A Review of National Guidelines for Management of COPD in Europe

The quality of care can be improved by the development and implementation of evidence-based treatment guidelines. Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years. Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process. Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden. The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines. There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia. However, there are differences in the definitions of patient subgroups and other recommended treatments.

Thoracic Duct Decompression for Protein-Losing Enteropathy in Failing Fontan Circulation

An infrequent but devastating late complication of Fontan circulation is protein-losing enteropathy (PLE), which results from unbalanced lymphatic homeostasis. Surgical decompression of the thoracic duct by redirecting its drainage to the pulmonary venous atrium has been introduced recently as a possible treatment. This report describes a single-institution experience with this innovative procedure in 2 patients with failing Fontan circulation with PLE refractory to optimized medical therapy.

Acute flare induced by the calcific tendonitis of the rotator cuff: inhibition of IL-1 a potential therapeutic target?

Introduction: Calcific tendonitis of rotator cuff is observed on plainradiographs in 10% of adults, but remains asymptomatic in half thesecases. Sometimes, these calcifications induce acute flares withmassive inflammation similar to gout or CPPD crisis. Analgesics/anti-inflammatory medications are usually not sufficient to controlssymptoms in these situations. Local steroid infiltration with or withoutremoval of the calcific deposition with a needle aspiration may beuseful. A new approach could be IL-1 inhibitors. Indeed, basic calciumphosphate crystals are capable of stimulating the release of activeIL-1β in vitro. These crystals trigger IL-1β release, in an analogousmanner to MSU crystals in acute gout, suggesting that IL-1β blockademay be clinically useful.Case presentation: This report describes a 70-year old woman withacute rest pain of the right shoulder since 48 hours. On examination,we found massive limitations of active and passive movements. Thepatient evaluated, on the visual scale, her symptoms at 10/10 the nightand 5/10 the day. The radiography and showed a rounded, 8 mmcalcification in the subscapularis tendon. The ultrasound aspectrevealed a heterogeneous calcification partially non solid, surroundedby massive inflammation on Doppler. C-reactive protein anderythrocyte sedimentation rate were high (74 mg/ml, 54 mm/hour).The patient received subcutaneous injections of anakinra: 100 mgdaily for 3 days (D1-D3). We evaluated the patient in our consult at dayD1, D2, D3, D7, D16 and by phone at D70.This treatment rapidly relieved the inflammatory symptoms (within afew hours with no relapse). The mobility of the shoulder, the biologicsparameters improved and the size of the calcification as well thedegree of inflammation regressed on ultrasound after 3 days.Conclusion: This is the first report of a woman with an acute flareinduced by calcific tendonitis who received anakinra. IL-1 inhibitionmay be a therapeutic target in calcific tendonitis. To analyse thisresponse more precisely and elaborate definitive conclusions, aprospective pilot study is on-going in our ambulatory institute.

Influence de deux milieux séquentiels pour la culture d'embryons sur la production d'hormone gonadotrophine chorionique et de progestérone par des cellules JEG-3 et BeWo [Effects of different embryo development media on hCG and progesterone release by JEG-3 and BeWo cells]

Current in vitro fertilisation (IVF) practice requires synchronisation between the¦environment of cultured oocytes and embryos and the surroundings to what they would have¦been exposed to in vivo. Commercial, sequential media follow this requirement but their exact¦composition is not available. We have compared two widely used IVF culture media systems using¦the two choriocarcinoma cell lines JEG-3 and BeWo. The two hormones hCG and progesterone¦were determined in the culture supernatants as endpoints. In both cell lines, but in a more¦pronounced way in JEG-3, progesterone rather than hCG production was stimulated, and a¦higher hormone release was observed in the fertilisation than in the cleavage media. Differences¦between manufacturers were small and did not favour one system over the other. We conclude¦that both sequential media systems can be equally well used in current IVF laboratory practice.¦© 2012 Elsevier Masson SAS. All rights reserved.

Sleep disorders in boys with Duchenne muscular dystrophy.

Aim:  Determine the frequency and predictors of sleep disorders in boys with Duchenne Muscular Dystrophy (DMD). Method:  Cross-sectional study by postal questionnaire. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children (validated on 1157 healthy children). A total sleep score and six sleep disturbance factors representing the most common sleep disorders were computed. Potential associations between pathological scores and personal, medical and environmental factors were assessed. Results:  Sixteen of 63 boys (25.4%) had a pathological total sleep score compared with 3% in the general population. The most prevalent sleep disorders were disorders of initiating and maintaining sleep (DIMS) 29.7%, sleep-related breathing disorders 15.6% and sleep hyperhydrosis 14.3%. On multivariate analysis, pathological total sleep scores were associated with the need to be moved by a carer (OR = 9.4; 95%CI: 2.2-40.7; p = 0.003) and being the child of a single-parent family (OR = 7.2; 95%CI: 1.5-35.1; p = 0.015) and DIMS with the need to be moved by a carer (OR = 18.0; 95%CI: 2.9-110.6; p = 0.002), steroid treatment (OR = 7.7; 95%CI: 1.4-44.0; p = 0.021) and being the child of a single-parent family (OR = 7.0; 95%CI: 1.3-38.4; p = 0.025). Conclusion:  Sleep disturbances are frequent in boys with DMD and are strongly associated with immobility. Sleep should be systematically assessed in DMD to implement appropriate interventions.

In vivo and in vitro effects of somatostatin and insulin on glucagon release in a human glucagonoma.

Inhibition of pancreatic glucagon secretion has been reported to be mediated by glucose, insulin and somatostatin. As no human pancreatic alpha-cell lines are available to study in vitro the relative importance of insulin and glucose in the control of pancreatic glucagon release, we investigated a patient presenting with a malignant glucagonoma who underwent surgical resection of the tumour. Functional somatostatin receptors were present as octreotide administration decreased basal glucagon and insulin secretion by 52 and 74%, respectively. The removed tumour was immunohistochemically positive for glucagon, chromogranin A and pancreatic polypeptide but negative for insulin, gastrin and somatostatin. The glucagonoma cells were also isolated and cultured in vitro. Incubation experiments revealed that change from high (10 mM) to low (1 mM) glucose concentration was unable to stimulate glucagon secretion. A dose-dependent inhibition of glucagon release by insulin was however, observed at low glucose concentration. These findings demonstrate that insulin could inhibit glucagon secretion in vitro in the absence of elevated glucose concentrations. These data suggest, as observed in vivo and in vitro in several animal studies, that glucopenia-induced glucagon secretion in humans is not mediated by a direct effect of low glucose on alpha-cells but possibly by a reduction of insulin-mediated alpha-cell suppression and/or an indirect neuronal stimulation of glucagon release.

Atrial natriuretic peptides: reproducibility of renal effects and response of liver blood flow.

To assess the variability of the response to exogenous atrial natriuretic peptide (ANP), it was infused at the rate of 1 microgram/min for 2 h in 6 salt-loaded normal volunteers under controlled conditions on 2 occasions at an interval of 1 week. The effect on solute excretion and the haemodynamic and endocrine actions were highly reproducible. The constant ANP infusion caused a delayed and prolonged excretion of sodium, chloride and calcium, no change in potassium or phosphate excretion or in glomerular filtration rate but a marked decrease in renal plasma flow. Blood pressure, heart rate and the plasma levels of angiotensin II, aldosterone, arginine vasopressin and plasma renin activity were unaltered. The effect of a 2-h infusion of ANP 0.5 microgram/min or its vehicle on apparent hepatic blood flow (HBF) was also studied in 14 normal volunteers by measuring the indocyanine green clearance. A 21% decrease in HBF was observed in subjects who received the ANP infusion (p less than 0.01 vs vehicle). Thus, ANP infused at a dose that did not lower blood pressure decreased both renal and liver blood flow in normotensive volunteers. The renal and endocrine responses to ANP were reproducible over a 1-week interval.

Controversies about a common etiology for eating and mood disorders.

Obesity and depression represent a growing health concern worldwide. For many years, basic science and medicine have considered obesity as a metabolic illness, while depression was classified a psychiatric disorder. Despite accumulating evidence suggesting that obesity and depression may share commonalities, the causal link between eating and mood disorders remains to be fully understood. This etiology is highly complex, consisting of multiple environmental and genetic risk factors that interact with each other. In this review, we sought to summarize the preclinical and clinical evidence supporting a common etiology for eating and mood disorders, with a particular emphasis on signaling pathways involved in the maintenance of energy balance and mood stability, among which orexigenic and anorexigenic neuropeptides, metabolic factors, stress responsive hormones, cytokines, and neurotrophic factors.

Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: results of the FACTS survey.

Background: Switzerland was the first country to approve certolizumab pegol (Cimzia, CZP) for the treatment of patients with moderate to severe Crohn's disease (CD) in September 2007. This phase IV study aimed to evaluate the efficacy and safety of CZP in a Swiss multicenter cohort of practice-based patients. Methods: Baseline and Week 6 evaluation questionnaires were sent to all Swiss gastroenterologists in hospitals and private practices. Disease activity was assessed with the Harvey-Bradshaw Index (HBI) and adverse events were evaluated according to WHO guidelines. Results: Fifty patients (31 women, 19 men) were included; 56% had complicated disease (stricture or fistula) and 52% had undergone prior CD-related surgery. All patients. had prior exposure to systemic steroids, 96% to immunomodulators, 78% to infliximab, and 50% to adalimumab. A significant decrease in HBI was observed at Week 6 (versus Week 0) following induction therapy with CZP 400 mg subcutaneously at Weeks 0, 2, and 4 (12.6 +/- 4.7 Week 0 versus 6.2 +/- 4.4 Week 6, P < 0.001). Response and remission rates at Week 6 were 54% and 40%, respectively. We identified 8/11 CD patients undergoing a 50% fistula response (P = 0.021). The frequency of adverse drug reactions attributed to CZP was 6%. CZP was continued in 80% of patients beyond Week 6. Conclusions: In a population of CD patients with complicated disease behavior, CZP induced a response and remission in 54% and 40% of patients, respectively. This series provides the first evidence of the effectiveness of CZP in perianal fistulizing CD.

A gene knockout approach in mice to identify glucose sensors controlling glucose homeostasis.

A key aspect of glucose homeostasis is the constant monitoring of blood glucose concentrations by specific glucose sensing units. These sensors, via stimulation of hormone secretion and activation of the autonomic nervous system (ANS), regulate tissue glucose uptake, utilization or production. The best described glucose detection system is that of the pancreatic beta-cells which controls insulin secretion. Secretion of other hormones, in particular glucagon, and activation of the ANS, are regulated by glucose through sensing mechanisms which are much less well characterized. Here I review some of the studies we have performed over the recent years on a mouse model of impaired glucose sensing generated by inactivation of the gene for the glucose transporter GLUT2. This transporter catalyzes glucose uptake by pancreatic beta-cells, the first step in the signaling cascade leading to glucose-stimulated insulin secretion. Inactivation of its gene leads to a loss of glucose sensing and impaired insulin secretion. Transgenic reexpression of the transporter in GLUT2/beta-cells restores their normal secretory function and rescues the mice from early death. As GLUT2 is also expressed in other tissues, these mice were then studied for the presence of other physiological defects due to absence of this transporter. These studies led to the identification of extra-pancreatic, GLUT2-dependent, glucose sensors controlling glucagon secretion and glucose utilization by peripheral tissues, in part through a control of the autonomic nervous system.

Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies.

BACKGROUND: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. METHODS: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. FINDINGS: Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons). INTERPRETATION: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. FUNDING: Cancer Research UK.

Corticosterone shifts reproductive behaviour towards self-maintenance in the barn owl and is linked to melanin-based coloration in females.

Trade-offs between the benefits of current reproduction and the costs to future reproduction and survival are widely recognized. However, such trade-offs might only be detected when resources become limited to the point where investment in one activity jeopardizes investment in others. The resolution of the trade-off between reproduction and self-maintenance is mediated by hormones such as glucocorticoids which direct behaviour and physiology towards self-maintenance under stressful situations. We investigated this trade-off in male and female barn owls in relation to the degree of heritable melanin-based coloration, a trait that reflects the ability to cope with various sources of stress in nestlings. We increased circulating corticosterone in breeding adults by implanting a corticosterone-releasing-pellet, using birds implanted with a placebo-pellet as controls. In males, elevated corticosterone reduced the activity (i.e. reduced home-range size and distance covered within the home-range) independently of coloration, while we could not detect any effect on hunting efficiency. The effect of experimentally elevated corticosterone on female behaviour was correlated with their melanin-based coloration. Corticosterone (cort-) induced an increase in brooding behaviour in small-spotted females, while this hormone had no detectable effect in large-spotted females. Cort-females with small eumelanic spots showed the normal body-mass loss during the early nestling period, while large spotted cort-females did not lose body mass. This indicates that corticosterone induced a shift towards self-maintenance in males independently on their plumage, whereas in females this shift was observed only in large-spotted females.