bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenomatous colonic polyps are rare in ulcerative colitis
Authors: Kitiyakara T. , Bailey D. M. , McIntyre A. S. , Gorard D. A. 
Published: April 2004

SummaryBackground : Uncertainty exists as to whether dysplastic polyps in ulcerative colitis should always be managed as dysplasia‐associated lesions/masses requiring colectomy, or whether some can be managed by polypectomy. The prevalence of non‐inflammatory polyps in ulcerative colitis is unknown.Aim : To compare dysplastic polyp occurrence in patients with ulcerative colitis and in patients without inflammatory bowel disease.Methods : The clinical, endoscopic and histological records of 150 ulcerative colitis patients (median disease duration, 10 years; 57% with pancolitis) undergoing colonoscopy were scrutinized for any polyp history. Two hundred and five patients undergoing colonoscopy for altered bowel habit, but without features suggestive of polyp presence, were used as a control group. Immunohistochemical staining of flat and polypoid mucosa for p16, β‐catenin, p53 and cyclo‐oxygenase‐2 was compared in the two groups.Results : Only six (4%) ulcerative colitis patients had ever had dysplastic polyps. Two had single adenomatous polyps proximal to the colitis segment. Of the four patients with dysplastic polyps within colitic mucosa, two were treated endoscopically, but in two the lesions were considered to be dysplasia‐associated lesions/masses and colectomy was advised. In contrast, 24 controls had at least one adenomatous polyp (χ2 = 6.7, P < 0.01). Ten (6.7%) ulcerative colitis patients and 24 (12%) control patients had metaplastic polyps (N.S.). Immunohistochemical staining was not discriminatory.Conclusion : Despite the increased cancer risk in long‐standing ulcerative colitis, adenomatous polyps arise less frequently in ulcerative colitis patients than in patients without ulcerative colitis.
Costs and efficacy of three different esomeprazole treatment strategies for long‐term management of gastro‐oesophageal reflux symptoms in primary care
Authors: Meineche‐Schmidt V. , Hauschildt Juhl H. , Østergaard J. E. , Luckow A. , Hvenegaard A. 
Published: April 2004

SummaryBackground: A prospective, open, randomized multi‐centre study with parallel group design was conducted in 155 general practice clinics, and included 1357 endoscopically uninvestigated patients with symptoms suggestive of gastro‐oesophageal reflux disease.Aim: To assess the differences in direct medical costs between a patient‐controlled on‐demand treatment strategy with esomeprazole, 20 mg daily, and general practitioner‐controlled intermittent treatment strategies with esomeprazole, 40 mg daily, for either 2 or 4 weeks. Secondary objectives were to measure other costs, total costs, patient satisfaction and time to first relapse.Methods: The primary cost analysis was carried out as a cost minimization analysis, comparing the direct medical costs in patients allocated to on‐demand treatment vs. those in patients allocated to either of the intermittent treatment strategies.Results: The mean direct medical costs were 182, 221 and 195 euros for patient‐controlled on‐demand treatment and 2 weeks and 4 weeks of general practitioner‐controlled intermittent treatment, respectively, showing no statistically significant difference. The comparable mean total costs were 211, 344 and 300 euros, i.e. significantly lower for patients treated on‐demand compared with either of the general practitioner‐controlled intermittent treatment strategies.Conclusions: The mean total costs, but not the mean direct medical costs, were higher in general practitioner‐controlled intermittent treatment strategies with esomeprazole compared with a patient‐controlled on‐demand treatment strategy.
Prospective, randomized, parallel‐group trial to evaluate the effects of lactulose and polyethylene glycol‐4000 on colonic flora in chronic idiopathic constipation
Authors: Bouhnik Y. , Neut C. , Raskine L. , Michel C. , Riottot M. , Andrieux C. , Guillemot F. , Dyard F. , Flourié B. 
Published: April 2004

SummaryBackground : Although lactulose and polyethylene glycol are osmotic laxatives widely used in the treatment of chronic constipation, no study has been conducted to compare their actions on the colonic bacterial ecosystem, which has an important influence on host health.Aim : To assess the effects of lactulose and polyethylene glycol on the composition and metabolic indices of the faecal flora in patients with chronic idiopathic constipation.Methods : Sixty‐five patients with chronic idiopathic constipation were included in this controlled, multi‐centre, randomized, parallel‐group study. Participants received lactulose (Duphalac) or polyethylene glycol‐4000 (Forlax) powders for the first week at a fixed dosage at night (20 g/day); in the second week, patients were given the option to vary the dose according to efficacy and tolerance (10–30 g/day); for the last 2 weeks, treatment was administered at a fixed dosage based on the results of the second week (10–30 g/day). Stools were recovered for bacteriological analysis at days − 1, 21 and 28.Results : Clinical efficacy and tolerance were similar with both treatments. In the lactulose group, an increase in faecal bifidobacteria counts (P = 0.04) and β‐galactosidase activity (P < 0.001) was observed from day − 1 to day 28, whereas, in the polyethylene glycol group, there was a decrease in total short‐chain fatty acids (P = 0.02), butyrate (P = 0.04), acetate (P = 0.02) and faecal bacterial mass (P = 0.001). No differences were observed in stools with regard to the following parameters: counts of Lactobacillus, clostridial spores, Bacteroides and enterobacteria, pH, biliary acids and neutral sterol concentrations.Conclusions : Both lactulose and polyethylene glycol are efficacious and well tolerated. However, although lactulose can be considered as a pre‐biotic in constipated patients, polyethylene glycol produces signs of decreased colonic fermentation in the stool.
Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis
Authors: Bloom S. , Kiilerich S. , Lassen M. R. , Forbes A. , Leiper K. , Langholz E. , Irvine E. J. , O'Morain C. , Lowson D. , Orm S. 
Published: April 2004

SummaryBackground : Heparin has anti‐inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis.Aim : To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis.Study design : A prospective, double‐blind, randomized, placebo‐controlled, multi‐centre trial comparing tinzaparin 175 anti‐Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti‐Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment.Results : One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty‐eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin‐placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo.Conclusion : This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.
Patient‐directed strategy to reduce prescribing for patients with dyspepsia in general practice: a randomized trial
Authors: Krol N. , Wensing M. , Haaijer‐Ruskamp F. , Muris J. W. M. , Numans M. E. , Schattenberg G. , van Balen J. , Grol R. 
Published: April 2004

SummaryBackground : The percentage of patients receiving long‐term treatment with acid suppressive drugs, mainly proton pump inhibitors, is higher than the prevalence of diseases that are commonly accepted as the proper indication for long‐term proton pump inhibitor use.Aim : To evaluate whether a patient‐directed intervention (direct mail) reduced the prescription of antisecretory medication for dyspepsia in general practice.Methods : A cluster‐randomized trial was performed. One hundred and thirteen chronic users of proton pump inhibitors were recruited by 20 general practitioners. An unsolicited information leaflet was sent to patients that suggested stopping or reducing the use of proton pump inhibitors. The number of patients who stopped or reduced proton pump inhibitor use was measured at 12 and 20 weeks after the intervention. Secondary outcome measures were dyspepsia symptom severity and perceived quality of life measured at 12 weeks after the intervention.Results : Fourteen of the 59 (24%) intervention group patients stopped or reduced their use of proton pump inhibitors, compared with three of the 45 (7%) control group patients (relative risk ratio 3.56; CI 95%: 1.088–11.642). Dyspepsia symptom severity and quality of life did not change.Conclusions : A simple patient‐directed intervention reduced the volume of long‐term prescriptions of proton pump inhibitors in patients with dyspepsia.
Natural history of irritable bowel syndrome
Authors: El‐Serag H. B. , Pilgrim P. , Schoenfeld P. 
Published: April 2004

SummaryBackground:  The natural history of irritable bowel syndrome is unclear, including the likelihood that these patients will be diagnosed with an alternative organic or functional gastrointestinal disorder. Understanding the stability of an irritable bowel syndrome diagnosis may limit repeated diagnostic evaluation among these patients.Methods:  The inclusion criteria included observational longitudinal studies of clinic‐based samples of adult patients with irritable bowel syndrome. Only studies published in the English language in full manuscript form were included. Literature searches, selection and review of eligible articles, and data abstraction were performed in a duplicate, independent manner.Results:  Fourteen studies met study selection criteria. In six studies with relevant information, 2–5% of irritable bowel syndrome patients were diagnosed with an alternative organic GI disorder after 6 months to 6 years of follow‐up. Long‐term follow‐up indicated that 2–18% of patients developed worse irritable bowel syndrome symptoms, approximately 30–50% of patients had unchanged symptoms, and the rest either improved or had symptoms disappear. Prior surgery (one study), higher somatic scores (one study), higher baseline anxiety (two studies), depression scores (one study) were predictive of worsening of symptoms during long‐term follow‐up.Conclusions:  Irritable bowel syndrome, a chronic disorder, is a stable diagnosis. Once initial investigations are negative, fewer than 5% are diagnosed with an alternative organic GI disorder. Repeated diagnostic evaluations of patients with recurrent or persistent symptoms similar to their baseline symptoms are not warranted.
Antigen specific correlations of cellular immune responses in human leishmaniasis suggests mechanisms for immunoregulation
Authors: ANTONELLI L R V , DUTRA W O , ALMEIDA R P , BACELLAR O , GOLLOB K J 
Published: April 2004

SUMMARYRegulation of the immune response directed against Leishmania is critical for the establishment of effective control of the disease. It is likely that some types of immune responses directed against Leishmania can lead to more severe clinical forms of leishmaniasis causing a poor control of the pathogen and/or pathology, while others lead to resolution of the infection with little pathology as in cutaneous leishmaniasis. To gain a better understanding of the possible role that subpopulations of T cells, and their associated cytokines have on disease progression and/or protective immune responses to L. braziliensis infection, a detailed study of the frequency of activated and memory T cells, as well as antigen specific, cytokine producing T cells was carried out. Following the determination of cytokine producing mononuclear cell populations in response to total Leishmania antigen (SLA), and to the recombinant antigen LACK, correlation analysis were performed between specific cytokine producing populations to identify models for cellular mechanisms of immunoregulation in human cutaneous leishmaniasis. These studies have shown: (1) a positive correlation between ex vivo CD45RO frequencies and antigen specific cytokine (IFN-gamma or IL-10) producing cells; (2) a negative correlation between ex vivo CD69 expression and the frequency of IFN-gamma producing cells; (3) a positive correlation amongst SLA specific, IFN-gamma or TNF-alpha and IL-10 producing lymphocytes with one another; and (4) a higher frequency of IL-10 producing, parasite specific (anti-SLA or anti-LACK), lymphocytes are correlated with a lower frequency of TNF-alpha producing monocytes, demonstrating an antigen specific delivery of IL-10 inducing negative regulation of monocyte activity.
High expression of interleukin-1βin the corneal epithelium of MRL/lpr mice is under the control of their genetic background
Authors: OKAMOTO M , TAKAGI M , KUTSUNA M , HARA Y , NISHIHARA M , ZHANG M C , MATSUDA T , SAKANAKA M , OKAMOTO S , NOSE M , OHASHI Y 
Published: April 2004

SUMMARYMRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop polyarthritis, sialoadenitis and dacryoadenitis, resembling rheumatoid arthritis (RA), and also corneal involvement such as keratopathy and scleritis, which is a major complication in RA patients. In this study, we found that the expression levels of IL-1β and MMP-1 mRNAs in cornea were high in both MRL/lpr and MRL/Mp-+/+ strains of mice at an age younger than when they develop any inflammatory lesions. This was not true of other inbred strains, even those bearing the lpr gene, and also not of (NZB × NZW) F1 lupus mice. There was no significant difference in the expression of IL-1α and TGFβ in cornea in these strains. Using crosses between MRL/lpr and C3H/HeJ-lpr/lpr (C3H/lpr) mice, at least the expression of IL-1β was found to be under the control of the MRL genetic background, likely with a recessive mode of inheritance. Considering that IL-1β in cornea was detected particularly in the epithelial layer, the high expression of IL-1β in cornea is most likely involved in the genetic predisposition for corneal involvement and possibly also for arthritis in an MRL strain of mice.
Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes
Authors: OKAZAWA A , KANAI T , NAKAMARU K , SATO T , INOUE N , OGATA H , IWAO Y , IKEDA M , KAWAMURA T , MAKITA S , URAUSHIHARA K , OKAMOTO R , YAMAZAKI M , KURIMOTO M , ISHII H , WATANABE M , HIBI T 
Published: April 2004

SUMMARYIntestinal epithelial cell (IEC)-derived cytokines, such as stem cell factor (SCF), interleukin (IL)-7 and IL-15 are known to be required for the development of intestinal intraepithelial lymphocytes (IELs). A newly described cytokine, IL-18, has also been shown to be produced by intestinal epithelial cells. To demonstrate the functional effects of IL-18 on human IELs, we assessed IL-18/IL-18 receptor expression in IEC/IEL and proliferation following stimulation of intestinal IELs by IL-18. IL-18 transcripts were detected both in freshly isolated human colonic epithelial cells and in various colonic epithelial cell lines. IL-18 protein was also detected by ELISA and flow cytometric analysis using antihuman IL-18-specific monoclonal antibody (MoAb). Furthermore, IELs constitutively expressed the IL-18 receptor in addition to the IL-2 and IL-7 receptors. More importantly, IL-18 augmented significant proliferative responses of IEL in combination with IL-2, IL-7 and IL-15 both in the presence and in absence of anti-CD3 MoAb. These results suggest that IL-18 might play a crucial role in the proliferation and maintenance of intestinal IELs.
Characterization of M cell formation and associated mononuclear cells during indomethacin-induced intestinal inflammation
Authors: LÜGERING A , FLOER M , LÜGERING N , CICHON C , SCHMIDT M A , DOMSCHKE W , KUCHARZIK T 
Published: April 2004

SUMMARYM cells represent an important gateway for the intestinal immune system by delivering luminal antigens through the follicle-associated epithelium to the underlying immune cells. The goal of this study was to characterize this route of antigen uptake during intestinal inflammation by characterizing M cell formation and M cell-associated lymphocytes after indomethacin challenge in rats. We demonstrated increased M cell formation as early as 12 h after a single injection of indomethacin. The elevated M cell counts were determined until day 3 and returned to basal levels after 7 days. Electron microscopic studies revealed an expansion of mononuclear cells inside the M cell pocket that were characterized predominantly as B cells, T cell receptor (TCR)αβ- and CD4-positve T cells, whereas other markers such as CD11b, CD8 and CD25 remained unchanged. In situ hybridization studies showed increased expression of interleukin (IL)-4 by lymphocytes during intestinal inflammation in the Peyer's patch follicle. These studies illuminate the relevance of M cells during intestinal inflammation and suggest that M cells derive from epithelial cells in a certain microenvironment.
Molecular analysis of B-cell differentiation in selective or partial IgA deficiency
Authors: ASANO T , KANEKO H , TERADA T , KASAHARA Y , FUKAO T , KASAHARA K , KONDO N 
Published: April 2004

SUMMARYSelective IgA deficiency is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, Iα germline transcript expression levels decreased and α circle transcripts were not detected. Stimulation with PMA and TGF-β1 up-regulated Iα germline and α circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, Iα germline, α circle transcripts and Cα mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of Iα germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.
Itraconazole antagonizes store-operated influx of calcium into chemoattractant-activated human neutrophils
Authors: STEEL H C , ANDERSON R 
Published: April 2004

SUMMARY
We have investigated the effects of itraconazole (0·1–10 µm), an antimycotic which is often used prophylactically in primary and secondary immunodeficiency disorders, including chronic granulomatous disease, on mobilization of Ca2+ and restoration of Ca2+ homeostasis following activation of neutrophils with FMLP or PAF. Transmembrane fluxes of Ca2+, as well as cytosolic concentrations of the cation were measured using a combination of spectrofluorimetric and radiometric procedures. The abruptly occurring increases in cytosolic Ca2+ following activation of the cells with either FMLP (1 µm) or PAF (200 nm) were unaffected by itraconazole. However, the subsequent store-operated influx of the cation was attenuated by itraconazole at concentrations of 0·25 µm and higher. The itraconazole-mediated inhibition of uptake of Ca2+ was not associated with detectable alterations in the intracellular concentrations of cyclic AMP, ATP or inositol triphosphate, and appeared to be compatible with antagonism of store-operated Ca2+ channels. Although a secondary property, this anti-inflammatory activity of itraconazole, if operative in vivo, may be beneficial in conditions associated with dysregulation of neutrophil Ca2+ handling such as CGD.
Genetic variants in the CCR gene cluster and spontaneous viral elimination in hepatitis C-infected patients
Authors: MASCHERETTI S , HINRICHSEN H , ROSS S , BUGGISCH P , HAMPE J , FOELSCH U R , SCHREIBER S 
Published: April 2004

SUMMARYHepatitis C virus (HCV) infection results in chronic hepatitis in more than 80% of infected patients while 10–20% of patients recover spontaneously. Host genetic factors may influence the ability to clear the virus after infection. Six single nucleotide polymorphisms and a 32 bp deletion in the genes coding for CCR3, CCR2 and CCR5 (which are all located in a cluster on chromosome 3) were investigated in 465 consecutively recruited patients infected with HCV and 370 matched controls. Genetic variants were tested for association with spontaneous viral elimination and, in the chronically infected patients, stage of fibrosis and response to antiviral therapy. The G190A polymorphism (variant allele Ile64) in the first transmembrane domain of CCR2 was under-represented in the 29 patients who had cleared the hepatitis C virus spontaneously (P = 0·018). None of the other variants in the CCR gene cluster showed association with the natural course of the infection, stage of fibrosis or response to therapy.
An imbalance of naive and memory/effector subsets and altered expression of CD38 on T lymphocytes in two girls with hyper-IgM syndrome
Authors: COSTA-CARVALHO B T , VIANA M A , BRUNIALTI M K C , KALLAS E G , SALOMAO R 
Published: April 2004

SUMMARYIn this report we evaluated CD4+ T, CD8+ T and natural killer (NK) cell counts, the levels of naive/memory subsets within the CD4+ T lymphocyte population, expression of CD38 on T lymphocytes, and CD4+ and CD8+ T cell cytokine production in two girls with hyper-IgM (HIM) syndrome. Both girls developed recurrent infections early in infancy, presenting a wide spectrum of clinical manifestations, with a strikingly different disease severity between them. CD4+ T cell counts were low in both children (patient 1: 214 cells/mm3 and patient 2: 392 cells/mm3), and the CD4/CD8 T cell ratio was 0·4 for patient 1, the patient with the more severe disease, and 1·4 for patient 2. NK cell numbers were low in patient 1 (60 cells/mm3) and borderline (286 cells/mm3) with regard to normal levels in patient 2. An imbalance of naive and memory/effector cell subsets was found in both girls, with the percentage of CD45RA+ 27+ (naive) CD4+ T lymphocytes being 5·8 and 12·4 for patients 1 and 2, respectively. Expression of CD38 on the surface of T lymphocytes was low in patient 1. Detection of intracellular interferon (IFN)-γ and tumour necrosis factor (TNF)-α in CD4+ and CD8+ T lymphocytes upon PMA-Io stimulus was preserved in both children. In conclusion, we found low numbers of CD4+ T lymphocytes and a dramatic redistribution of naive and memory/effector CD4+ T lymphocytes in two girls with non-X-linked HIM syndrome. Furthermore, we found low expression of CD38 on T lymphocytes and low numbers of NK cells in the patient with the more severe disease, indicating a possible role for these cells in the pathogenesis of this immunodeficiency.