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1.
Europace ; 20(3): 472-480, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28177452

RESUMO

Aims: To determine the incidence and the causes of sudden death (SD) in persons aged 1-35 years old and the diagnostic yield of clinically guided genetic screening in the sudden arrhythmic death syndrome (SADS) victims' families. Methods and results: Incidence and causes of SD in the Attica region of Greece in 2002-10 were determined using death certificates and autopsy reports. We evaluated clinically consecutive families of SADS victims and if a clinical diagnosis was established, we proceeded to targeted genetic analysis. Out of 6030 deaths, 56% were due to traumatic or violent causes, 40.5% were natural deaths, and 3.3% were of undetermined cause. There were 349 SD cases. Cardiovascular causes accounted for 65%, non-cardiovascular causes for 17%, and SADS for 18%. Clinical evaluation identified an inherited heart disease in 5/20 SADS families (25%). Targeted genetic analysis identified a causative mutation in all of the five screened families and reconfirmed the diagnosis in three of five proband victims. Clinical and genetic evaluation of 28 family members identified eight affected carriers and eight non-affected carriers. Molecular autopsy failed to identify any of these families. Conclusion: Sudden death in the young is of cardiovascular origin in the majority of cases. A considerable rate of SD cases remains of unknown cause on post-mortem. Apart from channelopathies, subclinical forms of inherited structural heart diseases would appear to be implicated in SADS. Clinically guided genetic screening has a significant diagnostic yield and identifies affected families that would have been missed by the current suggested molecular autopsy panel.


Assuntos
Arritmias Cardíacas/genética , Arritmias Cardíacas/mortalidade , Análise Mutacional de DNA , Morte Súbita Cardíaca/epidemiologia , Testes Genéticos/métodos , Mutação , Adolescente , Adulto , Idade de Início , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Autopsia , Causas de Morte , Criança , Pré-Escolar , Ecocardiografia , Eletrocardiografia , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Grécia/epidemiologia , Hereditariedade , Humanos , Incidência , Lactente , Masculino , Linhagem , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
2.
Tumour Biol ; 36(1): 315-27, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25252849

RESUMO

Hu-antigen R (HuR) is considered to play a central role in tumor formation, growth, and metastasis by binding to messenger RNAs (mRNAs) encoding proteins such as cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 protein expression in non-small-cell lung carcinoma (NSCLC). HuR and COX-2 expression was assessed immunohistochemically on tissue microarrays of 81 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients' survival. Enhanced total HuR expression was significantly associated with tumor histological type and presence of lymph node metastases, as well as with increased tumor proliferative capacity and poor patients' outcome (p = 0.039, p = 0.017, p = 0.033, and p = 0.022, respectively). Enhanced COX-2 expression was significantly associated with the presence of lymphovascular invasion and increased tumor proliferative capacity (p = 0.031 and p = 0.023, respectively). Concomitant elevated HuR/COX-2 expression levels were significantly associated with tumor histological type and increased proliferative capacity (p = 0.002 and p = 0.045, respectively). Enhanced total HuR expression, as well as its cytoplasmic localization, was significantly associated with increased COX-2 expression (p = 0.015 and p = 0.001, respectively). The present study supported evidence that HuR may participate in malignant transformation of NSCLC, reinforcing its usefulness as potential therapeutic target in this type of neoplasia.


Assuntos
Adenocarcinoma/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclo-Oxigenase 2/metabolismo , Proteínas ELAV/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Ciclo-Oxigenase 2/genética , Proteínas ELAV/genética , Proteína Semelhante a ELAV 1 , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
3.
Expert Opin Ther Targets ; 18(3): 269-75, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24329716

RESUMO

INTRODUCTION: Ephrin (Eph) receptors and their membrane-anchored ligands, the ephrins, participate in a wide spectrum of pathophysiological processes, regulating cellular adhesion, migration or chemo-repulsion and tissue/cell boundary formation. Recent evidence has further extended the role of Eph receptors and their ligands as critical regulators of vascular remodelling during embryogenesis. The role of Ephs/ephrins signalling in the angiogenic development of murine placentas and in the invasion of the maternal tissues and the development of the placental vasculature in humans has currently attracted considerable interest. AREAS COVERED: A literature review summarising the most recent data in terms of the role of Ephs/ephrins in normal placental development and disease, highlighting on their expression status in the different cellular populations of the placental vascularity. EXPERT OPINION: Despite the fact that the role of Eph/ephrins signalling in normal placental development is still unclear, some studies tried to investigate their potential implication in placental pathologies, such as preeclampsia and placenta accreta. Even though no evidence for their direct implication occurred, their role is an interesting field for future research.


Assuntos
Efrinas/metabolismo , Placentação/fisiologia , Receptores da Família Eph/metabolismo , Animais , Feminino , Humanos , Ligantes , Placenta Acreta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez
4.
J Forensic Sci ; 56(3): 645-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21361943

RESUMO

Sudden unexpected death is frequent in street heroin addicts. We conducted a histologic study of the sinus node (SN) to offer some evidence about the possible arrhythmogenic cause of death. Postmortem coronary angiography and microscopic examination of the SN and the perinodal area were performed in 50 heroin addicts (group 1) and in 50 nonaddicts (group 2), all men (16-40 years old). In heroin addicts, fatty and/or fibrous tissue replaced SN tissue in 21 cases (42%). Perinodal infiltration was found in 15 cases (30%). Fibromuscular dysplasia in branches of the sinus node artery (SNA) was found in eight cases (16%). Inflammation with focal and/or diffuse concentration of round cells was detected in the SN in 22 cases (44%). Old mural thrombi were also found in 13 cases (26%). The histologic changes in the SN and perinodal area offer an explanation about the possible mechanism of arrhythmia and sudden death in this population.


Assuntos
Morte Súbita , Dependência de Heroína/patologia , Miocárdio/patologia , Nó Sinoatrial/patologia , Adolescente , Adulto , Angiografia Coronária , Doença da Artéria Coronariana , Circulação Coronária , Edema/patologia , Displasia Fibromuscular/patologia , Fibrose , Patologia Legal , Átrios do Coração/patologia , Humanos , Drogas Ilícitas , Inflamação/patologia , Masculino , Fibras Nervosas/patologia , Trombose/patologia , Túnica Íntima/patologia , Adulto Jovem
5.
Dig Dis Sci ; 56(3): 777-85, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20694513

RESUMO

BACKGROUND: Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful biomarkers for cancer screening, surveillance and prognosis. The aim of the present study was to evaluate the clinical significance of MCM-2 and MCM-5 expression in gastric adenocarcinoma in comparison with Ki-67 proliferative marker. METHODS: MCM-2, MCM-5 and Ki-67 expression was assessed immunohistochemically in 66 tumoral samples of gastric adenocarcinoma patients and was statistically analyzed in relation to clinicopathological characteristics and patient survival. RESULTS: MCM-2 expression did not show significant associations with any clinicopathological parameters, while Ki-67 expression was merely significantly associated with tumor size (P = 0.0150). MCM-2 and Ki-67 expression were more frequently in intestinal (median values: 67.5 and 60%) compared to diffuse-type (median values: 60 and 45%) gastric adenocarcinoma cases without though reaching statistical significance (P > 0.05). MCM-5 expression was significantly associated with tumor size (P = 0.0295), presence of lymph node metastases (P = 0.0216) and tumor histopathological stage (P = 0.0098). Patients presenting high MCM-5 expression had significantly shorter survival times (log-rank test, P = 0.0042), whereas neither MCM-2 nor Ki-67 expression showed significant prognostic value (log-rank test, P = 0.9618 and P = 0.7174, respectively). In multivariate analysis, patient age, histopathological stage and grade of differentiation, but not MCM-5 expression, were identified as independent prognostic factors (Cox regression analysis, P = 0.0097, P = 0.0195, P = 0.0035 and P = 0.3245, respectively). CONCLUSIONS: The present study showed that MCM-5 expression was associated with clinicopathological parameters in gastric adenocarcinoma. However, further studies highlighting the distinct impact of the two histopathological types, intestinal and diffuse, are warranted to delineate whether MCMs could be used as diagnostic and prognostic markers in gastric neoplasia.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Antígeno Ki-67/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/metabolismo , Idoso , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Prognóstico , Neoplasias Gástricas/metabolismo
6.
Int J Androl ; 32(6): 675-86, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19515174

RESUMO

We evaluated the potential for growth and intrauterine development of embryos generated from the fertilization of oocytes with spermatozoa recovered from animals with chronic renal failure (CRF). Group A included sham-operated rats (n = 28), group B1 involved CRF rats that had undergone erythropoietin plus bromocryptine treatment (n = 28), and group B2 included CRF rats that had received normal saline. Embryos derived from the in vitro fertilization of oocytes with spermatozoa recovered from rats of group A or group B1 or group B2 were transferred to female recipients. We induced CRF in a group of rats (group B; n = 56; the total kidney volume was reduced to one-sixth with two operations). One week after the second operation, the rats of group B were randomly divided into group B1 (they subsequently received bromocryptine plus erythropoietin) and group B2 (they received injections of saline). Nine weeks after the second operation, the fertility of each male rat was assessed by mating tests and in vitro fertilization of oocytes. The mean litter size was significantly smaller in the subpopulation of fertile animals in group B2 than in the fertile rats of group B1 and in the fertile rats of group B1 than in the fertile rats of group A. Per cent of transferred blastocysts that developed into alive offspring were significantly lower in group B2 than in group B1 and in group B1 than in group A. Epididymal spermatozoa demonstrated a significantly larger DNA-oxidative damage in group B2 than in group B1 and in group B1 than in group A. These findings demonstrate that sperm-DNA damage because of CRF development is accompanied by a defect in the development of embryos generated in vitro. We may suggest that bromocryptine and erythropoietin protecting sperm DNA from oxidative damage improve reproductive potential in rats with CRF.


Assuntos
Eritropoetina/farmacologia , Fertilização/fisiologia , Falência Renal Crônica/fisiopatologia , Oócitos/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Epididimo , Feminino , Fertilidade , Fertilização in vitro , Rim/patologia , Masculino , Ratos , Ratos Wistar
7.
J Am Coll Cardiol ; 52(17): 1391-8, 2008 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-18940529

RESUMO

OBJECTIVES: We sought to examine the relationship between coronary flow reserve (CFR) and myocardial capillary density (MCD) in patients with idiopathic dilated cardiomyopathy, heart failure, and normal coronary arteries. BACKGROUND: Coronary flow reserve is depressed in patients with idiopathic dilated cardiomyopathy, particularly in those with end-stage congestive heart failure. METHODS: We studied 18 patients, 48 +/- 10 years of age, who had a mean New York Heart Association functional class of 2.9 +/- 1.3, mean left ventricular ejection fraction of 22 +/- 8%, and mean pulmonary capillary wedge pressure of 23 +/- 10 mm Hg. CFR measurements were made with a 0.014-inch pressure-temperature sensor-tipped guide wire placed in the distal left anterior descending coronary artery. Thermodilution curves were constructed in triplicate at baseline and during maximum hyperemia induced by intravenous adenosine. CFR was calculated from the ratio of mean transit times. Right heart endomyocardial biopsies were performed during the same procedure. Autopsied specimens from nonfailing hearts were used as controls. The tissue was histochemically stained with CD-34 for morphometric measurements of MCD. RESULTS: We observed a close linear relationship between CFR and MCD (r = 0.756, p = 0.0001). The MCD in 7 patients with a CFR >or=2.5 (73.2 +/- 16) was similar to that measured in normal control patients, (85 +/- 11, p = NS). In contrast, the MCD in 11 patients with a CFR <2.5 was 33.2 +/- 14, which was significantly lower than in patients with heart failure and normal CFR (73.2 +/- 16, p = 0.001) or in controls (85 +/- 11, p < 0.0001). CONCLUSIONS: A marked decrease in MCD was found in patients presenting with congestive heart failure as the result of idiopathic dilated cardiomyopathy and a depressed CFR.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Circulação Coronária , Vasos Coronários/patologia , Insuficiência Cardíaca/fisiopatologia , Miocárdio/patologia , Adulto , Estudos de Casos e Controles , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
8.
Int J Cardiol ; 126(2): e22-4, 2008 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-17397946

RESUMO

In this report we briefly describe a 54-year-old woman who was referred to our institution for evaluation and management of newly diagnosed congestive heart failure associated with a skin rash. Detailed investigations revealed the presence of restrictive cardiomyopathy due to isolated primary cardiac amyloidosis as well as the presence of a skin disease named 'porokeratosis of Mibellli'. Interestingly, porokeratotic lesions rarely have been associated with localized cutaneous amyloidosis. Presumably, porokeratosis induces secondary dermal amyloid deposition by a yet unknown mechanism. This is the first case of primary amyloidosis associated with porokeratosis reported in the literature.


Assuntos
Amiloidose/diagnóstico , Insuficiência Cardíaca/diagnóstico , Poroceratose/diagnóstico , Amiloidose/complicações , Amiloidose/genética , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Humanos , Pessoa de Meia-Idade , Miocárdio/patologia , Poroceratose/complicações , Poroceratose/genética
9.
Anal Quant Cytol Histol ; 29(4): 271-8, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17879636

RESUMO

OBJECTIVE: To develop a method for nonsupervised thresholding of transitional cell carcinoma nuclei of hematoxylin-eosin-stained histologic sections. STUDY DESIGN: For grayscale, RGB, HSL and L*a*b* thresholding we used an extension of a clustering method, based on a between-class/within-class criterion, applying optimal gray-level thresholding to distributions of R, G, B, or H and S or L* color domains. Algorithms were tested on 20 hematoxylin-eosin-stained sections of bladder carcinomas. RESULTS: Results were compared with corresponding results of manually selected nuclear areas. Images were compared pixel to pixel with matching reference images. Grayscale automatic thresholding presented unacceptably low pixel specificity, which complicated further nuclear segmentation. Nonsupervised thresholding in RGB or HSL, as well as semimanual thresholding in L*a*b* color space demonstrated significantly better accuracy and high values of pixel specificity and sensitivity, which permitted errors of only 4.27-5.83% in the subsequent mean area estimation of the transitional cell carcinoma nuclei. CONCLUSION: Nonsupervised multispectral thresholding in RGB or HSL color space extends single graylevel thresholding techniques to multilevel thresholding. This seems to be an effective, relatively simple and fast alternative to the widely used automatic grayscale or manual color thresholding for segmentation of nuclei in routine histologic sections.


Assuntos
Carcinoma de Células de Transição/patologia , Núcleo Celular/patologia , Processamento de Imagem Assistida por Computador/métodos , Neoplasias da Bexiga Urinária/patologia , Limiar Diferencial , Humanos
10.
Dig Dis Sci ; 52(9): 2305-11, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17393321

RESUMO

Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, is a key regulator of adipogenic differentiation and glucose homeostasis. PPAR-gamma ligands have recently been demonstrated to affect proliferation and differentiation in cancer cells lines. The aim of the present work was to examine PPAR-gamma expression in colon cancer cases. PPAR-gamma expression was examined immunohistochemically in 86 colon cancer cases and was correlated with clinicopathological parameters, tumor proliferative capacity, cell cycle-related molecule expression, and patient survival. Positive PPAR-gamma immunostaining was prominent in 48 of 86 cases (56%). PPAR-gamma positivity was not correlated with Dukes' stage, histological grade of differentiation, lymph node and liver metastasis, venous invasion, tumor proliferative capacity, or patient survival. A statistically significant correlation was found between PPAR-gamma and the expression of cell cycle-related molecules pRb (P < 0.016), cyclin D1 (P <0.009), p16 (P<0.032), and p21 (P<0.033), while a positive trend for cyclin E was also noted (P<0.057). The pattern, intensity, and extent of PPAR-gamma expression in positive cases were not correlated with any of the examined variables. Our findings support evidence for participation of this protein in the biological mechanisms underlying carcinogenic evolution in the colon, also suggesting the importance of specific PPAR-gamma ligands as cell cycle modulators for a future therapeutic approach in colon cancer.


Assuntos
Ciclo Celular/fisiologia , Neoplasias do Colo , Ciclina D1/metabolismo , Ciclina E/metabolismo , Proteínas Inibidoras de Quinase Dependente de Ciclina/metabolismo , PPAR gama/biossíntese , Proteína do Retinoblastoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antineoplásicos/imunologia , Biomarcadores Tumorais/biossíntese , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , PPAR gama/imunologia , Prognóstico , Taxa de Sobrevida
11.
Saudi Med J ; 27(10): 1588-90, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17013489

RESUMO

A rare case of splenic tuberculosis complicated by splenic rupture is reported. A 73-year-old man, hospitalized for peptic ulcer bleeding, presented in oligemic shock, was transferred to the operating room. Hemoperitoneum, due to rupture of an enlarged spleen was detected. The pathology revealed splenic tuberculosis. He had an uneventful recovery. Postoperatively, he received a combination of anti-tuberculous therapy for 6 months.


Assuntos
Ruptura Esplênica/etiologia , Tuberculose Esplênica/complicações , Idoso , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Humanos , Isoniazida/uso terapêutico , Lactonas/uso terapêutico , Masculino , Pirazinamida/uso terapêutico , Ruptura Espontânea , Sulfonas/uso terapêutico , Tuberculose Esplênica/tratamento farmacológico
12.
Surg Today ; 36(10): 908-13, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16998685

RESUMO

PURPOSE: Hemostasis is a fundamental principle of surgery. We compared the safety and efficacy of monopolar electrocoagulation (ME), bipolar electrocoagulation (BE), Ligasure (LS), a modern bipolar vessel sealing system, and Ultracision (UC), a system of ultrasound energy based shears. We also studied the healing process after their use. METHODS: We used each of the above methods to coagulate and divide the short gastric vessels of 16 white male New Zealand rabbits. The animals were killed after 3, 7, 14, or 21 days, and the coagulation sites and the adjacent gastric wall were examined histologically. RESULTS: LS and UC achieved complete hemostasis without any complications. Conversely, ME and BE often resulted in failed coagulation and perforation of the neighboring gastric wall from a side thermal injury. Histologically, LS demonstrated the mildest side thermal injury and the fastest healing process. We noted greater thermal injury and inflammatory response after UC than after LS on days 7 and 14; however, ME and BE caused the most severe lesions. CONCLUSIONS: LS and UC are clearly the safest and most efficient methods of coagulation, whereas ME and BE could cause serious clinical and histological complications. We found histological evidence that UC causes a slightly greater inflammatory response than LS, and the clinical implications of this warrant further investigation.


Assuntos
Eletrocoagulação/métodos , Hemorragia Gastrointestinal/terapia , Hemostasia Cirúrgica/métodos , Terapia por Ultrassom/métodos , Animais , Modelos Animais de Doenças , Seguimentos , Hemorragia Gastrointestinal/patologia , Ligadura/métodos , Masculino , Coelhos , Estômago/irrigação sanguínea , Resultado do Tratamento , Cicatrização
13.
Artif Organs ; 30(8): 622-5, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16911316

RESUMO

The objective of the study was to investigate the alterations of aortic function after interposition of a tubular graft in the descending porcine thoracic aorta. Eight healthy Landrace pigs were subjected to thoracotomy under sterile conditions. A 5-cm-long segment of descending thoracic aorta was replaced with a Dacron graft. Pulse wave velocity (PWV) was measured using simultaneous recordings of electrocardiogram and Doppler pressure waveforms, which were received from right carotid and femoral arteries. Then, the recordings were fed to a computer for analytical estimation of PWV in several occasions: right after the interposition (D0), and after 15 (D15) and 30 (D30) days time. Euthanasia was performed after the D30-recordings and the aortic graft area was removed. "Before graft" (BG) as well as "after graft" (AG) aortic regions were examined under light microscopy in order to determine the aortic thickness (T) and number of lamellar units (LU). Eight sham-operated pigs were used as controls. The results showed that PWV decreased as soon as the graft interposition took place and was maintained, until the end of experiment (P < 0.05). Aortic wall thickness was increased both at pregraft and postgraft areas (P < 0.05), and LUs were also increased at the same regions. It is concluded that the interposition of a tubular graft in the descending thoracic aorta resulted in a decrease in PWV, which may improve left ventricular performance and enhance myocardial perfusion, due to a delay in the arrival of the reflecting diastolic wave.


Assuntos
Aorta Torácica/fisiologia , Aorta Torácica/cirurgia , Prótese Vascular , Animais , Aorta/fisiologia , Velocidade do Fluxo Sanguíneo , Vasos Coronários/fisiologia , Diástole/fisiologia , Coração/fisiologia , Pulso Arterial , Suínos
14.
BMC Clin Pathol ; 5: 5, 2005 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-15941482

RESUMO

BACKGROUND: Lower vaccination coverage among foreign-born children is of concern because they live in households and communities characterized by more intense exposure to infectious diseases. Because of their higher prevalence rates, there is an increasing occurrence of infectious diseases imported into developed countries. This case report emphasizes the emerging necessity for new clinicians and pathologists of having competence with old infectious disease pathology. CASE PRESENTATION: A three and a half year old girl, who presented with croup history of 5 days and has been in severe respiratory distress, was admitted to the Pediatric Intensive Care Unit in shock and acute respiratory failure. The patient was immediately intubated, and a grayish nonadherent membrane extending through the glottis down into the larynx was apparent during the procedure. Echocardiographic findings, which were consistent with acute myocarditis, confirmed poor left ventricular contractility despite escalating high doses of inotropes. Autopsy showed numerous strains of toxigenic corynobacterium diphtheriae, which also grew on the Loeffler cultures of membranes received during the intubation. CONCLUSION: It is critical that new generations of clinicians and bio-pathologists not only be trained in the subspecialty of infectious disease pathology, but that they also be willing participants in the diagnosis and investigation of infectious diseases.

16.
Clin Cardiol ; 27(6): 352-8, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15237696

RESUMO

BACKGROUND: Early diagnosis of heart transplant rejection is mandatory, since even mild rejection can rapidly progress to more severe rejection. Noninvasive diagnosis of heart transplant rejection still remains a challenge. HYPOTHESIS: The purpose of the study was to determine a possible association between myocardial performance index (MPI) and biopsy score of the heart transplant. METHODS: This is a retrospective cohort analysis of 99 complete Doppler echocardiographic studies from 24 consecutive patients (23 men) performed within 24 h of endomyocardial biopsy. Mean age of the cohort was 50 +/- 9 years and mean time from transplantation was 19 +/- 21 months (1-81). All patients were in sinus rhythm. Myocardial performance index was calculated as the ratio of isovolumic contraction time plus isovolumic relaxation time divided by ejection time. Left ventricular dimensions, left ventricular mass, ejection fraction, and a number of Doppler indices (E-point velocity, A-point velocity, deceleration time, and deceleration slope) were also measured. The International Society for Heart and Lung Transplantation (ISHLT) grading system was used for the classification of endomyocardial biopsies. RESULTS: Myocardial performance index was significantly prolonged (0.60 +/- 0.13, 0.68 +/- 0.08, 0.75 +/- 0.20, in biopsy scores 0, IA, and IB, respectively; p<0.001). Isovolumic contraction time was significantly prolonged; isovolumic relaxation time was not significantly changed. Ejection time and deceleration time were significantly shortened. Multivariate stepwise regression analysis revealed that MPI and deceleration time were the only independent predictors of biopsy score (r=0.48, F=10.53, p<0.0001). CONCLUSION: Myocardial performance index seems to be a useful adjunct in the follow-up of cardiac transplant patients. These preliminary data suggest that a larger study may be indicated to clarify the relevance of myocardial performance index.


Assuntos
Rejeição de Enxerto/diagnóstico por imagem , Transplante de Coração/efeitos adversos , Contração Miocárdica/fisiologia , Miocárdio/patologia , Adulto , Biópsia , Ecocardiografia Doppler , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/diagnóstico por imagem , Transplante de Coração/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/imunologia , Miocárdio/imunologia , Prognóstico , Valores de Referência , Estudos Retrospectivos , Fatores de Tempo
17.
Basic Res Cardiol ; 99(4): 241-6, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15221341

RESUMO

OBJECTIVES: To evaluate the effect of bone marrow pluripotent stem cell mobilization with granulocyte-monocyte colony stimulating factor (GMCSF) on infarct size and left ventricular function, in the setting of acute myocardial infarction, with a protocol easily applicable in clinical practice. METHODS: Ten pigs underwent left thoracotomy and left anterior descending coronary artery occlusion for 1 h, followed by reperfusion. After 50 min of arterial occlusion, the animals were randomly divided between treatment with placebo (Group 1) and subcutaneous GM-CSF (Group 2). The thoracotomy was closed and the animals recovered. In Group 2, GM-CSF, 20 microg/kg, was administered daily, 5 days/week, for 3 weeks. Echocardiograms were obtained at 5 and 28 days after acute myocardial infarction. At 30 days, infarct size, expressed as a percentage of the whole left ventricular mass, was measured. RESULTS: The white blood cell count increased from 13000 +/- 3338/ microl to 28700 +/- 4916/ microl (p = 0.001) in the GM-CSF-treated group. Infarct size was 7.8 +/- 6.1% in Group 1 vs 7.5 +/- 7.7% in Group 2 (ns). Similarly, no significant difference was observed between the 2 study groups in any of the echocardiographic measurements made at 28 days. CONCLUSIONS: Subcutaneous GMCSF administered during the early post acute myocardial infarction period neither decreased infarct size nor improved left ventricular function. Other protocols for mobilization of stem cells and their concentration in the injured area should be developed to combine efficacy and clinical applicability.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Células-Tronco Pluripotentes , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Medula Óssea , Ecocardiografia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Infarto do Miocárdio/diagnóstico por imagem , Distribuição Aleatória , Projetos de Pesquisa , Suínos , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia
18.
Int J Cancer ; 107(4): 629-34, 2003 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-14520702

RESUMO

Smoking has recently been recognised as causally associated with the development of gastric cancer (GC). However, evidence on the effect by sex, duration and intensity of smoking, anatomic subsite and cessation of smoking is limited. Our objective was to assess the relation between tobacco use and GC incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC). We studied data from 521,468 individuals recruited from 10 European countries taking part in the EPIC study. Participants completed lifestyle questionnaires that included questions on lifetime consumption of tobacco and diet in 1991-1998. Participants were followed until September 2002, and during that period 305 cases of stomach cancer were identified. After exclusions, 274 were eligible for the analysis, using the Cox proportional hazard model. After adjustment for educational level, consumption of fresh fruit, vegetables and preserved meat, alcohol intake and body mass index (BMI), there was a significant association between cigarette smoking and gastric cancer risk: the hazard ratio (HR) for ever smokers was 1.45 (95% confidence interval [CI] = 1.08-1.94). The HR of current cigarette smoking was 1.73 (95% CI = 1.06-2.83) in males and 1.87 (95% CI = 1.12-3.12) in females. Hazard ratios increased with intensity and duration of cigarette smoked. A significant decrease of risk was observed after 10 years of quitting smoking. A preliminary analysis of 121 cases with identified anatomic site showed that current cigarette smokers had a higher HR of GC in the cardia (HR = 4.10) than in the distal part of the stomach (HR = 1.94). In this cohort, 17.6 % (95% CI = 10.5-29.5 %) of GC cases may be attributable to smoking. Findings from this large study support the causal relation between smoking and gastric cancer in this European population. Stomach cancer should be added to the burden of diseases caused by smoking.


Assuntos
Fumar/efeitos adversos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Adulto , Idoso , Índice de Massa Corporal , Dieta , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Neoplasias Gástricas/patologia , Inquéritos e Questionários
19.
Dig Dis Sci ; 48(9): 1745-50, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14560994

RESUMO

The aim of this study was to examine glucocorticoid receptor (GR) immunohistochemical expression in colon cancer histopathological specimens and to correlate it with clinicopathological parameters, tumor proliferative capacity, cell cycle-related molecule expression, and patients' survival. Primary tumoral samples from 91 colon cancer patients were immunostained for the detection of GR, cyclins D1 and E, Rb protein (pRb), p16, p21, and Ki-67, using the streptavidin-biotin-peroxidase technique. GR expression was correlated with tumor histopathological characteristics and proliferative capacity, cell cycle-related molecule expression, and patients' survival. GR positivity was prominent in 44 of 91 (48%) colon cancer cases and was positively correlated with the expression of cell cycle-related molecules pRb (P = 0.008) and p16 (P = 0.002), while lack of correlation was noted with cyclins D1 and E and p21. GR expression was not correlated with tumor location, grade of differentiation, Dukes' stage, lymph node and liver metastasis, venous invasion, tumor proliferative capacity (evident by Ki-67-labeling status) and patient survival. Our findings support evidence for GR participation in the biological mechanisms underlying the carcinogenic evolution in the colon, implying the use of glucocorticoids as an adjuvant treatment for cell cycle modulation in colon cancer cells.


Assuntos
Neoplasias do Colo/metabolismo , Receptores de Glucocorticoides/metabolismo , Idoso , Ciclo Celular , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fosforilação , Proteína do Retinoblastoma/metabolismo
20.
Int J Cardiol ; 90(2-3): 239-45, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12957757

RESUMO

BACKGROUND: This study examined the evolution of the heart to lung (H/L) ratio of monoclonal antimyosin antibody (MAA) uptake in patients with suspected acute myocarditis (AM) and its time-dependent diagnostic value in conjunction with echocardiographic findings. METHODS: The study included 20 patients with a short history (<4 months) of heart failure symptoms and normal coronary arteries. All patients underwent cardiac antimyosin scintigraphy, echocardiography, right-heart catheterization and endomyocardial biopsy. Patients who survived beyond 1 year were reevaluated with a cardiac antimyosin scintigraphy and an echocardiographic study. RESULTS: Endomyocardial biopsy in 8/20 patients revealed findings compatible with the diagnosis of idiopathic dilated cardiomyopathy (group I) and in the remaining 12/20 was diagnostic of AM (group II). At baseline evaluation of the antimyosin H/L ratio uptake was similar in groups I and II, at 1.95+/-0.19 and 2.16+/-0.51, respectively (P=0.222), while the left ventricular end diastolic diameter (LVEDd) was significantly higher in group I (68+/-12 mm) than in group II (56+/-11 mm, P=0.041). In these patients an initial positive MAA scintigraphy (H/L ratio>1.55) associated with an LVEDd

Assuntos
Anticorpos Monoclonais , Radioisótopos de Índio , Miocardite/diagnóstico por imagem , Miosinas/imunologia , Doença Aguda , Adulto , Ecocardiografia , Feminino , Humanos , Masculino , Miocardite/imunologia , Cintilografia , Sensibilidade e Especificidade , Estatísticas não Paramétricas
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