Evaluation of the effects of chronic occupational exposure to metallic mercury on the thyroid parenchyma and hormonal function.

INTRODUCTION: Experiments in animals exposed to mercury (Hg) in different chemical states have shown thyroid parenchymal and hormone alterations. However, these experiments did not allow the establishment of dose-response curves or provide an understanding of whether these Hg effects on the thyroid parenchyma occur in humans. OBJECTIVE: To evaluate the association between chronic occupational exposure to metallic Hg and alterations in thyroid hormones and gland parenchyma 14 years after the last exposure. METHODS: A cross-sectional study including 55 males exposed in the past to metallic Hg and 55 non-exposed males, paired by age, was conducted in the Hospital das Clínicas (Brazil) from 2016 to 2017. Serum concentrations of total and free triiodothyronine (TT3 and FT3), free thyroxine (FT4), thyrotropin (TSH), reverse T3 (RT3), selenium and antithyroid antibody titers were obtained. The Hg and iodine concentrations were measured in urine. The thyroid parenchyma was evaluated by B-mode ultrasonography with Doppler. The nodules with aspects suspicious for malignancy were submitted to aspiration puncture with a thin needle, and the cytology assessment was classified by the Bethesda system. The t test or Mann-Whitney test, Chi-square test and Spearman correlation were used to compare the exposed and non-exposed groups and examine the relationships between the variables. Univariate and multivariate logistic regression models were used to trace determinants of the risk of thyroid hormone alteration. Statistical significance was defined by p < 0.05. RESULTS: The urinary Hg average was significantly higher in the exposed group than in the non-exposed group (p < 0.01). The mean TSH serum concentration in the exposed group was higher, with a statistically significant difference between the groups (p = 0.03). Serum concentrations of TSH exceeded the normality limit (4.20 µIU/ml) in 13 exposed individuals (27.3%) and 4 non-exposed individuals (7.3%), with a statistically significant association between the hormonal increase and exposure to Hg (p = 0.02). In the logistic regression model, exposure to Hg (yes or no) showed an odds ratio = 4.86 associated with an increase of TSH above the normal limit (p = 0.04). The serum concentrations of RT3 showed a statistically borderline difference between the groups (p = 0.06). There was no statistically significant difference between the mean TT3, FT3 and FT4 serum concentrations in the Hg-exposed group compared to the non-exposed group. The proportions of the echogenicity alterations were higher in the exposed group compared to the non-exposed group (27.3% versus 9.1%; p = 0.03). Papillary carcinomas were documented in three exposed individuals and one non-exposed individual. A follicular carcinoma was recorded in one non-exposed individual. CONCLUSIONS: Due to the higher serum TSH concentration and the prevalence of parenchymal alterations in the Hg-exposed group, even after cessation of exposure, it is recommended that the thyroid status of exposed workers be followed for a long period.

A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes.

PURPOSE: To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT, evaluating the response in subgroups with different GPx1 genotypes. METHODS: CAT patients (n = 55) with positive antiTPO were randomized to selenomethionine (SeMet) 200 µg daily (n = 28) or placebo (n = 27) for 3 months. Assessments included GPx1 genotyping at baseline and serum levels of plasma selenium, erythrocyte GPx1 activity, antiTPO and thyroid echogenicity at baseline, and 3 and 6 months. RESULTS: In the SeMet group, the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes. In the overall cohort, patients randomized to SeMet showed a 5 % decrease in antiTPO levels at 3 months (p = non-significant) and 20 % at 6 months (p < 0.001 versus 3 months). In contrast, patients in the placebo group did not show significant changes in antiTPO levels at any time point. Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet. CONCLUSIONS: Selenium supplementation decreased serum antiTPO levels in CAT patients, with similar response among patients with different GPx1 genotypes.

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS.

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields.

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.

Synthetic Elastography Using B-Mode Ultrasound Through a Deep Fully Convolutional Neural Network.

Shear-wave elastography (SWE) permits local estimation of tissue elasticity, an important imaging marker in biomedicine. This recently developed, advanced technique assesses the speed of a laterally traveling shear wave after an acoustic radiation force "push" to estimate local Young's moduli in an operator-independent fashion. In this work, we show how synthetic SWE (sSWE) images can be generated based on conventional B-mode imaging through deep learning. Using side-by-side-view B-mode/SWE images collected in 50 patients with prostate cancer, we show that sSWE images with a pixel-wise mean absolute error of 4.5 ± 0.96 kPa with regard to the original SWE can be generated. Visualization of high-level feature levels through t -distributed stochastic neighbor embedding reveals substantial overlap between data from two different scanners. Qualitatively, we examined the use of the sSWE methodology for B-mode images obtained with a scanner without SWE functionality. We also examined the use of this type of network in elasticity imaging in the thyroid. Limitations of the technique reside in the fact that networks have to be retrained for different organs, and that the method requires standardization of the imaging settings and procedure. Future research will be aimed at the development of sSWE as an elasticity-related tissue typing strategy that is solely based on B-mode ultrasound acquisition, and the examination of its clinical utility.

Influence of diaphragmatic mobility on exercise tolerance and dyspnea in patients with COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) present increased airway resistance, air trapping, pulmonary hyperinflation, and diaphragm muscle alterations, all of which affect pulmonary mechanics. PURPOSE: To evaluate the influence diaphragmatic mobility has on exercise tolerance and dyspnea in patients with COPD. MATERIALS AND METHODS: Fifty-four COPD patients with lung hyperinflation were evaluated to assess pulmonary function, diaphragm mobility, exercise tolerance, and dyspnea (score). Twenty healthy (age- and body mass index-matched) subjects were evaluated as controls. RESULTS: The COPD patients presented lower diaphragmatic mobility than did the controls (36.27+/-10.96 mm vs. 46.33+/-9.46 mm). Diaphragmatic mobility presented a linear correlation with distance covered on the 6-min walk test (6MWT) (r=0.38; p=0.005) and a negative correlation with dyspnea (r=-0.36; p=0.007). Patients were then divided into two subgroups based on the degree of diaphragmatic mobility: G1 (or=34 mm). Those in G1 presented poorer 6MWT performance and greater dyspnea upon exertion than did those in G2 (distance covered on the 6MWT: 454.76+/-100.67 m vs. 521.63+/-70.82 m; dyspnea score: 5.22+/-3.06 vs. 3.48+/-2.77). The G1 patients also presented greater residual volume (in liters) and lower maximal voluntary ventilation (in % of predicted values) than did the G2 patients (266.20+/-55.30 vs. 209.74+/-48.49 and 39.00+/-14.94 vs. 58.11+/-20.96). CONCLUSION: Diaphragmatic mobility influences dyspnea and exercise tolerance in patients with COPD.

Ultrasonography evaluation of bone lesions of the jaw.

The ultrasonographic aspects of 72 intraosseous lesions of the jaws were evaluated to identify the usefulness of this type of examination. The principal aim of ultrasonography was to recognize the lesion's content before surgical treatment. Four groups of lesions were classified after the definitive histopathologic examination: lesions with solid, liquid, dense liquid, and mixed contents. The initial ultrasonography examination was in agreement with the histopathologic findings in 24 (92.3%) cases with solid content, 17 (73.9%) cases with liquid content, 7 (7.7%) cases with dense liquid content, and 13 (92.8%) cases with mixed content. On the basis of the results of this study, we propose the use of ultrasonography as a complementary examination for intraosseous lesions of the jaws. If a liquid component is identified in ultrasonography, a surgical procedure should be performed immediately. Otherwise, if a lesion with solid component is identified, it should be biopsied for histopathologic examination and final diagnosis before definitive surgery.

Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck.

Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 microg of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 microg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 microg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

Reference values for Doppler ultrasound parameters of the thyroid in a healthy iodine-non-deficient population.

The aim of this study was to describe normal Doppler parameter values in the thyroid arteries in an iodine-replete region. 165 individuals were randomly selected in a community located in the south-east of Brazil. We obtained a clinical history on each subject and determined serum thyrotropin, antiperoxidase antibodies, thyrotropin receptor antibody (TRAb) and thyroid volumes through ultrasound. Subjects with thyroid disease and those under 20 years of age were excluded. 84 representative subjects (30 men and 54 women) remained. The systolic peak velocity (SPV), resistive index (RI) and pulsatility index (PI) in the superior and inferior thyroid arteries were measured using a 5-12 MHz linear probe. Except for the RI, the distribution of all Doppler parameters was non-gaussian. The median and mean references for the SPV, RI and PI were 24.80 cm s(-1) and 25.85 cm s(-1), 0.60 and 0.62, and 0.98 and 1.04, respectively, for superior thyroid arteries; these reference values for the inferior thyroid artery were 20.92 cm s(-1) and 21.50 cm s(-1), 0.57 and 0.57, and 0.84 and 0.88, respectively (p<0.001). Women had greater SPV values (p<0.01). We have determined reference thyroid Doppler parameter values in our iodine-non-deficient population and prepared tables by sex and age.

Differentiation between the two types of amiodarone-associated thyrotoxicosis using duplex and amplitude Doppler sonography.

PURPOSE: To evaluate the usefulness of Doppler parameters in the differentiation between the two types of amiodarone-associated thyrotoxicosis (AAT). MATERIAL AND METHODS: One hundred thirty-seven individuals were selected at our institution. They were divided into four groups: 84 normal subjects (N), 30 euthyroids taking amiodarone (A), 14 AAT type 1 patients (AAT1), and nine AAT type 2 patients (AAT2). Each AAT type was classified according to (131)I uptake and clinical outcome. Blindly, the resistance and pulsatility indexes (RI, PI), systolic peak velocity, and color pixel density (CPD) were calculated. RESULTS: AAT1 had greater CPD than AAT2 (P = 0.02). The latter group had similar vascularization to the N and A groups (P = 0.45). The area under the receiver operating characteristic (ROC) curve showed that systolic peak velocity in the inferior thyroid arteries and CPD were the best parameters in the differentiation between AAT type 1 and AAT type 2 (Az = 0.83 and 0.84, respectively). Impedance indexes were useless. CONCLUSION: Our results demonstrate that objective tests such as systolic peak velocities in the thyroid arteries and CPD are reliable parameters for differentiating between the two types of AAT.

Transcranial duplex doppler ultrasonography in dogs with hydrocephalus / Ultrassonografia duplex Doppler transcraniana em cães com hidrocefalia

Transcranial duplex Doppler ultrasound was performed in 32 conscious dogs presenting ventriculomegaly detected in B-mode, obtaining measures of lateral ventricles and resistance parameters of main cerebral arteries before and after 30 days of clinical treatment. The animals were distributed divided in two groups: group 1, dogs that presented remission or decrease of the neurological signs of the disease after clinical therapy; and group 2, dogs that displayed worsening of the neurological signs or clinical stability. The data were all presented in tables and were submitted to paired t test and to logistic regression models to evaluate the influence of the RI reduction on both groups. There was no significant influence of the variables in the B-mode. After the treatment, the mean resistive index (RI) was significantly lower for the group that presented clinical improvement. There was no significant difference of the mean RI reduction for the same artery when the right and left sides were compared. It could be concluded that transcranial duplex Doppler ultrasound is a method of cerebral hemodynamic assessment able to monitor more precisely the treatment of hydrocephalus in dogs and verify the responses.

Foi realizada a ultrassonografia duplex Doppler transcraniana em 32 cães, conscientes, que apresentavam ventriculomegalia previamente detectada ao exame modo-B, para obter as medidas dos ventrículos laterais e os parâmetros de resistência das artérias cerebrais antes e depois de 30 dias de tratamento clínico. Os animais foram distribuídos em dois grupos: 1 - formado por cães que apresentaram remissão ou diminuição dos sinais clínicos após tratamento; 2 - por cães que apresentaram piora dos sinais neurológicos ou estabilidade do quadro clínico. Todos os dados foram dispostos em tabelas e submetidos ao teste t pareado e a modelos de regressão logística para avaliar a influência da redução do índice de resistividade (IR). Não foi observada influência das variáveis em modo-B. Após o tratamento, a média do IR foi significantemente menor para o grupo que apresentou melhora clínica; não houve diferença significativa da média de redução do IR para a mesma artéria quando comparados os lados direito e esquerdo. Concluiu-se que o duplex Doppler transcraniano é um métodos de avaliação hemodinâmica capaz de monitorar mais precisamente o tratamento da hidrocefalia em cães e verificar a resposta dos pacientes.

Uso do ultra-som dúplex Doppler no diagnóstico de shunt portossistêmico em gatos / Portosystemic shunt diagnosis using duplex Doppler ultrasonography in cats

Realizaram-se exames ultra-sonográficos dúplex-Doppler abdominal em dois gatos que apresentavam sinais clínicos de encefalopatia hepática. Os principais achados ultra-sonográficos foram: identificação de um vaso anômalo tortuoso desviando o fluxo portal, velocidade de pico sistólico portal aumentada, presença de fluxo turbulento na veia cava caudal e redução do tamanho do fígado e do calibre dos vasos portais. Os achados de necropsia confirmaram os resultados dos exames ultra-sonográficos e clínicos. Pode-se concluir que o diagnóstico de shunt portossistêmico deve ser uma hipótese a ser considerada em gatos com sinais clínicos de encefalopatia hepática.

Abdominal duplex Doppler ultrasonography was used in two cats with hepatic encephalopathy clinical signs. The main ultrasonographic findings were: identification of a tortuous strange vessel shunting portal flow; elevated portal flow velocity; turbulence in the caudal vena cava, and reduced size of liver and hepatic portal branches. Necropsy findings were similar to that found at ultrasonographic and clinical exams. It is concluded that portosystemic shunt diagnosis may be a real hypothesis to be considered in cats with clinical signs of hepatic encephalopathy.

Ultra-sonografia transcraniana em cães com distúrbios neurológicos de origem central / Transcranial ultrasonography in dogs with central neurologycal disorders

Avaliaram-se 55 cães com distúrbios neurológicos e verificou-se a ocorrência de afecções neurológicas de origem central, detectadas pela ultra-sonografia transcraniana (USTC). Vinte e nove (52,9 por cento) animais apresentaram diagnóstico compatível com hidrocefalia, e destes, 16 (55,1 por cento) eram fêmeas e 15 (51,7 por cento) tinham menos de dois anos. Quinze (27,3 por cento) cães apresentaram lesões focais, quatro (7,2 por cento), alterações difusas e quatro (7,2 por cento) apresentavam imagens sugestivas de lissencefalia; em três (5,4 por cento) não foram detectadas alterações pela USTC. A hidrocefalia foi o distúrbio neurológico de origem central mais freqüente e a USTC é uma alternativa viável para auxiliar na rotina clínica veterinária como ferramenta diagnóstica na detecção de alterações morfológicas e estruturais do cérebro no cão

In this work, 55 dogs with neurologycal disorder were examined and central neurological affections were detected by transcranial ultrasonography (TCUS). They were classifyed in hydrocephaly, lissencephaly, focal and difuse parenchimal disorders, and none changes. From the examinated dogs, 52.9 percent presented diagnosis compatible with hydrocephaly, being 55.1 percent female and 51.7 percent younger than 2 year-old. Fifteen dogs (27.3 percent) presented focal lesions, 7.2 percent diffuse lesions, 7.2 percent images that suggested lissencephaly, and in 5.4 percent no changes were detected by TCUS. It was concluded that hydrocephaly was the most frequent central neurologycal disorder and TCUS is a valuable alternative to be used in clinical routine as a tool of diagnostic to detect morphological and structural cerebral disorders in dogs