Using a discrete choice experiment to value the QLU-C10D: feasibility and sensitivity to presentation format.

PURPOSE: To assess the feasibility of using a discrete choice experiment (DCE) to value health states within the QLU-C10D, a utility instrument derived from the QLQ-C30, and to assess clarity, difficulty, and respondent preference between two presentation formats. METHODS: We ran a DCE valuation task in an online panel (N = 430). Respondents answered 16 choice pairs; in half of these, differences between dimensions were highlighted, and in the remainder, common dimensions were described in text and differing attributes were tabulated. To simplify the cognitive task, only four of the QLU-C10D's ten dimensions differed per choice set. We assessed difficulty and clarity of the valuation task with Likert-type scales, and respondents were asked which format they preferred. We analysed the DCE data by format with a conditional logit model and used Chi-squared tests to compare other responses by format. Semi-structured telephone interviews (N = 8) explored respondents' cognitive approaches to the valuation task. RESULTS: Four hundred and forty-nine individuals were recruited, 430 completed at least one choice set, and 422/449 (94 %) completed all 16 choice sets. Interviews revealed that respondents found ten domains difficult but manageable, many adopting simplifying heuristics. Results for clarity and difficulty were identical between formats, but the "highlight" format was preferred by 68 % of respondents. Conditional logit parameter estimates were monotonic within domains, suggesting respondents were able to complete the DCE sensibly, yielding valid results. CONCLUSION: A DCE valuation task in which only four of the QLU-C10D's ten dimensions differed in any choice set is feasible for deriving utility weights for the QLU-C10D.

QLU-C10D: a health state classification system for a multi-attribute utility measure based on the EORTC QLQ-C30.

PURPOSE: To derive a health state classification system (HSCS) from the cancer-specific quality of life questionnaire, the EORTC QLQ-C30, as the basis for a multi-attribute utility instrument. METHODS: The conceptual model for the HSCS was based on the established domain structure of the QLQ-C30. Several criteria were considered to select a subset of dimensions and items for the HSCS. Expert opinion and patient input informed a priori selection of key dimensions. Psychometric criteria were assessed via secondary analysis of a pooled dataset comprising HRQOL and clinical data from 2616 patients from eight countries and a range of primary cancer sites, disease stages, and treatments. We used confirmatory factor analysis (CFA) to assess the conceptual model's robustness and generalisability. We assessed item floor effects (>75 % observations at lowest score), disordered item response thresholds, coverage of the latent variable and differential item function using Rasch analysis. We calculated effect sizes for known group comparisons based on disease stage and responsiveness to change. Seventy-nine cancer patients assessed the relative importance of items within dimensions. RESULTS: CFA supported the conceptual model and its generalisability across primary cancer sites. After considering all criteria, 12 items were selected representing 10 dimensions: physical functioning (mobility), role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems. CONCLUSIONS: The HSCS created from QLQ-C30 items is known as the EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The next phase of the QLU-C10D's development involves valuation studies, currently planned or being conducted across the globe.

Healthcare provided by a homeopath as an adjunct to usual care for Fibromyalgia (FMS): results of a pilot Randomised Controlled Trial.

OBJECTIVES: To assess the feasibility of a Randomised Controlled Trial (RCT) design of usual care compared with usual care plus adjunctive care by a homeopath for patients with Fibromyalgia syndrome (FMS). METHODS: In a pragmatic parallel group RCT design, adults with a diagnosis of FMS (ACR criteria) were randomly allocated to usual care or usual care plus adjunctive care by a homeopath. Adjunctive care consisted of five in depth interviews and individualised homeopathic medicines. The primary outcome measure was the difference in Fibromyalgia Impact Questionnaire (FIQ) total score at 22 weeks. RESULTS: 47 patients were recruited. Drop out rate in the usual care group was higher than the homeopath care group (8/24 vs 3/23). Adjusted for baseline, there was a significantly greater mean reduction in the FIQ total score (function) in the homeopath care group than the usual care group (-7.62 vs 3.63). There were significantly greater reductions in the homeopath care group in the McGill pain score, FIQ fatigue and tiredness upon waking scores. We found a small effect on pain score (0.21, 95% CI -1.42 to 1.84); but a large effect on function (0.81, 95% CI -8.17 to 9.79). There were no reported adverse events. CONCLUSIONS: Given the acceptability of the treatment and the clinically relevant effect on function, there is a need for a definitive study to assess the clinical and cost effectiveness of adjunctive healthcare by a homeopath for patients with FMS.

Costs of NHS maternity care for women with multiple pregnancy compared with high-risk and low-risk singleton pregnancy.

OBJECTIVE: To compare antenatal and obstetric costs for multiple pregnancy versus singleton pregnancy risk groups and to identify factors driving cost differentials. DESIGN: Observational study over 15 months (2001-02). SETTING: Four district hospitals in southeast England. POPULATION: Consecutive women with multiple pregnancy and singleton women with risk factors for fetal congenital heart disease (CHD) (pregestational diabetes, epilepsy, or family history of CHD) or Down syndrome, and a sample of low-risk singleton women. METHODS: Clinical care was audited from the second trimester anomaly scan until postnatal discharge, and the resource items were costed. Multiple regression analysis determined predictors of costs. MAIN OUTCOME MEASURES: NHS mean costs of antenatal and obstetric care for different types of pregnancy. RESULTS: A total of 959 pregnancies were studied. Three percent of 243 women with multiple pregnancy reached 40 weeks of gestation compared with 54-55% of 163 low-risk and 322 Down syndrome risk women and 36% of 231 cardiac risk women. Antenatal costs for cardiac risk (1,153 pounds sterling) and multiple pregnancy (1,048 pounds sterling) were nearly double the costs for other two groups (P < 0.001). As 63% of multiple births were delivered by caesarean section, the obstetric cost for multiple pregnancy (3,393 pounds sterling) was 1,000 pounds sterling greater overall. Pregestational diabetes was the most influential factor driving singleton costs, resulting in similar total costs for multiple pregnancy women (4,442 pounds sterling) and for women with diabetes (4,877 pounds sterling). CONCLUSIONS: Our analyses confirm that multiple pregnancies are substantially more costly than most singleton pregnancies. Identifying women with diabetes as equally costly is pertinent because of the findings of the Confidential Enquiry into Maternal and Child Health that standards of maternal care for diabetics often are inadequate.

Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line.

The gene encoding proglucagon is expressed predominantly in the pancreas and intestine. The physiological importance of glucagon secreted from the islets of Langerhans has engendered considerable interest in the molecular control of proglucagon gene transcription in the endocrine pancreas. In contrast, little is known about the molecular control of proglucagon gene expression in the intestine. The recent demonstration that glucagon-like peptide-1 (GLP-1) secreted from the intestine is a potent regulator of insulin secretion and glucose homeostasis has stimulated renewed interest in the factors that control GLP-1 synthesis in the intestinal L-cell. To develop a model for the analysis of intestinal proglucagon gene expression, we have targeted expression of a proglucagon gene-simian virus-40 large T-antigen fusion gene to enteroendocrine cells in transgenic mice. These mice develop intestinal tumors that were used to derive a novel cell line, designated GLUTag, that expresses the proglucagon gene and secretes immunoreactive GLP-1 in vitro. GLUTag cells demonstrate morphological characteristics of enteroendocrine cells by electron microscopy and are plurihormonal, as shown by immunocytochemistry and RNA analyses. GLUTag cells express the proglucagon and cholecystokinin genes, consistent with the pattern of lineage-specific enteroendocrine differentiation described for mouse intestine. Proglucagon gene expression was induced by activators of the protein kinase-A pathway, and a combination of messenger RNA half-life and nuclear run-on experiments demonstrated that the protein kinase-A-induction is mediated by an increase in proglucagon gene transcription. In contrast, activators of protein kinase-C stimulated secretion, but not biosynthesis of the PGDPs in GLUTag cell cultures. Analysis of proglucagon processing in GLUTag cells demonstrated the liberation of glucagon, oxyntomodulin, glicentin, and multiple forms of GLP-1. These observations provide evidence for the direct induction of proglucagon gene transcription by a cAMP-dependent pathway and suggest that the GLUTag cell line represents a useful model for the analysis of the molecular determinants of enteroendocrine gene expression.

Frequency-dependent modulation of inhibition in the rat olfactory bulb.

Active sniffing in rodents at theta frequency during exploratory behavior has been hypothesized to enhance odorant access to the receptor sheet and to evoke activity patterns in olfactory and limbic structures which facilitate induction of synaptic plasticity. The present results demonstrate a third potential consequence of theta frequency sniffing -- reversible enhancement of lateral/feedback inhibition in the rat olfactory bulb. Suppression of mitral/tufted cell single-unit spontaneous activity evoked by single lateral olfactory tract (LOT) shocks was examined during LOT stimulation at either 1 or 5 Hz (theta frequency). Theta frequency stimulation rapidly and reversibly enhanced LOT-evoked suppression compared with 1 Hz stimulation. This enhancement was not stimulus intensity dependent. Sniffing-induced modification of lateral/feedback inhibition may enhance odor processing during exploration.

Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington's disease patients and transgenic mouse models.

Polyglutamine expansions in proteins are implicated in at least eight inherited neurodegenerative disorders, including Huntington's disease. These mutant proteins can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. Polyglutamine aggregates are ubiquitinated and sequester molecular chaperone proteins and proteasome components. To investigate other protein components of polyglutamine aggregates, cerebral cortex and striata from patients with Huntington's disease and full-length cDNA transgenic mouse models for this disease were examined immunohistochemically for alpha-synuclein reactivity. Our findings demonstrate that alpha-synuclein can be used as a marker for huntingtin polyglutamine aggregates in both human and mice. Moreover in the HD transgenic mice, the intensity of immunoreactivity increases with age. The significance of recruitment of alpha-synuclein into huntingtin aggregates and its translocation away from the synapses remains to be determined. We propose that aberrant interaction of mutant huntingtin with other proteins, including alpha-synuclein, may influence disease progression.

Comparison of case note review methods for evaluating quality and safety in health care.

OBJECTIVES: To determine which of two methods of case note review--holistic (implicit) and criterion-based (explicit)--provides the most useful and reliable information for quality and safety of care, and the level of agreement within and between groups of health-care professionals when they use the two methods to review the same record. To explore the process-outcome relationship between holistic and criterion-based quality-of-care measures and hospital-level outcome indicators. DATA SOURCES: Case notes of patients at randomly selected hospitals in England. REVIEW METHODS: In the first part of the study, retrospective multiple reviews of 684 case notes were undertaken at nine acute hospitals using both holistic and criterion-based review methods. Quality-of-care measures included evidence-based review criteria and a quality-of-care rating scale. Textual commentary on the quality of care was provided as a component of holistic review. Review teams comprised combinations of: doctors (n = 16), specialist nurses (n = 10) and clinically trained audit staff (n = 3) and non-clinical audit staff (n = 9). In the second part of the study, process (quality and safety) of care data were collected from the case notes of 1565 people with either chronic obstructive pulmonary disease (COPD) or heart failure in 20 hospitals. Doctors collected criterion-based data from case notes and used implicit review methods to derive textual comments on the quality of care provided and score the care overall. Data were analysed for intrarater consistency, inter-rater reliability between pairs of staff using intraclass correlation coefficients (ICCs) and completeness of criterion data capture, and comparisons were made within and between staff groups and between review methods. To explore the process-outcome relationship, a range of publicly available health-care indicator data were used as proxy outcomes in a multilevel analysis. RESULTS: Overall, 1473 holistic and 1389 criterion-based reviews were undertaken in the first part of the study. When same staff-type reviewer pairs/groups reviewed the same record, holistic scale score inter-rater reliability was moderate within each of the three staff groups [intraclass correlation coefficient (ICC) 0.46-0.52], and inter-rater reliability for criterion-based scores was moderate to good (ICC 0.61-0.88). When different staff-type pairs/groups reviewed the same record, agreement between the reviewer pairs/groups was weak to moderate for overall care (ICC 0.24-0.43). Comparison of holistic review score and criterion-based score of case notes reviewed by doctors and by non-clinical audit staff showed a reasonable level of agreement (p-values for difference 0.406 and 0.223, respectively), although results from all three staff types showed no overall level of agreement (p-value for difference 0.057). Detailed qualitative analysis of the textual data indicated that the three staff types tended to provide different forms of commentary on quality of care, although there was some overlap between some groups. In the process-outcome study there generally were high criterion-based scores for all hospitals, whereas there was more interhospital variation between the holistic review overall scale scores. Textual commentary on the quality of care verified the holistic scale scores. Differences among hospitals with regard to the relationship between mortality and quality of care were not statistically significant. CONCLUSIONS: Using the holistic approach, the three groups of staff appeared to interpret the recorded care differently when they each reviewed the same record. When the same clinical record was reviewed by doctors and non-clinical audit staff, there was no significant difference between the assessments of quality of care generated by the two groups. All three staff groups performed reasonably well when using criterion-based review, although the quality and type of information provided by doctors was of greater value. Therefore, when measuring quality of care from case notes, consideration needs to be given to the method of review, the type of staff undertaking the review, and the methods of analysis available to the review team. Review can be enhanced using a combination of both criterion-based and structured holistic methods with textual commentary, and variation in quality of care can best be identified from a combination of holistic scale scores and textual data review.

A paediatric telecardiology service for district hospitals in south-east England: an observational study.

OBJECTIVES: To compare caseloads of new patients assessed by paediatric cardiologists face-to-face or during teleconferences, and assess NHS costs for the alternative referral arrangements. DESIGN: Prospective cohort study over 15 months. SETTING: Four district hospitals in south-east England and a London paediatric cardiology centre. PATIENTS: Babies and children. INTERVENTION: A telecardiology service introduced alongside outreach clinics. MEASUREMENTS: Clinical outcomes and mean NHS costs per patient. RESULTS: 266 new patients were studied: 75 had teleconsultations (19 of 42 newborns and 56 of 224 infants and children). Teleconsultation patients generally were younger (49% being under 1 year compared with 32% seen personally (p = 0.025)) and their symptoms were not as severe. A cardiac intervention was undertaken immediately or planned for five telemedicine patients (7%) and 30 conventional patients (16%). However, similar proportions of patients were discharged after being assessed (32% telemedicine and 39% conventional). During scheduled teleconferences the mean duration of time per patient in sessions involving real-time echocardiography was 14.4 min, and 8.5 min in sessions where pre-recorded videos were transmitted. Mean cost comparisons for telemedicine and face-to-face patients over 14-day and 6-month follow-up showed the telecardiology service to be cost-neutral for the three hospitals with infrequently-held outreach clinics (1519 UK pounds vs 1724 UK pounds respectively after 14 days). CONCLUSION: Paediatric cardiology centres with small cadres of specialists are under pressure to cope with ever-expanding caseloads of new patients with suspected anomalies. Innovative use of telecardiology alongside conventional outreach services should suitably, and economically, enhance access to these specialists.

Trends in healthcare incident reporting and relationship to safety and quality data in acute hospitals: results from the National Reporting and Learning System.

BACKGROUND: Internationally, there is increasing recognition of the need to collect and analyse data on patient safety incidents, to facilitate learning and develop solutions. The National Patient Safety Agency (NPSA) for England and Wales has been capturing incident data from acute hospitals since November 2003. OBJECTIVES: This study analyses patterns in reporting of patient safety incidents from all acute hospitals in England to the NPSA National Reporting and Learning System, and explores the link between reporting rates, hospital characteristics, and other safety and quality datasets. METHODS: Reporting rates to the NPSA National Reporting and Learning System were analysed as trends over time, from the point at which each hospital became connected to the system. The relationships between reporting rates and other safety and quality datasets were assessed using correlation and regression analyses. RESULTS: Reporting rates increased steadily over the 18 months analysed. Higher reporting rates correlated with positive data on safety culture and incident reporting from the NHS Staff Survey, and with better risk-management ratings from the NHS Litigation Authority. Hospitals with higher overall reporting rates had a lower proportion of their reports in the "slips, trips and falls" category, suggesting that these hospitals were reporting higher numbers of other types of incident. There was no apparent association between reporting rates and the following data: standardised mortality ratios, data from other safety-related reporting systems, hospital size, average patient age or length of stay. CONCLUSIONS: Incident reporting rates from acute hospitals increase with time from connection to the national reporting system, and are positively correlated with independently defined measures of safety culture, higher reporting rates being associated with a more positive safety culture.

Teaching medical students to lie. The disturbing contradiction: medical ideals and the resident-selection process.

Although truthfulness and honesty have long been considered fundamental values within the medical profession, lying and deception have become standard practices within medicine's resident-selection process. Dishonesty is incorporated into and encouraged during this process, and there is little need for medical students and other participants to reflect upon their actions. This essay, which won the $1500 first prize in CMAJs 1996 Logie Medical Ethics Essay Contest, looks at the serious consequences of this lying and deception. Dr. Tara Young discusses the moral dilemma applicants for residencies face during their final year of undergraduate training.

The afferent pupillary defect.

Examination of the pupils is an essential component of both the neurologic and ocular evaluation of a child in the acute care setting. The manifestation of an afferent pupillary defect has significant clinical implications for diagnosis and management. Correctly assessing the pupils for an afferent defect is an important clinical skill for the pediatric emergency physician. An appreciation of the anatomy and understanding of the mechanisms involved in abnormal pupil responses, knowledge of the proper technique of the swinging flashlight test, and an awareness of potential pitfalls in performing this test will aid the physician in the detection of an afferent pupillary defect.

The shape of thrombomodulin and interactions with thrombin as determined by electron microscopy.

Studies have been carried out to investigate aspects of the structure of thrombomodulin, an endothelial cell glycoprotein that binds thrombin and accelerates both the thrombin-dependent activation of protein C and the inhibition of antithrombin III. We have determined the shape of SolulinTM, a soluble recombinant form of human thrombomodulin missing the transmembrane and cytoplasmic domains, by electron microscopy of preparations rotary-shadowed with tungsten. Solulin appears to be an elongated molecule about 20 nm long that has a large nodule at one end and a smaller nodule near the other end from which extends a thin strand. About half of the molecules form bipolar dimers apparently via interactions between these thin strands. Electron microscopy of complexes formed between Solulin and human alpha-thrombin revealed that a single thrombin molecule appears to bind to the smaller nodule of Solulin, suggesting that this region contains the epidermal growth factor-like domains 5 and 6. Epidermal growth factor-like domains 1-4 comprise the connector between the small and large nodule, which is the lectin-like domain; the thin strand at the other end of the molecule is the carbohydrate-rich region. With chondroitin sulfate-containing soluble thrombomodulin produced from either human melanoma cells Bowes or Chinese hamster ovary cells, a higher percentage of molecules bound thrombin and, in some cases, two thrombin molecules were attached to one soluble thrombomodulin in approximately the same region. These structural studies provide insight into the structure of thrombomodulin and its interactions with thrombin as well as aspects of the mechanisms of its actions.

Quantitative measurement for endothelial constitutive nitric oxide synthase in cultured human endothelial cells.

Constitutively expressed endothelial nitric oxide synthase (ecNOS) produces nitric oxide (NO) from L-arginine and is important for the maintenance of cardiovascular homeostasis. We report the development of a capture ELISA which is specific for ecNOS. The assay detection limit is 0.5 ng/ml ecNOS protein, allowing the measurement of ecNOS from as few as 6000 human endothelial cells cultured in 96-well microtiter plates. This ELISA has been used to measure a downregulation of ecNOS with 24-h TNFalpha treatment, consistent with results obtained by Western blot analysis. Quantitation of ecNOS in human endothelial cells showed a higher expression of ecNOS in human aortic endothelial cells (18.3+/-1.35 ng ecNOS per 10(6) cells, n = 3 donors) than in human umbilical vein endothelial cells (10.4+/-0.48 ng ecNOS per 10(6) cells, n = 3 donors). These studies demonstrate that this convenient, quantitative assay is currently the most sensitive method for investigating ecNOS protein regulation.

Identification of genes whose expression is altered during mitosuppression in livers of ethinyl estradiol-treated female rats.

In this study, our goal was to identify genes whose expression in liver is altered in female F-344 rats during mitosuppression induced by 42 days of ethinyl estradiol (EE) treatment (Yager et al., Carcinogenesis, 15, 2117-2123, 1994). Northern analysis demonstrated that the mRNA levels for transforming growth factor-beta1 (TGF-beta1) and the mannose 6-phosphate/insulin-like growth factor II receptor were significantly increased by EE treatment. Ten cDNA clones representing mRNAs whose expression was increased two- to four-fold in the mitosuppressed livers were identified by differential display. Sequence analysis revealed that one was homologous to the S-24 ribosomal protein and another to mitochondrial ATPase subunit e. The remaining clones showed no homology to known genes in GenBank. However, the expression of clones 15, 16 and 17 was increased in HepG2 cells following treatment with doxorubicin suggesting their induction by oxidative DNA damage. These results suggest that two independent but interrelated signalling pathways, one mediated through transforming growth factor-beta and the other through oxidative DNA damage, may contribute to hepatic mitosuppression caused by EE, perhaps through activation of cyclin-dependent kinase inhibitors.

Platelet factor 4 binds to glycanated forms of thrombomodulin and to protein C. A potential mechanism for enhancing generation of activated protein C.

Platelet factor 4 (PF4) is an abundant platelet alpha-granule heparin-binding protein. We have previously shown that PF4 accelerates up to 25-fold the proteolytic conversion of protein C to activated protein C by the thrombin.thrombomodulin complex by increasing its affinity for protein C 30-fold. This stimulatory effect requires presence of the gamma-carboxyglutamic acid (Gla) domain in protein C and is enhanced by the presence of a chondroitin sulfate glycosaminoglycan (GAG) domain on thrombomodulin. We hypothesized that cationic PF4 binds to both protein C and thrombomodulin through these anionic domains. Qualitative SDS-polyacrylamide gel electrophoresis analysis of avidin extracts of solutions containing biotinylated PF4 and candidate ligands shows that PF4 binds to GAG+ but not GAG- forms of thrombomodulin and native but not Gla-domainless protein C. Quantitative analysis using the surface plasmon resonance-based BIAcoreTM biosensor system confirms the extremely high affinity of PF4 for heparin (KD = 4 nM) and shows that PF4 binds to GAG+ thrombomodulin with a KD of 31 nM and to protein C with a KD of 0.37 microM. In contrast, PF4 had no measurable interaction with GAG- thrombomodulin or Gla-domainless protein C. Western blot analysis of normal human plasma extracted with biotinylated PF4 demonstrates PF4 binding to protein C in a physiologic context. Thus, PF4 binds with relative specificity and high affinity to the GAG- domain of thrombomodulin and the Gla domain of protein C. These interactions may enhance the affinity of the thrombin.thrombomodulin complex for protein C and thereby promote the generation of activated protein C.

Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver.

BACKGROUND: Alcohol-induced liver damage is associated with oxidative stress, which might be linked to disturbances in liver antioxidant defense mechanisms. The effect of chronic ethanol consumption on the mitochondrial and cytosolic glutathione/glutathione peroxidase-1 (GSHPx-1) system and oxidative modification of proteins was therefore studied in the rat. METHODS: Male Sprague-Dawley rats were fed liquid diets that provided 36% total calories as ethanol for at least 31 days. Pair-fed controls received isocaloric diets with ethanol calories substituted with maltose-dextrins. Mitochondrial and cytosolic fractions were prepared from livers and assayed for GSHPx-1 and glutathione reductase activities and total and oxidized concentrations of glutathione. Catalase activity was measured in the postmitochondrial supernatant. Levels of GSHPx-1, lactate dehydrogenase, and the beta subunit of the F1 portion of the ATP synthase protein were determined by western blot analysis. Concentrations of mitochondrial and cytosolic protein carbonyls were measured to assess ethanol-induced oxidation of proteins. RESULTS: Chronic ethanol consumption significantly decreased cytosolic and mitochondrial GSHPx-1 activities by 40% and 30%, respectively. Levels of GSHPx-1 protein in cytosol were unaffected by ethanol feeding, whereas there was a small decrease in GSHPx-1 protein levels in mitochondria isolated from ethanol-fed rats. Glutathione reductase activities were increased in both intracellular compartments and catalase activity was increased as a consequence of ethanol exposure. Cytosolic total glutathione was mildly decreased, whereas ethanol feeding increased mitochondrial levels of total glutathione. Chronic ethanol feeding significantly increased both cytosolic and mitochondrial concentrations of protein carbonyls by 30% and 60%, respectively. CONCLUSIONS: This study demonstrates that chronic ethanol-induced alterations in the glutathione/GSHPx-1 antioxidant system might promote oxidative modification of liver proteins, namely those of the mitochondrion, which could contribute to the adverse effects of ethanol on the liver.