bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of prolactinomas during pregnancy – A survey of four Canadian provinces
Authors: Almalki Mussa H , Ur Ehud , Johnson Michelle , Clarke David B , Imran Syed A
Published: May 2017

Purpose: The guidelines for management of prolactinomas during pregnancy are mostly based on retrospective evidence or expert opinion. We conducted a survey to assess the current trends in management of prolactinomas during pregnancy.

Methods: A case-based electronic questionnaire was sent in January 2011 to all practicing endocrinologists, in four Canadian provinces: Nova Scotia, New Brunswick, Prince Edward Island and British Columbia with three cases of varying severity; ranging from a microprolactinomas to a large macroprolactinomas compressing the optic chiasm.

Result: There was a considerable diversity among endocrinologists with regards to monitoring and managing prolactinomas during pregnancy. In case of microprolactinomas, 94% of specialists would discontinue dopamine agonist (DA) therapy upon confirmation of pregnancy, 79% would discontinue serum prolactin measurement during pregnancy, and 94% would not perform routine pituitary imaging in the absence of new symptoms whereas 32% would perform regular formal visual field (VF) testing throughout pregnancy. In the case of macroprolactinomas, 65% chose to discontinue DA therapy upon confirmation of pregnancy, 30% would either perform regular MRI during pregnancy or, if serum prolactin was thought to be elevated out of proportion, with clinical judgment and 40% would not perform regular formal VF monitoring during pregnancy. In management of large macroprolactinomas, 82% elected to continue DA therapy whereas 18% chose surgical excision as the treatment of choice. Forty nine percent would perform regular MRI during pregnancy and 94% would perform regular formal VF monitoring during pregnancy.

Conclusion: Among endocrinologists there is considerable diversity in management of prolactinomas during pregnancy, indicating a need for better consensus and clearer guidelines.
Evaluation of sleeping energy expenditure using the SenseWear Armband in patients with overt and subclinical hypothyroidism
Authors: Ulas Turgay , Buyukhatipoglu Hakan , Eren Mehmet A. , Dal Mehmet S. , Torun Aysenur , Aydogan Timucin , Demir Mehmet E. , Turan Mehmet N.
Published: May 2017

Purpose: The aim of the present study was to evaluate the average sleeping energy expenditure (EE) levels using the SenseWear Armband (SWA) in patients with overt and subclinical hypothyroidism.

Methods: Sixty patients with hypothyroidism and 30 healthy individuals were recruited for the study. Hypothyroid patients were divided into two groups: group 1 (n = 30) consisted of patients with overt hypothyroidism and group 2 (n = 30) consisted of patients with subclinical hypothyroidism. Lastly, group 3 (n = 30) consisted of healthy subjects. The average EE and metabolic equivalent of task (MET) values during sleep of all the hypothyroid participants were analyzed at baseline and at the end of the study. Data were also obtained from the healthy subjects at baseline.

Results: The average sleeping EE and METs values were not significantly different at baseline. Similarly, these values did not change significantly after achieving a euthyroid state via thyroid hormone replacement (both p > 0.05).

Conclusions: Contrary to what has been previously reported , the average sleeping EE and METs values in all hypothyroid patients and healthy individuals were similar at baseline and did not change in the patients with overt and subclinical hypothyroidism after achievement of a euthyroid state.
Re: Clin Invest Med. 2006 Jun;29(3):154-8
Authors: CIM _
Published: May 2017

Clinical and Investigative Medicine wishes to inform its readers of the following incident of redundant publication. The publication: de Lorgeril M, Salen P  The Mediterranean diet in secondary prevention of coronary heart disease. Clin Invest Med. 2006 Jun;29(3):154-8 contains a substantial amount of information and text reported in the previously published article, de Lorgeril M, Salen P. The Mediterranean-style diet for the prevention of cardiovascular diseases. Public Health Nutr. 2006 Feb;9(1A):118-23.
Zoledronic acid, an aminobisphosphonate, prolongs survival of skin allografts
Authors: Liu Chia-Yuan , Yang Po-Sheng , Cheng Shih-Ping , Huang Yu-Chuen , Lee Jie-Jen , Ko Chun-Chuan , Shieh Hui-Ru , Chen Yu-Jen
Published: May 2017

Purpose: Zoledronic acid (ZOL), an effective nitrogen-containing bisphosphonate used to prevent excessive bone loss in clinical practice, has been shown to affect the development of dendritic cells by redirecting differentiation toward a state of atypical maturation. The study was aimed to examine whether ZOL can reduce acute rejection of skin allografts.

Methods: A skin transplantation model using C57BL/6 to BALB/c mice was used. ZOL was injected intraperitoneally into transplant recipients post-surgically. Graft survival, body weight, leukocyte count, hepatic and renal functions were assessed.

Results: ZOL treatment significantly prolonged skin allograft survival in mice. In terms of toxicity, there were no significant differences in body weight, leukocyte count, plasma alanine aminotransferase or creatinine levels between the ZOL-treated and control groups. Histopathology showed that the loss of skin integrity seen in control group was prevented by ZOL treatment. In draining lymph nodes and spleen, the number and clustering extent of mononuclear cells were markedly declined by ZOL treatment. The plasma IL-6 levels were reduced by treatment of ZOL.

Conclusion: ZOL can prolong skin allograft survival without major toxicity.
BAP1 is a good prognostic factor in advanced non-small cell lung cancer
Authors: Fan Li-hong , Tang Li-na , Yue Lu , Yang Yi , Gao Zhong-li , Shen Zan
Published: May 2017

Purpose: Non-small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting epidermal growth factor receptor (EGFR) mutations have been developed, most advanced NSCLC is still incurable and new targets for anticancer drugs are in demand. BRCA1-associated protein-1 (BAP1) is a component of the ubiquitin proteasome system (UPS). UPS has emerged as a potential target for anticancer drugs. The aim of the present study was to investigate the expression of BAP1 protein in patients with NSCLC.

Methods: BAP1 expression was measured using Western blot analysis in 103 cases patients with advanced NSCLC.

Results: Results revealed 49 (47.5%) patients were classified with high expression of BAP1. Squamous cell carcinomas were more likely to be observed in BAP1 high expressers compared with adenocarcinomas (55.8% vs. 32.3%, p= 0.001). High BAP1 expression was associated with no lymph node metastasis (p= 0.002). There was also a significant association between BAP1 expression and histological type (p= 0.014), while expression of BAP1 was not correlated with other clinical or pathological characteristics. Kaplan-Meier survival analysis showed that patients with high BAP1 expression had a longer median survival compared with patients with low BAP1 expression (23.2 vs. 14.7 months, p= 0.021). Multivariate analysis revealed that high BAP1 expression was an independent lower risk for all 103 patients (HR = 0.61, 95% CI 0.32-0.71, p = 0.003).

Conclusions: BAP1 may be a useful prognostic factor of NSCLC patients and potential target for anticancer drugs.
A comparison of the application of fibrin glue and adhesive film for repair of anastomotic leaks in the rat
Authors: Ayhan Barıs , Erikoglu Mehmet , Tavlı Süleyman S. , Toy Hatice
Published: May 2017

Background: Anastomotic leaks constitute one of the most serious intraoperative complications and although many studies have been devoted to finding a solution for this problem, none of them has yet been able offer a decisive, successful method. In this study, the ability of fibrin glue and adhesive film to repair anastomotic leaks in an experimental model was compared.

Materials and methods: The sample comprised four groups of seven rats: Group 1 (Control): the distal colon was transected and anastomosis was performed. Group 2 (Primary repair): incomplete anastomosis produced a leak that was closed by primary repair on day 3. Group 3 (Fibrin glue): incomplete anastomosis produced a leak that was closed by primary repair and fibrin glue applied on day 3. Group 4 (Adhesive film): incomplete anastomosis produced a leak that was closed by primary repair and adhesive film was applied on day 3. The rats were sacrificed on day 6 following anastomosis. Anastomotic blast compressions were measured and fibroblast activation, inflammation, neovascularization and levels of collagen were evaluated.

Results: The results from Group 4 showed that blast compression values were high and statistically significantly increased over control values (p < 0.05). Inflammation in Group 2 was significantly higher than the other groups (p < 0.05). No significant differences were detected in the comparison of the groups regarding the other scoring criteria (p > 0.05).

Conclusion: Adhesive film is more effective in reducing anastomotic leakage than fibrin glue.
Serum CA-125: biomarker of pulmonary tuberculosis activity and evaluation of response to treatment
Authors: Şahin Füsun , Yildiz Pinar
Published: May 2017

Purpose: CA-125 is a high molecular weight mucin-like glycoprotein and an ovarian cancer antigen. Elevated CA-125 levels are also seen with various other benign and malignant conditions. In this study, the ability of CA-125 to predict pulmonary tuberculosis activity was investigated.

Methods: This analytical study included 42 cases with active tuberculosis (Group 1), 35 cases with  inactive tuberculosis  (Group 2) and 20 healthy subjects (Group 3). CA-125 measurements were taken in all three groups. Measurements in Group 1 were repeated after completing a two month anti-tuberculosis treatment in 38 of the 42 patients.

Results: Mean serum CA-125 level for Group 1 was 76.48±24.71 U/mL, which was significantly higher than levels in Group 2 (20.01±7.89 U/mL) and Group 3 (18.32±2.87 U/mL) (p < 0.001). Of the 38 patients in Group 1 who were studied both pre- and post-treatment, CA-125 levels decreased significantly: from 78.88±24.72 U/mL before treatment to 22.78±8.02 U/mL after treatment (p < 0.001). There was no statistically significant difference between the  post-treatment  values  of   Group 1 and either Group 2 and Group 3 values (p > 0.05).  Group 2 and Group 3 levels were not  significantly different (p > 0.05). The cut-off level for accurate determination of activity was 36.35 U/mL. The sensitivity at this level was 97.6% and specificity was 100%.

Conclusion: Our findings suggest that CA-125 can be a beneficial parameter in determination of pulmonary tuberculosis activity and the evaluation of response to treatment.
Effect of overweight and obesity on the left ventricular systolic and diastolic functions in patients with acute myocardial infarction
Authors: Poyraz Fatih , Turfan Murat , Kocaman Sinan A. , Yazici Huseyin U. , Sen Nihat , Tulmac Murat , Vatankulu Mehmet A. , Aygül Nazif , Ozdogru Ibrahim , Aydar Yuksel , Tavil Yusuf , Abaci Adnan
Published: May 2017

Purpose: The purpose of this study was to evaluate whether a association exits among overweight and obesity and left ventricular systolic and diastolic functions in patients admitted with first ST-elevation myocardial infarction (STEMI).

Methods: The present study was performed on 451 consecutive patients diagnosed with first STEMI (376 men, 75 women; mean age 56.1±10.8 years). The patients were classified into three groups based on their body mass index (BMI) as normal weight (BMI < 25 kg/m2), overweight (BMI: 25-29.9 kg/m2) and obese (BMI > 30 kg/m2). Echocardiographic features were evaluated and compared among the three groups.

Results: Mitral annulus E velocities were higher in obese individuals than normal weight group (p < 0.01). In contrast, mitral A velocities were lower (p =0.03); consequently, E\A and E'\A' ratios were lower (both p =0.01) in the obese group with respect to normal weight group. When the correction of entire variations existing among the groups were performed using multivariate linear regressions analyses, it turned out that BMI was independently associated with E/A (β= -0.19, p =0.044) and with E'/A' (β= -0.016, p=0.021). Ejection fraction, wall motion score index and myocardial S velocities were comparable among the study groups (p > 0.05).

Conclusion: These results suggest that while obesity has no adverse effect on the left ventricular systolic function, it has unfavorable consequences on the left ventricular diastolic function in the patients with first STEMI. In contrast, no unfavorable effects of overweight on the left ventricular systolic and diastolic function were detected.
PNPLA3 Polymorphisms and Liver Aminotransferase Levels in a Mexican American Population
Authors: Li Quan , Qu Hui-Qi , Rentfro Anne R. , Grove Megan L. , Mirza Shaper , Lu Yang , Hanis Craig L , Fallon Michael B , Boerwinkle Eric , Fisher-Hoch Susan P. , McCormick Joseph B.
Published: May 2017

Purpose: This study examined genetic associations of patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an extensively documented, randomly recruited Mexican American population at high risk of liver disease.

Methods: Two single nucleotide polymorphisms (SNP) in the PNPLA3 gene (i.e., rs738409 and rs2281135) were genotyped in 1532 individuals. Population stratification was corrected by the genotyping of 103 ancestry informative markers (AIMs) for Mexican Americans.

Results: Both PNPLA3 SNPs showed highly significant association with alanine aminotransferase (ALT) levels, but was also, in males, associated with aspartate aminotransferase (AST) levels. Haplotypic association test of the two SNPs suggested stronger genetic association with rs738409 than rs2281135. Obvious sex effects were observed: rs738409-sex interaction in ALT levels P=8.37x10-4; rs738409-sex interaction in AST levels P=5.03x10-3.

Conclusions: This population study highlights a sex-specific association of PNPLA3 polymorphisms and elevated liver enzymes in a population-based study, independent of common pathological factors of the metabolic syndrome. The strong genetic association found in women≤50 years old, but not in women > 50 years old, suggests that sex hormones may mediate the sex effect.
Sputum MicroRNA Profiling: A Novel Approach for the Early Detection of Non-Small Cell Lung Cancer
Authors: Roa Wilson H. , Kim Julian O. , Razzak Rene , Du Hongfei , Guo Linghong , Singh Ravinder , Gazala Sayf , Ghosh Sunita , Wong Eric , Joy Anil A. , Xing James Z. , Bedard Eric L.
Published: May 2017

Purpose: MicroRNAs (miRNAs) post-transcriptionally regulate hundreds of gene targets involved in tumorigenesis thereby controlling vital biological processes, including cellular proliferation, differentiation and apoptosis. MiRNA profiling is an emerging tool for the potential early detection of a variety of malignancies. This study was conducyed to assess the feasibility and methodological robustness of quantifying sputum miRNAs, employing quantitative real-time polymerase chain reaction (RT-qPCR) and cluster analysis on an optimized miRNA profile as a novel approach for the early detection of non-small cell lung cancer (NSCLC).

Methods: The relative expressions of 11 miRNAs in sputum (miR-21, miR-145, miR-155, miR-205, miR-210, miR-92, miR-17-5p, miR-143, miR-182, miR-372, and let-7a) in addition to U6 were retrospectively assessed in four NSCLC-positive and four negative controls. Subsequently, a set of five miRNAs (miR-21, miR-143, miR-155, miR-210, miR-372) was selected because of degree of relatedness observed in the cluster analysis and tested in the same sputum sample set. The five optimized miRNAs accurately clustered these eight retrospective patients into NSCLC positive cases and negative controls. The five miRNA panel was then prospectively quantified in the sputum of 30 study patients (24 NSCLC cases and six negative controls) in a double-blind fashion to validate a five miRNA panel using hierarchical cluster analysis.

Results: The optimized five miRNA panel detected NSCLC (83.3% sensitivity and 100% specificity) in 30 prospectively accrued study patients.

Conclusion: Sputum miRNA profiling using cluster analysis is a promising approach for the early detection of non-small cell lung cancer. Further investigation using this approach is warranted.
A new model of reversible obstructive jaundice using rapidly absorbable suture materials
Authors: Kahramansoy Nurettin , Erkol Hayri , Yilmaz Edip E , Şit Mustafa , Yilmaz Fahri , Tosun Mehmet , Çöl Cavit
Published: May 2017

Purpose: Reversible obstructive jaundice models have some limiting features, including the need for a second anaesthesia, re-laparotomy and surgical intervention after common bile duct ligation. The present study investigates the feasibility of a new application that can eliminate these limitations. Rapidly absorbable suture materials were used for ligation; therefore, spontaneous biliary decompression was anticipated by the self release of these rapidly degrading materials.

Methods: Common bile ducts in Wistar Albino rats were ligated with silk, polyglytone 6211, or irradiated polyglactine 910 (n=7 for each group). Rats were grouped according to both the suture materials and the experiments termination date: 5 days (sham, silk5, polyglytone5, polyglactine5) and 21 days (silk21, polyglytone21, polyglactine21) after the ligation. Biochemical and morphologic changes of liver were assessed.

Results: The group polyglactine21 showed significantly lower mean ALT, AST, GGT, total and direct bilirubin values when compared with the group polyglactine5 (p=0.004-0.037). Morphologic changes did not correlate with the biochemical amelioration. In the group polyglytone21, not only the biochemical but also the morphologic changes significantly ameliorated when compared with the group polyglytone5 (p=0.003-0.043). No procedure associated mortality was observed.

Conclusion: Common bile duct ligation with polyglytone offers a new reversible model for prolonged obstructive jaundice which abolishes the need for relaparotomy and a second surgical intervention and significantly reduces mortality.
Mentors And The Butterfly Effect: Triggers For Discovering Signalling by Proteinases via Proteinase-Activated Receptors (PARs) And More
Authors: Hollenberg Morley D
Published: May 2017

The essential role of proteinases as regulatory digestive enzymes, recognized since the late 1800s, has been underscored by the discovery that more than 2% of the genome codes for proteinases and their inhibitors. Further, by the early 1970s it was appreciated that in addition to their digestive actions, proteinases can affect cell function: (1) by the generation or degradation of peptide hormones and (2) by the direct regulation of signalling by receptors like the one for insulin. It was the discovery in the 1990s of the novel G-protein-coupled ‘proteinase-activated receptor’ (PAR) family that has caused a paradigm shift in the understanding of the way that proteinases can regulate cell signalling. This overview provides a perspective for the discovery of the PARs and my laboratory’s role in (1) understanding the molecular pharmacology of these fascinating receptors and (2) identifying the potential pathophysiological roles that the PAR family can play in inflammatory disease. In this context, the overview also portrays the essential impact that seemingly minor comments/insights provided by my lifelong mentors have had on kindling my intense interest in proteinase-mediated signalling. The ‘butterfly effect’ of those comments has led to an unexpectedly large impact on my own research directions. Hopefully my own ‘butterfly comments’ will also be heard by my trainees and other colleagues with whom I am currently working and will promote future discoveries that will be directly relevant to the treatment of inflammatory disease.
Effects of High Loading Dose of Clopidogrel in ST Elevated Myocardial Infarction Treated with Fibrinolytic Agent
Authors: Solmaz Hatice , Akbulut Mehmet , Korkmaz Hasan , Yavuzkir Mustafa F , Kaya Oğuz K , Kurtoğlu Ertuğrul , Kuzu Zülfiye , Karadağ Makbule K , Uysal Ayhan
Published: May 2017

Purpose: The purpose of the present study was to evaluate the effects of different loading doses of clopidogrel on ST segment resolution on ECG, changes in cardiac enzyme levels and serum levels of high-sensitivity C-reactive protein (Hs-CRP) in patients with ST elevated myocardial infarction (STEMI) treated with fibrinolytic therapy.

Methods: Patients admitted to our cardiology clinic with a diagnosis of STEMI and treated with fibrinolytic therapy were included: Group 1 (n=58) received a 300 mg loading dose of clopidogrel, Group 2 (n=55) a 450 mg loading dose and Group 3 (n=59) a 600 mg loading dose. A 75 mg/d maintanence dose of clopidogrel was given in all groups.

Results: All demographic characteristics and baseline laboratory parameters were statistically similar among three groups (p > 0.05). When ST resolution periods were compared, most patients in Group 3 had ST resolution at 30 minutes; Group 2 at 60 minutes and Group 1 at 90 minutes (p < 0.05). Peak levels of creatine kinase (CK) and CK-MB were as follows: Group 3, 8th hour, Group 1 and 2, 12th hour. Peak levels of those enzymes were significantly lower in Group 3 than in Group 1 and 2 ( < 0.05). Although basal hs-CRP levels of all groups were similar, the increase in hs-CRP levels at 48 hours was lower with higher clopidogrel loading doses (p < 0.05).

Conclusion: In this study comparing three different clopidogrel loading doses, the higher doses provided earlier ECG resolution, earlier and lower peak CK and CK-MB levels and lower levels of hs-CRP.
Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2
Authors: Zhang Hui , Zhang Jin-Ying , Sun Tong-Wen , Shen De-Liang , He Fei , Dang Yu-Hua , Li Ling
Published: May 2017

Purpose: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the pathogenesis of atherosclerosis, especially in advanced plaques. In the present study, the abilities of darapladib, a selective Lp-PLA2 inhibitor, and lentivirus-mediated Lp-PLA2 silencing on inflammation and atherosclerosis in apolipoprotein E-deficient mice were compared.

Methods: Apolipoprotein E-deﬁcient mice were fed on a high-fat diet and a constrictive collar was placed around the left carotid artery to induce plaque formation. The mice were randomly divided into control, negative control (NC), darapladib and RNA interference (RNAi) groups. Eight weeks after surgery, lentivirus-mediated RNAi construct or darapladib were used to decrease the expression of Lp-PLA2. Plaques were collected five weeks later for histological analysis. Inflammatory gene expression in the atherosclerotic lesions were then determined at the mRNA and protein level.

Results: The expression of pro-inflammatory cytokines was significantly reduced in the treatment group, compared to nontreatment group, whereas the plasma concentration of anti-inflammatory cytokines increased markedly. Moreover, our results demonstrated a significant reduction in plaque lipid content, as well as a rise in collagen content following Lp-PLA2 inhibition. Interestingly, when comparing the two methods of Lp-PLA2 inhibition, animals treated with Lp-PLA2 RNAi were found to exhibit lower plaque areas and enhanced improvement of plaque stability as compared with animals treated with darapladib. Darapladib had no attenuating effect on atherosclerotic plaque area. These therapeutic effects were independent of plasma lipoprotein levels.

Conclusions: Lp-PLA2 inhibition by darapladib or lentivirus-mediated RNAi ameliorated inflammation and atherosclerosis in apolipoprotein E-deficient mice. The effect was more prominent in the RNAi group.
Levels of indoxyl sulfate are associated with severity of coronary atherosclerosis
Authors: Hsu Chia-Chang , Lu Yung-Chuan , Chiu Cheng-An , Yu Teng-Hung , Hung Wei-Chin , Wang Chao-Ping , Lu Li-Fen , Chung Fu-Mei , Lee Yau-Jiunn , Tsai I-Ting
Published: May 2017

Purpose: Indoxyl sulfate (IS) is linked to endothelial damage, NF-κB activation and induced development of atherosclerosis. The purpose of this study was to investigate the relationship between serum IS levels and the severity of coronary artery stenosis. In addition, the relationship among IS and various cardiovascular risk factors was also explored.

Methods: Serum IS concentrations were measured using ultra performance liquid chromatography in 191 consecutive patients presenting with stable angina. The associations between serum IS levels and angiographic indexes of the number of diseased vessels, modified Gensini scores and calcium scores were determined.

Results: Patients with significant coronary artery stenosis were found to have higher serum IS levels than patients with normal coronary arteries. Using multivariate analysis, serum IS levels were found to be independently associated with the presence and severity of coronary artery disease (CAD). Furthermore, statistically significant correlation was observed between the serum IS levels and age, Agatston calcium score, volume calcium score, modified Gensini score, coronary lesions, coronary disease and Framingham-10 year risk score.

Conclusion:This study indicates that serum IS levels are significantly higher in the presence of CAD and correlate with the severity of the disease and coronary atherosclerosis scores, which suggest that increased serum IS may be involved in the pathogenesis of coronary atherosclerosis.
Scientific overview: CSCI-CITAC annual general meeting and young investigator's forum 2011
Authors: Jamshidi Farzad , Schmidt Anna R , Belrose Jillian C
Published: May 2017

In 2011, members of the Clinician Investigator Trainee Association of Canada - Association des cliniciens-chercheurs en formation du Canada (CITAC-ACCFC) and the Canadian Society for Clinician Investigators (CSCI) held a joint Annual General Meeting (AGM) and Young Investigator Forum (YIF) September 12-14 in Ottawa, ON, Canada. The theme of the meeting was “The Role of Government and Regulatory Organizations in Shaping the Environment of the Clinician Scientist”. The meeting was well attended by established clinician scientists and clinician investigator trainees from across Canada. The aim of this scientific overview is to highlight the research presented by trainees at both the oral plenary session as well as the poster presentation sessions of this meeting. This work covers a wide variety of medical disciplines, focusing on translational medicine, from the basic sciences to clinical application.
Interferon-γ and Interleukin-17 production from PPD-stimulated PBMCss of patients with pulmonary tuberculosis
Authors: Nunnari Giuseppe , Pinzone Marilia R , Vancheri Carlo , Palermo Filippo , Cacopardo Bruno
Published: May 2017

Purpose: The purpose of this study was to evaluate Interferon (IFN)-γ and Interleukin(IL)-17 profiles in patients with different clinical presentations of pulmonary tuberculosis (TB) and to compare them with those of tuberculin-negative and tuberculin-reactive healthy controls

Methods: Peripheral blood mononuclear cells (PBMCss), isolated from patients (n=52) and controls (n=30), were stimulated ex vivo with purified protein derivative (PPD) and IFN-γ and IL-17 levels in the supernatant were measured.

Results: At baseline, PBMCss from patients with TB released a significantly lower amount of IL-17 (p=0.043) than PBMCss from healthy controls, whereas IFN-γ levels were similar in the two groups. After PPD stimulation, a significant rise in IL-17 levels was found only among healthy controls (p=0.02). This rise in IL-17 levels was similar between tuberculin-reactive and tuberculin-negative subjects. After PPD stimulation, patients with infiltrative TB secreted higher levels of IL-17 and IFN-γ than those affected with chronic, miliary and cavitary TB (p < 0.01). IFN-γ production from patients with infiltrative TB was even higher than for healthy controls (p < 0.01). PBMCss from tuberculin-reactive patients released higher levels of IFN-γ than tuberculin-negative subjects after PPD stimulation (p < 0.01).

Conclusion: Ex vivo PPD stimulation of PBMCs from patients with pulmonary TB does not significantly stimulate IL-17 release; however, higher IL-17 and IFN-γ levels are found in patients with infiltrative disease, in comparison with those affected with miliary, cavitary and chronic TB.
Significance of CAVI, hs-CRP and Homocysteine in subclinical arteriosclerosis among a healthy population in China
Authors: Zhong Jinpeng , Wang Yonghong , Wang Xiaoling , Li Fengzeng , Hou Yulei , Luo Haixia , Chen Hui
Published: May 2017

Purpose: The purpose of this study is to evaluate the ability of cardio-ankle vascular index (CAVI), high-sensitivity C-reactive protein (hs-CRP) levels and homocysteine (Hcy) levels to screen for subclinical arteriosclerosis (subAs) in an apparently healthy population, with the view to obtaining an optimal diagnostic marker or profile for subAs.

Methods: Subjects (152) undergoing routine health examinations were recruited and divided into two groups: carotid arteriosclerosis (CA) and non-carotid arteriosclerosis (NCA), according to carotid intima-media thickness (CMIT). CAVI was calculated based on blood pressure and pulse wave velocity. Serum hs-CRP and Hcy levels were also measured. A Receiver Operating Characteristic (ROC) curve was plotted to evaluate the efficacy of each in carotid arteriosclerosis screening. Ten parameter combinations, designated W1 to W10, were compared in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Results: The levels of all three parameters were significantly higher in the CA group, compared with the NCA group. ROC curves showed that the area under the curve (AUC) for CAVI was 0.708 (95%CI: 0.615-0.800), which is significantly larger than that of either hs-CRP (0.622) or Hcy (0.630), respectively (P < 0.001). Maximum sensitivity (100%) and NPV (100%) were attained with W10, while maximum specificity (86.2%) and PPV (46.7%) were obtained with W7. With W9, the maximum Youden index (0.416) was obtained, with a sensitivity of 77.8% and specificity of 63.8%.

Conclusions: CAVI is more effective than hs-CRP or Hcy for subAs screening. The optimal profile was obtained with a combination of CAVI and other parameters.
The protective effect of dexmedetomidine on bupivacaine-induced sciatic nerve inflammation is mediated by mast cells
Authors: Tüfek Adnan , Kaya Savaş , Tokgöz Orhan , Fırat Uğur , Evliyaoğlu Osman , Çelik Feyzi , Karaman Haktan
Published: May 2017

Purpose: This study was designed to assess the correlation between the neuroprotective effect of dexmedetomidine and oxidative stress, neural inflammation and mast cell stability in rats with bupivacaine-induced sciatic nerve toxicity.

Methods: Forty adult Wistar Albino rats, eight rats per group, were used. Saline (0.3 ml of 0.9%), dexmedetomidine (20 µg/kg), 0.5% bupivacaine or 0.5% bupivacaine+dexmedetomidine (20 µg/kg) was injected into the sciatic nerve. A control group of rats received no injection. Fourteen days after injection, the sciatic nerves were harvested and total oxidant status, total anti-oxidant status, paraoxonase-1, galectin-3 and matrix metalloproteinase 2 and 9 levels were measured in the sciatic nerves. In addition, the presence and status of inflammation, edema, and mast cells were evaluated histopathologically.

Results: The combination of dexmedetomidine and bupivacaine alleviated oxidative stress. In addition, it decreased matrix metalloproteinase 9 and galectin-3 levels and increased matrix metalloproteinase 2 levels. Moreover, it stabilized recruited mast cells at the injury site; however, it did not significantly decrease inflammation or edema.

Conclusion: Dexmedetomidine may ameliorate bupivacaine-induced neurotoxicity by modulating mast cell degranulation. The neuroprotective effect of dexmedetomidine may make it a suitable adjuvant agent to local anesthetics in peripheral nerve blocks.
MiR-21 confers resistance against CVB3-induced myocarditis by inhibiting PDCD4-mediated apoptosis
Authors: He Jin , Yue Yan , Dong Chunsheng , Xiong Sidong
Published: May 2017

Purpose: The participation of microRNAs (miRNAs) in cardiovascular diseases suggests them as potential targets for novel preventive and therapeutic strategies. In this study, the key myocardial miRNA, miR-21, was identified in the murine coxsackievirus B3 (CVB3)-induced myocarditis model and its contribution to disease progression was explored.

Methods: Myocardial microRNA expression changes in CVB3-infected mice were analyzed by real-time PCR and miR-21 was found to be the miRNA whose expression was significantly reduced. Mice were injected with plasmid encoding miR-21 (pMDH-miR-21) at day 1 post CVB3 infection and myocarditis severity was evaluated 7 days post-infection. The underlying mechanism of miR-21 in viral myocarditis was also investigated.

Results: Myocardial miR-21 expression was negatively related to viral myocarditis severity. Recovery of miR-21 expression, by injecting with pMDH-miR-21, significantly relieved CVB3-induced myocarditis as shown by increased body weight, reduced myocardial injury, lowered myocarditis score and increased survival rate. Further study showed that miR-21 could protect myocardial apoptosis by specifically inhibiting its target programmed cell death 4 (PDCD4) expression.

Conclusion: miR-21 administration efficiently alleviated CVB3-induced myocarditis by repressing PDCD4-mediated apoptosis. Our study not only helps to better understand the pathogenesis of viral myocarditis, but also proves the potential of miR-21 as a novel therapeutic target for treatment of CVB3-induced myocarditis and other apoptosis-mediated cardiovascular diseases.
Burdens of Family Caregiving at the End of Life
Authors: Stajduhar Kelli I
Published: May 2017

A patient’s ability to be cared for and to die at home is heavily dependent upon the efforts of family caregivers. Considerable stresses are associated with such caregiving, including physical, psychosocial and financial burdens. Research has shown that unmet needs and dissatisfaction with care can lead to negative outcomes for caregivers. While many family caregivers also report caregiving as life-enriching, some report that they would prefer alternatives to care at home, primarily because of these associated burdens. Little is known about which interventions are most effective to support family caregivers ministering palliative care at home. Well-designed studies to test promising interventions are needed, followed by studies of the best ways to implement the most effective interventions. Clinically effective practice support tools in palliative home care are warranted to identify family caregiver needs and to ensure that patients and their family caregivers have a choice about where care is provided.
Devastating Metabolic Consequences of a Life of Plenty: Focus on the Dyslipidemia of Overnutrition
Authors: Lewis Gary F
Published: May 2017

Although undernutrition and starvation continue to affect a substantial portion of the world’s population, billions of people in both developed and developing countries are affected by the opposite problem: consumption of calories that exceed their daily energy expenditure, a condition of overnutrition. The body’s response to a positive net energy balance is to store energy, predominantly as triglyceride molecules, in the subcutaneous and visceral fat compartments that expand and ultimately manifest in obesity. The body’s fat depot, however, does not have an infinite capacity to store and expand, and at set points, which differ from individual to individual and are also influenced by ethnicity, energy substrates ‘spill over’, resulting in ‘ectopic’ fat storage in tissues and organs that are not typically major fat storage depots in lean individuals. A complex web of nutrient overload, chronic inflammation, hormonal action, mitochondrial dysfunction and insulin resistance, to mention some of the factors involved, results in devastating metabolic abnormalities that have far reaching implications for health and disease, leading ultimately to some of the most common chronic diseases of our time; i.e., diabetes mellitus, cancer, chronic liver disease and atherosclerosis. Given the complexity and wide-ranging manifestations of overnutrition (also referred to here as insulin resistant states), we will highlight a specific aspect of the condition, that of dyslipidemia. This review will draw mainly on knowledge acquired from whole body, integrative physiology research in animals and humans affected by overnutrition, and will demonstrate how these types of studies can shed light on our understanding of the pathophysiology of the typical dyslipidemia of obesity, insulin resistance and type 2 diabetes.
Influence of cardiac dysfunction and systemic inflammation on pulmonary function and airway responsiveness in obese subjects
Authors: Gagnon-Audet Andrée-Anne , Poirier Paul , Turcotte Hélène , Martin Julie , Bastien Marjorie , Simard Serge , Boulet Louis-Philippe
Published: May 2017

Purpose: Obesity is associated with left ventricular diastolic dysfunction and altered heart rate variability, as well as pulmonary dysfunction. The relationship between asthma and cardiac dysfunction in severely obese subjects is unknown, although it has been hypothesized that cardiac dysfunction may contribute to increase airway hyper-responsiveness (AHR). This study aimed to determine if AHR is associated with left ventricular diastolic dysfunction and heart rate variability in severely obese subjects.

Methods: Sixty-one subjects with severe obesity (BMI ≥35 kg/m2 with comorbidities) completed this study. All subjects completed respiratory questionnaires, spirometry, lung volume measurements, methacholine inhalation test, 24hour Holter monitoring and a complete echocardiography evaluation. Blood samples were obtained for measurement of metabolic markers. Subjects with AHR, defined by a provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) < 8 mg/ml, were compared with those with no AHR (PC20 ≥8 mg/ml).

Results: According to these criteria, 32 subjects had AHR and 29 had no AHR(mean PC201.70 mg/ml and 15.3 mg/ml respectively, p < 0.001). The groups were similar for anthropometric data and comorbidities. Fasting glucose, Hb1Ac, total cholesterol, LDL, triglycerides, Apo-B, C-reactive protein (CRP) and pro-BNP levels were also comparable between groups (p > 0.05). CRP level correlated with PC20 (AHR, r=0.38, p=0.03). Indices of heart rate variability and overall cardiac function were similar in subjects with or without AHR but grade 2 left ventricular diastolic dysfunction was more prevalent in subjects with AHR (p=0.037).

Conclusions: Altered cardiac function, dysglycemia and dyslipidemia do not seem to be significantly associated with AHR in severely obese subjects in contrast to systemic inflammation.
Obstructive sleep apnea is prevalent in patients with pulmonary embolism
Authors: Kosovalı Deniz , Uyar Meral , Elbek Osman , Bayram Nazan , Özsaraç İlker , Yarar Esra , Filiz Ayten
Published: May 2017

Purpose: Obstructive sleep apnea (OSA) syndrome causes systemic consequences due to hypoxia and endothelial dysfunction. The purpose of this study was to investigate whether OSA is more common in subjects with pulmonary embolism (PE).

Methods: This prospective study was conducted between November 2009 and December 2010 in the Department of Pulmonary Medicine of Gaziantep University. Twenty-eight patients with PE were included in the study group along with forty-five subjects with OSA as the control group. The control group was selected from among subjects who were referred to the sleep clinic. Full night polysomnography was performed for each subject.

Results: Mean apnea-hypopnea index (AHI) was found to be higher in the PE group compared with the control group (p=0.010). Severe OSA was detected in 21.4% of the PE group but in no controls (p=0.015). Sleep stage 2 was longer in control group whereas stage 1 and rapid eye movement (REM) sleep was longer in the PE group. Snoring and excessive daytime sleepiness were more common in the control group compared with the study group. AHI severity and thrombus localization were not significantly different between the groups (p=0.350).

Conclusion: Our study findings suggest that OSA is more prevalent and severe in subjects with PE compared with control subjects. The clinical significance of less prevalent excessive daytime sleepiness and snoring in subjects with PE should be evaluated in further studies.
Warning Letters to Sponsor-Investigators at Academic Health Centres – The Regulatory “Canaries in a Coal Mine”
Authors: O’Reilly Erin K , Holbein ME Blair , Berglund Jelena P , Parrish Amanda B , Roth Mary-Tara , Burnett Bruce K
Published: May 2017

Purpose: This study highlights Warning Letter (WL) findings issued to sponsor-investigators (S-Is) by the Food and Drug Administration (FDA).

Methods: The online index of WLs issued from October 1, 2007 through September 30, 2012 was reviewed [1]. Through a manual screening process, letters were evaluated if specifically issued to ‘clinical investigators’, ‘sponsors’ or ‘sponsor-investigators’. A particular focus was given to S-Is at Academic Health Centres (AHCs). Each letter was scored for the presence of violations in 40 general regulatory categories.

Results: A review of FDA WLs issued over a five-year period (FDA Fiscal Years 2008-2012) revealed that WLs to S-Is represent half of the WLs issued to all sponsors (16 of 32 letters). A review of these letters indicates that S-Is are not aware of, or simply do not meet, their regulatory responsibilities as either investigators or sponsors. In comparing total sponsor letters to those of S-Is, the most cited violation was the same: a lack of monitoring. A review of publicly available inspection data indicates that these 16 letters merely represent the tip of the iceberg.

Conclusion: This review of the WL database reveals the potential for serious regulatory violations among S-Is at AHCs. Recent translational funding initiatives may serve to increase the number of S-Is, especially among Academic Health Centres (AHCs) [2]; thus, AHCs must become aware of this S-I role and work to support investigators who assume both roles in the course of their research.
Association of serum YKL-40 levels with the presence and severity of coronary artery disease in patients with obstructive sleep apnea syndrome
Authors: Sui Xizhong , Gao Changqing
Published: May 2017

Purpose: Current evidence supports a robust association between obstructive sleep apnea syndrome (OSAS) and the risk of coronary artery disease (CAD). YKL-40, a 40 kDa heparin- and chitin-binding glycoprotein, is found to be associated with the presence of CAD. This study aims to examine the association of serum levels of YKL-40 with the presence and severity of CAD in patients with OSAS.

Methods: A total of 246 patients with OSAS who underwent coronary angiography for the evaluation of CAD (134 patients with CAD and 112 patients without CAD) were enrolled in this study. The severity of CAD was assessed using the coronary atherosclerosis index (CAI). Serum levels of YKL-40 were determined using enzyme-linked immunosorbent assay.

Results: Serum YKL-40 levels were significantly higher in OSAS patients with CAD compared with those without CAD. Multivariable logistic regression analysis revealed that serum YKL-40 levels were an independent determinant of the presence of CAD in patients with OSAS. In addition, Spearman correlation analysis showed that serum YKL-40 levels were positively correlated with CAI in OSAS patients with CAD. Patients with statin treatment showed significantly lower levels of serum YKL-40 compared with those without.

Conclusions: Elevated levels of serum YKL-40 are associated with the presence and severity of CAD in patients with OSAS.
Human hair cortisol analysis: Comparison of the internationally-reported ELISA methods
Authors: Albar Wed F , Russell Evan W , Koren Gideon , Rieder Michael J , Van Umm Stan H
Published: May 2017

Purpose: Recently, hair cortisol has become a topic of global interest as a biomarker of chronic stress. Different research groups have been using different methods for extraction and analysis, making it difficult to compare results across studies. A critical examination of the reported analytical methods is important to facilitate standardization and allow for a uniform interpretation.

Methods: This study qualitatively compared four published procedures from laboratories in Germany, the Netherlands, USA and Canada. Multiple aspects of their procedures were compared.

Results: A major difference among the laboratories was the ELISA kit used: the Canadian laboratory used the kit from ALPCO Diagnostics (Salem, MA, USA), the American laboratory used the kit from DRG International (Springfield, NJ, USA), the German laboratory used the kit from DRG Instruments GmbH (Marburg, Germany), or IBL (Hamburg, Germany), and the Dutch used the kit from Salimetrics (Suffolk, UK). In addition, there are noted differences in hair mass used as well as washing and extraction procedures. The range of hair cortisol levels determined in healthy volunteers by the four groups was within 2.3-fold: Koren, 46.1 pg/mg; Van Rossum, 29.72 pg/mg; Kirschbaum, 20 pg/mg and Laudenslager ~ 27 pg/mg.

Conclusions: The relative similarities in hair cortisol values in volunteers among the four laboratories should facilitate a quality assurance exchange program, as a necessary step toward clinical use of this novel test.
Tetramethylpyrazine improves oxazolone-induced colitis by inhibiting the NF-κB pathway
Authors: Lu Yunmin , Zhu Meiying , Chen Wei , Yin Li , Zhu Jinshui , Chen Niwei , Chen Weixiong
Published: May 2017

Purpose: Tetramethylpyrazine (TMP) is an effective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. The purpose of this study was to investigate the mechanisms involved in its therapeutic action.

Methods: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day after enema, mice were sacrificed. The inflammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells.

Results: Our results showed that TMP improved the colonic inflammatory status as evidenced by histological findings, as well as SASP. These effects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inflammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells.

Conclusion: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of pro-inflammatory factor production and oxidative stress.