bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lamivudine monotherapy in HBeAg‐negative chronic hepatitis B: prediction of response‐breakthrough and long‐term clinical outcome
Authors: MANOLAKOPOULOS S. , BETHANIS S. , ELEFSINIOTIS J. , KARATAPANIS S. , TRIANTOS C. , SOURVINOS G. , TOULOUMI G. , ECONOMOU M. , VLACHOGIANNAKOS J. , SPANDIDOS D. , AVGERINOS A. , TZOURMAKLIOTIS D. 
Published: February 2006

SummaryBackgroundFactors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg‐negative chronic hepatitis B have not been well defined.AimTo determine pre‐treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg‐negative chronic hepatitis B receiving long‐term lamivudine.MethodsSeventy‐nine patients, with chronic HBeAg‐negative hepatitis B, who received lamivudine for a median of 31 months were included in the study.ResultsInitial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre‐treatment serum hepatitis B virus DNA concentrations of more than 106 copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated.ConclusionsIn HBeAg‐negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 106 copies/mL is a strong predictor for breakthrough because of drug‐resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre‐existing cirrhosis.
Clinical and laboratory studies of the antacid and raft‐forming properties of Rennie alginate suspension
Authors: TYTGAT G. N. , SIMONEAU G. 
Published: February 2006

SummaryBackgroundAcid pockets at the gastro‐oesophageal junction escape buffering from meals in the stomach. Combining high‐dose antacid with alginate may therefore be of benefit in gastro‐oesophageal reflux disease.AimTo characterize the antacid and raft‐forming properties of Rennie alginate suspension (containing high‐dose antacid and alginate; Bayer Consumer Care, Bladel, the Netherlands).MethodsThe in vitro acid‐neutralizing capacity of Rennie algniate was compared with Gaviscon (Reckitt Benckiser, Slough, UK) by pH‐recorded HCl titration. Alginate raft weight formed in vitro at different pH was used to evaluate the pH dependency of raft formation with each product. A double‐blind, placebo‐controlled, randomized crossover study also compared the antacid activity of Rennie alginate vs. placebo in vivo using continuous intragastric pH monitoring in 12 healthy fasting volunteers.ResultsCompared with Gaviscon, Rennie alginate had a higher acid‐neutralizing capacity, greater maximum pH and longer duration of antacid activity in vitro. However, the two products produced comparable alginate rafts at each pH evaluated. In vivo, Rennie alginate provided rapid, effective and long‐lasting acid neutralization, with an onset of action of <5 min, and duration of action of almost 90 min.ConclusionsThe dual mode of action of Rennie alginate offers an effective treatment option for mild symptomatic gastro‐oesophageal reflux disease particularly considering recent findings regarding ‘acid pockets’.
Patients with irritable bowel syndrome in primary care appear not to be heavy healthcare utilizers
Authors: FARESJÖ Å. , GRODZINSKY E. , FOLDEVI M. , JOHANSSON S. , WALLANDER M.‐A. 
Published: February 2006

SummaryBackgroundIrritable bowel syndrome is a frequently diagnosed gastrointestinal condition in general practice. Managing this chronic condition requires a co‐ordinated effort between patient and doctor.AimTo explore the patterns of treatment and healthcare utilization of irritable bowel syndrome cases in a Swedish primary care setting.MethodsAll cases with a registered diagnosis of irritable bowel syndrome were identified retrospectively for a 5‐year period through computerized medical records at three primary healthcare centres in Sweden. Documentation of diagnosis, healthcare visits, treatments, investigations, medications, referrals, laboratory tests, mental and demographic data were retrieved from the records.ResultsOf all 723 irritable bowel syndrome patients identified, only 37% had a follow‐up appointment to their General Practitioner during the study period. For 80%, the General Practitioner initiated some treatment during the initial consultation and 75% were prescribed medication. Fibre and bulking laxatives and acid‐suppressive drugs were the most common medication. Almost a quarter was referred for complementary investigations at hospital, only 8.9% of the irritable bowel syndrome patients were referred to a specialist investigation. Laboratory investigations varied and were ordered more frequently (P = 0.05) for men.ConclusionsIrritable bowel syndrome patients appear not to be heavy utilizers of primary care and, of those who attend, the majority are managed by their General Practitioner.
Effect of hiatal hernia on proximal oesophageal acid clearance in gastro‐oesophageal reflux disease patients
Authors: EMERENZIANI S. , HABIB F. I. , RIBOLSI M. , CAVIGLIA R. , GUARINO M. P. L. , PETITTI T. , CICALA M. 
Published: February 2006

SummaryBackgroundProximal acid reflux is common in gastro‐oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton‐pump inhibitors.AimTo evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux.MethodsThirty seven consecutive gastro‐oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24‐h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis.ResultsAt videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non‐hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Δ + 2.5 min (95% confidence interval: 0.4–4.5); P < 0.02].ConclusionsThe presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro‐oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.
Review article: From gastrin to gastro‐oesophageal reflux disease – a century of acid suppression
Authors: MALFERTHEINER P. , FASS R. , QUIGLEY E. M. M. , MODLIN I. M. , MALAGELADA J. R. , MOSS S. F. , HOLTMANN G. , GOH K.‐L. , KATELARIS P. , STANGHELLINI V. , TALLEY N. J. , TYTGAT G. N. , WRIGHT N. A. 
Published: February 2006

SummaryTo commemorate Edkins’ discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro‐oesophageal reflux disease.Although initially ignored, Edkins’ observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori.Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non‐steroidal anti‐inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid‐suppressive agents.The major issue for the future resides within the epidemic of gastro‐oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century.
Decision analysis: an aid to the diagnosis of Whipple's disease
Authors: OLMOS M. , SMECUOL E. , MAURIÑO E. , BAI J. C. 
Published: February 2006

SummaryBackgroundDiagnosis of Whipple's disease, a rare systemic infection affecting predominantly the small bowel, is based on the identification of the bacterium Tropheryma whipplei.AimsTo make explicit diagnostic uncertainties in Whipple's disease through a decision analysis, considering two different clinical scenarios at presentation.MethodsUsing appropriate software, a decision tree estimated the consequences after testing different strategies for diagnosis of Whipple's disease. Probabilities and outcomes to determine the optimum expected value were based on MEDLINE search.ResultsIn patients with clinically‐predominant intestinal involvement, diagnostic strategies considering intestinal biopsy for histology (including appropriate staining) and the polymerase chain reaction testing for bacterial DNA were similarly effective. In case of failure of one procedure, the best sequential choice was a polymerase chain reaction analysis after a negative histology. Of the five strategies tested for cases with predominant focal neurological involvement, the stereotaxis cerebral biopsy evidenced the highest expected value. However, using quality‐adjusted life‐years considering the morbidity of methods, intestinal biopsy for PCR determination was the best choice.ConclusionsIn patients with Whipple's disease having predominant digestive involvement, intestinal biopsies for histology should be indicated first and, if negative, a bacterial polymerase chain reaction determination should be the next option. Although the molecular polymerase chain reaction assessment of cerebral biopsies has the highest diagnostic yield in neurological Whipple's disease, its associated morbidity means that analyses of intestinal samples are more appropriate.
Long‐term follow‐up of coeliac disease – what do coeliac patients want?
Authors: BEBB J. R. , LAWSON A. , KNIGHT T. , LONG R. G. 
Published: February 2006

SummaryBackgroundCoeliac disease affects up to 1% of the population and the British Society of Gastroenterology recommends long‐term follow‐up of these patients, although the absolute risk of complications is small.AimTo determine what proportion of patients with coeliac disease remain under specialist follow‐up and to examine patients’ perspectives on the long‐term management of coeliac disease.MethodsA questionnaire was sent to 183 patients who had a duodenal biopsy between July 1994 and July 2004 which was consistent with coeliac disease.ResultsA total of 126 (69%) patients returned their questionnaire. Patients had on average been diagnosed with coeliac disease 5.4 years earlier. Eighty‐eight percentage were trying to follow a strict gluten‐free diet. Sixty‐two percentage of patients were under regular follow‐up although this varied between hospital clinic (doctor/dietitian, 92%) and General Practitioner (8%). Most patients found at least one aspect of the hospital out‐patient clinic very useful. The preferred method of coeliac disease follow‐up was to see a dietitian with a doctor being available (P < 0.05 vs. all other options).ConclusionsRespondents to this study showed great variation in follow‐up of their coeliac disease – 38% were under no active follow‐up. Patients would prefer to see a dietitian for long‐term follow‐up.
Horse microsatellites and their amenability to comparative equid genetics
Authors: Moodley Y. , Baumgarten I. , Harley E. H. 
Published: February 2006

SummaryWe investigated the applicability of microsatellite primers, designed in horses, for use in plains and mountain zebras. Fifteen of the 20 tested horse‐isolated primer pairs reliably amplified polymorphic loci in two wild equid species. We used this information to assess whether levels of genetic variation and repeat size differed in species from which microsatellites were isolated and in closely related target species. Target equid species exhibited similar levels of genetic variation to the horse, the species from which primers were originally isolated. We show that ascertainment bias results in lower mean and modal repeat size in target species. The data also provide evidence for a bi‐directional mutational constraint in allele size across three equid species.
Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects?
Authors: Cuong Bui Tri , Binh Vu Quoc , Dai Bui , Duy Dinh Ngoc , Lovell Claire M. , Rieckmann Karl H. , Edstein Michael D. 
Published: February 2006

AimsTo evaluate the effects of gender, food and grapefruit juice on the pharmacokinetics of primaquine in healthy subjects.MethodsIn a randomized, two‐phase cross‐over study, 10 male and 10 female healthy Vietnamese subjects were administered 30 mg primaquine in the fasting state or with food, followed by administration of primaquine with grapefruit juice.ResultsThe pharmacokinetics of primaquine were comparable between male and female subjects, with geometric mean ratios of Cmax = 0.89 [95% confidence interval (CI) 0.65, 1.22] and AUC = 0.80 (95% CI 0.56, 1.15). The mean CL/F of primaquine was slightly higher in males than in females [0.52 l h−1 kg−1vs. 0.43 l h−1 kg−1, mean difference of 0.09 (95% CI –0.10, 0.28), P = 0.32]. When compared with fasting state values, food increased the geometric mean Cmax of primaquine by 26% (95% CI 12, 40) and the AUC by 14% (95% CI 3, 27). Similarly, grapefruit juice increased the geometric mean Cmax by 23% (95% CI 4, 45) and the AUC by 19% (95% CI 4, 37).ConclusionsThe disposition of primaquine was comparable between genders, suggesting no need to modify the dose of primaquine for malaria treatment or prophylaxis. Food increased the oral bioavailability of primaquine, which may lead to higher antimalarial efficacy. Grapefruit juice increased the bioavailability of primaquine, with marked interindividual differences suggesting that people should not take primaquine with grapefruit juice.
Effects of itraconazole and diltiazem on the pharmacokinetics of fexofenadine, a substrate of P‐glycoprotein
Authors: Shimizu Mikiko , Uno Tsukasa , Sugawara Kazunobu , Tateishi Tomonori 
Published: February 2006

AimsFexofenadine is a substrate of several drug transporters including P‐glycoprotein. Our objective was to evaluate the possible effects of two P‐glycoprotein inhibitors, itraconazole and diltiazem, on the pharmacokinetics of fexofenadine, a putative probe of P‐glycoprotein activityin vivo, and compare the inhibitory effect between the two in healthy volunteers.MethodsIn a randomized three‐phase crossover study, eight healthy volunteers were given oral doses of 100 mg itraconazole twice daily, 100 mg diltiazem twice daily or a placebo capsule twice daily (control) for 5 days. On the morning of day 5 each subject was given 120 mg fexofenadine, and plasma concentrations and urinary excretion of fexofenadine were measured up to 48 h after dosing.ResultsItraconazole pretreatment significantly increased mean (± SD) peak plasma concentration (Cmax) of fexofenadine from 699 (± 366) ng ml−1to 1346 (± 561) ng ml−1(95% CI of differences 253, 1040;P < 0.005) and the area under the plasma concentration‐time curve [AUC(0,∞)] from 4133 (± 1776) ng ml−1 h to 11287 (± 4552) ng ml−1 h (95% CI 3731, 10575;P < 0.0001). Elimination half‐life and renal clearance in the itraconazole phase were not altered significantly compared with those in the control phase. In contrast, diltiazem pretreatment did not affectCmax(704 ± 316 ng ml−1, 95% CI −145, 155), AUC(0, ∞) (4433 ± 1565 ng ml−1 h, 95% CI −1353, 754), or other pharmacokinetic parameters of fexofenadine.ConclusionsAlthough some drug transporters other than P‐glycoprotein are thought to play an important role in fexofenadine pharmacokinetics, itraconazole pretreatment increased fexofenadine exposure, probably due to the reduced first‐pass effect by inhibiting the P‐glycoprotein activity. As diltiazem pretreatment did not alter fexofenadine pharmacokinetics, therapeutic doses of diltiazem are unlikely to affect the P‐glycoprotein activityin vivo.
The endocrine function of adipose tissue: an update
Authors: Ronti Tiziana , Lupattelli Graziana , Mannarino Elmo 
Published: February 2006

SummaryAdipose tissue secretes bioactive peptides, termed ‘adipokines’, which act locally and distally through autocrine, paracrine and endocrine effects. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Enhanced activity of the tumour necrosis factor and interleukin 6 are involved in the development of obesity‐related insulin resistance. Angiotensinogen has been implicated in hypertension and plasminogen activating inhibitor‐1 (PAI‐1) in impaired fibrinolysis. Other adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Reducing adipose tissue mass, through weight loss in association with exercise, can lower TNF‐α and IL‐6 levels and increase adiponectin concentrations, whereas drugs such as thiazolinediones increase endogenous adiponectin production. In‐depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies designed to protect against atherosclerosis in obese patients
Physiological and catecholamine response to sympathetic stimulation in turner syndrome
Authors: Zuckerman‐Levin Nehama , Zinder Oren , Greenberg Avital , Levin Moshe , Jacob Giris , Hochberg Ze’ev 
Published: February 2006

SummaryObjective  Women with Turner syndrome have increased heart rate and high blood pressure (BP), and have been described as having high tolerance for emotional stress. We hypothesized that women with Turner syndrome have reduced catecholaminergic and physiological response to sympathetic stimulation, and that changes in BP and heart rate are related to their catecholamine response to sympathetic stimulation.Design and patients  Ten young women with Turner syndrome, age 17–34 years were the subjects of this study. Their response to sympathetic stimulation was compared to a group of 10 age‐matched healthy women.Measurements  After a period of 30 min resting, subjects and controls were subjected to an escalating series of sympathetic stimulation: orthostatic, cold pressor and exercise, and their plasma catecholamines and haemodynamic response were monitored and compared to resting levels.Results  Resting heart rate was higher in Turner syndrome patients at 83 ± 9 beats per min (bpm, mean ± SD), as compared to controls (74 ± 10 bpm, P < 0·05). Their supine BP was also higher at 122 ± 9/84 ± 6 vs. 106 ± 11/70 ± 9 mmHg (P < 0·02/< 0·02). The corresponding resting norepinephrine, but not epinephrine, was higher in Turner syndrome patients (2·54 ± 1·09 nmol/l) as compared to controls (1·69 ± 0·55 nmol/l, P < 0·02). In response to orthostatic stimulation and cold pressor test the systolic, but not the diastolic BP or heart rate, increased in Turner syndrome patients but not in the control group (P < 0·01). The change in blood catecholamine levels was comparable in both groups. Their physiological response to exercise was normal. Yet, the exercise‐induced surge of norepinephrine and epinephrine in Turner syndrome patients was lower (P < 0·02).Conclusions  Turner syndrome is associated with dysregulation of the sympathetic nervous system (SNS), leading to tachycardia and high BP, increased resting norepinephrine levels, and a greater tolerance of the cathecholamine response to exercise.
Decreased hepatic expression of PPAR‐γ coactivator‐1 in cholesterol cholelithiasis
Authors: Bertolotti M. , Gabbi C. , Anzivino C. , Mitro N. , Godio C. , De Fabiani E. , Crestani M. , Del Puppo M. , Ricchi M. , Carulli L. , Rossi A. , Loria P. , Carulli N. 
Published: February 2006

AbstractBackground  Cholesterol cholelithiasis (gallstone disease) is a common disease in the Western world. The aim of the present study was to analyze the hepatic expression of a number of nuclear receptors involved in bile acid metabolism in human cholesterol gallstone disease.Materials and methods  Surgical liver biopsies were obtained from 11 patients with untreated cholesterol cholelithiasis and nine gallstone‐free subjects; mRNA levels of cholesterol 7α‐hydroxylase (CYP7A1) and related nuclear receptors and coactivators were assayed by quantitative real‐time RT‐PCR.Results  No differences between the two groups were detected in mRNA levels of CYP7A1 and related nuclear receptors, with the exception of peroxysome proliferator‐activated receptor‐γ coactivator 1 (PGC‐1), which was significantly (P < 0·01) less expressed in gallstone subjects. Expression of PGC‐1 was linearly correlated with farnesoid X receptor (FXR) in gallstone patients (r = 0·87 on a log scale, P < 0·01), but not in control subjects; in gallstone patients PGC‐1 expression was also correlated with hepatocyte nuclear factor 4 (HNF‐4) (r = 0·78, P < 0·01).Conclusion  These findings suggest that PGC‐1 can play a role in the prevention of cholesterol gallstone disease in humans; this might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models and other coactivators. The present data might help to understand the pathophysiology and possibly focus on new therapeutical targets in cholesterol gallstone disease.