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INTRODUCTION: The Framingham risk model estimates a person's 10-year cardiovascular disease (CVD) risk. This study used this model to calculate the changes in sex- and age-specific CVD risks in the Hong Kong Population Health Survey (PHS) 2014/15 compared with two previous surveys conducted during 2003 and 2005, namely, PHS 2003/2004 and Heart Health Survey (HHS) 2004/2005. METHODS: This study included individuals aged 30 to 74 years from PHS 2014/15 (n=1662; n=4 445 868 after population weighting) and PHS 2003/2004 and HHS 2004/2005 (n=818; n=3 495 074 after population weighting) with complete data for calculating the risk of CVD predicted by the Framingham model. Sex-specific CVD risks were calculated based on age, total cholesterol and high-density lipoprotein cholesterol levels, mean systolic blood pressure, smoking habit, diabetic status, and hypertension treatment. Mean sex- and age-specific CVD risks were calculated; differences in CVD risk between the two surveys were compared by independent t tests. RESULTS: The difference in 10-year CVD risk from 2003-2005 to 2014-2015 was not statistically significant (10.2% vs 10.6%; P=0.29). After age standardisation according to World Health Organization world standard population data, a small decrease in CVD risk was observed, from 9.4% in 2003-2005 to 8.8% in 2014-2015. Analysis according to age-group showed that more participants aged 65 to 74 years were considered high risk in 2003 to 2005 (2003-2005: 66.8% vs 2014-2015: 53.1%; P=0.028). This difference may be due to the decrease in smokers among men (2003-2005: 30.5% vs 2014-2015: 24.0%; P<0.001). CONCLUSION: From 2003-2005 to 2014-2015, there was a small decrease in age-standardised 10-year CVD risk. A holistic public health approach simultaneously targeting multiple risk factors is needed to achieve greater decreases in CVD risk.
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Enfermedades Cardiovasculares , Encuestas Epidemiológicas , Humanos , Hong Kong/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Enfermedades Cardiovasculares/epidemiología , Anciano , Adulto , Medición de Riesgo/métodos , Factores de Riesgo de Enfermedad Cardiaca , Factores de Riesgo , Fumar/epidemiología , Factores de Edad , Hipertensión/epidemiología , Factores Sexuales , Presión SanguíneaRESUMEN
OBJECTIVE: Deliberate foreign body ingestion (DFBI) is characterised by recurrent presentations among patients with mental health conditions, intellectual disabilities and in prisoners. We aimed to profile the characteristics and evaluate the care of such patients in this study. METHODS: Adult patients with an endoscopic record of attempted foreign body retrieval between January 2013 and September 2020 were identified at three Australian hospitals. Those with a documented mental health diagnosis were included and their standard medical records reviewed. Presentation history, demographics, comorbidities and endoscopic findings were recorded and described. RESULTS: A total of 166 admissions were accounted for by 35 patients, 2/3 of which had borderline personality disorder (BPD). Repetitive presentations occurred in more than half of the cohort. There was an increased trend of hospital admissions throughout the years. At least half of the cohort had a documented mental health review during their admission. An average of 3.3 (2.9) foreign bodies were ingested per single episode. Endoscopic intervention was performed in 76.5% of incidents. The combined Length of stay for all patients was 680 days. CONCLUSION: Deliberate foreign body ingestion in mental health patients is a common, recurring and challenging problem that is increasing in frequency and requires collaborative research to further guide holistic management.
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Cuerpos Extraños , Trastornos Mentales , Adulto , Humanos , Australia/epidemiología , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Estudios Retrospectivos , Ingestión de Alimentos , Cuerpos Extraños/epidemiología , Cuerpos Extraños/terapiaRESUMEN
Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/radioterapia , Adolescente , Adulto , Anciano de 80 o más Años , Quimioradioterapia , Estudios de Cohortes , Esquema de Medicación , Femenino , Humanos , Linfoma Extranodal de Células NK-T/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Adulto JovenRESUMEN
In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. A total of 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, P = .03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, P = .03) and younger age (OR 0.98, 95% CI 0.97-0.99, P = .05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23, 95% CI 0.07-0.74, P = .01) and genotype 3 (OR 0.23, 95% CI 0.12-0.43, P ≤ .01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials; however, a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlight the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/farmacología , Continuidad de la Atención al Paciente , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Humanos , Análisis de Intención de Tratar , Perdida de Seguimiento , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Prospectivos , Australia del Sur/epidemiología , Respuesta Virológica SostenidaRESUMEN
BACKGROUND: Better understanding of complications and outcomes of adults hospitalized with respiratory syncytial virus (RSV) infection is necessary. METHODS: A retrospective cohort study was conducted on all adults (≥ 18 years) admitted to 3 acute care general hospitals in Hong Kong with virologically confirmed RSV infection during 2009-2011 (N = 607). Adults hospitalized for seasonal influenza during the period were used for comparison (n = 547). Both infections were prospectively diagnosed following a standard protocol. Independent reviews of chest radiographs were performed by radiologists. Main outcome measures were all-cause death, respiratory failure requiring ventilatory support, and hospitalization duration. Cox proportional hazards models were used for analyses. RESULTS: The mean age of RSV patients was 75 (SD, 16) years; 87% had underlying conditions. Lower respiratory and cardiovascular complications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic obstructive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterial superinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively. Crude all-cause mortality was 9.1% and 11.9% within 30 days and 60 days, respectively; mean length of stay of survivors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superinfection, and elevated urea level and white blood cell count were independently associated with poorer survival. Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall outcomes of survival and length of stay were not significantly different from those in influenza. CONCLUSIONS: RSV can cause severe lower respiratory complications in older adults, resulting in respiratory failure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet need for antiviral therapy and vaccination against RSV in adults should be promptly addressed.
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Infecciones por Virus Sincitial Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Estudios RetrospectivosRESUMEN
BACKGROUND: Invasive fungal disease (IFD) is an important problem complicating the therapy of haematologic patients. AIM: This study aimed to provide data on the epidemiology of IFD in an Asian teaching hospital, as well as the prescription practice of antifungal drugs. METHOD: We conducted a retrospective review of 275 haematologic patients who were prescribed antifungal drugs in a 4-year period (2007-2010), of whom 130 (47%) had undergone haematopoietic stem cell transplantation. RESULTS: Antifungal prophylaxis with either fluconazole or itraconazole was given in 214 patients (78%). There were 414 prescriptions of antifungal drugs (including liposomal amphotericin B, voriconazole, caspofungin, micafungin, anidulafungin), of which 361 prescriptions were empirical. There were 14 patients with proven IFD, 11 of whom had breakthrough infection while on itraconazole prophylaxis. Interestingly, seven of these cases were due to infection by itraconazole-sensitive candida. CONCLUSION: These results provide important epidemiologic data necessary for the formulation of strategies for prevention and treatment of IFD in Asian patients.
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Antifúngicos/uso terapéutico , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Hematológicas/epidemiología , Hospitales de Enseñanza/tendencias , Micosis/tratamiento farmacológico , Micosis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Asia/epidemiología , Femenino , Hospitales de Enseñanza/métodos , Hospitales Universitarios/tendencias , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Direct measurements of heat balance (turbulent heat transfer and evaporation heat consumption) by the method of turbulent pulsations in 1998-2000 and 2002-2004 were used to obtain information on the daily, seasonal, and annual dynamics of energy fluxes and mass transfer between the atmosphere and the typical ecosystems of Siberia (middle-taiga pine forest and raised bog, true four-grass steppe, with the use of data for typical tundra) along the Yenisei meridian (90 degrees E).
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Ecosistema , Fotosíntesis , Árboles , Atmósfera , Metabolismo Energético , Calor , Estaciones del Año , Siberia , TundraRESUMEN
We identified a predominant clone of Clostridium difficile PCR ribotype 002, which was associated with an increased sporulation frequency. In 2009, 3,528 stool samples from 2,440 patients were tested for toxigenic C. difficile in a healthcare region in Hong Kong. A total of 345 toxigenic strains from 307 (13.3%) patients were found. Ribotype 002 was the predominant ribotype, which constituted 35 samples from 29 (9.4%) patients. The mean sporulation frequency of ribotype 002 was 20.2%, which was significantly higher than that of the 56 randomly selected ribotypes other than 002 as concurrent controls (3.7%, p < 0.001). Patients carrying toxigenic ribotype 002 were more frequently admitted from an elderly home (p = 0.01) and received more ß-lactam antibiotics in the preceding 3 months compared with the controls (p = 0.04) . The identification of toxigenic ribotype 002 in 2009 was temporally related to a significant increase in both the incidence of toxigenic C. difficile from 0.53 to 0.95 per 1,000 admissions (p < 0.001) and the rate of positive detection from 4.17% to 6.28% (p < 0.001) between period 1 (2004-2008) and period 2 (2009). This finding should alert both the physician and the infection control team to the establishment of and possible outbreaks by ribotype 002 in our hospitals, as in the case of ribotype 027.
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Proteínas Bacterianas/genética , Clostridioides difficile/clasificación , Clostridioides difficile/fisiología , Enterocolitis Seudomembranosa/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/aislamiento & purificación , Análisis por Conglomerados , Enterotoxinas/metabolismo , Heces/microbiología , Femenino , Hong Kong/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Ribotipificación , Esporas Bacterianas , Adulto JovenRESUMEN
The LIM-only family of proteins comprises four members; two of these (LMO1 and LMO2) are involved in human T-cell leukemia via chromosomal translocations, and LMO2 is a master regulator of hematopoiesis. We have carried out gene targeting of the other members of the LIM-only family, viz., genes Lmo1, Lmo3 and Lmo4, to investigate their role in mouse development. None of these genes has an obligatory role in lymphopoiesis. In addition, while null mutations of Lmo1 or Lmo3 have no discernible phenotype, null mutation of Lmo4 alone causes perinatal lethality due to a severe neural tube defect which occurs in the form of anencephaly or exencephaly. Since the Lmo1 and Lmo3 gene sequences are highly related and have partly overlapping expression domains, we assessed the effect of compound Lmo1/Lmo3 null mutations. Although no anatomical defects were apparent in compound null pups, these animals also die within 24 h of birth, suggesting that a compensation between the related Lmo1 and 3 proteins can occur during embryogenesis to negate the individual loss of these genes. Our results complete the gene targeting of the LIM-only family in mice and suggest that all four members of this family are important in regulators of distinct developmental pathways.
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Sistema Nervioso Central/embriología , Proteínas de Unión al ADN/genética , Desarrollo Embrionario y Fetal , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Morfogénesis , Mutación , Proteínas Oncogénicas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Secuencia de Aminoácidos , Animales , Animales Recién Nacidos , Sistema Nervioso Central/patología , Sistema Nervioso Central/fisiología , Proteínas de Unión al ADN/metabolismo , Femenino , Marcación de Gen , Genotipo , Humanos , Proteínas con Dominio LIM , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Proteínas Oncogénicas/metabolismo , Alineación de SecuenciaRESUMEN
OBJECTIVE: The aim of this study was to examine the reasons why primary care doctors undertake postgraduate diploma studies in a mixed private/public Asian setting. METHODS: Twenty four past or current postgraduate diploma students of the family medicine unit (FMU) of the University of Hong Kong participated in three focus group interviews. A structured questionnaire was constructed based on the qualitative data collected and was sent to 328 former applicants of postgraduate diploma studies at FMU. RESULTS: "Upgrading medical knowledge and skills" and "improving quality of practice" were two of the factors that most of the respondents considered to be significant in motivating them to undertake postgraduate diploma studies. "Time constraint" and "workload in practice" were however the most significant demotivating factors. Financial issues were more seriously considered by the junior than the senior doctors. To be able to "expand patient base and/or number" was considered to be a significant factor by the private doctors who were also keen to "improve communication and relationship with patients". CONCLUSION: These findings suggest that there are mixed reasons for primary care doctors to undertake postgraduate diploma studies. Course organisers should take into consideration these various reasons in planning their programmes.
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Educación de Postgrado en Medicina , Médicos de Familia/educación , Adulto , Anciano , Actitud del Personal de Salud , Selección de Profesión , Toma de Decisiones , Femenino , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Motivación , Médicos de Familia/psicología , Sector Privado , Práctica Profesional/normas , Sector PúblicoRESUMEN
Two distal downstream enhancers controlling astrocyte expression of the human apolipoprotein E (apoE) gene in the brain were identified by analysis of transgenic mice generated with various constructs of the apoE/C-I/C-IV/C-II gene cluster. In wild-type mice, the highest overall levels of apoE mRNA were found in astrocytes in the glomerular layer of olfactory bulbs and in Bergmann glia in the cerebellum. This pattern of expression was reproduced in transgenic mice expressing the entire human apoE gene cluster and also in transgenic mice expressing specific enhancer segments within the cluster. Expression of the human apoE transgene at these sites was specified by two enhancer domains: one enhancer is located 3.3 kb downstream of the apoE gene, and a duplication of this sequence is located 15 kb downstream of the apoE gene. Astrocyte enhancer activity was contained within 620 and 619 bp segments of these domains that show subtle differences in regional expression. In the absence of these distal enhancers, the apoE gene was not expressed in astrocytes. The relatively high levels of apoE expression at specific sites in the olfactory bulb and cerebellum suggest the presence of unique regulatory signals at these locations that may reflect common cellular properties and apoE gene functions. The localization of the two astrocytic enhancers reveals an unexpected complexity in the control of apoE production that is essential to understanding apoE function in the brain.
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Apolipoproteínas E/genética , Astrocitos/metabolismo , Encéfalo/metabolismo , Elementos de Facilitación Genéticos/fisiología , Regulación de la Expresión Génica/fisiología , Animales , Apolipoproteínas E/metabolismo , Astrocitos/citología , Encéfalo/citología , Cerebelo/citología , Cerebelo/metabolismo , Genes Reporteros , Humanos , Inmunohistoquímica , Ratones , Ratones Transgénicos , Familia de Multigenes/genética , Bulbo Olfatorio/citología , Bulbo Olfatorio/metabolismo , Especificidad de Órganos , Regiones Promotoras Genéticas/fisiología , ARN Mensajero/metabolismo , Transgenes/genéticaRESUMEN
Germ line gene disruption and gene insertion are often used to study the function of selected genes in vivo. We used selected knockout and transgenic mouse models to attempt to identify lipoprotein-related genes and gene products that regulate the process of intravenous cationic liposome-DNA complex (CLDC)-based gene delivery. Several observations suggested that proteins involved in lipoprotein metabolism might be important in influencing the delivery and/or expression of CLDC. First, in vitro transfection of either K562 or CHO cells by CLDCs was enhanced by the presence of a functional low-density lipoprotein receptor (LDLR). Second, pretreatment of mice with 4-aminopyrazolopyrimidine (4APP), an agent that alters lipoprotein profiles in mice, significantly decreased expression of luciferase (luc) after intravenous injection of CLDC-luc complexes in mice. Therefore, we tested mouse model systems either deficient for, or overexpressing, selected genes involved in lipoprotein metabolism, for their potential to regulate intravenous, CLDC-based gene delivery. Although homozygous knockout mutation in the apoE gene caused a significant decrease in gene expression in many tissues of apoE-deficient mice, mice with homozygous deletion of both the apoE and LDLR genes showed wild-type levels of gene transfer efficiency. Thus, a secondary event, produced by homozygous deletion of apoE, but compensated for by the concomitant deletion of LDLR, and/or effects resulting from strain-related, genetic background differences, appeared to play a significant role in mediating intravenous, CLDC-based gene delivery. Secondary alterations resulting from germ line knockouts, as well as epigenetic effects produced by strain differences, may limit the ability to assign specific, gene transfer-related functions to the deleted gene.
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Técnicas de Transferencia de Gen , Lipoproteínas/metabolismo , Receptores de LDL/genética , Animales , Apolipoproteínas E/genética , Células CHO , Cationes , Cricetinae , Estudios de Evaluación como Asunto , Humanos , Células K562 , Liposomas , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Ratones TransgénicosRESUMEN
A distal enhancer that specifies apolipoprotein E gene expression in the skin was identified and characterized by in situ hybridization in transgenic mice generated with constructs of the human apolipoprotein E/C-I/C-IV/C-II gene cluster. Transgene constructs containing the enhancer expressed high levels of apolipoprotein E mRNA in the germinative cell layer of the sebaceous gland and in epithelial cells of the hair follicle root sheath. Apolipoprotein E mRNA was also detected in basal epithelial cells of the epidermis. Expression of the human apolipoprotein E transgene at these sites was specified by a unique 1.0 kb enhancer domain located 1.7 kb downstream of the apolipoprotein E gene. No transgene expression was detected in skin epithelial cells in transgenic mice when this enhancer was deleted from the apolipoprotein E gene cluster. The enhancer was used to construct a transgene expression vector that faithfully directed a heterologous cDNA to the normal sites of apolipoprotein E gene expression in epithelial cells of the skin.
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Apolipoproteínas E/genética , Elementos de Facilitación Genéticos/fisiología , Piel/metabolismo , Animales , Células Epiteliales/metabolismo , Expresión Génica , Folículo Piloso/citología , Humanos , Inmunohistoquímica , Ratones , Ratones Transgénicos , ARN Mensajero/metabolismo , Glándulas Sebáceas/metabolismo , Piel/químicaRESUMEN
Graft-versus-host disease (GVHD) is the commonest complication after donor lymphocyte infusion (DLI). In 19 patients undergoing DLI for relapses of hematologic malignancies post hematopoietic stem cell transplantation (HSCT), 11 developed GVHD, of whom nine had isolated liver involvement, and two had liver and skin involvement. The clinical diagnosis of liver GVHD was hepatitic in six patients (55%) and classical in five patients (45%). Patients with GVHD post-DLI showed a different clinical pattern when compared to a cohort of 106 cases of GVHD post-HSCT, in having significantly more isolated liver involvement (9/11 vs 17/106, P<0.001), and less skin (2/11 vs 80/106, P<0.001) and gut (0/11 vs 28/106, P<0.001) involvement. However, liver GVHD post-DLI and post-HSCT had comparable patient characteristics, underlying diseases, clinical subtypes (classical and hepatitic) and response to treatment.
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Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hepatopatías/etiología , Transfusión de Linfocitos/efectos adversos , Adolescente , Adulto , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/complicaciones , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Hepatopatías/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Berberine, an alkaloid, has been found to have a myriad of pharmacological effects including hypotensive, antisecretory, sedative, and antimicrobial effects, some of which are similar to those of clonidine, an alpha 2 adrenoceptor partial agonist. The interaction of berberine with human platelet alpha 2 adrenoceptor was investigated in this study. Berberine was found to inhibit competitively the specific binding of [3H]-yohimbine. The displacement curve was parallel to those of clonidine, epinephrine, norepinephrine, with the rank order of potency (IC50) being clonidine (0.4 microM) greater than epinephrine (7.5 microM) greater than norepinephrine (14.5 microM) = berberine (16.6 microM). Increasing concentrations of berberine from 0.1 microM to 10 microM inhibited [3H]-yohimbine binding, shifting the saturation binding curve to the right without decreasing the maximum binding capacity. In platelet cyclic AMP accumulation experiments, berberine at concentrations of 0.1 microM to 0.1 mM inhibited the cAMP accumulation induced by 10 microM prostaglandin E1 in a dose dependent manner, acting as an alpha 2 adrenoceptor agonist. In the presence of L-epinephrine, berberine blocked the inhibitory effect of L-epinephrine behaving as an alpha 2 adrenoceptor antagonist. These properties are similar to those of clonidine on human platelets, suggesting that berberine is a partial agonist of platelet alpha 2 adrenoceptors. These findings may provide potential mechanisms for the hypotensive, antisecretory, and sedative effects of berberine.
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Berberina/farmacología , Plaquetas/efectos de los fármacos , Receptores Adrenérgicos alfa/sangre , Adulto , Alprostadil/farmacología , Plaquetas/metabolismo , Clonidina/farmacología , AMP Cíclico/sangre , Epinefrina/farmacología , Humanos , Norepinefrina/farmacología , Receptores Adrenérgicos alfa/metabolismo , Yohimbina/metabolismoRESUMEN
In previous in situ and in vivo rat perfusion studies, the intestinal absorption of several low molecular weight drugs was increased by the presence of luminal D-glucose. The intent of this study was to determine the potential of this fed-state effect to improve the intestinal uptake of poorly permeable, small peptide and peptide-like drugs. Jejunal wall permeabilities (Pw*) of di-(D-kyotorphin), tri-(cephradine), hexa-(growth hormone releasing peptide, GHRP-6) and octa-(octreotide, a somatostatin analogue) peptides and corresponding net water fluxes were determined in rats using an in situ single-pass perfusion technique. Glucose was shown to enhance the uptake of the smaller (di- and tri-) peptides but not the larger peptides despite the fact that glucose elicited a significant net water absorption with each of the four peptide drugs. It is concluded that glucose enhances jejunal permeabilities of smaller peptides by solvent drag and the enhancement is limited in situ by peptide molecular size. The studies with nonmetabolizable 3-O-methylglucose suggest that the augmentation of the proton gradient across the transmucosal membrane by glucose contributes to the carrier-mediated transport observed with the smaller peptides.
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Glucosa/farmacología , Absorción Intestinal/efectos de los fármacos , Yeyuno/metabolismo , Oligopéptidos/farmacocinética , 3-O-Metilglucosa , Animales , Cefradina/farmacocinética , Endorfinas/farmacocinética , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Yeyuno/efectos de los fármacos , Metilglucósidos/farmacología , Octreótido/farmacocinética , Permeabilidad , RatasRESUMEN
Endothelin (ET-1) is a 21-amino acid, vasoconstrictive peptide originally isolated from endothelial cells. It is one member of a class of potent, purportedly paracrine substances that act at receptors in multiple target organs. Antagonists to the receptor subtypes, ETA and ETB, have been designed around the hydrophobic carboxy-terminus of ET-1. The resulting hexapeptides possess low nanomolar receptor affinity, but face formidable challenges to oral delivery, given their peptidic nature. Hence, it was important to discriminate between analogs, as well as to optimize structural features combining binding potency with stability in intestinal fluids and permeability across biological membranes. PD 142893 (Ac-DDip16-Leu-Asp-Ile-Trp21) and PD 145065 (Ac-DBhg16-Leu-Asp-Ile-Ile-Trp21), as well as the N-methyl-isoleucine20 analogs were studies, where DDip = 3,3diphenylalanine and DBhg = 10,11-dihydro-5H-dibenzo[a,d]cycloheptene glycine. Analyses were conducted with specific HPLC methods. Permeabilities across CACO-2 cell monolayers ranged from 2.0x10(-4) to 6.3x10(-4)cm/min. The results suggested that these compounds can be absorbed in vivo, based on comparison of permeabilities with those obtained with reference compounds. Much greater differences were observed between the analogs when stability half-lives were compared after incubation in rat intestinal perfusate. The parent peptides, PD 142893 and PD 145065, were unstable, with half-lives less than 20 min. N-Methylation of Ile20 resulted in large increases in stability half-lives to greater 500 min. Enzyme inhibition studies demonstrated the involvement of carboxypeptidase A in production of the primary metabolite, the des-Trp derivative. Identification of the primary metabolite of the parent peptide was made by differential UV scanning at 214/280 nm and mass spectral analyses.
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Antagonistas de los Receptores de Endotelina , Endotelinas/química , Animales , Captopril/farmacología , Cromatografía Líquida de Alta Presión , Propuestas de Licitación , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Masculino , Oligopéptidos/farmacología , Permeabilidad , Ratas , Ratas WistarRESUMEN
A series of 3-imino-1-oxoisoindolines were shown to be potent anti-inflammatory and analgesic agents at 8 mg/kg, intraperitoneally in mice. The compounds were also able to protect against lipopolysaccharide induced endotoxic shock and death better than the current clinical agents. These agents appear to function by blocking the release of TNF alpha and IL-1 from macrophages as well as competition with their respective high affinity receptors on target tissue, eg. fibroblasts, and macrophages. In addition lysosomal hydrolytic enzymes were inhibited as well as leukotriene synthesis in macrophages by the agents.
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Antiinflamatorios no Esteroideos/farmacología , Animales , Araquidonato 5-Lipooxigenasa/metabolismo , Hidrolasas/metabolismo , Técnicas In Vitro , Interleucina-1/farmacocinética , Lisosomas/enzimología , Masculino , Ratones , Ratones Endogámicos , Prostaglandina-Endoperóxido Sintasas/metabolismo , Receptores de Interleucina-1/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/farmacocinéticaRESUMEN
A comparison of mussels (Perna viridis) and semi-permeable membrane devices (SPMDs) was carried out at five sites, representing a gradient of contaminant concentrations, in Hong Kong coastal waters. Mussels, originally collected from a "clean" location, were deployed along with SPMDs at each site for 30 days. Analyses for chlorinated pesticides and polychlorinated biphenyls (PCBs) indicated that SPMDs have potential as monitoring tools, and to some extent can overcome the problems associated with mussels, such as natural variability, differing age, sex, and physical condition. However, in most cases, SPMDs failed to rank the sites in the same order as mussels in terms of contaminant concentrations. Nonetheless, in localities where mussels cannot survive--as shown at Kwun Tong in the present experiment--SPMDs may be valuable in providing an indication of potentially bio-available lipophilic pollutants.
Asunto(s)
Bivalvos , Insecticidas/análisis , Membranas Artificiales , Bifenilos Policlorados/análisis , Contaminantes Químicos del Agua/análisis , Animales , Disponibilidad Biológica , Monitoreo del Ambiente , Hong Kong , Permeabilidad , Distribución TisularRESUMEN
This report describes the cytologic, radiologic and histologic findings in a 76-year-old male who presented with a pathologic fracture of the first metacarpal bone as the result of metastatic transitional cell carcinoma. The primary neoplasm was sited in the right renal pelvis. Metastases were also detected in the liver and confirmed cytologically. Problems encountered with the cytologic diagnosis are explained by correlation with the histologic findings. The case also illustrates the importance of clinicopathologic correlation when interpreting fine needle aspiration biopsies.