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1.
Acta Gastroenterol Belg ; 86(3): 395-400, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37814555

RESUMO

Background: Pelvic abscess is a common complication of abdominal surgery or intestinal or gynecological diseases. Over the last decades, endoscopic ultrasound (EUS)-guided drainage has emerged as a minimally invasive alternative to percutaneous or surgical treatment of pelvic abscesses. Aim: To evaluate safety and efficacy of EUS-guided transrectal pelvic abscess drainage in a single center. Methods: From February 2017 to April 2023, all data on patients who were treated for pelvic abscesses by EUS-guided drainage in a single center, were retrospectively analyzed. Results: A total of 17 patients were treated for pelvic abscesses by EUS-guided drainage. The procedure was technically successful and uneventful in all 17 patients (100%). Etiology of the abscess was postsurgical (n=5, 29%), secondary to medical illness (n=10, 59%) or gastrointestinal perforation (n=2, 12%). The abscess was multilocular in 5 patients (29%), the mean largest diameter was 76 mm (range 40-146 mm). Drainage was performed using 2 double pigtail stents, and in 1 patient an additional 10 Fr drainage catheter was deployed. Two patients (12%) required a second endoscopic intervention. Treatment success, defined by complete abscess resolution on follow-up CT scan along with symptom relief, was 100%. There was no need for surgical intervention. The median post-procedural hospital stay was 5 days. No recurrence was reported within a median time of follow-up of 39 months. Conclusion: EUS-guided transrectal drainage of pelvic abscesses using double pigtail stents is safe and highly effective. This case series contributes to the cumulative evidence that, in expert hands, EUS-guided drainage should be considered as first-line approach for treatment of pelvic abscesses.


Assuntos
Abscesso Abdominal , Abscesso , Humanos , Abscesso/cirurgia , Estudos Retrospectivos , Drenagem/métodos , Endossonografia , Resultado do Tratamento , Ultrassonografia de Intervenção
2.
Int J Hyperthermia ; 39(1): 806-812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35710344

RESUMO

BACKGROUND: The use of heat to treat various diseases is called hyperthermia treatment (HT). Since the 1970s, the anti-cancer effects of HT have been investigated. Different HT techniques can be categorized as local, regional and whole-body hyperthermia treatment (WBHT). We aim to provide a summary of recent research done on HT to treat cancer. METHODS: In July 2020 ClinicalTrials.gov were systematically searched for all trials including hyperthermia and cancer registered between 2000 and 2020. Studies were excluded when they did not concern hyperthermal treatment, when they were not oncological studies, when they were observational or other non-interventional studies. RESULTS: Of 1654 identified trials, 235 were included. Of these 235 studies, 123 described the use of HIPEC (52.3%), 44 other types of regional HT (18.7%), 45 local HT (19.1%) and 15 WBHT (6.4%). A steady increase (720%) in research to hyperthermic intraperitoneal chemotherapy (HIPEC) can be observed in the last decade. Although HIPEC is the most researched HT modality, an evolution in other HT technologies could be observed during the past decade. CONCLUSIONS: Research to HT to treat cancer has expanded fast. Some techniques, for example HIPEC start to be used outside of research context, but overall, more research is needed to establish a clear effect of these HT techniques.


Assuntos
Hipertermia Induzida , Neoplasias , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Hipertermia Induzida/métodos , Neoplasias/terapia
3.
Int J Oral Maxillofac Surg ; 51(9): 1205-1210, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35221148

RESUMO

The aim of this study was to investigate the prevalence and characteristics of systemic conditions in patients undergoing orthognathic surgery at a tertiary centre. Ninety of the 838 patients undergoing orthognathic surgery between 2013 and 2019 had a systemic condition (prevalence of 10.7%). The most prevalent categories of systemic conditions were inflammatory joint disorders, endocrinological disorders, and syndromes. Patients with syndromes were significantly younger at the time of surgery than patients with endocrinological (P < 0.001), inflammatory joint (P = 0.003), or gastrointestinal disorders (P = 0.033). Endocrinological disorders, syndromes, and malignancies were more frequently associated with a skeletal class III malocclusion (P = 0.009, P < 0.001, and P = 0.048 respectively). Further research is needed to clarify the role of systemic conditions in the aetiology of malocclusion and postoperative outcomes.


Assuntos
Má Oclusão Classe III de Angle , Má Oclusão , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos , Má Oclusão/epidemiologia , Má Oclusão/cirurgia , Má Oclusão Classe III de Angle/epidemiologia , Má Oclusão Classe III de Angle/cirurgia , Prevalência , Estudos Retrospectivos , Síndrome
4.
Breast Cancer Res Treat ; 192(2): 293-301, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34982322

RESUMO

PURPOSE: The prevention of taxane-related toxicities at the extremities is highly important for patients' treatment and quality-of-life. Several studies endorse hand/foot-cooling using frozen gloves as a prophylactic intervention. Unlike frozen gloves, hilotherapy produces cooling at a constant temperature. Comparative data with frozen gloves are unavailable. METHODS: This prospective self-controlled study explores the efficacy of hilotherapy at the right hand and foot compared to frozen gloves at the left in patients with early breast cancer treated with weekly paclitaxel 80 mg/m2 or three-weekly docetaxel 75 mg/m2. Patient-reported outcomes were collected at baseline, 6, 12, 18 and 24 weeks after the start of treatment. Primary and secondary endpoints were the incidence of any-grade and ≥ grade 2 side-effects (peripheral neuropathy, pain and nail toxicities), and perceived comfort of both interventions. RESULTS: Sixty-two patients participated. The incidence of any-grade side-effects was similar on both sides, 85.5% with hilotherapy and 90.3% with frozen gloves (p = 1.000). The incidence of ≥ grade 2 side-effects at the extremities was significantly lower with hilotherapy: 43.6% compared to 61.3% with frozen gloves (p = 0.013). Perceived comfort was significantly better for hilotherapy than for frozen gloves (p < 0.0001). CONCLUSIONS: Compared to frozen gloves, continuous cooling of hands and feet using hilotherapy produces better prevention of ≥ grade 2 patient-reported side-effects at the extremities (peripheral neuropathy, pain and nail toxicities). Perceived comfort was significantly better for hilotherapy. From a clinical and patient perspective, hilotherapy is a better alternative for preventing clinically significant taxane-related side-effects.


Assuntos
Neoplasias da Mama , Doenças do Sistema Nervoso Periférico , Neoplasias da Mama/terapia , Crioterapia , Feminino , Humanos , Dor/etiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Estudos Prospectivos , Taxoides/efeitos adversos
5.
J Stomatol Oral Maxillofac Surg ; 122(6): 612-617, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33246182

RESUMO

Squamous odontogenic tumors (SOT) are rare, benign, odontogenic neoplasms of the jaws. The sporadically reported cases with multifocal SOTs seem to have a marked predilection for younger African American patients. In this case report a 14-year-old Caucasian male presented with swelling of the vestibular alveolar process, slight tooth divergence, and mobility. A multifocal squamous odontogenic tumor was diagnosed and subsequently treated twice with surgical enucleation. Two and a half years earlier his mother was diagnosed and treated for a similar multifocal SOT. Next-Generation-Sequencing targeted resequencing mutational analysis of the maternal surgical specimens was performed. No potential causal mutation could be identified. Postoperative follow-up of the patient showed no recurrence of the SOT after 2 years. This case report substantiates the possibility of a familial relationship in (multifocal) SOT, possibly changing current ideas concerning the etiology and treatment of these neoplasms.


Assuntos
Tumor Odontogênico Escamoso , Tumores Odontogênicos , Adolescente , Humanos , Masculino , Tumores Odontogênicos/diagnóstico , Tumores Odontogênicos/cirurgia , Relações Pais-Filho
6.
Neth J Med ; 77(7): 243-254, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31582582

RESUMO

Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). MGRS-associated kidney disorders are various and the list is still expanding. The kidney disorders can manifest as glomerular diseases, tubulopathies, and vascular involvement with varying clinical presentations. Diagnosis is often challenging because of the wide spectrum of MGRS, and it is difficult to establish a pathogenic link between the presence of the M-protein or serum free light chains and kidney diseases; further complicating accurate diagnosis is the high incidence of MGUS and/or kidney disorders, independent of MGRS, in elderly patients. However, MGRS can significantly impair kidney function. Because treatment can stop and also reverse kidney disease, early recognition is of great importance. A combined haematologic and nephrologic approach is crucial to establish the causative role of the M-protein in the pathogenesis of kidney disease. Clone-directed therapy, which may include autologous stem cell transplantation in eligible patients, often results in improved outcomes. In this review, we discuss the histopathologic classification of MGRS lesions, provide a renal and haematologic diagnostic workup, discuss treatment options for MGRS, and introduce a Benelux MGRS Working Group.


Assuntos
Nefropatias , Gamopatia Monoclonal de Significância Indeterminada , Transplante de Células-Tronco/métodos , Transplante Autólogo/métodos , Biópsia/métodos , Gerenciamento Clínico , Humanos , Nefropatias/imunologia , Nefropatias/patologia , Nefropatias/terapia , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/patologia , Gamopatia Monoclonal de Significância Indeterminada/terapia
7.
Acta Gastroenterol Belg ; 81(1): 15-21, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29562373

RESUMO

BACKGROUND AND STUDY AIMS: Anti-TNF monoclonal antibodies are a cornerstone in the treatment of Crohn's disease. Prospective data on switching from the subcutaneous and human adalimumab (ADM) to the intravenous and chimeric infliximab (IFX) are scarce. PATIENTS AND METHODS: In this prospective, observational, multicentre cohort study we included 21 patients with loss of response to ADM despite at least 4 consecutive weekly injections. Clinical response (CDAI drop≥70 points) and remission (CDAI≤150) were assessed after switching from ADM to IFX after 10 weeks, 6 and 12 months. Predictive factors of response/remission, the need for therapy intensification, discontinuation and safety were investigated. RESULTS: Short-term response and remission (10 weeks) were seen in 57% and 48% respectively. Mid- and long-term clinical response and remission were achieved in 40% and 25% after 6 months and in 45% and 20% after 12 months respectively. At 12 months, 81% still were on IFX. IFX therapy intensification was needed in half of the patients at 6 months and three quarter of patients at 12 months. Undetectable ADM trough levels (despite weekly injections) were a predictive factor for short-term response and remission to IFX. About half of the patients with response at week 10 maintained response at 6 and 12 months. CONCLUSIONS: Switching from ADM to IFX can be efficacious in patients with loss of response, in particular in case of undetectable ADM trough levels. The majority of patients however will need IFX therapy intensification during their first year of treatment.


Assuntos
Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Adulto , Idoso , Bélgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
8.
Acta Gastroenterol Belg ; 77(3): 306-11, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25509201

RESUMO

BACKGROUND AND STUDY AIMS: Although laparoscopic cholecystectomy is advocated for acute cholecystitis, debate still exists about its optimal timing. This retrospective study compares the outcome of laparoscopic cholecystectomy within versus later than 5 days of onset of symptoms in patients with acute cholecystitis. PATIENTS AND METHODS: One hundred thirty six patients with acute cholecystitis grade I or II were included in the study and divided in two groups. Group 1 received surgery within 5 days of symptoms and group 2 received conservative therapy and delayed surgery after 6 weeks. RESULTS: Group 1 and 2 consisted of 100 and 36 patients respec- tively. Because of failure of conservative therapy 5 patients of group 2 had surgery before 6 weeks. The remaining 31 patients underwent surgery after 6 weeks. Preoperative ERCP was indicated in 2 and 11 patients in groups 1 and 2 respectively (p < 0.001). The median total hospital stay was 3.0 days for group 1 and 11.0 days for group 2 (p < 0.001). In terms of operation time, conversion rates, intraoperative cholangiography, postoperative ERCP, morbidity or mortality both groups were comparable (p > 0.05). CONCLUSION: Laparoscopic cholecystectomy can be performed safely within 5 days after the onset of symptoms in patients with acute cholecystitis. Because of shortened total hospital stay and risk of failure of conservative therapy, early laparoscopic cholecystectomy should be favored.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda/diagnóstico , Colecistite Aguda/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
J Crohns Colitis ; 7(11): e588-98, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23664896

RESUMO

AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. METHODS: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18 y of age) were recruited over a 2 year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. RESULTS: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5 y (range: 1.6-18 y); median duration of symptoms prior to diagnosis was 3 m (range: 1-12 m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < -1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. CONCLUSION: In Belgium, the median age of children presenting with Crohn's disease is 12.5 y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Sistema de Registros , Adolescente , Distribuição por Idade , Idade de Início , Anti-Inflamatórios/uso terapêutico , Bélgica/epidemiologia , Criança , Pré-Escolar , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Quimioterapia Combinada , Humanos , Imunossupressores , Lactente , Modelos Logísticos , Monitorização Fisiológica/métodos , Análise Multivariada , Prevalência , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não Paramétricas
10.
J Crohns Colitis ; 7(8): 644-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23083698

RESUMO

BACKGROUND AND AIMS: Active inflammatory bowel disease (IBD) is associated with increased activity of inducible nitric oxide synthase (iNOS), which increases both mucosal and plasma nitric oxide (NO) levels. Increased fractional exhaled nitric oxide (FeNO) levels have been described in patients with IBD. Currently, hand-held FeNO measurement devices are available, enabling a fast in-office analysis of this non-invasive disease activity marker. In this pilot study, we investigated the utility of in-office FENO measurements in patients with Crohn's disease (CD). METHODS: Fifty CD patients and 25 healthy controls (HC) were included, all of whom were free of atopic or pulmonary disorders and respiratory symptoms at the time of inclusion. The Crohn's disease activity index (CDAI) was calculated, and the inflammatory parameters and fecal calprotectin levels were assessed. FeNO was measured with a hand-held device. RESULTS: A significant increase in FeNO (median, [interquartile range]) was observed in steroid-free CD patients with clinically active disease (CDAI>150; 22 [8] ppb) compared with CD patients in clinical remission (CDAI<150; 11 [6] ppb; P<0.001) and HC's (17 [9] ppb; P<0.05). Active CD patients treated with corticosteroids had significantly lower FeNO compared with active CD patients without steroids (12 [10] ppb vs 25 [19] ppb; P<0.05). FeNO displayed a strong correlation with the CDAI (R=0.68; P<0.001). Fair correlations were found between FeNO and several systemic inflammatory markers, but no significant correlation was found with fecal calprotectin. CONCLUSION: This pilot study suggests that hand-held FeNO measurements could be an attractive non-invasive indicator of systemic inflammation in Crohn's disease.


Assuntos
Doença de Crohn/patologia , Óxido Nítrico/análise , Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Biomarcadores/análise , Testes Respiratórios , Estudos de Casos e Controles , Doença de Crohn/tratamento farmacológico , Fezes/química , Humanos , Complexo Antígeno L1 Leucocitário/análise , Projetos Piloto , Índice de Gravidade de Doença
11.
Acta Gastroenterol Belg ; 75(4): 425-31, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23402086

RESUMO

Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in Belgian pediatric Crohn's disease patients. All patients on infliximab as part of the present or past treatment for Crohn's Disease until January 1st 2011 were selected from an existing database. Information on disease phenotype, medication and adverse events were extracted. Adverse events occurred in 25.9% of patients exposed to infliximab of which 29.6% were severe. In total 31.7% of patients stopped infliximab therapy. The main reasons for discontinuation were adverse events in 45.4% and loss of response in 30.3%. No malignancies or lethal complications occurred over this 241 patient year observation period. Immunomodulators were concomitant medication in 75% of patients and were discontinued subsequently in 38.4% of them. The cost of infliximab infusions per treated patient per year in the Belgian health care setting is approximately 9 474 euro, including only medication and hospital related costs. Even though infliximab is relatively safe in pediatric CD on the short term, close follow-up and an increased awareness of the possible adverse reactions is highly recommended. Adverse reactions appeared in 25.9% of all patients and were the main reason for discontinuation. Treatment cost has to be balanced against efficacy and modifications in disease course. In the Belgian health care system, the medication is available to all patients with moderate to severe CD.


Assuntos
Anticorpos Monoclonais , Doença de Crohn , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/economia , Bélgica/epidemiologia , Criança , Efeitos Psicossociais da Doença , Doença de Crohn/tratamento farmacológico , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/economia , Humanos , Infliximab , Infusões Intravenosas , Masculino , Conduta do Tratamento Medicamentoso , Farmacovigilância , Resultado do Tratamento
12.
Ann Rheum Dis ; 70(11): 2044-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21873332

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn's disease (CD) and peripheral synovitis in spondyloarthritis. OBJECTIVE: To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients. METHODS: Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed. RESULTS: Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p<0.001), mucosal vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with healthy controls), but not at all in CD. CONCLUSION: A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.


Assuntos
Colite/etiologia , Ileíte/etiologia , Mucosa Intestinal/irrigação sanguínea , Neovascularização Patológica/etiologia , Espondilartrite/complicações , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Colite/metabolismo , Colite/patologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Endotélio Vascular/metabolismo , Humanos , Ileíte/metabolismo , Ileíte/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fator de Crescimento Placentário , Proteínas da Gravidez/metabolismo , Espondilartrite/metabolismo , Espondilartrite/patologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Clin Biochem ; 44(13): 1062-1066, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21723857

RESUMO

BACKGROUND AND AIMS: TPMT deficiency is associated with azathioprine (AZA)-induced myelosuppression (MS). However, in one previous study, only about » of MS episodes in Crohn's Disease patients under AZA can be attributed to TPMT deficiency. Recently, new TPMT mutations have been described and our aim is to investigate their clinical relevance before and after a first MS episode on thiopurine therapy. METHODS: Clinical data from 61 IBD patients having developed MS during AZA therapy were collected. Sequencing analysis was carried out on TPMT cDNA for the presence of all currently known mutations. RESULTS: Only TPMT *2, *3A and *3C mutations were found in this cohort. TPMT mutations were observed in 15 out of 61 patients (25%). Four out of 15 were homozygous for a TPMT mutation (low methylator, LM genotype) and 11 were heterozygous (intermediate methylator, IM genotype). Median delays of MS onset were 2, 2.75 and 6months in the LM, IM and HM (high methylator, wild type TPMT) groups, respectively. After the first MS episode, 36 patients resumed thiopurine treatment of which 13 experienced a second MS episode. This second episode was also rarely associated with TPMT mutations. CONCLUSIONS: One quarter of MS episodes during AZA were associated with TPMT deficient genotype. After a first leucopenia episode, thiopurine therapy may be resumed in a majority of patients independently of their TPMT genotype.


Assuntos
Azatioprina/efeitos adversos , Hipersensibilidade a Drogas/complicações , Doenças Inflamatórias Intestinais/complicações , Metiltransferases/genética , Erros Inatos do Metabolismo da Purina-Pirimidina/complicações , Adolescente , Adulto , Idoso , Azatioprina/uso terapêutico , Análise Mutacional de DNA , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/genética , Feminino , Genótipo , Humanos , Imunossupressores , Doenças Inflamatórias Intestinais/tratamento farmacológico , Leucopenia , Masculino , Pessoa de Meia-Idade , Mutação , Pancitopenia/induzido quimicamente , Pancitopenia/genética , Erros Inatos do Metabolismo da Purina-Pirimidina/etiologia , Erros Inatos do Metabolismo da Purina-Pirimidina/genética , Estudos Retrospectivos , Adulto Jovem
14.
Am J Gastroenterol ; 106(4): 771-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21386832

RESUMO

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Ciclosporina/administração & dosagem , Resistência a Medicamentos , Terapia de Salvação/métodos , Esteroides/administração & dosagem , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Criança , Colectomia , Colite Ulcerativa/cirurgia , Ciclosporina/efeitos adversos , Feminino , Seguimentos , Humanos , Infecções/induzido quimicamente , Infliximab , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/induzido quimicamente , Embolia Pulmonar/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Facts Views Vis Obgyn ; 3(1): 15-21, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-24753843

RESUMO

First trimester spontaneous abortions occur in 15 to 20% of all clinically recognized pregnancies. Chromosomal -anomalies are responsible for more than 50% of spontaneous abortions. The majority (90%) of these chromosomal anomalies are numerical, particularly autosomal trisomies (involving chromosomes 13,16, 18, 21, 22), polyploidy and monosomy X. At birth chromosomal anomalies are still an important cause of congenital malformations occurring in 0,55% of newborns (autosomal: 0,40%, sex chromosomal: 0,15%). Autosomal trisomies result from maternal -meiotic nondisjunction of gametogenesis and the risk increases with maternal age. Polyploidy (triploidy (3n = 69) or tetraploidy (4n = 92)), results from a contribution of one or more extra haploid chromosome sets at fertilization. Unlike the risk for autosomal trisomies, the risk for polyploidies and for monosomy X (Turner syndrome) does not increase with maternal age. In the prenatal period the ultrasonographic diagnosis of some autosomal trisomies such as trisomy 13 and 18 is feasible based on the frequently seen major malformations while the diagnosis of trisomy 21 often remains challenging due to the absence of major malformations in > 50% of cases. For Turner syndrome (monosomy X), the lethal form will present with cystic hygroma colli and hydrops but the non lethal form is difficult to recognize by -ultrasound in the second trimester. The 5 frequently encountered chromosomal anomalies (Trisomy 13, 18, 21, Turner syndrome and Triploidy) referred here as the 5T's have specific hand features which will be discussed.

16.
Int J Immunogenet ; 34(3): 181-91, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17504508

RESUMO

Caspase activation and recruitment domain 15 (CARD15) and Toll-like receptor 4 (TLR4) are respectively intracellular and membrane-bound receptors for bacterial cell wall components [respectively muramyl dipeptide (MDP) and lipopolysaccharide (LPS)]. Polymorphisms in CARD15 and TLR4 have been linked with Crohn's disease (CD). Adherent-invasive Escherichia coli (AIEC) strains with particular adhesion and invasion characteristics have been specifically associated with CD ileal mucosa. The aim of this study was to investigate the functional impact of these polymorphisms on monocytes in patients with CD, in response to MDP, LPS and AIEC strain LF82. Monocytes were isolated from 40 patients with CD using magnetic cell sorting, stimulated with LPS or MDP or infected with AIEC. IL-1beta, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor alpha induction was assessed using quantitative real time-polymerase chain reaction, Cytometric Bead Array and ELISA. Bacterial intracellular survival and replication was assessed using a gentamicin protection assay. Results were linked with the presence of CARD15 and TLR4 polymorphisms. Monocytes of patients with CARD15 polymorphisms showed an early reduced cytokine response (IL-1beta, IL-6 and IL-10) to infection with AIEC, which was restored after 20 h. A gene-dose effect was seen, comparing wild-types, heterozygotes and homozygotes. We found no differences in intracellular survival and replication of AIEC. Heterozygous carriage of TLR4 polymorphisms did not influence monocyte response. In conclusion, patients with CD carrying CARD15 polymorphisms show a disturbed early inflammatory monocyte response after infection with AIEC strain LF82. For the first time, a functional defect was detected in single heterozygous carriers. These findings reflect the potential role of a genetically altered host response to disease-related bacteria in the pathogenesis of CD.


Assuntos
Doença de Crohn/genética , Doença de Crohn/imunologia , Infecções por Escherichia coli/imunologia , Monócitos/imunologia , Proteína Adaptadora de Sinalização NOD2/genética , Receptor 4 Toll-Like/genética , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Adjuvantes Imunológicos/farmacologia , Adulto , Idoso , Citocinas/genética , Citocinas/imunologia , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/imunologia , Escherichia coli/patogenicidade , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/microbiologia , Proteína Adaptadora de Sinalização NOD2/imunologia , Polimorfismo Genético , RNA Mensageiro/metabolismo
17.
Ann Rheum Dis ; 65(10): 1293-300, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16476712

RESUMO

BACKGROUND: Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn's disease. Inflammation is manifested clinically in Crohn's disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn's disease. AIMS: To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn's disease and to examine global gene expression in non-inflamed colon biopsy specimens and screen patients for differentially expressed genes. METHODS: Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn's disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn's disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass-based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn's disease and 10 controls. RESULTS: 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn's disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn's disease. CONCLUSION: The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn's disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn's disease in patients with SpA can be considered.


Assuntos
Doença de Crohn/genética , Espondiloartropatias/genética , Adulto , Idoso , Biópsia , Doença Crônica , Colite/genética , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Doença de Crohn/complicações , Doença de Crohn/patologia , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Ileíte/genética , Ileíte/metabolismo , Ileíte/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Espondiloartropatias/complicações , Espondiloartropatias/patologia
18.
Ned Tijdschr Geneeskd ; 149(32): 1799-801, 2005 Aug 06.
Artigo em Holandês | MEDLINE | ID: mdl-16121666

RESUMO

A 75-year-old man and a 53-year-old woman had longstanding joint pain, for which they had been treated with NSAIDs. When the symptoms worsened, a thorough diagnostic investigation was conducted that revealed myeloproliferative bone-marrow disorders in both patients. The man, who had polyarticular gout secondary to chronic myelomonocytic leukaemia, was able to maintain control of his joint pain with medical treatment. In the woman, with a history of stable joint pain due to polyarthritis, deterioration of the symptoms and the development of pancytopaenia led to a diagnosis of acute lymphocytic leukaemia; she died after receiving multiple courses of chemotherapy. The possibility of an underlying malignancy should be considered in patients with atypical symptoms in the locomotor system, an unexpected course or anomalous secondary symptoms.


Assuntos
Artralgia/etiologia , Transtornos Mieloproliferativos/complicações , Idoso , Artralgia/tratamento farmacológico , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/radioterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia
19.
Clin Exp Immunol ; 140(2): 354-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15807862

RESUMO

Carriage of CARD15 gene polymorphisms and the serological marker anti-Saccharomyces cerevisiae antibodies (ASCA) are two markers for Crohn's disease (CD). Similar phenotypes have been associated with both markers. In the present study we analysed whether both markers were associated with each other and, if so, whether this association could be explained by a direct link or by an indirect association with those phenotypes. Therefore, we included 156 consecutive Caucasian CD patients and assessed the prevalence of the three common single nucleotide polymorphisms in the CARD15 gene. Serum samples were analysed for IgA and IgG ASCA by ELISA. CD patients with CARD15 polymorphisms were more frequently ASCA positive (OR 2.7 (1.4-5.2); P = 0.002) and had higher titres for ASCA IgA (P = 0.005) and ASCA IgG (P < 0.001) compared to patients carrying the wild type polymorphisms. Multivariate analysis demonstrated that this association was independent from ileal disease, penetrating disease and stricturing disease, the need for resective bowel surgery, familial cases, smoking habits and early age at onset. Homozygotes or compound heterozygotes for CARD15 polymorphisms had significantly more frequent ASCA positivity compared to single heterozygotes (OR 9.1 (1.1-74.2), P(c) (corrected P-value) = 0.030). These data indicate that there is a significant association between the carriage of CARD15 polymorphisms and ASCA, independent of the described phenotypes. Moreover, ASCA positivity is more frequent in CD patients carrying 2 CARD15 polymorphisms compared to single heterozygotes.


Assuntos
Anticorpos Antifúngicos/sangue , Doença de Crohn/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Polimorfismo Genético , Saccharomyces cerevisiae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Crohn/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Marcadores Genéticos , Genótipo , Heterozigoto , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2
20.
Ann Rheum Dis ; 64(2): 321-4, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15166002

RESUMO

BACKGROUND: Crohn's disease is associated with an increased number of macrophages in ileal and colonic mucosa. Data on macrophages in gut mucosa of patients with spondyloarthritis (SpA) are scarce. OBJECTIVE: To investigate macrophages and other antigen presenting cells in gut mucosa from patients with SpA and Crohn's disease, given the relationship between both entities. METHODS: Biopsy specimens from patients with SpA, Crohn's disease, ulcerative colitis, and from controls were immunohistochemically stained with different markers for macrophages and dendritic cells. Slides were scored semiquantitatively on a four point scale. RESULTS: SpA and Crohn's disease were associated with large numbers of CD68+ macrophages. Colon mucosa of both patients with SpA and Crohn's disease, but not ulcerative colitis, showed increased numbers of macrophages expressing the scavenger receptor CD163. CONCLUSIONS: Macrophages expressing the scavenger receptor CD163 are increased in colonic mucosa in SpA and in Crohn's disease, highlighting the relationship between these entities. The increased number of CD163+ macrophages in colon mucosa of patients with SpA suggests this is another argument for a role of macrophage scavenger receptors in this group of diseases.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Colo/imunologia , Doença de Crohn/imunologia , Mucosa Intestinal/imunologia , Receptores de Superfície Celular/metabolismo , Espondilartrite/imunologia , Adolescente , Adulto , Idoso , Colite Ulcerativa/imunologia , Células Dendríticas/imunologia , Antígenos HLA-DR/análise , Humanos , Técnicas Imunoenzimáticas , Macrófagos/imunologia , Pessoa de Meia-Idade
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