Development and Implementation of a Registry of Patients Attending Multidisciplinary Pain Treatment Clinics: The Quebec Pain Registry.

The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them (mean age ± SD: 52.76 ± 4.60, females: 59.1%) consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a "real-world" context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management.

Stability of reference proteins in human placenta: general protein stains are the benchmark.

The stability of reference proteins in semi-quantitative Western blot experiments in normal and diseased placenta has never been studied. This study aims to determine the stability of five reference proteins and two general protein stains in placentas from preeclampsia, gestational diabetes mellitus and matched control pregnancies. The stability of the reference proteins was analysed using indicators of inter-group (P value) and intra-group (coefficient of variation) stability. The effect of different normalization strategies was determined by normalizing serotonin transporter (SERT) expression against the different reference protein markers. Results show significant expression variability of ß-actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1), peptidylprolyl isomerase A (PPIA) and α-tubulin, and that amido black staining is the most stable reference protein marker. Furthermore, results show that SERT expression significantly differs according to the reference protein markers used for its normalization. The present study demonstrated the importance of using stable reference protein markers and normalization strategy in order to get correct results in semi-quantitative Western blot experiments in placental tissues.

OS060. Exercise training promotes placental growth and development in an animal model of preeclampsia superimposed on chronic hypertension.

INTRODUCTION: Chronic hypertension is an important risk factor for preeclampsia, increasing the prevalence of the disease to 15-25% in pregnant women. Unfortunately there are no known treatments for this disease aside from inducing delivery of the fetus. Nonetheless, several studies have found exercise training to have a protective effect on the risk of developing preeclampsia. OBJECTIVES: To determine the mechanisms implicated in the preventive effect of exercise training on preeclampsia, by focusing on the placenta. METHODS: Double transgenic mice, overexpressing both human renin and angiotensinogen (R(+)/A(+)), were used to investigate the effect of exercise training on an animal model of preeclampsia superimposed on chronic hypertension. Mice were placed in cages with free access to an exercise wheel 4 weeks prior to and during pregnancy. At gestational day 18, mice were sacrificed and their organs were collected. Real time PCR and Western Blot were performed to evaluate placental genes and proteins, respectively. Circulating sFlt-1(soluble Fms-like tyrosine kinase-1) levels were investigated by ELISA. Placental alterations were assessed by histology and immunohistochemistry, while blood pressure was measured by radiotelemetry. RESULTS: Sedentary R(+)/A(+) mice presented with significantly greater placental pathology, which was normalized with exercise training. This was characterized by a normalization of cytokeratin and histone H3 protein expression, thereby restoring placental development, specifically looking at trophoblasts and trophoblast giant cells, respectively. This exercise training effect appears to normalize placental growth primarily by promoting angiogenesis and development. Indeed, a pro-angiogenic shift could be detected which was characterized by an increase in placental growth factor gene expression, along with a decrease in sFlt-1 gene expression, which produced a decrease in circulating sFlt-1. Sedentary R(+)/A(+) mice also presented with a significant increase in VEGF protein, which was significantly decreased with exercise. Of interest, since it has been observed to be decreased with preeclampsia, insulin regulated aminopeptidase (IRAP) gene expression was significantly increased in the trained transgenic mice. Finally, exercise training prevented the increase in blood pressure normally observed at the end of gestation in sedentary R(+)A(+) mice. CONCLUSION: Exercise training both before and during gestation appears to promote placental growth and development by producing a pro-angiogenic placental environment. Put together, along with the lack in blood pressure increase, these factors may be responsible for preventing the development of preeclampsia in our animal model of preeclampsia superimposed on chronic hypertension. Identifying the mechanisms implicated in exercise-induced preeclampsia risk reduction will be critical to improve preeclampsia prophylaxis.

Trichosporon mucoides fungemia in a liver transplant recipient: case report and review.

Four months after receiving an orthotopic liver transplant, a 51-year-old man was admitted for progressive liver failure and severe hepatocellular necrosis thought to be due to tacrolimus. During his hospitalization he experienced bloodstream infections including fungemia due to Trichosporon mucoides and prolonged undulating fever despite antifungal and antibacterial treatment. He underwent removal of the allograft and implantation of another liver. Fever continued postoperatively until therapy with posaconazole was initiated. Initiation of posaconazole led to clinical improvement until the patient's demise from bacteremic vancomycin-resistant enterococcal peritonitis. Trichosporonosis appears to be an emerging fungal infection among immunocompromised individuals (including both hematological and solid organ transplant recipients). T. mucoides is a rare cause of systemic infection. When it occurs, trichosporonosis usually is associated with hematological malignancies and, to the best of our knowledge, has not been previously reported in a liver transplant recipient. The optimal treatment is not well defined. We report here the first case using posaconazole for treatment of trichosporonosis in a liver transplant recipient caused by T. mucoides.

Nausea and vomiting of pregnancy: what about quality of life?

OBJECTIVE: The objective of this study was to determine the impact of nausea and vomiting of pregnancy (NVP) and other determinants on generic and NVP-specific health-related quality of life (QOL) in the first trimester of pregnancy. DESIGN: Prospective study. SETTING: Centre Hospitalier Universitaire (CHU) Sainte-Justine or René-Laennec clinics, Montreal, Quebec, Canada. POPULATION: Pregnant women attending the clinics for their prenatal care from 2004 to 2006. Women were eligible if they were > or =18 years of age and < or =16 weeks of gestation at the time of their first prenatal visit. METHODS: After their first prenatal visit, women were asked to fill out a questionnaire covering maternal characteristics, presence and severity of NVP, and health-related QOL. MAIN OUTCOME MEASURES: QOL was measured by the generic 12-item Short Form Health Survey v.1 (SF-12) and the NVP-specific Quality of Life for Nausea and Vomiting during Pregnancy. RESULTS: Of the 367 pregnant women included in the study, 78.5% of women reported NVP in the first trimester of pregnancy. Multivariable linear models showed that presence of NVP in the first trimester of pregnancy was significantly associated with a lower physical component summary scale (P < 0.0001) and mental component summary scale (P = 0.0066) of the SF-12 scores. More severe NVP (moderate versus mild: P = 0.0002; severe versus mild: P = 0.0177 as measured by the validated modified Pregnancy-Unique Quantification of Emesis and Nausea index), intensity of nausea symptoms reported on a visual analogue scale (P < 0.0001), and nonpharmacological methods used to ease NVP symptoms in the first trimester of pregnancy (P = 0.0059) were significantly associated with poorer NVP-specific QOL among women suffering from NVP. CONCLUSION: These findings show that presence and severity of NVP have a negative impact on health-related QOL, which emphasises the importance of an optimal management of NVP.

Upregulation of alpha(8)beta(1)-integrin in cardiac fibroblast by angiotensin II and transforming growth factor-beta1.

Using a novel pharmacological tool with (125)I-echistatin to detect integrins on the cell, we have observed that cardiac fibroblasts harbor five different RGD-binding integrins: alpha(8)beta(1), alpha(3)beta(1), alpha(5)beta(1), alpha(v)beta(1), and alpha(v)beta(3). Stimulation of cardiac fibroblasts by angiotensin II (ANG II) or transforming growth factor-beta1 (TGF-beta1) resulted in an increase of protein and heightening by 50% of the receptor density of alpha(8)beta(1)-integrin. The effect of ANG II was blocked by an AT(1), but not an AT(2), receptor antagonist, or by an anti-TGF-beta1 antibody. ANG II and TGF-beta1 increased fibronectin secretion, smooth muscle alpha-actin synthesis, and formation of actin stress fibers and enhanced attachment of fibroblasts to a fibronectin matrix. The alpha(8)- and beta(1)-subunits were colocalized by immunocytochemistry with vinculin or beta(3)-integrin at focal adhesion sites. These results indicate that alpha(8)beta(1)-integrin is an abundant integrin on rat cardiac fibroblasts. Its positive modulation by ANG II and TGF-beta1 in a myofibroblast-like phenotype suggests the involvement of alpha(8)beta(1)-integrin in extracellular matrix protein deposition and cardiac fibroblast adhesion.

Specific potentiation by cyclic AMP of natriuretic peptide-mediated cyclic GMP production in adipose tissue.

Adipose tissue of the mesenteric territory contains large quantities of natriuretic peptide receptors (NPR) mainly of the NPR-C subtype. Guanylyl cyclase-bound receptors are also present since atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are equally potent in activating this enzyme. While searching for a potential biological role for NP in adipocytes we observed that ANP-mediated generation of cyclic GMP (cGMP) was potentiated when the cells were simultaneously treated with isoproterenol. Indeed, isoproterenol, a beta-adrenergic agonist, and forskolin, an activator of adenylyl cyclase, can both double or triple cGMP production in response to ANF stimulation. There was a direct correlation between the level of cyclic AMP (cAMP) generated and the level of NP-mediated cGMP production suggesting that a cAMP-dependent mechanism may be responsible of this potentiation. To determine whether or not this phenomenon was unique to adipocytes, NPR subtypes were characterized in 4 established cell lines and their cAMP-dependent cGMP behavior examined. A10 and A7r5 smooth muscle cells showed identical ratio of NPR subtypes with about 95% NPR-C and 5% NPR-B. PC12 cells presented 100% NPR-A and NIH 3T3 fibroblasts 50% NPR-C and 50% NPR-B. Regardless of the NPR subtype, forskolin could not potentiate the cGMP generation in these cell lines. These data indicate that the cAMP-dependent potentiation of the NP-mediated cGMP production is unique to adipocytes, appears independent of the guanylyl cyclase-linked NPR subtypes and may be involved in the sensitization of the guanylyl cyclase domain of NPR for a potential biological role of NP in the adipose tissue.