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1.
Oncoimmunology ; 11(1): 2049487, 2022.
Article En | MEDLINE | ID: mdl-35309730

Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients.


Extracellular Traps , Myocarditis , Neoplasms , Animals , Biomarkers/metabolism , Extracellular Traps/metabolism , Humans , Inflammation/metabolism , Inflammation/pathology , Mice , Myocarditis/metabolism , Myocarditis/pathology , Neoplasms/pathology , Neutrophils
3.
Curr Oncol ; 25(6): e576-e584, 2018 12.
Article En | MEDLINE | ID: mdl-30607126

Introduction: Outside of randomized controlled clinical trials, the understanding of the effectiveness and costs associated with targeted therapies for metastatic renal cell carcinoma (mrcc) is limited in Canada. The purpose of the present study was to use real-world prospective data to assess the effectiveness and cost of targeted therapies for patients with mrcc. Methods: The Canadian Kidney Cancer Information System, a pan-Canadian database, was used to identify prospectively collected data relating to patients with mrcc. First- and subsequent-line time to treatment termination (ttt) was determined from therapy initiation time (sunitinib or pazopanib) to discontinuation of therapy. Kaplan-Meier survival curves were used to estimate the unadjusted and adjusted overall survival (os) by treatment. Unit treatment cost was used to estimate the cost by line of treatment and the total cost of therapy for the management of patients with mrcc. Results: The study included 475 patients receiving sunitinib or pazopanib in the first-line setting. Patients were treated mostly with sunitinib (81%); 19% of patients were treated with pazopanib. The median ttt in the first line was 7.7 months for patients receiving sunitinib and 4.6 months for those receiving pazopanib (p < 0.001). The adjusted os was 32 months with sunitinib and 21 months with pazopanib (hazard ratio: 1.61; p < 0.01). The total median cost of first- and second-line treatments was $56,476 (interquartile range: $23,738-$130,447) for patients in the sunitinib group and $46,251 (interquartile range: $28,167-$91,394) for those in the pazopanib group. Conclusions: For the two therapies, os differed significantly, with a higher median os being observed in the sunitinib group. The cost of treatment was higher in the sunitinib group, which is to be expected with longer survival.


Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Molecular Targeted Therapy , Adult , Aged , Canada/epidemiology , Carcinoma, Renal Cell/epidemiology , Carcinoma, Renal Cell/mortality , Combined Modality Therapy , Cost-Benefit Analysis , Female , Health Care Costs , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/epidemiology , Kidney Neoplasms/mortality , Male , Middle Aged , Molecular Targeted Therapy/adverse effects , Molecular Targeted Therapy/economics , Molecular Targeted Therapy/methods , Neoplasm Staging , Proportional Hazards Models , Treatment Outcome
4.
Acta Endocrinol (Buchar) ; 14(3): 384-388, 2018.
Article En | MEDLINE | ID: mdl-31149287

PURPOSE: Assessing cardiovascular risk in patients with acromegaly using traditional cardiovascular risk factors is inadequate. Endothelial dysfunction seems to be a much better indicator for assessing cardiovascular risk in acromegaly. The study aims to compare from this point of view two groups of patients, with hypertension and with acromegaly. METHODS: The first group consists of 54 patients with acromegaly and the second group of 64 hypertensive patients. Endothelial dysfunction was evaluated by the FMD method. The relationship between endothelial dysfunction, specific humoral markers of acromegaly and traditional cardiovascular risk factors was analysed in both groups. RESULTS: Although the presence of cardiovascular risk factors was statistically significantly higher in the group of hypertensives (the most important were age, blood pressure, glycemia, hypertriglyceridemia and SCORE), the presence of endothelial dysfunction was higher in the acromegaly group (61.10% vs. 32.10%, p=0.02). The best correlation with endothelial dysfunction in acromegaly group was the level of GH (28.9±28 vs. 11.7±10.3, p=0.003). CONCLUSIONS: The presence of endothelial dysfunction in patients with acromegaly is highly dependent on the level of GH and traditional cardiovascular risk factors are less important. In these patients the cardiovascular risk should not be evaluated in the same way as in normal population.

5.
Curr Oncol ; 24(4): 240-248, 2017 Aug.
Article En | MEDLINE | ID: mdl-28874892

INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases. Patient selection was based on death from a pca-related cause or therapy used according to the Canadian Urological Association guidelines on mcrpc management. Treatments included chemotherapy (mitoxantrone before 2005 and docetaxel after 2005), abiraterone, bone-targeted therapy (zoledronic acid or denosumab, or both), and palliative radiation therapy (rt). During the study period, neither enzalutamide nor cabazitaxel was publicly reimbursed in Quebec, and as a result, no capture of their use was possible for this study. Multivariate logistic regression was used to identify factors associated with the probability of receiving chemotherapy, bone-targeted therapies, and palliative rt before death from pca. RESULTS: Overall, the database search identified 3106 patients who died of pca between January 2001 and December 2013. Median age of death was 78 years. Of those 3106 patients, just 2568 (83%) received mcrpc-specific treatments: chemotherapy, abiraterone, palliative rt, or bone-targeted therapy; the other 17% of the patients were managed solely with maximum androgen blockade (androgen deprivation therapy plus anti-androgens) despite a record of pca-related death. Logistic regression analyses indicate that patients dying after 2005 were more likely to have received chemotherapy [odds ratio (or): 1.51; 95% ci: 1.22 to 1.85] and bone-targeted therapy (or: 1.97; 95% ci: 1.64 to 2.37). Age was a significant predictor for the use of chemotherapy, bone-targeted therapy, and palliative rt (ors in the range 0.96-0.98, p < 0.05). CONCLUSIONS: Patient age seems to be a strong determinant in the of selection mcrpc therapy, affecting the probability of the use of chemotherapy, bone-targeted therapy, or palliative rt. Although chemotherapy is still used only in a small percentage of patients, the introduction of new therapies-such as bone-targeted therapy, docetaxel, and abiraterone-affected treatment selection over time. The availability of enzalutamide since February 2014 will likely produce additional changes in mcrpc management.

6.
Encephale ; 43(5): 423-428, 2017 Oct.
Article Fr | MEDLINE | ID: mdl-27743676

INTRODUCTION: The Klinefelter syndrome (KS) is a genetic condition characterized by an X supernumerary sex chromosome in males. The syndrome is frequently associated with cognitive impairment. Indeed, the different areas of the executive sphere can be affected such as inhibition, cognitive flexibility but also attentional and visual-spatial domain. Social cognition disorders, predominantly on emotional recognition processes, have also been documented. In addition, the syndrome may be associated with psychiatric symptoms. MATERIAL AND METHOD: Our study aims to characterize of the various components of social cognition in the SK: facial emotional recognition, theory of mind and attributional style. For this two groups (SK group versus control group) of participants (n=16) matched for age and sociocultural level were recruited. Participants with intellectual disabilities, psychiatric or neurological disorders were excluded. Three social cognition tests were available: the TREF, the MASC, the AIHQ. Neurocognitive functions were assessed by the fNart, the subtest "logical memory" of the MEM-III, the subtests of the two VOSP battery, the d2, the TMT and the Stroop test. RESULTS: The SK group had specific social cognition disorders in comparison to the control group. Two emotions in particular were less well recognized: fear and contempt. In addition, the SK group had significantly lower results in theory of mind. Regarding the hostile attribution bias, no significant difference was found. Finally, the results showed correlations between specific attentional disorders and facial emotional recognition. DISCUSSION-CONCLUSION: Our study emphasizes social cognition disorders in SK. These disorders could be considered as a phenotypic trait in the syndrome. The interest of better characterizing the cognitive phenotype of genetic disorders that can affect the neurodevelopment is to offer specific cognitive remediation strategies.


Cognition/physiology , Klinefelter Syndrome/psychology , Social Behavior , Social Perception , Adolescent , Adult , Humans , Klinefelter Syndrome/physiopathology , Male , Neuropsychological Tests , Phenotype , Surveys and Questionnaires , Young Adult
8.
Curr Oncol ; 22(1): e20-6, 2015 Feb.
Article En | MEDLINE | ID: mdl-25684993

BACKGROUND: Evidence shows that wait times before bladder cancer surgery have been increasing, and wait time can negatively affect survival. We aimed to determine if a long delay caused by an indirect referral before a first urologist visit affects the survival of patients undergoing radical cystectomy for bladder cancer. METHODS: We analyzed data from 1271 patients who underwent surgery for bladder cancer during the decade 2000-2009. The cohort was obtained by linking two administrative databases in the province of Quebec. Patients were considered to have been directly referred to a urologist if they had 5 or fewer visits with a general practitioner before their first urologist visit; otherwise, they were considered to have been indirectly referred. The effect on survival after surgery of a longer delay before a first urologist visit was assessed using Cox regression models. RESULTS: Median referral delay for the study population was 30 days (56 days for women, 23 days for men; p < 0.0001). Indirect referral was observed for 49% of women and 33% of men. Compared with patients who were directly referred, those who were indirectly referred after first symptoms of bladder cancer experienced poorer survival (hazard ratio: 1.29; 95% confidence interval: 1.10 to 1.52). Women who were indirectly referred had a significant 47% greater risk of death after radical cystectomy. Men who were indirectly referred also experienced decreased survival (adjusted hazard ratio: 1.25; 95% confidence interval: 1.03 to 1.51). CONCLUSIONS: Patients indirectly referred to a urologist had an increased risk of mortality after surgery. Compared with men, women had longer wait times and poorer survival.

9.
Clin Exp Dermatol ; 39(1): 30-4, 2014 Jan.
Article En | MEDLINE | ID: mdl-24341478

Congenital skin fragility is a heterogeneous disorder with epidermolysis bullosa and various skin infections as the leading causes. However, even rare diseases must be considered in the differential diagnosis of neonatal skin blistering, including some genetic syndromes with extracutaneous involvement. One such syndrome is ectodermal dysplasia due to deficiency of desmoplakin, a desmosomal protein essential for cellular cohesion in both epithelia and cardiac tissues. Desmoplakin is encoded by the DSP gene, which is localized on chromosome 6p24. Both dominant and recessive mutations in this gene have been reported to cause skin fragility and keratinization defects. We report a child born with a fragile epidermis, alopecia, thick nails, and focal hyperkeratoses on the digits and knees. She was found to have a deficiency of desmoplakin caused by compound heterozygous DSP mutations. She has gradually developed signs of a left ventricular cardiomyopathy.


Alopecia/genetics , Desmoplakins/genetics , Skin Diseases, Vesiculobullous/genetics , Ventricular Dysfunction, Left/genetics , Child, Preschool , Female , Humans , Mutation , Sweden
10.
Curr Oncol ; 20(6): e522-31, 2013 Dec.
Article En | MEDLINE | ID: mdl-24311952

BACKGROUND: Prostate cancer (pca) is the most common non-skin cancer among men in Canada and other Western countries. Increased prevalence and higher cost of newer treatments have led to a significant rise in the economic burden of pca. The objectives of the present study were to systematically review the literature on direct costs for the initial management of pca, and to examine the methodologic considerations across studies. METHODS: Bibliographic databases were systematically searched for peer-reviewed articles in English. Studies were reviewed for methodologic considerations and mean direct cost of active surveillance or watchful waiting (as/ww) and initial treatments. Direct cost was standardized to 2011 Canadian dollars. RESULTS: After a review of abstracts and full-text papers, seventeen articles met the eligibility criteria and were included in the review. Studies were published during 1992-2010. The studies reported on health care systems in the United States, France, the United Kingdom, German, Italy, and Spain. Our review identified a lack of methodologic consensus, leading to variation in direct costs between studies. Nevertheless, results indicate a significant direct cost of pca treatments. CONCLUSIONS: The existing literature lacks methodologically rigorous studies on the direct costs of pca treatments specific to publicly funded health care systems. Additional studies are required to appreciate the direct costs of newer treatments and the impact of their adoption on the growing economic burden of pca management.

11.
Article En | MEDLINE | ID: mdl-24111476

A novel data-mining method was developed to gauge the experiences of the diabetes mellitus drug Januvia. Self-organizing maps were used to analyze forum posts numerically to infer user opinion of drug Januvia. Graph theory was used to discover influential users. The result is a word list compilation correlating positive and negative word cluster groups and a web of influential users on Januvia. The implications could open new research avenues into rapid data collection, feedback, and analysis that would enable improved solutions for public health.


Data Mining/methods , Diabetes Mellitus/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Pyrazines/therapeutic use , Sitagliptin Phosphate , Social Media , Treatment Outcome , Triazoles/therapeutic use
12.
Neurology ; 78(13): 957-63, 2012 Mar 27.
Article En | MEDLINE | ID: mdl-22422894

OBJECTIVE: To determine the effect of treatment gaps on the risk of institutionalization or death among community-dwelling elderly patients treated with cholinesterase inhibitors (ChIs). METHODS: A survival analysis was conducted among a cohort of community-dwelling elderly patients (age 66+) newly treated with ChIs identified in the Quebec drug claims databases (Régie de l'Assurance Maladie du Québec [RAMQ]) between January 1, 2000, and December 31, 2007. Treatment nonpersistence during the year following ChI initiation was defined as treatment discontinuation or gaps of at least 6 weeks. To account for reverse causality, Cox proportional hazard modeling was conducted only among patients who did not discontinue treatment, in order to assess the association between treatment nonpersistence and institutionalization or death. RESULTS: Among the 24,394 elderly ChI users, 4,108 (16.8) experienced a treatment gap during the year following ChI treatment initiation while 596 (2.4%) discontinued their treatment within the first 3 months (early stoppers) and 4,038 (16.6%) after 3 months of treatment (late stoppers). Of all treated patients, 4,409 (18.1%) were institutionalized or died during follow-up. In patients who did not stop their treatment, the risk of institutionalization or death appeared lower in patients who experienced a treatment gap (hazard ratio 0.91; 95% confidence interval 0.86-0.96). CONCLUSIONS: Our results suggest that, contrary to what was previously reported in clinical trials, treatment gaps do not compromise the outcome of patients treated with ChIs in a real-life setting.


Cholinesterase Inhibitors/therapeutic use , Dementia/drug therapy , Dementia/epidemiology , Medication Adherence , Aged , Aged, 80 and over , Cohort Studies , Dementia/psychology , Female , Follow-Up Studies , Humans , Male , Population Surveillance/methods , Treatment Outcome
13.
Osteoarthritis Cartilage ; 18(11): 1372-9, 2010 Nov.
Article En | MEDLINE | ID: mdl-20713163

OBJECTIVE: To estimate the lifetime risk of symptomatic hip osteoarthritis (OA). DESIGN: We analyzed data from the Johnston County Osteoarthritis Project [a longitudinal population-based study of OA in North Carolina, United States (n=3068)]. The weighted baseline sample comprised 18% blacks and 54% women, and the mean age was 63 years (range=45-93). Symptomatic hip OA was defined as a Kellgren-Lawrence (K-L) radiographic score of ≥ 2 (anterior-posterior pelvis X-rays) and pain, aching or stiffness on most days, or groin pain, in the same hip. Lifetime risk, defined as the proportion who developed symptomatic hip OA in at least one hip by age 85, among people who live to age 85, was modeled using logistic regression with repeated measures (through generalized estimating equations). RESULTS: Lifetime risk of symptomatic hip OA was 25.3% [95% confidence interval (CI)=21.3-29.3]. Lifetime risk was similar by sex, race, highest educational attainment, and hip injury history. We studied lifetime risk by body mass index (BMI) in three forms: at age 18; at baseline and follow-up; and at age 18, baseline and follow-up and found no differences in estimates. CONCLUSION: The burden of symptomatic hip OA is substantial with one in four people developing this condition by age 85. The similar race-specific estimates suggest that racial disparities in total hip replacements are not attributable to differences in disease occurrence. Despite increasing evidence that obesity predicts an increased risk of both hip OA and joint replacement, we found no association between BMI and lifetime risk.


Osteoarthritis, Hip/epidemiology , Aged , Aged, 80 and over , Body Mass Index , Female , Humans , Logistic Models , Longitudinal Studies , Male , Middle Aged , North Carolina/epidemiology , Osteoarthritis, Hip/diagnostic imaging , Radiography , Risk Factors , Sex Factors
14.
Osteoporos Int ; 21(9): 1471-85, 2010 Sep.
Article En | MEDLINE | ID: mdl-19937428

SUMMARY: Attendance at a fragility-fractures-prevention workshop by primary care physicians was associated with higher rates of osteoporosis screening and treatment initiation in elderly female patients and higher rates of treatment initiation in high-risk male and female patients. However, osteoporosis management remained sub-optimal, particularly in men. INTRODUCTION: Rates of osteoporosis-related medical practices of primary care physicians exposed to a fragility-fractures-prevention workshop were compared with those of unexposed physicians. METHODS: In a cluster cohort study, 26 physicians exposed to a workshop were matched with 260 unexposed physicians by sex and year of graduation. For each physician, rates of bone mineral density (BMD) testing and osteoporosis treatment initiation among his/her elderly patients 1 year following the workshop were computed. Rates were compared using multilevel logistic regression models controlling for potential patient- and physician-level confounders. RESULTS: Twenty-five exposed physicians (1,124 patients) and 209 unexposed physicians (9,663 patients) followed at least one eligible patient. In women, followed by exposed physicians, higher rates of BMD testing [8.5% versus 4.2%, adjusted OR (aOR) = 2.81, 95% CI 1.60-4.94] and treatment initiation with bone-specific drugs (BSDs; 4.8% vs. 2.4%, aOR = 1.95, 1.06-3.60) were observed. In men, no differences were detected. In patients on long-term glucocorticoid therapy or with a previous osteoporotic fracture, higher rates of treatment initiation with BSDs were observed in women (12.0% vs. 1.9%, aOR = 7.38, 1.55-35.26), and men were more likely to initiate calcium/vitamin D (5.3% vs. 0.8%, aOR = 7.14, 1.16-44.06). CONCLUSIONS: Attendance at a primary care physician workshop was associated with higher rates of osteoporosis medical practices for elderly women and high-risk men and women. However, osteoporosis detection and treatment remained sub-optimal, particularly in men.


Education, Medical, Continuing/methods , Osteoporosis/diagnosis , Physicians, Primary Care/education , Aged , Aged, 80 and over , Bone Density Conservation Agents/therapeutic use , Clinical Competence , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Osteoporosis/drug therapy , Osteoporotic Fractures/prevention & control , Outcome Assessment, Health Care/methods , Physicians, Primary Care/standards , Primary Health Care/standards , Professional Practice/standards , Professional Practice/statistics & numerical data , Quebec
15.
J Intern Med ; 266(2): 207 - 18, 2009 Aug.
Article En | MEDLINE | ID: mdl-19623691

AIMS: Antihypertensive (AH) agents have been shown to reduce the risk of major cardiovascular events including chronic heart failure (CHF). However, the impact of changes in patterns of AH agents use on CHF is unknown. Our objective was to estimate to which different patterns of AH agent use is associated with the occurrence of CHF in a population-based study. METHOD AND RESULTS: A cohort of 82 320 patients was reconstructed using the Régie de l'assurance maladie du Québec's databases. Patients were eligible if they were between 45 to 85 years of age, had no indication of cardiovascular disease and were newly treated with AH therapy between 1999 and 2004. A nested case-control design was used to study the occurrence of CHF. Every case of CHF was matched for age and duration of follow-up to a maximum of 15 randomly selected controls. Adherence level was reported as a medication possession ratio. Conditional logistic regression models were used to estimate the rate ratio (RR) of CHF adjusting for different covariables. The mean patient age was 65 years, 37% were male, 8% had diabetes, 19% had dyslipidaemia and mean time of follow-up at 2.7 years. High adherence level (95%) to AH therapy compared with lower adherence level (60%) was associated with an additional reduction of CHF events (RR: 0.89; 0.80-0.99). Risk factors for CHF were being on social assistance, diabetes, dyslipidaemia, higher chronic disease score and developing a cardiovascular condition during follow-up. CONCLUSION: Our study suggests that a better adherence is associated with a significant risk reduction of CHF. Adherence to AH therapy needs to be improved to optimize benefits.


Antihypertensive Agents/therapeutic use , Heart Failure/prevention & control , Medication Adherence/statistics & numerical data , Aged , Canada , Case-Control Studies , Coronary Disease/drug therapy , Coronary Disease/mortality , Databases, Factual , Female , Heart Failure/mortality , Humans , Logistic Models , Male , Middle Aged , Public Health/statistics & numerical data , Risk Reduction Behavior
16.
Osteoporos Int ; 20(9): 1571-81, 2009 Sep.
Article En | MEDLINE | ID: mdl-19107385

UNLABELLED: This population-based study aimed to compare direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. During a 2-year follow-up period, compared to those with medication possession ratio (MPR) > or = 80%, women with MPR < 80% incurred significantly higher physician care costs and hospital care costs. INTRODUCTION: This study aimed to compare direct health care costs related to the treatment of osteoporosis and osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. METHODS: A cohort of 15,027 women having initiated alendronate or risedronate was identified. MPR and direct health care costs (physician care, hospital care, drugs) were assessed during a 2-year period. Regression models were used to estimate mean predicted cost for compliant (MPR > or = 80%) and noncompliant (MPR < 80%) women. RESULTS: Mean predicted physician care cost (in Canadian dollars) was $51 among women with MPR < 80% and $34 among those with MPR > or = 80%: mean difference $17, 95% confidence interval (CI) $2-22. Mean predicted hospital care cost was $568 among women with MPR < 80% and $379 among those with MPR > or = 80%: mean difference $189, 95% CI $56-320. Mean predicted drug cost was $439 among women with MPR < 80% and $1,068 among those with MPR > or = 80%: mean difference $-639, 95% CI $-649 to -629. CONCLUSION: Compared to compliant women, noncompliant women incurred significantly higher physician care and hospital care costs. Due to lower drug costs, total direct health care costs were lower among noncompliant women.


Alendronate/therapeutic use , Bone Density Conservation Agents/therapeutic use , Etidronic Acid/analogs & derivatives , Fractures, Bone/drug therapy , Osteoporosis/drug therapy , Aged , Alendronate/economics , Bone Density Conservation Agents/economics , Confidence Intervals , Etidronic Acid/economics , Etidronic Acid/therapeutic use , Female , Fractures, Bone/economics , Fractures, Bone/prevention & control , Health Care Costs , Humans , Male , Osteoporosis/economics , Risedronic Acid , Risk Factors
17.
Osteoarthritis Cartilage ; 15(8): 966-71, 2007 Aug.
Article En | MEDLINE | ID: mdl-17395501

OBJECTIVE: High-sensitivity C-reactive protein (hsCRP) in serum is used as a marker of risk for cardiovascular disease (CVD); however CRP is a non-specific acute phase reactant. We evaluated the association between hsCRP concentrations and the most common form of arthritis, osteoarthritis (OA), and assessed the applicability of hsCRP for CVD risk prediction. METHODS: Participants (n=662) were selected from the population-based Johnston County Osteoarthritis Project, using stratified simple random sampling to achieve balance according to radiographic knee OA status, ethnic group, gender, and age group. The presence and severity of knee and hip OA were determined radiographically. CVD risk was estimated by hsCRP concentration and independently with the Framingham risk algorithm. RESULTS: Serum natural log-transformed hsCRP (ln hsCRP) was higher in African-Americans (P<0.0001) and women (P<0.0001), was higher in participants who had chronic pulmonary disease (P=0.01), hypertension (P<0.0001), or used pain medications (P=0.004), and correlated with body mass index (BMI) (r=0.40, P<0.0001) and waist circumference (r=0.33, P<0.0001), but not with age, CVD, or current smoking. Ln hsCRP was strongly positively associated with all definitions of radiographic OA (rOA; P<0.0001), but this association was not independent of BMI. Although 183 participants reported no CVD and were classified as low risk by the Framingham CVD score, 61% of them were classified as moderate or high risk for CVD using hsCRP; this proportion designated high risk for CVD on the basis of hsCRP consisted primarily of women (P<0.05) and individuals with OA (P<0.01). CONCLUSIONS: The pathogenic significance of hsCRP elevations in this subgroup is unclear. Serum hsCRP for predicting risk of CVD is confounded by obesity, ethnicity, gender and comorbidities.


Black or African American/statistics & numerical data , C-Reactive Protein/metabolism , Cardiovascular Diseases/ethnology , Lung Diseases/ethnology , Osteoarthritis/ethnology , White People/statistics & numerical data , Body Mass Index , Cardiovascular Diseases/blood , Comorbidity , Female , Humans , Lung Diseases/blood , Male , Middle Aged , Obesity/blood , Obesity/ethnology , Osteoarthritis/blood , Prevalence , Risk Factors , Sex Distribution
18.
IET Syst Biol ; 1(1): 41-50, 2007 Jan.
Article En | MEDLINE | ID: mdl-17370428

Reverse engineering problems concerning the reconstruction and identification of gene regulatory networks through gene expression data are central issues in computational molecular biology and have become the focus of much research in the last few years. An approach has been proposed for inferring the complex causal relationships among genes from microarray experimental data, which is based on a novel neural fuzzy recurrent network. The method derives information on the gene interactions in a highly interpretable form (fuzzy rules) and takes into account the dynamical aspects of gene regulation through its recurrent structure. To determine the efficiency of the proposed approach, microarray data from two experiments relating to Saccharomyces cerevisiae and Escherichia coli have been used and experiments concerning gene expression time course prediction have been conducted. The interactions that have been retrieved among a set of genes known to be highly regulated during the yeast cell-cycle are validated by previous biological studies. The method surpasses other computational techniques, which have attempted genetic network reconstruction, by being able to recover significantly more biologically valid relationships among genes.


Fuzzy Logic , Gene Regulatory Networks , Oligonucleotide Array Sequence Analysis/methods , Computational Biology/methods , Escherichia coli/genetics , Gene Expression Profiling , Saccharomyces cerevisiae/genetics
19.
Microsc Res Tech ; 69(4): 271-6, 2006 Apr.
Article En | MEDLINE | ID: mdl-16586482

The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL.


Body Fluids/chemistry , Cystic Fibrosis/metabolism , Kartagener Syndrome/metabolism , Nasal Lavage Fluid/chemistry , Nasal Mucosa/chemistry , Rhinitis/metabolism , Adolescent , Adult , Child , Chlorine/analysis , Electron Probe Microanalysis , Female , Heterozygote , Humans , Male , Middle Aged , Potassium/analysis , Salts/analysis , Sex Factors , Sodium/analysis
20.
Conf Proc IEEE Eng Med Biol Soc ; 2006: 5834-7, 2006.
Article En | MEDLINE | ID: mdl-17946338

We focus on developing a pattern recognition method suitable for performing supervised analysis tasks on molecular data resulting from microarray experiments. Molecular characterization of tissue samples using microarray gene expression profiling is expected to uncover fundamental aspects related to cancer diagnosis and drug discovery. There is therefore a need for reliable, accurate classification methods. With this study we propose a framework for constructing an ensemble of individually trained SVM classifiers, each of them specialized on subsets of the input space. The fuzzy approach used for partitioning the data produces overlapping subsets of the input space that facilitates subsequent classification tasks.


Computational Biology/methods , Gene Expression Profiling , Neoplasms/genetics , Algorithms , Cluster Analysis , Drug Design , Fuzzy Logic , Gene Expression Regulation, Neoplastic , Humans , Internet , Models, Statistical , Models, Theoretical , Neoplasms/diagnosis , Neoplasms/metabolism , Oligonucleotide Array Sequence Analysis , Pattern Recognition, Automated , Phenotype
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