Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): a pilot study

ObjectivesIt was previously shown that dehydroepiandrosterone (DHEA) reverses chronic hypoxia-induced pulmonary hypertension (PH) in rats, but whether DHEA can improve the clinical and hemodynamic status of patients with PH associated to chronic obstructive pulmonary disease (PH-COPD) has not been studied whereas it is a very severe poorly treated disease.Patients and methodsEight patients with PH-COPD were treated with DHEA (200 mg daily orally) for 3 months. The primary end-point was the change in the 6-minute walk test (6-MWT) distance. Secondary end-points included pulmonary hemodynamics, lung function tests and tolerance of treatment.ResultsThe 6-MWT increased in all cases, from 333 m (median [IQR]) (257; 378) to 390 m (362; 440) (P < 0.05). Mean pulmonary artery pressure decreased from 26 mmHg (25; 27) to 21.5 mmHg (20; 25) (P < 0.05) and pulmonary vascular resistance from 4.2 UI (3.5; 4.4) to 2.6 UI (2.5; 3.8) (P < 0.05). The carbon monoxide diffusing capacity of the lung (DLCO % predicted) increased significantly from 27.4% (20.1; 29.3) to 36.4% (14.6; 39.6) (P < 0.05). DHEA treatment did not change respiratory parameters of gas exchange and the 200 mg per day of DHEA used was perfectly tolerated with no side effect reported.ConclusionDHEA treatment significantly improves 6-MWT distance, pulmonary hemodynamics and DLCO of patients with PH-COPD, without worsening gas exchange, as do other pharmacological treatments of PH (trial registration NCT00581087).     

Is prenatal urethral descent a risk factor for urinary incontinence during pregnancy and the postpartum period?

Introduction and hypothesis

Obstetric trauma during childbirth is considered a major risk factor for postpartum urinary incontinence (UI), particularly stress urinary incontinence. Our aim was to investigate the relation between postpartum UI, mode of delivery, and urethral descent, and to define a group of women who are particularly at risk of postnatal UI.

Methods

A total of 186 women were included their first pregnancy. Validated questionnaires about urinary symptoms during pregnancy, 2 and 12 months after delivery, were administered. Urethral descent was assessed clinically and by ultrasound at inclusion. Multivariate logistic regression analysis was used to determine the risk factors for UI during pregnancy, at 2 months and 1 year after first delivery.

Results

The prevalence of UI was 38.6, 46.5, 35.6, and 34.4 % at inclusion, late pregnancy, 2 months postpartum, and 1 year postpartum respectively. No significant association was found between UI at late pregnancy and urethral descent assessed clinically or by ultrasound. The only risk factor for UI at 2 months postpartum was UI at inclusion (OR 6.27 [95 % CI 2.70–14.6]). The risk factors for UI at 1 year postpartum were UI at inclusion (6.14 [2.22–16.9]), body mass index (BMI), and urethral descent at inclusion, assessed clinically (7.21 [2.20–23.7]) or by ultrasound. The mode of delivery was not associated with urethral descent.

Conclusions

Prenatal urethral descent and UI during pregnancy are risk factors for UI at 1 year postpartum. These results indicate that postnatal UI is more strongly influenced by susceptibility factors existing before first delivery than by the mode of delivery.

     

The excess in 2-5 mm follicles seen at ovarian ultrasonography is tightly associated to the follicular arrest of the polycystic ovary syndrome

BACKGROUND: We previously hypothesized that the excess of 2–5 mmfollicles seen at ovarian ultrasonography might be involvedin the follicular arrest (FA) of polycystic ovary syndrome (PCOS),independently from the main putative contributors of FA, namelyhyperandrogenism and hyperinsulinism. METHODS: A multivariate statistical analysis was applied retrospectivelyto clinical, biological and ultrasound data that were consecutivelycollected during 5 years in 457 patients with polycystic ovariesand in 188 age-matched non-hyperandrogenic and regularly cyclingcontrols without PCO at ultrasound. RESULTS: Stepwise discriminant analysis indicated that in PCOS the 2–5 mmfollicle number (FN) gave the strongest correlation to severityof the FA, followed by age and then by fasting insulin level.The other variables [waist circumference (WC), 6–9 mmFN, serum testosterone, FSH, LH and ovarian area] were rejectedby the analysis. Multiple linear regression indicated a significantand independent negative relationship between the 2–5and 6–9 mm FN in the PCOS (r = – 0.186, P <0.01) and control groups (r = – 0.281, P < 0.01). InPCOS only, the 6–9 mm FN was negatively and independentlyrelated to the WC (r = – 0.108, P < 0.05). CONCLUSIONS: The size of the 2–5 mm follicle pool is an independentand important contributor to the FA of PCOS. This result couldbe explained by an exaggerated physiological inhibitory effectfrom this pool on the terminal follicle growth. The metabolicderangement of PCOS that also contributes to the FA would actthrough a different mechanism.     

Endovascular treatment of experimental wide neck aneurysms: comparison of results using coils or cyanoacrylate with the assistance of an aneurysm neck bridge device

BACKGROUND AND PURPOSE: Endovascular treatment of wide neck aneurysms often results in incomplete occlusion or aneurysm recurrence. The two goals of the present study were to compare results of coil embolization with or without the assistance of an aneurysm neck bridge device (ANBD) and to explore the use of this instrument to control cyanoacrylate embolization. METHODS: Wide necked bifurcation aneurysms were constructed in 28 dogs. Coil embolization of the aneurysms was performed 2 to 4 weeks later, with (n = 11) or without (n = 10) ANBD assistance. In seven other animals, embolization was performed with cyanoacrylate, injected under the protection of ANBDs. Angiographic results were compared immediately after and at 3 and 12 weeks. Neointima formation at the neck was also compared between groups at 12 weeks. RESULTS: Initial angiographic results and recurrences at 12 weeks were not significantly different in aneurysms coiled with or without ANBDs. Neointimal scores were also similar. The use of one ANBD at the neck was not sufficient to safely deliver cyanoacrylate into aneurysms. Cyanoacrylate embolization led to improved angiographic results (P =.05) and to better neointimal sealing of the neck of the aneurysms at 12 weeks (P =.004). CONCLUSION: ANBDs did not prevent recanalization and recurrences after coil embolization of wide neck aneurysms in this animal study. ANBD-assisted cyanoacrylate embolization was unsafe but could decrease recurrences at 12 weeks.     

Effect of granulocyte-macrophage colony-stimulating factor on post-weaning multisystemic wasting syndrome in porcine circovirus type-2-transfected piglets

Post-weaning multisystemic wasting syndrome (PMWS) is a complex disease syndrome in swine, affecting nursery and fattening pigs. Although ongoing evidence suggests that porcine circovirus type-2 (PCV2) is the causal agent of PMWS, the host immune system appears to have a crucial role in the PMWS pathogenesis of PCV2-affected pigs. Owing to difficulties in producing a biologically pure form of PCV2 devoid of the other viral agents commonly present in swine tissues, we decided to use a tandem-cloned PCV2 DNA providing highly pure grade reagent in order to monitor the virulence of PCV2 alone or with an immunostimulating co-factor, granulocyte-macrophage colony-stimulating factor (GM-CSF). A single intramuscular injection of tandem-cloned PCV2 DNA into 5-week-old piglets produced plasmid to viral genome progeny and infectious particles as early as 8 days post-injection in all the organs tested (the lung, the tonsil and the inguinal, mesenteric, bronchial and upper-right axial lymph nodes). The initial plasmid load was not detected with the help of primers designed to specifically detect the acceptor plasmid, thus confirming the replication of the viral genome. Despite the presence of a high level of PCV2 genome copies in the lymphoid organs--the tonsil and the lung--and the presence of infectious particles, no detectable clinical manifestations or pathological lesions were observed in the transfected pigs over the period of observation, regardless of whether they had been co-injected with plasmid containing GM-CSF DNA or had received plasmid containing PCV2 DNA alone. GM-CSF encoding DNA injection had no significant effect on viral replication or on the production of viral particles and appearance of the disease.     

Ureteral obstruction and Crohn's disease

Noncalculous ureteral obstructions in Crohn's disease are often asymptomatic and unidentified. Occurring in about 3% of patients, they occur on the right side in more than 70% of cases, because of frequently associated ileocecal disease. If they are associated with inflammation or fibrosis of retroperitoneal periureteral fat nephrectomy may become necessary. Conservative treatment should be considered first, with urine drainage (ureteral stent, or percutaneous nephrostomy), diet, and corticotherapy. However bowel resection is often necessary during follow up. If this fails to cure the ureteral obstruction, ureterolysis should be performed. We report the case of a 32 year old woman with noncalculous ureteral obstruction revealing Crohn's disease.     

Working conditions in call-centers,the impact on employee health: a transversal study. Part II

Purpose  The present study sought to assess the impact of telephone call center employees’ working conditions on health by identifying at-risk employment situations. Methods  A transversal study was performed in companies followed by 47 occupational physicians taking part (working conditions have been previously described). A self-administered medical questionnaire was used to collect data on absence due to sick leave, hearing and visual problems, musculoskeletal disorders, psychotropic drug use, etc. An analog-scale self-assessment of health status and a general health questionnaire (GHQ-12) were used. Personal or familial events that might underlie health problems and affect GHQ-12 results were quantified and taken into account in a logistic regression. Results  A total of 2,130 call-handlers were included. Workers who had availed sick leave during the previous 12 months were 60%. The most frequent musculoskeletal complaints over the previous 12-month period concerned the cervical region (59%). During the same period, 77.3% of subjects experienced visual fatigue, 50% reported auditory fatigue signs and 47% vocal disturbance or fatigue. According to the Likert scale, 39.4% of workers had showed psychological distress. Almost 24% of the workers had used psychoactive medication during the previous 12 months. A significant association was found between psychological distress and the frequency of musculoskeletal disorders. Psychological distress and musculoskeletal disorders were significantly greater in workers with Job Strain and Iso Strain. After taking non-occupational factors into account, some occupational factors were found to increase the risk of psychological distress (Likert >12): imposed full-time schedule, being unable to simultaneously meet both quality and quantity requirements, situations of tension with clients, negative comments from superiors, and lack of recognition from superiors. Conclusions  This survey of over 2,000 call center employees highlighted the high frequency of psychological distress in this population and the health impact of working conditions. Legal agreements  Approval by the French Ministry of Research (Comité consultatif pour le traitement de l’information en matière de recherche dans le domaine de la santé) and the French data protection authority (Commission Nationale de l’Informatique et des Libertés) was obtained before starting the study.     

Probes for narcotic receptor mediated phenomena. 34. Synthesis and structure-activity relationships of a potent mu-agonist delta-antagonist and an exceedingly potent antinociceptive in the enantiomeric C9-substituted 5-(3-hydroxyphenyl)-N-phenylethylmorphan series

Both of the enantiomers of 5-(3-hydroxyphenyl)-N-phenylethylmorphan with C9alpha-methyl, C9-methylene, C9-keto, and C9alpha- and C9beta-hydroxy substituents were synthesized and pharmacologically evaluated. Three of the 10 compounds, (1R,5R,9S)-(-)-9-hydroxy-5-(3-hydroxyphenyl-2-phenylethyl-2-azabicyclo[3.3.1]nonane ((1R,5R,9S)-(-)-10), (1R,5S)-(+)-5-(3-hydroxyphenyl)-9-methylene-2-phenethyl-2-azabicyclo[3.3.1]nonane ((1R,5S)-(+)-14), and (1R,5S,9R)-(-)-5-(3-hydroxyphenyl)-9-methyl-2-phenethyl-2-azabicyclo[3.3.1]nonane ((1R,5S,9R)-(+)-15) had subnanomolar affinity at mu-opioid receptors (Ki = 0.19, 0.19, and 0.63 nM, respectively). The (1R,5S)-(+)-14 was found to be a mu-opioid agonist and a mu-, delta-, and kappa-antagonist in [35S]GTP-gamma-S assays and was approximately 50 times more potent than morphine in a number of acute and subchronic pain assays, including thermal and visceral models of nociception. The (1R,5R,9S)-(-)-10 compound with a C9-hydroxy substituent axially oriented to the piperidine ring (C9beta-hydroxy) was a mu-agonist about 500 times more potent than morphine. In the single-dose suppression assay, it was greater than 1000 times more potent than morphine. It is the most potent known phenylmorphan antinociceptive. The molecular structures of these compounds were energy minimized with density functional theory at the B3LYP/6-31G* level and then overlaid onto (1R,5R,9S)-(-)-10 using the heavy atoms in the morphan moiety as a common docking point. Based on modeling, the spatial arrangement of the protonated nitrogen atom and the 9beta-OH substituent in (1R,5R,9S)-(-)-10 may facilitate the alignment of a putative water chain enabling proton transfer to a nearby proton acceptor group in the mu-opioid receptor.