Tumour necrosis factor (TNF)alpha -308 G/G promoter polymorphism and TNFalpha levels correlate with a better response to adalimumab in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNFalpha) promoter polymorphism and circulating TNFalpha levels in the clinical response to adalimumab treatment in patients with rheumatoid arthritis (RA). METHODS: Eighty-one patients with active RA were genotyped for the -308 TNFalpha polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and subdivided into two groups for each polymorphism (G/A and G/G genotype). All received 40 mg of adalimumab subcutaneously every other week. We compared the groups' clinical responses to adalimumab at 8, 16, and 24 weeks using the Disease Activity Score in 28 joints (DAS28). RESULTS: Both groups showed a significant improvement from baseline. A significant difference between groups was found at week 24. We found that 88.2% of G/G versus 68.4% of G/A for the -308 polymorphism were DAS28 responders (p = 0.05). The score improvement at week 24 was 2.5 +/- 1.3 in the G/G group and 1.8 +/- 1.3 in the G/A group for the -308 polymorphism (p = 0.04). The median of serum TNFalpha levels of the G/A group were lower than those of the G/G group, and statistically different at weeks 8 and 24 (p < 0.039 and p < 0.043). When comparing baseline levels to those achieved at 8, 16, and 24 weeks for the whole group, only responder patients showed a statistically significant overall increase in TNFalpha over time (p < 0.000001). CONCLUSION: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNFalpha levels was found in Chilean RA patients treated with adalimumab.

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

OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNF-alpha) promoter polymorphism and circulating TNF-alpha 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-alpha promoter by polymerase-chain reaction restriction fragment-length polymorphism (PCR-RFLP) analysis. Ten patients with the -308 TNF-alpha 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-alpha 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-alpha levels (p<0.03). CONCLUSION: A relationship was detected between ACR criteria of improvement and increased circulating TNF-alpha levels in RA patients subjected to anti-TNF-alpha therapy.

The -308 polymorphism in the tumour necrosis factor (TNF) gene promoter region and ex vivo lipopolysaccharide-induced TNF expression and cytotoxic activity in Chilean patients with rheumatoid arthritis.

OBJECTIVE: To investigate the association of the -308 polymorphism in the promoter region of the tumour necrosis factor (TNF) gene with susceptibility to the development of RA. We also explored the expression and cytotoxicity of TNF in relation to the -308 polymorphism. METHODS: We recruited 92 RA patients and 42 healthy control subjects. Genotyping for the TNF promoter was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. To study the overexpression of TNF we used a whole-blood culture system. TNF cytotoxicity was assessed in the L929 cell line. RESULTS: The TNF2 allele was found in 23% of RA patients and 10% of controls. Although both groups showed high variability in serum TNF concentration, in the lipopolysaccharide-induced TNF level and in the cytotoxicity of the cytokine in the L929 cell line, these differences were not associated with the -308 TNF polymorphism. CONCLUSION: No associations were found between the -308 TNF promoter polymorphism, serum and ex vivo TNF levels and the cytotoxic activity of TNF in RA patients.

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.

[Influence of maternal feeding restrictions on the mother-daughter dyad]. / Influencia de la restricción alimentaria sobre la díada madre-hija.

Alimentary restraint, cognitive variable related to eating behavior and obesity, is reportedly a valuable predictor for the development of therapeutic strategies. This paper addresses the relationship between maternal restraint and several psychological variables in their daughters (alexithymia, neuroticism, extraversion). From the study of 35 mother-daughter dyads it can be concluded that daughters of highly restrained mothers tend to present high scores in the Restraint scale of the Three Factor Eating Questionnaire of Stunkard and Messick, translated into Spanish and validated as Cuestionario de Conducta Alimentaria. Daughters of highle restrained mothers present also higher scores in the Neuroticism scale of the revised version of the Eysenck Personality Questionnaire. Daughters of mothers with low Restraint scores are in average higher than those of their mothers, although lower than those belonging to daughters of highle restrained mothers. Previous observations on the positive correlation between Disinhibition and Hunger of the Three Factor Eating Questionnaire are confirmed. These results add an additional risk factor for obesity (mothers with high Restraint) and contribute to delineate a set of psychometric indicators which might be useful in the diagnosis and prognosis of eating and body weight disorders.

[Medical certification of deaths by trauma in the Chilean health services]. / Certificación médica de las defunciones por traumatismos en los Servicios de Salud de Chile.

BACKGROUND: Trauma in the third cause of death in Chile and the most important among youngsters. AIM: To analyze the certification of deaths by trauma, studying those deaths in which it is not known if they were accidental or self inflicted. MATERIAL AND METHODS: Deaths certified as caused by trauma, poisoning or violence during the period 1992-1994 are analyzed. Those in which their accidental or self inflicted nature was ignored were specially considered. RESULTS: During the study period, 26,886 f 225,796 deaths were certified as caused by trauma, poisoning or violence. In 41.7% of these deaths, no defined cause (accidental or self inflicted) was reported) was reported. In the Metropolitan region 65.3% of deaths by trauma were not defined. Ninety seven percent of certificates in this area were extended by pathologists or coroners. In all health services, there was a positive correlation between the percentage of ill defined deaths by trauma and the percentage of certifications by pathologists or coroners. CONCLUSIONS: The deficiency in certification of deaths by trauma is possibly due to administrative causes and precludes the study of deaths caused by accidents, violence or suicide in Chile and its comparison with other countries. An effort should be done to solve this problem.

[Effects of estrogen supplementation on psychological variables in climacteric women]. / Estrógenos en climaterio femenino: efecto sobre variables psicológicas.

BACKGROUND: The beneficial effects of estrogen supplementation in climacteric women are clear. However, their psychological effects are not well documented. AIM: To study the effects of estrogen supplementation on psychological variables in climacteric women. SUBJECTS AND METHODS: Forty postmenopausal women were divided in two groups to receive a daily dose of 2 mg oestradiol valerate and 2.5 mg medroxyprogesterone acetate or an identical placebo during six months. Initially and at the end of the treatment period, they were subjected to a psychiatric interview and the Graffar, Hamilton and Eysenk personality tests were applied. Also, an Analysis of Verbal Behavior was used, that results in hope and hopeless scores. RESULTS: There were no differences in the initial assessment between the two treatment groups. In women receiving hormonal supplementation, the Hamilton score decreased from 11.2 to 4.9 (p < 0.002) and in women receiving placebo from 8.1 to 5.3 (NS). No other significant changes in psychological tests were observed. CONCLUSIONS: Hormonal supplementation decreases the Hamilton depression score in postmenopausal women.

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.