bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-strain variations of baroreflex sensitivity in young Wistar-Kyoto rats
Authors: Valenti Vitor E , Imaizumi Caio , De Abreu Luiz Carlos , Colombari Eduardo , Sato Monica A , Ferreira Celso
Published: May 2017

Purpose: To compare baroreflex sensitivity among conscious rats of the same strain.

Methods: Male WKY rats (eight weeks old) were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP) and heart rate (HR). Baroreflex gain was calculated as the ratio between variation of HR in function of the MAP variation (?HR/?MAP) tested with a depressor dose of sodium nitroprusside (SNP, 50µg/kg, iv) and with a pressor dose of phenylephrine (PE, 8µg/kg, iv). We divided the rats into four groups: 1) Low bradycardic baroreflex (LB), BG between -1 and -2 bpm/mmHg tested with PE; 2) High bradycardic baroreflex (HB), BG < -2 bpm/mmHg tested with PE; 3) Low tachycardic baroreflex (LT), BG between -1 and -2 bpm/mmHg tested with SNP and; 4) High tachycardic baroreflex (HT), BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05.

Results: Approximately 82% of the rats presented reduced bradycardic reflex while 22 showed attenuated tachycardic reflex. No alterations were noted regarding basal MAP and HR, tachycardic and bradycardic peak and HR range.

Conclusions: There was alteration in baroreflex sensitivity among rats of the same strain. Care should be taken when interpreting studies employing WKY as a control for the SHR.
DD3PCA3 gene expression in cancer and prostatic hyperplasia
Authors: Floriano-Sánchez E , Cárdenas-Rodríguez N , Castro-Marín M , Álvarez -Grave P , Lara-Padilla E
Published: May 2017

Purpose: DD3PCA3 is a novel gene with characteristics that indicate its potentially valuable role in early identification and diagnosis of malignancy and highly upregulated in transformed cells in PCa. The aim of this work was to validate and analyze, by real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR), the expression of the DD3PCA3 gene in a mexican population, both in intratumoral tissue with PCa and benign prostatic hyperplasia (BPH).

Methods: Human samples from patients with PCa (40 cases) and benign prostatic hyperplasia (40 cases) were analyzed for the mRNA expression of DD3PCA3 by RT-PCR

Results: The GAPDH gene showed better stability with a Pearson correlation of 0.953 (P < 0.007) for the determination of housekeeping gene. DD3PCA gene expression was 29.74 times higher in PCa tissue (P < 0.0001) than in BPH. The gene expression for the PCa and BPH was 1731±280 and 58.23±9.9 fold, respectively.

Conclusions: Determination of DD3PCA3 gene expression by RT-PCR could be a potentially tool for the early detection of PCa in clinical specimens.
A Canadian multi-centre, open-label long-term study of Pegvisomant treatment in refractory acromegaly
Authors: Ezzat Shereen , Gaspo Rania , Serri Omar , Ur Ehud , Chik Constance L
Published: May 2017

Purpose: Acromegaly is a rarely diagnosed condition with potentially serious complications including accelerated heart disease and reduced survival. After a mean interval of nearly 9 years from onset of disease, a significant proportion of patients are diagnosed with invasive adenomas precluding complete surgical resection. Furthermore, strict normalization of the growth hormone (GH) target insulin-like growth factor I (IGF-I) cannot always be achieved by adjunctive medical therapy with somatostatin analogues. Here we report the results of a Canadian multi-centre study open-label, dose-titrated long-term study examining safety and efficacy outcomes of a growth hormone receptor antagonist, pegvisomant in 19 patients with refractory acromegaly.

Methods: Previously pegvisomant-treated and treatment-naïve refractory acromegalic patients at least 18 yr of age were eligible (n=19). Patients received open-label daily subcutaneous injections of pegvisomant adjusted according to IGF-I levels. Safety and IGF-I levels were assessed every 4 to 6 wk. Baseline and follow-up visits at 3-month intervals also included administration of the Signs and Symptoms of Acromegaly Questionnaire. This study is registered with ClinicalTrials.gov, NCT00151437.

Results: We show that, in escalating doses, pegvisomant results in age-adjusted normalization of IGF-I in nearly all such patients. This IGF-I normalization occurred early on and was maintained throughout the study period of 27 months (IGF-I standard deviation score (SDS), mean ± SE: 1.66 ± 0.36, P=0.0003 vs baseline), with a nadir at 18 months (IGF-I SDS, mean ± SE: 1.50 ± 0.38, P=0.0010 vs baseline). IGF-I control was also accompanied by measurable improvements in disease-associated symptoms and without radiographic evidence of pituitary tumour progression. Overall, the safety profile of pegvisomant therapy in this patient population was found to be satisfactory and suitable for a long-term treatment.

Conclusion: Our findings provide support for the long-term safety and efficacy of the GH receptor antagonist pegvisomant in achieving IGF-I control in patients with refractory acromegaly.
Beta-Tubulin III mRNA expression and docetaxel sensitivity in non-small cell lung cancer
Authors: Wang Li-feng , Yin Hai-tao , Qian Xiao-ping , Wei Jia , Zhao Yang , Yu Li-xia , Liu Bao-rui
Published: May 2017

Purpose: Despite the success of docetaxel as an anti-tumour agent, the inter-individual variability in drug response still poses a major impediment to further use of this agent in the treatment of cancer. Current knowledge about predictive biomarkers of docetaxel sensitivity in malignant effusions is poor. The aim of this study was to investigate the association between ?-tubulin III mRNA expression and chemosensitivity to docetaxel in metastatic malignant effusions.

Methods: Real-time quantitative PCR was used for analysis of ?-tubulin III mRNA expression in 37 malignant effusions collected prospectively. Viable tumour cells obtained from malignant effusions were tested for sensitivity to docetaxel using ATP-TCA assay.

Results: ?-tubulin III expression was inversely correlated with sensitivity to docetaxel in pleural effusions of NSCLC patients (P =0.022). The lower level of ?-tubulin III mRNA expression in malignant effusions was associated with higher chemosensitivity to docetaxel in NSCLC patients in vitro. No correlation was found between ?-tubulin III mRNA expression and docetaxel sensitivity in malignant effusions of gastric cancer patient.

Conclusion: Our results demonstrated that ?-tubulin III mRNA expression level in malignant effusions, in which all cancer cells were metastatic, was correlated with docetaxel sensitivity in NSCLC. This highlights the potential role of biomarkers in malignant effusions in further customized chemotherapy.
Hypertension and hemostatic/fibrinolytic balance disorders
Authors: Tabak O , Gelisgen R , Uzun H , Kalender B , Balci H , Curgunlu A , Simsek G , Karter Y
Published: May 2017

Background: Hypertension is one of the principal risk factors for cardiovascular disease. We aimed to evaluate the impact of hypertension on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), tPA/PAI-1 complex and fibrinogen.

Methods: Patients enrolled into the study were divided into four groups: 22 essential hypertensive (EH), 22 white coat hypertensive (WCH), 22 renovascular hypertensive (RH) and 22 normotensive control subjects. Plasma PAI-1, tPA, tPA/PAI-1 complex levels were measured by enzyme linked immunosorbent assays.

Results: There was no difference in the systolic and diastolic blood pressure measurements of the EH and RH groups. The four groups were comparable for age, gender, smoking habits and BMI. Patients with EH, RH and WCH had increased plasma levels of PAI-1, tPA, tPA/PAI-1 complex and fibrinogen compared with controls. No fibrinolytic parameter was associated with blood pressure in hypretensive subjects.

Conclusion: This prospective study showed that fibrinolytic markers such as PAI-1, tPA, tPA/PAI-1 complex are independently associated with the development of hypertension. This supports the hypothesis that disturbances in fibrinolysis precede a cardiovascular event. Therefore, hypertension may be associated with impaired fibrinolysis.
Physiologic hyperleptinemia in obesity does not affect vasopressin secretion in acute hypo- or hyperosmolality
Authors: Coenraad Minneke J , Frölich Marijke , Meinders A E
Published: May 2017

Purpose. Abnormal water excretion after ingestion of a water load has been described in obesity. We hypothesized that AVP secretion is abnormal in obese subjects in acute hypo- and hyperosmolality and that the hormone leptin is partly responsible for this.

Methods. We studied the relation between leptin, AVP and serum osmolality in two separate tests: (1) after ingestion of a water load (20 ml/kg lean body mass plus 5 ml /kg of adipose tissue) and (2) after iv hypertonic saline (5% NaCl) at a rate of 0.1 ml/kg lean body mass/minute for 120 min in ten subjects of normal weight (BMI > 20 and < 25 kg/m2; controls) and ten obese females (BMI > 30 kg/m2). Obese subjects were tested before (98.6 ± 9.3 kg) and after weight loss (90.2 ± 8.5 kg).

Results. In the water load experiment, obese subjects excreted a smaller percentage of the water load than controls. Weight loss restored the ability to excrete the water load in the obese. In the water load and hypertonic saline infusion experiment, plasma AVP concentrations and the area under the curve (AUC) for AVP concentration were not different in obese from normal weight women. Baseline leptin concentration was not correlated with baseline AVP or the change in AVP during the experiment in any of the groups. Weight loss did not change AVP responses in obese subjects.

Conclusion. AVP secretion in response to acute hypo- and hyperosmolality is not different in normal weight and obese subjects. There is no correlation between leptin and AVP in normal weight or obese subjects.
The effect of MTHFR c.677C>T on plasma homocysteine levels depends on health, age and smoking
Authors: Semmler Alexander , Moskau Susanna , Stoffel-Wagner Birgit , Weller Michael , Linnebank Michael
Published: May 2017

Purpose: The role of homocysteine in the pathogenesis of arteriosclerosis and stroke is under debate. It is important to determine the interplay of factors that influence homocysteine plasma levels, such as age, gender, smoking and the genetic background. The T-allele of the common variant methylenetetrahydrofolate reductase (MTHFR) c.677C > T is the most prevalent known genetic cause of elevated plasma homocysteine levels, but the association of this allele with vascular disease has been controversial. The aim of the present study was to examine whether the influence of MTHFR c.677C > T on homocysteine levels depends on individual factors.

Methods: From an ongoing study on atherosclerosis, we analyzed 523 Caucasian individuals, including patients with cerebrovascular disease (n=141), their healthy spouses (n=106) and the offspring (n=276). ANOVA and regression analyses were employed to separately analyze the effect of MTHFR c.677C > T on homocysteine levels in patients, spouses and offspring as well as in subgroups defined by age, gender and smoking.

Results: MTHFR c.677C > T was associated with homocysteine plasma levels in the study sample (P < 0.001), but not in the patients with cerebrovascular disease, if analyzed separately. Analyses of subgroups divided by the age of 55 years revealed that the MTHFR c.677 C > T genotype was associated with homocysteine plasma levels in the younger (P < 0.001), but not in the older individuals. In addition, if individuals with at least less than ten cigarette package years were analyzed separately, MTHFR c.677C > T was associated with plasma homocysteine levels only in the group with the lower cigarette consumption (P=0.002).

Conclusion: In our study, the association of the MTHFR c.677C > T genotype with plasma homocysteine levels was weakened by other factors that impact homocysteine levels. The effect of MTHFR c.677C > T on plasma homocysteine levels may, thus, be of major importance for healthy, young, non-smoking persons. Such specifications may explain the controversial results of epidemiological studies on the relevance of MTHFR c.677C > T.
EVALUATION OF THE UNITED KINGDOM NATIONAL EXTERNAL QUALITY ASSESSMENT SERVICE 2008 (UK NEQAS 2008) GUIDELINES FOR THE DIAGNOSIS OF SUBARACHNOID HEMORRHAGE USING SPECTROPHOTOMETRIC XANTHOCHROMIA: A RETROSPECTIVE STUDY
Authors: Gangloff A , Nadeau L
Published: May 2017

Objective: Evaluation of the UK NEQAS 2008 guidelines for the interpretation of spectrophotometric xanthochromia.

Method: A search of the laboratory database for all the xanthochromia test results between May 1st 2008 and May 1st 2009 was performed. Medical charts were reviewed for patients of Hôpital de l’Enfant-Jésus (HEJ) that had at least one detectable pigment (bilirubin, oxyhemoglobin, or methemoglobin). Xanthochromia results obtained with 4 different criteria (Chalmers original, Modified Chalmers, Duiser and UK NEQAS 2008) were compared.

Results: We reviewed 41 medical charts (2 patients with duplicate lumbar punctures (LP) for a total of 43 LP). For these 41 patients there were 11 positive xanthochromia results, 5 of which were in concordance with a final diagnosis of subarachnoid hemorrhage (SAH). The diagnosis of the 6 other positive xanthochromia results were as follow: meningeal spread of a lymphoma, cerebral amyloid angiopathy, exertional headache, viral encephalitis with a possibility of petechiaes on the cerebral CT and second LP. Interpretation (negative/positive) of 40/43 LP was identical for the 4 methods. 2 LP were positive with Duiser and UK NEQAS 2008 but negative with Chalmers approaches (final diagnosis: SAH and cerebral amyloid angiopathy). 1 LP was positive only by the Duiser method (viral encephalitis).

Conclusions: UK NEQAS 2008 guidelines identified all SAH but are sensitive to traumatic and pathologic meningeal lesions. Except for a case of viral encephalitis with a suspicion of cerebral petechiaes on CT, UK NEQAS 2008 gave xanthochromia results similar to the one in use at HEJ (Duiser). Chalmers original and Modified Chalmers methods missed one of the five SAH.
RE-EVALUATION OF THE CORRECTION FACTOR FOR ETHANOL IN THE CALCULATION OF THE OSMOLAL GAP
Authors: Fung V , Pudek M , Rosenberg F , Holmes D
Published: May 2017

Background/objectives: It is well-known that ethanol (EtOH) demonstrates non-ideal solute behaviour in plasma. This is reflected by its larger than expected contribution to the plasma osmolality. Published multiplicative correction factors for the EtOH contribution range from 1.20 to 1.25. The objective of this study is to determine an optimal correction factor specific to the instrumentation at Vancouver General (VGH) and St. Paul's (SPH) Hospitals.

Methods: Laboratory data from patients presenting to the two respective emergency department between August 01, 2007 and November 30, 2008 were extracted from the Sunset database. Plasma sodium, urea, glucose, and EtOH were measured using the two high-volume chemistry analyzers employed at the sites: the Siemens (previously Dade) RXL (VGH) and the Siemens (previously Bayer) Advia 1650 (SPH). Plasma osmolality was measured by freezing-point depression and calculated (excluding the EtOH contribution) using the following standard formula (in SI units): 2 [Na] + [Urea] + [Glucose].

Patients without EtOH data or who had undetectable EtOH were excluded as were patients with methanol or ethylene glycol present. Standard regression statistics were employed.

Results: Twelve hundred and fifty-three patient samples (n=823 from SPH and n=430 from VGH) were included. Empirical correction factor m, satisfying, Osmol gap (mmol/kg) =m[EtOH] (mmol/L) was consistently found to be 1.15 for VGH, SPH and both combined.

Conclusions: The correction factor of 1.15 for ethanol from the current study appears to be more representative and reliable. Further studies to evaluate its validity in other hospital sites as well as its utility in screening patients with known toxic alcohol ingestion will be warranted.
METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) MULTIPLEX – PCR METHOD
Authors: Kary H , Gilfix B M
Published: May 2017

Introduction: Gene polymorphisms in human methylenetetrahydrofolate reductase (MTHFR) have been linked to the disorders of folate metabolism, and may contribute to such disease as neural tube defect, coronary heart disease, venous thrombosis, and several types of cancers.

Methodology: We have modified our current real-time PCR method (Clin Biochem 2000;33:535-539.) for the detection of the MTHFR c.677C > T variant to a real-time multiplex-PCR method for detection of MTHFR c.1298A > C and c.677C > T variants on a LightCycler 1.2. Our multiplex method is partly based on that of Agarwal et al.(J Mol Diag 2007;9:345).

Results: The genotyping results of c.677C > T variant analyzed by both methods were in agreement. All samples analyzed for the c.1298A > C variant by the Multiplex-PCR method gave clear-cut results. The LightCycler multiplex method was validated with 14 specimens previously genotyped by restriction fragment length polymorphism at Montreal Children’s Hospital. All results were in agreement except for one sample that failed to amplify. There was no significant difference in Tm between the Multiplex-PCR procedure and the previously reported Tm’s for both variants. When run alone but not as a multiplex, the progress curve of the c.1298A > C variant exhibited the “hook effect”. Asymmetric amplification was found to reduce this effect.

Conclusions: The multiplex assay is reliable, economical, fast and simple method to perform as compared with RFLP technique. Asymmetric PCR is a helpful tool to minimize the hook effect.
Mutations of the TGFBR2 gene in Chinese patients with Marfan-related syndrome
Authors: Chen JinLan , Li BuYun , Yang YiFeng , Hu JianGuo , Zhao TianLi , Gong YiBo , Tan ZhiPing
Published: May 2017

Purpose: Transforming growth factor beta receptors II gene (TGFBR2) mutations associated with Marfan syndrome and Marfan-associated disorders have been investigated. However, such studies are limited in China. To obtain more information about TGFBR2 mutations, we analyzed 6 unrelated Chinese patients with Marfan-associated disorders and without ocular manifestation.

Methods: The genomic DNA from blood leukocytes of these 6 patients and their relatives was isolated, and the entire coding region of TGFBR2 was amplified using PCR. We determined the sequence of TGFBR2 with the ABI 3100 Genetic Analyzer.

Results: Three mutations were identified in TGFBR2. Two mutations were associated with Loeys-Dietz syndrome (LDS), which were distributed as following: one missense mutation R528C (caused by a 1582C > T substitution) and one polymorphism T315M (a rare SNP). The third mutation was a novel silent mutation associated with MFS2, which was K291K caused by an 873 C > T substitution.

Conclusions: The TGFBR2 gene missense mutations are possibly causative mutations of Loeys-Dietz syndrome. This result suggests an increase in the mutation spectrum of Marfan-related disorders in China and possibly world-wide.
Localization of cyclo-oxygenase-2 in human recurrent colorectal cancer
Authors: Loukanov Ts , Kirilov M , Fürstenberger G , Müller-Decker K
Published: May 2017

Aim: The aim of this paper is to examine COX-2 expression in human recurrent colorectal carcinoma tissues using immunohistochemistry and quantative real-time PCR (qPCR).

Methods: Colon and rectal specimens were obtained from 26 patients with recurrent colorectal carcinomas. We examined COX-2 expression in human recurrent colorectal carcinoma tissues using immunohistochemistry and quantative real-time PCR (qPCR).

Results: In recurrent colorectal cancer a strong cytoplasmic and perinuclear staining of COX-2 was found. Moderate to strong immunosignals were detected in almost all of the carcinomas. We observed a strong specific staining of COX-2 in vascular endothelium. COX-2 immunoreactivity was also detected in stromal cells such as mononuclear cells, fibroblasts, and smooth muscle cells. The real-time PCR analyses demonstrated marked overexpression of the COX-2 gene in the cancer mucosa in concert with the immunohistochemistry data.

Conclusion: We investigated COX-2 expression at the level of its protein as well as its messenger RNA in a series of recurrent colorectal cancers. These observations give additional information about the possibility that COX-2 could be involved in tumor promotion during colorectal cancer progression.
State-Trait Anxiety Inventory (STAI) assessment of mothers with language delayed children
Authors: Çirpar Özden Çiftçi , Muluk Nuray Bayar , Yalçinkaya Fulya , Arikan Osman Kürşat , Oğuztürk Ömer , Aslan Filiz
Published: May 2017

Objectives: In this study, we evaluated the continuous and state anxiety levels of mothers with children with language delay.

Methods: The study group consisted of the mothers of 18 children with language delay. The control group consisted of the mothers of 29 healthy children without language delay. To gain data about mothers, a personal information form and Spielberger’s State-Trait Anxiety Inventory (STAI) form were applied to determine continuous and state-trait anxiety levels.

Results: State anxiety levels in the study group were significantly higher (by Student t-test) than that of the control group. For continuous anxiety level, no statistically significant difference was determined between two groups. In the study group, higher education levels of mothers and their husbands were associated with lower levels of both continuous and state anxiety.

Conclusion: In the majority of the group of mothers with language delayed children and even mothers of children with normal language development, there were high levels concern. Mothers’ concerns and anxiety levels may decrease with increasing levels of their education levels. We recommend providing detailed information regarding language development to the families at all stages of the childs’ training programme.
Association of an asporin repeat polymorphism with ankylosing spondylitis in Han Chinese Population: A case-control study
Authors: Liu Dongxia , Yang Qingrui , Li Ming , Mu Kun , Zhang Yuanchao
Published: May 2017

Objective: To investigate the role of a functional polymorphism consisting of an aspartic acid (D) repeat located in the asporin gene (ASPN) gene in the susceptibility to and clinical outcome of ankylosing spondylitis (AS).

Methods: A total of 374 Chinese patients with ankylosing spondylitis and 421 controls of the same ethnic origin matched for age and sex were included in the study. The asporin D repeat polymorphism was genotyped by polymerase chain reaction with a fluorescent primer.

Results: Significant differences between AS patients and controls were detected in the distribution of the 7 alleles found in our population. D14 and D16 alleles were significantly over-represented in AS patients (D14, P=0.001, odds ratio (OR)=1.857, 95% confidence interval(CI) 1.27-2.715; and D16, P < 0.0001, OR=2.605, 95% CI 1.75-3.879). D16 over-representation was more common in early-onset patients than in late-onset patients, although the difference did not reach significance (P= 0.071).

Conclusion: The results support a role for an asporin D repeat polymorphism in the susceptibility to AS and an influence of this gene on the outcome of the disease. D14 and D16 allele variants of ASPN might be the susceptibility alleles for AS in the Han Chinese population, whereas the D13 allele variant may have a protective effect on the onset of AS.
Effect of US State Certificate of Need regulation of operating rooms on surgical resident training
Authors: Fric-Shamji Elana C , Shamji Mohammed F
Published: May 2017

Purpose: Government regulation of health care services helps prevent costs associated with expansion and duplication of services in the United States. Certificate of Need (CON) helps restrict construction of ambulatory surgery facilities and hence controls delivery of surgical intervention, but concern exists about whether this affects resident exposure to an appropriate caseload. This study investigated how CON laws impact on surgical caseload as an index of resident surgical training.

Methods: This retrospective study used State Inpatient Data compiled by the Health Care Utilization Project. Mean per capita rates of 26 diverse surgical procedures were evaluated in 21 states with CON laws and 5 states without between 2004 and 2006. The proportion of procedures performed in teaching facilities was also assessed. Student’s t-tests were used to evaluate differences in these parameters between regulated and non-regulated states (a = 0.05). Multivariate analysis of variance permitted evaluation of the types of procedures that underwent shift in location performed.

Results: States with CON laws did not differ significantly in procedural rates for any of the investigated surgical procedures; however, such regulation was associated with different trends in teaching center caseload, depending on the type of procedure. Complex procedures, such as Whipple operations (p = 0.14) or resection of acoustic neuroma (p = 0.37), underwent no redistribution. Conversely, common procedures that might have previously been performed in private settings, such as total hip replacement (p = 0.003) or mastectomy (p = 0.01), did occur more commonly in teaching facilities under CON regulation. CON law did not result in relocation of surgical procedures away from teaching institutions.

Conclusions: These results suggest that government regulations do not discriminate against teaching facilities. Surgical residents in states with such regulation gain similar or superior exposure to procedures as residents in states without such laws.
Getting the message across: Pathophysiology and signaling via receptors for polypeptide hormones and proteinases
Authors: Hollenberg Morley D
Published: May 2017

This article provides a personalized overview of the role of proteinases in generating hormone-like cell signals. Also outlined is the unexpected route of discovery that led one investigator over a four-decade time span, from early studies of the interactions of oxytocin and vasopressin with their neurophysin binding proteins to current studies of the tethered ligand activation mechanism that is unique for the G-protein-coupled family of proteinase-activated receptors (PARs). The focus is not only on the intriguing PAR receptor family, but also on alternative mechanisms whereby proteinases activate signal transduction pathways. Also summarized are the potential physiological and pathophysiological roles that PARs may play in the setting of inflammatory disorders ranging from arthritis to colitis. The therapeutic implications of considering PARs as drug targets are also discussed.
Are serum levels of trace elements in children with auditory neuropathy within normal limits? – A pilot study
Authors: Muluk Nuray Bayar , Yalçınkaya Fulya , Arikan Osman Kürşat , Çırpar Özden , Kaygusuz Sedat , Ercan Varol
Published: May 2017

Objectives: To determine whether trace elements that are essential for neural function play a role in the pathophsiology and etiology of auditory neuropathy (AN)..

Materials and methods: Patients diagnosed with auditory neuropathy consisted of eight children (two male, six female). The blood tests including the measurement of sodium, potassium, chloride, calcium, phosphorus, iron, copper and magnesium were done in children with AN during their routine care.

Results: Of the eight children with AN, many had serum levels outside the normal range: one had low sodium, two had low potassium, one had low chloride, two had high zinc and three had low zinc, two had low calcium and two had higher than normal phosphorus.

Conclusion: Although some serum trace element levels in our patients were higher or lower than normal values, the mean values were within normal limits. Thus, we were unable to detect a relationship between serum trace element levels and AN-. In the future, larger studies should be conducted to confirm these findings.
Alberta’s new health research paradigms: Are graduate students being prepared for interdisciplinary team research?
Authors: Duthie Katherine , Riddell Meghan , Weller Carol , Coltan Lavinia I , Benzies Karen , Olson David M
Published: May 2017

Strategic prioritization of research agendas to address health problems with a large social and economic burden has increased the demand for interdisciplinary research. Universities have addressed the need for interdisciplinary research in their strategic documents. However, research training to equip graduates for careers in interdisciplinary research teams has not kept pace. We offer recommendations to graduate students, universities, health services organizations, and health research funders designed to increase the capacity for interdisciplinary research team training, and provide an example of an existing training program.
Clinical hallmarks and genetic polymorphisms in the CFTR gene contribute to the disclosure of the A1006E mutation
Authors: Tomaiuolo Anna Cristina , Alghisi Federico , Petrocchi Stefano , Surace Cecilia , Roberti Maria Cristina , Bella Sergio , Lucidi Vincenzina , Angioni Adriano
Published: May 2017

Since the identification of the Cystic Fibrosis transmembrane conductance regulator (CFTR) gene in 1989, many genetic mutations have been found in cystic fibrosis (CF) patients. Dysfunctions of the CFTR gene are responsible for the highly variable clinical presentation ranging from severe CF, disseminated bronchiectasis, idiopathic chronic pancreatitis and congenital bilateral absence of vas deferens (CBAVD). Linkage disequilibrium studies have shown that some mutations are stringently coupled with polymorphisms in a genetic complex called haplotype. From a familial study of a patient with CBAVD, carrier of the A1006E mutation, we have observed its strict association with the polymorphism 5T-TG11. In order to speed up the genetic diagnosis and to correlate the clinical setting to this genetic feature, we have directly investigated the exon 17a, where the A1006E mutation is located, of five cystic fibrosis patients belonging to two unrelated families. All patients had the 5T-TG11 tract, F508del and one unknown mutation. One more family with two affected individuals carrying the Q220X/A1006E mutations was investigated for the poly-T polymorphism. All the members were found to have the A1006E mutation and the 5T-TG11 in the same DNA strand, demonstrating that this strategy is a reliable and inexpensive method for genotyping the CFTR gene. A detailed description of the clinical presentation and follow-up are provided in order to highlight common phenotypic features useful to improve the management of cystic fibrosis patients.
CSCI/CITAC Young Investigators Forum Abstracts
Authors: CSCI _
Published: May 2017

CSCI/CITAC Young Investigators Forum Abstracts

Ottawa
20-23 September, 2010 / le 20-23 Septembre, 2010
C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population
Authors: Chen Ai-Rong , Zhang Hong-Gang , Wang Zhi-Ping , Fu Sheng-Jun , Yang Pei-Qi , Ren Jian-Gong , Ning Ying-Yuan , Hu Xue-Jian , Tian Ling-Hong
Published: May 2017

Purpose: Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are complex diseases affected by both dietary intake and genetic background. Whether N-5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, high-sensitivity C-reactive protein (hs-CRP) and dietary components folate and vitamin B12 are associated with MS in Asian has not been determined.

Methods: We hypothesized that MTHFR gene C677T, folate, vitamin B12 and hs-CRP are associated with MS and factors related to MS in northern Han Chinese. To test this hypothesis, MTHFR C677T gene polymorphism was determined by PCR-RFLP, serum insulin, folate and vitamin B12 levels by radioimmunoassay, and hs-CRP by immunoturbidimetry in newly diagnosed T2DM patients with MS (118) and without MS (40), and in 55 healthy subjects.

Results: Results indicated that MS-associated T2DM accounts for 75% of newly diagnosed T2DM in Han Chinese. Serum hs-CRP was higher and serum vitamin B12 was lower in subjects with TT genotype in comparison with those with CC or CT genotypes. Total T frequency was significantly higher in MS-associated T2DM patients (45.3%) compared to 26.3% in non-MS-associated T2DM patients. MTHFR C677T gene polymorphism and vitamin B12 levels were associated with MS-associated T2DM.

Conclusion: MTHFR C677T gene polymorphism may contribute to insulin resistance in Han Chinese with MS by increasing hs-CRP and decreasing vitamin B12, and consequently play an important role in development of MS-associated T2DM.
Diagnosis and treatment of juxta-ampullary duodenal diverticulum
Authors: Chen Qi , Li Zhaodong , Li Shengwei , Ding Xiong , Liu Zuojing , Wu Chuanxin , Gong Jianping , Zuo Guoqing
Published: May 2017

Objective: To summarize the diagnosis and treatment of juxta-ampullary duodenal diverticulum (JAD) in our hospital.

Methods: Of 5000 consecutive endoscopic retrograde cholangiopancreatography (ERCP) performed in our department, 225 patients were diagnosed with JAD and treated. All patients were classified based on the location of Ampullae of Vater in relation to the duodenal diverticulum. Of the 225 JAD patients, 96 patients (43%) required surgery.

Results: The 225 patients with JAD were divided into Type A (146 cases, 65%) or Type B (79 cases, 35%). Type A patients presented with papillae near the diverticulum or in its margin. In this type, 36 patients (25%) presented with diverticulitis, bleeding, perforation or cholelithiasis, and were treated surgically. Type B patients presented with papillae inside the diverticulum. Among them, 60 patients (76%) had complications requiring surgery.

Conclusions: JAD can be divided into two types based on location of the papillae. ERCP was the primary method of diagnosing JAD and patients with severe complications required surgical intervention.
Prior intense exercise reduces arterial carbon dioxide pressure in extreme obesity
Authors: Zavorsky Gerald S , Kim Do Jun , Cass Lauren M , Carli Franco
Published: May 2017

Purpose: Unlike normal weight individuals, individuals with extreme obesity do not show a decrease in arterial carbon dioxide pressure (PaCO2) from rest to peak exercise. This indicates that breathing is compromised. The objective of this study was to determine if prior high intensity exercise lowers PaCO2 in comparison with a first bout, normalized for the same metabolic rate.

Methods: Oxygen consumption during incremental, ramped exercise was matched to constant workload exercise (75% of peak power). Both protocols were to volitional exhaustion 39 ± 8 min apart. Eleven obese subjects (BMI = 47 ± 8 kg/m2, aerobic capacity = 2.3 ± 0.6 L/min) were evaluated. Forty paired samples were obtained at the same metabolic rate between the two protocols.

Results: The mean absolute difference and 95% CI were large for arterial oxygen pressure (PaO2) = 9 (6, 11) mmHg and alveolar to arterial oxygen pressure difference (AaDO2) = 7 (5, 8) mmHg. The mean absolute difference for arterial oxyhemoglobin saturation (%SaO2) = 0.5 (0.4, 0.7) %; PaCO2 = 4 (3, 4) mmHg; physiological dead space to tidal volume ratio (VD/VT) = 0.04 (0.03, 0.05); and alveolar ventilation (VA) = 3 (2, 4) L/min. The recovery period after the first bout of exercise reduced the PaCO2 by 3 mmHg when matched for similar metabolic rates. Constant workload exercise predicted VA, %SaO2, VD/VT, and PaCO2, but not PaO2 or AaDO2 during incremental exercise at similar metabolic rates.

Conclusion: Given a sufficient chemical stimulus, obese subjects will attempt to breathe more, although this does not mean more VA, which removes CO2.
Serum sLOX-1 levels are associated with the presence and severity of angiographic coronary artery disease in patients with metabolic syndrome
Authors: Li Bo , Zhang Li-hua , Yang Xin-guo , Liu Xiong-tao , Ren Yin-gang
Published: May 2017

Purpose: Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. Serum soluble lectin-like oxidized low-density lipoprotein receptor-1(sLOX-1) is associated with coronary artery disease (CAD) and metabolic disorders. We sought to assess whether serum sLOX-1 levels are correlated with the presence and severity of CAD in patients with metabolic syndrome (MetS) undergoing coronary angiography.

Methods: Serum sLOX-1 levels were measured in 112 consecutive patients with MetS, undergoing coronary angiography for the evaluation of CAD. The severity of CAD was assessed by angiographic Gensini score system.

Results: Serum sLOX-1 levels were significantly higher in MetS patients with CAD (n=69) than in those without CAD (n=43) (0.925 [range 0.137 to 1.432] ng/ml vs. 0.207 [range 0.063 to 0.774] ng/ml, P < 0.01). Multivariate logistic regression analysis revealed that serum sLOX-1 level was independently associated with the presence of CAD (odds ratio 2.489, 95% confidence interval 1.290-4.802; P < 0.01). Serum sLOX-1 levels were positively correlated with the Gensini score (ρ: 0.394, P < 0.01) after adjusting for other clinical characteristics.

Conclusions: High sLOX-1 levels are associated with the presence and severity of CAD in patients with MetS. The measurement of serum sLOX-1may be potentially useful in predicting the presence and severity of CAD in patients with MetS.
Variants in the fat mass and obesity associated (FTO) gene are associated with obesity and C-reactive protein levels in Chinese Han populations
Authors: Sun Yanlei , Sun Jiazhong , Wang Xiang , You Wei , Yang Mei
Published: May 2017

Purpose: Various genetic variants of the fat mass and obesity associated gene (FTO) have been linked to obesity in populations of Europeans. Low-grade inflammation is a key feature of obesity, characterized by elevated plasma levels of C-reactive protein (CRP). In the present study, we have investigated whether the FTO-risk variant is associated with obesity and CRP in the Chinese population.

Methods: 1799 individuals aged 50-70 years (896 men and 903 women), including both obese (560 cases) and control individuals, (1200 cases) were recruited. The FTO rs9939609 polymorphism was tested using sequences retrieval. Waist circumference, body fat, hs-CRP, blood total cholesterol, triglycerides and LDL-C were also measured.

Results: The FTO rs9939609 polymorphism per-A allele was associated with an increased odds ratio for obesity of 1.42 (95%CI 1.23-1.64). The genotypic odds ratio for obesity was 1.92 (95%CI 1.43-2.57) for the AA genotype, 1.71 (95%CI 1.35-2.16) for the AT genotype. The association between FTO rs9939609 polymorphism and CRP levels was r=0.78.

Conclusion: Our data support the hypothesis that FTO rs9939609 polymorphism is strongly associated with obesity and CRP levels in the Chinese population as reported in the European population.
Effects of montelukast on burn wound healing in a rat model
Authors: Turtay Muhammet G , Firat Cemal , Samdanci Emine , Oguzturk Hakan , Erbatur Serkan , Colak Cemil
Published: May 2017

Purpose: Montelukast, a selective cysteinyl leukotriene D4-receptor antagonist, is used in the treatment of asthma. In a rat model, our aim was to investigate the effects of montelukast, alone or in combination with topical antibiotics, on local burn wound healing.

Methods: Rats were randomly allocated to four groups after local burn development: Group 1; rats were left to secondary healing without treatment, Group 2; a dose of 10 mg/kg montelukast was given by gastric gavage once a day for 10 days, Group 3; rats were treated with topical pomade (bacitracin neomycin sulphate), and Group 4; rats were treat with a combination of topical antibiotic and montelukast (10 mg/kg were given by gastric gavage once a day for 10 days). Skin biopsies were taken on days 3, 10, 14, and 20 relative to burn induction.

Results: Reepithelialization in the pomade and montelukast+pomade groups on the 10th day was significantly greater, in comparison with control and montelukast groups (p < 0.05). For the montelukast group, edema (on the 14th day) and angiogenesis, fibroblast proliferation, edema and macrophage infiltration (on the 20th day) were statistically improved in comparison with the control group (p < 0.05). For the montelukast+pomade group, angiogenesis, fibroblast proliferation and macrophage infiltration (on the 10th day), and angiogenesis, fibroblast proliferation, edema and macrophage infiltration (on the 14th and 20th days) were statistically improved in comparison with the control group (p < 0.05).

Conclusion: In conclusion, montelukast was effective on burn wound healing. Moreover, the effect was amplified when combined with topical antibiotics applied in the early stage of burn wound healing.
Proportional changes of CD4+CD25+Foxp3+ Regulatory T cells in maternal peripheral blood during pregnancy and labor at term and preterm
Authors: Xiong Huijuan , Zhou Changju , Qi Guannan
Published: May 2017

Purpose: To evaluate the proportional changes of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in maternal peripheral blood during pregnancy and labor at term and preterm.

Methods: Peripheral blood was collected from 20 non-pregnant controls and 139 pregnant women (60 at different gestational ages, 48 at term with or without labor, and 31 in threatened or actual preterm labor). CD4+CD25+Foxp3+ Tregs in peripheral blood samples were analyzed in peripheral blood samples by flow cytometry. Placentas from preterm women were examined for the presence of histological chorioamnionitis (HC).

Results: The percentage of circulating CD4+CD25+Foxp3+ Tregs was significantly increased in women during the first trimester compared with non-pregnant controls (P < 0.0001), peaking during the second trimester and then declining slightly in the third trimester. There was a significantly lower level of CD4+CD25+Foxp3+ Tregs in women with term labor than in those at term without labor (P < 0.0001). Women admitted in preterm labor had a lower proportion of CD4+CD25+Foxp3+ cells than those admitted with threatening preterm labor (P < 0.0001). Preterm women with evidence of HC had decreased proportion of CD4+CD25+Foxp3+ cells than those without HC in preterm deliveries (P=0.008). Moreover, the percentages of CD4+CD25+Foxp3+ cells in preterm subjects, irrespective of the HC status, were significantly diminished compared with women with normal pregnancy at the same gestational age (P < 0.0001).

Conclusion: Our data reveal a marked elevation of peripheral blood CD4+CD25+Foxp3+ Tregs during early pregnancy, but a dramatic decline during labor, either at term or preterm, suggesting their involvement in the maintenance of pregnancy and the initiation of labor.
Continuous infusion of 5-FU with split-dose cisplatin: An effective treatment for advanced squamous-cell carcinoma of the head and neck
Authors: Luo Zhiguo , Chang Jianhua , Guo Ye , Yu Hui , Lu Fangfang , Wu Xianghua , Li Jin
Published: May 2017

Purpose: The purpose of this study was to determine if a combination chemotherapy, using continuous intravenous infusion of fluorouracil (5-FU) in combination with split-dose cisplatin, in patients with recurrent or metastatic head and neck squamous-cell could improve previously reported clinical outcomes.

Methods: Forty-two patients with recurrent or metastatic head and neck squamous-cell cancer were treated by cisplatin (25 mg/m2/day on days 1-3) and 5-FU (750 mg/m2/day for 120 hours; continuous intravenous infusion on days 1 through 5) with a cycle that repeated every 3 weeks.

Results: Of the 42 patients, 8 (19.1%) showed complete response and 12 (28.5%) demonstrated a partial response, giving an overall response rate of 47.6%. Response rates were significantly different for patients undergoing initial treatment vs. re-treatment:73.6% (14/19) vs. 25.9% (6/23), respectively (χ2=9.45, P < 0.05). Median time to progression was 7.2 months and median overall survival was 13.7 months. The 1 year survival was 57.1%. Toxicity mainly included myelo-suppression, mucositis, nausea and vomiting.

Conclusion: Chemotherapy with 5-FU by continuous intravenous infusion in combination with split-dose cisplatin is effective with a tolerable toxicity profile in patients with recurrent, or metastatic squamous-cell carcinoma of head and neck. The overall response was significantly higher in patients undergoing initial treatment in comparison with patients undergoing re-treatment after relapse.
The biomarker N-terminal pro-brain natriuretic peptide and liver diseases
Authors: Wang Ling , Geng Jiabao , Li Jie , Li Tong , Matsumori Akira , Chang Yibin , Lu Fengmin , Zhuang Hui
Published: May 2017

Purpose: NT-proBNP has emerged as a powerful diagnostic and prognostic biomarker in heart disease. Studies showed that NT-proBNP is a sensitive biomarker for identifying patients with heart failure caused by hepatitis C virus (HCV) related myocarditis. The purpose of this study was to evaluate the correlation between the serum concentration of NT-proBNP and hepatitis virus infection/liver disease.

Methods: 223 serum samples from blood donors (aged 19~50 years old) were collected as a control group, and 644 samples were obtained from patients infected by hepatitis viruses including 493 HBV: 364 chronic hepatitis (CH), 86 hepatocellular carcinoma (HCC) and 43 liver cirrhosis (LC) and 151 HCV (85 CH, 14 HCC, 52 LC). All samples were assayed with an Elecsys immunoassay analyzer for NT-proBNP concentration.

Results: The mean concentration of NT-proBNP in the control group was 21.77 pg/ml and showed no significant variation with either age or gender. Both the mean value and the rate of abnormality of NT-proBNP were significantly higher for the HBV- and HCV-infected groups in comparison with the control group. The mean NT-proBNP value (380.24 pg/ml) and abnormality rate (38.41%) in the HCV group were higher than that of the HBV group. For samples from patients with HBV/HCV-related hepatic disease/pathology, the mean NT-proBNP value (517.19 pg/ml/597.18 pg/ml) were the highest in the liver cirrhosis group.

Conclusions: Hepatic pathologic lesions, particularly cirrhosis, may contribute to the elevation of NT-proBNP in subjects with HBV/HCV infection.
Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer
Authors: Tang Dong , Liu Jun , Wang Dao-rong , Yu Hai-feng , Li Yong-kun , Zhang Jing-qiu
Published: May 2017

Purpose: The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC).

Methods: Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls.

Results: Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival.

Conclusion: Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.