Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis

Alterations within the retinoblastoma (Rb) gene, as detected by the VNTR probe p68RS2.0, and flow cytometric DNA pattern have been analysed in 255 colorectal carcinomas. A total of 35.3% of the tumours had alterations within the Rb gene. Amplification of one allele was demonstrated in 29.5% of the tumours, and loss of heterozygosity was found in 11.5%. No association was found between amplification within the Rb gene and clinicopathological characteristics of the patients. The high frequency of alterations demonstrated within the Rb gene, suggests that this gene is involved in colorectal carcinogenesis with amplification as by far the most abundant genetic alteration. This may imply that the Rb gene has an oncogene-like function in colorectal carcinomas, rather than acting as a tumour suppressor gene. Sixty-three per cent of the carcinomas were DNA aneuploid, and a significant association was demonstrated between amplification within the Rb gene and DNA aneuploidy (P less than 0.01). Two other chromosome loci were analysed, on chromosome 1p (probe pYNZ2) and on chromosome 2p (probe pYNH24), respectively. On chromosome 1p, heterozygous loss was found in 22.2% of the tumours, indicating an involvement of this chromosome in a subset of colorectal carcinomas.     

Sex Differences in the Association Between Bone Mineral Density and Coronary Artery Disease in Patients Referred for Cardiac Computed Tomography

Atherosclerosis and osteoporosis are both common and preventable diseases. Evidence supports a link between coronary artery disease (CAD) and low bone mineral density (BMD). This study aimed to assess the association between thoracic spine BMD and CAD in men and women with symptoms suggestive of CAD.This cross-sectional study included 1487 (mean age 57 years (range 40-80), 47% men) patients referred for cardiac computed tomography (CT). Agatston coronary artery calcium score (CACS), CAD severity (no, mild, moderate, and severe), vessel involvement (no, 1-, 2-, and 3/left main disease), and invasive measurements were evaluated. BMD of three thoracic vertebrae was measured using quantitative CT. We used the American college of radiology cut-off values for lumbar spine BMD to categorize patients into very low (<80 mg/cm³), low (80-120 mg/cm³), or normal BMD (>120 mg/cm³). BMD as a continuous variable was included in the linear regression analyses to assess associations between CACS (CACS=0, CACS 1- 399, and CACS ≥ 400) and BMD, and CAD severity and BMD.Significant lower BMD was present with increasing CACS and stenosis degree unadjusted. Multivariate linear regression analyses in women revealed a significant correlation between BMD and CACS groups (β = ?4.06, p<0.05), but no correlation between BMD and CAD severity (β = ?1.59, p = 0.14). No association was found between BMD and CACS (β = ?1.50, p = 0.36) and CAD severity (β = 0.07, p = 0.94) in men.BMD is significantly correlated to CACS after adjusting for confounders in women, but not in men, suggesting a possible sex difference in pathophysiology.     

Three days of high-dose glucocorticoid treatment attenuates large-vessel 18F-FDG uptake in large-vessel giant cell arteritis but with a limited impact on diagnostic accuracy

Purpose

To evaluate the in-treatment diagnostic accuracy of FDG PET/CT in large-vessel giant cell arteritis (LV-GCA) by serial scans before and after a short course of high-dose glucocorticoid treatment.

Methods

Twenty-four glucocorticoid-naïve patients with new-onset PET/CT verified LV-GCA (pre-treatment baseline PET) were prospectively included. Excluded were patients with a previous history of GCA or polymyalgia rheumatica, LV-GCA-mimicking conditions and patients on immunosuppressive therapy. All patients were treated with 60 mg of oral prednisolone daily and assigned for in-treatment FDG PET/CT after either 3 (PET3) or 10 days (PET10). Two experienced nuclear medicine physicians, blinded to patients’ clinical data, reviewed the FDG PET/CT images. A visual semi-quantitative approach was used. Segmental and homogenous FDG uptake in the wall of the aorta and/or supra-aortic branches with higher uptake intensity than liver was considered consistent with vasculitis. Inter-reader reliability was evaluated.

Results

Although glucocorticoid treatment attenuated FDG uptake in large vessels, LV-GCA was accurately diagnosed in 10/10 patients after 3 days of treatment, but only in 5/14 patients after 10 days of treatment (p?<?0.001). Interrater reliability was substantial (agreement 87%, Cohen’s weighted kappa 0.70). No correlation between CRP and FDG uptake was found.

Conclusions

Within 3 days of high-dose glucocorticoid treatment, FDG PET/CT can diagnose LV-GCA with high sensitivity. This window of opportunity ensures that prompt glucocorticoid treatment can be initiated to avoid debilitating GCA complications with a limited effect on diagnostic accuracy. After 10 days of treatment, FDG PET/CT sensitivity decreases significantly.

     

Internal complexity and environmental sensitivity in hospitals

Theory suggests that organizations should respond to external complexity with internal complexity. We examine whether "environmentally sensitive" hospitals are more internally complex than "environmentally insensitive" hospitals. Results show that environmentally sensitive and insensitive hospitals differed on three of the measures of internal complexity: goal complexity, strategic complexity, and relational complexity.     

Quality assurance of mammograms in the Norwegian Breast Cancer Screening Program

This study compared the proportion of mammograms classified as perfect, good, moderately good or inadequate by a radiographer specially trained for doing such a classification at a breast centre (local-PGMI radiographer) with the proportion similarly assessed by an expert-PGMI radiographer. The results were compared with the recommendations given in the quality assurance manual of the Norwegian Breast Cancer Screening Programme. The reasons for classifying the mammograms into other than perfect, such as good, moderately good or inadequate were investigated.The quality of the mammograms was measured by using the PGMI system, which is a quality-review model that classifies the images into the four categories according to positioning, compression, exposure, noise, artefacts, and movement. A total of 1280 mammograms from all 16 breast centres in the screening programme were classified.The distribution of perfect, good, moderately good, and inadequate mammograms differed between the local-PGMI radiographers and the expert radiographer, for both the cranio-caudal (CC) and mediolateral-oblique (MLO) mammograms (P < 0.001 for both). The expert radiographer classified a higher proportion of both CC (28%) and MLO (14%) mammograms as inadequate than did the local-PGMI radiographers (7% and 3%, respectively; P < 0.001 for both). The guidelines recommend ≤3% of the mammograms to be inadequate. The reason given for the inadequate classifications by the expert radiographer was predominantly “parts of the breast missing” for both the CC and the MLO mammograms.There is room to improve the quality of the mammograms in the screening programme in Norway. Attention should be given to positioning and the use of standardized terms in the PGMI classification.     

Late specialization: the key to success in centimeters, grams, or seconds (cgs) sports

A controversial question within elite sports is whether young athletes need to specialize early, as suggested by Ericsson et al., or if it is more beneficial to follow the path of early diversification proposed by Côté et al., which includes sampling different sport experiences during childhood and specializing later on during adolescence. Based on a Danish sample of 148 elite and 95 near‐elite athletes from cgs sports (sports measured in centimeters, grams, or seconds), the present study investigates group differences concerning accumulated practice hours during the early stages of the career, involvement in other sports, career development, as well as determining whether or not these variables predict membership in the elite group. The results clearly reveal that elite athletes specialized at a later age and trained less in childhood. However, elite athletes were shown to intensify their training regime during late adolescence more than their near‐elite peers. The involvement in other sports neither differs between the groups nor predicts success. It can be concluded that factors related to the organization of practice during the mid‐teens seem to be crucial for international success within cgs sports. Future research should adopt a longitudinal design with means of drawing causal inferences.     

Effects on bone geometry,density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: A case‐control study using HR‐pQCT

Patients with primary hyperparathyroidism (PHPT) have continuously elevated parathyroid hormone (PTH) and consequently increased bone turnover with negative effects on cortical (Ct) bone with preservation of trabecular (Tb) bone. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new technique for in vivo assessment of geometry, volumetric density, and microarchitecture at the radius and tibia. In this study we aimed to evaluate bone status in women with PHPT compared with controls using HR‐pQCT. The distal radius and tibia of 54 women—27 patients with PHPT (median age 60, range 44–75 years) and 27 randomly recruited age‐matched healthy controls (median age 60, range 44–76 years)—were imaged using HR‐pQCT along with areal bone mineral density (aBMD) by dual‐energy X‐ray absorptiomentry (DXA) of the ultradistal forearm, femoral neck, and spine (L1–L4). Groups were comparable regarding age, height, and weight. In the radius, patients had reduced Ct area (Ct.Ar) (p = .008), Ct thickness (Ct.th) (p = .01) along with reduced total (p = .002), Ct (p = .02), and Tb (p = .02) volumetric density and reduced Tb number (Tb.N) (p = .04) and increased Tb spacing (Tb.sp) (p = .05). Ct porosity did not differ. In the tibia, no differences in HR‐pQCT parameters were found. Moreover, patients had lower ultradistal forearm (p = .005), spine (p = .04), and femoral neck (p = 0.04) aBMD compared with controls. In conclusion, a negative bone effect of continuously elevated PTH with alteration of HR‐pQCT assessed geometry, volumetric density, and both trabecular and cortical microarchitecture in radius but not tibia was found along with reduced aBMD by DXA at all sites in female patients with PHPT. © 2010 American Society for Bone and Mineral Research     

Metacarpal morphometry in monozygotic dizygotic elderly twins

The relative importance of genetic factors in the pathogenesis of age related bone loss has been investigated in a study involving 17 monozygotic (MZ) and 8 dizygotic (DZ) pairs of twins aged 64 to 75 years. Radiographic morphometry was performed at the midpoints of the 2nd, 3rd and 4th metacarpals of both hands and the mean total and cortical widths were evaluated. The heritability, h2, was calculated as the difference between the intrapair variances in same sexed DZ and MZ pairs divided by the intrapair variance in DZ pairs. The mean intrapair variance of both total and cortical width was found to be four to five times higher in DZ than in MZ pairs. The differences are highly significant with an h2 value between 0.7 and 0.8, indicating a predominant genetic influence. It is stressed that this result applies only to the population from which the twin sample was drawn.     

Adaptor proteins: Flexible and dynamic modulators of immune cell signalling

To maintain homeostasis, all cells respond to environmental cues via a multitude of surface receptors. In order to act appropriately in their environment, cells are dependent on the transduction of the incoming signal through tightly regulated and interconnected signalling pathways to the cell nucleus. In particular, cells implicated in the immune system greatly depend on such systems to respond in a flexible and dynamic manner to environmental challenges. One major group of intracellular proteins that are involved in these signalling pathways are adaptor proteins. Although adaptor proteins are essential for normal immune cell operation, the functional role of this group of signalling proteins remains to be fully appreciated. So far, research on adaptor proteins has revealed their unique potential in building transient complexes in a reversible, dynamic and inducible manner. In this review, we explore the roles of adaptor proteins – in space and time of intracellular signalling – and their associations with human disease. Examples of adaptor proteins expressed in hematopoietic cells highlight their crucial role in the immune system. Lastly, we present challenges faced in elucidating roles of adaptor proteins, as illustrated by the T cell–specific adaptor (TSAd) protein encoded by the SH2D2A gene.