Early improvement of psychotic symptoms with lithium monotherapy as a predictor of later response in mania

Although lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithium's efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint. (C) 2012 Elsevier Ltd. All rights reserved.

Assessment of cavitated and active non-cavitated caries lesions in 3-to 4-year-old preschool children: a field study

Background. The prevalence of early childhood caries (ECC) is high in developing countries; thus, sensitive methods for the early diagnosis of ECC are of prime importance to implement the appropriate preventive measures. Aim. To investigate the effects of the addition of early caries lesions (ECL) into WHO threshold caries detection methods on the prevalence of caries in primary teeth and the epidemiological profile of the studied population. Design. In total, 351 3-to 4-year-old preschoolers participated in this cross-sectional study. Clinical exams were conducted by one calibrated examiner using WHO and WHO + ECL criteria. During the exams, a mirror, a ball-ended probe, gauze, and an artificial light were used. The data were analysed by Wilcoxon and Mc-Nemar's tests (a = 0.05). Results. Good intra-examiner Kappa values at tooth /surface levels were obtained for WHO and WHO + ECL criteria (0.93 /0.87 and 0.75 /0.78, respectively). The dmfs scores were significantly higher (P < 0.05) when WHO + ECL criteria were used. ECLs were the predominant caries lesions in the majority of teeth. Conclusions. The results strongly suggest that the WHO + ECL diagnosis method could be used to identify ECL in young children under field conditions, increasing the prevalence and classification of caries activity and providing valuable information for the early establishment of preventive measures.

Feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation

Objective: this study investigated the feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation. The aim of this study was to present the decision making process of women that chose for pregnancy termination and to present selected speeches of women about their feelings. Design: open psychological interviews conducted by a psychologist immediately after the diagnosis of fetal malformation by ultrasound. Analysis of the results was performed through a content analysis technique. Setting: the study was carried out at a public university hospital in Brazil. Participants: 249 pregnant women who had received the diagnosis of a severe lethal fetal malformation. Findings: fetal anencephaly was the most frequent anomaly detected in 135 cases (54.3%). Termination of pregnancy was decided by 172 (69.1%) patients and legally authorised by the judiciary (66%). The reason for asking for termination was to reduce suffering in all of them. In the 77 women who chose not to terminate pregnancy (30.9%), the reasons were related to feelings of guilt (74%). Key conclusions: the results support the importance of psychological counselling for couples when lethal fetal malformation is diagnosed. The act of reviewing moral and cultural values and elements of the unconscious provides assurance in the decision-making process and mitigates the risk of emotional trauma and guilt that can continue long after the pregnancy is terminated. (C) 2011 Elsevier Ltd. All rights reserved.

Inflammatory milieu as an early marker of kidney injury in offspring rats from diabetic mothers

The present study investigated the early presence of inflammatory response in renal tissue of young offspring from diabetic mothers. The effect of L-arginine (L-arg) supplementation was also investigated. The offspring was divided into four groups: group CO (controls); group DO (diabetic offspring); group CA (CO receiving 2% L-arg solution) and group DA (DO receiving the 2% L-arg solution). Glycemia, arterial pressure and renal function were evaluated; gene and protein expression of pro-inflammatory cytokines were also measured. Blood pressure levels were significantly increased in 2 and 6 month-old DO rats, whereas L-arg administration caused a significant decrease in the DA group, at both ages. DO rats showed a significantly blunted glycemic response to exogenous insulin. In 2 month-old DO animals, renal protein expression of pro-inflammatory molecules was significantly increased. At six months of age, we also observed an increase in gene expression of pro-inflammatory molecules, whereas L-arg supplementation prevented this increase at both ages. Our data suggest that activation of inflammatory pathways is present early in the kidney of DO rats, and that L-arg can attenuate the expression of these markers of tissue inflammation. Our results also reinforce the concept that intrauterine environmental factors are a fundamental determinant in the development of metabolic and vascular diseases later in life. (C) 2012 Elsevier B.V. All rights reserved.

The beta 2-Adrenoceptor Agonist Formoterol Improves Structural and Functional Regenerative Capacity of Skeletal Muscles From Aged Rat at the Early Stages of Postinjury

Skeletal muscles from old rats fail to completely regenerate following injury. This study investigated whether pharmacological stimulation of beta 2-adrenoceptors in aged muscles following injury could improve their regenerative capacity, focusing on myofiber size recovery. Young and aged rats were treated with a subcutaneous injection of beta 2-adrenergic agonist formoterol (2 mu g/kg/d) up to 10 and 21 days after soleus muscle injury. Formoterol-treated muscles from old rats evaluated at 10 and 21 days postinjury showed reduced inflammation and connective tissue but a similar number of regenerating myofibers of greater caliber when compared with their injured controls. Formoterol minimized the decrease in tetanic force and increased protein synthesis and mammalian target of rapamycin phosphorylation in old muscles at 10 days postinjury. Our results suggest that formoterol improves structural and functional regenerative capacity of regenerating skeletal muscles from aged rats by increasing protein synthesis via mammalian target of rapamycin activation. Furthermore, formoterol may have therapeutic benefits in recovery following muscle damage in senescent individuals.

Can neuroimaging be used as a support to diagnosis of borderline personality disorder? An approach based on computational neuroanatomy and machine learning

Several recent studies in literature have identified brain morphological alterations associated to Borderline Personality Disorder (BPD) patients. These findings are reported by studies based on voxel-based-morphometry analysis of structural MRI data, comparing mean gray-matter concentration between groups of BPD patients and healthy controls. On the other hand, mean differences between groups are not informative about the discriminative value of neuroimaging data to predict the group of individual subjects. In this paper, we go beyond mean differences analyses, and explore to what extent individual BPD patients can be differentiated from controls (25 subjects in each group), using a combination of automated-morphometric tools for regional cortical thickness/volumetric estimation and Support Vector Machine classifier. The approach included a feature selection step in order to identify the regions containing most discriminative information. The accuracy of this classifier was evaluated using the leave-one-subject-out procedure. The brain regions indicated as containing relevant information to discriminate groups were the orbitofrontal, rostral anterior cingulate, posterior cingulate, middle temporal cortices, among others. These areas, which are distinctively involved in emotional and affect regulation of BPD patients, were the most informative regions to achieve both sensitivity and specificity values of 80% in SVM classification. The findings suggest that this new methodology can add clinical and potential diagnostic value to neuroimaging of psychiatric disorders. (C) 2012 Elsevier Ltd. All rights reserved.

Clinical Diagnosis of Pulp Inflammation Based on Pulp Oxygenation Rates Measured by Pulse Oximetry

Introduction: The objective of this study was to investigate correlations between pulp oxygenation rates (%SpO(2)) and clinical diagnoses of reversible pulpitis (RP), irreversible pulpitis (IP), or pulp necrosis (PN). Methods: Sixty patients who presented with a tooth with endodontic pathology were grouped according to a clinical diagnosis of either RP (n = 20), IP (n = 20), or PN (n = 20). The clinical diagnosis was based on the patient's dental history, periapical radiographs, clinical inspection, and percussion and thermal sensitivity testing. Pulse oximetry (PO) was used to determine pulp oxygenation rates. For every patient, one additional endodontically treated tooth (negative control [NC], n = 60) and one additional healthy tooth with healthy pulp status (positive control [PC], n = 60) were evaluated. Analysis of variance, the Tukey HSD test, and the Student's t test were used for statistical analysis. Results: The mean % SpO(2) levels were as follows: RP: 87.4% (standard deviation [SD] +/- 2.46), IP: 83.1% (SD +/- 2.29), PN: 74.6% (SD +/- 1.96), PC: 92.2% (SD +/- 1.84), and NC: 0% (SD +/- 0.0). There were statistically significant differences between RP, IP, and PM compared with NC and PC and between RP, IP, and PN (all P <= .01). Conclusions: The evaluation of pulp oxygenation rates by PO may be a useful tool to determine the different inflammatory stages of the pulp to aid in endodontic diagnosis. (JEndod 2012;38:880-883)

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

Abstract Background Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of Mycobacterium tuberculosis (MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection. Methods To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB. Results In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%–78%) and specificity of 83% (CI 95%: 75%–89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%–84%) and specificity of 86% (CI 95%:78%–92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively. Conclusion PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital.

Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats

Abstract Background Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation. Methods Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge. Results Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1β (30%) and TNF-α (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1β, TNF-α and P-selectin, and neutrophil migration. Conclusion Data presented suggest that insulin modulates the production/release of TNF-α and IL-1β, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction.

Comparison of two laboratory-developed PCR methods for the diagnosis of Pulmonary Tuberculosis in Brazilian patients with and without HIV infection

Abstract Background Direct smear examination with Ziehl-Neelsen (ZN) staining for the diagnosis of pulmonary tuberculosis (PTB) is cheap and easy to use, but its low sensitivity is a major drawback, particularly in HIV seropositive patients. As such, new tools for laboratory diagnosis are urgently needed to improve the case detection rate, especially in regions with a high prevalence of TB and HIV. Objective To evaluate the performance of two in house PCR (Polymerase Chain Reaction): PCR dot-blot methodology (PCR dot-blot) and PCR agarose gel electrophoresis (PCR-AG) for the diagnosis of Pulmonary Tuberculosis (PTB) in HIV seropositive and HIV seronegative patients. Methods A prospective study was conducted (from May 2003 to May 2004) in a TB/HIV reference hospital. Sputum specimens from 277 PTB suspects were tested by Acid Fast Bacilli (AFB) smear, Culture and in house PCR assays (PCR dot-blot and PCR-AG) and their performances evaluated. Positive cultures combined with the definition of clinical pulmonary TB were employed as the gold standard. Results The overall prevalence of PTB was 46% (128/277); in HIV+, prevalence was 54.0% (40/74). The sensitivity and specificity of PCR dot-blot were 74% (CI 95%; 66.1%-81.2%) and 85% (CI 95%; 78.8%-90.3%); and of PCR-AG were 43% (CI 95%; 34.5%-51.6%) and 76% (CI 95%; 69.2%-82.8%), respectively. For HIV seropositive and HIV seronegative samples, sensitivities of PCR dot-blot (72% vs 75%; p = 0.46) and PCR-AG (42% vs 43%; p = 0.54) were similar. Among HIV seronegative patients and PTB suspects, ROC analysis presented the following values for the AFB smear (0.837), Culture (0.926), PCR dot-blot (0.801) and PCR-AG (0.599). In HIV seropositive patients, these area values were (0.713), (0.900), (0.789) and (0.595), respectively. Conclusion Results of this study demonstrate that the in house PCR dot blot may be an improvement for ruling out PTB diagnosis in PTB suspects assisted at hospitals with a high prevalence of TB/HIV.

The contrast-enhanced Doppler ultrasound with perfluorocarbon exposed sonicated albumin does not improve the diagnosis of renal artery stenosis compared with angiography

There are no studies investigating the effect of the contrast infusion on the sensitivity and specificity of the main Doppler criteria of renal artery stenosis (RAS). Our aim was to evaluate the accuracy of these Doppler criteria prior to and following the intravenous administration of perfluorocarbon exposed sonicated albumin (PESDA) in patients suspected of having RAS. Thirty consecutive hypertensive patients (13 males, mean age of 57 ± 10 years) suspected of having RAS by clinical clues, were submitted to ultrasonography (US) of renal arteries before and after enhancement using continuous infusion of PESDA. All patients underwent angiography, and haemodynamically significant RAS was considered when ≥50%. At angiography, it was detected RAS ≥50% in 18 patients, 5 with bilateral stenosis. After contrast, the examination time was slightly reduced by approximately 20%. In non-enhanced US the sensitivity was better when based on resistance index (82.9%) while the specificity was better when based on renal aortic ratio (89.2%). The predictive positive value was stable for all indexes (74.0%–88.0%) while negative predictive value was low (44%–51%). The specificity and positive predictive value based on renal aortic ratio increased after PESDA injection respectively, from 89 to 97.3% and from 88 to 95%. In hypertensives suspected to have RAS the sensitivity and specificity of Duplex US is dependent of the criterion evaluated. Enhancement with continuous infusion of PESDA improves only the specificity based on renal aortic ratio but do not modify the sensitivity of any index.

Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

Background:The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression. Methods Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes. Results and Discussion We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent in situ hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age. Conclusion Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches.

Observational study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers - protocol study

Abstract Background Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances. Methods/Design An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow. Discussion Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers.

Quantification of fractal dimension and Shannon’s entropy in histological diagnosis of prostate cancer

Background: Prostate cancer is a serious public health problem that affects quality of life and has a significant mortality rate. The aim of the present study was to quantify the fractal dimension and Shannon’s entropy in the histological diagnosis of prostate cancer. Methods: Thirty-four patients with prostate cancer aged 50 to 75 years having been submitted to radical prostatectomy participated in the study. Histological slides of normal (N), hyperplastic (H) and tumor (T) areas of the prostate were digitally photographed with three different magnifications (40x, 100x and 400x) and analyzed. The fractal dimension (FD), Shannon’s entropy (SE) and number of cell nuclei (NCN) in these areas were compared. Results: FD analysis demonstrated the following significant differences between groups: T vs. N and H vs. N groups (p < 0.05) at a magnification of 40x; T vs. N (p < 0.01) at 100x and H vs. N (p < 0.01) at 400x. SE analysis revealed the following significant differences groups: T vs. H and T vs. N (p < 0.05) at 100x; and T vs. H and T vs. N (p < 0.001) at 400x. NCN analysis demonstrated the following significant differences between groups: T vs. H and T vs. N (p < 0.05) at 40x; T vs. H and T vs. N (p < 0.0001) at 100x; and T vs. H and T vs. N (p < 0.01) at 400x. Conclusions: The quantification of the FD and SE, together with the number of cell nuclei, has potential clinical applications in the histological diagnosis of prostate cancer.

Clinical judgment to estimate pretest probability in the diagnosis of Cushing's syndrome under a Bayesian perspective

OBJECTIVE: To estimate the pretest probability of Cushing's syndrome (CS) diagnosis by a Bayesian approach using intuitive clinical judgment. MATERIALS AND METHODS: Physicians were requested, in seven endocrinology meetings, to answer three questions: "Based on your personal expertise, after obtaining clinical history and physical examination, without using laboratorial tests, what is your probability of diagnosing Cushing's Syndrome?"; "For how long have you been practicing Endocrinology?"; and "Where do you work?". A Bayesian beta regression, using the WinBugs software was employed. RESULTS: We obtained 294 questionnaires. The mean pretest probability of CS diagnosis was 51.6% (95%CI: 48.7-54.3). The probability was directly related to experience in endocrinology, but not with the place of work. CONCLUSION: Pretest probability of CS diagnosis was estimated using a Bayesian methodology. Although pretest likelihood can be context-dependent, experience based on years of practice may help the practitioner to diagnosis CS. Arq Bras Endocrinol Metab. 2012;56(9):633-7