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1.
Am J Otolaryngol ; 45(4): 104334, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38723380

RESUMO

PURPOSE: Tympanostomy tube (TT) placement is the most frequently performed ambulatory surgery in children under 15. After the procedure it is recommended that patients follow up regularly for "tube checks" until TT extrusion. Such visits incur direct and indirect costs to families in the form of days off from work, copays, and travel expenses. This pilot study aims to compare the efficacy of tympanic membrane (TM) evaluation by an artificial intelligence algorithm with that of clinical staff for determining presence or absence of a tympanostomy tube within the TM. METHODS: Using a digital otoscope, we performed a prospective study in children (ages 10 months-10 years) with a history of TTs who were being seen for follow up in a pediatric otolaryngology clinic. A smartphone otoscope was used by study personnel who were not physicians to take ear exam images, then through conventional otoscopic exam, ears were assessed by a clinician for tubes being in place or tubes having extruded from the TM. We trained and tested a deep learning (artificial intelligence) algorithm to assess the images and compared that with the clinician's assessment. RESULTS: A total of 123 images were obtained from 28 subjects. The algorithm classified images as TM with or without tube in place. Overall classification accuracy was 97.7 %. Recall and precision were 100 % and 96 %, respectively, for TM without a tube present, and 95 % and 100 %, respectively, for TM with a tube in place. DISCUSSION: This is a promising deep learning algorithm for classifying ear tube presence in the TM utilizing images obtained in awake children using an over-the-counter otoscope available to the lay population. We are continuing enrollment, with the goal of building an algorithm to assess tube patency and extrusion.


Assuntos
Aprendizado Profundo , Ventilação da Orelha Média , Humanos , Ventilação da Orelha Média/métodos , Criança , Pré-Escolar , Estudos Prospectivos , Lactente , Projetos Piloto , Masculino , Feminino , Membrana Timpânica/cirurgia , Otoscopia/métodos , Algoritmos , Otoscópios
2.
Med J Malaysia ; 76(3): 414-416, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34031342

RESUMO

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.


Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
3.
Malays J Pathol ; 41(3): 313-326, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31901916

RESUMO

INTRODUCTION: Quantitative polymerase chain reaction (qPCR) is commonly used in the investigation of acute myeloid leukaemias (AML). Stable reference genes (RG) are essential for accurate and reliable reporting but no standard method for selection has been endorsed. MATERIALS AND METHODS: We evaluated simple statistics and published model-based approaches. Multiplex-qPCR was conducted to determine the expression of 24 candidate RG in AMLs (N=9). Singleplex-qPCR was carried out on selected RG (SRP14, B2M and ATP5B) and genes of interest in AML (N=15) and healthy controls, HC (N=12). RESULTS: RG expression levels in AML samples were highly variable and coefficient of variance (CV) ranged from 0.37% to 10.17%. Analysis using GeNorm and Normfinder listed different orders of most stable genes but the top seven (ACTB, UBE2D2, B2M, NF45, RPL37A, GK, QARS) were the same. In singleplex-qPCR, SRP14 maintained the lowest CV in AML samples. B2M, one of most stable reference genes in AML, was expressed near significantly different in AML and HC. GeNorm selected ATP5B+SRP14 while Normfinder chose SRP14+B2M as the best two RG in combination. The median expressions of combined RG genes in AML compared to HC were less significantly different than individually implying smaller expression variation after combination. Genes of interest normalised with RG in combination or individually, displayed significantly different expression patterns. CONCLUSIONS: The selection of best reference gene in qPCR must consider all sample sets. Model-based approaches are important in large candidate gene analysis. This study showed combination of RG SRP14+B2M was the most suitable normalisation factor for qPCR analysis of AML and healthy individuals.


Assuntos
Expressão Gênica/genética , Leucemia Mieloide Aguda/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Adolescente , Adulto , Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto Jovem
4.
Med J Malaysia ; 74(6): 534-536, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31929481

RESUMO

Haematological cellular structures may be elucidated using automated full blood count (FBC) analysers such as Unicel DxH 800 via cell population data (CPD) analysis. The CPD values are generated by calculating volume, conductivity, and five types of scatter angles of individual cells which would form clusters or populations. This study considered 126 CPD parameter values of 1077 healthy Malaysian adults to develop reference intervals for each CPD parameter. The utility of the CPD reference interval established may range from understanding the normal haematological cellular structures to analysis of distinct cellular features related to the development of haematological disorders and malignancies.


Assuntos
Etnicidade , Doenças Hematológicas/sangue , Adulto , Contagem de Células Sanguíneas , Feminino , Doenças Hematológicas/etnologia , Humanos , Malásia/epidemiologia , Masculino , Morbidade/tendências , Valores de Referência
5.
J Viral Hepat ; 21(4): 288-96, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24597697

RESUMO

Suppression of hepatitis B virus (HBV)-DNA to undetectable levels is an important goal for HIV/HBV-co-infected patients receiving anti-HBV-active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1 year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1 year of tenofovir-based ART. We performed a cohort study among tenofovir-treated HIV/HBV-co-infected patients. Patients had HBV viraemia, initiated tenofovir-based ART and had HBV DNA measured at 1 year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA ≥2.6 log IU/mL) at 1 year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46-63%) had incomplete HBV suppression at 1 year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1-1.94) and detectable HIV viraemia at 1 year (OR, 2.52; 95% CI, 1.19-5.32). Among 66 patients with suppressed HIV RNA at 1 year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1 year occurred in a sizeable proportion of tenofovir-treated HIV/HBV-co-infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression.


Assuntos
Fármacos Anti-HIV/uso terapêutico , DNA Viral/sangue , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/fisiologia , Hepatite B/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Coinfecção , Farmacorresistência Viral , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepatite B/complicações , Hepatite B/virologia , Vírus da Hepatite B/genética , Humanos , Incidência , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Tenofovir , Carga Viral , Viremia
6.
Malays J Pathol ; 34(2): 133-43, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23424776

RESUMO

MicroRNAs (miRNAs) are mostly located at cancer-associated genomic regions or in fragile sites, suggesting their important role in the pathogenesis of human cancers. Multiple myeloma (MM) is a cancer of plasma cells, the third most common cancer of the blood after lymphoma and leukaemia. There are several published reports on miRNAs in MM, however most used bone marrow rather than peripheral blood samples. The aim of this study is to characterise miRNA expression in normal and MM patients using peripheral blood samples as it is less invasive and is readily available from patients. Blood samples from 35 MM patients were analysed using the microarray method. We identified up-regulation of 36 miRNAs (57%) and down-regulation of 27 miRNAs (43%). We also identified the CCND2, HMGA2 and IGF1R genes were among the highly predictive target genes (P(CT) > 0.80) for most of the deregulated miRNAs. These genes are known to play important roles in MM as well as other cancers. Five miRNAs (let-7c, miR-16, miR- 449, miR-181a and miR-181b) were found to exhibit similar expression patterns (p < 0.05) in peripheral blood when compared to data obtained by using bone marrow aspirates from MM patients in other studies. In conclusion, our study has demonstrated that miRNAs are also present and differentially expressed in the peripheral blood of MM patients compared to controls and may potentially serve as candidate tumour biomarkers in MM. In particular, let-7c and miR-16 have been shown to be significantly expressed in the bone marrow.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Mieloma Múltiplo/genética , Adulto , Idoso , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Análise Serial de Tecidos , Regulação para Cima
7.
Med J Malaysia ; 66(5): 522-4, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22390120

RESUMO

Thalassaemia is a common disorder in Malaysia. It is estimated that 4.5% of the population are carriers for beta- or alpha- thalassaemias. We set out to screen Form 4 students aged between 15 and 16 years old in a national school, for thalassaemia in March 2008. Written consent was obtained from 310 students. The carrier rate for the common thalassaemia syndromes was 6.8% (2.9% for beta-thalassaemia, 2.6% for HbE and 1.3% for two-gene deletion for alpha-thalassaemia). Carriers for beta-thalassaemia and two-gene deletion for alpha-thalassaemia were more common in the Chinese (4.3% and 1.4% respectively) while heterozygous HbE was more common in the Malays (3.8%). The laboratory cost of screening one student was RM 45 and the total number of man-hours spent in this screening activity was 600. This screening exercise showed that thalassaemia carriers are common among the Chinese and Malays and it is feasible to carry out a screening programme for secondary school students.


Assuntos
Programas de Rastreamento , Instituições Acadêmicas , Talassemia/epidemiologia , Adolescente , Portador Sadio , Feminino , Humanos , Malásia/epidemiologia , Masculino , Reação em Cadeia da Polimerase
8.
Med J Malaysia ; 63 Suppl C: 66-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19227675

RESUMO

Treatment option of Haematological malignancies has expanded over the last decade. The outcome of treatment is expected to be better compare to previously. However, study of treatment outcome for haematological malignancies has not been carried out in Malaysia. The goal of this study is to measure the treatment outcome in patients with haematological malignancy.


Assuntos
Neoplasias Hematológicas/epidemiologia , Sistema de Registros/estatística & dados numéricos , Coleta de Dados , Bases de Dados Factuais/normas , Bases de Dados Factuais/estatística & dados numéricos , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Malásia/epidemiologia , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Sistema de Registros/normas , Projetos de Pesquisa
9.
Singapore Med J ; 48(10): 932-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17909680

RESUMO

INTRODUCTION: The multidrug resistance gene, MDR1, is one of the genes responsible for resistance to chemotherapy in the treatment of leukaemia and other cancers. The discovery of RNA interference in mammalian cells has provided a powerful tool to inhibit the expression of this gene. However, very little is known about the transfection of leukaemia cells with short interfering RNA (siRNA) targeted at MDR1. This study aims to evaluate the effectiveness of two chemically-synthesised siRNA in modulating MDR1 gene and inhibiting P-glycoprotein expression in leukaemic cells. We also evaluated two siRNA delivery methods in this study. METHODS: K562/Adr was transfected with two MDR1-targeted siRNA or negative control siRNA, by using cationic lipid-based transfection reagents or electroporator. Gene expression of MDR1 was quantified by real-time polymerase chain reaction and calculated as a percentage relative to the negative control siRNA. P-glycoprotein expression was evaluated via flow cytometry and drug sensitivity after treatment was assessed by cytotoxicity assays. RESULTS: The percentage of MDR1 gene knockdown from cells transfected with an electroporator was significantly higher (84.4 percent, p-value is 0.094) compared to cells transfected with cationic lipid-based transfection reagents (52.8 percent). Both siRNA significantly reduced the expression of MDR1 by 84.9 percent (p-value is 0.001) and 86.0 percent (p-value is 0.011), respectively. P-glycoprotein expression was down-regulated and drug sensitivity was increased after treatment with the siRNA. CONCLUSION: This study shows that the two siRNA sequences are capable of modulating MDR1 and P-glycoprotein expressions and increased drug sensitivity. Transfection with an electroporator was superior to chemical transfection for leukaemia cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos , Leucemia/tratamento farmacológico , Leucemia/genética , RNA Interferente Pequeno/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes MDR/genética , Humanos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transfecção , Células Tumorais Cultivadas
10.
J Viral Hepat ; 13(4): 242-9, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16611190

RESUMO

In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1) infection. The aim of this community-based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or 48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22-0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92; P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3) have a lower SVR rate than non-Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions.


Assuntos
Antivirais/administração & dosagem , População Negra , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Biópsia , Relação Dose-Resposta a Droga , Feminino , Genótipo , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/efeitos adversos , Cirrose Hepática/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , RNA Viral/sangue , Ribavirina/efeitos adversos , População Branca
11.
J Clin Pathol ; 57(10): 1098-100, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15452169

RESUMO

Large cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare. A 55 year old woman presented with an ampullary tumour causing pancreaticobiliary obstruction and a pancreaticoduodenectomy was performed. Microscopically, the tumour was diagnosed as a CD117 positive large cell neuroendocrine carcinoma with glandular differentiation. Four months later the patient developed a general recurrence. The metastatic tumours showed CD117 negativity and pure neuroendocrine features. The patient died of disease six months after diagnosis. It is postulated that the two components originated from a common multipotential stem cell. The clinical behaviour of ampullary large cell neuroendocrine carcinomas appears to be highly aggressive, with early metastases and a fatal outcome.


Assuntos
Ampola Hepatopancreática/patologia , Carcinoma de Células Grandes/patologia , Neoplasias do Ducto Colédoco/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Complexas Mistas/patologia , Ampola Hepatopancreática/cirurgia , Biomarcadores Tumorais/análise , Carcinoma de Células Grandes/cirurgia , Diferenciação Celular , Neoplasias do Ducto Colédoco/cirurgia , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Neoplasias Complexas Mistas/cirurgia , Pancreaticoduodenectomia , Proteínas Proto-Oncogênicas c-kit/análise
12.
Oper Dent ; 28(6): 740-6, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14653289

RESUMO

This study investigated the effect of commercially available mouthrinses on the microhardness and wear of composite (Esthet-X, Dentsply) and compomer (Dyract Posterior, Dentsply) restoratives. Fifty-four hardness and 36 wear specimens of each material were fabricated and stored in distilled water at 37 degrees C for two weeks. The specimens were then randomly divided into six equal groups and exposed to the following solutions for 24 hours at 37 degrees C: distilled water [WC] (control); Listerine Original [AP] (alcohol-containing essential oil/phenolic compound mouthrinse); Colgate Chloropharm [AC] (alcohol-containing chlorhexidine mouthrinse); Oral B Tooth & Gum Care [AF] (alcohol-containing fluoride mouthrinse); Oral B Tooth & Gum Care Alcohol Free [OF] (alcohol free fluoride mouthrinse) and Oral B Sensitive [PF] (phosphoric acid containing fluoride mouthrinse). After conditioning, the specimens were subjected to hardness testing using a digital microhardness tester (load = 500 gf; dwell time = 15 seconds) and wear testing with a reciprocal compression-sliding system (contact stress = 20 MPa). Wear depth was measured every 1,000 cycles up to 10,000 cycles using profilometry. Data was analyzed using ANOVA/Scheffe's test at significance level 0.05. Dyract was significantly softened by AP, while Esthet-X was significantly softened by AC and AP. The wear resistance of Dyract was significantly reduced after exposure to PF, while the wear resistance of Esthet-X was significantly reduced by AC. The effect of mouthrinses on hardness and wear was material dependent.


Assuntos
Compômeros/química , Resinas Compostas/química , Desgaste de Restauração Dentária , Restauração Dentária Permanente , Antissépticos Bucais/química , Análise de Variância , Anti-Infecciosos Locais/química , Cariostáticos/química , Clorexidina/química , Combinação de Medicamentos , Etanol/química , Fluoretos/química , Dureza , Humanos , Teste de Materiais , Ácidos Fosfóricos/química , Salicilatos/química , Temperatura , Terpenos/química , Fatores de Tempo , Água/química
13.
J Exp Med ; 194(10): 1395-406, 2001 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-11714747

RESUMO

The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1-2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-gamma- CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38- and started producing IFN-gamma in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host-virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+ T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.


Assuntos
Hepatite C/imunologia , Doença Aguda , Adulto , Alanina Transaminase/sangue , Linfócitos T CD4-Positivos/imunologia , Feminino , Hepatite C/virologia , Humanos , Interferon gama/fisiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/análise
14.
Arch Oral Biol ; 46(11): 1065-78, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11543714

RESUMO

Fresh isolates of Actinobacillus actinomycetemcomitans (Aa) bind avidly to surfaces in vitro, but existing in vivo studies of the adherence of Aa are limited. This study had two goals: (1) to compare the oral colonization of two isogenic strains of Aa-CU1010, a clinical isolate that expresses the adherent phenotype, and CU1012, a minimally adherent laboratory variant-and (2) to check for phenotypic reversion of these strains in a clinical setting. Rifampicin-resistant strains, developed for tracking in Sprague-Dawley rats, were tested in vitro to determine their stability and binding. In study 1, after antibiotic suppression, six rats (group I) received CU1010 in their feed. The eight rats in group II received CU1012 in their feed and four were supplemented by oral swabbing and four by gastric gavage. Group III consisted of three sham-inoculated controls. All rats were inoculated for 4 days. Microbiological data were collected at 1, 4 and 8 weeks after inoculation. Supporting data were supplied by antibody titres and clinical measures of alveolar bone loss. Study 2 consisted of six rats in each of three groups as above, but tagged strains of Aa were delivered by food alone. At all time-points in both studies, Aa was absent before inoculation and controls had no Aa or antibody to Aa. In study 1, all six rats in group I yielded positive cultures for Aa at 8 weeks. In group II, five of eight had positive cultures for Aa at 1 week, two of eight at 4 weeks and none had Aa at 8 weeks (P < or =0.001). All six rats in group I had serum anti-Aa titres compared to group II, where titres were seen in four of eight rats (P < or =0.015). In vitro data paralleled those found in vivo. No phenotypic reversion of either strain was seen in vivo. In study 2, four of six rats in group I showed Aa and had titres to Aa, while no other animals showed Aa at any time. The model provides convincing evidence that, unlike laboratory variants, clinical isolates colonize, persist and integrate into an already established, albeit reduced, econiche.


Assuntos
Aggregatibacter actinomycetemcomitans/fisiologia , Boca/microbiologia , Infecções por Actinobacillus/microbiologia , Aggregatibacter actinomycetemcomitans/genética , Aggregatibacter actinomycetemcomitans/imunologia , Perda do Osso Alveolar/microbiologia , Análise de Variância , Animais , Antibióticos Antituberculose , Anticorpos Antibacterianos/análise , Aderência Bacteriana/genética , Células Cultivadas , Contagem de Colônia Microbiana , Farmacorresistência Bacteriana , Durapatita , Ecologia , Células Epiteliais/microbiologia , Microbiologia de Alimentos , Vida Livre de Germes , Humanos , Modelos Lineares , Masculino , Mucosa Bucal/microbiologia , Fenótipo , Ratos , Ratos Sprague-Dawley , Rifampina , Saliva/microbiologia , Estatísticas não Paramétricas , Estômago/microbiologia
15.
J Formos Med Assoc ; 100(4): 277-80, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11393129

RESUMO

Multiple myeloma associated with extramedullary plasmacytoma at initial presentation is rare. We describe a 45-year-old female patient with an initial presentation of low back pain and right side L5, S1 radiculopathy. There was no evidence of vertebral involvement but an epidural tumor was found later during neurosurgical intervention. The final diagnosis was immunoglobulin G, kappa multiple myeloma complicated with spinal root compression by an extramedullary plasmacytoma. No osteolytic lesion was noted over the length of the spine. Pathology revealed high-grade plasmablastic myeloma. During the clinical course, the patient was refractory to induction chemotherapy, and there was progressive deterioration of renal function. Urinary tract infection by Morganella morganii and pulmonary infection of unknown cause developed 5 months later, and the patient died.


Assuntos
Mieloma Múltiplo/complicações , Plasmocitoma/complicações , Compressão da Medula Espinal/etiologia , Raízes Nervosas Espinhais , Feminino , Humanos , Pessoa de Meia-Idade
16.
J Virol ; 75(8): 3984-7, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11264388

RESUMO

The recent identification of hepatitis B virus (HBV) epitopes restricted by multiple HLA alleles has greatly expanded the epitope repertoire available for T-cell-mediated therapeutic vaccine development. The HLA-B51-restricted peptide HBc19-27 is particularly interesting because it is located entirely within the HLA-A2-restricted HBc18-27 epitope. Here we show that HLA-B51-restricted cytotoxic T lymphocytes specific for HBc19-27 from a patient with acute HBV infection were also able to lyse HLA-B51-positive target cells pulsed with HBc18-27 and to produce gamma interferon when stimulated by that peptide, implying that HBc18-27 can be presented by HLA-B51 as well as by HLA-A2. These results demonstrate the concept of degenerate immunogenicity across HLA class supertype boundaries in a human viral disease setting. In addition, they could facilitate the development of an epitope-based therapeutic vaccine to terminate chronic HBV infection that could provide a broad and diverse population coverage with a single peptide.


Assuntos
Apresentação de Antígeno/imunologia , Epitopos de Linfócito T/imunologia , Antígeno HLA-A2/imunologia , Antígenos HLA-B/imunologia , Vírus da Hepatite B/imunologia , Nucleocapsídeo/imunologia , Linfócitos T Citotóxicos/imunologia , Doença Aguda , Células Apresentadoras de Antígenos/imunologia , Linfócitos B/imunologia , Linhagem Celular Transformada , Cromatografia Líquida de Alta Pressão , Deleção de Genes , Antígeno HLA-A2/genética , Antígeno HLA-B51 , Hepatite B/imunologia , Hepatite B/virologia , Humanos , Peptídeos/imunologia , Especificidade por Substrato , Fixação de Tecidos
17.
Hepatology ; 33(1): 267-76, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11124845

RESUMO

This study was performed to compare the vigor and phenotype of virus-specific CD4(+) and CD8(+) T-cell responses in patients with different virologic and clinical outcomes after hepatitis C virus (HCV) infection. The results show that a vigorous and multispecific CD4(+) proliferative T-cell response is maintained indefinitely after recovery from HCV infection whereas it is weak and focused in persistently infected patients. In contrast, the HCV-specific CD8(+) T-cell response was quantitatively low in both groups despite the use of sensitive direct ex vivo intracellular interferon gamma (IFN-gamma) staining. Furthermore, although HCV-specific cytolytic CD8(+) memory T cells were undetectable ex vivo, they were readily expanded from the peripheral blood of chronically HCV-infected patients but not from recovered subjects after in vitro stimulation, suggesting that ongoing viremia is required to maintain the HCV-specific memory CD8(+) T-cell response. HCV-specific CD8(+) T cells displayed a type 1 cytokine profile characterized by production of IFN-gamma despite persistent HCV viremia. The paradoxical observation that HCV-specific CD4(+) T cells survive and CD8(+) T cells are lost after viral clearance while the opposite occurs when HCV persists suggests the existence of differential requirements for the maintenance of CD4(+) and CD8(+) T-cell memory during HCV infection. Furthermore, the relative rarity of circulating CD8(+) effector T cells in chronically infected patients may explain the chronic insidious nature of the liver inflammation and also why they fail to eliminate the virus.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Hepatite C Crônica/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/fisiologia , Linhagem Celular , Sobrevivência Celular , Citocinas/metabolismo , Feminino , Hepacivirus/imunologia , Hepatite C Crônica/patologia , Humanos , Memória Imunológica , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Peptídeos/farmacologia
18.
Med J Malaysia ; 56(4): 508-11, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12014774

RESUMO

In the setting of transplantation and chronic hepatitis B viral infection there is a unique histological feature termed cholestatic fibrosing hepatitis. The use of nucleoside analogues in the treatment of this condition has been successful. We describe a case of cholestatic fibrosing hepatitis, which occurred after intense immunosuppression for graft versus host disease in a patient with bone marrow transplantations. She was commenced on lamivudine therapy and showed good clinical, biochemical and virological response. However she succumbed due to sepsis.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Colestase/etiologia , Hepatite B/etiologia , Hepatite/etiologia , Cirrose Hepática/etiologia , Adulto , Feminino , Humanos
19.
J Formos Med Assoc ; 100(11): 762-6, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11802536

RESUMO

BACKGROUND AND PURPOSE: Invasive pulmonary aspergillosis (IPA) is usually an acute life-threatening infection in cancer patients receiving chemotherapy and in organ transplant recipients receiving immunosuppressive therapy. In some immunocompetent patients, IPA has a chronic and indolent clinical course. We compared the clinical patterns among IPA patients who had received recent intensive immunosuppressive therapy (RIIT) and those who had not (N-RIIT). METHODS: We reviewed the medical records of patients with a diagnosis of IPA made between 1992 and 1999. RIIT was defined as chemotherapy or high-dose corticosteroid therapy (at least 500 mg/d methylprednisolone, or equivalent, for at least 3 d) within 2 weeks before the onset of symptoms. RIIT patients were divided into those with and without malignancy. We compared clinical characteristics including age, sex, chest image patterns, diagnostic methods, culture results, treatment conditions, mortality, and recurrence rate in IPA patients: RIIT versus N-RIIT, and RIIT with and without malignancy. RESULTS: A total of 24 patients with IPA, 17 patients who had received RIIT and seven patients who had not (N-RIIT), were included. In the RIIT group, 11 patients had malignancy and six did not. No significant differences in gender, chest image patterns, diagnostic methods, and culture results were found between the RIIT and N-RIIT groups. The N-RIIT group was older and was treated significantly later after the onset of symptoms than the RIIT group (mean +/- standard deviation, SD, 89.43 +/- 129.47 vs 9.70 +/- 9.33 d, p = 0.018). Only one of the seven N-RIIT patients died, while nine of the 17 RIIT patients died (p = 0.08). Among the RIIT patients, five of the six without malignancy died, while four of the 11 patients with malignancy died. IPA recurred in seven of the eight RIIT patients, all of whom had malignancy, but in none of the six N-RIIT patients during a similar follow-up period (mean +/- SD, 16.3 +/- 18.9 vs 27.0 +/- 54.5 mo, p = 0.505). CONCLUSIONS: No differences were noted in image and culture studies between RIIT and N-RIIT IPA patients. RIIT IPA patients had acute and fulminant clinical courses, especially patients without malignancy, even though they received treatment with a mean duration of about 10 days starting from the onset of symptoms. All patients with malignancy undergoing further chemotherapy had recurrence of IPA. N-RIIT IPA patients had chronic clinical courses, a trend of lower mortality rate even with delayed diagnosis, and no recurrence.


Assuntos
Aspergilose/diagnóstico , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Pneumopatias Fúngicas/diagnóstico , Adulto , Aspergilose/diagnóstico por imagem , Aspergilose/imunologia , Biópsia , Feminino , Humanos , Imunossupressores/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/imunologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Escarro/microbiologia , Tomografia Computadorizada por Raios X
20.
Zhonghua Yi Xue Za Zhi (Taipei) ; 63(2): 158-61, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10677929

RESUMO

Meningiomas in the ethmoid sinuses are a challenge to manage. A 50-year-old man suffered from a left olfactory groove meningioma. He underwent a bilateral craniotomy to remove the tumor mass in August, 1997. During the follow-up period, a tumor was found in the right posterior ethmoid sinus. Endoscopic sinus surgery was performed to remove the tumor mass in August, 1998. Pathologic examination of the mass revealed a meningioma. No intraoperative or postoperative complications occurred, except for an episode of seizure.


Assuntos
Seio Etmoidal , Meningioma/cirurgia , Neoplasias dos Seios Paranasais/cirurgia , Endoscopia , Humanos , Masculino , Pessoa de Meia-Idade
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