Adrenal-cortex autoantibodies and steroid-producing cells autoantibodies in patients with Addison's disease: comparison of immunofluorescence and immunoprecipitation assays

Autoimmune Addison's disease and premature ovarian failure are characterized by the presence of organ-specific autoantibodies. The main adrenal and gonadal autoantigens have been identified and cloned, and the relationship between the autoantibodies detected by immunofluorescence techniques and those detected by the new assays using recombinant autoantigens needed to be investigated. We studied 165 patients with Addison's disease: 143 patients had different forms of autoimmune Addison's disease (13 with idiopathic premature ovarian failure) and 22 had nonautoimmune Addison's disease. Adrenal-cortex autoantibodies and steroid-producing cell autoantibodies were measured by the immunofluorescence techniques. Autoantibodies to steroid 21-hydroxylase, 17alpha-hydroxylase, and P450 side chain cleavage enzyme were measured by immunoprecipitation assay using 35S-labeled recombinant proteins. Adrenal-cortex autoantibodies and autoantibodies to 21-hydroxylase were found in 81% of the patients with autoimmune Addison's disease. None of the patients with nonautoimmune Addison's disease had adrenal-cortex autoantibodies or autoantibodies to 21-hydroxylase. A high association between these two markers in patients with different forms of autoimmune Addison's disease and in those with short- or long-standing disease was found. Steroid-producing cells autoantibodies were found in 26% of the patients with autoimmune Addison's disease, and autoantibodies to 17alpha-hydroxylase and/or P450 side chain cleavage enzyme in 36% of the patients. Steroid-producing cells autoantibodies were found in 11/13 (85%) of patients with idiopathic premature ovarian failure associated with autoimmune Addison's disease, and autoantibodies to 17alpha-hydroxylase and/or P450 side chain cleavage were found 12/13 (92%) of patients; the only case negative for all these three markers suffered from Turner's syndrome. Provided that a high standard of immunofluorescence technique is maintained, measurement of adrenal cortex autoantibodies or steroid-producing cells autoantibodies by either immunofluorescence or immunoprecipitation assay is essentially equivalent.     

766 cases of oral cleft in Italy

Epidemiological and genetic variables for oral clefts were analysed for the years 1981–1989 in a case-control study of congenital malformations in the Emilia Romagna, Veneto, and Friuli regions, and in the Trento and Bolzano hospitals. Birth prevalence for all cases of cleft lip with or without cleft palate (CL(P)) was 8.2 per 10,000 births, and that for cleft palate only (CP) was 6.1 per 10,000. Coexisting abnormalities were found in 23% of CL(P) cases and in 43% of CP. No clusters in time or space were detected. For isolated clefts, a predominance of males among CL(P) and of females among CP was found; epilepsy was the only maternal risk factor correlated with clefts, and an association between clefting and consanguinity was found. Empirical recurrence risks were calculated in both isolated CL(P) and CP.     

Aging bone in men and women: beyond changes in bone mineral density

Using peripheral quantitative computed tomography (pQCT) we assessed trabecular and cortical bone density, mass and geometric distribution at the tibia level in 512 men and 693 women, age range 20–102 years, randomly selected from the population living in the Chianti area, Tuscany, Italy. Total, trabecular and cortical bone density decreased linearly with age (p<0.0001 in both sexes), and the slope of age-associated decline was steeper in women than in men. In men, the cortical bone area was similar in different age groups, while in women older than 60 years it was significantly smaller by approximately 1% per year. The total cross-sectional area of the bone became progressively wider with age, but the magnitude of the age-associated increment was significantly higher in men than in women (p<0.001). The minimum moment of inertia, an index of mechanical resistance to bending, remained stable with age in men, while it was significantly lower in older compared with younger women (0.5% per year). The increase in bone cross-sectional area in aging men may contribute to the maintenance of adequate bone mechanical competence in the face of declining bone density. In women this compensatory mechanism appears to be less efficient and, accordingly, the bone mechanical competence declines with age. The geometric adaptation of increasing cross-sectional bone size is an important component in the assessment of bone mechanical resistance which is completely overlooked, and potentially misinterpreted, by traditional planar densitometry.     

Frailty of older age: the role of the endocrine--immune interaction

The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself such as disability and frailty. Understanding the pathophysiology of frailty, a syndrome characterized by a reduced functional reserve and impaired adaptive capacity that results from cumulative declines of multiple subsystems, and causes increased vulnerability to adverse outcomes, is a major topic in aging research. Aging processes induce multiple changes in the hormones network (menopause, andropause, somatopause and adrenopause), in the immune system, and can modulate their efficiency and effectiveness in determining a response to stressors. These triggering events can unmask frailty in older people. Starting from these assumptions, we analyzed the relationship of the endocrine and immune networks in aging and in the different domains that are characteristically associated with the frailty syndrome, such as disability and sarcopenia, as well as in diseases related to aging such as Alzheimer's dementia and Congestive Heart Failure.     

Clinical evaluation of a nanofilled composite in posterior teeth: 12-month results

This study compared the clinical performance of a nanofilled resin composite for posterior restorations with 2 microhybrid and 1 packable composite after 12 months of clinical service. Forty-two patients with at least 5 Class I or II restorations under occlusion were enrolled in this study. A total of 148 restorations were placed, 25% for each material (Filtek Supreme, Pyramid, Esthet-X or Tetric Ceram). Two calibrated operators placed all restorations, according to the manufacturers' instructions. One week later, the restorations were finished/polished. Two independent examiners evaluated the restorations at baseline and after 12 months according to the USPHS modified criteria. All patients attended the 12-month recall and 148 restorations were evaluated. Friedman repeated measures analysis of variance by rank and Wilcoxon sign-ranked test for pair-wise comparison was used for data analysis (alpha=0.05). All materials showed only minor modifications, and no differences were detected between their performance at baseline and after 12 months. After 1 year, the nanofilled resin composite showed similar performance to the other packable and microhybrid resin composites.     

Preservation of FGF-2 bioactivity using heparin-based nanoparticles, and their delivery from electrospun chitosan fibers

Here we present a novel matrix-mimetic nanoassembly based on polysaccharides. Chitosan electrospun fiber networks are decorated with heparin-containing polyelectrolyte complex nanoparticles (PCNs) that present basic fibroblast growth factor (FGF-2), both stably adsorbed to the surfaces and released into solution. These FGF-2/PCN complexes can be released from the fibers with zero-order kinetics over a period of 30 days. Further modification of fibers with a single bilayer of polyelectrolyte multilayer (PEM) composed of N,N,N-trimethyl chitosan and heparin completely prevent release, and the FGF-2/PCN complexes are retained on the fibers for the duration of the release experiment (30 days). We also compare the mitogenic activity of these FGF-2/PCN complexes delivered in two different states: adsorbed to a surface and dissolved in solution. FGF-2/PCN complexes exhibit mitogenic activity with respect to ovine bone marrow-derived mesenchymal stem cells, even after being preconditioned by incubating for 27 days at 37°C in solution. However, when the FGF-2/PCN complexes are adsorbed to chitosan and coated with PEMs, the mitogenic activity of the FGF-2 steadily decreases with increasing preconditioning time. This work demonstrates a new system for stabilizing and controlling the delivery of heparin-binding growth factors, using polysaccharide-based matrix-mimetic nanomaterials. This work also contributes to our understanding of the preferred mode of growth factor delivery from porous scaffolds.     

Patient awareness about drugs prescribed after medical appointment and prescription

Information provided to patients about medication is important for the success of the treatment, since the lack of such information is one of the main reasons why patients fail to take medicines as prescribed. The aim of this study was to verify patients' awareness about prescribed drugs distributed at the Gr?o Pará (Santa Catarina) primary healthcare unit after a medical appointment. One hundred and eleven patients were interviewed, seventy after a medical appointment and forty-one after drugs were distributed. Patient awareness was tested by asking questions about the name, usage, dosage, length of treatment, side effects, and precautions. After a medical appointment 28.5% of patients were classified as having a good level of awareness, 17.1% fair and 64.4% insufficient. After drugs were distributed 4.9% of patients were classified as having a good level of awareness, 87.8% fair and 7.3% insufficient. The majority of those interviewed had a low level of awareness about the use of the prescribed drugs. Results after drugs were distributed were better in comparison to results after a medical appointment, suggesting the importance of the pharmacist in informing patients about the correct use of drugs.     

Association between VO2 peak estimated by a 1-km treadmill walk and mortality. A 10-year follow-up study in patients with cardiovascular disease

Purpose

The aim of this study is to assess the association between peak oxygen uptake (VO₂ peak), determined using a perceptually regulated 1-km walking test (1 k-TWT), and all-cause mortality in cardiac patients.

Methods

1255 male patients, aged 25–85 years, completed a moderate 1 k-TWT to estimate VO₂ peak. Subjects were followed for all-cause mortality for up to 10 years. Cox proportional hazard models were employed to determine variables associated with mortality. Based on the estimated VO₂ peak, the sample was subdivided into quartiles and mortality risks were calculated. To assess the discriminatory accuracy of the estimated VO₂ peak for estimating survival, receiver-operating-characteristics curves were constructed.

Results

During a median 8.2 year follow-up, a total of 141 deaths from any cause occurred, yielding an average annual mortality of 1.4%. The strongest predictor of all-cause mortality was the estimated VO₂ peak (c-statistic 0.71, 95% confidence intervals: 0.69–0.74, P < 0.0001). Survival decreased in a graded fashion from the highest estimated VO₂ peak quartile to the lowest quartile. Compared to the lowest quartile, the hazard ratios (95% confidence intervals) for the second, third, and fourth quartiles were 0.77 (0.35–1.33), 0.43 (0.20–0.91), and 0.16 (0.05–0.54) respectively (P for trend < 0.0001). An 89% reduction in mortality risk was observed among a subset of subjects in the fittest quartile who improved their estimated VO₂ peak over the follow-up period relative to subjects in the least fit quartile who did not improve.

Conclusion

VO₂ peak estimated by a novel 1 k-TWT predicts survival in subjects with stable cardiovascular disease.     

Predictors of response to group cognitive-behavioral therapy in the treatment of obsessive-compulsive disorder

PurposeTo identify the presence of factors associated with treatment outcome in patients under group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).Subjects and methodsThis study evaluated 181 patients with OCD that attended a 12-session weekly GCBT program. Response criteria were: ≥35% reduction in Y-BOCS scores and global improvement score of the Clinical Global Impression (CGI) ≤ 2 at post-treatment evaluation. Sociodemographic data, OCD characteristics, and treatment data were studied.ResultsIn the bivariate analysis, the following variables showed statistical significance (p < 0.20) to enter the regression model: being woman (p = 0.074), greater insight (p = 0.017) and better quality of life (QOL) in all domains before treatment (p = 0.053), overall severity of disease according to the CGI (p = 0.007), number of associated comorbidities (p = 0.063), social phobia (p = 0.044), and dysthymia (p = 0.072). In the final regression model, these variables were associated with response to GCBT: female gender (p = 0.021); WHOQOL-BREF psychological domain (p = 0.011); insight (p = 0.042); and global improvement score of the CGI severity-scale before therapy (p = 0.045).ConclusionSpecial attention should be paid to patients with poor insight, increasing the cognitive aspects of the therapy in an attempt to modify the rigidity and fixity of their beliefs. In addition, male patients should be more observed, since they showed lower chance of response to GCBT when compared to women. Patients with more severe global symptoms (CGI) are poorer responders to GCBT, which indicates that not only obsessive-compulsive symptoms (OCS) should be evaluated, since other symptoms, such as depression and anxiety, may affect the treatment; therefore, an attempt to reduce these symptoms, prior to the treatment of OCD, should be considered as an option in some cases.