RESUMO
Colorectal cancer is one of the most frequent causes of death in Western countries. Most patients develop metastasis traveling through the lymphatic system, and regional lymph node metastasis is considered a marker for dissemination, increased stage, and worse prognosis. Despite rapid advances in tumor biology, the processes that underpin lymphatic invasion and lymph node metastasis remain poorly understood. The aim of this study was to establish an easy protocol for isolation of pure tumor lymphatic endothelial cells derived from lymph nodes to study differences compared with normal endothelial cells of uninvolved tissue from the same patients. Cells were isolated with very high purity via magnetic cell sorting and express the specific lymphatic markers Prox-1 and Lyve-1. They show differences in expression of adhesion molecules, chemokines, and growth factor secretion, and capability to form capillaries when seeded on basal membrane, thereby, revealing important differences between the two cell type. These cultures may provide a promising platform for the comparative analysis of both cell types at the molecular and biological level and to optimize treatment strategies.
Assuntos
Neoplasias Colorretais/patologia , Células Endoteliais/fisiologia , Movimento Celular , Separação Celular , Células Cultivadas , Quimiocina CCL2/análise , Citocinas/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/análise , Linfangiogênese , Metástase Linfática , FenótipoRESUMO
BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.
Assuntos
Tumores do Estroma Gastrointestinal , Margens de Excisão , Humanos , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Prognóstico , Europa (Continente) , Adulto , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Intervalo Livre de Doença , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC. PATIENTS AND METHODS: Patients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months. RESULTS: From March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%). CONCLUSIONS: Cabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.
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Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/etiologia , Carcinoma Adrenocortical/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Progressão da Doença , Humanos , Mitotano/efeitos adversos , TaxoidesRESUMO
BACKGROUND: A prevalence study aimed to update the epidemiological scenario of Hospital-Acquired Infections (HAI) was performed at the San Martino University Hospital of Genoa, the Regional Reference Adult-care Center in Liguria, Italy, with more than 1300 beds. MATERIALS AND METHODS: The investigation was performed in all the wards, except the Psychiatric Units, between 19th March and 6Ih April, 2007, using a one-day monitoring system for each ward. International standardized criteria and definitions for the surveillance of HAI were used for the collection of data, which were recorded in specific software for subsequent consolidation, analysis and quality control. RESULTS: The hospital infection control staff actively monitored 912 inpatients: a total of 84 HAI among 72 patients were diagnosed, with an overall prevalence of infections and affected cases of 9.2% (95% CI: 7.3-11.1) and 7.9% (95% CI: 6.1-9.7), respectively. Urinary Tract Infections (UTI) (30.9%), Respiratory Tract Infections (RTI) (28.6%) and Blood Stream Infections (BSI) (21.4%) were found to be the most frequent infections. As expected, both specific prevalence and localization of HAI varied considerably between wards, with the highest values recorded in Intensive Care Units (ICU) and in Functional Rehabilitation wards. RTI (26.3%) and BSI (13.2%) were found primarily represented in ICU, while the highest values of UTI (13.3%) were registered in Functional Rehabilitation Units. Enterococcus spp. (16.8%), Candida spp. (14%), Pseudomonas spp. (12.2), Staphylococcus aureus (10.7%), Escherichia coli (10.3%) and Coagulase-negative staphylococci (CNS) (9.3%) were the most frequent pathogens isolated. The overall rate of administration of antibiotics was 55.3% and penicillin (26.7%), cephalosporins (22.8%) and fluoroquinolones (17.9%) were found to be the leading antibacterial administered. CONCLUSION: Results of the present study have been, and are currently, used for orientating surveillance and control hospital policies, planning activities according to a rational and evidence-based approach.
Assuntos
Infecção Hospitalar/epidemiologia , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/epidemiologia , Controle de Infecções/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Criança , Pré-Escolar , Infecção Hospitalar/prevenção & controle , Feminino , Bactérias Gram-Negativas/classificação , Infecções por Bactérias Gram-Negativas/prevenção & controle , Bactérias Gram-Positivas/classificação , Infecções por Bactérias Gram-Positivas/prevenção & controle , Hospitais Públicos/organização & administração , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Prevalência , Sepse/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecções Urinárias/epidemiologia , Adulto JovemRESUMO
This paper presents the first experience of the Spanish Society of Internal Medicine in the development of an Internet-based Continuing Medical Education program for Society members, accredited by the Health Ministry and the Autonomous University of Barcelona, and funded by the Menarini Group SA. Academic performance and satisfaction of participants in this course have been very satisfactory, both with respect to scientific content and the virtual learning environment. This experience shows that Internet-based continuing medical education is a field with a great future that is well accepted by participating physicians, and that the scientific societies, with the collaboration of other institutions and companies, can lead Internet-based Continuing Medical Education programs especially designed and tailored to their members.
Assuntos
Educação Médica Continuada/métodos , Medicina Interna/educação , Internet , Sociedades Médicas , EspanhaRESUMO
In spite of the lung being the target organ par excellence of tuberculosis, any other organ and system can be affected. In this article we review the forms of extrapulmonary tuberculosis, with the exception of the pleural form that requires the use of good diagnostic skills. From the dreaded tuberculous meningitis, by way of the insidious affectation of the spondylodiscitis, the so-called ganglionary affectation , the genitourinary affectation, pericarditis, and ending with less frequent forms such as ocular and cutaneous tuberculosis. In each section we will indicate what is most characteristic with the aim of providing a diagnostic and therapeutic orientation.
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Tuberculose/diagnóstico , Tuberculose/terapia , HumanosRESUMO
OBJECTIVE: To describe the main characteristics of a cohort of patients with uveitis referred to a multidisciplinary unit in northern Spain. MATERIAL AND METHODS: Retrospective analysis of clinical records of patients evaluated in the Multidisciplinary Unit of the Navarra Hospital Complex from the period January 2010 until March 2015. An analysis was performed on the demographic characteristics, origin, types of uveitis, laterality, and aetiology. The present series was also compared with 2 previous series from Castilla y León and Barcelona. RESULTS: A total of 500 patients were identified, with a mean age of 47.9±16.4 years, with 50% women. The most frequent type of uveitis was anterior uveitis (65.4%), followed by posterior uveitis (17.6%), panuveitis (15.2%), and intermediate uveitis (1.8%). The origin was unclassifiable in 31.2%, followed by non-infectious systemic disease in 29.2%. Ankylosing spondylitis was the most frequent cause in 10.8% of patients, followed by herpes infection in 9.2%, and toxoplasmosis in 7.8%, respectively. Compared with the 2other cohorts, the present cohort showed a higher proportion of unilateral anterior uveitis. Furthermore, the patients from the Navarra series had a higher prevalence of unilateral and idiopathic uveitis compared to the series from Barcelona. CONCLUSIONS: The main characteristics of the present cohort of patients with uveitis are similar to those of patients from other regions of our country. Unilateral anterior uveitis and idiopathic uveitis were the most frequent in our series.
Assuntos
Ambulatório Hospitalar/estatística & dados numéricos , Uveíte/epidemiologia , Adulto , Idoso , Comorbidade , Emigrantes e Imigrantes , Feminino , Antígeno HLA-B27/análise , Infecções por Herpesviridae/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Socioeconômicos , Espanha/epidemiologia , Espondilite Anquilosante/epidemiologia , Toxoplasmose Ocular/epidemiologia , Uveíte/diagnóstico , Uveíte/etiologiaRESUMO
We present the case of a 46 year-old man with Multiple Symmetric Lipomatosis (MSL), an infrequent disease with an unknown aetiology. MSL is characterized by multiple masses of adipose tissue and it is usually associated with alcoholism, metabolic disorders and neuropathy. We describe the clinical-morphological characteristics of the lesions it presents, the exploratory findings, cervical CAT, the analytical results and the results of subcutaneous biopsy. MSL type I disease was diagnosed. The treatment of choice, the lipectomy, was performed, making it possible to obtain a substantial disease improvement, both physical and aesthetically.
Assuntos
Lipomatose Simétrica Múltipla/patologia , Biópsia , Humanos , Lipomatose Simétrica Múltipla/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To investigate clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. METHODS: Retrospective multi-center chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. RESULTS: One hundred and five patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting of the disease. In 89 cases a R0 resection was achieved, while in 16 a R+ hepatic resection was performed. Adjuvant chemotherapy was administered to 29 patients. Surgical mortality was 1% and morbidity 13.3%. Median disease-free survival was 10 months, median overall survival was 14.6 months. Overall 1, 3, and 5-year survival rates were 58.2%, 20.3%, and 13.1%, respectively. Survival was influenced independently by the factor T of the gastric primary (p < 0.001), by the curativity of surgical procedure (p = 0.001), by the timing of hepatic involvement (p < 0.001) and by adjuvant chemotherapy (p < 0.001). T4 gastric cancer, R+ resection, synchronous metastases, and abstention from adjuvant chemotherapy were associated with a worse prognosis; T4 gastric cancer and R+ resections displayed a cumulative effect (p < 0.001). CONCLUSIONS: Our data show that R0 resection must be pursued whenever possible. Furthermore, in the synchronous setting, the coexistence of T4 gastric primaries and R+ resections suggests prudence and probably abstention from hepatectomy. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results.
Assuntos
Hepatectomia , Neoplasias Hepáticas/cirurgia , Metastasectomia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/cirurgia , Idoso , Fístula Anastomótica/epidemiologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Hemorragia Pós-Operatória/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: Data on cardiac and vascular structure in secondary hypertension are generally scarce, and no data on the interrelations between cardiac mass and structural characteristics of the vessel wall, both in large and in small resistance arteries, are presently available. OBJECTIVES: The aim of this study was to investigate the relation between structural changes in subcutaneous small arteries, left ventricular mass and wall thickness of the common carotid artery in patients with primary and secondary hypertension. METHODS: Seventy-four subjects were included in the study: 11 patients with pheochromocytoma, 14 with primary aldosteronism (PA), 19 with renovascular hypertension (RVH), 18 with essential hypertension (EH) and 12 normotensive (NT) control subjects. All subjects were submitted to a biopsy of subcutaneous fat. Morphologic characteristics of subcutaneous small resistance arteries (relaxed diameter <300 microm) were directly evaluated using a micromyographic technique. All subjects were submitted to calculation of left ventricular mass index (LVMI) and common carotid artery intima-media thickness (CCIMT), using ultrasound technique. RESULTS: The correlation coefficients between the media to lumen ratio in subcutaneous small arteries (M/L) and LVMI or between M/L and CCIMT were closer in RVH than in pheochromocytoma, EH or NT; in PA the correlation coefficients were slightly less close than those in RVH. An excess prevalence of carotid plaques in RVH was observed. CONCLUSIONS: A close relation between small resistance artery morphology and cardiac or carotid artery structure may be observed in those hypertensive patients in whom the renin-angiotensin-aldosterone system is activated. In constrast, in NT, EH and pheochromocytoma no significant correlation between M/L and LVMI or CCIMT was observed.
Assuntos
Arteríolas/patologia , Artéria Carótida Primitiva/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Hipertensão/patologia , Artéria Carótida Primitiva/patologia , Ecocardiografia , Feminino , Ventrículos do Coração/patologia , Humanos , Hiperaldosteronismo/complicações , Hipertensão/diagnóstico por imagem , Hipertensão/etiologia , Hipertensão Renovascular/diagnóstico por imagem , Hipertensão Renovascular/patologia , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Feocromocitoma/complicações , Pele/irrigação sanguíneaRESUMO
BACKGROUND: Patients who have experienced a recent major bleeding episode are usually excluded from clinical studies of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials may not be suitable for these patients. The Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) is a multicenter, observational registry designed to gather and analyze data on VTE treatment practices and clinical outcomes in patients with acute VTE. OBJECTIVES: The aim of this analysis was to study outcomes of patients with VTE who had experienced recent major bleeding (< 30 days prior to VTE diagnosis). METHODS: Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3 months were recorded. RESULTS: Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding: 69 (40.6%) gastrointestinal tract, 60 (35.3%) intracranial, 41 (24.1%) other. The incidences of major bleeding (4.1%) and recurrent pulmonary embolism (PE) (2.4%) were significantly higher in patients with recent major bleeding. Among them, patients with cancer had an increased incidence of major bleeding [odds ratio (OR) 10.0, 95% confidence interval (CI) 2.3, 50; P < 0.001] and fatal PE (OR 4.1, 95% CI 0.98, 17; P < 0.05). CONCLUSIONS: Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to enrollment, those with cancer had a poorer clinical outcome than those without cancer.
Assuntos
Hemorragia , Tromboembolia/diagnóstico , Trombose Venosa/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Razão de Chances , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Tromboembolia/complicações , Tromboembolia/mortalidade , Terapia Trombolítica/métodos , Resultado do Tratamento , Trombose Venosa/complicações , Trombose Venosa/mortalidadeRESUMO
BACKGROUND: Coeliac disease (CD) has been reported in several patients affected by chromosomal disorders, including Down syndrome (DS) and Turner syndrome (TS). CD has also been found in sporadic Williams syndrome (WS) patients. In this study, CD was evaluated in a consecutive series of patients with WS, in order to estimate if the prevalence of CD in WS patients is higher than in the general population. METHODS AND RESULTS: A consecutive series of 63 Italian patients with WS was studied by analysing the dosage of antigliadin antibodies (AGA) IgA and antiendomisium antibodies (AEA). In patients with positive AGA and AEA, small bowel biopsy was performed. The prevalence of CD in our WS population was compared with that estimated in a published series of 17 201 Italian students. Seven WS patients were found to be positive for AGA IgA and AEA. Six of them underwent small bowel biopsy, which invariably disclosed villous atrophy consistent with CD. The prevalence of CD in the present series of WS patients was 9.5% (6/63), compared to 0.54% (1/184) in the Italian students (p<0.001). CONCLUSION: The present results suggest that the prevalence of CD in WS is higher than in the general population and is comparable to that reported in DS and TS. AGA and AEA screening is recommended in patients with WS.
Assuntos
Doença Celíaca/patologia , Síndrome de Williams/patologia , Adolescente , Doença Celíaca/sangue , Doença Celíaca/complicações , Criança , Pré-Escolar , Feminino , Gliadina/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Masculino , Síndrome de Williams/sangue , Síndrome de Williams/complicaçõesRESUMO
We reviewed 33 consecutive patients with diaphragmatic injuries. Twenty-nine were admitted in emergency conditions after blunt (22 patients) or penetrating injury, presenting shock, dyspnoea, coma or acute abdomen in 21 cases; major associated lesions were found in 23 patients. Four patients presented acute complications of visceral herniation 2, 4, 84 and 216 months after the trauma. The diagnosis was preoperative in 23 cases, intraoperative in 9; in one case it was missed at laparotomy, becoming evident the day after. The sensibility of preoperative chest x-ray and CT was 86% and 100% in presence of visceral herniation, 14% and 0% in absence of visceral hernia. The diaphragmatic repair was always obtained by direct suture, following 20 haemostatic procedures (liver, spleen, mesenterium) and two bowel resections. The mortality rate was 24.4%; the morbidity rate was 48%. Traumatic lesions of the diaphragm are generally expression of particularly severe trauma whose outcome is mainly influenced by the associated lesions. They are also correlated to specific morbidity and mortality, so the surgical exploration is mandatory whenever this injury is suspected, considering that the preoperative diagnosis relies on visceral dislocation. Associated lesions influence the surgical strategy but a direct suture is usually effective in preventing specific complications.
Assuntos
Diafragma/lesões , Diafragma/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: In January 2002 an occupational respiratory diseases record was established in Navarre so that the number and characteristics of the occupational respiratory pathology could be analysed. METHODS: The cases reported by doctors who collaborated in 2002, 2003 and 2004, were entered in a database for subsequently analysis. This database has several variables: gender, age, tobacco habit, hospital department and notifying doctor, diagnosis, job and causal agent. RESULTS: 125 cases were reported. 97 males (77.6%) and 28 females (22.4%). Average age was 55,4 years old. Eighty-eight were non-smokers (70.4%) and 37 were smokers (29.6%). Pneumology reported 84 cases (67.2%) and Allergology 41 (32.8%). The diagnoses were: 50 bronchial asthma (40%), 31 benign pleural disease (24.8%), 8 extrinsic allergic alveolitis (6.4%), 8 mesothelioma (6.4%), 7 bronchopulmonary cancer (5.6%), 5 acute inhalations (4%), 3 amianthinopsy (2.4%), 2 rhinitis (1.6%), 1 RADS (0.8%) and 1 COPD (0.8%). The most reported jobs were: 13 painting and varnishing (10.4%), 12 spinning asbestos yarn (9.6%) and 8 bakery and confectionery (6.4%). The main causal agents were: 49 cases of asbestos (39.2%), 15 isocyanates (12%) and 8 silica (6.4%). CONCLUSIONS: The most frequent pathology was bronchial asthma, followed by benign pleural disease. The most reported job was painting and varnishing and secondly spinning asbestos yarn. Asbestos was the first substance involved and the second was isocyanates. Most of the patients were males and non-smokers. The Pneumology Service of the Virgen del Camino Hospital reported most of the cases. Ratio contrast analysis showed a certain tendency towards a statistical significance in rhinitis, occupational asthma and amianthinopsy.
Assuntos
Doenças Profissionais/epidemiologia , Sistema de Registros , Doenças Respiratórias/epidemiologia , Adulto , Área Programática de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologiaRESUMO
Atrial fibrillation (AF) in the elderly is a complex condition due to the high number of frequently associated comorbidities, such as cardiovascular and kidney disease, cognitive disorders, falls and polypharmacy. Except when contraindicated, anticoagulation is necessary for preventing thromboembolic events in this population. Both vitamin K antagonists and direct oral anticoagulants (dabigatran, rivaroxaban and apixaban) are indicated in this context. Renal function should be closely monitored for this age group when these drugs are used. In recent years, various clinical practice guidelines have been published on patients with AF. The majority of these guidelines make specific recommendations on the clinical characteristics and treatment of elderly patients. In this update, we review the specific comments on the recommendations concerning antithrombotic treatment in elderly patients with nonvalvular AF.
RESUMO
Phospholipases A2 (PLA2s) are enzymes responsible for inflammatory effects, edema formation, myotoxicity, neurotoxicity and other manifestations from envenoming. In this paper we report the isolation and biochemical characterization of Lmr-PLA2, the first acidic PLA2 found in Lachesis muta rhombeata venom. Furthermore, this study compared biological effects of Lmr-PLA2 and crotoxin B (CB), a PLA2 from Crotalus durissus terrificus venom. Lmr-PLA2 was isolated by molecular exclusion and reversed phase chromatography. The purified enzyme showed a molecular mass of 13,975 Da, pI of 5.46 and its partial amino acid sequence showed a high identity with PLA2s already described in the literature. In addition, this enzyme possesses the residue D49 in its amino acid sequence, indicating that it is a catalytically active PLA2. Lmr-PLA2 presented high phospholipase activity and was able to inhibit platelet aggregation. Studies of biochemical characterization of new PLA2s, as Lmr-PLA2, are relevant since they help to clarify the structure-function relationship of this important class of toxins.
Assuntos
Fosfolipases A2/química , Fosfolipases A2/isolamento & purificação , Proteínas de Répteis/química , Proteínas de Répteis/isolamento & purificação , Venenos de Víboras/química , Sequência de Aminoácidos , Animais , Creatina Quinase/análise , Creatina Quinase/metabolismo , Crotoxina/química , Edema/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Fragmentos de Peptídeos/análise , Fosfolipases A2/toxicidade , Agregação Plaquetária/efeitos dos fármacos , Proteínas de Répteis/toxicidade , Alinhamento de Sequência , ViperidaeRESUMO
The aim of our study was to evaluate the relationships between endothelial function, small resistance artery structure, and blood pressure in patients with primary or secondary hypertension. Sixty subjects were included in the study: 9 patients with pheochromocytoma, 10 with primary aldosteronism, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotensive subjects who served as controls. Clinic and 24-hour ambulatory blood pressure (ABPM) were evaluated. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph and the media/lumen ratio was calculated. A dose-response curve to acetylcholine was performed at cumulative concentrations from 10(-9) to 10(-5) mol/L. The vasodilator response to acetylcholine was similarly impaired in the four groups of hypertensive patients (ANOVA P<.05 versus normotensive controls), without any significant difference among them. In subcutaneous small arteries of patients with either primary aldosteronism or renovascular hypertension, a marked increase in media:lumen ratio was observed, while in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in essential hypertension. No significant correlation between media-lumen ratio or clinic blood pressure and maximum acetylcholine-induced vasodilatation was observed. On the contrary, a significant, albeit not very close, correlation between ABPM values and maximum acetylcholine-induced vasodilatation was observed (r=34, P<.05 with 24-hour systolic blood pressure, r=0.36, P<.05 with 24-hour diastolic blood pressure). In conclusion, endothelial dysfunction seems to be independent from the degree of vascular structural alterations and from the etiology of hypertension, and it is probably more linked to the hemodynamic load.
Assuntos
Arteríolas/fisiopatologia , Pressão Sanguínea , Endotélio Vascular/fisiopatologia , Hipertensão Renovascular/fisiopatologia , Hipertensão/etiologia , Hipertensão/fisiopatologia , Acetilcolina/farmacologia , Tecido Adiposo/irrigação sanguínea , Neoplasias das Glândulas Suprarrenais/complicações , Aldosterona/sangue , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Colesterol/sangue , Diástole , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Epinefrina/urina , Feminino , Humanos , Hiperaldosteronismo/fisiopatologia , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Nitroprussiato/farmacologia , Norepinefrina/urina , Feocromocitoma/complicações , Valores de Referência , Análise de Regressão , Renina/sangue , Sístole , Triglicerídeos/sangue , Resistência VascularRESUMO
OBJECTIVE: Arterial hypertension is frequently associated with the presence of endothelial dysfunction in human subcutaneous small resistance arteries, as evaluated by responses to acetylcholine or bradykinin; however it is not known whether patients with diabetes mellitus show similar alterations. Therefore, we have investigated endothelial function in subcutaneous arteries of normotensive subjects (NT), of patients with essential hypertension (EH), of patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as of patients with both essential hypertension and non-insulin-dependent diabetes mellitus (NIDDM+EH). PATIENTS AND METHODS: All subjects were submitted to a biopsy of the subcutaneous fat Small arteries were dissected and mounted on a micromyograph. The media to lumen ratio (M/L) was calculated. A concentration-response curve to acetylcholine, to bradykinin as well as to the endothelium-independent vasodilator sodium nitroprusside were performed. We also evaluated the contractile response to endothelin-1. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) plasma levels were also measured. RESULTS: The vasodilatation to acetylcholine and bradykinin (but not to sodium nitroprusside) was significantly and similarly reduced in EH, in NIDDM, and in NIDDM+EH compared with NT. The contractile response to endothelin-1 was similarly reduced in EH, in NIDDM and in NIDDM+EH. Plasma ICAM-1 and VCAM-1 concentrations were higher in EH, NIDDM and NIDDM+EH than in NT. CONCLUSIONS: An evident endothelial dysfunction was detected in patients with NIDDM, and the simultaneous presence of EH did not seem to exert an additive effect. The contractile responses to endothelin-1 were reduced possibly as a consequence of ET(A) receptor down-regulation.
Assuntos
Artérias/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Resistência Vascular , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Valores de Referência , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
Trichinosis is an infection contracted by ingestion of meat containing viable larvae of the nematode Trichinella spiralis. This report concerns an outbreak of infections with this parasite in Navarra, Spain that was associated with home-prepared pork products. After the detection of a person with trichinosis, a study of all subjects that had ingested meat from the presumably infected pork was carried out. Forty-four members of eight families were enrolled in the study. Ten had symptoms suggestive of trichinosis, 20 had hypereosinophilia, and 15 had positive serologic test results for anti-Trichinella antibodies. Three groups could be distinguished according to the kind of product each subject had ingested (pork sausage, blood pudding, and loin). Twelve months later, all had a normal eosinophil count and a negative serology.
Assuntos
Surtos de Doenças , Parasitologia de Alimentos , Produtos da Carne/parasitologia , Trichinella spiralis/imunologia , Triquinelose/epidemiologia , Animais , Anticorpos Anti-Helmínticos/análise , Humanos , Espanha/epidemiologia , SuínosRESUMO
S-100 is a protein originally believed to be unique to the nervous system. We report here on the presence of S-100 in rat adipocytes, using immunohistochemical and immunochemical methods. We demonstrate that the protein in adipose tissue is present at a concentration comparable to that measured in the nervous tissue and is immunologically identical to brain S-100, indicating that the protein can no longer be regarded as being specific to the nervous system.