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1.
Cureus ; 13(11): e19551, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34917433

RESUMO

Methamphetamine is the second most commonly abused drug worldwide. It is a sympathomimetic agent that works by inhibiting the reuptake of monoamine neurotransmitters, including dopamine, norepinephrine, and serotonin. Methamphetamine use is associated with early mortality, and cardiovascular complications are the leading cause of increased mortality. We discuss the case of a 41-year-old man who presented to the emergency department with a sudden abdominal pain of eight hours' duration. The pain was located in the epigastric area with radiation to the back. Upon examination, the patient appeared agitated and diaphoretic. His pupils were dilated bilaterally. His vital signs included tachycardia (120 bpm), tachypnea (24 bpm), hypertension (150/90 mmHg), and normal temperature (36.9 ℃). Abdominal examination revealed a soft and lax abdomen with no tenderness. His bowel sounds were normal. Given the physical signs, a toxicology screen was conducted and was positive for methamphetamine use. The patient reported that he used recreational drugs occasionally and admitted that the abdominal pain developed a few hours following methamphetamine use. The patient was treated with fluid resuscitation, analgesic, antihypertension medications, and anticoagulant therapy. The patient had significant improvement in his condition within 48 hours with complete resolution of the abdominal pain. Isolated superior mesenteric artery dissection is a very rare clinical condition. This case report highlights the importance of recognizing the cardiovascular adverse effects that may develop after methamphetamine use.

4.
Br J Biomed Sci ; 78(1): 18-22, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32573389

RESUMO

BACKGROUND: Hepatitis B and C viruses are leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Toll-like receptor 7 (TLR-7) has been implicated in the pathogenesis of HCC linked to hepatitis B. We hypothesised a role of leukocyte TLR-7 mRNA in hepatitis C related liver cirrhosis and HCC, using alpha-fetoprotein (AFP) and liver function tests as comparators. METHODS: We recruited 102 patients with HCV-related HCC, 97 with HCV-related liver cirrhosis and 60 healthy controls. Quantification of TLR-7 mRNA was performed using real-time PCR, AFP and routine LFTs by standard techniques. RESULTS: TLR-7 mRNA levels were significantly lower in HCC patients compared to cirrhotic patients and lower again in healthy controls (p < 0.001 for trend). In multivariate analysis, age, aspartate transaminase (AST), AFP, and TLR-7 mRNA were significant predictors of HCC. The ROCC/AUC for age, AST and TLR-7 mRNA were all between 0.64 and 0.78 (all P < 0.01), but for AFP was 0.57 (95% CI 0.48-0.65, P = 0.09). We derived an index score using age, AST and TLR-7 mRNA for the diagnosis of HCC. The ROCC/AUC for the index was superior to all three root indices in the prediction of HCC. The index linked significantly with the Tokyo and Vienna liver cancer staging systems, but not with those of the CLIP and Okuda systems, in distinguishing HCC from liver cirrhosis. CONCLUSION: The combination of TLR-7 mRNA levels with age and AST improves the performance of TLR-7 in HCC diagnosis, out-performs alpha-fetoprotein and predicts early HCC.


Assuntos
Carcinoma Hepatocelular/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , RNA Mensageiro/genética , Receptor 7 Toll-Like/genética , alfa-Fetoproteínas/genética , Adulto , Aspartato Aminotransferases/genética , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/virologia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade
5.
Br J Biomed Sci ; 78(2): 72-77, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33016838

RESUMO

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) is crucial in providing more effective therapies. As routine laboratory variables are readily accessible, this study aimed to develop a simple non-invasive model for predicting hepatocellular cancer. METHODS: Two groups of patients were recruited: an estimation group (n = 300) and a validation group (n = 625). Each comprised two categories: hepatocellular cancer and liver cirrhosis. Logistic regression analyses and receiver operating characteristic (ROC) curves were used to develop and validate the HCC-Mark model comprising AFP, high-sensitivity C-reactive protein, albumin and platelet count. This model was tested in cancer patients classified by the Barcelona Clinic Liver Cancer (BCLC), Cancer of Liver Italian Program (CLIP) and Okuda systems, and was compared with other non-invasive models for predicting hepatocellular cancer. RESULTS: HCC-Mark produced a ROC AUC of 0.89 (95% CI 0.85-0.90) for discriminating hepatocellular carcinoma from liver cirrhosis in the estimation group and 0.90 (0.86-0.90) in the validation group (both p < 0.0001). This AUC exceeded all other models, that had AUCs from 0.41 to 0.81. AUCs of HCC-Mark for discriminating patients with a single focal lesion, absent macrovascular invasion, tumour size <2 cm, BCLC (0-A), CLIP (0-1) and Okuda (stage Ι) from cirrhotic patients were 0.88 (0.85-0.90), 0.87 (0.85-0.89), 0.89 (0.85-0.93), 0.87 (0.84-0.89), 0.85 (0.82-0.87) and 0.86 (0.83-0.89), respectively (all p < 0.0001). CONCLUSION: HCC-Mark is an accurate and validated model for the detection of hepatocellular cancer and certain of its clinical features.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Hepacivirus , Humanos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Curva ROC
6.
Br J Biomed Sci ; 77(4): 196-201, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32546046

RESUMO

INTRODUCTION: Early detection of breast cancer is important in diagnosis and treatment, and so in enhancing patient survival and reducing death rates. Because of the low diagnostic sensitivity and specificity of widely used breast cancer biomarkers such as CA15-3, we hypothesised that a panel of new metabolic markers would provide superior sensitivity and specificity for this disease. MATERIAL & METHODS: We recruited 120 women with malignant breast cancer, 47 with benign breast disease and 55 females as a healthy control group. Metabolites 8-hydroxy-2'-deoxyguanosine, 1-methylguanosine, and 1-methyl adenosine were detected and quantified by gas chromatography-mass spectrometry, CA15.3 by ELISA. Cut-off values of individual and combined metabolome with CA15-3 were analysed using the receiver operating characteristics curve (ROCC) to test the efficiency of the candidate metabolome in identifying breast cancer. RESULTS: The overall linear trend of biomarkers across the groups was significant with highest levels in breast cancer (all p < 0.05). Using cut-off values of CA15-3, 8-hydroxy-2'-deoxyguanosine, 1-methylguanosine and 1-methyl adenosine of 30.5 U/l, 15.0 µg/l, 18.5 µg/l and 22.0 µg/l, respectively, diagnostic performance analyses of combined metabolome with CA15-3 gave a ROCC area under the curve of 0.94 (95% CI: 0.91-0.98)(p < 0.01) with good sensitivity (88.8%), specificity (86.8%) and efficiency (90.6%). Unlike CA15.3, the highest levels of each of the metabolite were in the early stage of breast cancer. CONCLUSION: The diagnostic combination test of candidate metabolome with CA15.3 may be a useful tool for the early detection of breast cancer and used as a metabolomics signature in this disease.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Metaboloma/fisiologia , Adenosina/sangue , Adulto , Biomarcadores Tumorais/sangue , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Desoxiguanosina/sangue , Detecção Precoce de Câncer/métodos , Feminino , Guanosina/análogos & derivados , Guanosina/sangue , Humanos , Pessoa de Meia-Idade , Mucina-1/sangue , Curva ROC , Sensibilidade e Especificidade
7.
Br J Surg ; 107(1): 64-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31609482

RESUMO

BACKGROUND: The aim was to characterize end-of-life care in patients who have had a leg amputated for peripheral artery disease (PAD) or diabetes. METHODS: This was a population-based retrospective cohort study of patients with PAD or diabetes who died in Ontario, Canada, between 2011 and 2017. Those who had a leg amputation within 3 years of death were compared with a control cohort of deceased patients with PAD or diabetes, but without leg amputation. The patients were identified from linked health records within the single-payer healthcare system. Place and cause of death, as well as health services and costs within 90 days of death, were compared between the amputee and control cohorts. Among amputees, multivariable regression models were used to characterize the association between receipt of home palliative care and in-hospital death, as well as time spent in hospital at the end of life. RESULTS: Compared with 213 300 controls, 3113 amputees were less likely to die at home (15·5 versus 24·9 per cent; P < 0·001) and spent a greater number of their last 90 days of life in hospital (median 19 versus 8 days; P < 0·001). Amputees also had higher end-of-life healthcare costs across all sectors. However, receipt of palliative care was less frequent among amputees than controls (inpatient: 13·4 versus 16·8 per cent, P < 0·001; home: 14·5 versus 23·8 per cent, P < 0·001). Among amputees, receipt of home palliative care was associated with a lower likelihood of in-hospital death (odds ratio 0·49, 95 per cent c.i. 0·40 to 0·60) and fewer days in hospital (rate ratio 0·84, 0·76 to 0·93). CONCLUSION: Palliative care is underused after amputation in patients with PAD or diabetes, and could contribute to reducing in-hospital death and time spent in hospital at the end of life.


ANTECEDENTES: Caracterizar la atención al final de la vida en pacientes con amputación de la extremidad inferior por enfermedad arterial periférica (peripheral arterial disease, PAD) o diabetes. MÉTODOS: Se trata de un estudio de cohortes retrospectivo de base poblacional en sujetos fallecidos con PAD o diabetes en Ontario, Canadá (2011-2017). A partir de los registros sanitarios incluidos en un sistema de salud de una sola entidad pagadora, se identificaron los individuos con amputación de la extremidad inferior en los 3 años previos al fallecimiento y una cohorte control de fallecidos con PAD o diabetes sin amputación. Entre las cohortes de amputados y controles se comparó el lugar del fallecimiento y la causa, así como el uso de servicios sanitarios y costes en los últimos 90 días de vida. En el grupo de los amputados, se utilizaron modelos de regresión para caracterizar la asociación entre recibir cuidados paliativos domiciliarios y el fallecimiento en el hospital, así como los días de estancia hospitalaria al final de la vida. RESULTADOS: En comparación con los controles (n = 213.300), los sujetos con amputación (n = 3.113) era menos probable que fallecieran en el domicilio (16% versus 25%, P < 0,001) y pasaron un mayor número de sus últimos 90 días de vida en el hospital (mediana 19 versus 8 días, P < 0,001). Los costes de atención sanitaria al final de la vida en todos los sectores también fueron mayores para los amputados. Sin embargo, recibir cuidados paliativos fue menos frecuente en los amputados que en los controles (en el hospital 13% versus 17%, P < 0,001; domiciliarios 14% versus 24%, P < 0,001). En el grupo de los amputados, recibir cuidados paliativos domiciliarios se asociaba con una menor probabilidad de fallecimiento en el hospital (razón de oportunidades, odds ratio 0,49, i.c. del 95% 0,40-0,60) y menos días de hospitalización (tasa de riesgo 0,84, i.c. del 95% 0,76-0,93). CONCLUSIÓN: Los cuidados paliativos están infrautilizados en pacientes con PAD o diabetes y pueden contribuir a disminuir los fallecimientos en el hospital y los días de hospitalización al final de la vida.


Assuntos
Amputação Cirúrgica/mortalidade , Complicações do Diabetes/mortalidade , Doença Arterial Periférica/mortalidade , Assistência Terminal/métodos , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica/economia , Causas de Morte , Complicações do Diabetes/economia , Complicações do Diabetes/cirurgia , Feminino , Custos de Cuidados de Saúde , Serviços de Assistência Domiciliar/economia , Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Ontário/epidemiologia , Cuidados Paliativos/economia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Doença Arterial Periférica/economia , Doença Arterial Periférica/terapia , Assistência Terminal/economia , Assistência Terminal/estatística & dados numéricos
8.
Br J Biomed Sci ; 75(3): 122-127, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29734875

RESUMO

BACKGROUND: Although established markers such as CEA and CA19-9 are important for diagnosing early stages of colon cancer, they are not ideal. Developing promising markers include cytokeratin 1 (CK1) and mucin-1 (MUC1), but the combined value of each of these markers is unclear. We therefore evaluated the value of a combined laboratory-based score of these four markers in the diagnosis of colon cancer. METHODS: Two hundred patients who had undergone colonoscopic examination (150 colon cancer, 50 benign growths) were recruited. The study was controlled by 35 healthy subjects. CEA, CA19-9, CK1 and MUC1 were measured by ELISA and evaluated for cancer diagnosis using area under the receiver operating characteristic curve (AUC). RESULTS: Serum levels of all four markers were increased in the order colon cancer > benign disease > healthy controls (p < 0.001). In multivariate analysis, CA19.9 (p = 0.025), CK1 (p < 0.001) and MUC1 (p = 0.009) were significant independent predictors of colon cancer. A score that gave the greatest power of discrimination for colon cancer was defined as 1.06 + [0.001 × CA19.9 result] + [0.003 × CEA result] + [0.03 × CK1 result] + [0.05 × MUC1 result]. The colon score provided superior discrimination, AUC, and sensitivity and specificity for colon cancer versus benign growth than each of the individual markers. Similarly, the colon score provided superior AUC, and sensitivity and specificity that each individual marker for tumour stage, lymph node invasion and distant organ metastases than each individual marker. CONCLUSION: A colon score derived from serum CEA, CA19-9, CK1 and MUC1 is a potential valuable non-invasive index that could be used for detection and screening early stage colon cancer patients.


Assuntos
Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias do Colo/sangue , Queratina-1/sangue , Mucina-1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias do Colo/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade
9.
J Comput Biol ; 25(2): 170-181, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29172679

RESUMO

Familial hypercholesterolemia (FH) is a metabolic disorder that leads primarily to premature cardiovascular diseases, the main cause of mortality in Saudi Arabia (SA). FH is underreported and underdiagnosed in SA with statistical evidence of high expected prevalence in such a consanguineous community. Lacking knowledge of which and how these alterations are actually impacting lipid metabolism is one of the main reasons why FH is insufficiently diagnosed in the region. The aim of this study was to develop a fast prediction approach using an integrated bioinformatics method for future screening of the potential causative variants from national registries. A total of 21 variants were detected with majority rate in LDLR (81%). Variants were classified based on the type of mutation. Missense variants resulting in amino acid changes, c.1429G>A (p.D477N), c.1474G>A (p.D492N), c.1731G>T (p.W577C), and c.1783C>T (p.R595W) in LDLR gene, in addition to c.9835A>G (p.S3279G) in APOB, were shown to be deleterious by concordant analysis. Furthermore, functional interaction deformities showed a significant loss and gain of energies in the mutated proteins. These findings will help in distinguishing the most harmful mutations needed to be screened for clinically diagnosed FH patients in SA. Such computational research is necessary to avoid time consumption and the usage of expensive biological experiments. This can be a fast track to facilitate the future filtering and screening of causative mutations from national registries.


Assuntos
Hiperlipoproteinemia Tipo II/genética , Mutação com Perda de Função , Simulação de Acoplamento Molecular , Receptores de LDL/genética , Humanos , Taxa de Mutação , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Receptores de LDL/química , Receptores de LDL/metabolismo , Arábia Saudita
10.
Br J Biomed Sci ; 74(4): 170-175, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28705056

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a multistage process resulting from various genetic changes. We aimed to determine nuclear phosphoprotein c-Myc and cellular phosphoprotein p53 expression and to evaluate their importance in HCC diagnosis. METHODS: One hundred and twenty chronic hepatitis C (CHC) patients (60 non-HCC CHC patients and 60 HCC patients who had a single small (<5 cm) tumour) were recruited. The gene products of c-Myc and p53 were identified in liver tissues and serum samples using immunostaining, western blot and ELISA. RESULTS: Immunohistochemical detection of c-Myc and p53 with monospecific antibodies revealed intense and diffuse cytoplasmic staining patterns. Accumulated mutant proteins, released from tumour cells into the extracellular serum, were detected at 62 KDa, for c-Myc, and 53 KDa, for p53, using western blotting. In contrast to alpha feto-protein, there was a significant increase (p < 0.0001) in the positivity rate of c-Myc (86.7% vs. 6.7%) and p53 (78.3% vs. 8.3%) in the malignant vs. non-malignant patients. The parallel combination of c-Myc and p53 reach the absolute sensitivity (100%), for more accurate and reliable HCC detection (specificity was 87%). CONCLUSION: c-Myc and p53 are potential HCC diagnostic biomarkers, and convenient combinations of them could improve diagnostic accuracy of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Núcleo Celular/metabolismo , Hepatite C Crônica/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sensibilidade e Especificidade
11.
Case Rep Gastrointest Med ; 2016: 4398401, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27403353

RESUMO

Pyogenic granuloma (PG), more accurately known as lobular capillary hemangioma, is a benign vascular tumor that usually occurs in the skin or oral mucosa. This lesion is rarely reported in the gastrointestinal tract but is known to bleed if not resected. We herein describe a case series with the clinical, endoscopic, and histologic findings of four cases of gastrointestinal PG at our institution. In addition, we provide a review of the literature and summation of all reported cases of PG specific to the gastrointestinal tract. Based on our experience, we suggest that the actual incidence of gastrointestinal PG may in fact be higher than reported because PG can be unrecognized or improperly diagnosed. It is important for the clinician to properly recognize this lesion as a source of anemia and its propensity to bleed during biopsy or resection.

13.
Indian J Med Microbiol ; 33 Suppl: 143-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25657135

RESUMO

AIM: To investigate if any mutations in hepatitis C virus (HCV) internal ribosome entry site (IRES) can inhibit the translation of viral polyprotein. MATERIALS AND METHODS: A 26-year-old male patient infected with HCV 10 years ago was followed up. After 9 years of chronic infection. The patient had managed to resolve the infection for a period of 9 months, after which the patient experienced a viral recurrence characterized by high viral load and diverse HCV quasispecies. The IRES structures of the viral strains that disappeared were comparable with those that are currently active using structural mutational analysis. RESULTS: A novo mutational position 254 combined with a rarely observed mutation at position 253 in the stem of the IIId subdomain were observed and the new conformation had an octa-apical loop (AGUGUUGG) and a shift in the 3 ` GU from the loop to the stem. CONCLUSIONS: These mutations were found to be highly deleterious, and they affected the direct binding of the IIId loop to the 40S ribosomal subunit with a subsequent inhibition of translation of viral polyprotein and clearance of the virus.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/virologia , Sequências Repetidas Invertidas , Conformação de Ácido Nucleico , RNA Viral/química , RNA Viral/genética , Regiões 5' não Traduzidas , Adolescente , Sequência de Bases , Sequência Consenso , Ensaio de Imunoadsorção Enzimática , Hepacivirus/imunologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/imunologia , Humanos , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Carga Viral , Viremia
14.
Surgery ; 154(6): 1436-46; discussion 1446-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24075674

RESUMO

BACKGROUND: Although recurrence and death can occur in patients with papillary thyroid cancer (PTC) several years after being diagnosed, the necessary duration of follow-up for these patients remains unclear. METHODS: This was a single-institution, retrospective review of 269 patients with PTC. Cox proportional hazards model and Kaplan-Meier curves were used to identify risk factors for recurrence and death. Risk predictors included age, sex, radiation exposure history, extent of operation, radioactive iodine treatment, follicular variant of PTC (FVPTC), extrathyroidal invasion, multifocality, TNM status, and stage. RESULTS: Median follow-up was 27 years. Of 269 patients, 180 (66%) were female, and 196 (73%) were ≤45 years of age. Recurrence and cancer-specific death rates were 28% and 9%, respectively. Time to recurrence (±SD) was 8.1 (± 8.3) years and to cancer-specific death was 9.0 (± 11.0) years; however, 11% of recurrences and 17% of deaths occurred after 20 years. Risk factors for recurrence were older age, FVPTC, T4 tumors, cervical lymph node involvement, metastases, and stage ≥ 4a. Predictors of death from PTC were older age, metastases, and stage ≥ 3. CONCLUSION: Both recurrences and death from PTC can occur more than 30 years after being treated, thus lifelong follow-up of patients with PTC is necessary.


Assuntos
Carcinoma Papilar/mortalidade , Carcinoma/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Idoso , Carcinoma/patologia , Carcinoma/terapia , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Chicago/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Fatores de Tempo
15.
Br J Cancer ; 109(6): 1657-65, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23982602

RESUMO

BACKGROUND: A simple scoring system is needed to discriminate HCC from patients with chronic liver diseases (CLD). The simplest score would be one that requires only variables that can be documented simply from routine laboratory tests without the need for sophisticated tests. METHODS: Data from the estimation group (1351 patients) and the validation group (2208 patients) were retrospectively analysed. Liver fibrosis-negative control and liver cirrhosis were compared with HCC. Area under ROC curve (AUC) were used to develop HCC-α-fetoprotein-routine test (HCC-ART). RESULTS: Hepatocellular carcinoma-AFP-routine test showed diagnostic accuracy for liver cirrhosis vs HCC with ROC curves of 0.99%, sensitivity of 97%, and specificity of 96% in the estimation, and 0.95%, 90%, and 83%, respectively, in the validation. Sensitivity (97%) and specificity (100%) were obtained to discriminate HCC from liver fibrosis. Area under curve for AFP at 400 U l(-1) was 0.70, sensitivity was 41%, and specificity was 99% in the estimation, and 0.77%, 54%, and 99%, respectively, in the validation. The AUC for HCC-ART in HCC with single tumour, absent vascular invasion, size <2 cm and CLIP score (0-1) were 0.95, 0.93, 0.86, 0.87, respectively, compared with 0.72, 0.71, 0.71, 0.50, respectively, for AFP. CONCLUSION: Hepatocellular carcinoma-AFP-routine test could increase the accuracy of HCC screening and surveillances and could be used worldwide without extra efforts.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Estudos Retrospectivos
16.
Gene Ther ; 20(1): 51-61, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22257935

RESUMO

Sepsis-related complications and mortality remain a major clinical problem. Increased cell death and unresolved cellular repair have been implicated as key upstream mediators of sepsis-induced organ dysfunction and death. We hypothesised that gene therapy with BRCA1, a critical regulator of DNA damage repair and cell survival, would attenuate the sequelae of sepsis and peritonitis in mice subjected to caecal ligation and perforation (CLP) and thioglycollate stimulation. C57Bl/6J mice underwent sham or CLP surgery 3 days following treatment with either human BRCA1 adenovirus (AdBRCA1) or the adeno-CMV-null vector (Adnull). The 24-h post-CLP mortality was 2.8% vs 17.9% (P<0.001) and the median post-CLP survival was 50.5 vs 33 h (P<0.05) for AdBRCA1- vs Adnull-treated mice, respectively. AdBRCA1 therapy blunted CLP-associated cardiac, pulmonary, hepatic and renal dysfunction and also reduced CLP-elicited double strand breaks and apoptosis in the liver. BRCA1 gene therapy was associated with lower CLP-evoked cardiac and hepatic superoxide generation that in the liver was in part due to improved reactive oxygen species removal. CLP also elevated mesenteric arteriolar and serum intercellular adhesion molecule-1, both of which were partially abrogated with AdBRCA1 administration. Thioglycollate-challenged AdBRCA1-treated mice displayed reduced peritoneal neutrophil recruitment and dampened cytokine elaboration relative to their Adnull-treated counterparts. Taken together, we report a novel role of BRCA1 gene therapy in limiting systemic inflammation, multiple-organ failure and mortality in experimental sepsis.


Assuntos
Proteína BRCA1/genética , Terapia Genética , Insuficiência de Múltiplos Órgãos/terapia , Sepse/terapia , Adenoviridae/genética , Animais , Apoptose , Citocinas/análise , Vetores Genéticos/genética , Humanos , Molécula 1 de Adesão Intercelular/análise , Camundongos , Camundongos Endogâmicos C57BL , Sepse/metabolismo , Superóxidos/análise
17.
J Pediatr Urol ; 9(6 Pt A): 754-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23009885

RESUMO

OBJECTIVES: To compare surgical outcomes and donor site complications of buccal and lingual mucosa used as ventral onlay graft for complex hypospadias cases. PATIENTS & METHODS: Forty four cases with complex hypospadias after failed previous surgery were prospectively included. All had severely scarred penile skin with reasonable residual urethral plate. Cases were categorized into two groups: Group I (23) where buccal mucosal graft [BMG] was used and group II (21) where lingual mucosal graft [LMG] was used. Donor site complications as well as functional and esthetic outcomes were recorded for each group. RESULTS: Mean follow up was 20.8 months (range 12-24). Average graft harvesting time was 24 min for BMG and 19 min for LMG. Donor site pain was reported with both techniques but recovery was earlier with LMG. Slurred speech and difficult tongue protrusion were reported with lingual but not buccal grafts; however mouth tightness, peri-oral numbness and persistent oral discomfort were reported only with buccal grafts. Successful urethroplasty was obtained in 78.2% of BMG compared to 76.1% of LMG. CONCLUSION: Surgical outcomes of LMG urethroplasty were comparable to those of BMG in complex hypospadias cases. Compared to buccal mucosa, LMG is easy to harvest, with minimal donor site complications.


Assuntos
Hipospadia/cirurgia , Mucosa Bucal/transplante , Reoperação/métodos , Língua/transplante , Uretra/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Adolescente , Criança , Cicatriz/cirurgia , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Coleta de Tecidos e Órgãos/métodos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Adulto Jovem
18.
Colorectal Dis ; 14(10): e708-12, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22757608

RESUMO

AIM: The safety and efficacy of laparoscopic surgery for colon cancer is well established but its uptake in the province has not been previously explored. We report an investigation of the trends of open and laparoscopic surgery for colon cancer in Ontario, Canada. METHOD: A retrospective cross-sectional time-series analysis examining population-based rates of elective surgery for colon cancer among 10.5 million adults in Ontario was conducted from 1 April 2002 to 31 March 2009. Databases were linked to assess quarterly elective procedure rates over time. RESULTS: During the study period, 3950 laparoscopic and 13 048 open elective colon cancer operations were performed in Ontario. The overall quarterly rate of colon cancer surgery remained stable at an average of 5.8 per 100000 population (P=0.10). From the first and last quarter, the rate of laparoscopic operations increased nearly threefold from 0.8 to 2.2 per 100000 population with a notable increase after 2005 (P<0.01). In contrast, open surgery decreased by more than 30% from 5.3 to 3.5 per 100 000 population (P<0.01). If current trends continue, the projected proportion of laparoscopic colon operations is estimated to reach 41% by 2015. Patients receiving open surgery had a significantly higher preoperative comorbidity (Charlson comorbidity score≥3) than those having laparoscopy (47.8%vs 39.1%, standardized difference 0.26). CONCLUSION: Trends in Ontario of laparoscopic colon cancer surgery show an increase between 2002 and 2009, but the incidence remains lower than for open surgery.


Assuntos
Colectomia/tendências , Neoplasias do Colo/cirurgia , Procedimentos Cirúrgicos Eletivos/tendências , Laparoscopia/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , Colectomia/métodos , Colectomia/estatística & dados numéricos , Estudos Transversais , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Humanos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ontário , Estudos Retrospectivos
19.
Colorectal Dis ; 14(12): 1467-72, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22487101

RESUMO

AIM: The safety and efficacy of laparoscopic surgery for colon cancer have been demonstrated in large, multicentre clinical trials. The study aimed to determine the use of laparoscopic surgery for rectal cancer in Ontario over a 7-year period. METHOD: We conducted a retrospective study examining rates of elective rectal cancer surgery among 10.5 million adults in Ontario, Canada, from 1 April 2002 to 31 March 2009. We linked the Canadian Institute for Health Information Discharge Abstract Database, the Registered Persons Database and the database of the Ontario Cancer Registry to assess procedures used over the period. Data on demographics were collected. Trends were assessed using time series analysis. RESULTS: Over the 7-year period, 8189 open and 1079 laparoscopic elective operations for rectal cancer were identified. The annual rate of laparoscopic rectal cancer procedures increased from 0.60 per 100,000 population in 2003 to 2.24 per 100,000 population in 2008 (P < 0.01). Laparoscopic patients were similar to open with respect to age (66.5 ± 11.8 vs 66.2 ± 12.1 years; standardized difference 0.02), gender (63.2%vs 59.4%; standardized difference 0.08), Charlson Comorbidity Index score (standardized difference < 0.1) and socioeconomic status (standardized difference < 0.1). CONCLUSION: Laparoscopic rectal cancer surgery rates are increasing in Ontario. Ongoing research regarding the long-term safety and effectiveness of the laparoscopic approach for rectal cancer surgeries may lead to greater increases in its utilization.


Assuntos
Procedimentos Cirúrgicos Eletivos/tendências , Laparoscopia/tendências , Neoplasias Retais/cirurgia , Idoso , Feminino , Humanos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ontário , Estudos Retrospectivos
20.
Mo Med ; 106(5): 356-60, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19902717

RESUMO

Crohn's disease is a complex disease process causing transmural inflammation of the gastrointestinal tract, which produces a constellation of symptoms including abdominal pain, frequent loose stools, fistula formation, and extraintestinal manifestations. Biologic therapy, including tumor necrosis factor alpha inhibitors, are a growing class of agents, which have demonstrated efficacy in the treatment of moderate to severe Crohn's disease. Their indications for use have grown, as has the understanding of their associated safety concerns.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais/efeitos adversos , Humanos
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