Comparison study of procedures for aspiration of biopsy samples

Introduction: The samples obtained from fine needle aspiration in liquid base cytology (FNAC) are often limited by scarce cellularity compared to the amount of colloid and presence of blood. Accordingly, it was important to test alternative technical procedures so as to maximize the cellularity of each sample. Objective: To compare the morphological features and cellularity of the three procedures in the FNAC cytodiagnosis of the thyroid. Methods: A total of 31 cases were each subjected to a cell block and ThinPrep preparation as well as a routine smear. The observation and analysis was performed using an optical microscope. Cytological diagnosis of each cell block case was objectively analysed for cellularity, presence of background and cellular preservation. Each smear and ThinPrep case was analysed for the presence or absence of cells. The data was analysed with Microsoft Excel (Office 2010) and SPSS (Statistical Package of Social Science) version 15.0 for Windows. Results: Of 31 cases, only 20 had thyroid cells in the cell block and ThinPrep preparations, however, all smear cases contained thyroid cells. Some background was found in 30 Cell block cases with only 5 of these containing well preserved cells for cytodiagnosis. Conclusions: As indicated by the results, smear is the most appropriate procedure for FNAC of the thyroid.

Proof of Concept of the Electrochemical Sensing of 3-Iodothyronamine (T1AM) and Thyronamine (T0AM)

Recent studies have shown that, besides the well-recognized T3 and T4 hormones, there are other relevant thyroid hormones circulating in the human body. In particular, this is the case for 3-iodothyronamine (T1AM) and thyronamine (T0AM). One of the reasons for the lack of studies showing their precise importance is the absence of analytical methodologies available. Herein, for the first time, T1AM and T0AM are electrochemically characterized. T0AM was sensed by means of a glassy carbon electrode; furthermore, T1AM was sensed both with a graphitic surface (oxidatively) as well as with mercury (reductively). For both compounds, after oxidation, it was possible to observe the reversible redox reaction concerning the benzoquinone/hydroquinone couple, thus increasing the specificity of the electroanalysis. Therefore, this work provides the basis for an ‘at-point-of-use’ electrochemical strip test for T1AM and T0AM.

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.

Autoantibodies before, during and after administration of recombinant interferon-alpha for chronic viral hepatitis

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.

TRH-TSH test in patients with schistosomiasis chronic forms

Diversas alterações na concentração sérica dos hormônios tiroidianos têm sido descritas em associação a doenças crônicas não-tiroidianas. Com relação às doenças hepáticas crônicas, a síndrome do T3 baixo foi descrita em pacientes cirróticos, enquanto a síndrome do T4 elevado foi encontrada em esquistossomóticos com a forma hepatoesplênica compensada. Com o intuito de verificar se as alterações relatadas na esquistossomose mansônica eram de origem "periférica" ou "central", realizamos a prova do TRH-TSH em 12 pacientes esquistossomóticos "puros" (6 hepatointestinais e 6 hepatoesplênicos compensados) e em 5 indivíduos controle. Os resultados obtidos demonstram que o eixo hipotálamo-hipofisário é normal nas formas crônicas da esquistossomose e que provavelmente as alterações previamente relatadas devem ser '"periféricas" e não " centrais".

ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

Treatment with mebendazole is not associated with distal migration of adult Angiostrongylus costaricensis in the murine experimental infection

Abdominal angiostrongyliasis is a zoonotic infection produced by a metastrongylid intra-arterial nematode, Angiostrongylus costaricensis. Human accidental infection may result in abdominal lesions and treatment with anti-helminthics is contra-indicated because of potential higher morbidity with excitement or death of worms inside vessels. To evaluate the effect of mebendazole on localization of the worms, male Swiss mice, 5 week-old, were infected with 10 third stage larvae per animal. Twelve infected mice were treated with oral mebendazol, at 5 mg/kg/day, for 5 consecutive days, begining 22 days after inoculation. As control groups, 12 infected but non-treated mice and other 12 non-infected and non-treated mice were studied. The findings at necropsy were, respectively for the treated (T) and control (C) groups: 92% and 80% of the worms were inside the cecal mesenteric arterial branch; 8% and 10% were located inside the aorta. Only in the group C some worms (10%) were found inside the portal vein or splenic artery. These data indicate that treatment with mebendazole does not lead to distal or ectopic migration of A. costaricensis worms.

Mixomas Cardíacos, 13 Anos de Experiência no seu Diagnóstico Ecocardiográfico

INTRODUCTION: Transthoracic echocardiography is the method of choice for the diagnosis of cardiac myxomas, but the transesophageal approach provides a better definition of the location and characteristics of the tumor. The authors review their thirteen years' experience on the echocardiographic diagnosis of this pathology. METHODS: From 1994 to 2007, 41 cardiac tumors were diagnosed in our echocardiographic laboratory, of which 27 (65.85%) were cardiac myxomas. The exams and the patients' clinical files were retrospectively reviewed. RESULTS: Of the 27 patients, 22 (81.5%) were female, with a mean age of 62.1 +/- 13.6 years (25-84 years). The predominant clinical features were due to the obstruction caused by the tumor in more than two thirds of the patients, followed by constitutional symptoms in one third and embolic events in 30%. In the lab results, anemia was found in three patients and elevated sedimentation rate and CRP in two. In two patients the myxoma was found by chance. All the cases were of the sporadic type, although we found a prevalence of thyroid disease of 14% (4 patients). All patients underwent urgent surgical resection except one, in whom surgery was refused due to advanced age and comorbidities. The myxomas followed a typical distribution with 24 (88.8%) located in the left atrium, 18 of them attached to the atrial septum (AS) and two to the mitral valve. In one patient, the tumor involved both atria. The other two cases originated in the right atrium at the AS. Embolic phenomena were more frequent in small tumors (p = 0.027) and in those with a villous appearance (p = 0.032). Obstructive manifestations were associated with larger tumors (p = 0.046) and larger left atria (p = 0.048). In our series, there were no deaths during hospitalization or in the follow-up period of 5.2 +/- 3.7 years in 19 patients. There were two recurrences, both patients being successfully reoperated. CONCLUSION: Myxoma is the most common cardiac tumor. Transesophageal echocardiography provides excellent morphologic definition, aiding in diagnosis and follow-up. Most clinical manifestations are obstructive and are associated with larger tumors. Small tumors with a friable appearance have a higher chance of embolization. Surgical resection is usually curative and the long-term prognosis is excellent.

Miosite Orbitária

Orbital myositis is a subgroup of the nonspecific inflammatory syndrome or orbital pseudotumor and is characterized by a primary inflammation of extraocular muscles. The authors describe a 70-year-old patient with acute proptosis, ocular pain and right ophthalmoplegia, whose orbital computed tomographic scan showed enlargement of the homolateral extraocular muscles. Clinical presentation and complementary tests were compatible with the diagnosis of orbital myositis however, because of the particular aspects, which included retinal central vein occlusion, optic nerve lesion, distension of the superior ophthalmic vein and the homolateral cavernous sinus, the differential diagnosis with cavernous sinus pathology and thyroid ophthalmopathy was considered. The importance of a rapid diagnosis and treatment is stressed.

Relação entre Hipotiroidismo Subclínico e Doença Coronária: um Estudo com Angiografia

INTRODUCTION: The definition of subclinical hypothyroidism (SH) is an asymptomatic state in which free thyroxine (T4) is normal and thyroid-stimulating hormone (TSH) levels are elevated. Its relationship with coronary disease is not clear and has been the subject of recent interest. Current evidence is conflicting and there is a lack of studies supported by coronary angiography. OBJECTIVE: To assess the relationship between SH and the presence and extent of coronary disease diagnosed by angiography. METHODS: We prospectively studied 354 consecutive patients referred for elective coronary angiography. Those with known thyroid disease, documented coronary disease or previous myocardial infarction were excluded. Fasting blood specimens were collected to measure thyroid hormones, lipid profile, high-sensitivity C-reactive protein, fibrinogen and NT-proBNP. Patients with SH were compared with those without to assess differences in clinical characteristics and biochemical and angiographic results. Significant coronary disease was defined as the presence of at least one lesion with > or = 50% luminal stenosis. Lesions with <50% stenosis were considered minimal. RESULTS: SH was diagnosed in 32 (9%) patients. Mean age was similar between the groups. There were more women (66% vs. 39%; p=0.003) and atrial fibrillation was more frequent (25% vs. 11%; p=0.016) in the group of patients with SH. There were no significant differences in the other baseline clinical parameters, and blood biochemistry results were similar in the two groups, with the exception of higher levels of NT-proBNP in SH patients, although without statistical significance. The angiographic results were as follows: significant coronary disease (SH 28.1% vs. non-SH 43.8%; p=0.087); three-vessel disease (9.4% vs. 9.9%; p=0.919); two-vessel disease (12.5% vs. 13.4%; p=0.892); single-vessel disease (6.3% vs. 29.5%; p=0.051); minimal lesions (9.4% vs. 10.9%; p=0.794); and no coronary disease (62.4% vs, 45.3%; p=0.064). CONCLUSION: In this population SH was not associated with the presence or extent of coronary disease diagnosed by coronary angiography.

Dispersão da Refractariedade Auricular como Substrato Electrofisiológico da Vulnerabilidade Auricular em Doentes com Fibrilhação Auricular Paroxística

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.

Does Cleome droserifolia have anti-schistosomiasis mansoni activity?

The present study was undertaken to assess the effect of the crude extract of Cleome droserifolia (CD) leaves on experimentally infected mice with Schistosoma mansoni. Two groups of mice, showing a patent infection of S. mansoni, one of them was daily treated with an alcoholic extract of CD leaves (0.31 g kg-1 body weight, i.p.) for 21 days. The schistosomicidal activity of the CD extract was evaluated, three weeks post-treatment, on some parasitological and histopathological aspects including worm load, oogram pattern, faecal eggs releasing and granuloma formation. In addition, serum thyroid hormones levels (tri-iodothyronine; T3 and tetra-iodo-thyronin; T4), serum total protein contents and hepatic reduced glutathione (GSH) were evaluated. Treatment using CD extract resulted in a weak reduction in worm burden (32.46%) and affected the viability of both mature and immature eggs as indicated by the increase in the percentage of dead eggs and the decrease in the percentage of live ones. In addition, a week post-treatment, eggs elimination was observed in the stool of the infected-treated group which was low compared to the infected group. There was a suppressive effect of the extract on granuloma formation that could be due to the antioxidant effect of the extract. These data are confirmed by increasing hepatic GSH, serum total proteins and thyroid hormone levels in the infected-treated group as compared to the infected group. Treatment significantly enhanced b globulin fractions of the protein. Based on these assumptions, CD extract has beneficial effects on thyroid hormones status and anti-schistosomiasis activity. The beneficial effects of CD extract could be related to its direct effects on the parasite, and secondary to its effect on the antioxidant capacity of the host. The present study could emphasize the precise mechanism (s) of CD extract protection.

Clinical and Pathological Findings in Women with Fabry Disease

Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance. Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings. Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated glomerular filtration rate (CKD EPI equation) was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristic histologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease.

Two Gestational Sacs, Two Locations - Heterotopic Pregnancy - Case Report

Introduction: Heterotopic pregnancy (HP) is defined as two gestational sacs simultaneously present in two different locations, being the uterus and the fallopian tubes the more common. Sporadic HP is a very rare condition (1:30,000 pregnancies). With the use of medically assisted reproduction the prevalence is significantly higher(1:7,000). Considering spontaneous pregnancy, HP is associated with risk factors, being prior inflammatory pelvic disease the most common. The clinical presentation is similar to that of ectopic pregnancy or spontaneous miscarriage although it is usually a more late diagnosis. Case report: 25 year-old pregnant woman, OI 0000, previously healthy; admitted at the Emergency Department (ED) with acute pelvic pain mainly at the right iliac fossa and moderate vaginal bleeding confirmed by speculum examination. She was hemodynamically stable and the bimanual palpation was painful; no prior medically assisted reproduction technique had been performed. The haemoglobin value was within normal range and the serum β-hCG was 2,763mUI/mL. The ultrasonography at the ED showed an in uterus gestational sac and another one inside the right fallopian tube; in both gestational sacs cardiac activity was absent. HP diagnosis was then established and the patient was admitted at the Obstetrics Ward for surveillance and ultrasonographic/laboratorial reassessment; complete miscarriage of the uterine pregnancy occurred but methotrexate was necessary for the treatment of persistent tubarian pregnancy. Conclusion: When evaluating a pregnant woman with pelvic pain and vaginal bleeding one should always be aware of several differential diagnosis amongst which HP should be considered. If the patient has in uterus viable pregnancy the treatment of the ectopic concomitant gestational sac should be as conservative as possible; methotrexate should not be used in that situation as it leads to uterine pregnancy miscarriage in about one third of the patients.

Hipertiroidismo na Gravidez – um Caso Clinico

Thyroid disease is common in pregnant women.We report a 10 weeks gestation pregnancy with hyperemesis gravidarum, hypertension crisis and hyperthyroidism