Wilson’s disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene

OBJECTIVE: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.

Temporomandibular disorders in headache patients

Objective: To identify the frequency of signs and symptoms of temporomandibular disorder (TMD) and its severity in individuals with headache. Study Design: 60 adults divided into three groups of 20 individuals: chronic daily headache (CDH), episodic headache (EH) and a control group without headache (WH). Headache diagnosis was performed according to the criteria of International Headache Society and the signs and symptoms of TMD were achieved by using a clinical exam and an anamnestic questionnaire. The severity of TMD was defined by the temporomandibular index (TMI). Results: The TMD signs and symptoms were always more frequent in individuals with headache, especially report of pain in TMJ area (CDH, n=16; EH, n=12; WH, n=6), pain to palpation on masseter (CDH, n=19; EH, n=16; WH, n=11) which are significantly more frequent in episodic and chronic daily headache. The mean values of temporomandibular and articular index (CDH patients) and muscular index (CDH and EH patients) were statistically higher than in patients of the control group, notably the articular (CDH=0.38; EH=0.25; WH=0.19) and muscular (CDH=0.46; EH=0.51; WH=0.26) indices. Conclusions: These findings allow us to speculate that masticatory and TMJ pain are more common in headache subjects. Besides, it seems that the TMD is more severe in headache patients.

How Should the Articular Disk Position Be Analyzed?

Purpose: To compare 2 methods used to determine the disk position based on sagittal magnetic resonance images. Patients and Methods: A cross-sectional study of patients with the signs and symptoms of temporomandibular disorders was conducted. The patients' ages and gender distributions were collected. The disk position diagnosis from the clinical examination was considered the primary outcome. Three observers evaluated the presence of anterior displacement on magnetic resonance images according to 2 criteria: method 1 (12-o'clock position) and method 2 (location of the intermediate zone). To assess the intraobserver variability of the 2 methods, the examiners evaluated the same magnetic resonance images at the beginning of the study (time 1) and 40 days later (time 2). The intraobserver agreement was assessed using the observed agreement and the kappa statistic. McNemar's test was used to assess the differences between each method and the clinical examination findings (P < .05). The accuracy, sensitivity, specificity, and positive and negative predictive values were calculated by comparing the diagnosis from each method with that from the clinical examination (considered the reference standard). Results: The final sample was composed of 20 subjects with a mean age of 33.0 +/- 33.7 years; 3 were men (15%) and 17 were women (85%). A statistically significant difference between the 2 methods was found. Method 1 yielded a greater percentage of anterior displaced disks (52.5%). The agreement between the clinical diagnosis and method 1 was lower (70.0%) than that between the clinical diagnosis and method 2 (87.5%). No statistically significant difference was found between the clinical diagnosis and method 2. Conclusion: The disk position should be judged according to the intermediate zone criterion. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:1534-1539, 2012

Delay in the search for health services for the diagnosis of tuberculosis in Ribeirao Preto, Sao Paulo

The scope of this paper is to analyze delays in locating health services for the diagnosis of tuberculosis in Ribeirao Preto in 2009. An epidemiological and cross-sectional study was conducted with 94 TB patients undergoing treatment. A structured questionnaire, based on the Primary Care Assessment Tool adapted for TB care was used. A median (15 days or more) was established to characterize delay in health attendance. Using the Prevalence Ratio, the variables associated with longer delay were identified. The first healthcare services sought were the Emergency Services (ES) (57.5%). The longest period between seeking assistance occurred among males, aged between 50 and 59, who earned less than five minimum wages, had pulmonary TB, were new cases, were not co-infected with TB/HIV, did not consume alcohol, had satisfactory knowledge about TB before diagnosis (with a statistically significant association with delay) and who did not seek healthcare close to home before developing TB. There is a perceived need for training healthcare professionals about the signs and symptoms of the disease, reducing barriers of access to timely diagnosis of TB and widely disseminating it to the community in general.

Low Level Laser Therapy as an Adjunctive Technique In the Management of Temporomandibular Disorders

The purpose of this study was to assess the effect of low level laser therapy on subjects with intra-articular temporomandibular disorders (IA-TMD), and to quantify and compare severity of signs and symptoms before, during, and after the laser applications. The sample consisted of 45 subjects randomly divided into three groups (G) of 15 subjects each: G-I: 15 individuals with IA-TMD submitted to an energy dose of 52.5 J/cm(2); G-II: dose of 105.0 J/cm(2); and G-III: placebo group (0 J/cm(2)). In all groups, the applications were performed on condylar points on the masseter and anterior temporalis muscles. Two weekly sessions were held for five weeks, totaling 10 applications. The assessed variables were: mandibular movements and painful symptoms evoked by muscle palpation. These variables were measured before starting the study, then immediately after the first, fifth, and tenth laser application, and finally, 32 days after completing the applications. The results showed that there were statistically significant differences for G-I and G-II at the level of 1% between the doses, as well as between assessments. Therefore, it was concluded that the use of low level laser increased the mean mandibular range of motion and reduced painful symptoms in the groups that received effective treatment, which did not occur in the placebo group.

A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease

BACKGROUND Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. METHODS In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 mu g (82 patients) or 900 mu g (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 mu g twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. RESULTS Twelve of the 82 patients in the 600-mu g group and 21 of the 80 patients in the 900-mu g group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose- lowering medication was initiated in 74 of 162 patients. CONCLUSIONS The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropinsecreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.)

Quantification of Orbital Apex Crowding for Screening of Dysthyroid Optic Neuropathy Using Multidetector CT

BACKGROUND AND PURPOSE: DON, a serious complication of GO, is frequently difficult to diagnose clinically in its early stages because of confounding signs and symptoms of congestive orbitopathy. We evaluated the ability of square area measurements of orbital apex crowding, calculated with MDCT, to detect DON. MATERIALS AND METHODS: Fifty-six patients with GO were studied prospectively with complete neuro-ophthalmologic examination and MDCT scanning. Square measurements were taken from coronal sections 12 mm, 18 mm, and 24 mm from the interzygomatic line. The ratio between the extraocular muscle area and the orbital bone area was used as a Cl. Intracranial fat prolapse through the superior orbital fissure was recorded as present or absent. Severity of optic nerve crowding was also subjectively graded on corona! images. Orbits were divided into 2 groups (with or without clinical evidence of DON) and compared. RESULTS: Ninety-five orbits (36 with and 59 without DON) were studied. The CIs at all 3 levels and the subjective crowding score were significantly greater in orbits with DON (P<.001). No significant difference was observed regarding intracranial fat prolapse (P=.105). The area under the ROC curves was 0.91, 0.93, and 0.87 for CIs at 12, 18, and 24 mm, respectively. The best performance was at 18 mm, where a cutoff value of 57.5% corresponded to 91.7% sensitivity, 89.8% specificity, and an odds ratio of 97.2 for detecting DON. A significant correlation (P<.001) between the CIs and VF defects was observed. CONCLUSIONS: Orbital Cls based on area measurements were found to predict DON more reliably than subjective grading of orbital crowding or intracranial fat prolapse.

Sintomas depressivos em idosos: análise dos itens da Escala de Depressão Geriátrica

OBJETIVOS: Verificar a estrutura fatorial da Escala de Depressão Geriátrica de 15 itens em uma amostra de idosos assistidos pela Estratégia Saúde da Família, descrever o perfil social e analisar as respostas aos itens da Escala de Depressão Geriátrica. MÉTODOS: Estudo de delineamento transversal com 503 idosos assistidos pela Estratégia Saúde da Família, em Dourados, MS. Para analisar as respostas da EDG 15, utilizou-se o teste de Qui-quadrado de Mantel-Haenzsel (p <0,05). A análise fatorial, a consistência interna e a generalidade dos resultados para a população foram realizadas. RESULTADOS: Dos 503 idosos pesquisados 69,0% eram mulheres, 53,1% não letrados, 53,7% tinham 70 anos ou mais e 34,4% apresentavam depressão. A análise fatorial identificou quatro fatores (apatia, desesperança, desmotivação e isolamento). A estrutura da EDG 15 não se mostrou apropriada para a generalização de resultados. CONCLUSÃO: Dentre os idosos com depressão, predominaram a apatia e o isolamento. Cabe às equipes de saúde promover atividades físicas, recreativas e culturais para minimizar esse quadro. Novas pesquisas serão necessárias, sobretudo para análise da estrutura fatorial.

Erythema induratum of Bazin associated with Addison's disease: first description

CONTEXT: Erythema induratum of Bazin (EIB) is considered to be a tuberculid reaction and consists of recurrent painful nodules. The differential diagnosis includes diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. CASE REPORT: We report the case of a woman with EIB who developed Addison's disease during treatment with anti-tuberculosis drugs with good response to glucocorticoid replacement. The diagnosis was obtained through the clinical picture, positive tuberculin test and positive BCG (bacillus Calmette-Guérin) test on the histological sample. Anti-tuberculosis drugs and glucocorticoid replacement led to disappearance of the signs and symptoms. CONCLUSIONS: This is the first description of an association between EIB and Addison's disease. It should be borne in mind that tuberculosis is an important etiological factor for Addison's disease.

Frequency of Toxocara infection in children attended by the health public service of Maringá, south Brazil.

The lack of specific laboratorial diagnosis methods and precise symptoms makes the toxocariasis a neglected disease in Public Health Services. This study aims to determine the frequency of Toxocara spp. infection in children attended by the Health Public Service of Hospital Municipal de Maringá, South Brazil. To evaluate the association of epidemiological and clinical data, and observational and cross-section study was carried out. From 14,690 attended children/year aged from seven month to 12 years old, 450 serum samples were randomly collected from September/2004 to September/2005. A questionnaire was used to evaluate epidemiological, clinical and hematological data. An ELISA using Toxocara canis larval excretory-secretory products as antigen detected 130 (28.8%) positive sera, mainly between children from seven month to five years old (p = 0.0016). Significant correlation was observed between positive serology for Toxocara, and frequent playing in sandbox at school or daycare center (p = 0.011) and the presence of a cat at home (p = 0.056). From the families, 50% were dog owners which exposed soil backyards. Eosinophilia (p = 0.776), and signs and symptoms analyzed (fever p = 0.992, pneumonia p = 0.289, cold-like symptoms p = 0.277, cough p =0.783, gastrointestinal problems p = 0.877, migraine p = 0.979, abdominal pain p = 0.965, joint pain p = 0.686 and skin rash p = 0.105) could not be related to the presence of anti-Toxocara antibodies. Therefore, two asthmatics children showed titles of1:10,240 and accentuated eosinophilia (p = 0.0001). The authors emphasize the needs of prevention activities.

Late-onset social anxiety disorder following traumatic brain injury

Background: Neuropsychiatric sequelae are the predominant long-term disability after traumatic brain injury (TBI). This study reports a case of late-onset social anxiety disorder (SAD) following TBI. Case report: A patient that was spontaneous and extroverted up to 18-years-old started to exhibit significant social anxiety symptoms. These symptoms became progressively worse and he sought treatment at age 21. He had a previous history of traumatic brain injury (TBI) at age 17. Neuroimaging investigations (CT, SPECT and MRI) showed a bony protuberance on the left frontal bone, with mass effect on the left frontal lobe. He had no neurological signs or symptoms. The patient underwent neurosurgery with gross total resection of the lesion and the pathological examination was compatible with intradiploic haematoma. Conclusions: Psychiatric symptoms may be the only findings in the initial manifestation of slowly growing extra-axial space-occupying lesions that compress the frontal lobe from the outside. Focal neurological symptoms may occur only when the lesion becomes large. This case report underscores the need for careful exclusion of general medical conditions and TBI history in cases of late-onset SAD and may also contribute to the elucidation of the neurobiology of this disorder.

Occurrence and behavior of butyltins in intertidal and shallow subtidal surface sediments of an estuarine beach under different sampling conditions

Contamination by butyltin compounds (BTs) has been reported in estuarine environments worldwide, with serious impacts on the biota of these areas. Considering that BTs can be degraded by varying environmental conditions such as incident light and salinity, the short-term variations in such factors may lead to inaccurate estimates of BTs concentrations in nature. Therefore, the present study aimed to evaluate the possibility that measurements of BTs in estuarine sediments are influenced by different sampling conditions, including period of the day (day or night), tidal zone (intertidal or subtidal), and tides (high or low). The study area is located on the Brazilian southeastern coast, Sao Vicente Estuary, at Pescadores Beach, where BT contamination was previously detected. Three replicate samples of surface sediment were collected randomly in each combination of period of the day, tidal zone, and tide condition, from three subareas along the beach, totaling 72 samples. BTs were analyzed by GC-PFPD using a tin filter and a VF-5 column, by means of a validated method. The concentrations of tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) ranged from undetectable to 161 ng Sn g(-1) (d.w.). In most samples (71%), only MBT was quantifiable, whereas TBTs were measured in only 14, suggesting either an old contamination or rapid degradation processes. DBT was found in 27 samples, but could be quantified in only one. MBT concentrations did not differ significantly with time of day, zones, or tide conditions. DBT and TBT could not be compared under all these environmental conditions, because only a few samples were above the quantification limit. Pooled samples of TBT did not reveal any difference between day and night. These results indicated that, in assessing contamination by butyltin compounds, surface-sediment samples can be collected in any environmental conditions. However, the wide variation of BTs concentrations in the study area, i.e., over a very small geographic scale, illustrates the need for representative hierarchical and composite sampling designs that are compatible with the multiscalar temporal and spatial variability common to most marine systems. The use of such sampling designs will be necessary for future attempts to quantitatively evaluate and monitor the occurrence and impact of these compounds in nature

Leakage of Saliva Through the Implant-Abutment Interface: In Vitro Evaluation of Three Different Implant Connections Under Unloaded and Loaded Conditions

Purpose: Bacterial leakage along the implant-abutment interface, with consequent species harboring the inner parts of two-part dental implant systems, has been reported in the literature. The aim of this in vitro study was to evaluate bacterial leakage from human saliva to the internal part of the implants along the implant-abutment interface under loaded and unloaded conditions using DNA Checkerboard. Materials and Methods: Sixty denial implants-20 each of external-hexagon, internal-hexagon, and Morse cone-connection designs-and their conical abutments were used in this study. Each group was subdivided into two groups of 10 loaded and 10 unloaded implants. The assemblies were immersed in human saliva and either (1) loaded with 500,000 cycles at 120 N (experimental group) or (2) incubated in static conditions for 7 days at 35 degrees C (unloaded control group). Results: Microorganisms were found in the internal surfaces of all types of connections. The Morse cone connection presented the lowest count of microorganisms in both the unloaded and loaded groups. Loaded implants presented with higher counts of microorganisms than unloaded implants for external- and internal-hex connections. Conclusion: Bacterial species from human saliva may penetrate along the implant-abutment interface under both unloaded and loaded conditions for all connections evaluated. Morse cone-connection implants showed the lowest counts of microorganisms for both conditions. External- and internal-hex implants showed a higher incidence of bacteria and higher bacterial counts after simulated loading. INT J ORAL MAXILLOFAC IMPLANTS 2012;27:551-560.

Analytical method for determination of nitric oxide in zebrafish larvae: Toxicological and pharmacological applications

Zebrafish are currently used at various stages of the drug discovery process and can be a useful and cost-effective alternative to some mammalian models. Nitric oxide (NO) plays an important role in physiology of zebrafish. The availability of appropriate analytical techniques to quantify the NO is crucial for studying its role in physiological and pathological conditions. This work aimed at establishing a high-performance liquid chromatography method for determination of NO levels in zebrafish larvae. Attempts were also made to assess the normal levels of NO at the first days postfertilization and the possible changes under pathological conditions. The method validation was quantitatively evaluated in terms of sensitivity, specificity, precision, accuracy, linearity, and recovery. NO levels from zebrafish larvae at the first days postfertilization and larvae challenged to N(G)-nitro-L-arginine methyl ester, sodium nitroprusside, Escherichia coil lipopolysaccharide, and copper sulfate were analyzed. The samples were derivatized with 2,3-diaminonaphthalene, and fluorescence detection was used for the indirect determination of NO. The method showed a good performance for all validation parameters evaluated and was efficient to monitor changes in NO concentration under physiological and pathophysiological conditions. This method might represent a powerful tool to be applied in NO studies with zebrafish larvae. (C) 2011 Elsevier Inc. All rights reserved.

Maximum Phonation Time and s/z Ratio in a Large Child Cohort

Aim. The purpose of this study was to provide normal values for maximum phonation time (MPT) and the s/z ratio by examining 1660 children aged 4-12 years and without vocal signs or symptoms. Methods. The technique was based on the sustained emission of the /a/ vowel and fricatives /s/ and /z/. Results. The average of the MPT in children of the different age groups was as follows: 6.09 seconds for the age group 4-6 years (males, 5.97; female, 6.21 seconds), 7.94 seconds for the age group 7-9 years (males, 8.07; females, 7.79 seconds), and 8.98 for the age group 10-12 years (males, 9.05; females, 8.92 seconds). The overall average for males was 7.78 and females 7.64 seconds. The s/z ratio was near 1.0 in most children but above 1.2 in 133 children and below 0.8 in 133 children. Conclusion. These values of MPT and s/z ratio can be used as normative in further pediatric studies.