bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: the laryngological manifestations of reflux disease; why the scepticism?
Authors: MAHIEU H. F. 
Published: July 2010

SummaryBackground  Despite increasing clinical and experimental evidence of its existence, otolaryngological manifestations of reflux disease remain controversial, concerning diagnosis as well as treatment.Aim  Proper understanding of laryngopharyngeal reflux disease (LPRD).Method  Review of literature.Results  Scepticism concerning LPRD is based upon differences between gastro‐oesophageal reflux disease and LPRD; lack of specificity and sensitivity of diagnostic tests to confirm LPRD; non‐specificity of laryngological symptoms, which are difficult to distinguish from other causes of upper respiratory tract inflammation; non‐specificity of laryngological signs in laryngoscopy, with high intra‐ and inter‐observer variability in evaluation; diagnosis of LPRD is essentially only based on a combination of diagnostic signs and symptoms, which cannot be attributed to other pathology; slow, or sometimes lack of, response of LPRD symptoms to proton pump inhibitor (PPI) medication and lack of evidence concerning efficacy of PPIs in placebo‐controlled trials.Conclusions  LPRD remains a diagnosis by exclusion and resolution of symptoms following 4‐month trial of 40 mg PPI twice daily is, for all practical purposes, considered proof of the initial diagnosis. However, non‐response does not exclude LPRD as PPIs have no influence on noxious non‐acid components of the refluxate.
Review article: inflammatory bowel disease and genetics
Authors: WEERSMA R. K. , VAN DULLEMEN H. M. , VAN DER STEEGE G. , NOLTE I. M. , KLEIBEUKER J. H. , DIJKSTRA G. 
Published: July 2010

SummaryIntroduction  Inflammatory bowel disease (IBD) comprising ulcerative colitis (UC) and Crohn's disease (CD) is multigenic disorder. Tremendous progress has been achieved in unravelling the genetic background of IBD. It has led to the discovery of mutations in NOD2 associated with ileal CD and numerous other genes have been found to be associated with IBD susceptibility.Methods  A review of the literature on the genetic background of IBD was performed.Results  It is only partially understood how mutations in NOD2 lead to CD. Mouse models, in vitro data and studies in humans offer conflicting data as regards whether there is a loss or gain of function of NOD2 in CD. Several additional genes have been identified of which only a few are currently being recognized as potential disease causing or disease modifying genes. Promising candidate genes include TLR4, MDR1, NOD1 (CARD4), DLG5 as well as the IBD5 locus including SLC22A4/5.Conclusions  Although genetic research has not yet led to a better prediction of the disease course or patient selection for medical therapy, remarkable progress has been made in the understanding of the pathogenesis of IBD. For future genetic research, accurate phenotyping of patients is very important and large population‐based cohorts are needed. Eventually, genetic research may be able to classify different disease phenotypes on a more detailed molecular basis and may provide important contributions in the development of new therapeutic approaches.
Review article: stem cell transplantation for the treatment of gastrointestinal diseases – current applications and future perspectives
Authors: AL‐TOMA A. , MULDER C. J. J. 
Published: July 2010

SummaryBackground  Haematopoietic stem cell transplantation (HSCT) can be used to cure or ameliorate a variety of non‐malignant diseases. These range from inherent defects of haematopoiesis, through metabolic diseases, to severe autoimmune diseases. The rationale for this strategy is based on the concept of immunoablation using high‐dose chemotherapy, with subsequent regeneration of naïve T‐lymphocytes derived from reinfused haematopoietic progenitor cells. Possibly the use of SCT allows the administration of high‐dose chemotherapy resulting in a prompt remission in these therapy‐refractory patients.Aim  This review highlights the major scientific developments and defines the areas of successful use of HSCT in gastrointestinal disorders and gives a perspective on possible future applications.Methods  A search in the Medline has been conducted and all relevant published data were analysed.Results  HSCT has been proved successful in treating refractory Crohn’s disease. A selected group of refractory coeliac patients having a high risk of developing enteropathy associated T‐cell lymphoma has been recently treated with promising results. In cryptogenic cirrhosis, basic research and unpublished data concerning mesenchymal SCT are encouraging.Conclusion  In refractory autoimmune gastrointestinal diseases, it seems that high‐dose chemotherapy followed by HSCT is feasible and safe and might result in long‐term improvement of disease activity.
Review article: success and failure of nucleoside and nucleotide analogues in chronic hepatitis B
Authors: LEEMANS W. F. , TER BORG M. J. , DE MAN R. A. 
Published: July 2010

SUMMARYBackground  Strong suppression of viral replication and normalization of alanine aminotransferase is feasible with nucleos(t)ide analogues. It is estimated viral replication and liver inflammation can be controlled in 90% of patients with chronic hepatitis B with the current available treatments.Aim  To review the studies currently available on the management of chronic hepatitis B with nucleos(t)ide analogues.Results  Although very potent, nucleos(t)ide analogues are not effective in every patient. Some factors are known to influence treatment outcome, but many host and viral factors are still unknown. Stopping rules have to be defined to assess treatment efficacy in an early stage and change the regimen. Discontinuation of nucleos(t)ide analogues is often followed by reactivation of HBV. Data on the risk factors for relapse are necessary in order to decide if treatment can be safely discontinued. Another major drawback of nucleos(t)ide analogues is the emergence of resistance. The efficacy of compounds for the treatment of mutant virus and the impact of cross‐resistance is largely unknown. The use of combination therapy to prevent resistance looks promising, but has to be proven.Conclusions  HBV has become a treatable disease, however much research is needed to optimize treatment for individual patients and treatment failures.
Review article: non‐alcoholic fatty liver disease in morbidly obese patients and the effect of bariatric surgery
Authors: DE RIDDER R. J. J. , SCHOON E. J. , SMULDERS J. F. , VAN HOUT G. C. M. , STOCKBRÜGGER R. W. , KOEK G. H. 
Published: July 2010

SummaryBackground  Morbid obesity is strongly associated with non‐alcoholic fatty liver disease. The effects of bariatric surgery on liver tests an histolological abnormalities after weight loss are controversial.Aim  To review the literature on the prevalence of non‐alcoholic fatty liver disease in patients with morbid obesity with respect to laboratory and histopathological parameters and the effect of weight loss on these parameters after bariatric surgery.Results  Standard liver tests do not seem to be a sensitive tool for the assessment and follow‐up of non‐alcoholic fatty liver disease in obesity. In nearly all patients with morbid obesity, histological abnormalities reflecting non‐alcoholic fatty liver disease are present. Bariatric surgery in these patients will decrease the grade of steatosis. However, there are some concerns about the effect of bariatric surgery on hepatic inflammation and fibrosis. In particular, older follow‐up studies reported negative results as opposed to more recent studies, which also showed improvement in hepatic inflammation and fibrosis. Unfortunately, most studies had limitations because of the selection of patients.Conclusion  Despite limitations in many studies, bariatric surgery seems to be a promising treatment in patients with obesity presenting with non‐alcoholic fatty liver disease.
Original article: new surgical approaches to the Klatskin tumour
Authors: VAN GULIK T. M. , DINANT S. , BUSCH O. R. C. , RAUWS E. A. J. , OBERTOP H. , GOUMA D. J. 
Published: July 2010

SummaryBackground Surgical treatment of hilar cholangiocarcinoma (Klatskin tumours) is difficult because of its central location in the liver hilum. Recent developments in surgical techniques have improved the outcome after resection.Aim To describe the surgical approaches currently applied in our centre and the impact of these strategies on outcome and criteria for resection.Methods From 1988 to 2003, 99 consecutive patients underwent resection for hilar cholangiocarcinoma. Patients were analysed for rate of R0 resections in relation with Bismuth classification. Morbidity, mortality and survival were assessed.Results The rate of hilar resections in combination with (extended) liver resections for type III and IV tumours increased from 24% to 95% in the last 5 years of the study period. Eight patients (8%) had Bismuth type IV tumours. Four of these patients underwent palliative local excisions of the hepatic duct confluence whereas the other four patients underwent hilar resection in combination with partial liver resection, resulting in microscopically radical resections. There was no mortality in this group. Overall postoperative morbidity and mortality were 68% and 10%, respectively.Conclusions An aggressive surgical approach consisting of hilar resections combined with partial liver resections including segments 1 and 4, resulted in a higher rate of R0 resections. Even Bismuth type IV tumours may be resectable depending on the biliary anatomy of the hepatic duct confluence.
Review article: the prevalence and clinical relevance of cytochrome P450 polymorphisms
Authors: WIJNEN P. A. H. M. , OP DEN BUIJSCH R. A. M. , DRENT M. , KUIPERS P. M. J. C. , NEEF C. , BAST A. , BEKERS O. , KOEK G. H. 
Published: July 2010

SummaryBackground Most drugs currently used in clinical practice are effective in only 25% to 60% of patients, while adverse drug reactions (ADRs) as a consequence of treatment are estimated to cost billions of US dollars and tens of thousands of deaths.Aim To review the prevalence and clinical significance of cytochrome P450 polymorphisms.Results The cytochrome P450 enzyme families 1–3 are responsible for 70 to 80% of all phase I dependent drug metabolisms. In 90% metabolic activity dependents on six enzymes: CYP1A2, CYP3A, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. Polymorphisms in the CYP450 gene can influence metabolic activity of the subsequent enzymes. A poor metabolizer (PM) has no or very poor enzyme activity. A consequence of PM is drug toxicity if no other metabolic route is available, or when multiple drugs are metabolized by the same cytochrome. In that case dose reduction is an option to prevent toxic effects.Conclusions In the future genotyping should be considered to identify patients who might be at risk of severe toxic responses, in order to guide appropriate individual dosage. Medical therapy should be a close cooperation between clinicians, pharmacologists and laboratory specialists, leading to reduced therapeutic errors, ADRs and health care costs.
Meta‐analysis: the use of non‐steroidal anti‐inflammatory drugs and pancreatic cancer risk for different exposure categories
Authors: CAPURSO G. , SCHÜNEMANN H. J. , TERRENATO I. , MORETTI A. , KOCH M. , MUTI P. , CAPURSO L. , DELLE FAVE G. 
Published: July 2010

SummaryBackground  A better understanding of predictors of risk for pancreatic ductal adenocarcinoma (PDAC) could inform preventive efforts against this lethal cancer. While aspirin (ASA) and non‐steroidal anti‐inflammatory drugs (NSAIDS) might protect against several gastrointestinal cancers, their role in the development of PDAC remains unclear.Aim  To conduct a systematic review and meta‐analysis on the relation between ASA/NSAIDs exposure and the risk of PDAC.Methods  We searched Pubmed, Embase, Scopus, Cochrane database of systematic reviews and reference lists of identified papers and included observational (cohort or case‐control) studies and randomized controlled trials examining exposure to ASA and/or NSAIDs and the incidence or mortality of PDAC. We defined three categories (low, intermediate, high), based on exposure duration and dose.Results  Eight studies fulfilled our inclusion criteria (four cohort, three case controls, and one randomized controlled trial studies) enrolling 6301 patients between 1971–2004; all but one study took place in the US. The pooled OR were 0.99 (0.83–1.19), 1.11 (0.84–1.47) and 1.09 (0.67–1.75) in the low, intermediate and high exposure groups respectively, with considerable heterogeneity (I2 ranging 60–86%). Sensitivity analysis by ASA use only, study design or sex did not reveal additional important information.Conclusions  This study did not show an association between ASA/NSAIDs and PDAC. The large baseline exposure in controls in North‐America may have obscured an association. There is need for additional studies, especially in Europe, to clarify this issue.
Review article: a pharmacoeconomic analysis of thrombocytopenia in chronic liver disease
Authors: BROWN R. S. 
Published: July 2010

SummaryBackground  Patients with chronic liver disease commonly experience thrombocytopenia resulting from disease or treatment. Such patients often require multiple platelet transfusions, and consequently can experience associated complications including systemic infection, iron overload, and platelet refractoriness.Aim  To discuss the limited data available on the impact of thrombocytopenia on the medical procedures and their associated costs.Results  Thrombocytopenia and its treatment can have a negative impact on outcomes and cost of therapy; costs associated with platelet transfusion can constitute a significant portion of the hospital budget. Inability to initiate or complete antiviral therapy for chronic hepatitis C infection due to low platelet counts can lead to dose reduction or discontinuation, lower efficacy, increased risks, and increased overall costs. Routine medical procedures can be complicated, prolonged, or precluded as a result of severe thrombocytopenia.Conclusion  Novel therapies can safely and effectively prevent or treat thrombocytopenia in this patient population with chronic liver disease resulting in improved quality of care and significant cost savings in addition to improving treatment outcomes and quality of life (QOL) measures.
Review article: coagulation disorders in chronic liver disease
Authors: PECK‐RADOSAVLJEVIC M. 
Published: July 2010

SummaryBackground  The liver is the site for synthesis of the vast majority of proteins that play a central role in maintaining hemostasis, by participating in the regulation of coagulation and fibrinolysis.Aim  To summarize the available data on the impact of coagulation disorders in patients with chronic liver disease.Results  Hepatocellular damage in patients with severe liver disease can lead to abnormalities in the production and function of coagulation and fibrinolytic factors, disrupting the balance between coagulation and anticoagulation systems.Conclusions  Hemostatic abnormalities (eg. impaired synthesis of clotting factors, heightened fibrinolysis, disseminated intravascular coagulation, thrombocytopenia, and platelet dysfunction) can increase the risk of bleeding in cirrhotic patients.
Review article: pharmacological approaches for the treatment of thrombocytopenia in patients with chronic liver disease and hepatitis C infection
Authors: AFDHAL N. H. , MCHUTCHISON J. G. 
Published: July 2010

SummaryBackground  Patients with chronic liver disease and hepatitis C virus (HCV) frequently experience thrombocytopenia that complicates the management of their disease. Traditional therapy for thrombocytopenia consists of platelet transfusion, which can be associated with significant safety and economic issues. Consequently, efforts have been directed toward developing novel approaches for the treatment of thrombocytopenia.Aim  To summarize the available data on the limitations of traditional therapies and the effects of novel therapies currently in clinical development for the treatment of thrombocytopenia.Results  Recent research has begun to reveal the complex mechanisms that regulate thrombopoiesis. Cytokines and growth factors, such as interleukin‐11 and thrombopoietin (TPO), play a key role in the production of platelets. A number of recent clinical studies have provided evidence that pharmacologic agents that target megakaryocyte precursors and stimulate thrombopoiesis can effectively reverse thrombocytopenia. Here, we review the regulation of thrombopoiesis, the role of TPO, and a number of novel compounds that stimulate platelet production by acting through the TPO receptor. Agents that stimulate TPO include the orally available nonpeptidic agonists eltrombopag and AKR‐501, peptidic agonists AMG‐531 and Peg‐TPOmp, and small engineered antibodies.Conclusion  Results from clinical trials with these agents in healthy subjects confirm that activation of thrombopoiesis via the TPO pathway is an effective method of stimulating platelet production. This approach may provide safer, more effective treatment for thrombocytopenia in patients with chronic liver disease. Several of these agents are currently being tested in large scale trials.
Review article: the measurement of non‐acid gastro‐oesophageal reflux
Authors: SMOUT A. J. P. M. 
Published: July 2010

SummaryBackground  Oesophageal pH monitoring has been used for three decades to study gastro‐oesophageal reflux, but it does not allow detection of non‐acid reflux episodes.Aim  To discuss the techniques by which non‐acid reflux can be measured and to evaluate the clinical relevance of such measurements.Methods  Review of the literature on non‐acid reflux monitoring.Results  Ambulatory oesophageal impedance monitoring (using a catheter with ring electrodes) allows one to detect all types of gastro‐oesophageal reflux, acid as well as non‐acid. Measurement of intra‐oesophageal bilirubin concentration also detects reflux irrespective of the pH, but only when there is bilirubin in the gastric juice and technical short‐comings limit the applicability of this technique. In untreated subjects, about 50% of reflux episodes are non‐acid (nadir pH > 4). In patients on acid inhibition, up to 95% of reflux episodes are non‐acid. Treatment with an acid inhibitor leads to a significant decrease in the incidence of acid reflux episodes, but not to a reduction in the total number of reflux episodes. This shift is associated with a shift in symptoms from heartburn to regurgitation. With impedance monitoring, the temporal association between symptoms that persist during inhibition of acid secretion and non‐acid reflux events can be demonstrated. In a proportion of patients with chronic cough, the coughing episodes are preceded by non‐acid reflux.Conclusions  Intraluminal impedance monitoring of gastro‐oesophageal reflux is a feasible technique, which provides clinically important information about the relationships between symptoms and non‐acid reflux events.
Review article: the diagnosis and management of gastroparesis
Authors: HAANS J. J. L. , MASCLEE A. A. M. 
Published: July 2010

SummaryBackground  Gastroparesis is a disorder characterized by a delay in gastric emptying of a meal in the absence of a mechanical gastric outlet obstruction.Aim  To provide an evidence based overview on diagnosis and management of gastroparesis.Methods  A PubMed search was performed using search terms including gastroparesis, gastric retention, gastric emptying, accommodation, manometry, prokinetics, antiemetics, metoclopramide, domperidone, erythromycin, botulinum toxin, gastric pacing. Relevant studies were identified and original articles and reviews were collected. References in these articles were examined for relevance and included where appropriate.Results  Diagnosis of gastroparesis is based on the presence of symptoms such as nausea, vomiting and postprandial abdominal fullness and on an objectively determined delay in gastric emptying. The true prevalence of gastroparesis is unknown. Gastric emptying can be assessed by scintigraphy and stable isotope breath tests. Management of gastroparesis consists of dietary and lifestyle measures and/or pharmacological interventions (prokinetics, antiemetics, intrapyloric botulinum toxin injection) or other interventions that focus on adequate nutrient intake either through a nasoduodenal tube, percutaneous gastrostomy or jejunostomy.Conclusions  Accurate diagnosis of gastroparesis requires an adequate protocol to measure gastric emptying. Treatment options in gastroparesis remain limited despite the disabling nature of the disorder.
Oral pathology in untreated coelic disease
Authors: CAMPISI G. , DI LIBERTO C. , IACONO G. , COMPILATO D. , DI PRIMA L. , CALVINO F. , DI MARCO V. , LO MUZIO L. , SFERRAZZA C. , SCALICI C. , CRAXÌ A. , CARROCCIO A. 
Published: July 2010

SummaryBackground Many coeliac disease patients with atypical symptoms remain undiagnosed.Aim To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis.Patients and methods One hundred and ninety‐seven coeliac disease patients and 413 controls were recruited and the oral examination was performed.Results Forty‐six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten‐free diet. Multi‐logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427–4.926) and soft tissue lesions (OR = 41.667, CI = 18.868–90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis.Conclusions The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive‐predictive value of these lesions for coeliac disease diagnosis was low.
Four‐day continuous gastric pH monitoring following anti‐acid secretory drug administration: cross‐over test to assess the early effects
Authors: SUZUKI T. , YAMAGUCHI T. , ODAKA T. , KOBAYASHI M. , SEZA A. , KOUZU T. , YOKOSUKA O. 
Published: July 2010

SummaryBackground There have been few reports that compare the effect of histamine H2‐receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) using continuous gastric pH monitoring for a long duration.Aim To assess the early effects of both drugs on gastric pH using a wireless pH monitoring system.Methods The test was conducted by a cross‐over test: 10 healthy male volunteers were administered famotidine 20 mg twice a day and lansoprazole 30 mg once a day. Monitoring of gastric pH over four consecutive days was performed using a unique method we have developed that is an elaboration of the Bravo system.Results The time to reach a pH level of 3 or more with famotidine was significantly shorter than that for lansoprazole. The pH3 holding time ratio of famotidine during the first 4 h of administration was significantly higher than that of lansoprazole. The pH3 holding time ratio on each day from day 1 to day 3 was significantly higher following lansoprazole administration compared with famotidine administration.Conclusions Famotidine was shown to act quickly in elevating gastric pH; however, lansoprazole was superior to famotidine in terms of its ability to elevate gastric pH for a long duration.