Validity and applicability of the Mini International Neuropsychiatric Interview administered by family medicine residents in primary health care in Brazil

Objective: To evaluate the validity and applicability of the Mini International Neuropsychiatric Interview (MINI) used by family medicine residents in primary health care (PHC) in Brazil. Methods: Training for administrating the MINI was given as part of a broad psychiatry education program. Interviews were held with 120 PHC patients who were at least 15 years old. MINI was administered by 25 resident physicians, while the Structured Clinical Interview for Diagnosis (SCID) was administered by a psychiatrist blind to patients` results on the MINI, and the diagnoses on both interviews were compared. The resident physicians answered questions on the applicability of the MINI. Results: Concordance levels for any mental disorder, the broader current diagnostic categories and the most common specific diagnoses were analyzed. Kappa coefficients ranged between 0.65 and 0.85; sensitivity, between 0.75 and 0.92; specificity, between 0.90 and 0.99; positive predictive values (PPV), between 0.60 and 0.86; negative predictive values (NPV), between 0.92 and 0.99; and accuracy, between 0.88 and 0.98. The resident physicians considered MINI comprehensibility and clinical relevance satisfactory. Conclusions: These good psychometric results in a real-world setting may be related to a special training program, which is more frequent, intensive and diversified. In these conditions, the MINI is a useful tool for general practitioners. (c) 2008 Elsevier Inc. All rights reserved.

Anxiolytic and panicolytic effects of escitalopram in the elevated T-maze

Escitalopram is a highly selective inhibitor of serotonin re-uptake that is used to treat anxiety disorders. In the present study, we investigated the effects of acute, sub-chronic ( 14 days) and chronic ( 21 days) administration of escitalopram ( 2, 4 and 8 mg/kg, P0) on the performance of rats in the elevated T-maze. For comparison, imipramine ( 15 mg/ kg, P0) was also studied. The apparatus is made of three elevated arms of equal dimension, one enclosed transversal to the two open arms. Inhibitory avoidance of the open arms, trained in the enclosed arm, has been related to generalised anxiety disorder, while one-way escape from one open arm, to panic disorder. After acute administration, the three doses of escitalopram impaired avoidance ( anxiolytic effect), while imipramine was ineffective. Escape was unaffected by either drug. With sub-chronic administration, both drugs were ineffective on either avoidance or escape. After chronic treatment, avoidance was impaired by imipramine and by the two highest doses of escitalopram. In addition, escape was impaired (panicolytic effect) by imipramine and by the highest dose of escitalopram. Locomotion measured in a square arena was increased by the three doses of escitalopram, given chronically. Therefore, both imipramine and escitalopram had anxiolytic and panicolytic-like effects after chronic administration, but acutely only escitalopram decreased anxiety. Since no such effect was observed following subchronic administration, it is likely that the mechanisms of the early and late anxiolytic actions of escitalopram are different.

Glutamate and the neural basis of the subjective effects of ketamine

Context: Ketamine evokes psychosislike symptoms, and its primary action is to impair N-methyl-D-aspartate glutamate receptor neurotransmission, but it also induces secondary increases in glutamate release. Objectives: To identify the sites of action of ketamine in inducing symptoms and to determine the role of increased glutamate release using the glutamate release inhibitor lamotrigine. Design: Two experiments with different participants were performed using a double-blind, placebo-controlled, randomized, crossover, counterbalanced-order design. In the first experiment, the effect of intravenous ketamine hydrochloride on regional blood oxygenation level dependent (BOLD) signal and correlated symptoms was compared with intravenous saline placebo. In the second experiment, pretreatment with lamotrigine was compared with placebo to identify which effects of ketamine are mediated by increased glutamate release. Setting: Wellcome Trust Clinical Research Facility, Manchester, England. Participants: Thirty-three healthy, right-handed men were recruited by advertisements. Interventions: In experiment 1, participants were given intravenous ketamine (1-minute bolus of 0.26 mg/ kg, followed by a maintenance infusion of 0.25 mg/ kg/ h for the remainder of the session) or placebo (0.9% saline solution). In experiment 2, participants were pretreated with 300 mg of lamotrigine or placebo and then were given the same doses of ketamine as in experiment 1. Main Outcome Measures: Regional BOLD signal changes during ketamine or placebo infusion and Brief Psychiatric Rating Scale and Clinician- Administered Dissociative States Scale scores. Results: Ketamine induced a rapid, focal, and unexpected decrease in ventromedial frontal cortex, including orbitofrontal cortex and subgenual cingulate, which strongly predicted its dissociative effects and increased activity in mid- posterior cingulate, thalamus, and temporal cortical regions (r= 0.90). Activations correlated with Brief Psychiatric Rating Scale psychosis scores. Lamotrigine pretreatment prevented many of the BOLD signal changes and the symptoms. Conclusions: These 2 changes may underpin 2 fundamental processes of psychosis: abnormal perceptual experiences and impaired cognitive- emotional evaluation of their significance. The results are compatible with the theory that the neural and subjective effects of ketamine involve increased glutamate release.

NF-kappa b expression predicts clinical outcome for nasal polyposis

Objective: To correlate clinical prognosis of patients with nasal polyps to the expression of p65, c-Fos, GR alpha and GR beta. Methods: A biopsy was obtained at the first evaluation of patients with nasal polyps, and at rhinoplasty for control mucosa. Patients with nasal polyps were treated with glucocorticoids and followed for at least 60 months. The expression of p65, c-Fos, GR alpha and GR beta was determined by Real Time-PCR and correlated to clinical outcome. The end-point of resistance to glucocorticoid therapy was considered when surgery was indicated. Results: Patients with nasal polyps presented a higher expression of p65, a lower expression of GR alpha, and a lower GR alpha/GR beta ratio than control mucosa. The patients with nasal polyps who had a higher expression of p65 correlated with a poorer response to glucocorticoids, with a 3.5-fold higher risk for surgery. Conclusion: Patients with a higher p65 (NF-kappa B) expression at diagnosis were associated to a worse response to clinical treatment, suggesting one of the mechanisms of cell resistance to glucocorticoid treatment in patients with nasal polyps.

Epidemiologic aspects and clinical outcome of fungal keratitis in southeastern Brazil

PURPOSE. Fungal keratitis (FK) is a sight-threatening disease, more prevalent in developing regions. The present retrospective study was conducted in order to evaluate the epidemiologic and clinical aspects and the progression of FK in patients treated at two ophthalmologic reference centers in Southeast Brazil. METHODS. The charts of patients with infectious keratitis treated between 2000 and 2004 were reviewed. For the 66 cases of FK confirmed by microbiological analysis, data related to patient, disease, and therapeutic approaches were obtained. RESULTS. Mean patient age was 40.7 +/- 16 years. Fifty-three were men and 13 were women. Ocular trauma occurred in 40% of cases (27). Previous medications taken by the patients were quinolone in 72.5% and antimycotics in 30%. Visual acuity (VA) at presentation was >0.3 in 16% and <0.1 in 74.5%. Penetrant keratoplasty was performed in 38% and evisceration in 15%. The causing agents were Fusarium sp in 67%, Aspergillus sp in 10.5%, and Candida sp in 10%. Medication alone resolved 39% of cases within a mean period of 24.5 +/- 12 days. Final VA was >0.3 in 28%, and <0.1 in 63%. CONCLUSIONS. Fungal keratitis presented as a disease with severe complications, predominantly among young males, and was mostly caused by filamentous fungi. The present information permits the establishment of preventive strategies. Reducing the time between onset and treatment and using more accessible specific medication would reverse the negative prognosis. (Eur J Ophthalmol 2009; 19: 355-61)

Clinical Validity of the Protocol for Multi-Professional Centers for the Determination of Signs and Symptoms of Temporomandibular Disorders. Part II

The aims of this study were to analyze the criterion and construct validity of Part II of the protocol for multi-professional centers for the determination of signs and symptoms of temporomandibular disorders (ProTMDMulti) as a measure of TMD severity. The study was conducted on eight asymptomatic subjects (CG) and 30 subjects with articular TMD (TMDG), according to the Research Diagnostic Criteria for TMD (RDC/TMD). The ProTMDMulti-Part II was validated using the Helkimo Clinical Dysfunction Index (Di). The construct validity was tested using the analysis of the ability of ProTMDMulti-part II to differentiate the CG from the TMDG and to measure the changes that occurred in the TMDG between the period before and after TMD treatment. Correlations between the Di and the ProTMDMulti-Part II scores were calculated using the Spearman test. Inter- and intragroup comparisons were made (p<0.05). There was a statistically significant correlation between the Helkimo Clinical Dysfunction Index (Di) and the severity scores of the ProTMDMulti-Part II. There was a significant difference between TMDG and CG regarding the severity of signs and symptoms. The present study provides statistical evidence of the clinical validity of the ProTMDmulti-Part II as a measure of the severity of TMD symptoms.

Dry eye in childhood: Epidemiological and clinical aspects

Because dry eye disease is rare in children and its pathogenesis is less well known than in adults, its diagnosis is often overlooked. It can occur in association with a number of congenital, autoimmune, endocrine, and inflammatory disorders, or under certain environmental and nutritional conditions. In some cases, early detection allows the underlying cause of the dry eye to be successfully treated and eliminated. In other cases, the disease may represent a lifelong problem, whose proper management can prevent ulceration and scarring of the ocular surface. Because of the association of pediatric dry eye with other conditions, a multidisciplinary approach to diagnosis and treatment is usually required. The purpose of this review is to enhance physician awareness of dry eye in children, to describe the most frequently associated conditions, and to discuss the diagnostic and therapeutic options available.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis

Objective To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America. Methods Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course. Results Four hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron`s papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians. Conclusion The demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

Is Suppression of Hypothalamic-Pituitary-Adrenal Axis Significant During Clinical Treatment of Phimosis?

Purpose: Corticoids have been an option for phimosis treatment since 1993. However, long-term use or repeated cycles pose a concern regarding drug absorption and consequent systemic effects. The aim of this study was to investigate the effect of topical corticoids used in treating phimosis on the hypothalamus-pituitary-adrenal axis in children. Materials and Methods: A total of 31 children were included in the study. Cortisol secretion was evaluated by the measurement of salivary cortisol in saliva samples collected at 9:00 a.m, before starting treatment and after 8 weeks of topical treatment with 0.05% clobetasol propionate. Salivary cortisol was determined by radioimmunoassay. To confirm that use of clobetasol propionate was not detected by the assay, the presence of cortisol circadian rhythm was checked by an extra saliva sample obtained at 11:00 p.m. from 10 children, and was observed to be maintained in all of them. Results: No significant difference in salivary cortisol levels was observed between samples obtained at 9:00 a.m. before starting treatment and after completing treatment when the entire group was analyzed. However, in 2 children the salivary cortisol levels after treatment were lower than the cutoff value (358 ng/dl) assumed to be suggestive of hypothalamus-pituitary-adrenal axis suppression. Conclusions: Topical clobetasol propionate used twice daily for clinical treatment of phimosis does not affect the hypothalamus-pituitary-adrenal axis in most patients. However, salivary cortisol level should be considered as a laboratory marker in long-term treatment or during repeated cycles to detect possible hypothalamus-pituitary-adrenal axis suppression.

Methotrexate Withdrawal at 6 vs 12 Months in Juvenile Idiopathic Arthritis in Remission A Randomized Clinical Trial

Context Novel therapies have improved the remission rate in chronic inflammatory disorders including juvenile idiopathic arthritis (JIA). Therefore, strategies of tapering therapy and reliable parameters for detecting subclinical inflammation have now become challenging questions. Objectives To analyze whether longer methotrexate treatment during remission of JIA prevents flares after withdrawal of medication and whether specific biomarkers identify patients at risk for flares. Design, Setting, and Patients Prospective, open, multicenter, medication-withdrawal randomized clinical trial including 364 patients (median age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of the phagocyte activation marker myeloid-related proteins 8 and 14 heterocomplex (MRP8/14) were determined. Intervention Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after induction of disease remission. Main Outcome Measures Primary outcome was relapse rate in the 2 treatment groups; secondary outcome was time to relapse. In a prespecified cohort analysis, the prognostic accuracy of MRP8/14 concentrations for the risk of flares was assessed. Results Intention-to-treat analysis of the primary outcome revealed relapse within 24 months after the inclusion into the study in 98 of 183 patients (relapse rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2. The odds ratio for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P=.86). The median relapse-free interval after inclusion was 21.0 months in group 1 and 23.0 months in group 2. The hazard ratio for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P=.61). Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares (median, 715 [IQR, 320-1110] ng/mL) compared with patients maintaining stable remission (400 [IQR, 220-800] ng/mL; P=.003). Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test (area under the receiver operating characteristic curve, 0.76; 95% CI, 0.62-0.90). Conclusions In patients with JIA in remission, a 12-month vs 6-month withdrawal of methotrexate did not reduce the relapse rate. Higher MRP8/14 concentrations were associated with risk of relapse after discontinuing methotrexate.

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.

Tolerance to the cataleptic effect that follows repeated nitric oxide synthase inhibition may be related to functional enzymatic recovery

Systemic or intra-striatal acute administration of nitric oxide synthase (NOS) inhibitors causes catalepsy in rodents. This effect disappears after sub-chronic treatment. The aim of the present study was to investigate if this tolerance is related to changes in the expression of NOS or dopamine-2 (D(2)) receptor or to a recovery of NOS activity. Male albino Swiss mice (25-30 g) received single or sub-chronic (once a day for 4 days) i.p. injections of saline or L-nitro-arginine (L-NOARG, 40 mg/kg), a non-selective inhibitor of neuronal nitric oxide synthase (nNOS). Twenty-four hours after the last injection, the animals were killed and their brains were removed for immunohistochemistry assay to detect the presence of nNOS or for `in-situ` hybridisation study using (35)S-labeled oligonucleotide probe complementary to D(2) receptor mRNA. The results were analysed by computerised densitometry. Independent groups of animals received the same treatment, but were submitted to the catalepsy test and had their brain removed to measure nitrite and nitrate (NOx) concentrations in the striatum. Acute administration of L-NOARG caused catalepsy that disappeared after sub-chronic treatment. The levels of NOx were significantly reduced after acute L-NOARG treatment. The decrease in NOx after drug injection suffered a partial tolerance after sub-chronic treatment. The catalepsy time after acute or sub-chronic treatment with L-NOARG was negatively (r = -0.717) correlated with NOx levels. Animals that received repeated L-NOARG injections also showed an increase in the number of nNOS-positive neurons in the striatum. No change in D(2) receptor mRNA expression was found in the dorsal striatum, nucleus accumbens and substantia nigra. Together, these results suggest that tolerance to L-NOARG cataleptic effects do not depend on changes in D(2) receptors. They may depend, however, on plastic changes in nNOS neurons resulting in partial recovery of NO formation in the striatum.

Clinical and Immunological Insights on Severe, Adverse Neurotropic and Viscerotropic Disease following 17D Yellow Fever Vaccination

Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-gamma R in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3(+) CD16(+/-) CD56(+/-)/CD3(+) ratio), activated T cells (CD4(+) and CD8(+) cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated ex vivo intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-gamma(+)], tumor necrosis factor alpha positive [TNF-alpha(+)], and IL-4 positive [IL-4(+)]), CD8(+) T cells (IL-4(+) and IL-5(+)), and B lymphocytes (TNF-alpha(+), IL-4(+), and IL-10(+)). The analysis of CD4(+) T cells revealed a complex profile that consisted of an increased frequency of IL-12(+) and IFN-gamma(+) cells and a decreased percentage of TNF-alpha(+), IL-4(+), and IL-5+ cells. Depressed cytokine synthesis was observed in monocytes (TNF-alpha(+)) following the provision of antigenic stimuli in vitro. These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD.

Validation of the Brazilian version of the quality of life scale for patients with Alzheimer`s disease and their caregivers (QOL-AD)

Quality of life (QOL) has been extensively studied in clinical trials and in research on chronic degenerative diseases and dementia. The aim of this study was to assess the reliability and construct validity of the Brazilian version of the QOL scale in Alzheimer`s disease (AD; QOL-AD). The QOL-AD was administered to 60 patients with mild or moderate AD and to their caregivers. The construct validation was accomplished through correlations amongst total scores of patients` and caregivers` reports on patients` quality of life (PQOL and C-PQOL, respectively), and data related to cognitive impairment, depressive symptoms, functional performance, behavioral disturbances and a generic instrument of quality of life (WHOQOL-brief), as well as correlation of total score of caregivers` reports on their own quality of life (CQOL) with the measurements cited above, QOL-AD patient reports, and depressive symptoms. The reliability was high for PQOL, C-PQOL, and CQOL versions (Cronbach`s alpha = 0.80, 0.83, and 0.86, respectively). We observed significant correlations in the construct validity of all three versions regarding the variables associated with the disease and also with WHOQOL-brief. The scale took, on average, six min for each version. The results indicate reliability and construct validity of the Brazilian version of the QOL-AD in the studied sample.

Evaluation of the performance of normal elderly in a limb praxis protocol: Influence of age, gender, and education

Limb praxis can be influenced by age, gender, and education. The present Study investigated the influence of these variables on gesture production by healthy elderly Subjects. We evaluated 96 individuals divided into two age groups (60-74 and 75-88 years). Each group contained 48 men and 48 women and was subdivided into four groups according to education: illiterates and 1-3, 4-7, and 8 or more years of education. Individuals were requested to carry Out tasks oil verbal command and imitation. There were no differences between the performance of men and women, while older individuals performed worse than their younger counterparts. Regarding educational level, three major groups emerged: illiterates, individuals with 1-7 years of education, and those with 8 or more years of education. In conclusion, age and education significantly influenced the performance of individuals in limb praxis tests. (JINS, 2009, 157 618-622.)