Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
1.
Aliment Pharmacol Ther ; 43(11): 1132-41, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27060985

RESUMEN

BACKGROUND: Acute severe ulcerative colitis is categorised using the Truelove & Witts criteria. The Travis and the Ho scores are calculated following 72 h of steroid treatment to identify patients at risk of failing steroid therapy who require colectomy or second-line medical therapy. AIM: To compare the Travis and the Ho scores in a large unselected cohort to determine which might be more clinically relevant. METHODS: We analysed 3049 patients with ulcerative colitis from the 2010 round of the UK IBD audit of which 984 had acute severe ulcerative colitis. 420 patients had sufficient data for analysis. Patients were allocated into either a Travis high- or low-risk group and either a Ho high-, intermediate- or low-risk group. We assessed whether further medical or surgical intervention and outcomes varied between groups. RESULTS: High-risk patients in Travis and the Ho groups, when compared to lower risk groups, were more likely to fail steroid therapy: 64.5% (131/203) vs. 38.7% (84/217) (P < 0.0001) for Travis and 66.2% (96/145) vs. 46.7% (85/182) vs. 36.6% (34/93) (P < 0.0001) for Ho. They were also more likely to undergo surgery 34.0% (69/203) vs. 9.7% (21/217) for Travis and 33.1% (48/145) vs. 17.0% (31/182) vs. 11.8% (11/93) (P < 0.0001) for Ho. Travis high patients were more likely to be refractory to second-line medical therapy: 44.6% (37/83) vs. 20.0% (9/45) (P = 0.01). CONCLUSIONS: Patients identified as high risk using the Travis or the Ho scoring systems are more likely to be resistant to IV steroids and require surgery. Risk of surgery in both high-risk populations is lower than previously reported.


Asunto(s)
Colectomía/métodos , Colitis Ulcerosa/terapia , Esteroides/administración & dosificación , Adulto , Colitis Ulcerosa/fisiopatología , Colitis Ulcerosa/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento
3.
Aliment Pharmacol Ther ; 38(10): 1255-66, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24117596

RESUMEN

BACKGROUND: Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re-treatment with mercaptopurine in these individuals. AIMS: To determine the rate of tolerance when trialling mercaptopurine in azathioprine-intolerant patients and the factors predictive of success, and to perform a systematic review and meta-analysis of these data with other published data sets. METHODS: A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta-analysis was undertaken of all published studies of mercaptopurine use in azathioprine-intolerant patients (455 patients in 11 included studies). RESULTS: Mercaptopurine was tolerated by 58% of azathioprine-intolerant patients in the Edinburgh cohort. In the meta-analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta-analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu-like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine. CONCLUSIONS: This meta-analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two-thirds of azathioprine-intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Mercaptopurina/uso terapéutico , Adulto , Azatioprina/efectos adversos , Azatioprina/uso terapéutico , Femenino , Humanos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Mercaptopurina/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos
4.
Aliment Pharmacol Ther ; 38(8): 935-45, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24004000

RESUMEN

BACKGROUND: Approximately one third of patients with acute severe ulcerative colitis (ASUC) fail response to steroids. Ciclosporin and anti-TNFα are proven second-line therapies, but evidence of their efficacy has come mainly from tertiary centres and/or selective clinical trial recruitment. AIM: To assess ASUC outcomes in a large unselected cohort. METHODS: UK-wide audits of IBD care were conducted in 2008 (209 hospital sites) and 2010 (198 hospital sites), covering >87% of admitting hospitals. Each site entered data from 20 consecutive UC admissions onto a web-based proforma. Admissions included 852 (2008) and 984 (2010) with ASUC, accounting for 35% and 39% of UC admissions, respectively. RESULTS: ASUC in-hospital mortality was 1.2% in 2008; 0.7% in 2010 (P = 0.22). Response to first-line steroid therapy was 61% (2008); 58% (2010) and mortality was higher in non-responders: 2008: 2.9% (9/315) vs. 0.19% (1/537; P < 0.001); 2010: 1.8% (7/391) vs. 0.0% (0/593; P = 0.002). In 2010, more patients (56%) received second-line medical therapy than in 2008 (47%, P = 0.02). In-hospital mortality was similar to second-line medical therapy vs. surgery without further medical therapy; 2008: 2.7% vs. 2.8%, P = 0.99; 2010: 0.9% vs. 3.1%, P = 0.17. Second-line therapy response was more frequently observed with anti-TNFα than ciclosporin: (2008: 76% vs. 46%, P < 0.001; 2010: 80% vs. 58%, P < 0.001). CONCLUSIONS: Mortality in acute severe ulcerative colitis was low, but higher in steroid non-responders. Patients treated with second-line medical therapies had no higher risk of in-hospital mortality than those undergoing surgery. Second-line 'rescue' medical therapy usage is increasing; however, ciclosporin response rates were relatively low.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Esteroides/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Auditoría Clínica , Estudios de Cohortes , Colitis Ulcerosa/mortalidad , Colitis Ulcerosa/cirugía , Femenino , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Reino Unido/epidemiología
5.
Inflamm Bowel Dis ; 16(7): 1219-26, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19924804

RESUMEN

BACKGROUND: Magnetic resonance follow-through (MRFT) is a new cross-sectional imaging modality with the potential to accurately stage ileal Crohn's disease (CD), while avoiding ionizing radiation and the discomfort associated with enteroclysis. We aimed to assess the reliability of this technique in assessing the extent and activity of ileal CD, and to assess its influence on subsequent management. METHODS: Out of a total of 342 patients undergoing MRFT between 2004 and 2008, 221 were performed in 191 patients with confirmed CD. Case notes were reviewed in detail with documentation of all investigations pre- and post-MRFT. Agreement between inflammatory markers, histopathology, and MRFT findings was determined. RESULTS: Overall, 116/221 (52.5%) of MRFTs showed active ileal CD, and 76/221 (34.4%) quiescent CD, while 29/221 (13.1%) were suboptimal. Overall, 66 strictures and 18 fistulae were identified. There was substantial agreement between active ileal CD on MRFT and histopathology (n = 59; kappa = 0.66; P = 0.0006; sensitivity 85.1%, specificity 85.7%) and fecal calprotectin (n = 14; kappa = 0.72; P = 0.047), while C-reactive protein (CRP) showed moderate agreement (n = 107; kappa = 0.402; P = 0.00028). Management was influenced by MRFT reports following active (52/84, 62% treated medically) or quiescent (48/62, 77.4% managed conservatively) disease. Fibrotic strictures were predominantly treated surgically (7/14, 50%). In all, 13/32 (40.6%) patients with inflammatory ileal strictures required surgery, mostly due to steroid-resistant disease. Overall, 75 MR findings were documented in 221 MRFTs, including 1 renal cancer. CONCLUSIONS: MRFT provides accurate information on ileal CD activity, with close agreement to inflammatory markers and histopathology. It represents a substantial advance in the staging of CD, while avoiding painful enteroclysis and radiation exposure in young patients.


Asunto(s)
Enfermedad de Crohn/diagnóstico , Enfermedades del Íleon/patología , Imagen por Resonancia Magnética/métodos , Adulto , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Colonoscopía , Heces/química , Femenino , Estudios de Seguimiento , Humanos , Complejo de Antígeno L1 de Leucocito/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
6.
Inflamm Bowel Dis ; 15(11): 1621-9, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19618462

RESUMEN

BACKGROUND: It has been variously reported that women with inflammatory bowel disease (IBD) have an increased risk of cervical dysplasia. We aimed to assess in a large, accurately phenotyped, case-controlled population whether women with IBD had increased rates of abnormal cervical smears and if this was affected by immunosuppressant therapy or disease phenotype. METHODS: Women with IBD diagnosed prior to the age of 60 were studied at a single tertiary referral center in Scotland. Full cervical smear histories were available on 411 women (204 Crohn's disease, 207 ulcerative colitis, median age at diagnosis 28.4 years, median current age 44.1 years). All the cases were matched 1:4 to healthy controls (n = 1644) from the same geographical location. RESULTS: There was no difference in rates of abnormal smears between patients with IBD (80.5% negative, 10.5% low-grade, and 9.0% high-grade dysplasia) and controls (85.4%, 7.7%, and 6.9%, P = 0.37). The use of immunosuppressant therapy had no impact on rates of cervical dysplasia or neoplasia. Furthermore, there was no effect of disease location, behavior, or oral contraceptive use. However, there were significantly more abnormal cervical smears in IBD patients who were current smokers compared with exsmokers and those who had never smoked (27.4% versus 11.4%, P = 0.001, odds ratio = 2.95, 95% confidence interval = 1.55-5.50). CONCLUSIONS: Women with IBD are not at increased risk of abnormal cervical smears unless they smoke. These data suggest that young women with IBD should be managed as per the background population; attending for regular smear testing, and undergoing vaccination against cervical cancer when available.


Asunto(s)
Adenocarcinoma/epidemiología , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adenocarcinoma/patología , Adulto , Distribución por Edad , Estudios de Casos y Controles , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Anticonceptivos Orales/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Escocia/epidemiología , Fumar/epidemiología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Frotis Vaginal
7.
J Pediatr Gastroenterol Nutr ; 48(2): 161-7, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19179877

RESUMEN

OBJECTIVES: To determine anti-Saccharomyces cerevisiae antibodies (ASCA) status and its relation to disease phenotype in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: A total of 301 Scottish patients with early-onset IBD-197 Crohn disease (CD), 76 ulcerative colitis (UC), 28 indeterminate colitis (IC)-and 78 healthy control individuals were studied. ASCA status (IgA, IgG) was determined by enzyme-linked immunosorbent assay. ASCA status was then analyzed in relation to CD phenotype. RESULTS: Patients with CD had a higher prevalence of ASCA than patients with UC and healthy controls: 82/197 versus 12/76, odds ratio (OR) 3.80 (1.93-7.50) and 82/197 versus 6/78, OR 8.56 (3.55-20.62), respectively. Univariate analysis showed that positive ASCA status was associated with oral CD (17/25 vs 59/153, OR 3.39 [1.38-8.34]), perianal CD (39/77 vs 38/108, OR 1.89 [1.04-3.44]) and the presence of granulomata (63/132 vs 15/52, OR 2.25 [1.13-4.48]) and also with markers of disease severity: raised C-reactive protein (44/90 vs 12/49, OR 2.95[1.36-6.37]), hypoalbuminemia (44/85 vs 20/74, OR 2.28[1.19-4.37]), and surgery (27/49 vs 54/147, OR 2.11 [1.10-4.06]). From multivariate analysis, the presence of oral disease (adjusted P = 0.001, OR 22.22 [3.41-142.86]) and hypoalbuminemia (adjusted P = 0.01, OR 4.78 [1.40-16.39]) was found to be independently associated with ASCA status. No association was demonstrated between ASCA and IBD candidate genes. CONCLUSIONS: Patients with CD had a higher prevalence of ASCA than did other patients with IBD. ASCA status described patients with CD who had a specific phenotype, showing an association with markers of disease severity and oral CD involvement.


Asunto(s)
Anticuerpos Antifúngicos/sangre , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Saccharomyces cerevisiae/inmunología , Adolescente , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Colitis Ulcerosa/sangre , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/patología , Enfermedad de Crohn/sangre , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Estado de Salud , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Análisis Multivariante , Oportunidad Relativa , Estudios Seroepidemiológicos , Índice de Severidad de la Enfermedad
8.
Aliment Pharmacol Ther ; 29(3): 286-97, 2009 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-19132970

RESUMEN

BACKGROUND: Anti-TNF agents are now widely used in Crohn's disease (CD), and in ulcerative colitis (UC). AIM: To review the safety profile of anti-TNF agents in all patients treated with infliximab in Edinburgh from 1999 to 2007. METHODS: Complete data were available on 202/207 patients comprising 157 CD, 42 UC and three coeliac disease. Median follow-up was 2.4 years (1.0-4.9) with a total of 620 patient-years follow-up. About 19.1% of CD patients were subsequently treated with adalimumab. RESULTS: Seven deaths (3.3%) occurred in follow-up; only one death was <1 year post-infliximab (at day 72, from lung cancer). A total of six malignancies (three haematological, three bronchogenic) and six cases of suspected demyelination (three with confirmed neurological disease) were reported. In the 90 days following infliximab, 95 adverse events (36 serious) occurred in 58/202 (28.7%) patients. In all, 42/202 (20.8%) had an infectious event (22 serious) and 27/202 (13.4%) of patients had an infusion reaction: 19 acute (four serious) and eight delayed (three serious). CONCLUSIONS: Serious infections, malignancies and neurological disease complicate anti-TNF use in clinical practice. Although evidence for causality is unclear, potential mechanisms and predisposing factors need to be explored. In individual patients, the risk/benefit analysis needs to be carefully assessed and discussed prior to commencement of therapy.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Fármacos Gastrointestinales/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Adalimumab , Adolescente , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/mortalidad , Monitoreo de Drogas , Femenino , Estudios de Seguimiento , Fármacos Gastrointestinales/administración & dosificación , Humanos , Infecciones/inducido químicamente , Infecciones/mortalidad , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/mortalidad , Infliximab , Masculino , Neoplasias/inducido químicamente , Neoplasias/mortalidad , Estudios Retrospectivos , Enfermedad del Suero/inducido químicamente , Enfermedad del Suero/mortalidad , Adulto Joven
10.
Genes Immun ; 9(6): 556-60, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18563169

RESUMEN

The high incidence of Scottish Crohn's disease (CD) is not explained by the common three NOD2/CARD15 variants. We aimed to identify population-specific NOD2/CARD15 coding variants. A total of 1478 (320 inflammatory bowel disease patients <16 years, 343 adult CD patients, 542 parents and 273 controls). All NOD2/CARD15 exons were sequenced in 24 CD patients. Sequencing identified 18 single-nucleotide polymorphisms (SNPs) including 4 non-synonymous coding SNPs altering the structure of the Leucine-rich region--two were well established (1007-/C and 908G/R). Two other variants, valine955isoleucine (955V/I) and methionine863valine (863M/V), were genotyped in all subjects. 863M/V carriage was not significantly higher in CD patients vs controls (1.35 vs 0.37%, P=0.27). 955V/I carriage was no higher in CD or ulcerative colitis patients (12.8 and 15.8%, respectively) compared to controls (16.2%). Transmission disequilibrium test analysis was negative. 955V/I carriage was higher in indeterminate colitis patients (n=29) compared to controls (41.4 vs 16.2%, P=0.001, OR=3.6 (1.6-8.2)). Population-specific NOD2/CARD15 exonic variants do not account for the high-CD prevalence in Scotland.


Asunto(s)
Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad , Proteína Adaptadora de Señalización NOD2/genética , Adolescente , Niño , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/genética , Enfermedad de Crohn/epidemiología , Humanos , Proteína Adaptadora de Señalización NOD2/química , Polimorfismo de Nucleótido Simple , Estructura Terciaria de Proteína , Escocia/epidemiología
12.
Aliment Pharmacol Ther ; 27(3): 220-7, 2008 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-17988235

RESUMEN

BACKGROUND: Azathioprine intolerance is a common clinical problem, requiring drug withdrawal in up to 30% of patients. The successful use of mercaptopurine is described, but data to support this strategy are needed. AIMS: To assess the tolerability of mercaptopurine in inflammatory bowel disease patients previously intolerant of azathioprine, and identify predictive factors. METHODS: Sixty-one azathioprine-intolerant patients (31 males, median age at diagnosis 32 years, 31 with Crohn's disease, 30 with ulcerative colitis) who had been treated with mercaptopurine were identified. Intolerances included nausea and vomiting, flu-like illness, neutropenia, hepatotoxicity and pancreatitis. RESULTS: Mercaptopurine was tolerated by 59% (36 of 61) of azathioprine-intolerant patients (median dose 1.0 mg/kg), 61% (17 of 28) in patients with azathioprine-related nausea and vomiting, 61% (11 of 18) with flu-like illness, 33% (three of nine) with hepatotoxicity, 100% (one of one) with neutropenia, 100% (three of three) with rash and 0% (zero of one) with pancreatitis. Mercaptopurine intolerance was frequently for a different adverse event. Those intolerant of mercaptopurine were younger (28.4 years vs. 37.0 years; P = 0.014) and more frequently female (14/30 vs. 2/29, P = 0.027). Mercaptopurine tolerability was not affected by diagnosis, location, behaviour, surgery, smoking, family history or extra-intestinal manifestations. CONCLUSION: Mercaptopurine may be tolerated in up to 60% of azathioprine-intolerant patients, and treatment should be considered, particularly if intolerance was due to nausea, vomiting, flu-like illness or rash.


Asunto(s)
Azatioprina/efectos adversos , Hipersensibilidad a las Drogas , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mercaptopurina/uso terapéutico , Adulto , Distribución por Edad , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/inmunología , Esquema de Medicación , Femenino , Humanos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/inmunología , Masculino , Persona de Mediana Edad , Distribución por Sexo , Estadísticas no Paramétricas
14.
Aliment Pharmacol Ther ; 26(3): 411-9, 2007 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-17635376

RESUMEN

BACKGROUND: Forty per cent of patients with acute severe ulcerative colitis will not respond to intravenous corticosteroids and require second-line medical therapy or colectomy. A recent controlled trial has suggested that infliximab may be effective as rescue therapy. AIM: To assess the value of infliximab as rescue therapy for acute severe colitis in a retrospective cohort of ulcerative colitis patients in Scotland. METHODS: All patients satisfied Truelove and Witts criteria on admission, failed to respond to intravenous corticosteroids and received infliximab (5 mg/kg) as rescue therapy. Response was defined as need for colectomy at hospital discharge and by 90 days. RESULTS: A total of 39 patients (median age 31.7 years) were treated. 26/39 (66%) responded, avoiding colectomy during the acute admission, and were followed up for a median of 203 days (Interquartile range = 135.5-328.5). Hypoalbuminaemia was a consistent predictor of non-response on univariate and multivariate analysis. At day 3 of intravenous steroids, 9/18 (50.0%) with serum albumin <34 g/L had urgent colectomy vs. 1/13 (7.7%) >or=34 g/L (P = 0.02, OR = 12.0, C.I. 1.28-112.7). Two serious adverse events occurred - one death due to Pseudomonas pneumonia, and one post-operative fungal septicaemia. CONCLUSIONS: Infliximab represents a moderately effective rescue therapy for patients with acute severe ulcerative colitis. Serious adverse events, including death, do occur and should be discussed with patients prior to therapy.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Enfermedad Aguda , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
15.
Aliment Pharmacol Ther ; 24(2): 319-30, 2006 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-16842459

RESUMEN

BACKGROUND: Corticosteroids remain the mainstay of first-line therapy in active inflammatory bowel disease. AIMS: To determine the clinical outcome after the first corticosteroid-therapy and to identify factors which predict response/failure. METHODS: 216 (136 ulcerative colitis and 80 Crohn's disease) patients were identified in this 5-year inception cohort. The outcomes of early (30 days) and late (1 year) responses were used. Multivariate analyses were performed to identify factors associated with outcome. RESULTS: 86 (63%) and 60 (75%) ulcerative colitis and Crohn's disease required corticosteroid therapy, respectively. In ulcerative colitis, at 30 days, 69 (51%), 42 (31%) and 25 (18%) patients demonstrated complete response, partial response and no response, respectively. For Crohn's disease, these outcomes were observed in 32 (40%), 28 (35%) and 20 (25%). After 1 year, 75 (55%), 23 (17%) and 29 (21%) patients with ulcerative colitis demonstrated prolonged response, corticosteroid-dependence or required surgery, respectively. For Crohn's disease, these outcomes were observed in 30 (38%), 19 (24%) and 27 (35%) patients. Extensive ulcerative colitis was a predictor of surgery (P = 0.001, OR: 15.2). In Crohn's disease, inflammatory disease behaviour was negatively associated with surgery (P = 0.02, OR: 0.13). CONCLUSION: Although corticosteroids are effective, dependence/resistance remains common. Patients with extensive ulcerative colitis and fistulizing/stricturing Crohn's are most at risk of failing corticosteroid therapy.


Asunto(s)
Corticoesteroides/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Adulto , Estudios de Cohortes , Colitis Ulcerosa/cirugía , Enfermedad de Crohn/cirugía , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Análisis de Regresión , Factores de Riesgo , Resultado del Tratamiento
16.
Gut ; 54(10): 1416-20, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15843420

RESUMEN

INTRODUCTION: Recent data have suggested that specific haplotypic variants of the DLG5 gene on chromosome 10q23 may be associated with susceptibility to inflammatory bowel disease (IBD) in Germany. Haplotype D, notably characterised by the presence of a G-->A substitution at nucleotide 113, was associated with susceptibility to Crohn's disease (CD) whereas an extended haplotype A conferred protection. AIMS: Association of DLG5 haplotypic variants with disease susceptibility, genotype-phenotype relationships, and epistasis with CARD15 was investigated in the Scottish population. PATIENTS AND METHODS: A total of 374 CD, 305 ulcerative colitis (UC), and 294 healthy controls (HC) were studied. Genotyping for the variants rs1248696 (113A, representing haplotype D) and the single nucleotide polymorphism tag rs2289311 (representing haplotype A) were typed using the Taqman system. RESULTS: On analysis of the DLG5 variant 113A, there were no associations with IBD when allelic frequency (11.4% IBD v 13.2% HC; p = 0.30) and carrier frequency (19.2% IBD v 24.6% HC; p = 0.069) were analysed. No associations were observed between 113A variant allelic frequency (p = 0.37), carrier frequency (p = 0.057), and CD. In fact, 113A heterozygosity rates were lower in CD (16%) and IBD (16.9%) than in HC (23%) (p = 0.029 and p = 0.033, respectively). No associations between DLG5 and UC were observed. Haplotype A was not protective and there was no evidence of epistasis between DLG5 and CARD15. CONCLUSIONS: The present data contrast strongly with previous data from Germany. DLG5 113A is not associated with disease susceptibility and haplotype A does not confer resistance. Further work is required to evaluate the significance of DLG5 in other populations from geographically diverse regions.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Enfermedades Inflamatorias del Intestino/genética , Proteínas de la Membrana/genética , Proteínas Supresoras de Tumor/genética , Adulto , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/genética , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/genética , Epistasis Genética , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Haplotipos/genética , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Persona de Mediana Edad , Proteína Adaptadora de Señalización NOD2 , Fenotipo , Escocia/epidemiología
18.
Genes Immun ; 5(5): 417-25, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15190267

RESUMEN

NOD2/caspase recruitment domain (CARD)15 variants are identified in up to 50% of Crohn's disease (CD) patients. Functional variants of toll-like receptor-4 (TLR4) and CD14 genes may also be relevant to disease pathophysiology. We aimed to assess the contribution of NOD2/CARD15, TLR4 and CD14 variants in Scottish and Irish CD patients. In all, 612 patients with well-characterised inflammatory bowel disease (252 Scottish CD, 247 Scottish UC, 113 Irish CD) and 304 controls were genotyped for variants of NOD2/CARD15 (1007fsinsC, G908R, R702W, P268S), TLR4 (A299G) and CD14 (T-159C). Genotype-phenotype analyses were performed. Variant 1007fsinsC (P=0.003) and G908R (P=0.008) but not R702W (P=0.269) alleles were more prevalent in Scottish CD (4.7, 1.8 and 7.1%, respectively) than Scottish control (2.3, 0.3 and 5.4%). CD allelic frequencies were lower than the series from Europe (P<0.00001) and North America (P<0.00001) but not Scandinavia (P<0.7). Associations were identified with age at diagnosis (P=0.002), ileal disease (P<0.02), penetrating disease (P=0.04) and inflammatory joint disease (P<0.02). TLR4 and CD14 variants did not differ between CD and controls. In conclusion, we present compelling evidence for genetic heterogeneity within Europe. These NOD2/CARD15 variants have a minor contribution in Scottish and Irish CD patients, consistent with an emerging pattern from Northern Europe.


Asunto(s)
Enfermedad de Crohn/genética , Heterogeneidad Genética , Péptidos y Proteínas de Señalización Intracelular/genética , Receptores de Lipopolisacáridos/genética , Glicoproteínas de Membrana/genética , Receptores de Superficie Celular/genética , Adulto , Enfermedad de Crohn/etnología , Femenino , Frecuencia de los Genes , Humanos , Irlanda , Masculino , Mutación , Proteína Adaptadora de Señalización NOD2 , Escocia , Receptor Toll-Like 4 , Receptores Toll-Like , Población Blanca/genética
19.
Clin Exp Immunol ; 135(3): 490-6, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15008984

RESUMEN

Anti-Saccharomyces cerevisiae antibodies (ASCAs) have been proposed as serological markers, which may differentiate Crohn's disease (CD) from ulcerative colitis (UC) and predict disease phenotype. Their importance in pathogenesis is unproven. We investigated the relationship between ASCAs, disease phenotype and NOD2/CARD15 genotype in CD and whether ASCAs were related to antibodies to other fungal proteins. Serum from 228 patients [143 CD, 75 UC, 10 with indeterminate colitis (IC)] and 78 healthy controls (HC) were assayed for ASCA. Antibodies (IgA, IgG) to other fungal proteins (Fusarium species ATC20334, Mycoprotein) were measured in the same samples using an in-house enzyme-linked immunosorbent assay (ELISA) assay. ASCAs were present in 57% of CD, 19% of UC, 30% of IC and 8% of HCs. ASCA-positive status was a predictor for CD with sensitivity of 57%, specificity of 87%, positive predictive value of 78% and negative predictive value of 68%. ASCA was associated with proximal (gastroduodenal and small bowel involvement) rather than purely colonic disease (P < 0.001) and with a more severe disease phenotype and requirement for surgery over a median follow-up time of 9 years (P < 0.0001). No associations with NOD2/CARD15 mutations were seen. There was no association between ASCA and antibodies to MP (IgA or IgG). These data implicate ASCA as a specific marker of disease location and progression in CD, emphasizing the heterogeneity within IBD.


Asunto(s)
Anticuerpos Antifúngicos/sangre , Proteínas Portadoras/genética , Enfermedad de Crohn/inmunología , Péptidos y Proteínas de Señalización Intracelular , Mutación , Saccharomyces cerevisiae/inmunología , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Anticuerpos Antifúngicos/biosíntesis , Biomarcadores/sangre , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Inmunoglobulina A/biosíntesis , Inmunoglobulina G/biosíntesis , Masculino , Persona de Mediana Edad , Proteína Adaptadora de Señalización NOD2 , Fenotipo , Sensibilidad y Especificidad
20.
Gut ; 52(7): 998-1002, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12801957

RESUMEN

BACKGROUND: Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis. METHODS: We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later. RESULTS: After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo. CONCLUSION: These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Proteína C-Reactiva/análisis , Método Doble Ciego , Resistencia a Medicamentos , Femenino , Glucocorticoides/uso terapéutico , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Calidad de Vida , Inducción de Remisión , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA