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1.
Expert Opin Biol Ther ; 24(1-2): 101-109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250818

RESUMO

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.


Assuntos
Colite Ulcerativa , Humanos , Pessoa de Meia-Idade , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Ustekinumab/efeitos adversos , Estudos Retrospectivos , Indução de Remissão , Estudos de Coortes , Corticosteroides/uso terapêutico , Complexo Antígeno L1 Leucocitário/uso terapêutico , Resultado do Tratamento
2.
Dig Liver Dis ; 56(4): 628-634, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37880017

RESUMO

BACKGROUND: Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD), and Ulcerative Colitis (UC) may have extraintestinal manifestations, including disorders of the urinary tract. The prevalence of lower urinary tract symptoms (LUTS) in IBD patients remains unclear. AIMS: Assess the prevalence of LUTS in patients with CD or UC, evaluate the variables implicated in any difference in LUTS prevalence between CD or UC, and assess any relationship between disease activity and LUTS METHODS: LUTS were evaluated in 301 IBD patients through standardised questionnaires: Bristol Female Lower Urinary Tract Symptoms (BFLUTS), NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Prostate Symptom Score (IPSS). IBD activity was determined through the Crohn's Disease Activity Index (CDAI), Partial Mayo Score (PMS), and Total Mayo Score (TMS). RESULTS: BFLUTS total score for females was 6 (3-11). Patients with a higher age at diagnosis had worse filling symptoms (p = 0.049) and a worse quality of life (p = 0.005). In males, 67.1% had mild, 28.5% moderate, and 4.4% severe IPSS symptom grades. The overall NIHCPSI prevalence of chronic prostatitis-like symptoms was 26.8%. The questionnaires revealed some significant differences in the subgroups analysed. CONCLUSION: LUTS should be evaluated in IBD patients by urologic-validated questionnaires for prompt diagnosis and early treatment.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Sintomas do Trato Urinário Inferior , Prostatite , Masculino , Humanos , Feminino , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Qualidade de Vida , Prostatite/complicações , Prostatite/epidemiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/diagnóstico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia
3.
Expert Opin Biol Ther ; 23(3): 293-304, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36843568

RESUMO

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Proteína C-Reativa/análise , Indução de Remissão , Itália , Fármacos Gastrointestinais/uso terapêutico , Resultado do Tratamento , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico
4.
Inflamm Bowel Dis ; 29(3): 376-383, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579320

RESUMO

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.


We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.


Assuntos
Medicamentos Biossimilares , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Adalimumab/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Resultado do Tratamento
5.
J Gastrointestin Liver Dis ; 31(4): 411-416, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36535057

RESUMO

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.


Assuntos
Medicamentos Biossimilares , Doenças Inflamatórias Intestinais , Humanos , Adalimumab , Medicamentos Biossimilares/efeitos adversos , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Itália , Resultado do Tratamento , Infliximab/uso terapêutico
6.
Expert Opin Biol Ther ; 22(2): 313-320, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34904510

RESUMO

BACKGROUND: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.


Assuntos
Medicamentos Biossimilares , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Anticorpos Monoclonais , Medicamentos Biossimilares/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Itália , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
7.
Med Oncol ; 38(3): 24, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570712

RESUMO

A subset of colorectal cancer (CRC) with a mesenchymal phenotype (CMS4) displays an aggressive disease, with an increased risk of recurrence after surgery, reduced survival, and resistance to standard treatments. It has been shown that the AXL and TGFß signaling pathways are involved in epithelial-to-mesenchymal transition, migration, metastatic spread, and unresponsiveness to targeted therapies. However, the prognostic role of the combination of these biomarkers and the anti-tumor effect of AXL and TGFß inhibition in CRC still has to be assessed. To evaluate the role of AXL and TGFß as negative biomarker in CRC, we conducted an in-depth in silico analysis of CRC samples derived from the Gene Expression Omnibus. We found that AXL and TGFß receptors are upregulated in CMS4 tumors and are correlated with an increased risk of recurrence after surgery in stage II/III CRC and a reduced overall survival. Moreover, we showed that AXL receptor is differently expressed in human CRC cell lines. Dual treatment with the TGFß galunisertib and the AXL inhibitor, bemcentinib, significantly reduced colony formation and migration capabilities of tumor cells and displayed a strong anti-tumor activity in 3D spheroid cultures derived from patients with advanced CRC. Our work shows that AXL and TGFß receptors identify a subgroup of CRC with a mesenchymal phenotype and correlate with poor prognosis. Dual inhibition of AXL and TGFß could represent a novel therapeutic strategy for patients with this aggressive disease.


Assuntos
Adenocarcinoma/tratamento farmacológico , Benzocicloeptenos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal , Recidiva Local de Neoplasia/tratamento farmacológico , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pirazóis/farmacologia , Quinolinas/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo II/antagonistas & inibidores , Triazóis/farmacologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Transdução de Sinais , Esferoides Celulares , Receptor Tirosina Quinase Axl
8.
Cancer Treat Rev ; 86: 102023, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32474402

RESUMO

Colorectal cancer (CRC) represents a global health problem, being one of the most diagnosed and aggressive tumors. Cetuximab and panitumumab monoclonal antibodies (mAbs) in combination with chemotherapy are an effective strategy for patients with RAS Wild Type (WT) metastatic colorectal cancer (mCRC). However, tumors are often unresponsive or develop resistance. In the last years, molecular alterations in principal oncogenes (RAS, BRAF, PI3KCA, PTEN) in the downstream pathway of the epidermal growth factor receptor (EGFR) and in other receptors (HER2, MET) that converge on MAPK-ERK signalling have been identified as novel mechanisms of resistance to anti-EGFR strategies. However, further efforts are needed to better stratify CRCs and ensure more individualized treatments. Herein, we describe the consolidated molecular drivers of resistance and the therapeutic strategies available so far, with an overview on potential biomarkers of response that could be integrated in clinical practice.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Receptores ErbB/antagonistas & inibidores , Humanos , Metástase Neoplásica , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Dig Dis ; 36(2): 130-135, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29339645

RESUMO

BACKGROUND: Mesalazine 1 g suppository/die is used for mild to moderately active ulcerative proctitis (UP). Whether addiction of Multi Matrix System (MMX) mesalazine increases the remission rate of UP and prevents proximal extension of disease is unknown. METHODS: This is a retrospective study on 116 outpatients with UP who had been treated with one of the following regimens: (1) MMX mesalazine 1.2 g/die plus mesalazine suppositories for 8 ± 2 weeks and, subsequently, MMX mesalazine 1.2 g/die plus rectal mesalazine 1 g every other day for at least 6 months; (2) mesalazine 1 g suppositories/die alone for 8 ± 2 weeks and, subsequently, rectal mesalazine 1 g every other day for 6 more months. Patients were evaluated clinically at 2 months (±2 weeks) and endoscopically at 6 months (±2 weeks). For categorical variables, Pearson chi-square test was used. RESULTS: A total of 46 of 55 patients (84%) on combined therapy and 49 of 61 patients (80%) on rectal mesalazine reached clinical remission (p > 0.05; OR 0.79, 95% CI 0.30-2.07). At 6 months follow-up, proximal extension of disease was observed in 7 of 55 (14%) patients on combined therapy and in 18 of 61 (29%) patients on rectal mesalazine alone (p < 0.05; OR 2.87, 95% CI 1.09-7.53). CONCLUSIONS: Oral MMX mesalazine plus rectal mesalazine combined treatment is associated with prevention of proximal extension of the disease compared with rectal mesalazine alone.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Mesalamina/uso terapêutico , Proctite/tratamento farmacológico , Reto/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem
10.
World J Gastroenterol ; 23(26): 4675-4688, 2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28765689

RESUMO

In the last two decades, great efforts have been made in the treatment of metastatic colorectal cancer (mCRC) due to the approval of new target agents for cytotoxic drugs. Unfortunately, a large percentage of patients present with metastasis at the time of diagnosis or relapse after a few months. The complex molecular heterogeneity of this disease is not completely understood; to date, there is a lack of predictive biomarkers that can be used to select subsets of patients who may respond to target drugs. Only the RAS-mutation status is used to predict resistance to anti-epidermal growth factor receptor agents in patients with mCRC. In this review, we describe approved targeted therapies for the management of metastatic mCRC and discuss new candidate targets on the horizon.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Antineoplásicos/farmacologia , Quimioterapia Adjuvante , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Medicina de Precisão
11.
BMC Res Notes ; 5: 533, 2012 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-23009068

RESUMO

BACKGROUND: A higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C. MATERIALS AND METHODS: Two hundred-ten consecutive patients (M/F = 140/70, range of age 35-58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18-74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent. RESULTS: 1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological. CONCLUSIONS: 1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.


Assuntos
Doença Celíaca/epidemiologia , Hepatite C Crônica/epidemiologia , Adulto , Antivirais/efeitos adversos , Autoanticorpos/sangue , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Feminino , Proteínas de Ligação ao GTP , Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/efeitos adversos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Estudos Prospectivos , Proteína 2 Glutamina gama-Glutamiltransferase , RNA Viral/sangue , Fatores de Risco , Transglutaminases/imunologia , Carga Viral
12.
J Crohns Colitis ; 6(3): 324-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22405169

RESUMO

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) of unknown aetiology. The 'hygiene hypothesis' (HH) suggests that several hygiene-related factors may have contributed to the increased incidence of IBD. The aim of the study was to evaluate risk factors for IBD related to HH in a cohort of IBD patients from the south of Italy. METHODS: We prospectively performed a one-year, questionnaire-based, case-control, multi-centre study focusing on the principal risk factors for IBD according to HH. We investigated the main surrogate markers of HH (helmintic infections and antibiotics in childhood; breastfeeding; family size/sibship;urban upbringing; personal and domestic hygiene in childhood) in UC and CD patients, in comparison with a control group of healthy subjects. In addition, the traditional risk factors for IBD were also recorded. RESULTS: The study population included 527 cases of UC, 468 CD and 562 controls. None of the surrogate risk factors of HH was significantly associated with IBD. On the contrary, the traditional risk factors confirmed their statistical significance in this IBD population. Familial aggregation: OR 4.07 for UC; OR 4.83 for CD; smoking: OR 0.38 for UC; OR 1.40 for CD; appendectomy: OR 0.28 for UC; OR 1.61 for CD. CONCLUSION: Even though risk factors associated to the HH have been proposed as a possible explanation for the increasing calendar trend of IBD incidence, their role does not appear to be statistically significant. Familial aggregation, smoking habits and appendectomy still remain the main risk factors associated with IBD.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Hipótese da Higiene , Adolescente , Adulto , Antibacterianos/uso terapêutico , Apendicectomia/efeitos adversos , Aleitamento Materno , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Colite Ulcerativa/genética , Doença de Crohn/genética , Características da Família , Feminino , Helmintíase/epidemiologia , Humanos , Higiene , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e Questionários , População Urbana , Adulto Jovem
13.
Gut ; 59(11): 1465-70, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20947881

RESUMO

BACKGROUND AND AIMS: Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori-infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin containing sequential therapy. METHODS: 375 patients who were infected with H pylori and naïve to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily +clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily +amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily +tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. RESULTS: Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9%to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. CONCLUSION: In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin containing sequential therapy.


Assuntos
Antibacterianos/administração & dosagem , Claritromicina/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Levofloxacino , Ofloxacino/administração & dosagem , Adolescente , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/economia , Claritromicina/efeitos adversos , Claritromicina/economia , Custos de Medicamentos/estatística & dados numéricos , Farmacorresistência Bacteriana , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ofloxacino/efeitos adversos , Ofloxacino/economia , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
14.
Skinmed ; 6(4): 179-85, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17618178

RESUMO

Crohn's disease (CD) is a chronic inflammatory disorder primarily affecting the lower gastrointestinal tract but potentially involving the skin, musculoskeletal system, and eyes. The origin remains unknown, although diverse etiologic agents have been proposed. Characteristic pathologic appearances include the formation of "skip" lesions (discrete regions of inflamed bowel separated by uninvolved mucosae), aphthous ulceration, and fistulation; these signs relate to the presence of an underlying granulomatous transmural inflammation. Cutaneous and oral lesions frequently occur in CD. They may be classified as specific manifestations (in particular, perianal fissures, abscesses, sinuses, and fistulae in ano) with a granulomatous noncaseating inflammation on histologic examination, and nonspecific manifestations (eg, erythema nodosum, neutrophilic dermatoses) with a nonspecific histologic pattern. The diagnosis of CD is based on clinical, endoscopic, radiologic, and histopathologic features. Therapy is mainly aimed at the control of the acute disease and prevention of relapse through the use of mesalazine, corticosteroids, immunosuppressive agents and very recently, anti-tumor necrosis factor-alpha antibodies.


Assuntos
Doença de Crohn , Mucosa/patologia , Pele/patologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/complicações , Doença de Crohn/genética , Doença de Crohn/patologia , Doença de Crohn/terapia , Predisposição Genética para Doença , Humanos , Imunossupressores/uso terapêutico , Intestinos/patologia , Boca/patologia , Proteína Adaptadora de Sinalização NOD2/genética , Fatores de Risco , Dermatopatias/etiologia
15.
Dis Colon Rectum ; 50(5): 650-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17195901

RESUMO

PURPOSE: Pathophysiology of pouchitis after ileal pouch-anal anastomosis is controversial because of the potential for development of carcinoma. Cyclooxygenase-2-derived prostaglandins may be involved in the inflammatory process and play a role in the pathogenesis of colon cancer. Vascular endothelial growth factor plays a major role in neoangiogenesis and is overexpressed in a number of gastrointestinal malignancies. The goal of this study was to evaluate the expression of cyclooxygenase-2 and vascular endothelial growth factor and to assess neoangiogenesis and epithelial cell proliferation in patients with ileal pouch-anal anastomosis. METHODS: Endoscopic biopsies were obtained from 15 patients with ileal pouch-anal anastomosis without pouchitis (10 biopsies from the ileal pouch and 10 from ileal nonpouch mucosa) and from 15 subjects with irritable bowel syndrome (10 biopsies from normal-appearing ileum and rectum). Cyclooxygenase-1, cyclooxygenase-2, and vascular endothelial growth factor messenger ribonucleic acid expression was determined by reverse transcriptase polymerase chain reaction. Cyclooxygenase-2 and vascular endothelial growth factor protein expression was evaluated by Western blot. Cyclooxygenase-2, vascular endothelial growth factor, CD34 (neoangiogenesis marker), and Ki67 (proliferation marker) mucosal localizations were evaluated by immunohistochemistry. RESULTS: Expression of cyclooxygenase-2 and vascular endothelial growth factor was increased in ileal pouch mucosa compared with ileal nonpouch mucosa, normal ileum, and rectum. Cyclooxygenase-2 and vascular endothelial growth factor immunostaining in ileal pouch mucosa was more intense in the crypt area than in the surface epithelium compared with ileal nonpouch mucosa. CD34 (neoangiogenesis marker) and Ki67 (proliferation marker) expression was increased in ileal pouch mucosa. CONCLUSIONS: Cyclooxygenase-2 and vascular endothelial growth factor are overexpressed in the ileal pouch mucosa. This is associated with increased proliferative activity and neoangiogenesis. Cyclooxygenase-2 and vascular endothelial growth factor overexpression might play a role in the pathogenesis of pouchitis.


Assuntos
Colite Ulcerativa/cirurgia , Bolsas Cólicas , Ciclo-Oxigenase 2/metabolismo , Mucosa Intestinal/metabolismo , Proctocolectomia Restauradora , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Western Blotting , Colite Ulcerativa/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Regulação para Cima
17.
J Pathol ; 207(3): 277-84, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16184519

RESUMO

Host response plays a major role in the pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of the distal stomach. Vascular endothelial growth factor (VEGF) is an important modulator of gastric mucosal repair and is overexpressed in gastric cancer. The present study sought to evaluate the expression of VEGF in the gastric mucosa of H. pylori-infected and H. pylori-non-infected dyspeptic patients. Fifteen H. pylori-infected and 15 H. pylori-non-infected dyspeptic patients were studied. Diagnosis of H. pylori infection was based on rapid urease test and histology. VEGF protein expression was assessed by western blotting. VEGF mRNA expression was assessed by RT-PCR. VEGF localization in the gastric mucosa and neo-angiogenesis were determined by immunohistochemistry. VEGF protein and mRNA expression was significantly greater in H. pylori-infected than in non-infected patients. Immunohistochemistry showed that VEGF expression was more intense in the gastric gland compartment of H. pylori-infected mucosa than in the non-infected mucosa. The increase in VEGF expression was associated with a significant increase in neo-angiogenesis as assessed by determination of CD34-positive micro-vessels. H. pylori gastritis is therefore associated with up-regulation of VEGF expression, which parallels the increased formation of blood vessels in the gastric mucosa. It is postulated that increased VEGF expression and neo-angiogenesis may contribute to H. pylori-related gastric carcinogenesis.


Assuntos
Gastrite/fisiopatologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori , Neovascularização Patológica/fisiopatologia , Fatores de Crescimento do Endotélio Vascular/análise , Idoso , Antígenos CD34/análise , Doença Crônica , Dispepsia/metabolismo , Dispepsia/microbiologia , Dispepsia/fisiopatologia , Feminino , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/metabolismo , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Regulação para Cima/fisiologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise
19.
Clin Gastroenterol Hepatol ; 1(4): 273-8, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15017668

RESUMO

BACKGROUND & AIMS: The major obstacle to 100% effective eradication of Helicobacter pylori infection is represented by antimicrobial-resistant H. pylori strains. This randomized study was designed to evaluate whether regimens based on pretreatment susceptibility testing were more effective and cost saving compared with standard nonsusceptibility testing-based therapy in the eradication of H. pylori infection. METHODS: We studied 150 consecutive H. pylori-infected dyspeptic subjects. Patients were randomly assigned to omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily for 7 days or to omeprazole 20 mg twice daily and 2 antimicrobials chosen based on susceptibility testing. H. pylori status was reevaluated 12 weeks after the end of treatment by the (13)C-urea breath test. RESULTS: Susceptibility testing-based regimens led to the following results. (1) Eradication rates were 97.3% (95% confidence interval [CI], 91.2%-99.5%) (71 of 73) and 94.6% (95% CI, 87.6%-98.3%) (71 of 75) in the per-protocol and intention-to-treat analysis, respectively. These were significantly higher (P < 0.005) than eradication rates obtained without susceptibility testing, that is, 79.4% (95% CI, 69.1%-87.6%) (58 of 73) and 77.3% (95% CI, 66.9%-85.7%) (58 of 75) in the per-protocol and intention-to-treat analyses, respectively. (2) There were savings of approximately $5 U.S. per patient compared with standard triple therapy. CONCLUSIONS: Pretreatment antimicrobial susceptibility testing is more effective and cost saving and, in health systems that confirm cost advantage, microbial susceptibility testing should be routinely used for eradication of H. pylori infection.


Assuntos
Redução de Custos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/economia , Helicobacter pylori/efeitos dos fármacos , Adulto , Amoxicilina/economia , Amoxicilina/uso terapêutico , Antibacterianos/economia , Antibacterianos/uso terapêutico , Antiulcerosos/economia , Antiulcerosos/uso terapêutico , Claritromicina/economia , Claritromicina/uso terapêutico , Análise Custo-Benefício/economia , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , Dispepsia/tratamento farmacológico , Dispepsia/economia , Dispepsia/microbiologia , Endoscopia Gastrointestinal , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Itália/epidemiologia , Masculino , Metronidazol/economia , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana/economia , Pessoa de Meia-Idade , Omeprazol/economia , Omeprazol/uso terapêutico , Prevalência , Inibidores da Bomba de Prótons , Bombas de Próton/economia , Bombas de Próton/uso terapêutico , Estatística como Assunto , Tetraciclina/economia , Tetraciclina/uso terapêutico , Resultado do Tratamento
20.
Int J Cardiol ; 83(3): 209-15; discussion 215-6, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12036523

RESUMO

Pulse ischemia-dependent submaximal increase in adenosine levels in plasma and in the interstitium is believed to mediate the phenomenon of ischemic preconditioning of the heart, by the interaction with the specific A1 and A3 receptors on myocytes. The aim of the study was to evaluate the effects of chronic oral treatment with dipyridamole (75 mg twice a day for 5 days) in coronary artery disease (CAD) patients with positive echocardiographic stress test with high-dose dipyridamole (DET). We evaluated positivity to DET, adenosine plasma levels in 12 patients treated with dipyridamole in comparison to eight patients treated with placebo. After oral administration of dipyridamole we observed a significant reduction in the number of patients positive to DET (5/12; P=0.02), a pulse increase in adenosine plasma levels (from 220+/-55 to 450+/-70 nmol/l), without any significant haemodynamic effects. Our results suggest that dipyridamole, administered orally at a low dose, but sufficient to increase adenosine plasma level, was able to prevent myocardial ischemia induced by high-dose dipyridamole echo-stress test in CAD patients.


Assuntos
Dipiridamol/administração & dosagem , Dipiridamol/efeitos adversos , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/prevenção & controle , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos , Adenosina/sangue , Administração Oral , Idoso , Dor no Peito/etiologia , Ecocardiografia sob Estresse , Teste de Esforço , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia
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