Juan de Dios Luna

Relation Between Vitamin D Insufficiency, Bone Density, and Bone Metabolism in Healthy Postmenopausal Women

Although only few postmenopausal women exhibit biochemical signs of hypovitaminosis D, vitamin D insufficiency has been shown to have adverse effects on bone metabolism and could be an important risk factor for osteoporosis and fracture. We determined serum levels of 25‐hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), bone turnover markers, dietary calcium intake, and bone mineral density (BMD; measured by dual X‐ray absorptiometry) in 161 consecutive ambulatory women, healthy except for osteoporosis, referred to a bone metabolic unit. The prevalence of vitamin D insufficiency [25(OH)D ≤ 15 ng/ml] was 39.1%. 25(OH)D was lower in the osteoporotic subjects (15.7 ± 5.3 ng/ml vs. 21.8 ± 9.7 ng/ml; p < 0.001). After controlling for all other variables, lumbar spine (LS) BMD was found to be significantly associated with 25(OH)D, body mass index (BMI), and years after menopause (YSM) (R2 = 0.253; p < 0.001). For femoral neck (FN), significant independent predictors of BMD were YSM, BMI, iPTH, and 25(OH)D (R2 = 0.368; p < 0.001). The probability of meeting osteoporosis densitometric criteria was higher in the vitamin D insufficiency group (odds ratio [OR], 4.17, 1.83‐9.48) after adjusting by YSM, BMI, iPTH, and dietary calcium intake. Our study shows that vitamin D insufficiency in an otherwise healthy postmenopausal population is a common risk factor for osteoporosis associated with increased bone remodeling and low bone mass.

Bone Mineral Density Measured by Dual X-Ray Absorptiometry in Spanish Patients with Insulin-Dependent Diabetes Mellitus*

Previous studies suggest that low bone mass is a potential complication of insulin-dependent diabetes mellitus. Nevertheless, the factors that influence diabetic osteopenia are not well established. In order to evaluate the prevalence and magnitude of diabetic osteopenia and its association with clinical and metabolic variables, we studied 94 consecutive patients with insulin-dependent diabetes mellitus. Their age ranged from 20 to 56 years and duration of diabetes varied from 1 to 35 years. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at lumbar spine and proximal femur and the values were expressed as z-score. The presence and extent of microvascular complications, degree of metabolic control, and other risk factors for osteoporosis were recorded and some biochemical markers of bone metabolism were assessed. Diabetic patients showed reduced BMD in all sites (lumbar spine: −0.89±1.21; femoral neck: −0.99±1.24; Ward triangle; −1.05±1.24;P<0.0001). Of the 94 patients 19.1% met diagnostic criteria for osteoporosis. BMD correlated with body mass index in all sites and with the duration of disease in Wards triangle. Presence and extent of diabetic complications were associated with lower BMD, as was smoking. No correlation was found between BMD and biochemical markers. In conclusion, osteopenia is a common complication in patients with insulin-dependent diabetes mellitus. Microvascular complications are a critical point in the progression of diabetic osteopenia. Other risk factors for osteoporosis (nutritional status and smoking) must be taken into account.

The risk for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype: evidence from the Spanish PREDICT-Gene cohort

We report results from the PREDICT-Gene case-control study nested in a prospective cohort designed to identify predictors of the onset of depression among adult primary-care attendees. We tested the potential gene-by-environment interaction between 5HTTLPR genotype at the serotonin transporter gene and previous exposure to threatening life events (TLEs) in depression. A total of 737 consecutively recruited participants were genotyped. Additional information was gathered on exposure to TLEs over a 6-month period, socio-demographic data and family history of psychological problems among first-degree relatives. Diagnoses of depression were ascertained using the Composite International Diagnostic Interview (CIDI) by trained interviewers. Two different depressive outcomes were used (ICD-10 depressive episode and ICD-10 severe depressive episode). Both the s/s genotype and exposure to increasing number of TLEs were significantly associated with depression. Moreover, the 5HTTLPR s/s genotype significantly modified the risk conferred by TLEs for both depressive outcomes. Thus, s/s homozygous participants required minimal exposure to TLE (1 TLE) to acquire a level of risk for depression that was only found among l/s or l/l individuals after significantly higher exposure to TLEs (two or more TLEs). The interaction was more apparent when applied to the diagnosis of ICD-10 severe depressive episode and after adjusting for gender, age and family history of psychological problems. Likelihood ratios tests for the interaction were statistically significant for both depressive outcomes (ICD-10 depressive episode: LR X2=4.7, P=0.09 (crude), LR-X2=6.4, P=0.04 (adjusted); ICD-10 severe depressive episode: LR X2=6.9, P=0.032 (crude), LR-X2=8.1, P=0.017 (adjusted)).

Infectious agents associated with schizophrenia: A meta-analysis

Schizophrenia is a highly disabling and limiting disorder for patients and the possibility that infections by some microorganisms may be associated to its development may allow prevention and recovery. In the current study we have done a meta-analysis of studies that have assessed the possible association between detection of different infectious agents and schizophrenia. We report results that support the idea that there is a statistically significant association between schizophrenia and infection by Human Herpesvirus 2 (OR=1.34; CI 95%: 1.09-1.70; p=0.05), Borna Disease Virus (OR=2.03; CI 95%: 1.35-3.06; p<0.01), Human Endogenous Retrovirus W (OR=19.31; CI 95%: 6.74-55.29; p<0.001), Chlamydophila pneumoniae (OR=6.34; CI 95%: 2.83-14.19; p<0.001), Chlamydophila psittaci (OR=29.05; CI 95%: 8.91-94.70; p<0.001) and Toxoplasma gondii (OR=2.70; CI 95%: 1.34-4.42; p=0.005). The implications of these findings are discussed and further research options are also explicated.

The 5‐HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: The PREDICT‐gene study

Previous reports and meta‐analyses have yielded inconclusive results as to whether the s/s genotype at the 5‐HTTLPR serotonin transporter polymorphism confers increased risk for depression. We tested the association between s/s genotype and depression in a large cohort (n = 737) of Spanish primary care consecutive attendees participating in a European study on predictors for depression in primary care (PREDICT study). Participants were administered the Composite International Diagnostic Interview (CIDI) depression subscale allowing diagnoses using ICD‐10 criteria for depressive episodes. Participants were genotyped to establish 5HTTLPR genotype. Both univariable and multivariable associations between the s/s genotype and depression were tested twice using two different depressive outcomes (ICD‐10 depressive episode and ICD‐10 severe depressive episode). We found an association between the s/s genotype and both depressive outcomes that was independent of age, sex, family history of psychological problems among first degree relatives and presence of comorbid generalized anxiety disorder. When comparing s/s homozygous versus the rest, the adjusted odds ratio for any ICD‐10 depressive episode and for severe ICD‐10 depressive episode were 1.50 (95% CI: 1.0–2.2; P = 0.045) and 1.79 (95% CI: 1.1–2.8; P = 0.016), respectively. The association was significantly stronger with increasing severity of depression (χ2 for linear association=6.1; P = 0.013) suggesting a dose‐dependent relationship. Our results are consistent with previous reports suggesting a small but independent effect by the s/s 5‐HTTLPR genotype increasing the risk for depression.

Comparative effects of melatonin, l‐deprenyl, Trolox and ascorbate in the suppression of hydroxyl radical formation during dopamine autoxidation in vitro

Degeneration of nigrostriatal dopaminergic neurons is the major pathogenic substrate of Parkinsons disease (PD). Inhibitors of monoamine oxidase B (MAO‐B) have been used in the treatment of PD and at least one of them, i.e., deprenyl, also displays antioxidant activity. Dopamine (DA) autoxidation produces reactive oxygen species implicated in the loss of dopaminergic neurons in the nigrostriatal pathway. In this study we compared the effects of melatonin with those of deprenyl and vitamins E and C in preventing the hydroxyl radical (•OH) generation during DA oxidation. The rate of production of 2,3‐dihydroxybenzoate (2,3‐DHBA) in the presence of salicylate, an •OH scavenger, was used to detect the in vitro generation of •OH during iron‐catalyzed oxidation of DA. The results showed a dose‐dependent effect of melatonin, deprenyl and vitamin E in counteracting DA autoxidation, whereas vitamin C had no effect. Comparative analyses between the effect of these antioxidants showed that the protective effect of melatonin against DA autoxidation was significantly higher than that of the other compounds tested. Also, when melatonin plus deprenyl were added to the incubation medium, a potentiation of the antioxidant effect was found. These findings suggest that antioxidants may be useful in brain protection against toxicity of reactive oxygen species produced during DA oxidation, and melatonin, alone or in combination with deprenyl, may be an important component of the brains antioxidant defenses to protect it from dopaminergic neurodegeneration.

Personality traits associated with caffeine intake and smoking.

OBJECTIVES Some studies find a relationship between certain personality traits, as impulsivity or sensation seeking, and caffeine consumption, but these studies do not consider the potential confounding effect of smoking on caffeine intake, a co-occurrence that has been well demonstrated in epidemiological and clinical studies. The main objective of this cross-sectional study was to analyze the association of personality with caffeine intake controlling for the effects of smoking; a secondary objective was to explore the effect of caffeine intake on the previously known relationship between personality and smoking. METHODS A sample of 498 adults answered a self-questionnaire including socio-demographic variables, and items regarding consumption of tobacco and caffeine. Personality was measured by the Temperament and Character Inventory (TCI-125). We analyzed the association of personality traits with both caffeine intake and smoking, controlling the possible confounding effects of sex, age and each substance with the other one. RESULTS Logistic regression analyses showed that the temperamental dimension of novelty seeking was associated with heavy caffeine consumption (>200 mg/day) (adjusted OR=2.0; 95% CI: 1.1-3.9), controlling for the effect of smoking. Moreover, novelty seeking was associated with both smoking (adjusted OR=1.8; 95% CI: 1.1-2.9) and heavy smoking (>20 cigarettes/day) (adjusted OR=1.8; 95% CI: 1.0-3.7), after controlling for the effect of caffeine intake. CONCLUSION Our study offers an epidemiological evidence of the relationship of novelty seeking, considered to be associated with low basal dopaminergic activity, with both nicotine consumption and heavy caffeine intake, two substances that enhance dopaminergic neurotransmission.

Influence of the doctor's gender in the satisfaction of the users.

This study was carried out in the framework of a wider research project concerning the degree of patient satisfaction with the various types of primary health care. We have studied the relationship among the gender of the doctor, the gender of the patient and the type of primary health care center involved. In 1 type of primary care center (health centers) the medical staff work as a team, whereas in the other (ambulatory care services), the doctor works alone. The survey was conducted among 86 doctors and 860 patients from urban areas in Andalusia, Spain. The degree of patient satisfaction was tested on Likert scales. Both male and female patients attended by female doctors were more satisfied than those attended by male doctors (P < 0.005). Both male and female patients were attended in equal proportions by both male and female doctors (P > 0.20). Overall patient satisfaction values were not affected by the patients gender (P > 0.40). In comparing overall satisfaction among patients according with the doctors gender and type of primary health care center, there was a greater degree of satisfaction with female doctors working in health centers (P < 0.01) and no difference existed in ambulatory care services in this area.

Validity of self reported utilisation of primary health care services in an urban population in Spain

STUDY OBJECTIVE To assess the validity and factors related with the validity of self reported numbers of visits to a primary health care centre, in comparison with the recorded number. DESIGN Cross sectional study. SETTING The urban area served by the Zaidín-Sur Primary Health Care Centre (Granada, Spain). PARTICIPANTS Two population samples (236 high users and 420 normal users) who were seen at the centre from 1985 to 1991 were interviewed in 1993. MAIN RESULTS A net tendency to overreport the actual number of visits was observed. Absolute concordance between self reported and recorded utilisation decreased as time interval lengthened, although this mainly reflected the increase in maximum variability both with time interval length and with the number of recorded visits. Corrected Spearman ρ coefficients obtained between the number of self reported and recorded visits ranged from 0.602 for the two weeks before the interview to 0.678 for the year before. Regression slopes of self reported utilisation upon recorded utilisation did not change between periods. In multiple regression analyses the actual number of visits was the main factor associated with both underreporting and overreporting. Older age was also significantly associated with underreporting. Poor health status and high satisfaction with health care were significantly associated with overreporting. CONCLUSIONS There was a substantial degree of inaccuracy in self reported utilisation, with a net tendency to overreport the number of visits. In relative terms, however, accuracy of self reports did not seem to decrease appreciably as the recall time lengthened. To compare the accuracy of different measures, it is important to take into account the maximum variability of each one. Otherwise, contradictory results may be obtained.

Improvement in the determination of HIV-1 tropism using the V3 gene sequence and a combination of bioinformatic tools.

Assessment of HIV tropism using bioinformatic tools based on V3 sequences correlates poorly with results provided by phenotypic tropism assays, particularly for recognizing X4 viruses. This may represent an obstacle for the use of CCR5 antagonists. An algorithm combining several bioinformatic tools might improve the correlation with phenotypic tropism results. A total of 200 V3 sequences from HIV‐1 subtype B, available in several databases with known phenotypic tropism results, were used to evaluate the sensitivity and specificity of seven different bioinformatic tools (PSSM, SVM, C4.5 decision tree generator and C4.5, PART, Charge Rule, and Geno2pheno). The best predictive bioinformatic tools were identified, and a model combining several of these was built. Using the 200 reference sequences, SVM and geno2‐pheno showed the highest sensitivity for detecting X4 viruses (98.8% and 93.7%, respectively); however, their specificity was relatively low (62.5% and 86.6%, respectively). For R5 viruses, PSSM and C4.5 gave the same results and outperformed other bioinformatic tools (95.7% sensitivity, 82% specificity). When results from three out of these four tools were concordant, the sensitivity and specificity, taking as reference the results from phenotypic tropism assays, were over 90% in predicting either R5 or X4 viruses (AUC: 0.9701; 95% CI: 0.9358–0.9889). An algorithm combining four distinct bioinformatic tools (SVM, geno2pheno, PSSM and C4.5), improves the genotypic prediction of HIV tropism, and merits further evaluation, as it might prove useful as a screening strategy in clinical practice. J. Med. Virol. 81:763–767, 2009.