Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Catatonia due to systemic lupus erythematosus

Objectives Discuss neuropsychiatric aspects and differential diagnosis of catatonic syndrome secondary to systemic lupus erythematosus (SLE) in a pediatric patient. Methods Single case report. Result A 13-year-old male, after two months diagnosed with SLE, started to present psychotic symptoms (behavioral changes, hallucinations and delusions) that evolved into intense catatonia. During hospitalization, neuroimaging, biochemical and serological tests for differential diagnosis with metabolic encephalopathy, neurological tumors and neuroinfections, among other tests, were performed. The possibility of neuroleptic malignant syndrome, steroid-induced psychosis and catatonia was also evaluated. A complete reversal of catatonia was achieved after using benzodiazepines in high doses, associated with immunosuppressive therapy for lupus, which speaks in favor of catatonia secondary to autoimmune encephalitis due to lupus. Conclusion Although catatonia rarely is the initial clinical presentation of SLE, the delay in recognizing the syndrome can be risky, having a negative impact on prognosis. Benzodiazepines have an important role in the catatonia resolution, especially when associated with parallel specific organic base cause treatment. The use of neuroleptics should be avoided for the duration of the catatonic syndrome as it may cause clinical deterioration.

Influência do fator visão do céu na propagação do ruído em zonas urbanas

Dissertação de mestrado integrado em Engenharia Civil

Longitudinal analysis of tumor marker CEA of breast cancer patients from Braga's hospital

Allied to an epidemiological study of population of the Senology Unit of Braga’s Hospital that have been diagnosed with malignant breast cancer, we describe the progression in time of repeated measurements of tumor marker Carcinoembryonic antigen (CEA). Our main purpose is to describe the progression of this tumor marker as a function of possible risk factors and, hence, to understand how these risk factors influences that progression. The response variable, values of CEA, was analyzed making use of longitudinal models, testing for different correlation structures. The same covariates used in a previous survival analysis were considered in the longitudinal model. The reference time used was time from diagnose until death from breast cancer. For diagnostic of the models fitted we have used empirical and theoretical variograms. To evaluate the fixed term of the longitudinal model we have tested for a changing point on the effect of time on the tumor marker progression. A longitudinal model was also fitted only to the subset of patients that died from breast cancer, using the reference time as time from date of death until blood test.

HOXA9 as a key regulator in glioma initiation, aggressiveness and response to therapy

Tese de Doutoramento em Ciências da Saúde

Ontological representation of tumor-node-metastasis classification and an ontology-driven classifier: a study on colorectal cancer

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Informática Médica)

Contributo para a compreensão das causas de exclusão de ilicitude e da culpa no crime de acesso ilegítimo

Dissertação de mestrado em Direito e Informática

Myocardial perfusion by contrast echocardiography. Establishment of normal pattern of intracoronary injection and safety in humans

OBJECTIVE: To establish the normal pattern and safety of echocardiographic contrast in patients with no significant obstruction of epicardial coronary arteries. METHODS: 67 patients with normal coronary arteries or obstructions < 50% were selected from 277 patients who underwent coronary angiography (CA). Mean age was 56 ± 11years and 36 were males. At the end CA, echocardiographic contrast was selectively injected into each coronary artery. The parasternal short axis of the left ventricle (LV) was divided into six segments: anterior (A), antero-lateral (AL), postero-lateral (PL), posterior (P), infero-septal (IS) and antero-septal (AS). Anterolateral (ALPM) and posteromedial papillary muscles (PMPM) were also considered. The pattern and intensity of the appearance of the myocardial contrast was visually analyzed. RESULTS: The right coronary artery (RCA) was dominant in 60 patients. Contrast appearance was sudden and simultaneous in the 3 muscle layers. All segments could be contrasted after the injection in both coronary arteries. 100% of the AS, A and AL segments, 97% of the PL and 98% of the ALPM were perfused by the left coronary artery (LCA). P and IS segments were perfused by the RCA in 85% and 82%, respectively, and by a dominant LCA in 71% of the cases. The PMPM was perfused by a dominant RCA in 77% and by a dominant LCA in 86%. There were no symptoms. CONCLUSION: Intracoronary injection of the sonicated solution is a safe procedure that allows for an excellent opacification of the myocardium and can potentially be used during routine CA.

Noninvasive diagnosis of allograft vascular disease after heart transplantation

OBJECTIVE: To determine the predictive values of noninvasive tests for the detection of allograft vascular disease. METHODS: We studied 39 patients with mean ages of 48±13 years and a follow-up period of 86±13 months. The diagnosis of allograft vascular disease was made by cine-coronary arteriography, and it was considered as positive if lesions existed that caused > or = 50% obstruction of the lumen. Patients underwent 24h Holter monitoring, thallium scintigraphy, a treadmill stress test, and dobutamine stress echocardiography. Sensitivity, specificity, and positive and negative predictive values were determined in percentages for each method, as compared with the cine-coronary arteriography results. RESULTS: Allograft vascular disease was found in 15 (38%) patients. The Holter test showed 15.4% sensitivity, 95.5% specificity. For the treadmill stress test, sensitivity was 10%, specificity was 100%. When thallium scintigraphy was used, sensitivity was 40%, specificity 95.8%. On echocardiography with dobutamine, we found a 63.6% sensitivity, 91.3% specificity. When the dobutamine echocardiogram was associated with scintigraphy, sensitivity was 71.4%, specificity was 87%. CONCLUSION: In this group of patients, the combination of two noninvasive methods (dobutamine echocardiography and thallium scintigraphy) may be a good alternative for the detection of allograft vascular disease in asymptomatic patients with normal ventricular function.

Calcified aneurysms in coronary arteries of a 48-year-old patient

This is a case report of a 48-year-old female patient with a compatible history of Kawasaki disease during childhood, who was admitted to the emergency coronary unit with unstable angina pectoris. Coronary angiography identified two coronary aneurysms, one causing right coronary occlusion and the other causing severe obstruction of the left anterior descending coronary artery. Coronary artery bypass surgery was indicated.

Primary Cardiac Angiosarcoma: A Therapeutical Dilemma

Cardiac angiosarcomas are malignant tumors that almost invariably have a short and fatal evolution. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. Heart transplantation is an attractive option in nonresectable tumors, even though the current experience is still limited. However, in most patients, the diagnosis is still established late, and survival is only slightly altered by the proposed treatments, mainly due to previously existing and undetected metastases. We report a case that illustrates the therapeutic dilemma faced with this neoplasia, and we discuss the case based on a literature review.

Detection of Altered Risk Factors in Hospitalized Patients with Coronary Artery Disease

OBJECTIVE: To assess biochemical, anthropometric, and dietary variables considered risk factors for coronary artery disease. METHODS: Using anthropometrics, dietary allowance, and blood biochemistry, we assessed 84 patients [54 males (mean age of 55± 8 years) and 30 females (mean age of 57±7 years)], who had severe ( > or = 70% coronary artery obstruction) and nonsevere forms of coronary artery disease determined by cardiac catheterization. The severe form of the disease prevailed in 70% of the males and 64% of the females, and a high frequency of familial antecedents (92% ' 88%) and history of acute myocardial infarction (80% ' 70%) were observed. Smoking predominated among males (65%) and diabetes mellitus among females (43%). RESULTS: Males and females had body mass index and body fat above the normal values. Females with nonsevere lesions had HDL > 35 mg/dL, and this constituted a discriminating intergroup indicator. Regardless of the severity of the disease, hyperglycemia and hypertriglyceridemia were found among females, and cholesterolemia > 200 mg/dL in both sexes, but only males had LDL fraction > 160 mg/dL and homocysteine > 11.7 mmol/L. The male dietary allowance was inadequate in nutrients for homocysteine metabolism and in nutrients with an antioxidant action, such as the vitamins B6, C, and folate. Individuals of both sexes had a higher lipid and cholesterol intake and an inadequate consumption of fiber. The diet was classified as high-protein, high-fat, and low-carbohydrate. CONCLUSION: The alterations found had no association with the severity of lesions, indicating the need for more effective nutritional intervention.

Comparison between young males and females with acute myocardial infarction

OBJECTIVE: To assess the differences between young males and females after acute myocardial infarction. METHODS: We retrospectively studied 236 patients (54 females and 182 males) after acute myocardial infarction and during hospital stay assessed the following parameters: risk factors; the treatment used; the pattern of coronary artery obstruction; left ventricular ejection fraction; complications; and, using a logistic regression model, the factors related to the occurrence of reinfarction and death. RESULTS: No significant difference was observed between the sexes in risk factors, pattern of coronary artery obstruction, and left ventricular function. The time interval between symptom onset and treatment was longer in females (p=0.03), who underwent thrombolysis (p=0.01) and angioplasty (p=0.03) less frequently than males did, but not myocardial revascularization. Female sex (OR = 5.98) and diabetes (OR = 14.52) were independent factors related to the occurrence of reinfarction and death. CONCLUSION: Young males and females after acute myocardial infarction did not differ in coronary risk factors, and clinical and hemodynamic characteristics. Females had their treatment started later, and they underwent chemical thrombolysis and angioplasty less frequently than males did. Female sex and diabetes were related to the occurrence of reinfarction and death.

Endomyocardial fibrosis in infancy

The patient was a 4-month-old infant, who underwent persistent ductus arteriosus interruption with titanium clips at the age of 13 days and, since the age of 2 months, had crises of hypoxia and hypertonicity. After clinical investigation, the presence of pulmonary hypertension was confirmed and left ventricular inflow tract obstruction was suspected. The patient underwent surgical treatment at the age of 4 months, during which right and left ventricular endocardial fibrosis was identified. The fibrosis was resected, but the infant had an unfavorable clinical evolution with significant diastolic restriction and died on the sixth postoperative day. Anatomicopathological and surgical findings suggested endomyocardial fibrosis, although that pathology is very rare at the patient's age.

Comparative study of the use of diltiazem as an antispasmodic drug in coronary angiography via the transradial approach

OBJECTIVE: To evaluate the impact of the use, prior to the procedure, of injectable diltiazem to prevent complications. METHODS: Between September 2000 and July 2001, 50 patients underwent transradial coronary angiography and were randomized to receive placebo (GI) or diltiazem (GII) through a catheter inserted into the radial artery. All patients received isosorbide mononitrate. Ultrasound analyses of the radial artery were performed before examination, 30 minutes afterwards, and 7 days afterwards to evaluate the flow, the diameter, and the artery output. RESULTS: The radial artery diameter of GI was 2.4± 0.5 mm before the procedure and 2.3±0.5 mm after 30 minutes (NS), whereas in GII the diameter was 2.2±0.3 mm before the examination and 2.5±0.4 mm 30 minutes after it (P<0.001). Radial artery output in group 1 was 7.3±5.l2 mL/min before the examination and 6.1±3.5 mL/min 30 minutes after the examination (NS), and GII had an increase of 5.9±2.5 mL/min before examination to 9.05± 7.78 mL/min after the examination (P=0.04). Complications (spasm, occlusion, and partial obstruction) occurred in 4 patients (17.4%) in GI and did not occur in GII (P=0.04). CONCLUSION: The study suggests a decrease in vascular complications through the transradial access for coronary angiography with the use of diltiazem as an antispasmodic drug, resulting in the significant increase in the diameter of the radial artery and radial artery output.