Browsing by Author "Thulaseedharan, JV"

Now showing 1 - 6 of 6
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    Effect of Screening on Variation in Cervical Cancer Survival by Socioeconomic Determinants - a Study from Rural South India.
    (Asian Pac J Cancer Prev., 2015-09) Thulaseedharan, JV; Malila, N; Swaminathan, R; Esmy, PO; Cherian, M; Hakama, M; Muwonge, R; Sankaranarayanan, R
    Background: Socioeconomic factors are associated with screening in terms of reducing the risk of cervical cancer. This study aimed to clearly establish the effect of screening on variation in socio-economic factor-specific survival estimates. Materials and Methods: Survival estimates were calculated using the life table method for 165 women from the routine care control arm and 67 from the visual inspection with acetic acid screening arm diagnosed with cervical cancer during 2000-2006 in rural south India. Kaplan-Meier survival curves were plotted to compare the variation in survival by socioeconomic factors. Results: Whereas there was a significant variation in survival estimates of the different categories of age at diagnosis among the screen-detected cancers with women aged<50 years having an improved survival, no significant variation was noted among women diagnosed with cervical cancer from the control arm. Compared to the variation among the cancer cases detected in the unscreened control group, screening widened the variation in survival estimates by age and type of house, and reduced the variation by education. The direction of the magnitude of the survival estimates was reversed within the different categories of occupation, marital status and household income in the screen-detected cancer cases compared to control group cancer cases. Also, women diagnosed with stage 1 disease had a very good survival. Conclusions: Screening changed the pattern of survival by socio-economic factors. We found improved survival rates in screened women aged <50 years, with no formal education, manual workers and married women.
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    Enhanced P-selectin expression on platelet-a marker of platelet activation, in young patients with angiographically proven coronary artery disease
    (MOLECULAR AND CELLULAR BIOCHEMISTRY, 2016) George, R; Bhatt, A; Narayani, J; Thulaseedharan, JV; Sivadasanpillai, H; Tharakan, JA
    P-selectin (CD62p) exposure is an established marker for platelet activation. P-selectin exposure can trigger variety of thrombotic and inflammatory reactions. In patients with coronary artery disease (CAD), platelets are activated, and hence, there is increased P-selectin exposure. The role of P-selectin exposure in patients on treatment with statins and anti-platelets is conflicting. A case-control study was performed to determine P-selectin exposure in consecutively recruited 142 patients (age aecurrency sign 55 years) with angiographically proven CAD on treatment and 92 asymptomatic controls. P-selectin exposure was determined by flow cytometry. Data on conventional risk factors were obtained along with estimation of levels of thrombotic [fibrinogen, lipoprotein (a), tissue plasminogen activator, plasminogen activator inhibitor-1, homocysteine and von Willebrand factor] and anti-thrombotic factors (antithrombin III). The P-selectin exposure was compared among patient groups who had different modes of presentation of CAD and categories of CAD disease severity. The patients were followed up for a period of 26 months. The results indicate that P-selectin exposure was significantly elevated in patients (mean +/- SD 9.24 +/- 11.81) compared to controls (mean +/- SD 1.48 +/- 2.85) with p < 0.0001. Similarly, conventional risk factors were significantly elevated in patients. P-selectin exposure showed significant negative correlation with antithrombin III levels. P-selectin exposure was higher in patients who presented with acute coronary syndromes than those who presented with effort angina. Cardiovascular event rate was 6 % on follow-up. The study establishes that thrombotic-inflammatory pathways enhancing P-selectin exposure unrelated to treatment might be activated in patients, while the event rate remained lowered, and hence, treatment strategies should be inclusive to control these factors.
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    Forkhead box C2 Promoter Variant c.-512C > T Is Associated with Increased Susceptibility to Chronic Venous Diseases
    (PLOS ONE, 2014) Surendran, S; Girijamma, A; Nair, R; Ramegowda, KS; Nair, DH; Thulaseedharan, JV; Lakkappa, RB; Kamalapurkar, G; Kartha, CC
    Chronic venous disease (CVD) is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (Fox(2) gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 5' and 3' flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 5' flanking region and one in 3' flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 4 +/- 1.42 fold increased compared to saphenous veins from 20 normal subjects (p<0.01). FoxC2 protein was also significantly upregulated in varicose veins compared to control samples. The c.-512C>T (rs34221227: C>T) variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C>T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C>T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers 0114 and Hey2 and downregulation of venous marker COUP-TFIL Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in patients with varicose veins.
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    Risk of invasive cancer among women visually screened and colposcopy triaged by trained nurses in rural South India
    (Int J Gynaecol Obstet., 2015-09) Thulaseedharan, JV; Malila, N; Esmy, PO; Muwonge, R; Hakama, M; Sankaranarayanan, R
    Objective: To estimate the long-term risk of cervical cancer among women screened by visual inspection with acetic acid (VIA) and to evaluate the benefit of additional colposcopy triage in rural south India. Methods: A retrospective analysis was conducted among 31 343 women who had undergone VIA at Dindigul district, India between January 1, 2000, and August 5, 2003, as part of a randomized screening trial. Women with positive VIA test results were offered colposcopy triage by trained nurses. Cervical cancer incidence data during follow-up (January 1, 2000, to December 31, 2012) were obtained from a regional cancer registry. Results: Among 3021 screen-positive women free of cancer at baseline, 2974 women underwent colposcopy; colposcopic abnormalities suggestive of precancerous lesions were detected among 2792 of these women (93.9%). Compared with the women with negative VIA screening results, the hazard ratio (HR) of cervical cancer during follow-up among the VIA-positive women without colposcopic abnormalities was 6.5 (95% confidence interval [CI], 1.6–27.1). The risk was similar among VIA-positive women with colposcopic abnormalities but without histological confirmation (HR 5.2; 95% CI, 1.9–14.6). Conclusion: The high risk of cancer among women without colposcopic abnormalities who tested positive by VIA suggested that screening without triage is potentially effective.
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    Socio demographic and reproductive risk factors for cervical cancer - a large prospective cohort study from rural India
    (Asian Pac J Cancer Prev., 2013-02) Thulaseedharan, JV; Malila, N; Hakama, M; Esmy, PO; Cheriyan, M; Swaminathan, R; Muwonge, R; Sankaranarayanan, R
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    Transesophageal Echocardiographic Evaluation of Left Ventricular Systolic and Diastolic Function in Response to 20% Mannitol and 3% Hypertonic Saline Infusion in Neurosurgical Patients Undergoing Craniotomy
    (JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY, 2014) Gayatri, P; Misra, S; Menon, G; Arulvelan, A; Thulaseedharan, JV
    Background: Mannitol and hypertonic saline (HS) are routinely used during craniotomy. Both increase myocardial preload and reduce afterload, and may improve cardiac output. It is not currently known whether this results in an improvement in the global myocardial function. Thus, the aim of this study was to compare the effects of a single equiosmolar bolus of 20% mannitol (5 mL/kg) or 3% HS (5 mL/kg) on the global myocardial function by tissue Doppler-derived myocardial performance index (TD-MPI) in patients undergoing craniotomy. Methods: Fifty adult patients were included and randomized to receive either mannitol or 3% HS. Transesophageal echocardiography was performed in all patients. Early (E) and late (A) peak mitral inflow velocity, early diastolic mitral annular velocity (E prime), isovolumetric relaxation time (IVRT), ejection time (ET), and isovolumetric contraction time (IVCT) were recorded at baseline and at 15, 30, 60, and 120 minutes after administration of the hyperosmolar solutions. TD-MPI was calculated as IVRT + IVCT/ET. Results: There were no significant differences in the TD-MPI (HS vs. mannitol: 0.43 vs. 0.44 [baseline], 0.45 vs. 0.43 [15 min], 0.44 vs. 0.45 [30 min], 0.47 vs. 0.45 [60 min], 0.45 vs. 0.46 [120 min]), E/A ratio, IVCT, and E/E' either within or between the 2 groups at any time point. IVRT was prolonged in HS group as compared with baseline at 15, 30, and 60 minutes postinfusion. ET was decreased in both the groups at 120 minutes postinfusion. Neither of these altered the TD-MPI. Conclusions: Equiosmolar administration of 20% mannitol and 3% HS did not show any difference in global myocardial performance as measured by TD MPI.