a visual analog scale (VAS) where investigators marked a 100 mm horizontal line representing the span in image quality based on experience from the first examination. The hardest and softest inclusions were imaged more clearly than the inclusions with elasticity more similar to the background material. Intraobserver agreement on elastogram quality was good (kappa: 0.67 - 0.75) and interobserver agreement average (kappa: 0.55 - 0.56) when using the categorical scale. The subsequent VAS evaluation gave intraclass-correlation coefficients for the two observers of 0.98 and 0.93, respectively, and an interclass-correlation coefficient of 0.93. Real-time elastography adequately visualized isoechoic inclusions with different elastic properties in a TM-phantom with acceptable intra- and interobserver agreement. Dynamic range of elasticity was the parameter with most impact on the elastographic visualization of inclusions.     

Bradykinin induced sustained anti-adrenergic actions in guinea pig heart muscle involves PKC

OBJECTIVES: Adenosine attenuates the effect of beta-adrenergic stimulation upon contractile force, both when present during beta-adrenergic stimulation and for a period after washout of adenosine. Protein kinase C (PKC) mediates the sustained effect. The present study investigated if bradykinin (500 nM) could induce anti-beta-adrenergic actions. DESIGN: Guinea pig papillary muscles (36.5 degrees C, 1 Hz) were subjected to 15 min exposure to and 20 min washout of bradykinin. Isoproterenol 100 nM was added for 3 min at the end of test exposure and at the end of washout. The PKC-inhibitor bisindolylmaleimide (20 nM) was given to investigate the importance of PKC. RESULTS: Bradykinin significantly reduced the increase in contractile force in response to isoproterenol, both when present and after washout of test substance. Inhibition of PKC abolished the sustained effect, while inhibition of PI3-kinase with wortmannin did not seem to affect the results. CONCLUSIONS: Anti-beta-adrenergic effects of bradykinin on contractile force and action potential duration were demonstrated. PKC was important for the sustained effect on contractile force, but not for the acute effect and the effect on action potential duration.     

Overweight and obesity in Norwegian children: prevalence and socio‐demographic risk factors

Aim: The aim of this study was to estimate the prevalence of childhood overweight and obesity and to identify socio‐demographic risk factors in Norwegian children. Methods: The body mass index of 6386 children aged 2–19 years was compared with the International Obesity Task Force (IOTF) cut‐off values to estimate the prevalence of overweight including obesity (OWOB) and obesity (OB). The effect of socio‐demographic factors on this prevalence was analysed using multiple ordinal logistic regression analysis in a subsample of 3793 children. Results: The overall prevalence of OWOB was 13.8% (13.2% in boys and 14.5% in girls, p = 0.146), but the prevalence was higher in primary school children aged 6–11 years (17%, p < 0.001). The risk of being OWOB or OB increased in children with fever siblings (p = 0.003) and with lower parental educational level (p = 0.001). There was no association with parental employment status, single‐parent families or origin. Conclusion: The prevalence of OWOB and OB in Norwegian primary school children is of concern. Socio‐demographic factors have pronounced effects on the current prevalence of overweight and obesity in a cohort of Norwegian children. This knowledge could help to work out strategies to reduce the burden of overweight and obesity in children.     

Does rain really cause pain? A systematic review of the associations between weather factors and severity of pain in people with rheumatoid arthritis

Objective: To examine the association between weather and pain in rheumatoid arthritis (RA). Methods: Systematic review of longitudinal observational studies (up to September 2009) with data on the association between weather variables and severity of pain in RA. The methodological quality was rated independently by the two authors according to an adapted Newcastle–Ottawa Scale. We analyzed the data on an aggregated (group) level with a meta‐analysis of correlations between pain and weather, and at an individual level as the proportion of patients for whom pain was significantly affected by the weather. Results: Nine studies were included. Many different weather variables have been studied, but only three (temperature, relative humidity and atmospheric pressure) have been studied extensively. Overall group level analyses show that associations between pain and these three variables are close to zero. Individual analyses from two studies indicate that pain reporting in a minority (<25%) of RA patients is influenced by temperature, relative humidity or atmospheric pressure. We were not able to relate the findings to methodological quality or other aspects of the studies. Conclusion: The studies to date do not show any consistent group effect of weather conditions on pain in people with RA. There is, however, evidence suggesting that pain in some individuals is more affected by the weather than in others, and that patients react in different ways to the weather. Thus, the hypothesis that weather changes might significantly influence pain reporting in clinical care and research in some patients with RA cannot be rejected.     

Distribution patterns of muscle fibre types in major muscles of the bull (Bos taurus).

Summary The study describes the variations in distribution and cross-sectional area (fibre size) of three muscle fibre types (I, IIA, IIB) in 34 of the largest muscles of the bull (Bos taurus). The animals had been kept strictly unexercised for one year before slaughter. Representative sampling was done at 15 positions within each muscle, and from 2700 to 4500 fibres were analysed in each muscle. Different intermuscular patterns are described. The overall volume fraction (%) of type I fibres was about 10% higher in the forepart muscles than in the hindpart muscles (41% and 31%, respectively), while the mean content of type IIB fibres was similar. Type I fibres were particularly abundant in antigravity muscles. Of these, the hindlimb muscles contained 50% more type I fibres (by weight) than those of the forelimb. Typical antigravity antagonists contained very few type I fibres. In the thigh cross-section the proportion of type I fibres was highest in the anterior and medial parts, while the IIB fibres tended to be concentrated in the superficial and posterior parts. Intramuscular patterns were revealed, with type I fibres becoming gradually more abundant from superficial to deep regions, while IIB fibres had an opposite distribution. This was particularly evident in the thigh proper and in the scapular region. Within each fasciculus of all the muscles, the I fibres in the muscles of the forepart were on average about 15% larger than those of the muscles in the hindpart. The IIB fibres were on average about 10% larger in the hindpart than in the forepart muscles. A covariation between the proportion of type I and IIB fibres and their cross-sectional area was indicated.