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AIM: Non-steroidal anti-inflammatory drug (NSAID) use is widespread and associated with gastrointestinal symptoms and complications. The aims of this study were to assess (i) gastrointestinal symptoms in users of prescribed and over-the-counter (OTC) NSAIDs and (ii) proton pump inhibitor (PPI) co-prescription rates in NSAID users at increased risk for gastrointestinal complications. METHODS: Surveys were sent to a randomly selected sample of the adult Dutch general population in December 2008. Questions included demographics, gastrointestinal symptoms, medication use and comorbidity. Main outcome measure was presence of gastrointestinal symptoms. RESULTS: A total of 18,317 surveys were returned (response rate 35%), of which 16,758 surveys were eligible for analysis. Of these, 3233 participants (19%) reported NSAID use. NSAID users more frequently reported gastrointestinal symptoms than persons not using NSAIDs (33% vs. 24%, p < 0.01). Respondents who specified on prescription NSAID use (n = 683) were older, reported more comorbidity, and experienced more gastrointestinal symptoms (41%) compared with OTC users (n = 894, 33%, p < 0.01). This difference was not statistically significant after adjustment for confounders (0.99, 95% CI 0.71-1.37). In respondents with an increased gastrointestinal risk profile, PPI co-prescription rates were 51% for on prescription users and 25% for OTC users. CONCLUSIONS: Prevalence of gastrointestinal symptoms was high in both prescribed and OTC NSAID users, emphasising the side effects of both types of NSAIDs. PPI co-prescription rates in NSAID users at risk for gastrointestinal complication were low.
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Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Adulto , Anciano , Interacciones Farmacológicas , Femenino , Enfermedades Gastrointestinales/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Medicamentos sin Prescripción/efectos adversos , Medicamentos bajo Prescripción/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy volunteers, but at lower cardiovascular doses no beneficial effects were observed. AIM: To compare the prevalence of self-reported gastrointestinal symptoms between low-dose plain aspirin and ECC. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Questions about demographics, gastrointestinal symptoms in general and specific symptoms, comorbidity, and medication use including bioequivalent doses of ECC (100 mg) and plain aspirin (80 mg) were stated. We investigated the prevalence of self-reported gastrointestinal symptoms on ECC compared with plain aspirin using univariate and multivariate logistic regression analyses. RESULTS: A total of 16,715 questionnaires (32 %) were returned and eligible for analysis. Of these, 911 (5 %) respondents reported the use of plain aspirin, 633 (4 %) ECC and 15,171 reported using neither form of aspirin (91 %). The prevalence of self-reported gastrointestinal symptoms in general was higher in respondents using ECC (27.5 %) compared with plain aspirin (26.3 %), but did not differ significantly with either univariate (OR 1.06, 95 %CI 0.84-1.33), or multivariate analysis (aOR 1.08, 95 %CI 0.83-1.41). Also, none of the specific types of symptoms differed between the two aspirin formulations. CONCLUSIONS: In this large cohort representative of the general Dutch population, low-dose ECC is not associated with a reduction in self-reported gastrointestinal symptoms compared with plain aspirin.
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Usually, colorectal cancer presents with complaints in a late stage, but can be detected in an earlier stage, with better prognosis, by colonoscopy. Using colonoscopy, also precancerous tumours, adenomas, can be detected and excised, but only in a national screening programme. However primary screening with colonoscopy is too burdensome and expensive. Out of all the screening alternatives, only of the faecal occult blood tests (faeces tests) a decreased colorectal cancer mortality has been proven. It stands to reason that the new generation immunochemical faeces tests, can reduce colorectal cancer mortality more effectively, and these tests have, more than the alternatives, a good balance between efficiency, straightforwardness and costs. Recently, the Dutch National Health Council recommended to introduce nationwide colorectal cancer screening, using an immunochemical faecal occult blood test.
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Colonoscopía , Neoplasias Colorrectales/diagnóstico , Sangre Oculta , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/prevención & control , Humanos , Tamizaje MasivoRESUMEN
BACKGROUND: The cutoff of semi-quantitative immunochemical faecal occult blood tests (iFOBTs) influences colonoscopy referrals and detection rates. We studied the performance of an iFOBT (OC-Sensor) in colorectal cancer (CRC) screening at different cutoffs. METHODS: Dutch screening participants, 50-75 years of age, with average CRC risk and an iFOBT value >or=50 ng ml(-1) were offered colonoscopy. The detection rate was the percentage of participants with CRC or advanced adenomas (>or=10 mm, >or=20% villous, high-grade dysplasia). The number needed to scope (NNTScope) was the number of colonoscopies to be carried out to find one person with CRC or advanced adenomas. RESULTS: iFOBT values >or=50 ng ml(-1) were detected in 526 of 6157 participants (8.5%) and 428 (81%) underwent colonoscopy. The detection rate for advanced lesions (28 CRC and 161 with advanced adenomas) was 3.1% (95% confidence interval: 2.6-3.5%) and the NNTScope was 2.3. At 75 ng ml(-1), the detection rate was 2.7%, the NNTScope was 2.0 and the CRC miss rate compared with 50 ng ml(-1) was <5% (N=1). At 100 ng ml(-1), the detection rate was 2.4% and the NNTScope was <2. Compared with 50 ng ml(-1), up to 200 ng ml(-1) CRC miss rates remained at 16% (N=4). CONCLUSIONS: Cutoffs below the standard 100 ng ml(-1) resulted in not only higher detection rates of advanced lesions but also more colonoscopies. With sufficient capacity, 75 ng ml(-1) might be advised; if not, up to 200 ng ml(-1) CRC miss rates are acceptable compared with the decrease in performed colonoscopies.
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Neoplasias Colorrectales/diagnóstico , Sangre Oculta , Anciano , Colonoscopía , Femenino , Humanos , Inmunoquímica , Masculino , Tamizaje Masivo , Persona de Mediana EdadRESUMEN
The two major primary antibody deficiency disorders are X-linked hypogammaglobulinaemia (XLA) and common variable immunodeficiency (CVID). CVID patients have an elevated risk for gastric cancer and extra-nodal marginal zone lymphoma. Both diseases are associated with Helicobacter pylori infection. We investigated whether antibody deficiency leads to defective serum bactericidal activity against H. pylori. We also investigated the correlation with immunoglobulin (Ig)M levels and observed the terminal complement complex (TCC) activity. Sera of 13 CVID patients (four H. pylori positive), one patient with hyper-IgM syndrome, one patient with Good syndrome (both H. pylori positive), five XLA patients, four H. pylori seropositive controls, four H. pylori seronegative controls and a sample of pooled human serum (PHS) were incubated in vitro with bacterial suspensions of H. pylori for 30 min. After 72 h of culture, colony-forming units were counted. TCC formation was measured by enzyme-linked immunosorbent assay. We found that normal human serum is bactericidal for H. pylori, whereas heat-inactivated serum shows hardly any killing of H. pylori. Serum (1%) of hypogammaglobulinaemia patients has a decreased bactericidal activity against H. pylori. Helicobacter pylori-positive (HP(+)) normal individuals show more than 90% killing of H. pylori, whereas CVID patients show 35% killing (P = 0.007) and XLA patients only 19% (P = 0.003). Serum (1%) of HP(+) volunteers showed significantly better killing compared with serum of H. pylori-negative (HP(-)) volunteers (P = 0.034). No correlation between (substituted) IgG levels and serum bactericidal activity was found, but a weak correlation between total serum IgM and serum bactericidal activity was found. In conclusion, serum bactericidal activity against H. pylori is decreased in patients with hypogammaglobulinaemia. Heat treatment of the serum abolished the bactericidal capacity, indicating that complement activity is essential for the bactericidal effect.
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Agammaglobulinemia/inmunología , Actividad Bactericida de la Sangre , Infecciones por Helicobacter/inmunología , Helicobacter pylori , Infecciones Oportunistas/inmunología , Adulto , Agammaglobulinemia/complicaciones , Anciano , Recuento de Colonia Microbiana , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/inmunología , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Infecciones por Helicobacter/complicaciones , Humanos , Persona de Mediana Edad , Infecciones Oportunistas/complicaciones , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/complicaciones , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/inmunología , Adulto JovenRESUMEN
OBJECTIVES: Participation in screening should be the outcome of an informed decision. We evaluated whether invitees in the first Dutch colorectal cancer (CRC) screening programme were adequately informed after having received a detailed information leaflet. METHODS: A total of 20,623 subjects aged 50-75 years were invited to the fecal occult blood test (FOBT) screening programme. All received a detailed information leaflet by mail between May 2006 and January 2007. After two weeks, a reminder letter was sent to all invitees, accompanied by a survey on CRC and screening. RESULTS: The survey was completed by 9594 invitees (47%). Almost all responders (99%) found the leaflet clear and readable. Almost all indicated that CRC can be treated better if found early (99%). Only 20% of the responders answered all knowledge-related answers correctly. Almost half of the responders (47%) believed that a negative FOBT excludes the presence of CRC. Older age and having a positive family member for CRC were correctly identified as risk factors by 80%. CONCLUSION: This study demonstrates that although an information leaflet was reported as being clear and readable, the information provided in it was not always understood well. This suggests that other educational options should be investigated in order to improve general knowledge of CRC in screening invitees.
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Neoplasias Colorrectales/diagnóstico , Tamizaje Masivo/psicología , Sangre Oculta , Anciano , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/psicología , Conocimientos, Actitudes y Práctica en Salud , Encuestas Epidemiológicas , Humanos , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Países Bajos/epidemiología , FolletosRESUMEN
BACKGROUND: Compared with screening programs for breast and cervical cancer, reported participation rates for colorectal cancer (CRC) screening are low. The effectiveness of a screening program is strongly influenced by the participation rate. The aim of this study was to investigate the main reasons not to participate in a population-based, invitational CRC screening program. METHODS: In the Dutch study program for CRC screening, a random selection of 20 623 persons were invited received a faecal occult blood test. Of the non-participants, 500 were randomly selected and contacted for a standardized telephone interview from November 2006 to May 2007 to document the main reason not to participate. RESULTS: In total, 312 (62%) non-participants could be included for analysis. Most frequently, reported reasons for non-participation were time-related or priority-related (36%), including 'did not notice test in mailbox' (13%) and 'forgot' (8%). Other reasons were health-related issues, such as 'severe illness' (9%), or emotional reasons, such as 'family circumstances' (7%). CONCLUSIONS: The majority of the reported reasons not to participate reflect low priority for screening. Adding extra instructions and information, and addressing specific concerns through additional interventions should be considered to improve individual decision-making about participation in future CRC population-based screening programs.
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Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Promoción de la Salud , Tamizaje Masivo/estadística & datos numéricos , Sangre Oculta , Aceptación de la Atención de Salud/estadística & datos numéricos , Anciano , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Vigilancia de la Población , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Salud Pública , Mercadeo SocialRESUMEN
BACKGROUND: Results from studies conducted in the late 1980s and early 1990 s showed that gastrointestinal symptoms were common among the general population. Meanwhile, lifestyle habits have changed and important treatment options have been introduced. This might have influenced symptom prevalence. METHODS: This study aimed to describe the current prevalence of upper and lower gastrointestinal symptoms within the general population. For this purpose, a demographically representative sample of the Dutch population within the city of Nijmegen and surrounding areas was selected after careful comparison with demographic figures from a government demographic database. Participants were invited to fill in a valid self-report questionnaire about gastrointestinal symptoms and prevalence figures were calculated. RESULTS: A total of 5000 questionnaires was sent and 1616 (32%) were returned. Of these, 839 (52%) subjects reported having had upper (43%) or lower (38%) gastrointestinal symptoms in the past four weeks. The most prevalent individual symptoms reported were flatulence (47%), abdominal rumbling (40%), bloating (37%), alternating solid and loose stools (31%), belching (25%) and postprandial fullness (25%). People who smoked or used a proton pump inhibitor had an increased risk for reporting upper as well as lower gastrointestinal symptoms (OR 1.99; 95% CI 1.56 to 2.55, and OR 1.37; 95% CI 1.01 to 1.75, respectively for smoking; and OR 3.17; 95% CI 2.17 to 4.72, and OR 2.14; 95% CI 1.49 to 3.08, respectively for PPIs). CONCLUSION: Both upper and lower gastrointestinal symptoms are very common in a representative sample of a general Western population.
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Enfermedades Gastrointestinales/epidemiología , Tracto Gastrointestinal/fisiopatología , Bases de Datos como Asunto , Dispepsia/epidemiología , Dispepsia/fisiopatología , Femenino , Enfermedades Gastrointestinales/fisiopatología , Encuestas Epidemiológicas , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Prevalencia , Inhibidores de la Bomba de Protones , Encuestas y CuestionariosRESUMEN
An individual's lifetime risk of developing colorectal cancer is estimated at 5%. Currently, screening the asymptomatic population is the only way to effectively reduce mortality. Colorectal cancer screening meets prospectively defined scientific criteria for screening and is more cost-effective than existing screening programmes for cancers of the cervix and breast. Therefore, screening for colorectal cancer should be implemented.
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Neoplasias Colorrectales/diagnóstico , Tamizaje Masivo/métodos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/prevención & control , Análisis Costo-Beneficio , Humanos , Masculino , Tamizaje Masivo/economíaRESUMEN
BACKGROUND: Serotonin is associated with symptoms of the irritable bowel syndrome, its action is terminated by the serotonin transporter protein. AIM: To assess the association between a functional polymorphism in the gene encoding for activity of the serotonin transporter protein and the irritable bowel syndrome. METHODS: Meta-analysis of studies identified through a Medline, PubMed and Web of Science search, describing the prevalence of a polymorphism in the serotonin transporter gene creating long and short alleles. RESULTS: Eight eligible studies described a total of 1034 patients with the irritable bowel syndrome, and 1377 healthy controls. Presence of the short allele is not associated with an increased risk for the irritable bowel syndrome: OR 1.0; 95% CI: 0.7-1.4 for homozygous subjects, and OR 1.0; 95% CI: 0.8-1.2 for homozygous subjects and heterozygotes together. Although Caucasians and Asians had diverging genotypic frequencies, no association with the shot allele and irritable bowel syndrome was observed in subgroups: Asians OR 1.2; 95% CI: 0.9-1.6 and OR 1.1; 95% CI: 0.2-5.9; Caucasians OR 0.9; 95% CI: 0.5-1.7 and OR 0.9; 95% CI: 0.7-1.2, respectively, for homozygous subjects alone and for homozygous subjects and heterozygotes together. CONCLUSION: A genetic polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel.
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Síndrome del Colon Irritable/genética , Polimorfismo Genético/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Alelos , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , MasculinoRESUMEN
BACKGROUND AND STUDY AIM: The total number of upper gastrointestinal endoscopies is increasing, and despite guidelines for endoscopy referral for general practitioners, the proportion of patients found to have no endoscopic abnormalities is still up to 60% (and increasing). The aim of this study was to assess the association between general practitioners' referral indications and endoscopic findings. PATIENTS AND METHODS: General practitioners of patients referred for an open-access endoscopy between January 2002 and December 2004 were asked to specify the reason for referral on a specially designed form. The relative frequency of patients actually having an endoscopic abnormality was assessed for each referral indication. RESULTS: A total of 1298 people were included in the study. A relevant endoscopic abnormality was found in 48% of patients. Patients with an endoscopic abnormality were not more often referred with "alarm" symptoms or failure of empirical treatment than patients without an abnormal endoscopic finding (31% with an endoscopic abnormality vs. 30% without an endoscopic abnormality had alarm symptoms; 57% of people in both groups experienced failure of empirical treatment). Referral with alarm symptoms had a positive predictive value of 4% for cancer (prevalence 2%; P < 0.01), and referral with reflux-like symptoms had a positive predictive value of 33% for finding reflux esophagitis (prevalence 22%; P < 0.01). CONCLUSIONS: General practitioners' referral indications for open-access endoscopy did not add any relevant predictive value for endoscopic findings in comparison with what might have been expected from overall prevalence. Only alarm symptoms slightly increased the probability of finding cancer and only reflux-like symptoms slightly increased the probability of finding reflux esophagitis.
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Endoscopía Gastrointestinal , Enfermedades Gastrointestinales/diagnóstico , Derivación y Consulta , Adulto , Anciano , Endoscopía Gastrointestinal/estadística & datos numéricos , Medicina Familiar y Comunitaria , Femenino , Enfermedades Gastrointestinales/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
BACKGROUND: In previous trials, budesonide 6 mg/day was able to prolong the time to relapse in patients with quiescent Crohn's disease and budesonide 9 mg/day was effective in active disease with limited side effects. The aim of this study was to compare the effectiveness of budesonide 9 mg vs 6 mg once daily on the maintenance of remission and occurrence of adverse events. METHODS: Double-blind, randomised trial in patients with Crohn's disease in remission. Patients were randomised to receive 6 mg/day or 9 mg/day of budesonide (Budenofalk) without concomitant treatment for Crohn's disease. Endpoints were the time to relapse and relapse rates after one year. RESULTS: Seventy-six patients were randomised to 6 mg/day and 81 patients to 9 mg/day. Survival analysis showed no differences in the time to relapse. One-year relapse rates were not significantly different (6 mg group 24%; 9 mg group 19%). Any adverse event was reported in 61 and 68% of patients in the 6 mg and 9 mg groups, respectively; none of the 12 serious adverse events were drug related. CONCLUSION: The one-year relapse rates were low and not significantly different between the group of patients treated with budesonide 6 mg vs 9 mg/day. Also, time to relapse and the number of adverse events were similar in both treatment groups.
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Budesonida/administración & dosificación , Enfermedad de Crohn/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Budesonida/efectos adversos , Budesonida/uso terapéutico , Método Doble Ciego , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Prevención Secundaria , Análisis de SupervivenciaRESUMEN
BACKGROUND: Cardiovascular disease has been associated with both homocysteine and vitamin B12 levels. However, little information is available about the mutual relation in cardiovascular patients. The aim of this study was to assess the prevalence of vitamin B12 deficiency in patients with cardiovascular disease, and to study the correlation with homocysteine levels. METHODS: Blood samples were taken from 229 patients who had been admitted to the Coronary Care Unit of the Heart-Lung Centre of the Radboud University Medical Centre in Nijmegen, the Netherlands. Patient demographics and clinical characteristics were assessed from medical files. Adjusted logistic regression was used to study the associations between vitamin B12, homocysteine and ischaemic heart disease. RESULTS: In 70 patients (33%) serum vitamin B12 levels were below the lower limit of normal (<203 ng/l). Sixty-nine patients (33%) had vitamin B12 concentrations in the lower normal range (between 203 and 339 ng/l). Plasma homocysteine levels above the upper limit of normal were found in 83 out of the 229 patients (36%). Adjusted odds ratios for both vitamin B12 (0.76, 95% CI 0.44-1.30) and homocysteine (1.27, 95% CI 0.74-2.18) levels did not show a statistical association with ischaemic heart disease. No association was found between serum vitamin B12 levels and plasma homocysteine. CONCLUSION: Our data suggest that hyperhomocysteinaemia and low serum vitamin B12 concentrations are independent and cannot be used as a diagnostic tool for ischaemic heart disease. (Neth Heart J 2007;15:291-4.).
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BACKGROUND: Small intestinal malignancies in humans are rare; however, patients with coeliac disease have a relatively high risk for such tumours. Intestinal UDP-glucuronosyltransferases are phase II drug metabolism enzymes also involved in the detoxification of ingested toxins and carcinogens. As many toxins and carcinogens are ingested via food, the human gastrointestinal tract not only has an important role in the uptake of essential nutrients, but also acts as a first barrier against such harmful constituents of the food. Therefore, the gastrointestinal mucosa contains high levels of detoxification enzymes such as cytochromes-P450, glutathione S-transferases and UDP-glucuronosyltransferases. AIM: To compare the UDP-glucuronosyltransferase detoxification capacity in small intestinal mucosa of patients with coeliac disease vs. that in normal controls. METHODS: We assessed UDP-glucuronosyltransferase enzyme activities towards 4-methylumbelliferone in small intestinal biopsies of patients with coeliac disease (n = 22) and age- and sex-matched controls (n = 27). RESULTS: Small intestinal UDP-glucuronosyltransferase enzyme activity in controls was significantly higher than in patients with coeliac disease: 0.55 +/- 0.27 vs. 0.35 +/- 0.16 nmol/min mg protein, respectively (mean +/- s.d., P = 0.005). DISCUSSION: The low small intestinal UDP-glucuronosyltransferase detoxification activity in patients with coeliac disease may result in a deficient detoxification of potential carcinogens, and thus could explain in part the relatively high small intestinal cancer risk in these patients.
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Enfermedad Celíaca/metabolismo , Glucuronosiltransferasa/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Carcinógenos/metabolismo , Femenino , Glucuronosiltransferasa/deficiencia , Humanos , Himecromona/análogos & derivados , Himecromona/metabolismo , Masculino , Persona de Mediana Edad , Toxinas Biológicas/metabolismoRESUMEN
Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.
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Dolor/tratamiento farmacológico , Pancreatitis Crónica/tratamiento farmacológico , Animales , Dieta , Humanos , Estrés Oxidativo , Dolor/etiología , Pancreatitis Crónica/complicaciones , Calidad de VidaRESUMEN
BACKGROUND: Xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. Genetic variations that reduce the expression or activity of detoxifying phase II biotransformation enzymes such as the UDP-glucuronosyltransferases might be important in this respect. Recently, a UGT1A7 low detoxification activity allele, UGT1A7*3, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. OBJECTIVE: To investigate whether UGT1A7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. METHODS: Genetic polymorphisms in the UGT1A7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the Czech Republic (n = 93), Germany (n = 638), Netherlands (n = 136), and Switzerland (n = 106), and in healthy (n = 1409) and alcoholic (n = 123) controls from the same populations. Polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. In addition, 229 Dutch subjects were analysed by restriction fragment length polymorphism. RESULTS: The frequencies of UGT1A7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls. CONCLUSIONS: The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.
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Predisposición Genética a la Enfermedad , Glucuronosiltransferasa/genética , Enfermedades Pancreáticas/enzimología , Polimorfismo Genético , Adenocarcinoma/metabolismo , Adulto , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/enzimología , XenobióticosRESUMEN
We describe two patients with common variable immunodeficiency (CVID) who developed extranodal marginal zone lymphoma (formerly described as mucosa-associated lymphoid tissue lymphoma or MALT lymphoma). One patient, with documented pernicious anaemia and chronic atrophic gastritis with metaplasia, developed a Helicobacter pylori-positive extranodal marginal zone lymphoma in the stomach. Three triple regimens of antibiotics were necessary to eliminate the H. pylori, after which the lymphoma completely regressed. Patient B had an H. pylori-negative extranodal marginal zone lymphoma of the parotid gland, which remarkably regressed after treatment with clarithromycin. Reviewing the literature, we found eight cases of extranodal marginal zone lymphoma complicating CVID, but probably many more cases labelled as non-Hodgkin's lymphoma are hidden in the literature. Until more data are available on the predictive value of noninvasive screening for pathology of the stomach, we recommend endoscopy to assess the gastric status in CVID patients in order to detect these malignancies at an early stage. Elimination of H. pylori infection is the treatment of choice in Helicobacter-positive extranodal marginal zone lymphoma. The possibility of elimination failure, most probably due to frequent and prolonged exposure to antibiotics in this patient group, should be taken into account. Treatment with antibiotics in Helicobacter-negative extranodal marginal zone lymphoma must be considered.
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Inmunodeficiencia Variable Común/diagnóstico , Infecciones por Helicobacter/diagnóstico , Linfoma de Células B de la Zona Marginal/diagnóstico , Adulto , Anciano , Amoxicilina/uso terapéutico , Claritromicina/uso terapéutico , Inmunodeficiencia Variable Común/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/etiología , Helicobacter pylori/aislamiento & purificación , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/etiología , Masculino , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
AIM: Most patients treated for H. pylori infection receive empirical therapy based on epidemiological data of antibiotic resistance. However, previous European studies indicate that resistance patterns may be changing. Therefore, the aim of this study was to investigate the prevalence of primary clarithromycin and/or metronidazole resistant H. pylori strains over a six-year period (1997-2002) in a regional hospital. METHODS: All patients visiting Slingeland Hospital in Doetinchem, the Netherlands between 1997 and 2002 with a positive H. pylori culture were included in this study. Susceptibility to metronidazole and clarithromycin was determined by disk diffusion. RESULTS: Of the 1355 patients with an H. pylori positive culture, 1127 did not have a history of H. pylori eradication, 58 did, and for 170 this information was not available. Mean rates of primary resistance to metronidazole and clarithromycin were 14.4% (162/1125) and 1.0% (11/1123), respectively. Primary metronidazole resistance was stable throughout the study period and primary clarithromycin resistance showed a decreasing trend. Patients of foreign descent and from secondary care had a higher chance of harbouring primary metronidazole-resistant H. pylori (adjusted OR (95% CI) 1.75 (1.1 to 2.8), and 1.60 (1.1 to 2.2), respectively). Patients with failed H. pylori eradication had a higher chance of harbouring metronidazole-resistant H. pylori (43 vs 14%, p<0.0001) and clarithromycin-resistantH. pylori (5.3 vs 1.0%, p=0.004) than untreated patients. CONCLUSION: Primary metronidazole resistance is stableat a low level, while primary clarithromycin resistance isvirtually absent in the eastern part of the Netherlands.Therefore, triple therapy with a proton pump inhibitor,clarithromycin and amoxicillin can remain the empiricaltreatment of choice in the Netherlands.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Claritromicina/uso terapéutico , Farmacorresistencia Bacteriana , Dispepsia/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Metronidazol/uso terapéutico , Pruebas de Sensibilidad Microbiana/tendencias , Úlcera Péptica/tratamiento farmacológico , Inhibidores de la Bomba de Protones , Femenino , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Factores de TiempoRESUMEN
BACKGROUND: Recent studies have shown inconsistent results about the association between body mass index (BMI) and gastrointestinal disorders. The aim of this study was to assess the association between BMI and gastrointestinal disorders in patients referred for endoscopy. METHODS: Consecutive patients received a questionnaire about gastrointestinal symptoms prior to upper gastrointestinal endoscopy. The association between BMI and gastrointestinal disease and related symptoms was determined by adjusted logistic regression analyses. RESULTS: A total of 1023 subjects were included, 303 (35%) subjects were overweight (BMI 25 to 30 kg/m2), an additional 118 (14%) subjects were obese (BMI >30 kg/m2). Overall, 42% of the patients experienced symptoms of gastro-oesophageal reflux disease (GERD ), 70% dyspepsia and 55% lower abdominal symptoms. In obese patients the prevalence of GERD was higher (52%) compared with normal weight (44%) and overweight (44%) (ns). Reflux oesophagitis was found in 13, 17 and 19% for normal weight, overweight and obese, hiatus hernia in 7, 9 and 11% and Barrett's oesophagus in 6, 7 and 8%, respectively. CONCLUSION: More than half the patients undergoing upper gastrointestinal (GI ) endoscopy were overweight or obese. In this patient population, no relation between BMI and GI disorders and symptoms was found. However, a small but statistically insignificant trend was observed toward obesity for patients with GERD-associated symptoms.
Asunto(s)
Índice de Masa Corporal , Enfermedades Gastrointestinales/fisiopatología , Obesidad/fisiopatología , Comorbilidad , Endoscopía Gastrointestinal , Femenino , Enfermedades Gastrointestinales/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: There is much debate about the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication. The few studies investigating the influence of pre-treatment on triple and quadruple therapies did not find differences in eradication rates. However, the high eradication rates make it difficult to study factors associated with therapy failure in small populations. In order to overcome this problem we performed a meta-analysis. METHODS: The literature was searched in order to identify randomized clinical trials comparing modern triple/quadruple therapies for H. pylori eradication without pre-treatment with a proton pump inhibitor with exactly the same regimen with pre-treatment. The overall risk difference (with - without pre-treatment) was calculated by pooling the risk differences of the individual studies weighted by the inverse of their variances. RESULTS: Nine studies, investigating a total of 773 patients, were identified. There was considerable variation regarding therapy regimen and duration. Pooled eradication rates were 81.3% (312 of 384) for patients with pre-treatment and 81.2% (316 of 389) for patients without pre-treatment. The (weighted) overall risk difference was 0.1% (95% CI: -5%; 5%). CONCLUSION: Pre-treatment with a proton pump inhibitor does not influence H. pylori eradication.