RESUMO
Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, are on long-term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end-stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23-84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment-related complication of CCRT.
Assuntos
Quimiorradioterapia/efeitos adversos , Infecções por Citomegalovirus , Esofagite , Infecções por HIV/epidemiologia , Neoplasias , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/fisiopatologia , Endoscopia do Sistema Digestório/métodos , Esofagite/diagnóstico , Esofagite/epidemiologia , Esofagite/fisiopatologia , Esofagite/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Retrospectivos , Fatores de Risco , Avaliação de Sintomas/métodos , Taiwan/epidemiologiaRESUMO
BACKGROUND: This study evaluated the efficacy and safety of ziv-aflibercept in combination with cisplatin and pemetrexed in non-small cell lung cancer (NSCLC). METHODS: This single arm, multicentre phase II trial enrolled patients with previously untreated, locally advanced or metastatic non-squamous NSCLC. Patients received intravenous ziv-aflibercept 6 mg kg(-1), pemetrexed 500 mg m(-2), and cisplatin 75 mg m(-2), every 21 days for up to six cycles. Maintenance administration of ziv-aflibercept was to continue until disease progression, intolerable toxicity or other cause for withdrawal. The co-primary end points were objective response rate (ORR) and progression-free survival (PFS). Planned sample size was 72 patients. RESULTS: The study was closed prematurely because of three confirmed and two suspected cases of reversible posterior leukoencephalopathy syndrome (RPLS). A total of 42 patients were enrolled. Median age was 61.5 years; 55% were male, 86% Caucasian and 50% had Eastern Cooperative Oncology Group performance status (ECOG PS)=0. A median of four cycles of ziv-aflibercept was administered. The most common treatment-emergent adverse events (TEAEs) of any grade were nausea (69%) and fatigue (67%), with hypertension (36%) as the most common grade 3/4 TEAE. Of the 38 evaluable patients, ORR was 26% and median PFS was 5 months. CONCLUSION: Cases of RPLS had been observed in other studies in the ziv-aflibercept clinical development programme but the rate observed in this study was higher than previously observed. This might be related to declining renal function and/or hypertension. Although ORR and PFS were in accordance with most historical first-line NSCLC studies, this combination of ziv-aflibercept/cisplatin/pemetrexed will not be further explored in NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Glutamatos/administração & dosagem , Guanina/análogos & derivados , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pemetrexede , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Resultado do TratamentoRESUMO
Enterohaemorrhagic Escherichia coli (EHEC) causes life-threatening infections in humans as a consequence of the production of Shiga-like toxins. Lack of a good animal model system currently hinders in vivo study of EHEC virulence by systematic genetic methods. Here we applied the genetically tractable animal, Caenorhabditis elegans, as a surrogate host to study the virulence of EHEC as well as the host immunity to this human pathogen. Our results show that E. coli O157:H7, a serotype of EHEC, infects and kills C. elegans. Bacterial colonization and induction of the characteristic attaching and effacing (A/E) lesions in the intact intestinal epithelium of C. elegans by E. coli O157:H7 were concomitantly demonstrated in vivo. Genetic analysis indicated that the Shiga-like toxin 1 (Stx1) of E. coli O157:H7 is a virulence factor in C. elegans and is required for full toxicity. Moreover, the C. elegans p38 mitogen-activated protein kinase (MAPK) pathway, an evolutionarily conserved innate immune and stress response signalling pathway, is activated in the regulation of host susceptibility to EHEC infection in a Stx1-dependent manner. Our results validate the EHEC-C. elegans interaction as suitable for future comprehensive genetic screens for both novel bacterial and host factors involved in the pathogenesis of EHEC infection.
Assuntos
Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/microbiologia , Escherichia coli O157/patogenicidade , Interações Hospedeiro-Patógeno , Toxina Shiga I/metabolismo , Fatores de Virulência/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese , Animais , Caenorhabditis elegans/imunologia , Infecções por Escherichia coli , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Modelos Animais , Análise de SobrevidaRESUMO
Foreign bodies should not be allowed to remain in the esophagus beyond 24 hours after presentation. However, some patients with esophageal foreign body ingestion do not come to the hospital immediately and may delay medical intervention from the time of ingestion. The aim of this study was to investigate the outcomes of adults with suspected esophageal foreign body ingestion according to the time of ingestion and types of foreign bodies. A total of 326 adult patients (151 men and 175 women) were analyzed, and divided into two groups according to the time period: within or beyond 24 hours from ingestion to endoscopic intervention. A total of 172 patients (52.7%) were found to have ingested foreign bodies; 73.5% were removed smoothly, 10.3% were treated by push technique and 16.0% with failed retrieval received alternative treatments. A higher proportion of patients in the beyond-24 hours group suffered from odynophagia (25.9 vs. 12.9%, P < 0.05). Negative identification of esophageal foreign bodies was more frequent in the beyond-24 hours group (67 vs. 40.2%, P < 0.05), but these patients showed higher proportions of esophageal ulcers (21.1 vs. 7.2%, P < 0.05). The beyond-24 hours group also showed a significantly higher rate of foreign bodies in the lower esophagus (40.0 vs. 15.3%, P < 0.05). Patients with esophageal food bolus impaction had significant delayed endoscopic intervention, longer therapeutic endoscopic time, higher proportions of esophageal cancer, stricture and fewer complications. Endoscopic intervention within 24 hours from the time of ingestion should be considered early in adults, because delaying intervention may produce more symptomatic esophageal ulcerations with odynophagia.
Assuntos
Esôfago , Corpos Estranhos/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esofagoscopia , Feminino , Alimentos , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Carcinosarcoma of the esophagus is a rare neoplasm with both carcinomatous and sarcomatous components. This study aimed to investigate its clinicopathologic features and endoscopic characteristics. The data of patients diagnosed to have esophageal carcinosarcoma pathologically in the past 30 years (January 1976-December 2007) were reviewed. Of 3318 cases of esophageal malignancy, 12 were diagnosed as esophageal carcinosarcoma, with an incidence of 0.36%. All of the cases were male with a mean age of 62.3 years. Of the 12 tumors, 8 were polypoid type, and 4 were ulcerative type. In the endoscopic ultrasonography examination, the tumors show heterogeneous hypoechoic lesions with irregular outer margins and internal multicystic components. Four patients (33.3%) had previous head and neck squamous cell carcinoma that occurred metachronously. This is the first report about the characteristics of esophageal carcinosarcoma under endoscopic ultrasonography examination. The relationship between esophageal carcinosarcomas and head and neck cancer needs further investigation.
Assuntos
Carcinossarcoma/epidemiologia , Neoplasias Esofágicas/epidemiologia , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Areca , Carcinoma de Células Escamosas/epidemiologia , Carcinossarcoma/secundário , Endoscopia do Sistema Digestório , Endossonografia , Seguimentos , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Incidência , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/epidemiologia , Pólipos/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fumar/epidemiologia , Taxa de Sobrevida , Taiwan/epidemiologia , Úlcera/epidemiologiaRESUMO
Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.
Assuntos
Axônios/fisiologia , Caenorhabditis elegans/fisiologia , Movimento Celular , Colágeno/metabolismo , Neurônios/fisiologia , Fragmentos de Peptídeos/metabolismo , Estrutura Terciária de Proteína , Sequência de Aminoácidos , Inibidores da Angiogênese/genética , Inibidores da Angiogênese/metabolismo , Animais , Animais Geneticamente Modificados , Western Blotting , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Colágeno/química , Colágeno/genética , Colágeno Tipo XVIII , Endostatinas , Genes Reporter/genética , Masculino , Microscopia de Fluorescência , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Isoformas de Proteínas , RNA/antagonistas & inibidores , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de SequênciaRESUMO
Collagen XVIII (c18) is a triple helical endothelial/epithelial basement membrane protein whose noncollagenous (NC)1 region trimerizes a COOH-terminal endostatin (ES) domain conserved in vertebrates, Caenorhabditis elegans and Drosophila. Here, the c18 NC1 domain functioned as a motility-inducing factor regulating the extracellular matrix (ECM)-dependent morphogenesis of endothelial and other cell types. This motogenic activity required ES domain oligomerization, was dependent on rac, cdc42, and mitogen-activated protein kinase, and exhibited functional distinction from the archetypal motogenic scatter factors hepatocyte growth factor and macrophage stimulatory protein. The motility-inducing and mitogen-activated protein kinase-stimulating activities of c18 NC1 were blocked by its physiologic cleavage product ES monomer, consistent with a proteolysis-dependent negative feedback mechanism. These data indicate that the collagen XVIII NC1 region encodes a motogen strictly requiring ES domain oligomerization and suggest a previously unsuspected mechanism for ECM regulation of motility and morphogenesis.
Assuntos
Proteínas de Bactérias , Movimento Celular/fisiologia , Colágeno/metabolismo , Endotélio Vascular/citologia , Matriz Extracelular/fisiologia , Fragmentos de Peptídeos/metabolismo , Estrutura Terciária de Proteína , Inibidores da Angiogênese/genética , Inibidores da Angiogênese/metabolismo , Animais , Toxinas Bacterianas/farmacologia , Western Blotting , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/química , Colágeno/genética , Colágeno Tipo XVIII , Citotoxinas/farmacologia , Dimerização , Endostatinas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/crescimento & desenvolvimento , Humanos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Morfogênese , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
AIMS: For nearly a century, the incidence of cancer in people with schizophrenia was lower than in the general population. In the recent decade, the relationship between cancer and schizophrenia has become obscured. Thus, we investigated the cancer risk among young and middle-aged patients with schizophrenia. METHODS: Records of newly admitted patients with schizophrenia (n = 32 731) from January 2000 through December 2008 were retrieved from the Psychiatric Inpatient Medical Claims database in Taiwan, and the first psychiatric admission of each patient during the same period was defined as the baseline. We obtained 514 incident cancer cases that were monitored until December 2010. Standardised incidence ratios (SIRs) were calculated to compare the risk of cancer between those with schizophrenia and the general population. Stratified analyses of cancer incidences were performed by gender, site of cancers and duration since baseline (first psychiatric admission). RESULTS: The incidence of cancer for all sites was slightly higher than that of the general population for the period (SIR = 1.15 [95% CI 1.06-1.26], p = 0.001). Men had a significantly higher incidence of colorectal cancer (SIR = 1.48 [95% CI 1.06-2.06], p = 0.019). Women had a higher incidence of breast cancer (SIR = 1.47 [95% CI 1.22-1.78], p < 0.001). Intriguingly, the risk for colorectal cancer was more pronounced 5 years after the first psychiatric admission rather than earlier (SIR = 1.94 [1.36-2.75], p < 0.001) and so was the risk for breast cancer (SIR = 1.85 [1.38-2.48], p < 0.001). The cancer incidence was higher in patients with schizophrenia contradicting the belief that schizophrenia was protective of cancers. CONCLUSIONS: Our analyses suggest that men and women with schizophrenia were more vulnerable to certain types of cancers, which indicates the need for gender-specific cancer screening programs. The fact that risk of colorectal cancer was more pronounced 5 years after the first psychiatric admission could imply the impact of unhealthy lifestyles or the possibility of delayed diagnoses.
Assuntos
Neoplasias/epidemiologia , Esquizofrenia/complicações , Adolescente , Adulto , Distribuição por Idade , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esquizofrenia/epidemiologia , Distribuição por Sexo , Taiwan/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Fas (APO-1/CD95) is a member of the tumor necrosis factor receptor (TNF-R) family and induces apoptosis when crosslinked with either Fas ligand or agonistic antibody (Fas antibody). The Fas-Fas ligand system has an important role in the immune system where it is involved in the downregulation of immune responses and the deletion of peripheral autoreactive T lymphocytes. The intracellular domain of Fas interacts with several proteins including FADD (MORT-1), DAXX, RIP, FAF-1, FAP-1 and Sentrin. The adaptor protein FADD can, in turn, interact with the cysteine protease caspase-8 (FLICE/MACH/Mch5). RESULTS: In a genetic screen for essential components of the Fas-mediated apoptotic cascade, we isolated a Jurkat T lymphocyte cell line deficient in caspase-8 that was completely resistant to Fas-induced apoptosis. Complementation of this cell line with wild-type caspase-8 restored Fas-mediated apoptosis. Fas activation of multiple caspases and of the stress kinase p38 and c-Jun NH2-terminal kinase (JNK) was completely blocked in the caspase-8-deficient cell line. Furthermore, the cell line was severely deficient in cell death induced by TNF-alpha and was partially deficient in cell death induced by ultraviolet irradiation, adriamycin and etoposide. CONCLUSIONS: This study provides the first genetic evidence that caspase-8 occupies an essential and apical position in the Fas signaling pathway and suggests that caspase-8 may participate broadly in multiple apoptotic pathways.
Assuntos
Apoptose/fisiologia , Caspases/metabolismo , Glicoproteínas de Membrana/fisiologia , Proteínas Quinases Ativadas por Mitógeno , Receptor fas/fisiologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Caspase 8 , Caspase 9 , Doxorrubicina/farmacologia , Etoposídeo/farmacologia , Proteína Ligante Fas , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno , Células Jurkat , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Estaurosporina/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/fisiologia , Raios Ultravioleta , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
The Fas receptor mediates a signalling cascade resulting in programmed cell death (apoptosis) within hours of receptor cross-linking. In this study Fas activated the stress-responsive mitogen-activated protein kinases, p38 and JNK, within 2 h in Jurkat T lymphocytes but not the mitogen-responsive kinase ERK1 or pp70S6k. Fas activation of p38 correlated temporally with the onset of apoptosis, and transfection of constitutively active MKK3 (glu), an upstream regulator of p38, potentiated Fas-induced cell death, suggesting a potential involvement of the MKK3/p38 activation pathway in Fas-mediated apoptosis. Fas has been shown to require ICE (interleukin-1 beta-converting enzyme) family proteases to induce apoptosis from studies utilizing the cowpox ICE inhibitor protein CrmA, the synthetic tetrapeptide ICE inhibitor YVAD-CMK, and the tripeptide pan-ICE inhibitor Z-VAD-FMK. In this study, crmA antagonized, and YVAD-CMK and Z-VAD-FMK completely inhibited, Fas activation of p38 kinase activity, demonstrating that Fas-dependent activation of p38 requires ICE/CED-3 family members and conversely that the MKK3/p38 activation cascade represents a downstream target for the ICE/CED-3 family proteases. Intriguingly, p38 activation by sorbitol and etoposide was resistant to YVAD-CMK and Z-VAD-FMK, suggesting the existence of an additional mechanism(s) of p38 regulation. The ICE/CED-3 family-p38 regulatory relationship described in the current work indicates that in addition to the previously described destructive cleavage of substrates such as poly(ADP ribose) polymerase, lamins, and topoisomerase, the apoptotic cysteine proteases also function to regulate stress kinase signalling cascades.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Caspases , Cisteína Endopeptidases/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno , Transdução de Sinais/fisiologia , Proteínas Virais , Receptor fas/fisiologia , Clorometilcetonas de Aminoácidos/farmacologia , Apoptose/fisiologia , Proteínas de Caenorhabditis elegans , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Caspase 1 , Dactinomicina/farmacologia , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Etoposídeo/farmacologia , Proteínas de Helminto/fisiologia , Humanos , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno , Células Jurkat , MAP Quinase Quinase 3 , Inibidores de Proteases/farmacologia , Proteínas Serina-Treonina Quinases/genética , Inibidores da Síntese de Proteínas/farmacologia , Proteínas Tirosina Quinases/genética , Piridinas/farmacologia , Serpinas/fisiologia , Sorbitol/farmacologia , Transcrição Gênica/fisiologia , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Rapamycin is an immunosuppressant which antagonizes cellular proliferation by inhibiting the function of mTOR. The mTOR:FKBP12: rapamycin complex blocks G1/S transition by inhibiting downstream targets essential for cell cycle progression. One such target is p70S6k1 (S6K1), a serine/threonine kinase which is inactivated by the mTOR : FKBP12 : rapamycin complex, and which has been linked to translational control by virtue of its ability to phosphorylate the ribosomal protein S6. In the current work, we describe cloning and characterization of a novel S6K1 homolog, p54 S6 kinase 2 (p54S6k2/S6K2). Similar to S6K1, S6K2 is activated by mitogens and by constitutively active PI3K, and is inhibited by rapamycin as well as wortmannin. Differences between activation of S6K1 and S6K2 by PDK1 were observed, suggesting potential differences in the regulation of these homologs. Strikingly, S6K2 activity and S6 phosphorylation were both intact in S6K1-/-ES cell, indicating a possible role for S6K2 in in vivo S6 phosphorylation. Interestingly, we found two isoforms of S6K2 which are localized to distinct cellular compartments; the smaller form resides in the detergent-soluble fraction, whereas the larger form is found in the particulate fraction. Our findings demonstrate the existence of a family of rapamycin-sensitive protein kinases potentially involved in S6 phosphorylation, translational control, and transduction of mTOR signals.
Assuntos
Isoenzimas/genética , Proteínas Quinases S6 Ribossômicas/genética , Homologia de Sequência do Ácido Nucleico , Linhagem Celular , Etiquetas de Sequências Expressas , Isoenzimas/metabolismo , Dados de Sequência Molecular , Fosforilação , Proteínas Quinases S6 Ribossômicas/metabolismo , Sirolimo/farmacologiaRESUMO
AIMS: The causes of death among a series of patients with substance dependence were investigated. SETTING: A psychiatric teaching hospital in Taipei, Taiwan (Taipei City Psychiatric Center). PARTICIPANTS: A total of 1698 patients with various diagnostic categories of substance dependence, who had been admitted to TCPC for detoxification were followed-up from 1985 to 1996. DESIGN: A record-linkage study was performed using the patient's national identification number to link between TCPC chart records and the mortality file compiled by the National Department of Health. Risk factor analyses for mortality included socio-demographic data, clinical diagnosis and cause of death. FINDINGS: A total of 141 patients died during the study period. Among them, 83 had a diagnosis of alcohol dependence, 41 of heroin dependence and the remaining 17 cases of sedative, glue or hallucinogen dependence. The annual mortality rate of patients with heroin dependence was 1.94%. Accidental death is the leading cause of death among patients with heroin dependence. However, the patients with alcohol dependence had a higher mortality risk than those with heroin dependence (relative hazard = 1.91, p < 0.001) in this study. The proportion of non-violent death was significantly higher among the patients with alcohol dependence than those with heroin dependence (p < 0.005). CONCLUSION: The causes of death among patients with substance dependence found in this Taiwanese series were very similar to those reported in the western literature. However, differences included the absence of death among heroin addicts due to HIV-related disease and a markedly high percentage of alcoholic patients who died of liver diseases.
Assuntos
Registro Médico Coordenado , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Acidentes/estatística & dados numéricos , Adulto , Idoso , Transtornos Relacionados ao Uso de Álcool/mortalidade , Causas de Morte , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Transtornos Relacionados ao Uso de Opioides/mortalidade , Admissão do Paciente , Modelos de Riscos Proporcionais , Fatores de Risco , Estatísticas não Paramétricas , Taiwan/epidemiologia , Violência/estatística & dados numéricosRESUMO
BACKGROUND: Circulating soluble interleukin-2 receptors (sIL-2Rs) and soluble interleukin-6 receptors (sIL-6Rs) are stable immune measures. Elevated plasma sIL-2R levels are present in patients with schizophrenia, major depression, and bipolar mania, but not with minor psychiatric disorders. The increased plasma sIL-2R levels are state-dependent in bipolar mania. However, altered production of plasma sIL-6R and the effects of clinical characteristics on plasma sIL-6R and sIL-2R levels in bipolar disorder remains uncertain. METHODS: Plasma sIL-2R and sIL-6R levels were measured in 31 Taiwanese bipolar manic (DSM-IV) patients with Young Mania Rating Scale (YMRS) scores of > or =26 as well as during the subsequent remission (YMRS< or =12), and equal numbers of age- and gender-matched healthy controls. The relationships of clinical variables such as age, age of onset, smoking, medication status, coexisting psychotic features, number of prior episodes, duration of illness, presence of depression before or following the manic episode, and manic severity to plasma sIL-2R and sIL-6R levels in acute mania along with remission were examined. RESULTS: Plasma sIL-2R but not sIL-6R levels were significantly higher in acute mania than in subsequent remission (P<0.05) and controls (P<0.0005). In acute mania, the plasma sIL-2R levels were significantly correlated to YMRS scores (r=0.34, P<0.05). The remaining clinical variables had no effect on plasma sIL-2R and sIL-6R levels in acute mania or remission. There was a significantly positive relationship between the reduction of plasma sIL-2R levels from the acute to follow-up measurements (DeltasIL-2R) and symptomatic improvement of acute mania (DeltaYMRS) (r=0.61, P<0.001). LIMITATIONS: Our sample included medicated and unmedicated patients in acute mania. The psychotropic medication may have divergent effects on the plasma sIL-2R levels in acute mania and subsequent remission. CONCLUSIONS: Elevation of plasma sIL-2R but not sIL-6R levels in bipolar mania supports the idea that the immunomodulatory mechanism may vary in different psychotic disorders. In contrast to being a trait marker in schizophrenia and depressive disorder, plasma sIL-2R levels may be considered a biological indicator of manic severity in a group of bipolar affective patients.
Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Receptores de Interleucina-2/sangue , Doença Aguda , Adulto , Biomarcadores/sangue , Ritmo Circadiano/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Receptores de Interleucina-6/sangue , Indução de Remissão , Índice de Gravidade de Doença , Solubilidade , Inquéritos e QuestionáriosRESUMO
Antimony compounds are widely used in various manufacturing and semiconducting industries. Previously, it has been shown that antimony trichloride (SbCl3) elevates sister chromatid exchange (SCE) rates in V79 cells after a 28-h incubation. However, only limited data on its genotoxic effects are available so far. The present results demonstrate that a 4-h exposure to > 50 microM SbCl3 could induce micronuclei (MN) formation in cultured Chinese hamster ovary (CHO-K1) cells, human bronchial epithelial (BES-6) cells and human fibroblasts (HF). The order of sensitivity to SbCl3 determined by Sulforhodamine B (SRB)-staining survival assay is HF > BES-6 cells > CHO-K1 cells, with LD50 values in these cells being approximately 40, 80 and 180 microM, respectively. Apoptosis and DNA fragmentation was not found in cells immediately following 4-h SbCl3 treatment. However, DNA fragmentation was detected in CHO-K1 cells after 4-h SbCl3 treatment and a 16 h or more post incubation in fresh medium by 1.5% agarose gel electrophoresis. The delayed apoptosis was also observed under microscopic examination in HF, BES-6 and CHO-K1 cells after similar treatment protocol. In addition, an increase in calcium accumulation appeared in CHO-K1 cells and HF immediately after a 4-h SbCl3 treatment, or after a 24-h post incubation in fresh medium. The present results provide important genotoxic and cytotoxic information characterizing the cellular changes induced by short-term SbCl3 exposure in rodent and human cells.
Assuntos
Antimônio/toxicidade , Apoptose/efeitos dos fármacos , Cloretos/toxicidade , Dano ao DNA , DNA/efeitos dos fármacos , Animais , Células CHO , Cálcio/metabolismo , Cricetinae , Fragmentação do DNA/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacosRESUMO
OBJECTIVE: To quantitatively define the coronary vascular bed in the 21-day-old rat fetus with gestational normoxia and hypoxia; to determine if maternal supplemental oxygen and/or oxygen-carrying perfluorocarbons (PFCs) influence development of coronary vessels; and to compare the results using purified and unpurified PFC treatment. DESIGN: Unilateral uterine artery ligation was introduced on gestational day 17 in pregnant animals. Control fetuses were from unligated uterine horns. Experimental intervention occurred during gestational days 17 to 21, with fetuses recovered on day 21. Developing coronary vessels were analyzed quantitatively via light microscopy. ANIMALS: Pregnant Sprague Dawley rats. INTERVENTIONS: Following ligation, pregnant rats received no further treatment, supplemental oxygen inhalation alone, or daily intravenous purified PFC treatment, with or without supplemental oxygen. MAIN RESULTS: Hypoxia caused an increase in resorptions (P less than 0.001), and decreased fetal body weight (P less than 0.001) and heart weight (P less than 0.05). Although the area occupied by developing coronary vessels (sinusoids) was substantially increased, maturation was unchanged. Oxygen supplementation alone did not appreciably influence fetal resorptions or body weight in ligated horns, but did increase fetal heart weight. Sinusoidal area decreased (P less than 0.01), with no effect on sinusoidal maturity. Purified PFC treatment did not alter maternal weight gain or fetal body weight, and moderately decreased resorptions in ligated horns. Fetal heart weight was augmented with purified perflurochemical, while unpurified perfluorochemical treatment diminished heart weight. Both PFC emulsions substantially decreased sinusoidal area. CONCLUSIONS: Perflurocarbon treatment associated with supplemental oxygen is capable of improving the hypoxic effects on fetal heart and coronary vessel development if the emulsion used is appropriately purified.
Assuntos
Vasos Coronários/embriologia , Coração Fetal/crescimento & desenvolvimento , Hipóxia Fetal/terapia , Poloxaleno/uso terapêutico , Animais , Desenvolvimento Embrionário e Fetal , Feminino , Oxigenoterapia , Gravidez , Complicações na Gravidez/terapia , Ratos , Ratos EndogâmicosRESUMO
A multiresolution approach based on a modified wavelet transform called the tree-structured wavelet transform or wavelet packets is proposed. The development of this transform is motivated by the observation that a large class of natural textures can be modeled as quasi-periodic signals whose dominant frequencies are located in the middle frequency channels. With the transform, it is possible to zoom into any desired frequency channels for further decomposition. In contrast, the conventional pyramid-structured wavelet transform performs further decomposition in low-frequency channels. A progressive texture classification algorithm which is not only computationally attractive but also has excellent performance is developed. The performance of the present method is compared with that of several other methods.
RESUMO
The domain pool design is one of the dominant issues which affect the coding performance of fractal image compression. In this paper, we employ the LBG algorithm and propose a block averaging method to design the efficient domain pools based on a proposed iteration-free fractal image codec. The redundancies between the generated domain blocks are reduced by the proposed methods. Therefore, we can obtain the domain pools that are more efficient than those in the conventional fractal coding schemes and thus the coding performance is improved. On the other hand, the iteration process in the conventional fractal coding scheme not only requires a large size of memory and a high computation complexity but also prolongs the decoding process. The proposed iteration-free fractal codec can overcome the problems above. In computer simulation, both the LBG-based and block-averaging methods for the domain pool design in the proposed iteration free scheme achieve excellent performances. For example, based on the proposed block-averaging method, the decoded Lena image has at least a 0.5 dB higher PSNR (under the same bit rate) and an eight-time faster decoding speed than the conventional fractal coding schemes that require iterations.
RESUMO
By using the wavelet transform, the authors develop a hierarchical planar curve descriptor that decomposes a curve into components of different scales so that the coarsest scale components carry the global approximation information while the finer scale components contain the local detailed information. They show that the wavelet descriptor has many desirable properties such as multiresolution representation, invariance, uniqueness, stability, and spatial localization. A deformable wavelet descriptor is also proposed by interpreting the wavelet coefficients as random variables. The applications of the wavelet descriptor to character recognition and model-based contour extraction from low SNR images are examined. Numerical experiments are performed to illustrate the performance of the wavelet descriptor.
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We propose a new method called incremental Fourier synthesis to generate 2-D self-similar images based on a 2D fractional Brownian motion (fBm) model. With this method, the stationary increments of fBm are created by a Fourier synthesis method and the increments are added up to generate the nonstationary 2D fBm process. Since the new method takes advantage of the FFT, its computational complexity is only O(N(2)log(2)(N)), and its memory requirement is only O(N(2)) for a self-similar image of size NxN.
RESUMO
Data representation and content description are two basic components required by the management of any image database. A wavelet based system, called the WaveGuide, which integrates these two components in a unified framework, is proposed in this work. In the WaveGuide system, images are compressed with the state-of-the-art wavelet coding technique and indexed with color, texture, and object shape descriptors generated in the wavelet domain during the encoding process. All the content descriptors are extracted by machines automatically with a low computational complexity and stored with a low memory space. Extensive experiments are performed to demonstrate the performance of the new approach.