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1.
Zhonghua Yi Xue Za Zhi ; 104(4): 276-281, 2024 Jan 23.
Artigo em Zh | MEDLINE | ID: mdl-38246772

RESUMO

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)-1·min-1; ci1 group: (181.7±29.3) ml·(100 g)-1·min-1; ci2 group: (158.8±39.2) ml·(100 g)-1·min-1; ci3 group: (123.1±27.2) ml·(100 g)-1·min-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.


Assuntos
Transplante de Rim , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Rim , Fibrose , Aloenxertos
2.
Neuropsychol Rehabil ; 29(1): 144-159, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28051902

RESUMO

This study examined the use of the Hong Kong version of the Rivermead Behavioral Memory Test-Third Edition (RBMT-3) for older adults, and by presenting the optimal cut-off scores for patients with cognitive impairments, and for a group of peers who have functional everyday cognition. Hundred older adults residing in community dwellings were recruited from three non-government organisations and completed the RBMT-3: 29 patients with mild to moderate dementia, 34 persons at risk for MCI, and 37 matched older adults with everyday functional cognition for a healthy control group (NC). The test has excellent inter-rater (ICC [2, 1] = 0.997), intra-rater (ICC [3, 1] = 0), and parallel version (ICC [3, 1] = 0.990) reliabilities, as well as satisfactory internal consistency (Cronbach's alpha: 0.643-0.832). The scores of the MCI group were significantly lower than those of NC group in four subtests. The optimal cut-off scaled scores of ≤ 41.5, ≤ 102.5, and ≤ 131.5 are suggested for the RBMT-3 to discriminate between patients with mild and moderate dementia, mild dementia and MCI, and MCI and NC, with sensitivities 73%, 100% and 94.1%, respectively. This version is useful to differentiate those with or without risk of cognitive impairments.


Assuntos
Transtornos Cognitivos/psicologia , Transtornos Cognitivos/reabilitação , Testes de Memória e Aprendizagem/normas , Terapia Ocupacional/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Psicometria , Reprodutibilidade dos Testes
3.
Int J Immunopathol Pharmacol ; 25(4): 923-34, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23298483

RESUMO

Fulminant hepatic failure (FHF) is a devastating clinical syndrome with extremely poor prognosis and high mortality. Therefore, better treatment is urgently needed. Polydatin (PD), a traditional anti-inflammatory drug, has been described to protect against liver injury induced by certain hepatotoxins. The present study investigated the protective effect of PD against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF in mice and the underlying mechanism. Mice were pretreated with an increasing dose of PD (10, 30, and 100 mg/kg), following LPS/D-GalN challenge. The liver injury was assessed biochemically and histologically. We found that PD exerted a protective effect on LPS/D-GalN-induced FHF as evidenced by reducing sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, diminishing liver histopathological injury, and lowering mortality in a dose-dependent manner. In addition, pretreatment mice with PD dose-dependently suppressed tumor necrosis factor-alpha (TNF-alpha) production, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ECAM-1) expression, caspase-3 activation, and transcription factor nuclear factor-kappa B(NF-kB) activity induced by LPS. These results suggested that PD could effectively protect from LPS/D-GalN-induced FHF and the protective effect afforded by PD probably contributed to reduce TNF-alpha production via inhibiting NF-kB activation.


Assuntos
Galactosamina/toxicidade , Glucosídeos/farmacologia , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/prevenção & controle , Estilbenos/farmacologia , Animais , Caspase 3/metabolismo , Moléculas de Adesão Celular/análise , Molécula 1 de Adesão Intercelular/análise , Falência Hepática Aguda/induzido quimicamente , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese
4.
Genes Immun ; 12(2): 116-25, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21179116

RESUMO

The IL-2/IL-2R signaling pathway has an important role in autoimmunity. Several genes identified in genome-wide association (GWA) studies encode proteins in the IL-2/IL-2R signaling cascade that are associated with autoimmune diseases. One of these, PTPN2, encodes a protein tyrosine phosphatase that is highly expressed in T cells and regulates cytokine signaling. An intronic risk allele in PTPN2, rs1893217(C), correlated with decreased IL-2R signaling in CD4(+) T cells as measured by phosphorylation of STAT5 (phosphorylated STAT5 (pSTAT5)). We modeled an additive single nucleotide polymorphism (SNP) genotype, in which each copy of the risk allele conferred a decrease in IL-2R signaling (P=4.4 × 10(-8)). Decreased pSTAT5 impacted IL-2Rß chain signaling resulting in reduced FOXP3 expression in activated cells. This phenotype was not due to overt differences in expression of the IL-2R, molecules in the IL-2R signaling cascade or defects in STAT5. However, the rs1893217(C) risk variant did correlate with decreased PTPN2 expression in CD4(+)CD45RO T cells (P=0.0002). Thus, the PTPN2rs1893217(C) risk allele associated with reduced pSTAT5 in response to IL-2 and reduced PTPN2 expression. Together, these data suggest that decreased expression of PTPN2 may indirectly modulate IL-2 responsiveness. These findings, identified through genotype/phenotype relationships, may lead to identification of novel mechanisms underlying dysregulation of cytokine signaling in autoimmunity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo , Receptores de Interleucina-2/imunologia , Receptores de Interleucina-2/metabolismo , Adulto , Alelos , Autoimunidade/imunologia , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-2/metabolismo , Masculino , Fenótipo , Fosforilação , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais
5.
Inflamm Res ; 60(4): 357-66, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21063746

RESUMO

OBJECTIVE: Protein kinase D (PKD) is a newly described serine/threonine protein kinase that plays a pivotal role in inflammatory response. In the present study, we examined the protective effect of Gö6976, a PKD inhibitor, on lipopolysaccharide (LPS) and D: -galactosamine (D: -GalN)-induced acute liver injury in mice. MATERIALS AND METHODS: Mice were pretreated intraperitoneally with Gö6976 30 min before LPS/D: -GalN administration . The mortality and degree of hepatic injury was subsequently assessed. RESULTS: The results indicated that LPS/D: -GalN administration markedly induced hepatic PKD activation, lethality and liver injury, while pretreatment of the PKD inhibitor Gö6976 significantly inhibited LPS-induced PKD activation, improved the survival of LPS/D: -GalN-administered mice and attenuated LPS/D: -GalN-induced liver injury, as evidenced by reduced levels of serum aminotransferases as well as reduced histopathological changes. In addition, the protective effects of Gö6976 were paralleled by suppressed activation of mitogen-activated protein kinases (MAPKs), decreased expression of tumor necrosis factor-α (TNF-α) and adhesion molecules, and reduced apoptosis and myeloperoxidase (MPO) activity in liver. CONCLUSIONS: Our experimental data indicated that Gö6976, a PKD inhibitor, could effectively prevent LPS/D: -GalN-induced acute liver injury by inhibition of MAPKs activation to reduce TNF-α production. This suggests the potential pharmacological value of PKD inhibitors in the intervention of inflammation-based liver diseases.


Assuntos
Carbazóis/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Inibidores Enzimáticos/uso terapêutico , Galactosamina/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Proteína Quinase C/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Carbazóis/farmacologia , Caspases/metabolismo , Ativação Enzimática/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
Eur Rev Med Pharmacol Sci ; 24(12): 6818-6824, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633374

RESUMO

OBJECTIVE: To explore the expression of linc00324 in papillary thyroid cancer (PTC) and its effect on the biological function of PTC cells. PATIENTS AND METHODS: A total of 60 pairs of PTC and para-carcinoma normal tissues surgically excised were collected. The expression of linc00324 in PTC tissues and cells was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the expression of linc00324 in PTC cells was silenced using the small-interfering RNA (siRNA). Then, the effects of linc00324 on the PTC cell proliferation, apoptosis, and cycle and the downstream Notch signaling pathway were determined via methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, flow cytometry, and Western blotting, respectively. RESULTS: The expression of linc00324 was upregulated in 48 out of 60 cases of PTC tissues, and it was increased in PTC cells compared with that in human thyroid follicular epithelial cells Nthy-ori 3-1. The results of MTT assay and colony formation assay showed that the proliferation of PTC cells declined after interference in linc00324 expression. The findings of flow cytometry revealed that the cell cycle was arrested in G1/G0 phase with a higher apoptosis rate in si-linc00324 group compared with that in the si-NC group. According to the data of Western blotting, the molecular markers for the downstream Notch signaling pathway were altered after interference in linc00324 expression. CONCLUSIONS: The expression of linc00324 is significantly increased in PTC tissues and cells. Silencing linc00324 may inhibit the proliferation of PTC cells, arrest the cell cycle in G1/G0 phase, and promote the apoptosis by inhibiting the Notch signaling pathway.


Assuntos
RNA Longo não Codificante/metabolismo , Receptores Notch/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Apoptose , Proliferação de Células , Células Cultivadas , Humanos , RNA Longo não Codificante/genética , Transdução de Sinais , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
8.
Clin Transl Oncol ; 22(7): 1013-1022, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31650468

RESUMO

OBJECTIVE: Chronic inflammation is recognized as a risk factor for colorectal cancer (CRC) development. Baicalin (BI), a major constituent in an anti-inflammatory herb Scutellaria baicalensis, can be biotransformed into baicalein (BE) by the intestinal microbiota. We evaluated the anti-inflammation and anti-CRC effects of the metabolite BE. METHODS: The in vitro biotransformation by human intestinal microbiota from BI into BE has been determined with HPLC. Using a gut-specific ApcMin/+ mouse model, the effects of oral BE on the life span, organ index, and tumor multiplicity were evaluated. The expressions of inflammatory cytokines were determined using ELISA. To verify the in vivo data, the anti-inflammatory and antiproliferative effects of BE were determined with an in vitro cell model. RESULTS: HPLC analysis showed that BI was quickly transformed into BE by the intestinal microbiota. Oral BE (30 mg/kg/day) significantly increased the life span, from 125.2 to 218.4 days (P < 0.01%). BE treatment also decreased intestine index and increased spleen index. Compared with the model group, following BE treatment, tumor numbers were significantly reduced in the small intestine and colon (P < 0.01, P < 0.05, respectively). In the gut tissues, BE treatment significantly reduced inflammatory cytokine levels such as IL-1ß, IL-2, IL-6, IL-10, G-CSF, and GM-CSF. In vitro data supported our in vivo results that the anti-CRC effects of BE were via the inhibition of gut inflammation and induction of cancer cell death. CONCLUSION: Our results suggest that the parent compound BI can be quickly converted into its microbial metabolite BE, which has stronger bioactive effects than BI. Baicalein is an active chemopreventive metabolite for inflammatory associated CRC.


Assuntos
Antioxidantes/farmacologia , Colo/efeitos dos fármacos , Neoplasias Colorretais/patologia , Citocinas/efeitos dos fármacos , Flavanonas/farmacologia , Intestino Delgado/efeitos dos fármacos , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Colo/imunologia , Colo/patologia , Neoplasias Colorretais/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Flavanonas/metabolismo , Flavonoides/metabolismo , Microbioma Gastrointestinal , Células HT29 , Humanos , Inflamação/metabolismo , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Longevidade , Camundongos , Carga Tumoral
10.
Clin Transl Oncol ; 20(3): 302-312, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28808878

RESUMO

OBJECTIVE: Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment. METHODS: Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined. After establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. The alpha and beta diversities of microbiome were analyzed. RESULTS: American ginseng significantly attenuated AOM/DSS-induced colon inflammation and tumorigenesis by reducing the colitis score and colon tumor multiplicity. The MiSeq results showed that the majority of sequences fell into three phyla: Firmicutes, Bacteroidetes and Verrucomicrobia. Further, two significant abundance shifts at the family level, Bacteroidaceae and Porphyromonadaceae, were identified to support ginseng's anti-colitis and anti-tumor effects. In addition, alpha and beta diversity data demonstrated that ginseng led to a profound recovery from the AOM/DSS-induced dysbiosis in the microbial community. CONCLUSION: Our results suggest that the CRC chemopreventive effects of American ginseng are mediated through enteric microbiome population-shift recovery and dysbiosis restoration. Ginseng's regulation of the microbiome balance contributes to the maintenance of enteric homeostasis.


Assuntos
Carcinogênese/efeitos dos fármacos , Neoplasias do Colo/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Panax , Extratos Vegetais/farmacologia , Animais , Azoximetano/toxicidade , Carcinogênese/induzido quimicamente , Carcinogênese/patologia , Colite/etiologia , Colite/microbiologia , Colite/patologia , Neoplasias do Colo/etiologia , Neoplasias do Colo/microbiologia , Sulfato de Dextrana/toxicidade , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Raízes de Plantas
12.
Oncogene ; 36(4): 491-500, 2017 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-27321183

RESUMO

Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade, including ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility, invasion of PDAC cells-all collectively contributing to PDAC progression. Interestingly, all of these phenotypic effects of MUC13-HER2 co-localization could be effectively compromised by depleting MUC13 and mediated by the first and second EGF-like domains of MUC13. Further, MUC13-HER2 co-localization also holds true in PDAC tissues with a strong functional correlation with events contributing to increased degree of disorder and cancer aggressiveness. In brief, findings presented here provide compelling evidence of a functional ramification of MUC13-HER2: this interaction could be potentially exploited for targeted therapeutics in a subset of patients harboring an aggressive form of PDAC.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Mucinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptor ErbB-2/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Mucinas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Receptor ErbB-2/genética , Transdução de Sinais , Transfecção
13.
J Thromb Haemost ; 4(6): 1279-87, 2006 06.
Artigo em Inglês | MEDLINE | ID: mdl-16706972

RESUMO

BACKGROUND: Previous genotype-phenotype association studies of fibrinogen have been limited by incomplete knowledge of genomic sequence variation within and between major ethnic groups in FGB, FGA, and FGG. METHODS: We characterized the linkage disequilibrium patterns and haplotype structure across the human fibrinogen gene locus in European- and African-American populations. We analyzed the association between common polymorphisms in the fibrinogen genes and circulating levels of both 'functional' fibrinogen (measured by the Clauss clotting rate method) and total fibrinogen (measured by immunonephelometry) in a large, multi-center, bi-racial cohort of young US adults. RESULTS: A common haplotype tagged by the A minor allele of the well-studied FGB-455 G/A promoter polymorphism (FGB 1437) was confirmed to be strongly associated with increased plasma fibrinogen levels. Two non-coding variants specific to African-American chromosomes, FGA 3845 A and FGG 5729 G, were each associated with lower plasma fibrinogen levels. In European-Americans, a common haplotype tagged by FGA Thr312Ala and several other variant alleles across the fibrinogen gene locus was strongly associated with decreased fibrinogen levels as measured by functional assay, but not by immunoassay. Overall, common polymorphisms within the three fibrinogen genes explain < 2% of the variability in plasma fibrinogen concentration. CONCLUSIONS: In young adults, fibrinogen multi-locus genotypes are associated with plasma fibrinogen levels. The specific single nucleotide polymorphism and haplotype patterns for these associations differ according to population and also according to phenotypic assay. It is likely that a substantial proportion of the heritable component of plasma fibrinogen concentration is due to genetic variation outside the three fibrinogen genes.


Assuntos
Doenças Cardiovasculares/genética , Fibrinogênio/genética , Variação Genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Negro ou Afro-Americano/genética , Testes de Coagulação Sanguínea , Doenças Cardiovasculares/sangue , Fibrinogênio/metabolismo , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Imunoensaio/métodos , Desequilíbrio de Ligação , Fenótipo , Reprodutibilidade dos Testes , População Branca/genética
14.
Am J Med Sci ; 331(3): 124-30, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16538072

RESUMO

OBJECTIVE: Mitral annulus calcification (MAC) is an independent predictor of cardiovascular mortality in the general population. The purpose of the current historical cohort study is to assess risk factors for long-term mortality in end-stage renal disease (ESRD) patients with MAC (n = 30; age, 62 +/- 2 yr), as compared to ESRD patients without MAC (n = 30; age, 63 +/- 2 yr). Additional analysis compared ESRD patients with MAC to non-ESRD patients with MAC (n = 32; age, 66 +/- 2 yr). METHODS: The groups included age-matched male patients followed at a single center. Long-term survival was assessed by Kaplan-Meier analysis. Regular and stepwise Cox proportional hazards models were used to determine risk factors for mortality. RESULTS: There was a similarly high prevalence of cardiovascular complications, including hypertension, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, and congestive heart failure, in all three groups. Median survival time was significantly longer in non-ESRD patients (90 months), compared with the ESRD with MAC (45 months) and ESRD without MAC (45 months) patients (log-rank test; P < 0.001). With stepwise Cox proportional hazards model, including ESRD patients with MAC and ESRD patients without MAC, increased calcium x phosphate product, decreased serum creatinine concentration, and the presence of coronary artery disease and lower extremity amputations were independent predictors of mortality for patients with ESRD. With stepwise Cox proportional hazards model, including ESRD patients with MAC and non-ESRD patients with MAC, the presence of ESRD, atrial fibrillation, diabetes, aortic valve calcification, coronary artery disease, and tricuspid regurgitation were independent predictors of mortality. CONCLUSION: The mortality rate was high in ESRD patients, approximately 15% per year. After accounting for baseline cardiovascular disease and traditional risk factors, the presence of MAC did not confer additional risk for mortality.


Assuntos
Calcinose/etiologia , Doenças das Valvas Cardíacas/etiologia , Falência Renal Crônica/mortalidade , Valva Mitral/patologia , Calcinose/epidemiologia , Estudos de Coortes , Doenças das Valvas Cardíacas/epidemiologia , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida
15.
Clin Cancer Res ; 7(4): 791-4, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11309323

RESUMO

The association between autoimmune hemolytic anemia (AIHA) and subsequent appearance of lymphoproliferative disorders (LPDs) has not been properly addressed in large-scale studies. We evaluated 107 patients with idiopathic (67 patients) or underlying (40 patients) immune disorders diagnosed with AIHA between 1992 and 1999. The following variables were examined in univariate and multivariate analysis: age; sex; type of AIHA (warm- or cold-active antibodies); presence of underlying immune disorders; and serum monoclonal protein. Of the 107 patients, 19 (18%) developed malignant LPDS: The median time to develop malignancy was 26.5 months (range, 9-76 months). At multivariate analysis, advanced age (P = 0.005), underlying autoimmune diseases (P = 0.002), and the presence of serum gammopathy (P = 0.045) were risk factors for future development of LPDs in these patients. Also, serum monoclonal IgM protein was a significant predictor (P = 0.0001) for the appearance of LPDs in patients with AIHA. The present study provides evidence that AIHA in some patients should be considered as a precursor of malignant LPDS: Knowledge of certain characteristics may help identify patients at risk for this transformation; periodic clinical and laboratory assessment of these patients is warranted.


Assuntos
Anemia Hemolítica/complicações , Transtornos Linfoproliferativos/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Transtornos Linfoproliferativos/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
16.
AIDS ; 7(11): 1493-9, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8280417

RESUMO

OBJECTIVE: To investigate the relationship between psychological distress, alcohol, drug and condom use in HIV-serodiscordant heterosexual couples. METHODS: Structured interviews were conducted to collect demographic information, detailed data on psychological distress, drug and alcohol use and sexual behavior. RESULTS: Analyses were based on 106 pairs of sexually active discordant couples. Significant differences among heterosexual condom users and non-users varied according to gender and HIV serostatus. Affect domains of interpersonal sensitivity and hostility were significant, as were the variables of regular drug or alcohol use and combining sex with drugs or alcohol. Employment was strongly associated with condom use in HIV-negative women whose regular sexual partners were HIV-positive men. CONCLUSION: The risk of vaginal sex without condoms in HIV-serodiscordant heterosexual couples may be reduced by specific psychological counseling and attention to drug and alcohol use as risk factors. Further research on the effect of employment of HIV-negative women is required.


PIP: The authors investigated the relationship of psychological distress and drug and alcohol use to reported condom use in 106 sexually active HIV-serodiscordant heterosexual couples. Significant differences were found among heterosexual condom users and non-users which varied according to gender and HIV serostatus. Affect domains of interpersonal sensitivity and hostility were significant, as were the variables of regular drug or alcohol use and combining sex with drugs or alcohol. Further, employment was strongly associated with condom use HIV-negative women whose regular sex partners were HIV-positive men. The authors therefore conclude that the risk of vaginal sex without condoms in HIV-serodiscordant heterosexual couples may be reduced by specific psychological counseling and attention to drug and alcohol use as risk factors. Further research is, however, called for on the effect of employment on HIV-negative women.


Assuntos
Alcoolismo/complicações , Preservativos/estatística & dados numéricos , Infecções por HIV/psicologia , Soronegatividade para HIV , Estresse Psicológico/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Adolescente , Adulto , Alcoolismo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/psicologia
17.
J Hypertens ; 18(8): 1149-54, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10954008

RESUMO

OBJECTIVE: To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients. DESIGN: Cohort study in a randomized trial. SETTING: Cohort of hypertensive patients. PARTICIPANTS: A total of 4327 men and women, aged > or = 60 years, with isolated systolic hypertension, randomized to placebo or chlorthalidone, with the addition of atenolol or reserpine if needed, were observed for 5 years. MAIN OUTCOME MEASURES: Major cardiovascular events, coronary events, stroke and all-cause mortality. RESULTS: Cardiovascular event rates for quartiles of baseline serum uric acid were: I, 32.7 per 1000 person-years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV, 41.4 per 1000 person-years (P for trend = 0.02). The adjusted hazard ratio (HR), of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 (95% CI, 1.03-1.69). The benefit of active treatment was not affected by baseline serum uric acid. After randomization, an increase of serum uric acid < 0.06 mmol/l (median change) in the active treatment group was associated with a HR of 0.58 (0.37-0.92) for coronary events compared with those with a serum uric acid increase > or = 0.06 mmol/l. This difference was not explained by blood pressure effects. Those with a serum uric acid increase > or = 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group. CONCLUSIONS: Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension. Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/etiologia , Clortalidona/uso terapêutico , Diuréticos/uso terapêutico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Ácido Úrico/sangue , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Atenolol/uso terapêutico , Biomarcadores , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reserpina/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
18.
Thromb Haemost ; 86(3): 828-33, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11583315

RESUMO

Disseminated intravascular coagulation (DIC) is a well known hemostatic complication of solid tumors. We evaluated the occurrence of DIC in 1117 patients with solid tumors. Of these patients, 76 (6.8%) were diagnosed with DIC. There were a total of 145 bleeding and clotting episodes reported in the 76 patients. Thrombocytopenia, hypofibrinogemia, elevated D-dimer and fibrinogen degradation products were the most common coagulation abnormalities encountered in patients with DIC. In multivariate analysis, older age (p = .0001), male gender (p = .009), advanced malignancies (p = .027), breast cancer (p = .038) and the presence of necrosis in the tumor specimen (p = .004), emerged as independent factors significantly related to the occurrence of DIC in patients with solid tumors. Of the 76 patients, 25 (33%) achieved response to treatment of DIC as defined in the study. Patients with early stage and advanced malignancies who developed DIC had inferior survival when compared with their counterparts without DIC (p = .039 and p = .005, respectively). Taken together, this study indicates that certain clinical and laboratory features are more common in patients with solid tumors who developed DIC. The occurrence of DIC appears to have an independent effect on survival of patients with cancer. Cooperative studies are encouraged to better address the usefulness and optimal prophylactic heparin regimen in patients at risk for DIC.


Assuntos
Coagulação Intravascular Disseminada/etiologia , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/análise , Coagulação Intravascular Disseminada/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Seguimentos , Hemorragia/etiologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Necrose , Neoplasias/sangue , Neoplasias/patologia , Trombocitopenia/etiologia , Trombose/etiologia
19.
J Am Geriatr Soc ; 42(10): 1062-9, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7930330

RESUMO

OBJECTIVE: To assess colonization and infection with methicillin-resistant Staphylococcus aureus (MRSA), high-level gentamicin-resistant enterococci (R-ENT) and gentamicin and/or ceftriaxone-resistant Gram-negative bacilli (R-GNB) and the factors that are associated with colonization and infection with these organisms. DESIGN: Monthly surveillance for colonization and infection over a period of 2 years. In the second year, an intervention to decrease MRSA colonization by the use of mupirocin ointment was carried out. SETTING: Long-term care facility attached to an acute care Veterans Affairs Medical Center. PATIENTS: A total of 551 patients in the facility were followed for a period of 2 years. MEASUREMENTS: Colonization and infection rates with MRSA, R-ENT, and R-GNB. Analysis of risk factors associated with colonization and infection with these three groups of organisms. MAIN RESULTS: In the first year, colonization rates were highest for MRSA (22.7 +/- 1% patients colonized each month) and R-ENT (20.2 +/- 1%) and lower for R-GNB (12.6 +/- 1%). After introduction of decolonization of nares and wounds with mupirocin, the rate of MRSA colonization fell significantly to 11.5 +/- 1.8%, but rates remained unchanged for R-ENT and R-GNB. Risk factors for MRSA colonization included the presence of wounds and decubitus ulcers. For R-ENT, the presence of wounds, renal failure, intermittent urethral catheterization, low serum albumin, and poor functional level were significant. For R-GNB, intermittent urethral catheterization, chronic renal disease, inflammatory bowel disease, presence of wounds, and prior pneumonia were significantly associated with colonization. Overall, of infections caused by known organisms, 49.6% were due to MRSA, R-ENT, or R-GNB, and 50.4% were due to susceptible organisms. Infections were more commonly due to R-GNB (21.1% of all infections) than to R-ENT (8.3%) or MRSA (4.6%). The most common infections were urinary tract infections (42.9% of all infections) and skin and soft tissue infections (31.9% of all infections). Risk factors for MRSA infections were diabetes mellitus and peripheral vascular disease, for R-GNB infections were intermittent urethral catheterization and indwelling urethral catheters, and no one factor was associated with R-ENT infection. CONCLUSIONS: In our long-term care facility, colonization with resistant MRSA and R-ENT was more common than R-GNB, but infections were more often due to R-GNB than R-ENT and MRSA. Several host factors, which potentially could be modified in order to prevent infections, emerged as important in colonization and infection with these antibiotic-resistant organisms.


Assuntos
Infecções Bacterianas/microbiologia , Portador Sadio/microbiologia , Resistência Microbiana a Medicamentos , Casas de Saúde/estatística & dados numéricos , Idoso , Infecções Bacterianas/epidemiologia , Portador Sadio/tratamento farmacológico , Portador Sadio/epidemiologia , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Feminino , Gentamicinas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitais de Veteranos , Humanos , Assistência de Longa Duração , Masculino , Resistência a Meticilina , Michigan/epidemiologia , Pessoa de Meia-Idade , Mupirocina/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
20.
J Am Geriatr Soc ; 46(7): 849-53, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9670871

RESUMO

OBJECTIVES: To assess colonization and serious infection with yeasts and the risk factors that are associated with colonization by these organisms. DESIGN: Monthly surveillance for colonization and infection over a period of 2 years. SETTING: A long-term-care facility (LTCF) attached to an acute-care Veterans Affairs Medical Center. PARTICIPANTS: The 543 men and 10 women in the facility. MEASUREMENTS: Colonization and serious infection rates with yeasts. Analysis of risk factors associated with yeast colonization of residents. RESULTS: Colonization rates were relatively stable during the 2-year period (53+/-1.8% patients colonized per month). Candida albicans was the most common colonizer, found in 35+/-.9% of patients colonized per month. The pharynx was the most commonly colonized site, with 41+/-1.4% of patients per month with pharyngeal colonization. Eighty-four percent of patients remaining in the facility for 3 or more months were colonized by yeast at some time during their stay. Presence of neurogenic bladder, leg amputation, or a low serum albumin were independently associated with yeast colonization; neither diabetes mellitus nor functional status was a risk factor for colonization by yeasts. Only four serious yeast infections in four patients (esophagitis and three urinary tract infections) were found during the 2-year period; all infections occurred in patients who were colonized by yeasts previously. CONCLUSION: In our LTCF, colonization of patients by yeasts occurred commonly in those residents remaining in the facility for 3 or more months. However, serious yeast infections occurred infrequently. It is likely that colonization of residents of LTCFs by yeasts may only become clinically important when the patient is transferred to an acute-care hospital where additional risk factors may allow the development of serious yeast infection.


Assuntos
Candidíase/epidemiologia , Infecção Hospitalar/epidemiologia , Idoso , Candida/isolamento & purificação , Candidíase/microbiologia , Infecção Hospitalar/microbiologia , Feminino , Hospitais com 300 a 499 Leitos , Hospitais de Veteranos , Humanos , Incidência , Assistência de Longa Duração , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco
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