Breast cancer--new and emerging technologies for diagnosis and management

Part six of this series discusses established and emerging technologies in breast cancer care, with an emphasis on technologies in diagnosis and treatment supported by evidence. These include percutaneous core biopsy techniques and breast imaging in diagnosis. From the surgical perspective, we discuss the emerging role of sentinel node biopsy as a potentially less invasive method of staging the axilla in women with breast cancer. We also review advances in radiotherapy techniques that have allowed delivery of radiotherapy with more precision and improved safety.     

Opposing cartilages in the patellofemoral joint adapt differently to long-term cruciate deficiency: chondrocyte deformation and reorientation with compression

OBJECTIVE: The purposes of this study were to quantify patellofemoral histology in the feline knee 67 months post-anterior cruciate ligament transection (ACL-T) and to apply an in situ static load of physiological magnitude to the articular cartilage and evaluate the resulting cartilage and chondrocyte deformation. DESIGN: Six cats were sacrificed 67+/-6 months post-unilateral ACL-T. Static compression was applied to the cartilage surfaces of the patellofemoral joint using a cylindrical metal indentor. After fixation, full thickness osteochondral blocks were harvested and sections cut from not-indented and indented areas. Chondrocyte shape, orientation and volumetric fraction as well as cartilage thickness were evaluated. RESULTS: Experimental and contralateral patellae were histologically different compared to normal with thickened cartilage, rounded superficial chondrocytes, and uneven proteoglycan staining throughout. In contrast, no differences were apparent in 10 of the 12 femoral groove samples. The structural reorganisation of the experimental patellae cartilage that occurred with load was also different compared to normal. Specifically, the indentation shape was deeper and had steeper sides and the realignment of deep zone cells at angles of 45 degrees and 135 degrees observed in normal cartilage was no longer apparent in the experimental tissue. CONCLUSIONS: Two directly articulating cartilage surfaces of the feline patellofemoral joint have completely contrasting responses to long-term ACL-T. We speculate that this could be a result of the different nature of the loads experienced by the two surfaces (intermittent vs constant) and/or the differences in the histology and material properties of the two tissues in their normal state, and/or an inherent difference in the biological response capabilities of the articular cartilages.     

Self-neglect: the role of judgements and applied ethics

Self-neglect is more common than currently recognised. This article highlights the issue of self-neglect and the accompanying ethical values and judgements associated with it. A multidisciplinary framework for managing self-neglect is also described.     

The Behavioural Responses to Illness Questionnaire (BRIQ): a new predictive measure of medically unexplained symptoms following acute infection

BACKGROUND: The aim of this study was to design a self-report measure of behavioural responses during the acute phase of an illness, in order to assess the importance of these behaviours in the development of ongoing medically unexplained syndromes. METHOD: An initial pool of items derived from theoretical models and clinical observation, was piloted on a group of 312 university students to assess the factor structure of the scale and the best fit items. The scale was further validated in a second study of 758 patients who were experiencing Campylobacter gastroenteritis. At 3 months post-infection, patients were sent a second questionnaire assessing symptoms of irritable bowel syndrome (IBS). RESULTS: Principal components analysis of the items in the student sample yielded a four-factor solution, labelled all-or-nothing behaviour, limiting behaviour, emotional support seeking and practical support seeking. The factor structure was confirmed in the Campylobacter sample, and internal reliability was good. All-or-nothing behaviour was associated with IBS at 3 months post-infection. In contrast, limiting behaviour and practical support seeking at the time of infection appeared to be protective. CONCLUSION: The results suggest that this is a valid and reliable measure that can predict the development of a medically unexplained syndrome after acute infection. Overdoing things at the time of infection and then needing to rest for prolonged periods (all-or-nothing behaviour), appears to be a particular risk factor for the development of IBS. Targeted interventions at the time of infection may improve coping and prevent symptoms from becoming chronic.     

The CD200 and CD200 receptor cell surface proteins interact through their N-terminal immunoglobulin-like domains

CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts with a receptor on myeloid cells (CD200R) involved in regulation of macrophage function. Both CD200 and CD200R contain two Ig superfamily domains like many other leukocyte membrane proteins. Site-directed mutagenesis of CD200R showed that, like CD200, it interacted through its N-terminal domain. This indicated that the cell-cell interaction spans four Ig superfamily domains and this distance is similar to many interactions found between T cells and antigen-presenting cells. This suggests that this topology is also important in interactions of CD200 on a variety of cells with CD200R on myeloid cells, and comparable contact sites may be important mediating regulation in other cell-cell interactions. The mutagenesis showed that the binding involved the predicted GFCC' face of its N-terminal domain, like that of CD200, suggesting that the interaction evolved from a homotypic interaction.     

The short-term effects of treatment of chronic periodontitis on circulating levels of endotoxin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6

BACKGROUND: The acute-phase response involves molecules including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP). This study aimed to determine whether subgingival scaling resulted in rapid changes in plasma concentrations of these molecules. METHODS: Twenty-three non-smoking adults with chronic periodontitis received subgingival scaling for 60 minutes. Venous blood samples were taken at 0, 15, 30, 60, and 120 minutes. TNF-alpha and IL-6 were assayed from all samples and CRP from the baseline and final samples. Lipopolysaccharide (LPS) was assayed at 0, 15, and 30 minutes using limulus lysate assay (LAL) and EndoCAb Ig assays. RESULTS: LPS assays were suggestive of a transient low-grade bacteremia, but changes in LPS approaching significance (P=0.061) were seen with LAL only. There was a significant increase in circulating TNF-alpha (P=0.0387) and IL-6 (P<0.0001), and the degree of change in TNF-alpha was correlated with the severity of periodontal breakdown (P=0.001). There was also a significant correlation between levels of IL-6 and TNF-alpha (P<0.001). CONCLUSIONS: Chronic periodontitis patients undergoing an episode of subgingival scaling show a significant elevation in circulating TNF-alpha and IL-6. This may account for anecdotal reports of pyrexia following treatment and may be significant in terms of the relationship between periodontal disease, bacteremia, and cardiovascular disease.     

The effects of intrathecal diamorphine on gastric emptying after elective Caesarean section

This study investigated whether intrathecal diamorphine affects gastric emptying following elective Caesarean section. Forty women were randomly allocated to receive either diamorphine 300 microg or 0.9% saline as part of a standard spinal anaesthetic. Gastric emptying was measured in the immediate postoperative period using paracetamol absorption. Paracetamol concentrations were measured by enzymatic assay method using a Beckman CX-7 automated analyser. The time to maximum concentration (Tmax) was statistically longer in the diamorphine group (control 41.8, SD 20.8 min; diamorphine 72.6 SD 41.9 min; p < 0.01). During the 2-h study period, mean morphine consumption via a patient controlled analgesia device was significantly higher in the control group (control 9.3, SD 3.6 mg; diamorphine 2.1, SD 2.1 mg; p < 0.01). We conclude that intrathecal diamorphine may contribute to the delay in gastric emptying that occurs immediately following elective spinal Caesarean section.     

Effects of usual nutrient intake and vitamin D status on markers of bone turnover in Swiss adolescents

OBJECTIVE: To evaluate the effects of nutrient intake and vitamin D status on markers of type I collagen formation and degradation in adolescent boys and girls. DESIGN: Cross-sectional study. SETTING: Canton of Vaud, West Switzerland. SUBJECTS: A total of 92 boys and 104 girls, aged 11-16 y. Data were collected on height, weight, pubertal status (self-assessment of Tanner stage), nutrient intake (3-day dietary record) and fasting serum concentration of 25-hydroxyvitamin D (25OHD), and markers of collagen formation (P1NP) and degradation (serum C-terminal telopeptides: S-CTX). RESULTS: Tanner stage was a significant determinant of P1NP in boys and girls and S-CTX in girls. Of the nutrients examined, only the ratio of calcium to phosphorus (Ca/P) was positively associated with P1NP in boys, after adjustment for pubertal status. 25OHD decreased significantly at each Tanner stage in boys. Overall, 15% of boys and 17% of girls were identified as being vitamin D insufficient (serum 25OHD <30 nmol/l), with the highest proportion of insufficiency at Tanner stage 4-5 (29%) in boys and at Tanner stage 3 (24%) in girls. A significant association was not found between 25OHD and either bone turnover marker, nor was 25OHD insufficiency associated with higher concentrations of the bone turnover markers. CONCLUSIONS: The marked effects of puberty on bone metabolism may have obscured any possible effects of diet and vitamin D status on markers of bone metabolism. The mechanistic basis for the positive association between dietary Ca/P ratio and P1NP in boys is not clear and may be attributable to a higher Ca intake per se, a critical balance between Ca and P intake or higher dairy product consumption. A higher incidence of vitamin D insufficiency in older adolescents may reflect a more sedentary lifestyle or increased utilisation of 25OHD, and suggests that further research is needed to define their requirements. SPONSORSHIP: Nestec Ltd and The Swiss Foundation for Research in Osteoporosis.