Handling knowledge on osteoporosis – a qualitative study

The aim of this qualitative study was to increase understanding of the importance of osteoporosis information and knowledge for patients’ ways of handling osteoporosis in their everyday lives. Interviews were performed with 14 patients recruited from two English university hospitals and 12 patients from a Danish university hospital. Critical psychology was used as a theoretical framework for the data analysis, which aimed at shedding light on patients’ ways of conducting everyday life with osteoporosis. The themes that emerged from the analysis showed that life conditions influenced the way in which risk, pain and osteoporosis were handled. Everyday life was also influenced by patients’ attitude to treatment. The patients who were experiencing emotional difficulties in handling osteoporosis were not those suffering from severe osteoporosis and fractures. Approaches to living with knowledge of future fracture risk varied according to the individual patient’s resourcefulness and experiences.     

Role of Wake‐Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep‐Promoting Effects of Ethanol

Background: Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake‐promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol‐induced sleep associated with the inhibition of the BF wake‐promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep‐promoting effects of ethanol? Methods: To address these questions, we performed 3 experiments in Sprague–Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c‐Fos expression (a marker of neuronal activation) in the BF wake‐promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol‐induced sleep. Results: Significant increase in non‐rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake‐promoting neurons with c‐Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8‐cyclopentyl‐1, 3‐dipropylxanthine into the BF significantly attenuated sleep‐promoting effects of ethanol. Conclusion: These results suggest that the inhibition of BF wake‐promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol.     

Drug metabolism and clearance system in tumor cells of patients with multiple myeloma

Resistance to chemotherapy is a major limitation of cancer treatments with several molecular mechanisms involved, in particular altered local drug metabolism and detoxification process. The role of drug metabolism and clearance system has not been satisfactorily investigated in Multiple Myeloma (MM), a malignant plasma cell cancer for which a majority of patients escapes treatment. The expression of 350 genes encoding for uptake carriers, xenobiotic receptors, phase I and II Drug Metabolizing Enzymes (DMEs) and efflux transporters was interrogated in MM cells (MMCs) of newly-diagnosed patients in relation to their event free survival. MMCs of patients with a favourable outcome have an increased expression of genes coding for xenobiotic receptors (RXRα, LXR, CAR and FXR) and accordingly of their gene targets, influx transporters and phase I/II DMEs. On the contrary, MMCs of patients with unfavourable outcome displayed a global down regulation of genes coding for xenobiotic receptors and the downstream detoxification genes but had a high expression of genes coding for ARNT and Nrf2 pathways and ABC transporters. Altogether, these data suggests ARNT and Nrf2 pathways could be involved in MM primary resistance and that targeting RXRα, PXR, LXR and FXR through agonists could open new perspectives to alleviate or reverse MM drug resistance.     

Small bowel perforation due to blunt trauma to an inguinal hernia: a case report and literature review

We report the case of a 41-year-old man with a known right inguinal hernia presenting with groin pain following a fall while dog walking. Operative findings showed a small bowel perforation affecting the loop of bowel in the hernial sac. Bowel perforations caused by blunt abdominal injury in patients with an inguinal hernia is a rare and not well recognised problem, and are confined to a handful of case reports in the surgical literature.     

Intravascular Low Power Red Laser Light as an Adjunct to Coronary Stent Implantation Evaluated in a Porcine Coronary Model

BACKGROUND: It is believed that restenosis following coronary interventions is the result of endothelial denudation that leads to thrombus formation, vascular remodeling, and smooth muscle cell proliferation. We previously demonstrated that low power red laser light (LPRLL) irradiation enhances endothelial cell growth in vitro and in vivo and reduces restenosis in a small animal model. The present study investigated the effectiveness of intravascular LPRLL therapy in the reduction of restenosis following stenting in a porcine model. METHODS AND RESULTS: Stents were placed in the right coronary artery of domestic cross-bred pigs. After stent deployment, an additional inflation was performed with the laser-balloon. In group I (n = 18) no LPRLL was used; group II (n = 10) received LPRLL dosage of 10 mW for 1 minute; group III (n = 10) received LPRLL dosage of 34 mW for 1 minute. Quantitative coronary analysis of the stented vessel was performed before, immediately after stenting, and at 6 weeks. The pigs were sacrificed and histologic and planimetric analysis conducted. At 6 weeks, minimal luminal stent diameter was significantly narrower in the control group compared to the higher dose group (p < 0.05), late loss correlated inversely proportional to the dose used (r = 0.9; p < 0.03), these results were confirmed by morphometric analysis. Neointimal area was also significantly decreased in the higher dose group. CONCLUSIONS: Intravascular LPRLL contributes to reduction of angiographic restenosis and hyperplastic reaction in this animal model and seems to be dose dependent.     

Long-term follow-up after coronary stenting and intravascular red laser therapy

A high restenosis rate remains a limiting factor for coronary angioplasty and stenting. Recently, use of intravascular red light therapy (IRLT) has been shown to be effective in different animal models and in humans in reducing the restenosis rate. Sixty-eight patients were treated with IRLT in conjunction with coronary stenting procedures. Mean age was 64 +/- 9 years. Treated lesions were type A (11), type B (42), and type C (18) with a mean lesion length of 16.5 +/- 2.4 mm. Reference vessel diameter and minimal lumen diameter (MLD) before therapy were 2.90 +/- 0.15 and 1.12 +/- 0.36 mm, respectively. After stenting and laser irradiation, MLD was 2.76 +/- 0.39 mm. No procedural complications or in-hospital adverse events occurred. All patients were followed up as depicted in the protocol. Sixty-one patients underwent angiographic restudy, which revealed restenosis in 9 patients (14.7%). Observed restenosis rate by artery size was > 3 mm (n = 21, 0%), 2.5 to 3.0 mm (n = 28, 14.2%), and <2.5 mm (n = 12, 41.6%). We conclude that IRLT is safe and feasible and reduces the expected restenosis rate in patients after coronary stenting in arteries of >2.5 mm.     

Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study.

BACKGROUND: calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss, with an enhanced risk of osteoporotic fractures. Although hip fractures are a serious consequence, few therapeutic measures are given for primary or secondary prevention. A combination of calcium and vitamin D may not be the most effective treatment for all patients. OBJECTIVE: to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis, bone mineral density and fracture type, and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients. DESIGN: a population-based, prospective cohort study. METHODS: 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture. This ward accepts people who live at home and are independent in activities of daily living. All subjects had a baseline medical examination, biochemical tests (parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) and were referred for bone densitometry. RESULTS: at 68%, the prevalence of hypovitaminosis D (25-hydroxyvitamin D<30 nmol/l) was high. However, only half the patients had evidence of secondary hyperparathyroidism, the rest having a low to normal level of parathyroid hormone ('functional hypoparathyroidism'). Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium, higher 1,25-dihydroxyvitamin D, lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the 'functional hypoparathyroid' group (P<0.01). CONCLUSION: there is a high prevalence of hypovitaminosis D in active, elderly people living at home who present with a hip fracture. However, secondary hyperparathyroidism occurs in only half of these patients. This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover, leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures. Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients, but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and 'vitamin D-replete' subjects needs further evaluation.