Antioxidant therapy attenuates oxidative insult caused by benzonidazole in chronic Chagas` heart disease

Chronic chagasic cardiac patients are exposed to oxidative stress that apparently contributes to disease progression. Benznidazole (BZN) is the main drug used for the treatment of chagasic patients and its action involves the generation of reactive species. 41 patients with Chagas` heart disease were selected and biomarkers of oxidative stress were measured before and after 2 months of BZN treatment (5 mg/kg/day) and the subsequent antioxidant supplementation with vitamin E (800 UI/day) and C (500 mg/day) during 6 months. Patients were classified according to the modified Los Andes clinical hemodynamic classification in groups IA, IB, II and III, and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR), as well as the contents of reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), protein carbonyl (PC), vitamin E and C and nitric oxide (NO), myeloperoxidase (MPO) and adenosine deaminase (ADA) activities were measured in their blood. Excepting in group III, after BZN treatment SOD, CAT, GPx and GST activities as well as PC levels were enhanced while vitamin E levels were decreased in these groups. After antioxidant supplementation the activities of SOD, GPx and GR were decreased whereas PC, TBARS, NO, and GSH levels were decreased. In conclusion, BZN treatment promoted an oxidative insult in such patients while the antioxidant supplementation was able to attenuate this effect by increasing vitamin E levels, decreasing PC and TBARS levels, inhibiting SOD, GPx and GR activities as well as inflammatory markers, mainly in stages with less cardiac involvement. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Labile Plasma Iron Generation After Intravenous Iron is Time-dependent and Transitory in Patients Undergoing Chronic Hemodialysis

Iron supplementation in hemodialysis patients is fundamental to erythropoiesis, but may cause harmful effects. We measured oxidative stress using labile plasma iron (LPI) after parenteral iron replacement in chronic hemodialysis patients. Intravenous iron saccharate (100 mg) was administered in patients undergoing chronic hemodialysis (N = 20). LPI was measured by an oxidant-sensitive fluorescent probe at the beginning of dialysis session (T0), at 10 min (T1), 20 min (T2), and 30 min (T3) after the infusion of iron and at the subsequent session; P < 0.05 was significant. The LPI values were significantly raised according to the time of administration and were transitory: -0.02 +/- 0.20 mu mol/L at the beginning of the first session, 0.01 +/- 0.26 mu mol/L at T0, 0.03 +/- 0.23 mu mol/L at T1, 0.09 +/- 0.28 mmol/L at T2, 0.18 +/- 0.52 mmol/L at T3, and -0.02 +/- 0.16 mmol/L (P = 0.001 to 0.041) at the beginning of the second session. The LPI level in patients without iron supplementation was -0.06 +/- 0.16 mmol/L. Correlations of LPI according to time were T1, T2, and T3 vs. serum iron (P = 0.01, P = 0.007, and P = 0.0025, respectively), and T2 and T3 vs. transferrin saturation (P = 0.001 and P = 0.0003, respectively). LPI generation after intravenous saccharate administration is time-dependent and transitorily detected during hemodialysis. The LPI increment had a positive correlation to iron and transferrin saturation.

Predictive models for chronic renal disease using decision trees, naïve bayes and case-based methods

Data mining can be used in healthcare industry to “mine” clinical data to discover hidden information for intelligent and affective decision making. Discovery of hidden patterns and relationships often goes intact, yet advanced data mining techniques can be helpful as remedy to this scenario. This thesis mainly deals with Intelligent Prediction of Chronic Renal Disease (IPCRD). Data covers blood, urine test, and external symptoms applied to predict chronic renal disease. Data from the database is initially transformed to Weka (3.6) and Chi-Square method is used for features section. After normalizing data, three classifiers were applied and efficiency of output is evaluated. Mainly, three classifiers are analyzed: Decision Tree, Naïve Bayes, K-Nearest Neighbour algorithm. Results show that each technique has its unique strength in realizing the objectives of the defined mining goals. Efficiency of Decision Tree and KNN was almost same but Naïve Bayes proved a comparative edge over others. Further sensitivity and specificity tests are used as statistical measures to examine the performance of a binary classification. Sensitivity (also called recall rate in some fields) measures the proportion of actual positives which are correctly identified while Specificity measures the proportion of negatives which are correctly identified. CRISP-DM methodology is applied to build the mining models. It consists of six major phases: business understanding, data understanding, data preparation, modeling, evaluation, and deployment.

Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly

OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence. METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL( ) min(-1)  1.73 m(-) ²) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315). RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05]. CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.

Alteration of GSH level, gene expression and cell transformation in NIH3T3 cells by chronic exposure to low dose of arsenic

It is well established that arsenic toxicity is postulated to be primarily due to the binding of As(III) to sulfhydryl-containing enzymes. However, the mechanism of carcinogenesis induced by arsenic is still unclear. The interaction of arsenic with GSH and related enzymes seems a very important issue regarding mechanism of arsenical induced toxicity or carcinogenesis. The purpose of this work is to investigate the effect of chronic exposure to low dose of As(III) on GSH level, gene expression and cell transformation in NIH3T3 cells. The results showed that long-term, low dose arsenic treatment makes 3T3 cell more resistant to acute arsenic treatment. There were morphology changes after long-term arsenic treatment. First, partially immortalized 3T3 cell became immortalized. In addition, the cells were doubling more quickly than the control cells and attained higher density than the control cells at confluence. Second, cells treated with 0.1 µ.M As(III) exhibited anchorage-independent growth. Arsenic could enhance GSH level at 0.5 -10 µM dose of arsenic in 24 h treatment and decrease it at 25 µM and above. In long-term treatment with low dose of arsenic, GSH levels were decreased. As(I1I) can increase both glutathione S-transferase (GST) and glutathione reductase (GR) activities at low dose (0.5-10 M), but decreased GST and GR activities at 25 M and higher dose of arsenic, while in long-term As(III) treatment, GST and GR activities are increased. Both long-term and short-term treatments with As(III) can induce GR gene expression. GPx mRNA levels were decreased both in acute and chronic arsenic treated cells. Chronic treatment with As(III) also decreased the p53 mRNA level. Taken together, our results suggest that As(III) can alter GST, GR enzyme activities as well as GSH level and related gene expression both in long-term and short-term treatment but in a different manner in different doses. Alteration of cellular GSH level by As(III) might play all important role in gene expression and arsenic induced cell transformation.

Fuzzy logic for decision support in chronic care

Computerized clinical guidelines can provide significant benefits in terms of health outcomes and costs, however, their effective computer implementation presents significant problems. Vagueness and ambiguity inherent in natural language (textual) clinical guidelines makes them problematic for formulating automated alerts or advice. Fuzzy logic allows us to formalize the treatment of vagueness in a decision support architecture. In care plan on-line (CPOL), an intranet-based chronic disease care planning system for general practitioners (GPs) in use in South Australia, we formally treat fuzziness in interpretation of quantitative data, formulation of recommendations and unequal importance of clinical indicators. We use expert judgment on cases, as well as direct estimates by experts, to optimize aggregation operators and treat heterogeneous combinations of conjunction and disjunction that are present in the natural language decision rules formulated by specialist teams.

Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety and fatigue

Objective: This study was designed to investigate the role of depression, anxiety, and fatigue in Chronic Fatigue Syndrome (CFS) sufferers' objective and subjective cognitive performance. Methods: Twenty-three CFS sufferers and 23 healthy control participants were compared on objective and subjective assessments of cognitive performance. Depression, anxiety, and fatigue were also evaluated. Results: CFS sufferers did not demonstrate any impairment in objective cognitive functioning compared to the control group, and objective performance was not related to their higher levels of depression or their level of fatigue. Depression scores only accounted for a small amount of the variance in CFS sufferers' lower subjective assessment of their cognitive performance compared to control participants. There were no differences between the groups on anxiety scores. Conclusion: The results are discussed in terms of the heterogeneity of the CFS population and the complex interaction of symptomatological factors that characterise CFS.

Overcoming the stigma of chronic illness: strategies for normalisation of a 'spoiled identity'

This paper addresses the concept of chronic illness as a socially constructed experience of stigma. The stigma of having a chronic illness affects the person's self-concept, capacity to adapt to the illness and the quality of his/her social networks. Social stigma is a delegitimising social process derived from both popular and medical views of chronic illness. Based on research into the coping strategies of a range of people with long-term, serious chronic illnesses, the paper argues that government health policies and services in Australia can best help people with chronic illness by supporting their self-help groups and community-based activities.

A contested disease state : chronic fatigue syndrome

This paper aims firstly to look at characteristics of the condition, and current issues related to the symptomatology and presentation of ME-CFS. Secondly, it identifies methodological problems in researching ME/CFS and demonstrates that the experimental approach to researching the condition can be informed by more qualitative, constructivist approaches. Thirdly, it argues that ME-CFS is a contested state whose acceptance by the medical profession requires the legitimation of a demonstrated biomedical basis

Effect of three wound dressings on infection, healing comfort, and cost in patients with sternotomy wounds - a randomized trial

Study objective: To compare three dressing types in terms of their ability to protect against infection and promote healing, patient comfort, and cost-effectiveness.

Design: Prospective, randomized controlled trial.

Setting: Major metropolitan, academically affiliated, tertiary referral center.

Patients: Seven hundred thirty-seven patients were randomized to receive a dry absorbent dressing (n = 243) [Primapore; Smith & Nephew; Sydney, NSW, Australia], a hydrocolloid dressing (n = 267) [Duoderm Thin ConvaTec; Mulgrave, VIC, Australia], or a hydroactive dressing (n = 227) [Opsite; Smith & Nephew] in the operating theater on skin closure.

Results: There was no difference in the rate of wound infection or wound healing between treatment groups. The Primapore dressing was the most comfortable and cost-effective dressing option for the sternotomy wound. Duoderm Thin dressings were associated with increased wound exudate (p < 0.001), poor dressing integrity (p < 0.001), more frequent dressing changes (p < 0.001), more discomfort with removal (p < 0.05), and increased cost (p < 0.001).

Conclusions: In the context of no additional benefit for the prevention of wound infection or the rate of wound healing for any of the three dressing products examined, dry absorbent dressings are the most comfortable and cost-effective products for sternotomy wounds following cardiac surgery.

Physical activity, emotional stress, sleep disturbances, and daily fluctuations in chronic fatigue symptomatology

The current study explored the relationships between physical and emotional stress and the symptomatology of chronic fatigue syndrome (CFS). Fifty-four CFS patients were studied using a longitudinal design. A self-report format was used to collect daily measures of major physical (sleep disturbance and physical activity) and emotional (subjective emotional stress level) stressors, as well as measures of levels of fatigue and secondary symptoms. The variables accounted for a moderate variance at the individual and occasion levels. Sleep disturbance and emotional stress were found to be positively associated with levels of fatigue and symptomatology, whereas physical activity was found to have a negative relationship with fatigue only. The severity of fatigue and symptoms were found to fluctuate daily in relation with the variables, indicating the complex nature of the associations.