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2.
Am J Cardiol ; 200: 32-39, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37295177

RESUMO

Data are limited regarding the impact of ischemic cardiomyopathy (ICM) or non-ICM (NICM) on the trajectory of in-hospital decongestion among patients with acute decompensated heart failure (ADHF). Therefore, we aimed to assess the course of decongestion among patients admitted for ADHF by history of ICM and NICM. Patients included in the DOSE (Diuretic strategies in patients with acute decompensated heart failure), ROSE (ROSE acute heart failure randomized trial), and Ultrafiltration in decompensated heart failure with cardiorenal syndrome (CARRESS-HF) trials of patients with ADHF were categorized into ICM and NICM based on history. Among 762 patients included in our meta-analysis, 433 (56.8%) had a history of ICM. Patients with ICM were older (70.8 vs 63.9 years; p ≤0.001) and had higher rates of co-morbidities. After covariate adjustment, there was no significant differences between NICM and ICM regarding net fluid loss (4,952 vs 4,384 ml, p = 0.81) or mean change in serum N-terminal pro-brain natriuretic peptide (-2,162 vs -1,809 pg/ml, p = 0.092). Mean change in weight showed modest improvement in favor of patients with NICM, but this did not meet statistical significance (-8.24 vs -7.70 pounds, p = 0.068). After adjustment, there was no significant difference in the risk of 60-day composite all-cause mortality or hospitalization for HF among those with ICM versus NICM. Among patients with left ventricular ejection fraction <40%, NICM was associated with higher scoring on global sense of well-being (global visual analog scale; +25.5 vs +19.1, p = 0.023) and improvement in serum creatinine (-0.031 mg/100 ml vs +0.042 mg/100 ml, p = 0.009) at 72 hours. Among patients with left ventricular ejection fraction >40%, NICM was associated with decreased scoring on global visual analog scale at 72 hours (+15.7 vs +21.2, p = 0.049). In conclusion, more than half of the patients admitted for ADHF had ICM. History of ICM was not independently associated with a difference in course of decongestion, self-assessment of well-being and dyspnea, or short-term clinical outcomes.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Isquemia Miocárdica , Humanos , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Cardiomiopatias/complicações , Cardiomiopatias/terapia , Isquemia Miocárdica/complicações
3.
J Clin Transl Res ; 8(6): 476-487, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36457898

RESUMO

Background: Endothelial progenitor cells (EPCs) have been well-studied for their differentiation potential and paracrine activity in vitro and in experimental animal studies. EPCs are the precursors of endothelial cells (ECs) and a rich source of pro-angiogenic factors, and hence, possess enormous potential to treat ischemic heart through myocardial angiogenesis. Their proven safety and efficacy observed during the pre-clinical and clinical studies have portrayed them as a near ideal cell type for cell-based therapy of ischemic heart disease.In response to the chemical cues from the ischemic heart, EPCs from the bone marrow and peripheral circulation home-in to the ischemic myocardium and participate in the intrinsic repair process at the molecular and cellular levels through paracrine activity and EC differentiation. EPCs also release small extracellular vesicles (sEVs) loaded with bioactive molecules as part of their paracrine activity for intercellular communication to participate in the reparative process in the heart. Aim: This literature review is based on the published data regarding the characteristic features of EPC-derived sEVs and their proteomic and genomic payload, besides facilitating safe and effective repair of the ischemic myocardium. In light of the encouraging published data, translational and clinical assessment of EPC-derived sEVs is warranted. We report the recent experimental animal studies and their findings using EPC-derived sEVs on cardiac angiogenesis and preservation of cardiac function. Relevance for Patients: With the promising results from pre-clinical studies, clinical trials should be conducted to assess the clinical utility of EPC-derived sEVs in the treatment of the ischemic myocardium.

4.
J Family Med Prim Care ; 11(7): 3992-3995, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36387629

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction carrying a mortality rate of up to 10%. We present a rare case of DRESS syndrome induced by amoxicillin-clavulanate, initially masquerading as red man syndrome. A 32-year-old male was admitted with flu-like symptoms and a maculopapular rash on the trunk and face that was exacerbated with vancomycin infusion, concerning for red man syndrome. He was receiving systemic antibiotics (vancomycin, ceftriaxone, and metronidazole) for infective endocarditis and previously took amoxicillin-clavulanate for a dental abscess. Despite the discontinuation of vancomycin, the exanthem continued to worsen, extending to involve >50% of his body surface area. Eosinophilia, hepatosplenomegaly, and acute kidney and liver injuries prompted consideration of DRESS syndrome. All antibiotics were discontinued, and systemic glucocorticoids were initiated. Punch biopsy revealed interface dermatitis with eosinophilic infiltrates; a high RegiSCAR score confirmed the diagnosis of DRESS. Amoxicillin-clavulanate was flagged as a severe allergy and deemed the culprit owing to the timing of exposure and personal/family history of hypersensitivity.

5.
Int J Mol Sci ; 23(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36430952

RESUMO

Histological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase+ and neutrophil-elastase+) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.


Assuntos
Armadilhas Extracelulares , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , Fator de von Willebrand/metabolismo , Histonas , Acidente Vascular Cerebral/patologia , Trombose/patologia , Fibrina/metabolismo , DNA
6.
Am J Cardiol ; 178: 72-79, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35773043

RESUMO

The 6-minute walk distance (6MWD) carries prognostic value in patients with heart failure with reduced ejection fraction (HFrEF). We performed this systematic review and meta-analysis to evaluate the effect of heart failure therapies on improvement in 6MWD. A systematic search of MEDLINE and Embase was conducted for randomized controlled trials measuring 6MWD at baseline and at follow-up in at least 50 patients with HFrEF across both arms. The primary outcome was improvement in 6MWD at follow-up. Meta-analysis was stratified in groups on the basis of medical therapy, device-based therapy, autonomic modulation, and exercise. Mean differences (MDs) with 95% confidence interval (CI) were reported across multiple studies that were included in the meta-analysis. A total of 44 studies met the inclusion criteria for systematic review; 17 of which were included for meta-analysis. Statistical analysis showed a statistically significant improvement in 6MWD in meters (m) at follow-up for device-based therapy (MD 20.01 m, 95% CI 18.71 to 21.31), autonomic modulation (MD 76.64 m, 95% CI 54.10 to 99.19), and exercise group (MD 39.52 m, 95% CI 19.68 to 59.35). Pooled analysis of medical therapy did not show statistically significant improvement in 6MWD at follow-up (MD 31.69 m, 95% CI -6.52 to 69.91). Device-based therapy (cardiac resynchronization therapy and cardiac contractility modulation), autonomic modulation, and exercise training programs are associated with improvement in 6MWD in patients with HFrEF. 6MWD is a useful test to gauge improvement in functional capacity among patients with HFrEF, especially those with severe symptomatic heart failure.


Assuntos
Insuficiência Cardíaca , Terapia por Exercício , Tolerância ao Exercício , Insuficiência Cardíaca/terapia , Humanos , Qualidade de Vida , Volume Sistólico
7.
J Am Heart Assoc ; 10(14): e020888, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34259032

RESUMO

Background The association of cardiac wall motion abnormalities (CWMAs) in patients with stroke who have major adverse cardiovascular events (MACE) remains unclear. The purpose of this study was to estimate the 50-month risk of MACE, including stroke recurrence, acute coronary events, and vascular death in patients with stroke who have CWMAs. Methods and Results We performed a retrospective analysis of prospectively collected acute stroke data (acute stroke and transient ischemic attack) over 50 months by electronic medical records. Data included demographic and clinical information, vascular imaging, and echocardiography data including CWMAs and MACE. Of a total of 2653 patients with acute stroke/transient ischemic attack, CWMA was observed in 355 (13.4%). In patients with CWMAs, the embolic stroke of undetermined source (50.7%) was the most frequent index stroke subtype and stroke recurrences (P=0.001). In multivariate Cox regression after adjustment for demographics, traditional risk, and confounding factors, CWMA was independently associated with a higher risk of MACE (adjusted hazard ratio [HR], 1.74; 95% CI, 1.37-2.21 [P=0.001]). Similarly, CWMA independently conferred an increased risk for ischemic stroke recurrence (adjusted HR, 1.50; 95% CI, 1.01-2.17 [P=0.04]), risk of acute coronary events (aHR, 2.50; 95% CI, 1.83-3.40 [P=0.001]) and vascular death (adjusted HR, 1.57; 95% CI, 1.04-2.40 [P=0.03]), in comparison to the patients with stroke without CWMA. Conclusions In a multiethnic cohort of ischemic stroke with CWMA, CWMA was associated with 1.7-fold higher risks of MACE independent of established risk factors. Embolic stroke of undetermined source was the most common stroke association with CWMA. Patients with stroke should be screened for CWMA to identify those at higher risk of MACE.


Assuntos
Ventrículos do Coração/fisiopatologia , Contração Miocárdica/fisiologia , Medição de Risco/métodos , Acidente Vascular Cerebral/complicações , Disfunção Ventricular/fisiopatologia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Catar/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/fisiopatologia , Tomografia Computadorizada por Raios X , Disfunção Ventricular/epidemiologia , Disfunção Ventricular/etiologia
8.
J Cardiovasc Electrophysiol ; 32(7): 1995-2004, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33861494

RESUMO

INTRODUCTION: To evaluate the safety of uninterrupted versus interrupted direct oral anticoagulation (DOAC) for patients undergoing catheter ablation (CA) of atrial fibrillation (AF). METHODS: We conducted a systematic search of MEDLINE and EMBASE for randomized controlled trials (RCT) and observational studies comparing uninterrupted versus interrupted DOAC for patients undergoing CA of AF. Primary outcome was major bleeding. Secondary outcomes included minor bleeding, stroke or transient ischemic attack (TIA) or thromboembolism (TE), silent cerebral ischemic events, and cardiac tamponade. Meta-analysis was stratified by study design. Risk ratios (RR) with 95% confidence intervals were calculated using random effects model and Mantel-Haenszel method was used to pool RR. RESULTS: A total of 13 studies (7 randomized, 6 observational) comprising 3595 patients were included. The RCT restricted analysis did not show any difference in terms of major bleeding (risk ratio [RR] = 0.79; [0.35-1.79]), minor bleeding (RR = 0.99 [0.68-1.43]), stroke or TIA or TE (RR = 0.80 [0.19-3.32]), silent cerebral ischemic events (RR = 0.64 [0.32-1.28]), and cardiac tamponade (RR = 0.61 [0.20-1.92]). Observational study restricted analysis showed a protective effect of uninterrupted DOAC on silent cerebral ischemic events (RR = 0.45 [0.31-0.67]) and no difference in other outcomes. CONCLUSIONS: There is no difference in bleeding and thromboembolic outcomes with uninterrupted versus interrupted DOAC for CA of AF and observational data suggests that uninterrupted DOACs are protective against silent cerebral ischemic lesions.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Humanos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
9.
Bratisl Lek Listy ; 121(12): 878-880, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33300357

RESUMO

OBJECTIVES: To determine the psychological impact of the social distancing measures in place due to the coronavirus pandemic. METHODS: We conducted a cross-sectional study on the Pakistani population. Informed consent was taken from all the participants. The data was collected through an online questionnaire. Cronbach's alpha was used to assess the internal consistency of the questionnaire, and it was found to be 0.80. The data obtained was analyzed on IBM's statistical package for the social sciences (SPSS) version 26. RESULTS: Out of 706 participants, 489 (69.26 %) were males and 217 (30.74 %) were females. The mean age of the participants was 35.24 ± 12.08 years. The majority of the participants were from Punjab (66.00 %).The mean time since quarantine measures had been established was 10.35 ± 5.09 days. The mean total score was 9.08 ± 2.38 points. A majority of the participants (25.64 %) were daily wage workers. t-test was significant when the time of quarantine was compared to the psychological impact. Significant results were also found when gender was compared to the impact. CONCLUSIONS: Social distancing measures have an impact on psychology and endocrinology of people in general. The impact can take the shape of long-lasting consequences (Tab. 3, Ref. 19).


Assuntos
COVID-19/psicologia , Distanciamento Físico , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
10.
Regen Med ; 13(4): 457-475, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29985118

RESUMO

Nearly two decades of experimental and clinical research with bone marrow cells have paved the way for Phase III pivotal trials in larger groups of heart patients. Despite immense advancements, a multitude of factors are hampering the acceptance of bone marrow cell-based therapy for routine clinical use. These include uncertainties regarding purification and characterization of the cell preparation, delivery protocols, mechanistic understanding and study end points and their methods of assessment. Clinical data show mediocre outcomes in terms of sustained cardiac pump function. This review reasons that the modest outcomes observed in trials thus far are based on quality of the cell preparation with a focus on the chronological aging of cells when autologous cells are used for transplantation in elderly patients.


Assuntos
Envelhecimento , Transplante de Medula Óssea/métodos , Cardiopatias , Miocárdio/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Autoenxertos , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Humanos
11.
Stud Health Technol Inform ; 210: 681-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25991238

RESUMO

There currently exists a gap between medical data and the clinicians who wish to use the data as the foundation for evidence-based medicine. The current disjointed workflow often requires statisticians to act as bridges in order to answer inquiries from clinicians. This can lead to suboptimal results as due to a gap between the fundamental understanding of clinical underpinnings and formal statistical interpretation of the data. To address this challenge, we have created a multi-platform application that allows clinicians to quickly and easily navigate and analyse the data. This application has been successfully implemented and tested within the Urology department at Mount Sinai Hospital for comprehensive analysis of complex urological data.


Assuntos
Interpretação Estatística de Dados , Conjuntos de Dados como Assunto , Registros Eletrônicos de Saúde/organização & administração , Armazenamento e Recuperação da Informação/métodos , Software , Interface Usuário-Computador , New York
12.
J Neuroimmunol ; 278: 271-6, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25468776

RESUMO

Inflammation plays a key role in the pathophysiology of Glioblastoma Multiforme (GBM). Here we focus on the contribution of the so far largely ignored complement system. ELISA and immunohistochemistry were combined to assess levels and localization of critical components of the initiation- and effector pathways of the complement cascade in sera and tumor tissue from GBM patients and matched controls. Serum levels of factor-B were decreased in GBM patients whereas C1q levels were increased. C1q and factor-B deposited in the tumor tissue. Deposition of C3 and C5b-9 suggests local complement activation.MBL deficiency, based on serum levels, was significantly less frequent among GBM patients compared to controls (14% vs. 33%). Therefore low levels of MBL may protect against the initiation/progression of GBM.


Assuntos
Neoplasias Encefálicas , Ativação do Complemento , Glioblastoma , Adulto , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/fisiopatologia , Complemento C1q/metabolismo , Fator B do Complemento/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Glioblastoma/sangue , Glioblastoma/imunologia , Glioblastoma/fisiopatologia , Humanos , Masculino , Lectina de Ligação a Manose/metabolismo , Pessoa de Meia-Idade , Análise de Sobrevida
13.
G Chir ; 36(6): 263-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26888702

RESUMO

INTRODUCTION: Informed consent, as the declaration of patients' will, forms the basis of legality of medical procedures. A standard form based on the Department of Health model is widely used in the National Health Service (NHS). The aim of this audit process was to assess the current consent practice in comparison to the UK's General Medical Council guidance and local policy and make any appropriate improvements. PATIENTS AND METHODS: 254 adult consent forms were reviewed during the patients' admission. Data collected included legible documentation, grade of health professional completing the consent form, providing additional written information, use of abbreviations, securing the consent form in the medical records and, providing a copy to the patient. After initial assessment, interventions in an attempt to improve adherence to guidelines were introduced. A repeat audit of a further set of 110 notes was completed to assess the effectiveness of our interventions. RESULTS: Our baseline assessment of 254 consent forms comprised of 198 (78%) elective and 56 (22%) emergency procedures. 87 (34%) consent forms were secure in the medical records. Grade of health professional was recorded in 211 (83%). 191 (75%) forms were legible. 48 (19%) patients were given copy of the consent. Only 24 (9%) patients were given additional written information. Abbreviations were used in 68 (27%) forms. Only 12 (5%) of consent forms met all criteria simultaneously. Re-audit after intervention assessed 110 consent forms; 30 (27%) for elective and 80 (72%) for emergency procedures. 52 (47%) of consent forms were secure in medical records, grade of health professional was recorded in 94 (85%), 101 (75%) forms were legible, 42 (38%) patients received copy of consent and 41 (37%) of patients received additional written information. CONCLUSION: Initially only 5% of consent forms completely met GMC guidelines. This demonstrates an alarmingly poor adherence to such guidance that plays a vital role in patient safety, patient ethics autonomy, not to mention potential medico-legal and clinical governance implications for surgical practice. Our intervention has improved the quality of consenting within our hospital according to these guidelines. With these interventions set to continue and further develop, we expect that the quality of the consenting process will continue to provide patients with all that it is designed to.


Assuntos
Termos de Consentimento , Hospitais Gerais , Adulto , Auditoria Clínica , Humanos , Prontuários Médicos , Melhoria de Qualidade
14.
Regen Med ; 7(1): 47-57, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22168497

RESUMO

AIM: To determine whether our novel approach of diazoxide-induced stem cell preconditioning might be extrapolated to human skeletal myoblasts to support their survival under lethal oxidant stress. METHODS & RESULTS: Using an in vitro model of H(2)O(2) treatment of human skeletal myoblasts, we report the ability of diazoxide-preconditioned human skeletal myoblasts to express cytokines and growth factors, which act in an autocrine and paracrine fashion to promote their own survival. Preconditioning of skeletal myoblasts was cytoprotective and significantly reduced their apoptotic index (p < 0.05). IL-11 gene and protein expression was significantly increased in preconditioned skeletal myoblasts. Transfection of skeletal myoblasts with IL-11-specific siRNA incurred their death under oxidant stress. The cytoprotective effect of diazoxide preconditioning was blocked by Erk1/2 inhibitor PD98059 (20-100 µM), which abrogated STAT-3 phosphorylation, thus confirming a possible involvement of Erk1/2/STAT3 signaling downstream of IL-11 in cell survival. We also investigated the time course of subcellular changes and signaling pathway of skeletal myoblasts apoptosis under oxidant stress before and after preconditioning. Apoptosis was induced in skeletal myoblasts with 100-500 µM H(2)O(2) for time points ranging from 1 to 24 h. Release of lactate dehydrogenase, disruption of the mitochondrial membrane potential and cytochrome-c translocation into cytoplasm were the earliest signs of apoptosis. Total Akt protein remained unchanged whereas marked reduction in pAkt was observed in the native skeletal myoblasts. Terminal dUTP nick end-labeling and annexin-V positivity were significantly increased after 4 h. Ultra-structure studies showed condensed chromatin, shriveled nuclei and swollen mitochondria. CONCLUSION: These data suggest that skeletal myoblasts undergo apoptosis under oxidant stress in a time-dependent manner and preconditioning of skeletal myoblasts significantly prevented their apoptosis via IL-11/STAT3 signaling.


Assuntos
Apoptose/efeitos dos fármacos , Interleucina-11/metabolismo , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/metabolismo , Oxidantes/farmacologia , Fator de Transcrição STAT3/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Anexina A5/metabolismo , Western Blotting , Linhagem Celular , Citocromos c/metabolismo , Citoproteção/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Marcação In Situ das Extremidades Cortadas , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/ultraestrutura , Fosforilação/efeitos dos fármacos , Propídio/metabolismo , Interferência de RNA/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Coloração e Rotulagem , Fatores de Tempo
15.
PLoS One ; 6(9): e25265, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21980409

RESUMO

METHODS AND RESULTS: The cardiac stem/progenitor cells from adult mice were seeded at low density in serum-free medium. The colonies thus obtained were expanded separately and assessed for expression of stem cell antigen-1 (Sca-1). Two colonies each with high Sca-1 (CSH1; 95.9%; CSH2; 90.6%) and low Sca-1 (CSL1; 37.1%; CSL2; 17.4%) expressing cells were selected for further studies. Sca-1⁺ cells (98.4%) isolated using Magnetic Cell Sorting System (MACS) from the hearts were used as a control. Although the selected populations were similar in surface marker expression (low in c-kit, CD45, CD34, CD31 and high in CD29), these cells exhibited diverse differentiation potential. Unlike CSH1, CSH2 expressed Nanog, TERT, Bcrp1, Nestin, Musashi1 and Isl-1, and also showed differentiation into osteogenic, chondrogenic, smooth muscle, endothelial and cardiac lineages. MACS sorted cells exhibited similar tendency albeit with relatively weaker differentiation potential. Transplantation of CSH2 cells into infarcted heart showed attenuated infarction size, significantly preserved left ventricular function and anterior wall thickness, and increased capillary density. We also observed direct differentiation of transplanted cells into endothelium and cardiomyocytes. CONCLUSIONS: The cardiac stem/progenitor cells isolated by a combined clonal selection and surface marker approach possessed multiple stem cell features important for cardiac regeneration.


Assuntos
Antígenos Ly/metabolismo , Proteínas de Membrana/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/terapia , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Animais Recém-Nascidos , Antígenos Ly/genética , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Ecocardiografia , Feminino , Citometria de Fluxo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
BMJ Case Rep ; 20112011 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-22696738

RESUMO

A 72-year-old Caucasian man presented with subtle and insidious symptoms of pain in the left iliac fossa and vomiting. The first clinical impression was of diverticulitis but he did not improve with conservative management. An initial contrast tomography (CT) scan demonstrated no diagnostic features. Four days later, a repeat CT scan demonstrated intramural gas in the ascending colon and in the intrahepatic portal venous radicles. There was a thrombus in the superior mesenteric artery with infarction of the caecum and ascending colon. An urgent right hemicolectomy was carried out. Although there was resolution of the thrombus and air in the portal system, the patient died 8 days later from intestinal haemorrhage.


Assuntos
Colo Ascendente/patologia , Doenças do Colo/diagnóstico , Embolia Aérea/diagnóstico , Veia Porta/patologia , Idoso , Colectomia , Colo Ascendente/irrigação sanguínea , Doenças do Colo/complicações , Doenças do Colo/cirurgia , Embolia Aérea/patologia , Evolução Fatal , Hemorragia Gastrointestinal/etiologia , Humanos , Isquemia/diagnóstico , Isquemia/cirurgia , Masculino
17.
BMJ Case Rep ; 20112011 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-22707667

RESUMO

This report describes an acute presentation of obstructive jaundice, with a clinical picture of cholecystitis. A primary carcinoid tumour in the terminal ileum with hepatic secondaries was found to be the cause. Additionally, in the terminal ileum was a closely associated lipoma leading to an ileo-caecal intussusception. There are few such cases in the literature, particularly in the absence of any changes in bowel habit or lower abdominal pain. The majority of cases of intussusception in clinical practice occur in the paediatric population. Of the small numbers (<5%) that occur in adulthood, the underlying aetiology is most commonly a primary adenocarcinoma, with a far smaller number being attributable to lipoma, lymphoma and polyps.


Assuntos
Tumor Carcinoide/diagnóstico , Colecistite/diagnóstico , Neoplasias do Íleo/complicações , Neoplasias do Íleo/diagnóstico , Valva Ileocecal , Intussuscepção/etiologia , Lipoma/complicações , Idoso , Tumor Carcinoide/secundário , Diagnóstico Diferencial , Feminino , Humanos , Doenças do Íleo/etiologia , Neoplasias do Íleo/secundário
18.
Mol Cancer Res ; 8(4): 604-14, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20332211

RESUMO

Overexpression of neuropeptide Y (NPY) and its receptor system has been reported in various types of cancers. NPY Y5 receptor (Y5R) has been implicated in cell growth and angiogenesis. However, the role of Y5R in breast cancer is unknown. To identify the role of Y5R in breast cancer, we screened several breast cancer cell lines to examine the expression of Y5R and its function in breast cancer. All screened cell lines express both Y1 receptor and Y5R except BT-549, which expresses mainly Y5R. Binding studies showed that NPY, Y5R-selective agonist peptide, and Y5R-selective antagonist (CGP71683A) displaced (125)I-PYY binding in BT-549 cell membranes in a dose-dependent manner. The displacement studies revealed the presence of two binding sites in Y5R with IC(50) values of 29 pmol/L and 531 nmol/L. NPY inhibited forskolin-stimulated cyclic AMP accumulation with an IC(50) value of 52 pmol/L. NPY treatment of BT-549 cells induced extracellular signal-regulated kinase phosphorylation but did not alter intracellular calcium. Y5R activation stimulates BT-549 cell growth, which is inhibited by CGP71683A, pertussis toxin, and extracellular signal-regulated kinase blockade. CGP71683A alone induced cell death in a time- and dose-dependent manner in Y5R-expressing cells. The stimulation of MDA MB-231 cell migration by NPY is inhibited by CGP71683A. Together, our results suggest that Y5R plays an important role in cancer cell growth and migration and could be a novel therapeutic target for breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neuropeptídeo Y/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Ligação Competitiva/efeitos dos fármacos , Ligação Competitiva/fisiologia , Neoplasias da Mama/genética , Carcinoma/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células , Colforsina/antagonistas & inibidores , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/genética , Feminino , Humanos , Naftalenos/farmacologia , Invasividade Neoplásica/genética , Neuropeptídeo Y/farmacologia , Fosforilação/efeitos dos fármacos , Pirimidinas/farmacologia , Receptores de Neuropeptídeo Y/efeitos dos fármacos , Receptores de Neuropeptídeo Y/genética
19.
Int J Surg ; 7(1): 62-5, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19095510

RESUMO

BACKGROUND: Raised patient expectations and the 2-week rule for the investigation of suspected malignancy have led to heightened demands on surgical outpatient clinics. In this context, the utility of benign post-operative or investigative follow-ups requires justification. METHODS: The surgical outpatient clinic workload of four substantive general surgeons at a typical DGH was analysed over a 4-week period. All notes were examined to identify referral source, management plan and whether that clinic attendance was justified. RESULTS: Twenty three clinics (410 patients) were examined over the period of this study. Three hundred and twenty one patient episodes were examined; 52 episodes did not occur due to patient non-attendance and 37 episodes were not accounted for ('missing/incomplete data'). Thirty three percent of the patients underwent consultant review whilst 57% were reviewed by middle grade surgeons and 9% by SHO/ST2 doctors. Forty eight percent of the consultations were new referrals: 37% of these patients were added to the elective surgical waiting list. One hundred and sixty eight follow-up consultations occurred, which included cancer patients (6%), review patients (12%), patients attending for investigative results (13%) and benign post-operative follow-ups (22%). Forty six of the 69 (66%) post-operative follow-ups were deemed unnecessary as patients were being seen after benign procedures (hernia repair, anorectal surgery or laparoscopic cholecystectomy). CONCLUSION: Over 50% attendances (21/41) for 'normal' results could have been avoided by the use of a directed informative letter. Outpatient clinics are an important resource whose usage must be optimised.


Assuntos
Assistência Ambulatorial/organização & administração , Procedimentos Cirúrgicos Ambulatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/estatística & dados numéricos , Criança , Pré-Escolar , Seguimentos , Humanos , Auditoria Médica , Pessoa de Meia-Idade , Encaminhamento e Consulta/organização & administração , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Carga de Trabalho , Adulto Jovem
20.
Dig Surg ; 23(4): 265-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17035701

RESUMO

BACKGROUND: Digestive tract schwannomas (DTS) are rare benign mesenchymal tumours usually affecting females between 30 and 60 years old. METHODS: We retrospectively reviewed 2 cases of DTS treated at our hospital. The first case is a 38-year-old female with gastric schwannoma presenting with acute upper gastro-intestinal bleeding. The second case is a 36-year-old female with mesenteric schwannoma presenting with chronic right iliac fossa pain. Both patients underwent surgical resection of the tumour. RESULTS: Histology and immunohistochemistry revealed the typical appearance of a DTS. CONCLUSION: DTS is most commonly found in the stomach. It is usually asymptomatic but can present with variable symptoms. Definitive diagnosis can only be made on the basis of immunohistochemistry. Surgical resection is the treatment of choice.


Assuntos
Neurilemoma/cirurgia , Neoplasias Peritoneais/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Mesentério/patologia , Neurilemoma/diagnóstico , Neoplasias Peritoneais/diagnóstico , Neoplasias Gástricas/diagnóstico , Tomografia Computadorizada por Raios X
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