ASSOCIATION BETWEEN SMOKING,CRACK COCAINE ABUSE AND THE DISCONTINUATION OF COMBINATION ANTIRETROVIRAL THERAPY IN RECIFE,PERNAMBUCO, BRAZIL

Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.     

Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen‐induced eczema model

Proteasome inhibition (PI) has been reported to interfere with antibody‐driven autoimmune diseases. The impact of PI on the allergic immune response and on skin diseases like atopic dermatitis (AD) has not been thoroughly explored, however. Here, we examined whether the PI bortezomib interferes with the allergic immune response and the severity of AD by using an established mouse model of allergen‐driven dermatitis, to which bortezomib was applied after the establishment of systemic sensitization to ovalbumin. The treatment indeed resulted in a remarkable decrease in total and allergen‐specific plasma cells/antibody‐secreting cells, as evidenced by flow cytometry and ELISpot, respectively. This was accompanied by rapid reductions in serum antibody titres, including a prominent reduction of the IgE isotype. CD4+ and CD8+ cells were greatly diminished in lesional skin on immunohistological staining. The impressive effects at the level of immune modulation did not result in any improvement in the eczema, however. Following up on this unexpected result, we found that the skin itself was susceptible to bortezomib, by which it was instructed to lower the expression of critical skin barrier genes, especially transglutaminase‐1 and filaggrin. Together, bortezomib eliminates plasma cells and decreases immunoglobulin responses, including allergenic IgE. Although anti‐inflammatory effects are detectable in the skin, counter‐regulatory effects from PI on resident skin cells likely undermine improvement in the eczema. These results caution against the therapeutic use of bortezomib for inflammatory skin disorders, which are characterized by inherently impaired barrier function, especially AD.     

Pain evaluation during gynaecological surveillance in women with Lynch syndrome

To evaluate perceived pain during repetitive annual endometrial sampling at gynaecologic surveillance in asymptomatic women with Lynch syndrome (LS) over time and in addition to symptomatic women without LS, undergoing single endometrial sampling. In this prospective study, 52 women with LS or first degree relatives who underwent repetitive annual gynaecological surveillance including endometrial sampling of which 33 were evaluated twice or more and 50 symptomatic women without LS who had single endometrial sampling, were included. Pain intensity was registered with VAS scores. Differences in pain intensities between subsequent visits (in LS) and between the two groups were evaluated. The use of painkillers before endometrial sampling was registered. If women with LS decided for preventive surgery, the reason was recorded. The LS group reported a median VAS score of 5.0 (range 0–10) at the first surveillance (n = 52) and at the second visit (n = 24). Women who repeatedly underwent endometrial sampling more often used painkillers for this procedure. During the study period 7/52 (13 %) women with LS choose for preventive surgery, another 4/52 (8 %) refused further endometrial sampling. Painful endometrial sampling was mentioned as main reason to quit screening. The median VAS score of the 50 symptomatic women was 5.0 (range 1–9). Endometrial sampling, irrespective of indication, is a painful procedure, with a median VAS score of 5.0. During subsequent procedures in women with LS, the median pain score does not aggravate although one in five women chose an alternative for endometrial sampling.     

Acute esophageal necrosis

Acute esophageal necrosis (AEN) or “black esophagus” is a rare condition presented by patients with critical state of health and characterized by a darkened esophagus, usually the distal third, in upper digestive endoscopy. The main clinical manifestation is upper gastrointestinal bleeding and there may be abdominal pain, dysphagia, nausea, vomiting, fever and syncope associated. The diagnosis depends on clinical suspicion and performing endoscopy, the biopsy not being required. In this article we present a case of a patient who had lots of comorbidities and developed AEN during a post-operative period, and discuss the importance of AEN in an increasingly ageing population.     

Beta‐amyloid protein (25–35) disrupts hippocampal network activity: Role of Fyn‐kinase

Early cognitive deficit characteristic of early Alzheimer's disease seems to be produced by the soluble forms of β‐amyloid protein. Such cognitive deficit correlates with neuronal network dysfunction that is reflected as alterations in the electroencephalogram of both Alzheimer patients and transgenic murine models of such disease. Correspondingly, recent studies have demonstrated that chronic exposure to βAP affects hippocampal oscillatory properties. However, it is still unclear if such neuronal network dysfunction results from a direct action of βAP on the hippocampal circuit or it is secondary to the chronic presence of the protein in the brain. Therefore, we aimed to explore the effect of acute exposure to βAP_25–35 on hippocampal network activity both in vitro and in vivo, as well as on intrinsic and synaptic properties of hippocampal neurons. We found that βAP_25–35, reversibly, affects spontaneous hippocampal population activity in vitro. Such effect is not produced by the inverse sequence βAP_35–25 and is reproduced by the full‐length peptide βAP_1–42. Correspondingly βAP_25–35, but not the inverse sequence βAP_35–25, reduces theta‐like activity recorded from the hippocampus in vivo. The βAP_25–35‐induced disruption in hippocampal network activity correlates with a reduction in spontaneous neuronal activity and synaptic transmission, as well as with an inhibition in the subthreshold oscillations produced by pyramidal neurons in vitro. Finally, we studied the involvement of Fyn‐kinase on the βAP_25–35‐induced disruption in hippocampal network activity in vitro. Interestingly, we found that such phenomenon is not observed in slices obtained from Fyn‐knockout mice. In conclusion, our data suggest that βAP acutely affects proper hippocampal function through a Fyn‐dependent mechanism. We propose that such alteration might be related to the cognitive impairment observed, at least, during the early phases of Alzheimer's disease. © 2009 Wiley‐Liss, Inc.     

Effect of sulfonylurea agents on pyruvate dehydrogenase activity in circulating lymphocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM)

In circulating lymphocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM) subnormal pyruvate dehydrogenase (PDH) activity returns to normal following patient treatment with sulfonylurea (gliclazide^*, 80 mg twice daily/5 weeks). Moreover, in vitro in cells from diabetic patients exposed to insulin at 50 μU/mL PDH activation also occurs; in cells of controls the same happens for insulin at 5 μU/mL, whereas at 50 μU/mL inhibition takes place. Therefore, the low PDH activity in cells of NIDDM patients might be caused by defective insulin control on the enzyme and its recovery in gliclazide-treated patients by drug-mediated removal of the defect. The validity of the hypothesis was verified in this study where cells of NIDDM patients before and after gliclazide treatment were exposed, in vitro, to insulin at 5 and 50 μU/mL and then tested for PDH activity. In such conditions, the profile of PDH behavior in treated patients was no longer comparable to that in untreated patients but closer to that in euglycemic controls, thus supporting the view that the recovery of PDH activity in NIDDM patients following gliclazide treatment might be the expression of an additional effect that the drug would have in these patients, aimed to renew cell responsiveness to insulin.     

Breast density in dedicated breast computed tomography: Proposal of a classification system and interreader reliability

The aim of this study was to develop a new breast density classification system for dedicated breast computed tomography (BCT) based on lesion detectability analogous to the ACR BI-RADS breast density scale for mammography, and to evaluate its interrater reliability.In this retrospective study, 1454 BCT examinations without contrast media were screened for suitability. Excluding datasets without additional ultrasound and exams without any detected lesions resulted in 114 BCT examinations. Based on lesion detectability, an atlas-based BCT density (BCTD) classification system of breast parenchyma was defined using 4 categories. Interrater reliability was examined in 40 BCT datasets between 3 experienced radiologists.Among the included lesions were 63 cysts (55%), 18 fibroadenomas (16%), 7 lesions of fatty necrosis (6%), and 6 breast cancers (5%) with a median diameter of 11 mm. X-ray absorption was identical between lesions and breast tissue; therefore, the lack of fatty septae was identified as the most important criteria for the presence of lesions in glandular tissue. Applying a lesion diameter of 10 mm as desired cut-off for the recommendation of an additional ultrasound, an atlas of 4 BCTD categories was defined resulting in a distribution of 17.5% for density A, 39.5% (B), 31.6% (C), and 11.4% (D) with an intraclass correlation coefficient (ICC) among 3 readers of 0.85 to 0.87.We propose a dedicated atlas-based BCTD classification system, which is calibrated to lesion detectability. The new classification system exhibits a high interrater reliability and may be used for the decision whether additional ultrasound is recommended.