Irene Schiattino

Tumour necrosis factor-α (tnf-α) levels and influence of -308 TNF-α promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis

Objective: To investigate the influence of −308 tumour necrosis factor‐α (TNF‐α) promoter polymorphism and circulating TNF‐α levels in the clinical response to the infliximab treatment in patients with rheumatoid arthritis (RA). Methods: One hundred and thirty‐two RA patients were genotyped for TNF‐α promoter by polymerase‐chain reaction restriction fragment‐length polymorphism (PCR‐RFLP) analysis. Ten patients with the −308 TNF‐α gene promoter genotype G/A, and 10 with the G/G genotype were selected and received 3 mg/kg of infliximab at Weeks 0, 2, 6, and 14. Results: Both groups showed a significant improvement with treatment in all variables studied. Total mean TNF‐α levels increased significantly with respect to basal levels in most of patients after treatment [probability (p)=0.04]. Only patients from G/A showed a statistically significant correlation between ACR 50 and the increase of TNF‐α levels (p<0.03). Conclusion: A relationship was detected between ACR criteria of improvement and increased circulating TNF‐α levels in RA patients subjected to anti‐TNF‐α therapy.

Genetic polymorphism at position -308 in the promoter region of the tumor necrosis factor (TNF): Implications of its allelic distribution on susceptibility or resistance to diseases in the Chilean population

Several single-nucleotide polymorphisms have been identified in the human TNF gene promoter. The polymorphism at position-308 (TNF-308), which involves substituting G for A and designing the TNF2 allele, leads to a higher rate of TNF gene transcription than the wild-type TNF1 allele in in vitro expression studies. It has also been linked to increased susceptibility to a variety of illnesses. Using PCR-RFLP analysis we detected significant differences in the TNF-308 genotypes of Chilean and other populations. We conclude that there is a gradient in the distribution of the TNF2 allele according to ethnicity; we have also hypothesized that populations bearing a higher proportion of the TNF2 allele may have an increased predisposition toward or incidence of several chronic metabolic, degenerative, inflammatory and autoimmune diseases.

Impact of large industrial emission sources on mortality and morbidity in Chile: A small-areas study.

Chile suffers significant pollution from large industrial emitters associated with the mining, metal processing, paper production, and energy industries. The aim of this research was to determine whether the presence of large industrial facilities (i.e. coal- and oil-fired power plants, pulp and paper mills, mining facilities, and smelters) affects mortality and morbidity rates in Chile. For this, we conducted an ecological study that used Chilean communes as small-area observation units to assess mortality and morbidity. Public databases provided information on large pollution sources relevant to Chile. The large sources studied were oil- and coal-fired power plants, copper smelters, pulp and paper mills, and large mining facilities. Large sources were filtered by first year of production, type of process, and size. Mortality and morbidity data were acquired from public national databases, with morbidity being estimated from hospitalization records. Cause-specific rates were calculated for the main outcomes: cardiovascular, respiratory, cancer; and other more specific health outcomes. The impact of the large pollution sources was estimated using Bayesian models that included spatial correlation, overdispersion, and other covariates. Large and significant increases in health risks (around 20%-100%) were found for communes with power plants and smelters for total, cardiovascular, respiratory, all-cancer, and lung cancer mortality. Higher hospitalization rates for cardiovascular disease, respiratory disease, cancer, and pneumonia (20-100%) were also found for communes with power plants and smelters. The impacts were larger for men than women in terms of both mortality and hospitalizations. The impacts were also larger when the sources were analyzed as continuous (production volume) rather than dichotomous (presence/absence) variables. In conclusion, significantly higher rates of total cardiovascular, respiratory, all-cancer and lung cancer mortality and cardiovascular, respiratory, cancer and pneumonia hospitalizations were observed in communes with power plants and smelters.

Quality of life in climacteric Chilean women treated with low-dose estrogen.

OBJECTIVES To evaluate the impact of low-dose oral estrogen therapy on the health-related quality of life (HRQoL) in 45-64-year-old women from the East Metropolitan Health Service (SSMO) in Santiago, Chile. MATERIAL AND METHODS We conducted an observational cross-sectional study. A random population sample of women between 45 and 64 years of age was obtained through an invitation to contact one of 15 primary health care centers of the SSMO of Santiago, Chile. Out of the 927 women who were originally contacted, 844 women were able to complete the Menopausal Rating Scale (MRS) questionnaire. Information about demographic parameters, health issues, and modality of hormonal therapy (HT) were registered. Three groups were compared: group 1 (n=647; non-users of HT), group 2 (n=82; users of low-dose oral estrogen HT), and group 3 (n=115; users of non low-dose estrogens HT). RESULTS There were no differences among groups in terms of demographic and health issue parameters. The results of the MRS scores (total score and somatic, psychological and urogenital domain scores) showed significant differences across the 3 study groups, with more favorable results for HRQoL in groups 2 and 3 (p<0.01 for total, somatic, and psychological scores; p=0.05 for urogenital score). CONCLUSION Climacteric women in the 45-64 age range using HT were shown to have a more favorable impact on HRQoL than non-HT users. Women using low-dose oral estrogen HT had a positive effect on HRQoL, similar to that obtained using non low-dose estrogen regimens.

Multiple imputation procedures allow the rescue of missing data: An application to determine serum tumor necrosis factor (TNF) concentration values during the treatment of rheumatoid arthritis patients with anti-TNF therapy

Longitudinal studies aimed at evaluating patients clinical response to specific therapeutic treatments are frequently summarized in incomplete datasets due to missing data. Multivariate statistical procedures use only complete cases, deleting any case with missing data. MI and MIANALYZE procedures of the SAS software perform multiple imputations based on the Markov Chain Monte Carlo method to replace each missing value with a plausible value and to evaluate the efficiency of such missing data treatment. The objective of this work was to compare the evaluation of differences in the increase of serum TNF concentrations depending on the -308 TNF promoter genotype of rheumatoid arthritis (RA) patients receiving anti-TNF therapy with and without multiple imputations of missing data based on mixed models for repeated measures. Our results indicate that the relative efficiency of our multiple imputation model is greater than 98% and that the related inference was significant (p-value < 0.001). We established that under both approaches serum TNF levels in RA patients bearing the G/A -308 TNF promoter genotype displayed a significantly (p-value < 0.0001) increased ability to produce TNF over time than the G/G patient group, as they received successively doses of anti-TNF therapy.

Percepción de cambios en la práctica médica y estrategias de afrontamiento

Background: A change in the social structure of medicine and its impact on clients has occurred in the last decades. Aim: To perform a survey about subjective wellbeing among physicians. Material and Methods: A physician’ professional satisfaction survey consisting in 90 questions, was applied to 580 physicians (70% males), working in Metropolitan Santiago. Results: Physicians perceive changes in all the examined professional domains and approximately 50% of the changes are evaluated as negative. Change perception is a general phenomena among physicians, since there were no differences in relation to gender and only in few aspects with respect to age and medical specialty. There was a predominant positive attitude, based on the profession, to face changes. Conclusions: The positive evaluation of changes and the frequent use of managing strategies are associated with a higher satisfaction among physicians.

Anxiety and hostility in written verbal samples of male and female subjects : A content analytic study

Nonclinical populations of male and female subjects of middle socioeconomic level and different age ranges were assessed by means of the content analysis method developed by Gottschalk and associates. Verbal samples consisted of written productions in response to a standard ambiguous instruction to narrate a dramatic or interesting life experience and were scored for anxiety and hostility. Results show that the method shows no influence of gender under the conditions of this study and can be employed for diagnostic purposes, assuming that personality factors and psychopathological influences might have a more pronounced impact on affect scores.