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1.
Neurobiol Dis ; 112: 85-90, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29369793

RESUMEN

Glucocerebrosidase (GCase, deficient in Gaucher disease) enzymatic activity measured in dried blood spots of Parkinson's Disease (PD) cases is within healthy range but reduced compared to controls. It is not known whether activities of additional lysosomal enzymes are reduced in dried blood spots in PD. To test whether reduction in lysosomal enzymatic activity in PD is specific to GCase, we measured GCase, acid sphingomyelinase (deficient in Niemann-Pick disease types A and B), alpha galactosidase A (deficient in Fabry), acid alpha-glucosidase (deficient in Pompe) and galactosylceramidase (deficient in Krabbe) enzymatic activities in dried blood spots of PD patients (n = 648) and controls (n = 317) recruited from Columbia University. Full sequencing of glucocerebrosidase (GBA) and the LRRK2 G2019S mutation was performed. Enzymatic activities were compared between PD cases and controls using t-test and regression models adjusted for age, gender, and GBA and LRRK2 G2019S mutation status. Alpha galactosidase A activity was lower in PD cases compared to controls both when only non-carriers were included (excluding all GBA and LRRK2 G2019S carriers and PD cases with age-at-onset below 40) [2.85 µmol/l/h versus 3.12 µmol/l/h, p = 0.018; after controlling for batch effect, p = 0.006 (468 PD cases and 296 controls)], and when including the entire cohort (2.89 µmol/l/h versus 3.10 µmol/l/h, p = 0.040; after controlling for batch effect, p = 0.011). Because the alpha galactosidase A gene is X-linked, we stratified the analyses by sex. Among women who were non-carriers of GBA and LRRK2 G2019S mutations (PD, n = 155; control, n = 194), alpha galactosidase A activity was lower in PD compared to controls (2.77 µmol/l/h versus 3.10 µmol/l/h, p = 0.044; after controlling for a batch effect, p = 0.001). The enzymatic activity of acid sphingomyelinase, acid alpha-glucosidase and galactosylceramidase was not significantly different between PD and controls. In non-carriers, most lysosomal enzyme activities were correlated, with the strongest association in GCase, acid alpha-glucosidase, and alpha galactosidase A (Pearson correlation coefficient between 0.382 and 0.532). In a regression model with all five enzymes among non-carriers (adjusted for sex and age), higher alpha galactosidase A activity was associated with lower odds of PD status (OR = 0.54; 95% CI:0.31-0.95; p = 0.032). When LRRK2 G2019S PD carriers (n = 37) were compared to non-carriers with PD, carriers had higher GCase, acid sphingomyelinase and alpha galactosidase A activity. We conclude that alpha galactosidase A may have a potential independent role in PD, in addition to GCase.


Asunto(s)
Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , alfa-Galactosidasa/genética , alfa-Galactosidasa/metabolismo , Anciano , Estudios de Cohortes , Activación Enzimática/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico
2.
J Neuroophthalmol ; 35(1): 16-21, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25259863

RESUMEN

BACKGROUND: Ocular motor abnormalities reflect the varied neuropathology of spinocerebellar ataxias (SCAs) and may serve to clinically distinguish the different SCAs. We analyzed the various eye movement abnormalities detected prospectively at the baseline visit during a large multicenter natural history study of SCAs 1, 2, 3, and 6. METHODS: The data were prospectively collected from 12 centers in the United States in patients with SCAs 1, 2, 3, and 6, as part of the Clinical Research Consortium for Spinocerebellar Ataxias (NIH-CRC-SCA). Patient characteristics, ataxia rating scales, the Unified Huntington Disease Rating Scale functional examination, and clinical staging were used. Eye movement abnormalities including nystagmus, disorders of saccades and pursuit, and ophthalmoparesis were recorded, and factors influencing their occurrence were examined. RESULTS: A total of 301 patients participated in this study, including 52 patients with SCA 1, 64 with SCA 2, 117 with SCA 3, and 68 with SCA 6. Although no specific ocular motor abnormality was pathognomonic to any SCA, significant differences were noted in their occurrence among different disorders. SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades. SCA 1 and SCA 3 subjects had a more even distribution of eye movement abnormalities. CONCLUSIONS: Prospective data from a large cohort of patients with SCAs 1, 2, 3, and 6 provide statistical validation that the SCAs exhibit distinct eye movement abnormalities that are useful in identifying the genotypes. Many of the abnormalities correlate with greater disease severity measures.


Asunto(s)
Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/etiología , Ataxias Espinocerebelosas/complicaciones , Adulto , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Ataxias Espinocerebelosas/clasificación , Ataxias Espinocerebelosas/genética , Estados Unidos
3.
Blood Cancer J ; 4: eXX, 2014 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-25303370

RESUMEN

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r(2)=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4(+) T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Infecciones por Helicobacter , Helicobacter pylori , Interleucinas , Linfoma de Células B de la Zona Marginal , Proteínas de Neoplasias , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas , Linfocitos T CD4-Positivos/metabolismo , Línea Celular Tumoral , Femenino , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/terapia , Humanos , Interleucinas/biosíntesis , Interleucinas/genética , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/microbiología , Linfoma de Células B de la Zona Marginal/terapia , Masculino , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/terapia , Interleucina-22
4.
Hong Kong Med J ; 20(6): 474-80, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25345997

RESUMEN

OBJECTIVE: To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. DESIGN: Case series. SETTING: Prince of Wales Hospital, Hong Kong. PATIENTS: A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. RESULTS: Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. CONCLUSIONS: The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Hong Kong , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Resultado del Tratamiento
5.
Blood Cancer J ; 4: e220, 2014 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-24949857

RESUMEN

We recently showed that Helicobacter pylori (HP)-positive gastric 'pure' diffuse large B-cell lymphoma (DLBCL) may respond to HP eradication therapy. However, whether these HP-related 'pure' DLBCL of the stomach may differ fundamentally from those unrelated to HP remains unclear. In this study, we compared the clinicopathologic features of these two groups of patients who had been uniformly treated by conventional chemotherapy. Forty-six patients were designated HP-positive and 49 were HP-negative by conventional criteria. HP-positive patients had a lower International Prognostic Index score (0-1, 65% vs 43%, P=0.029), a lower clinical stage (I-IIE1, 70% vs 39%, P=0.003), a better tumor response to chemotherapy (complete pathologic response, 76% vs 47%, P=0.004) and significantly superior 5-year event-free survival (EFS) (71.7% vs 31.8%, P<0.001) and overall survival (OS) (76.1% vs 39.8%, P<0.001). To draw a closer biologic link with HP, HP-positive tumors were further examined for CagA expression in lymphoma cells. Compared with CagA-negative cases (n=16), CagA-positive cases (n=27) were associated with high phosphorylated SHP-2 expression (P=0.016), and even better 5-year EFS (85.2% vs 46.3%, P=0.002) and OS (88.9% vs 52.9%, P=0.003). HP-related gastric 'pure' DLBCL may be a distinct tumor entity, which is less aggressive, and responds better to conventional chemotherapy.


Asunto(s)
Infecciones por Helicobacter/fisiopatología , Helicobacter pylori/aislamiento & purificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/microbiología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/microbiología , Antígenos Bacterianos/biosíntesis , Proteínas Bacterianas/biosíntesis , Supervivencia sin Enfermedad , Femenino , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/metabolismo , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología
6.
Strahlenther Onkol ; 189(12): 1001-8, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24158634

RESUMEN

PURPOSE: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97% of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. RESULTS: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1%, respectively. A total of 27 patients had locoregional recurrence: 85.2% in-field failures, 11.1% marginal failures, and 3.7% out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9%) compared to those receiving conservative treatment (32.0%, p=0.051). In patients treated with 1 course of radiotherapy, grade ≥3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6% of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. CONCLUSION: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome.


Asunto(s)
Quimioradioterapia Adyuvante/mortalidad , Cisplatino/uso terapéutico , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/prevención & control , Radioterapia Conformacional/mortalidad , Adolescente , Adulto , Anciano , Antineoplásicos/uso terapéutico , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Prevalencia , Medición de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Taiwán/epidemiología , Resultado del Tratamiento , Adulto Joven
7.
Blood Cancer J ; 3: e125, 2013 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-23852160

RESUMEN

We previously reported that CagA can be translocated into B cells in Helicobacter pylori (HP) coculture media, and the translocation appears biologically significant as activation of the relevant cellular pathways was noticed. In this study, we further explore if CagA can be detected in malignant B cells of HP-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Expression of CagA was evaluated by immunohistochemistry. CagA expression was further confirmed by western blot analysis. The association between CagA expression in malignant B cells and tumor response to HP eradication therapy (HPE) was evaluated in 64 stage IE gastric MALT lymphoma patients. We detected CagA expression in 31 (48.4%) of 64 patients: 26 (68.4%) of the 38 HP-dependent cases and 5 (19.2%) of the 26 HP-independent cases (P<0.001). Patients with CagA expression responded to HPE quicker than those without (median time to complete remission, 3.0 vs 6.5 months, P=0.025). Our results indicated that CagA can be translocated into malignant B cells of MALT lymphoma, and the translocation is clinically and biologically significant.

8.
Strahlenther Onkol ; 188(10): 878-86, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22911240

RESUMEN

BACKGROUND AND PURPOSE: In this study, the clinical outcome and prognostic factors of adult medulloblastoma patients receiving multimodal treatment were investigated. PATIENTS AND METHODS: The clinical manifestations, treatment variables, and outcome of adult patients with medulloblastoma at our institution between 1983 and 2009 were retrospectively reviewed. RESULTS: A total of 20 adult patients were included (median age 22 years). Craniospinal irradiation (CSI) was given postoperatively. The craniospinal axis received a median of 30 Gy (range 23.4-39.6 Gy) in fractions of 1.6-2 Gy/day, and the tumor was boosted to a total median dose of 50 Gy (range 50-55.25 Gy). The 3-year disease-free survival (DFS) and overall survival (OS) rates for all patients were 45% and 50%, respectively. In univariate analysis, Karnofsky Performance Scale (KPS) > 70, neurologic symptoms duration > 30 days, lateral tumor location, standard risk patients, no hydrocephalus, radiotherapy (RT) treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were associated with better DFS. Standard-risk patients, RT treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were also significantly associated with better OS. CONCLUSION: The combined modality treatment results in a favorable outcome for adult medulloblastoma patients. Further investigation of the prognostic factors, radiation-related factors, and systemic chemotherapy is needed.


Asunto(s)
Neoplasias Cerebelosas/mortalidad , Neoplasias Cerebelosas/radioterapia , Meduloblastoma/mortalidad , Meduloblastoma/radioterapia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/prevención & control , Radioterapia Conformacional/mortalidad , Adulto , Anciano , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento
10.
Eur Respir J ; 31(1): 54-61, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17928311

RESUMEN

The aim of the present study was to investigate whether imprint cytology can improve the diagnostic accuracy of computed tomography-guided transthoracic core biopsy. Between October 1997 and June 2004, thoracic lesions in 622 patients underwent biopsy using 19-gauge coaxial guiding needles and 20-gauge biopsy needles under computed tomography guidance. Touch imprint cytology and histopathology were performed for all biopsy specimens. Of these lesions, 431 (74.1%) were diagnosed as malignant, 151 (25.9%) as benign and 40 (6%) as nondiagnostic. Imprint cytology plus histology shows an improved diagnostic accuracy of 96.4% compared with that of imprint cytology alone (92.3%) or histopathology alone (93.0%). Procedure-related complications requiring further treatment occurred in eight (1.4%) patients. In conclusion, imprint cytology combined with histopathology can improve the diagnostic accuracy of computed tomography-guided transthoracic needle biopsy.


Asunto(s)
Técnicas Citológicas , Enfermedades Pulmonares/diagnóstico , Nódulo Pulmonar Solitario/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Biopsia con Aguja , Femenino , Humanos , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Nódulo Pulmonar Solitario/patología
11.
J Pathol ; 211(3): 296-304, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17167822

RESUMEN

We recently reported that low-grade mucosa-associated lymphoid tissue lymphoma (MALToma) and diffuse large B-cell lymphoma (DLBCL) with MALToma (DLBCL[MALT]) of stomach are equally responsive to H. pylori eradication therapy (HPET) and that H. pylori-independent status is closely associated with nuclear translocation of BCL10. However, co-existing MALToma and DLBCL components of gastric DLBCL(MALT) may respond differentially to HPET and the underlying mechanism remains unclear. Tumour tissue samples from 18 patients with microdissectable co-existing MALToma and DLBCL cells were studied. The clonality of lymphoma cells was examined by polymerase chain reaction-based amplification of the CDR3 region of the IgH gene and confirmed by DNA sequence analysis. BCL10 expression was determined by immunohistochemistry. Differential response of co-existing MALToma and DLBCL to HPET was defined as complete eradication of one component while the other component remained. Five (27.8%) of the 18 patients showed different IgH gene rearrangements in the two components and three (60%) of these five patients had differential response of MALToma and DLBCL to HPET. By contrast, 13 patients showed identical IgH gene rearrangements and only one (8%) of them had differential response of the two components to HPET (p = 0.044). Further, all four patients with differential response of MALToma and DLBCL to HPET showed nuclear expression of BCL10 in the H. pylori-independent component and cytoplasmic expression of BCL10 in the H. pylori-dependent component while the expression patterns of BCL10 were identical in both of these components in the 14 patients who had similar tumour response to HPET. We conclude that different clonality is a common reason for the differential response of co-existing MALToma and DLBCL of gastric DLBCL(MALT) to HPET and that immunohistochemical examination of BCL10 expression may help to identify the co-existence of these components.


Asunto(s)
Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , Gastropatías/microbiología , Proteínas Adaptadoras Transductoras de Señales/análisis , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Proteína 10 de la LLC-Linfoma de Células B , Biomarcadores de Tumor/análisis , Distribución de Chi-Cuadrado , Células Clonales , Femenino , Estudios de Seguimiento , Mucosa Gástrica/química , Mucosa Gástrica/microbiología , Reordenamiento Génico , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica/métodos , Linfoma de Células B/microbiología , Linfoma de Células B de la Zona Marginal/microbiología , Linfoma de Células B Grandes Difuso/microbiología , Masculino , Persona de Mediana Edad , Gastropatías/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/microbiología
12.
Eur Respir J ; 24(6): 905-9, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15572530

RESUMEN

The aim of this study was to investigate the possible additional diagnostic information provided by imprint cytology when performing ultrasound-guided transthoracic core biopsy and to evaluate whether it could optimise the biopsy procedure. A total of 155 transthoracic core biopsies with touch imprint smears were performed under ultrasound guidance, with 127 malignant and 28 benign lesions. The imprint smears were stained using Riu's method and interpreted by a cytopathologist. These were compared with the histopathology of core biopsy specimens and the final diagnosis of malignant versus benign disease. The overall diagnostic accuracy of imprint cytology was 94% (146 out of 155). Histopathological analysis showed an overall accuracy of 94% (146 out of 155), with a sensitivity of 94% (119 out of 127) and negative predictive value of 79% (27 out of 34). The combination of these two methodologies had an increased overall accuracy and negative predictive value of 98% (152 out of 155) and 90% (28 out of 31), respectively. The results of imprint cytology and histopathology were in agreement in 143 patients (92%). In conclusion, imprint cytology of ultrasound-guided transthoracic core biopsy is a sensitive procedure for diagnosing peripheral thoracic lesions, and it may increase the diagnostic accuracy and cancer negative prediction of biopsy alone. With an on-site approach, imprint cytology may help to assess the adequacy of biopsy specimens and optimise the biopsy procedure.


Asunto(s)
Biopsia con Aguja/métodos , Neoplasias Torácicas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Ultrasonografía Intervencional
15.
Int J Tuberc Lung Dis ; 6(5): 454-60, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12019922

RESUMEN

SETTING: National Taiwan University Hospital, Taipei, Taiwan. OBJECTIVE: To study the variations in the NRAMP1 gene using five genotypes (274C/T, 577-18G/A, A318V, D543N and 3' untranslated region [UTR]), and the susceptibility of tuberculosis and HIV infection in Taiwanese. DESIGN: The study sample included 49 patients with tuberculosis, 48 healthy control subjects and 60 HIV-infected patients. The polymerase chain reaction (PCR) products amplified from their genomic DNA were subjected to restriction enzyme digestion and were analysed using agarose gel electrophoresis. RESULTS: A318V was not polymorphic in the studied population. Only D543N and 3'UTR were more heterozygous. In 274 C/T and 577-18G/A, the allele frequencies showed the predominant type to be the homozygous patterns C/C (94%) and G/G (94%), respectively. There were no statistically significant differences between the tuberculosis patients and the healthy control subjects. Despite the high susceptibility to Mycobacterium tuberculosis in HIV-infected patients, genotypic frequencies in the HIV-positive patients were not significantly different between tuberculous (n = 29) and non-tuberculous patients (n = 31). In comparison with previous studies, there were significant differences between different ethnic groups in allele frequencies for 274C/T, D543N and 3'UTR. CONCLUSION: The allele and genotype of NRAMPI polymorphism among Taiwanese differed from those of Caucasians, Africans and Hispanics. No allelic associations were identified between the NRAMP1 alleles and tuberculosis susceptibility.


Asunto(s)
Proteínas de Transporte de Catión/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Tuberculosis/genética , Adulto , Anciano , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Taiwán
16.
J Asthma ; 38(7): 575-83, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11714080

RESUMEN

This retrospective study was conducted to assess Taiwanese emergency physicians for their preference in management and adherence to guidelines in treating patients with acute exacerbation of asthma. One hundred twenty patients from hospitals of three different levels were evaluated by reviewing their medical records. Our study revealed that physicians from medical centers and regional hospitals assessed patients more often with arterial blood gas or pulse oximetry; prescribed more doses of beta2-agonist nebulizers; administered more doses of beta2-agonist nebulizers before administering parenteral aminophylline; and prescribed ipratropium nebulizers more often as adjunctive therapy. On the other hand, physicians from district hospitals more frequently prescribed parenteral aminophylline as the first-line medication and more often prescribed only a single dose of beta2-agonist nebulizer. Most emergency physicians in Taiwan did not adhere to guidelines. Specifically, these included omission of peak expiratory flow as the means to assess the severity of asthma exacerbation and response to treatment; suboptimal use of inhaled bronchodilators, such as beta2-agonists and ipratropium; and inappropriate use of parenteral aminophylline as the first-line medication.


Asunto(s)
Asma/terapia , Servicio de Urgencia en Hospital , Pautas de la Práctica en Medicina , Enfermedad Aguda , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Ápice del Flujo Espiratorio , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Taiwán
17.
J Formos Med Assoc ; 100(8): 553-6, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11678007

RESUMEN

Methamphetamine, heroin, and cannabis are three of the most commonly misused drugs in Asia. In Taiwan, cases of misuse of methamphetamine have been increasing. In this paper, we report the case of a 23-year-old woman who had a 10-year history of smoking methamphetamine and intermittent use of heroin for 3 to 4 years. She developed pulmonary toxic effects associated with misuse of heroin and methamphetamine. She was brought to the emergency room because of consciousness disturbance and acute respiratory failure. Her symptoms of rapid progression of refractory hypoxemia, ill-defined densities over both lung fields, and normal pulmonary artery wedge pressure were consistent with acute respiratory distress syndrome. Rapid resolution of infiltrations and improvement of oxygenation were observed after mechanical ventilation with positive end-expiratory pressure support and oxygen therapy. She was discharged on the fifteenth hospital day without any sequela except for mild exertional dyspnea.


Asunto(s)
Dependencia de Heroína/complicaciones , Metanfetamina/efectos adversos , Síndrome de Dificultad Respiratoria/inducido químicamente , Trastornos Relacionados con Sustancias/complicaciones , Adulto , Femenino , Humanos
18.
Am J Respir Crit Care Med ; 164(7): 1312-8, 2001 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-11673227

RESUMEN

Aberrant expression of mucin genes occurs frequently in advanced cancer. Using quantitative competitive reverse transcriptase/polymerase chain reaction (QC RT-PCR), the expression of three mucin genes--MUC1 (widely expressed in epithelial cells), MUC2 (mainly expressed in intestinal epithelial cells), and MUC5AC (mainly from airway and gastric epithelial cells)--was evaluated in 112 patients with pleural effusions (including 54 cytologically positive malignant pleural effusions, 35 benign exudative pleural fluids, and 23 cytologically negative pleural effusions from cancer patients). The expression ratios of MUC1 and MUC5AC, but not MUC2 gene, were significantly higher in malignant than benign pleural fluids (p < 0.000). The cutoff value, sensitivity, and specificity of MUC1 expression ratio were: 0.126, 64.6%, and 95.7%; and were 0.028, 72.3%, and 95.7%, respectively, for MUC5AC. In combined evaluation with both MUC1 and MUC5AC, the sensitivity was 86.1% and specificity was 91.5%. The positive and negative predictive values were 93.3%, and 82.7%, respectively. We considered mucin QC RT-PCR to be a useful tool in assisting the diagnosis of malignant pleural effusion.


Asunto(s)
Mucina-1/análisis , Mucinas/análisis , Proteínas de Neoplasias/análisis , Derrame Pleural Maligno/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Humanos , Mucina 5AC , Mucina-1/genética , Mucina 2 , Mucinas/genética , Proteínas de Neoplasias/genética , Estudios Prospectivos
19.
J Clin Ultrasound ; 29(2): 78-86, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11425092

RESUMEN

PURPOSE: The aim of this study was to investigate the value of chest sonography in the diagnosis and management of patients with chest radiograph opacities in an emergency department. METHODS: Seventy-eight patients with acute chest complaints whose chest radiographs showed opacities underwent chest sonography. The initial diagnosis (based on clinical manifestations and the chest radiograph), the sonographic diagnosis (before any invasive procedures), and the final diagnosis were compared. The impact of chest sonography on the management of patients with chest opacities was also analyzed. RESULTS: The initial diagnosis was in concordance with the final diagnosis in 60 (77%) of the 78 patients, while the sonographic diagnosis was in concordance with the final diagnosis in 75 (96%) of the patients. Chest sonography therefore significantly increased the rate of correct diagnoses from 77% (95% confidence interval, 67-87%) to 96% (95% confidence interval, 92-100%; p < 0.0001). Sonography provided new information in 52 patients (67%): a different diagnosis from the initial diagnosis in 18 patients and additional diagnostic information in 34 patients. New information gained from sonography affected the management of 35 patients. Sonography also provided help in guiding 42 (70%) of 60 invasive diagnostic procedures and 22 (73%) of 30 invasive therapeutic procedures for which chest radiography and physical examination had failed to or were unsuitable to provide guidance. Overall, sonography assisted in the management of 64 (82%) of 78 patients. Sonography was of no benefit in 14 patients (18%). CONCLUSIONS: We conclude that chest sonography can complement chest radiography and is of value in the diagnosis and management of emergency department patients with acute chest diseases presenting as opacities on chest radiographs.


Asunto(s)
Enfermedades Torácicas/diagnóstico por imagen , Enfermedad Aguda , Manejo de la Enfermedad , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Ultrasonografía Intervencional
20.
Respir Med ; 95(3): 221-6, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11266240

RESUMEN

Integrins play key roles in cell-to-cell and cell-to-extracellular matrix (ECM) adhesion. We investigated integrin expression on pleural mesothelial cells (PMCs) and the inhibitory effect of arginine-glycine-asparate (RGD)-containing peptide on the adhesion of PMCs to fibronectin and collagen. Using flow cytometry and immunostaining, PMCs freshly isolated from pleural effusions and one mesothelial cell line were screened for different integrins. Intact pleural tissue was evaluated by immunohistochemistry. The adhesion of Met-5A cells to fibronectin and collagen types I, III and IV was assayed with prior treatment of various concentrations of glycine-arginine-glycine aspartate-serine (GRGDS). On primary PMCs, alpha2, alpha3, alpha5, beta1, beta3 and alphavbeta3 were highly expressed (>70%); alpha1 expression was intermediate (30-70%); and alpha4 and alpha6 expressions were low (< 30%). On Met-SA cells, alpha3, alpha5, alpha6 and beta1 were highly expressed (>70%); alpha1 was intermediate (30-70%); and alpha2, alpha4, beta3 and alphavbeta3 were low (<30%). The patterns of immunostaining on pleural tissues were similar to the results of flow cytometry for primary PMCs except for beta3. There was no statistically different expression in various disease states (transudate vs. exudate, benign vs. malignant). The inhibitory effect of GRGDS peptide on Met-5A cell adhesion to all four matrix proteins was dose-dependent.


Asunto(s)
Células Epiteliales/metabolismo , Integrinas/metabolismo , Péptidos/fisiología , Pleura/citología , Adolescente , Adulto , Anciano , Análisis de Varianza , Arginina/fisiología , Ácido Aspártico/fisiología , Adhesión Celular/fisiología , Células Cultivadas , Femenino , Citometría de Flujo , Glicina/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas
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