Multiple Mechanical Complications in ST-Segment Elevation Myocardial Infarction with Angiographically Normal Coronary Arteries

This case report discusses an unusual presentation of ST-segment elevation myocardial infarction (STEMI) with normal coronary arteries and severe mechanical complications successfully treated with surgery. An 82-year-old man presented STEMI with angiographically normal coronary arteries and no major echocardiographic alterations at discharge. At the first month follow-up, he complained of fatigue and dyspnea, and contrast echocardiography complemented by cardiac magnetic resonance imaging revealed a large left ventricular apical aneurysm with a thrombus communicating by two jets of a turbulent flow to an aneurysmatic formation of the right ventricular apex. The patient underwent a Dor procedure, which was successful. Ventricular septal defects and ventricular aneurysms are rare but devastating complications of STEMI, with almost all patients presenting multivessel coronary artery disease. Interestingly in this case, the angiographic pattern was normal.

Disruption of Urate Transport in Familial Renal Glucosuria and Report on SGLT2 Expression in Normal and Pathological Kidney

Familial renal glucosuria (FRG) is a rare co -dominantly inherited benign phenotype characterized by the presence of glucose in the urine. It is caused by mutations in the SLC5A2 gene that encodes SGLT2, a Na+ -glucose co -transporter. The purpose of our current work was twofold: to characterize the molecular and phenotype findings of an FRG cohort and, in addition, to detail the SGLT2 expression in the adult human kidney. The phenotype of FRG pedigrees was evaluated using direct sequencing for the identification of sequence variations in the SLC5A2 gene. The expression of SGLT2 in the adult human kidney was studied by immunofluorescence on kidney biopsy specimens. In the absence of renal biopsies from FRG individuals, and in order to evaluate the potential disruption of SGLT2 expression in a glucosuric nephropathy, we have selected cases of nucleoside analogues induced proximal tubular toxicity. We identified six novel SLC5A2 mutations in six FRG pedigrees and described the occurrence of hyperuricosuria associated with hypouricaemia in the two probands with the most severe phenotypes. Histopathological studies proved that SGLT2 is localized to the brush -border of the proximal tubular epithelia cell and that this normal pattern was found to be disrupted in cases of nucleoside analogues induced tubulopathy. We present six novel SLC5A2 mutations, further contributing to the allelic heterogeneity in FRG, and identified hyperuricosuria and hypouricaemia as part of the FRG phenotype. SGLT2 is localized to the brush -border of the proximal tubule in the adult human normal kidney, and aberrant expression of the co -transporter may underlie the glucosuria seen with the use of nucleoside analogues.

Lack of Spontaneous Venous Pulsation: Possible Risk Indicator in Normal Tension Glaucoma?

PURPOSE: Recently, the absence of spontaneous venous pulsation (SVP) has been suggested as a vascular risk factor for primary open-angle glaucoma (POAG). As the mechanism behind this phenomenon is still unknown, the authors have studied this vascular component using colour Doppler imaging (CDI). METHODS: A total of 236 patients were divided into three diagnostic groups: healthy controls (81), POAG (86) and normal tension glaucoma (NTG; 69). All subjects were submitted to CDI studies of the retrobulbar circulation, intraocular pressure measurements and assessment of SVP existence. Mann-Whitney, chi-square contingency tables and Spearman correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: Eighty-two percent of healthy controls had SVP (66/81), while a smaller numbers were registered in both glaucoma groups: POAG - 50% (43/86); NTG - 51% (35/69). In NTG patients, but not in POAG patients, the prevalence of the SVP phenomenon decreases with increased glaucoma damage (p = 0.04; p = 0.55, respectively). Overall glaucoma patients from both groups had lower central retinal vein (CRV) velocities than the healthy controls (p < 0.05). NTG patients with SVP had less severe visual field defects (mean defect -6.92 versus -11.1, p < 0.05), higher [correction added after online publication 21 September 2012; the word 'higher' has been inserted to replace the word 'lower'] peak systolic and mean flow velocities in the central retinal artery (p < 0.01; p < 0.05, respectively) as well as higher [correction added after online publication 21 September 2012; the word higher has been inserted to replace the word lower] maximal velocities and RI of the CRV (p < 0.02; p < 0.05, respectively). CONCLUSIONS: Glaucoma patients have a decrease in CRV velocities. SVP is less prevalent in glaucoma patients than in healthy individuals. This phenomenon apparently reflects different hemodynamic patterns in the central retinal vessels. This variable may be of particular importance in NTG patients, where it may be associated with more advanced functional damage.

Post-Treated Prostate Cancer: Normal Findings and Signs of Local Relapse on Multiparametric Magnetic Resonance Imaging

The use of multiparametric magnetic resonance imaging (mp-MRI) for prostate cancer has increased over recent years, mainly for detection, staging, and active surveillance. However, suspicion of recurrence in the set of biochemical failure is becoming a significant reason for clinicians to request mp-MRI. Radiologists should be able to recognize the normal post-treatment MRI findings. Fibrosis and atrophic remnant seminal vesicles after prostatectomy are often found and must be differentiated from local relapse. Moreover, brachytherapy, external beam radiotherapy, cryosurgery, and hormonal therapy tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images (T2WI) due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2WI and functional studies like diffusion-weighted imaging and dynamic contrast-enhanced improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration either within or outside the gland. The authors provide a pictorial review of the normal findings and the signs of local tumor relapse after radical prostatectomy, external beam radiotherapy, brachytherapy, cryosurgery, and hormonal therapy.

Revision based total semantics for extended normal logic programs

Dissertação para obtenção do Grau de Doutor em Matemática - Lógica e Fundamentos da Matemática

Alterações contráteis segmentares e sua associação com arritmias ventriculares complexas, em pacientes chagásicos com eletrocardiograma normal ou borderline

INTRODUÇÃO: Morte súbita representa a principal causa de óbito em chagásicos. Eventos fatais em pacientes saudáveis, com anormalidades contráteis, foram documentados. O objetivo deste trabalho é determinar a associação entre alteração contrátil e arritmias ventriculares complexas em pacientes chagásicos, classe funcional I, eletrocardiograma normal ou borderline e função ventricular preservada. MÉTODOS: Quarenta e nove pacientes com doença de Chagas e eletrocardiograma normal ou borderline realizaram ecocardiograma, teste ergométrico e Holter. Avaliou-se a contratilidade global e segmentar dos ventrículos e a presença de arritmias ventriculares complexas induzidas no esforço e espontâneas, respectivamente. A análise estatística foi feita pelo modelo Log-Linear geral. RESULTADOS: Idade média de 56 anos; 55% mulheres. Alterações contráteis segmentares em 24,5% dos pacientes; 12% dos Holter e 18% dos testes ergométricos positivos. Houve associação entre arritmia e alteração segmentar condicionada à presença da disfunção sistólica leve do ventrículo esquerdo. CONCLUSÕES: Alterações contráteis, na presença de disfunção global leve, indicam pacientes sob maior risco de arritmias complexas.

Functional MRI of stimulus interference on auditory processing in normal listeners and tinnitus patients

We are constantly immersed in stimuli. Upon reaching our senses, stimuli are processed within various brain systems along various pathways into the brain, and eventually turned into a percept. However, there are percepts that do not result from responses to external source stimuli. A particular case of this situation is the auditory percept known as tinnitus. Tinnitus can be seen as a task-irrelevant auditory percept, commonly reported to interfere with normal daily tasks. This is known from reports made by tinnitus sufferers that refer to their phantom percept as distracting, and that it diverts their focus from the task-relevant stimuli.(...)

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

Help-seeking for 'memory loss' by older adults in India : patient, caregiver and health providers' perspectives

ABSTRACT: Background. In India, prevalence rates of dementia and prodromal amnestic Mild Cognitive Impairment (MCI) are 3.1% and 4.3% respectively. Most Indians refer to the full spectrum of cognitive disorders simply as ‘memory loss.’ Barring prevention or cure, these conditions will rise rapidly with population aging. Evidence-based policies and practices can improve the lives of affected individuals and their caregivers, but will require timely and sustained uptake. Objectives. Framed by social cognitive theories of health behavior, this study explores the knowledge, attitudes and practices concerning cognitive impairment and related service use by older adults who screen positive for MCI, their primary caregivers, and health providers. Methods. I used the Montreal Cognitive Assessment to screen for cognitive impairment in memory camps in Mumbai. To achieve sampling diversity, I used maximum variation sampling. Ten adults aged 60+ who had no significant functional impairment but screened positive for MCI and their caregivers participated in separate focus groups. Four other such dyads and six doctors/ traditional healers completed in-depth interviews. Data were translated from Hindi or Marathi to English and analyzed in Atlas.ti using Framework Analysis. Findings. Knowledge and awareness of cognitive impairment and available resources were very low. Physicians attributed the condition to disease-induced pathology while lay persons blamed brain malfunction due to normal aging. Main attitudes were that this condition is not a disease, is not serious and/or is not treatable, and that it evokes stigma toward and among impaired persons, their families and providers. Low knowledge and poor attitudes impeded help-seeking. Conclusions. Cognitive disorders of aging will take a heavy toll on private lives and public resources in developing countries. Early detection, accurate diagnosis, systematic monitoring and quality care are needed to compress the period of morbidity and promote quality of life. Key stakeholders provide essential insights into how scientific and indigenous knowledge and sociocultural attitudes affect use and provision of resources.

Analysis of metabolic flux distributions in relation to the extracellular environment in Avian cells

Continuous cell lines that proliferate in chemically defined and simple media have been highly regarded as suitable alternatives for vaccine production. One such cell line is the AG1.CR.pIX avian cell line developed by PROBIOGEN. This cell line can be cultivated in a fully scalable suspension culture and adapted to grow in chemically defined, calf serum free, medium [1]–[5]. The medium composition and cultivation strategy are important factors for reaching high virus titers. In this project, a series of computational methods was used to simulate the cell’s response to different environments. The study is based on the metabolic model of the central metabolism proposed in [1]. In a first step, Metabolic Flux Analysis (MFA) was used along with measured uptake and secretion fluxes to estimate intracellular flux values. The network and data were found to be consistent. In a second step, Flux Balance Analysis (FBA) was performed to access the cell’s biological objective. The objective that resulted in the best predicted results fit to the experimental data was the minimization of oxidative phosphorylation. Employing this objective, in the next step Flux Variability Analysis (FVA) was used to characterize the flux solution space. Furthermore, various scenarios, where a reaction deletion (elimination of the compound from the media) was simulated, were performed and the flux solution space for each scenario was calculated. Growth restrictions caused by essential and non-essential amino acids were accurately predicted. Fluxes related to the essential amino acids uptake and catabolism, the lipid synthesis and ATP production via TCA were found to be essential to exponential growth. Finally, the data gathered during the previous steps were analyzed using principal component analysis (PCA), in order to assess potential changes in the physiological state of the cell. Three metabolic states were found, which correspond to zero, partial and maximum biomass growth rate. Elimination of non-essential amino acids or pyruvate from the media showed no impact on the cell’s assumed normal metabolic state.

A segurança ao uso normal na decisão de intervenção em parques edificados

O estado de degradação de edifícios em Portugal tem aumentado significativamente ao longo dos últimos anos, devido, entre outros aspectos, ao envelhecimento e à falta de manutenção. Estes factores aceleram o processo de deterioração dos edifícios, motivando o aparecimento de anomalias. No entanto, existem diversas ferramentas para o levantamento dessas anomalias e para avaliação do estado de conservação de edifícios. Em 2006, foi desenvolvido no Laboratório Nacional de Engenharia Civil (LNEC), o Método de Avaliação do Estado de Conservação de imóveis (MAEC), que permite determinar, de forma expedita, o estado de conservação de edifícios, através da realização de inspecções visuais ao local por técnicos qualificados. Contudo, algumas situações que possam causar riscos na utilização corrente dos edifícios, caso não derivem de anomalias físicas construtivas, não são tomadas em consideração para efeitos de definição de intervenções de reabilitação. Considera-se importante que no momento do levantamento das condições de degradação física, a avaliação da segurança ao uso normal tenha igual relevância, através da identificação de alguns perigos. Em países como o Reino Unido e França são utilizadas metodologias de avaliação que integram em simultâneo estas duas dimensões. Neste sentido, o MAEC poderá ser complementado de forma a concretizar e a viabilizar este tipo de avaliações. Assim, o estudo visa desenvolver uma ferramenta aplicável em inspecções para avaliação das condições de segurança dos imóveis (MACS), integrando o MAEC neste processo de intervenção. Para isso analisaram-se outros métodos de avaliação (nacional e estrangeiros) que serviram de apoio ao desenvolvimento da proposta. Para testar a viabilidade do novo método foi avaliada uma amostra de imóveis no âmbito do MAEC e do MACS, através da inspecção de edifícios de uso habitacional, com épocas construtivas distintas. De uma forma geral, concluiu-se que a metodologia permitiu criar padrões actuais de risco, e a sua aplicação possibilitou a comparação das condições de segurança de diferentes edifícios. Também foi possível identificar os perigos com maior risco de ocorrência de acidentes, permitindo a definição de níveis de urgência de intervenção das situações consideradas perigosas.

Blocking tumor exosome release using nanovectorization systems

Exosomes are small membrane vesicles secreted by most cell types, either normal or malignant and are found in most body fluids such as saliva, plasma and breast milk. In the past decade, the interest in these vesicles has been growing more and more since it was found that besides their beneficial functions such as the removal of cellular debris and unnecessary proteins during cell maturation process, they can also interact with other cells and transfer information between them, thus helping diseases like cancer to progress. The present work intended to use gold nanoparticles as vehicles for gene silencing in an attempt to reduce the tumor-derived exosome secretion, regulated by Rab27a protein, and also aimed to compare the exosome secretion between two breast cell lines, MCF7 and MDA. Changes in RAB27A gene expression were measured by Real-time Quantitative PCR and it was revealed a decreased in RAB27A gene expression, as expected. Exosomes were isolated and purified by two different methods, ultracentrifugation and the commercial kit ExoQuick™ Solution, and further characterized using Western Blot analysis. ExoQuick™ Solution was proven to be the most efficient method for exosome isolation and it was revealed that MDA cells secrete more exosomes. Furthermore, the isolated MCF7-derived exosomes were placed together with a normal bronchial/tracheal epithelial cell line (BTEC) for an additional assay, which aimed to observe the uptake of exosomes by other cells and the exosomes’ capability of promoting cell-cell communication. This observation was made based on alterations in the expression levels of c-Myc and miR-21 genes and the fact that they both have an increased expression in BTEC cells incubated with tumor-derived exosomes when compared to control cells (without incubation with the exosomes) lead us to the conclusion that the exosome uptake and exchange of information between the exosomes and the normal cells did occurred.

Parasitic thyroid nodule in a patient with Hashimoto's chronic thyroiditis

A case of parasitic thyroid nodule is presented. The patient was a non symptomatic 53-year-old white woman, on irregular course of L-thyroxine to treat hypothyroidism due to Hashimoto's thyroiditis. Without a history of thyroid trauma or surgery, she presented a 1.6 x 0.7 x 0.5cm right pre-laryngeal lymph node-like mass which, on ultrasonography, appeared distinct from the gland. TSH, thyroid peroxidase antibody and thyroglobulin antibody serum levels were elevated and T4-free level was normal. Thyroid and total body 99mTc isonitrile scintiscan showed a topic thyroid without radionuclide uptake in the nodule. Fine-needle aspiration of the nodule showed epithelial cells with nuclear atypia and oncocytic changes plus intense lymphoid infiltration and germinative center formation, simulating lymph node metastasis of papillary thyroid carcinoma. Conventional biopsy revealed a parasitic thyroid nodule with Hashimoto's chronic thyroiditis. Parasitic thyroid nodule must always be remembered so that unnecessary surgical assessment and undesirable sequels may be avoided.

Normal bone density in male pseudohermaphroditism due to 5alpha- reductase 2 deficiency

Bone is an androgen-dependent tissue, but it is not clear whether the androgen action in bone depends on testosterone or on dihydrotestosterone. Patients with 5alpha-reductase 2 deficiency present normal levels of testosterone and low levels of dihydrotestosterone, providing an in vivo human model for the analysis of the effect of testosterone on bone. OBJECTIVE: To analyze bone mineral density in 4 adult patients with male pseudohermaphroditism due to 5alpha-reductase 2 deficiency. RESULTS: Three patients presented normal bone mineral density of the lumbar column (L1-L4) and femur neck, and the other patient presented a slight osteopenia in the lumbar column. CONCLUSION: Patients with dihydrotestosterone deficiency present normal bone mineral density, suggesting that dihydrotestosterone is not the main androgen acting in bone.

Cystic fibrosis with normal sweat chloride concentration: case report

Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.