bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omeprazole is more effective than cimetidine for the relief of all grades of gastro‐oesophageal reflux disease‐associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis
Authors: BATE C. M. , GREEN J. R. B. , AXON A. T. R. , MURRAY F. E. , TILDESLEY G. , EMMAS C. E. , TAYLOR M. D. 
Published: November 2003

Background: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro‐oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double‐blind study compared omeprazole and cimetidine in the treatment of GERD‐associated heartburn both in patients with symptomatic non‐ulcerative oesophagitis and in those with heartburn but without oesophagitis. Methods: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double‐blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks. Results: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment. Conclusion: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.
A new 1‐week therapy for Helicobacter pylori eradication: rani‐ tidine bismuth citrate plus two antibiotics
Authors: SAVARINO V. , MANSI C. , MELE M. R. , BISSO G. , MELA G. S. , SAGGIORO A. , CAROLI M. , VIGNERI S. , TERMINI R. , OLIVIERI A. , TOSATTO R , CELLE G. 
Published: November 2003

Background: One‐week triple regimens are currently the most recommended therapy for the eradication of Helicobacter pylori. No previous study has evaluated the efficacy of a short‐term regimen combining ranitidine bismuth citrate with two antibiotics. Methods: Seventy‐two consecutive H. pylori‐positive dyspeptic patients were recruited for this randomized, three‐centre, open, parallel‐group study. They were subdivided into two groups receiving either ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (group A) or ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s (group B) for 1 week. H. pylori infection was assessed by CLO‐test and histology on both antral and corpus biopsies before and at least 4 weeks after the end of therapy. The bacterium was considered eradicated when both tests were negative. Eradication rates and the number of side‐effects were evaluated in each group. The Chi‐squared test was used for statistical analysis. Results: One patient with only CLO‐test positivity was erroneously randomized to group B and four patients dropped out of the study (two in group A and two in group B), mainly because they refused the second endoscopy. In group A, H. pylori was eradicated in 31 of 36 patients intention‐to‐treat = 86%; 95% CI = 71–95% and (per protocol 31/34 = 91%; 95% CI = 76–98%). Side‐effects occurred in 10 patients (27%) and they were generally mild. In group B, H. pylori was eradicated in 29 of 35 patients (intention‐to‐treat = 83%; 95% CI = 66–93%; and per protocol 29/33 = 88%; 95% CI = 72–97%). Seven patients (20%) complained of modest side‐effects. There was no significant difference between the two treatment arms (P = N.S.); no severe adverse events occurred and none of the patients was withdrawn from the study because of them. Conclusions: The co‐administration of ranitidine bismuth citrate plus clarithromycin at low dosage and metronidazole in twice daily doses for 1 week is a short, effective and well‐tolerated regimen for the eradication of H. pylori. These findings should provide the impetus for large‐scale investigations.
Three‐day intravenous triple therapy is not effective for the eradication of Helicobacter pyloriinfection in patients with bleeding gastro‐duodenal ulcer
Authors: Romero‐Gómez M. , Martínez‐Delgado C. , Hergueta P. , Navarro J.‐M. , Garrido‐Serrano A. , Santos O. , Montojo C. 
Published: November 2003

SummaryAim : To test the efficacy of an ultra‐short intravenous triple therapy against Helicobacter pylori infection in patients with bleeding peptic ulcer against standard oral 1‐week triple therapy in a randomised, double‐blind prospective trial.Methods: Patients : (n = 75) with haemorrhagic peptic ulcer and H. pylori infection were randomised into: an Intravenous Group to receive omeprazole, clarithromycin and amoxicillin–clavulanic acid intravenously b.d. for 3 days followed by 7 days of oral omeprazole plus placebo of clarithromycin and amoxicillin; an Oral Group to receive intravenous omeprazole plus placebo of clarithromycin and amoxicillin–clavulanic acid followed by 7 days of oral omeprazole, clarithromycin and amoxicillin b.d. Gastric biopsies were obtained for urease test. A 13C‐urea breath test was performed to check for H. pylori eradication.Results : Intention‐to‐treat eradication was 50% (19/38) in the Intravenous Group and 78% (29/37) in the Oral Group (odds ratio 3.63; 95% confidence interval 1.32–9.94; P < 0.01; number needed to treat (NNT) = 4). Per protocol eradication was 50% (14/28) in the Intravenous Group and 86% (24/28) in the Oral Group (P < 0.005). There were no statistically significant differences in adverse events between the two treatment groups.Conclusions : An ultra‐short, 3‐day, intravenous, triple therapy containing omeprazole, clarithromycin and amoxicillin–clavulanic acid cannot be recommended as an effective eradication regimen for H. pylori infection related to haemorrhagic gastro‐duodenal ulcer.
Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre study
Authors: Bader‐Meunier Brigitte , Miélot Françoise , Tchernia Gil , Buisine Jacqueline , Delsol Georges , Duchayne Eliane , Lemerle Sophie , Leverger Guy , De Lumley Lionel , Manel Anne‐Marie , Nathanson Mireille , Plantaz Dominique , Robert Alain , Schaison Gérard , Sommelet DaniÈle , Vilmer Etienne 
Published: November 2003

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as ‘primary’ (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the four girls studied exhibited a polyclonal pattern of X‐inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues.This study suggests that some MDS in childhood can exhibit particular features such as congenital anomalies associated with MDS, bone marrow hypoplasia, polyclonality, and spontaneous remission. It emphasizes that the FAB classification is not adequate for children and addresses the question of whether these MDS are always malignant diseases.
The use of IgH fingerprinting and ASO‐dependent PCR for the investigation of residual disease (MRD) in ALL
Authors: Chim James C. S. , Coyle Luke A. , Yaxley John C. , Cole‐Sinclair Merrole F. , Cannell Paul K. , Hoffbrand Victor A. , Foroni Letizia 
Published: November 2003

In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease by conventional morphology and immunology fails to detect levels of residual disease of <1 leukaemic in 10–100 normal cells. The use of polymerase chain reaction (PCR) to exploit the diversity of the complementarity determining region (CDR) and immunoglobulin variable heavy chain (VH) family specific usage has greatly improved the sensitivity up to one leukaemic cell in 105–106 normal bone marrow cells. Here we report on a prospective study of 14 patients with ALL of B‐cell lineage by using a combined PCR approach which estimates levels of disease between 1:103 and 1:105. The sequential use of allele‐specific oligoprimer (ASO) independent tests (using framework 1, FR1 and 3, FR3 primers with a JH consensus primer, sensivity up to 1:5×103) and ASO‐dependent PCR (sensitivity up to 1:105) assays were applied to 64 bone marrow (BM) follow‐up samples in a sequential array of tests.Results presented in this study indicate high concordance of MRD among different tests for samples with level of residual disease >1:5×103. Consequently, samples positive by the FR1 and FR3 fingerprinting tests were confirmed by the more sensitive ASO‐dependent tests, as expected. However, the ASO‐dependent assays revealed levels of disease undetected by the FR1 and FR3 test. Although a higher level of sensitivity is provided by the ASO‐dependent tests, the FR1 and FR3 fingerprinting tests allow MRD investigation in patients with oligoclonal B cell proliferations, CDR3 region of size <15bp or with ASO primers unsuitable for PCR investigation on technical grounds (i.e. background signal). If a sequential order of investigation from less (e.g. FR1 and FR3 fingerprinting) to more sensitive tests (ASO‐dependent) is applied, an indirect estimate of MRD is obtained for patients with level of disease <1:103
The impact of prophylactic treatment on children with severe haemophilia
Authors: Liesner R. J. , Khair K. , Hann I. M. 
Published: November 2003

Twenty‐seven children with severe haemophilia receiving regular prophylactic factor concentrate were evaluated to examine the overall effectiveness of prophylaxis in modern haemophilia care. The median age at the start of prophylaxis was 6.2 years (range 1.3–15.9 years) and the cumulative length of follow‐up was 808 months (mean 30, range 7–76 months).Nine patients required a central venous catheter for venous access (age range 1.3–5.2 years), eight boys could cannulate themselves and in 10 the parents performed regular venepuncture. The mean dose of concentrate given at the time of study was 31.8 U/kg three times weekly (range 12.5–52.6U/kg) or 4900 U/kg/year (range 1900–8200). None developed an inhibitor on prophylaxis, though four had previously had an antibody.The median average annual number of bleeds in the 27 patients prior to prophylaxis was 14.7 (range 3.7–35.4). On prophylaxis this fell to 1.5 (range 0–12.5) (P < 0.001) and in the group as a whole the frequency of bleeds diminished in successive years on prophylaxis.All 20 children with evidence of arthropathy improved on prophylaxis and eight had reversal of chronic damage such that their joints appeared normal at the time of study. There were reductions in the need for walking aids, in hospital admissions, and in numbers of school days lost for bleeding episodes. All families feel that prophylaxis has brought about an improvement in quality of life.
Cryosupernatant as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura
Authors: ROCK G. , SHUMAK KENNETH H. , SUTTON DAVID M. C. , BUSKARD NOEL A. , NAIR RAMA C. , and the Members of the Canadian Apheresis Group  
Published: November 2003

The current established treatment of thrombotic thrombocytopenic purpura (TTP) is plasma exchange with fresh frozen plasma (FFP). With this treatment, there is a 49% response after seven exchanges and a 78% survival at 1 month. Although the exact cause of TTP is unknown, the presence of von Willebrand factor (VWF) multimers has been implicated in the disease. Accordingly, it has been suggested that cryosupernatant (plasma from which cryoprecipitate has been removed), which is relatively deficient in VWF multimers, might be an effective replacement fluid during plasma exchange.Patients from six centres were treated by plasma exchange with cryosupernatant. 18 patients who had failed a first course (average 7.7 exchanges) of plasma exchange with FFP, received a further seven exchanges with cryosupernatant. Subsequently, 40 previously untreated patients were exchanged with cryosupernatant.Of the 18 previously treated patients, 11 responded (defined as an increase in platelet count to >150 × 109/l and no neurological events) after seven exchanges and 15 (83%) of the patients were alive at 1 month. The response rate in the 40 previously untreated patients was 75% at the end of seven exchanges and 95% of the patients were alive at 1 month. These values are significantly different (P<0.05) from those reported in our earlier study and in other patients concurrently treated at the same centres with FFP when cryosupernatant was not available.Some patients who have failed to respond to plasma exchange with FFP replacement will respond to further exchange with cryosupernatant. Cryosupernatant replacement may be more effective as first‐line treatment of TTP than FFP.
Pulsed high‐dose dexamethasone in chronic autoimmune haemolytic anaemia of warm type
Authors: Meyer Oliver , Stahl Dorothea , Beckhove Philipp , Huhn Dieter , Salama Abdulgabar 
Published: November 2003

The management of patients with autoimmune haemolytic anaemia of warm type (AIHA) is often problematic. Recently, pulsed high‐dose dexamethasone (HDD) has been shown to be effective in the treatment of autoimmune thrombocytopenic purpura (AITP).In this study we treated seven patients with AIHA with HDD. The regimen recommended for treatment of refractory AITP (40 mg dexamethasone for 4 d at the beginning of each 28 d cycle) was employed in almost all cases. Prior to dexamethasone administration, haemolysis was decompensated in all seven patients. HDD was well tolerated and led to an improvement of haemolysis in all cases.
Autologous stem cell transplantation: evaluation of erythropoietic reconstitution by highly fluorescent reticulocyte counts, erythropoietin, soluble transferrin receptors, ferritin, TIBC and iron dosages
Authors: TESTA UGO , RUTELLA SERGIO , MARTUCCI ROBERT , SCAMBIA GIOVANNI , D'ONOFRIO GIUSEPPE , PIERELLI LUCA , SICA SIMONA , LUIGI PIER , PANICI BENEDETTI , MENICHELLA GIACOMO , FOTI ELVIRA , MASTROBERARDINO G. , MANCUSO SALVATORE , LEONE GIUSEPPE , PESCHLE CESARE 
Published: November 2003

The plasma concentrations of erythropoietin (Ep), soluble transferrin receptors (sTfRs), iron, total iron binding capacity (TIBC) and ferritin were monitored in five leukaemia patients undergoing autologous bone marrow stem cell transplantation (BMSCT) and in 10 lymphoma and 21 ovarian cancer patients undergoing autologous peripheral blood SCT (PBSCT); 9/21 ovarian cancer patients received recombinant human G‐CSF and Ep and six recombinant human GM‐CSF and Ep following SCT. All parameters were evaluated in relation to the kinetics of erythroid reconstitution as evaluated by haemoglobin (Hb) and reticulocyte levels [including the fraction of immature reticulocytes, also called highly fluorescent reticulocytes (HFR)].Leukaemia patients undergoing BMSCT showed only a delayed (occurring at days 35–50 after SCT) and partial RBC, neutrophil and platelet recovery, whereas all patients undergoing PBSCT exhibited a rapid (occurring at days 10–15 after SCT) and sustained haemopoietic recovery. The various levels of erythroid rescue observed among these patients markedly influenced the kinetics of the different parameters investigated: (i) in leukaemia BMSCT patients sTfRs declined following SCT and remained at low levels thereafter, whereas Ep, iron, TIBC and ferritin showed a progressive and significant increase; (ii) in the different groups of patients undergoing PBSCT: (a) sTfR levels first declined following SCT and then returned to pre‐therapy values at days 12–16, this response preceded erythropoietic recovery; (b) Ep, total iron, TIBC and ferritin showed an initial increase in the first days following SCT and then returned to pre‐therapy values.Altogether, these observations indicate that: (i) both sTfR levels and reticulocyte counts are predictive parameters of erythropoietic recovery; (ii) coordinated changes of biochemical parameters underlying iron metabolism (iron, TIBC and ferritin) accompany erythroid rescue following SCT.
Intrathecal release of pro- and anti-inflammatory cytokines during stroke
Authors: TARKOWSKI E , ROSENGREN L , BLOMSTRAND C , WIKKELSÖ C , JENSEN C , EKHOLM S , TARKOWSKI A 
Published: November 2003

SUMMARY
A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1β and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0–3, 7–9, 21–26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-α) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.
Modulation of hu/mu severe combined immunodeficient (SCID) mouse arthritis by local application of human recombinant IL-1β, IL-2 and IL-6
Authors: Kuhn H , Ermann J , Sack U 
Published: November 2003

Abstract
The contribution of interleukins produced by most inflammatory cells to chronic arthritis is not well understood. Therefore, we investigated the influence of several human recombinant interleukins (IL-1β, IL-2 and IL-6) on joint swelling, on the inflammatory process, and on serological parameters in a novel animal model of arthritis, the human/murine SCID arthritis. In this model an arthritis is induced by implanting human synovial tissue from patients with rheumatoid arthritis (RA) into the knee joint of mice with SCID. These mice tolerate the xenogeneic implant and develop a mixed human/murine pannus tissue. The interleukins were injected daily for 7 or 14 days after implantation. IL-1β led to a significant increase in joint swelling. It intensified the inflammatory process accompanied by enhanced migration of murine inflammatory cells into the knee joint. The production of human IL-6 in the transplanted tissue was stimulated through the application of IL-1β, and the serum level of human IL-6 was thus significantly higher than in controls. We could not observe a significant influence of IL-1β on the production of human IgG or IgM by the implant. The application of human IL-2 had a weak effect similar to that of IL-1β, but without statistical significance. Although IL-6 is a good marker for inflammation in RA, the application of recombined human IL-6 had no influence on the inflammatory process in this model.
IL-5 but not interferon-gamma (IFN-γ) inhibits eosinophil apoptosis by up-regulation of bcl-2 expression
Authors: Ochiai K , Kagami M , Matsumura R , Tomioka H 
Published: November 2003

Abstract
In order to determine regulatory mechanisms of eosinophil apoptosis, we examined the effect of recombinant IL-5 and interferon-gamma (IFN-γ) on eosinophil apoptosis and bcl-2 expression. rhIL-5 (2.5 ng/ml) significantly inhibited eosinophil apoptosis in 96 h in vitro culture compared with medium only-cultured eosinophils (89.4 ± 3.6% versus 31.3 ± 12.2% (mean ± s.d.); n = 7, P &lt; 0.05). Further, rhIL-5 significantly increased bcl-2 protein and mRNA expression on cultured eosinophils. A phosphorothioate antisense oligonucleotide targeted at the ATG translation initiation codon of bcl-2 (10−5 m) could significantly block the supportive effect of rhIL-5 (0.25 ng/ml) for eosinophil survival compared with sense cDNA of bcl-2 on 96 h culture (inhibition rate 28.01 ± 4.56% versus 0.07 ± 1.73%; n = 4, P &lt; 0.05). In contrast, rhIFN-γ (100 U/ml) significantly inhibited eosinophil apoptosis on 96 h in vitro culture (72.7 ± 10.5%; n = 7, P &lt; 0.05), but did not significantly up-regulate bcl-2 protein and mRNA. These results indicate that IL-5 has inhibitory effects on eosinophil apoptosis by regulation of bcl-2 expression.
Distinct δ T cell receptor repertoires in monozygotic twins concordant for coeliac disease
Authors: Holtmeier W , Rowell D L , Nyberg A , Kagnoff M F 
Published: November 2003

Abstract
One of the hallmarks of coeliac disease, both active and treated, is an increased number and proportion of γ/δ intraepithelial T lymphocytes in the small intestinal mucosa, and an increased number of γ/δ T cells in the small intestinal mucosa of coeliac disease patients has been associated with the inheritance of specific HLA class II DQ alleles. Nonetheless, the contribution of genetic factors to the development of the T cell receptor (TCR) δ repertoire in coeliac disease is not known. We have assessed the contribution of genetic factors to development of the TCR δ repertoire in coeliac disease, by characterizing the junctional diversity of TCR δ transcripts expressed in the intestine and peripheral blood of a pair of monozygotic (MZ) twins concordant for coeliac disease. TCR Vδ1, Vδ2 and Vδ3 transcripts from small intestinal and colon biopsies, and from peripheral blood mononuclear cells, were amplified by polymerase chain reaction (PCR) and the complementarity determining region (CDR)3 domains of TCR δ transcripts were analysed by denaturing PAGE and direct nucleotide sequencing. The repertoire of TCR δ transcripts and CDR3 amino acid motifs in the intestine and peripheral blood of MZ twins concordant for coeliac disease exhibited no overlap. The TCR δ repertoire in each twin was oligoclonal, and complexity of the junctional regions of their TCR δ transcripts was typical of the repertoire in healthy adults. Thus, genetically identical individuals with coeliac disease have distinct, non-overlapping TCR δ repertoires. Moreover, genetic factors that determine disease susceptibility do not appear to select for specific TCR δ sequences or CDR3 amino acid motifs.