bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metronidazole and risk of acute pancreatitis: a population‐based case–control study
Authors: Nørgaard M. , Ratanajamit C. , Jacobsen J. , Skriver M. V. , Pedersen L. , Sørensen H. T. 
Published: February 2005

SummaryBackground : Use of metronidazole has been suggested to be associated with an increased risk of acute pancreatitis in case reports.Aim : To examine this issue within a proper epidemiological design.Methods : We identified 3083 incident cases of acute pancreatitis from Hospital Discharge Registries in three Danish counties and 30 830 matched population controls. From prescription databases, we extracted information on use of metronidazole with or without concomitant use of proton‐pump inhibitors and/or amoxicillin, macrolides or tetracycline.Results : Adjusted odds ratios for acute pancreatitis in study subjects who redeemed a prescription for metronidazole within 30, 31–180, or 181–365 days before hospitalization or index date among controls were 3.0 [95% confidence interval (CI): 1.4–6.6], 1.8 (95% CI: 1.2–2.9) and 1.1 (95% CI: 0.6–1.8), respectively. Among subjects with a concomitant prescription for proton‐pump inhibitors and/or amoxicillin, macrolides or tetracycline within 30, 31–180, or 181–365 days before hospitalization, or index date among controls, adjusted odds ratios were 8.3 (95% CI: 2.6–26.4), 2.7 (95% CI: 1.4–5.5), and 1.7 (95% CI: 0.6–4.8), respectively.Conclusion : Metronidazole may increase the risk of acute pancreatitis. However, the risk seems mainly to increase when metronidazole is used in combination with other drugs used for Helicobacter pylori eradication.
Grown‐up coeliac children: the effects of only a few years on a gluten‐free diet in childhood
Authors: Ciacci C. , Iovino P. , Amoruso D. , Siniscalchi M. , Tortora R. , Di Gilio A. , Fusco M. , Mazzacca G. 
Published: February 2005

SummaryAim : To evaluate clinical and psychological status of adults with childhood diagnosis of coeliac disease who were re‐exposed to gluten after only a few years and now on a gluten‐containing diet, compared with adults with recent diagnosis of coeliac disease, and adults who remained on gluten‐free diet after childhood diagnosis.Methods : A total of 195 adults with a biopsy suggestive of coeliac disease in childhood, who either had adhered to a gluten‐free diet for at least 1 year after diagnosis and now are either on gluten‐free diet (n = 110) or on gluten‐containing diet (n = 85), and adults with newly diagnosed coeliac disease (n = 165) underwent a medical check‐up.Results : Body mass index and main laboratory indices were statistically different among groups (lowest in never on gluten‐free diet, highest in gluten‐free diet). The lowest average levels of bone mineral density were found among never on gluten‐free diet patients. Prevalence of autoimmune disorders was increased in never on gluten‐free diet when compared with the transient gluten‐free diet and gluten‐free diet groups. Histology revealed villous subatrophy in all patients of never on gluten‐free diet group, in 39 of 110 patients of gluten‐free diet and in 84 of 85 of transient gluten‐free diet groups. Herpetiform dermatitis was found in three patients of gluten‐free diet, three of transient gluten‐free diet and three of never on gluten‐free diet. Dental enamel defects were found in 15 patients of transient gluten‐free diet, 43 of never on gluten‐free diet and in zero of the gluten‐free diet group. Pregnancy outcome was not significantly different between the two groups, but neonatal weight was lower and breast feeding was shorter in the never on gluten‐free diet group. Sexual habits, alcohol intake and cigarette smoking were significantly different in the never on gluten‐free diet group when compared with the other two groups.Conclusion : Gluten withdrawal in childhood partly protects coeliac adults from clinical and behavioural effects of gluten sensitivity.
Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia
Authors: Kaito Ken , Otsubo Hiroko , Usui Noriko , Yoshida Miyuki , Tanno Jyunko , Kurihara Etsuko , Matsumoto Kozue , Hirata Ryuzo , Domitsu Kenichi , Kobayashi Masayuki 
Published: February 2005

SummaryWe investigated the significance of the platelet indices, mean platelet volume (MPV), platelet size deviation width (PDW), and platelet‐large cell ratio (P‐LCR), in the diagnosis of thrombocytopenia by comparing these levels in 40 patients with hypo‐productive thrombocytopenia (aplastic anaemia; AA) and 39 patients with hyper‐destructive thrombocytopenia (immune thrombo‐cytopenia; ITP). The sensitivity and specificity of platelet indices to make a diagnosis of ITP were also compared. All platelet indices were significantly higher in ITP than in AA, and platelet indices showed sufficient sensitivity and specificity. The area under the curve (AUC) of the receiver operating characteristics curve of platelet indices was large enough to enable the diagnosis of ITP. P‐LCR and PDW had the largest AUCs, which indicated that these values were very reliable for immune thrombocytopenia. Our results suggest that these indices provide clinical information about the underlying conditions of thrombocytopenia. More attention should be paid to these indices in the diagnosis of thrombocytopenia.
Toxicity in standard melphalan–prednisone therapy among myeloma patients with renal failure – a retrospective analysis and recommendations for dose adjustment
Authors: Carlson Kristina , Hjorth Martin , Knudsen Lene Meldgaard ,   The Nordic Myeloma Study Group
Published: February 2005

SummaryHaematological and infectious toxicity was correlated to renal function in 272 newly diagnosed myeloma patients given standard dose melphalan–prednisone (MP) as initial treatment without dose adjustment for renal impairment. The glomerular filtration rate (GFR) was estimated by calculated creatinine clearance. Haematological toxicity was found to be significantly related to renal dysfunction. Haematological toxicity World Health Organization (WHO) grades 3–4 after the first MP course was seen in 18%, 28% and 36% of patients with a creatinine clearance of >50, 30–50 and <30 ml/min respectively. WHO grades 3–4 infections occurred in 6% and were not significantly related to renal function. We conclude that MP therapy can be used for initial therapy in myeloma patients with renal impairment but suggest that reduction of the melphalan dose should be considered in patients with a GFR of <30 ml/min. As only 2% of our patients had a clearance of ≤10 ml/min no conclusions can be drawn for this subgroup.
Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo
Authors: Zhou Ping , Kalakonda Nagesh , Comenzo Raymond L. 
Published: February 2005

SummaryMultiple myeloma (MM) is an incurable plasma cell malignancy marked by eventual resistance to therapy. Although arsenic trioxide (ATO) can induce apoptosis in MM cell lines, the in vivo activity of ATO in MM has been disappointing. The existence of ATO resistance mechanisms in MM can be inferred. We sought to generate hypotheses for ATO resistance by studying the gene expression profiles of MM cells that survived in culture with 0·5 μmol/l ATO. Among the 31 genes whose quantitative levels of expression (QLE) significantly increased in ATO were haem oxygenase 1 (HO‐1) and metallothionein‐2A (MT‐2A). Among the 56 genes whose QLE were significantly decreased were genes that modulate cell cycling [BTBD2 and IGFBP7 (mac25)] and sensitivity to reactive oxygen species (ROS) (BACH2). HO‐1 exerts an anti‐apoptotic effect in ischaemic cells, and MT‐2A chelates ATO intracellularly. Inhibition of HO‐1 with tin protoporphyrin enhances ROS in MM cells in ATO, and addition of N‐acetylcysteine increases MT‐2A. Protective antioxidant responses occur in MM cells exposed to ATO, and may occur in stromal cells as well, and act to quench ROS and provide diffusible anti‐apoptotic factors. They may also involve cysteine‐rich proteins that chelate ATO and modulate redox‐sensitive residues on proteins, such as nuclear factor κB and p53. A better understanding of ATO resistance will enable ATO to be combined with other agents for MM.
Pregnancy improves neutropenia in T‐cell large granular lymphocyte leukaemia
Authors: Osuji Nnenna , Matutes Estella , Dearden Claire , Catovsky Daniel 
Published: February 2005

SummaryThe effect of pregnancy on T‐cell large granular lymphocyte (LGL) leukaemia has not been previously described. We retrospectively reviewed the clinical features of three patients with T‐cell LGL leukaemia; each of them had one or more pregnancies during disease evolution. Pregnancy was associated with sustained improvement in neutrophil count and concurrent reduction in lymphocytosis. Neutropenia returned in the non‐pregnant state in all cases. A similar effect, induced by exogenous progesterone in one patient, suggests a role for progesterone in overcoming mechanisms of neutropenia in this disease. Pregnancy thus appears to have a beneficial effect on neutrophil count in T‐cell LGL leukaemia.
Airway remodelling and inflammation in sheep lungs after chronic airway challenge with house dust mite
Authors: Snibson K. J. , Bischof R. J. , Slocombe R. F. , Meeusen E. N. 
Published: February 2005

SummaryBackground
Remodelling of airway walls is a significant morbidity factor in patients suffering from chronic asthma. The relationship between airway remodelling and the inflammatory response is not well defined. Sheep have been used extensively to model airway disease in humans and represent a suitable model to examine airway remodelling.Objective
The aim of the present study was to develop a model for airway remodelling in sheep after repeated challenge with a relevant human allergen to assess the relationship of airway remodelling with inflammation.Methods
Repeated challenges of house dust mite (HDM) extract or saline (control) were administered to local lung segments of sheep for a period of 6 months. After the last challenge, lung tissues from both challenged and unchallenged lung compartments of the same sheep were compared using morphometric image analysis and (immuno) histological studies.Results
All HDM‐challenged sheep developed significant bronchoalveolar lavage eosinophilia during challenge. At the end of the challenge period, significant increases in airway collagen and airway smooth muscle content were found in a proportion (3/7) of the HDM‐challenged sheep. Hyperplasia of goblet cells and epithelial cells were observed in small bronchi and bronchioles exposed to allergen. Irrespective of airway remodelling changes, all HDM‐challenged, but no saline‐challenged sheep, displayed significant increases in mast cells in alveolar septa and airway walls of challenged lungs compared with untreated lung compartments of the same sheep. Significant increases were also observed in CD5 and γδ T cell subpopulations in all allergen‐exposed lung parenchyma.Conclusion
A proportion of atopic sheep develop typical airway remodelling changes after chronic allergen challenge, which is not directly related to the level of allergic inflammation.
Individuals with occupational allergy to detergent enzymes display a differential transcriptional regulation and cellular immune response
Authors: Lindstedt M. , Schiött Å. , Johnsen C. R. , Roggen E. , Johansson‐Lindbom B. , Borrebaeck C. A. K. 
Published: February 2005

SummaryBackground
In spite of significant safety measures, allergy to industrial enzymes remains a major concern. The increasing prevalence of occupational allergy emphasizes the need to investigate the functional properties of enzyme‐exposed dendritic cells (DCs), as DCs possess a potent ability to activate allergen‐specific T cells.Objective
This study aims at elucidating the molecular mechanisms underlying allergic immune responses to lipase, an industrial enzyme. For this purpose, we studied the effect of both hypoallergenic and wild‐type lipase on the transcriptional regulation in DCs and their stimulatory effect on memory CD4+ T cells.Methods
Five individuals with documented lipase allergy were tested for specific serum IgE. DCs from these individuals, stimulated with lipases, were assayed for their ability to affect proliferation and polarization of memory T cells. The effect of lipases on transcriptional activity in DCs was evaluated using global expression analysis.Results
Lipase‐specific IgE levels varied considerably between donors, with donor 4 exhibiting highest levels, and a potent specific CD4+ T cell recall response was demonstrated only for donor 4. No difference was detected in cytokine profile when T cells from donor 4 were co‐cultured with DCs pulsed with either hypoallergenic or wild‐type lipase, as demonstrated by high IL‐4 and IL‐13, and low IFN‐γ production. However, the lipases induced different genetic signatures in DCs from donor 4, as compared with the non‐responders.Conclusions
DCs from individuals with clinically diagnosed allergy to lipase displayed a differential response to stimulation with hypoallergenic and wild‐type lipase in vitro. Only allergen‐pulsed DCs from donor 4 were able to induce CD4+ T cell proliferation. The lipase‐specific T cells displayed a T‐helper type 2 phenotype, which was not altered by hypoallergenic lipase‐pulsed DCs. Furthermore, DCs derived from donor 4 and stimulated with either of the lipases displayed different transcriptional profiles, as compared with the other donors. These signatures represent genes of potential importance for an immunoregulatory role of DC in an ongoing allergic response.
Atopic sensitization and atopic dermatitis in Estonian and Swedish infants
Authors: Voor T. , Julge K. , Böttcher M. F. , Jenmalm M. C. , Duchén K. , Björkstén B. 
Published: February 2005

SummaryBackground
Early life events seem to have a major impact on the development of tolerance or sensitization.Objective
The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden.Methods
Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months.Results
The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%; P=0.06 and 13% vs. 24%; P=0.03), while circulating IgE antibodies were more common (39% vs. 27%; P=0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio=1.7, 95% confidence interval=1.1−2.5), but not in the Swedish infants. This may be explained by the use of broad‐spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed.Conclusions
The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad‐spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor.
Oral antihistamines for the symptom of nasal obstruction in persistent allergic rhinitis – a systematic review of randomized controlled trials
Authors: Hore I. , Georgalas C. , Scadding G. 
Published: February 2005

SummaryBackground
Oral antihistamines are recommended by a World Health Organisation working group as a first‐line pharmacological treatment in mild persistent allergic rhinitis. There is, however, uncertainty with respect to their effectiveness for a common symptom, that of nasal obstruction.Objective
To test the null hypothesis that oral antihistamines have no effect on the symptom of nasal obstruction in a clinical setting in patients with persistent allergic rhinitis.Methods
Protocol based review of double‐blind randomized controlled trials of oral antihistamine (i.e. drugs considered to act as a histamine receptor type‐1 antagonist) vs. placebo. A search was carried out for published and unpublished trials. Individuals had to be age 12 years or older (with a diagnosis confirmed by skin prick tests, IgE blood tests or nasal allergen challenge), experiencing their normal allergen exposure. A symptom score for nasal obstruction had to be recorded. Predetermined quality criteria were applied. Treating their data as 4‐point scores, a meta‐analysis was carried out for studies, which provided enough data to be pooled.Results
Meta‐analysis found a weighted mean difference of −0.52 in favour of treatment for patient‐assessed symptom scores (95% confidence interval (CI)−0.73,−0.31, P<0.00001), and of −0.33 in favour of treatment for healthcare worker assessed scores (95% CI −0.49, −0.16, P=0.0001).Conclusion
Oral antihistamines cause statistically significant improvement in the symptom of nasal obstruction in patients with persistent allergic rhinitis.
Vaccination for birch pollen allergy: comparison of the affinities of specific immunoglobulins E, G1 and G4 measured by surface plasmon resonance
Authors: Jakobsen C. G. , Bodtger U. , Poulsen L. K. , Roggen E. L. 
Published: February 2005

SummaryBackground
Allergen‐specific immunotherapy (SIT) is associated with increased levels of allergen‐specific IgG in serum. However, it is not clear to what extent qualitative changes in the allergen binding capacity of IgG may be induced as well.Objective
The purpose of this study was to investigate the influences of SIT on antibody affinity.Methods
The binding affinity of purified serum IgG1, IgG4 and IgE to the major allergen in birch (Betula verrucosa) pollen, Bet v 1, was analysed by surface plasmon resonance. The antibodies were obtained from 10 birch pollen‐allergic patients receiving SIT and from 10 patients with no SIT.Results
The patients having received SIT have a significant higher titre of anti‐Bet v 1 antibodies in their blood, but the affinity to Bet v 1 of allergen‐specific IgE, IgG1 and IgG4 does not differ between the two groups. For IgG1 and IgG4, correlations between less allergic symptoms and affinity of the antibodies were observed both in the SIT group and to a smaller extent in the non‐SIT group.Conclusion
SIT has no effect on antibody affinity of allergen‐specific IgE, IgG1 or IgG4. Allergic patients with high‐affinity IgG1 and IgG4 antibodies report less symptoms than patients with low‐affinity antibodies.
Co‐cultivation of mast cells and FcɛRIα+ dendritic‐like cells from human hip bone marrow
Authors: Kaur D. , Berger P. , Duffy S. M. , Brightling C. E. , Bradding P. 
Published: February 2005

SummaryBackground
Mast cells contribute to the pathogenesis of asthma and allergy through the release of a plethora of pro‐inflammatory mediators and cytokines. Their study is hampered by the difficult access to human tissue samples. Human mast cells have been cultured from CD34+ progenitors in the bone marrow of normal volunteers following iliac crest bone marrow biopsy but this is invasive. Hip bone marrow could provide a more convenient less invasive source of mast cell progenitors.Objective
To characterize mast cells cultured from human bone marrow obtained at routine hip surgery.Methods
Mononuclear cells were isolated from the bone marrow reamings of patients undergoing routine hip replacement surgery and were cultured with recombinant stem cell factor (SCF), IL‐6 and IL‐10. Cell surface markers were examined using flow cytometry, protease expression monitored using immunohistochemistry, histamine measured by radioenzymic assay, Ca2+ responses analysed using ratiometric Ca2+ imaging, and ion currents recorded via the patch‐clamp technique.Results
Mast cells were absent at baseline, but accounted for 65±7% of cells after 8–12 weeks of culture, equating to a mean 0.6±0.14 × 106 mast cells per culture. Fifty‐three percent of tryptase+ cells also contained chymase. The remaining cells comprised a population of large CD1a+ HLA‐DR+ and FcɛRIα+ cells, most likely dendritic cells. All mast cells expressed CD117 and the high‐affinity IgE receptor α‐chain (FcɛRIα) constitutively, and developed a Ca2+ response following IgE‐dependent activation. These cells exhibited 7.8±2.9% net IgE‐dependent histamine release, and demonstrated a similar ion channel profile to human lung mast cells. In particular, the intermediate conductance Ca2+‐activated K+ channel opened following IgE‐dependent activation.Conclusions
Mast cells grown from human hip marrow provide a rich non‐invasive source of functionally mature mast cells. In addition, this culture system may be useful for the generation of FcɛRIα+ dendritic cells.
Molecular cloning of a class IV chitinase allergen from Japanese cedar (Cryptomeria japonica) pollen and competitive inhibition of its immunoglobulin E‐binding capacity by latex C‐serum
Authors: Fujimura T. , Shigeta S. , Suwa T. , Kawamoto S. , Aki T. , Masubuchi M. , Hayashi T. , Hide M. , Ono K. 
Published: February 2005

SummaryBackground
Japanese cedar (Cryptomeria japonica) pollinosis is one of the most prevalent allergic diseases in Japan. Only three C. japonica allergens, Cry j 1, Cry j 2, and CJP‐6, have been characterized. The full IgE‐binding spectrum of C. japonica pollen allergens demonstrates that many allergens remain to be identified.Objective
The aim of this study was to characterize a novel allergen with a high frequency of IgE binding.Methods
The cDNA coding for a high‐frequency IgE‐binding protein, designated CJP‐4, was cloned from the total mRNA of C. japonica pollen. The corresponding native allergen was purified by affinity precipitation with colloidal chitin and gel chromatography. The IgE‐binding ability of purified native CJP‐4 was characterized by ELISA and ELISA inhibition.Results
The CJP‐4 cDNA encoded 281 amino acids with significant sequence homology to class IV chitinases. Purified native CJP‐4, migrated as a homogeneous 34‐kDa protein on SDS‐PAGE, revealed endochitinase activity on native PAGE. The purified protein displayed the ability to bind IgE from all patients tested (31/31) in ELISA, whereas Cry j 1 bound to IgE at a 71% frequency (22/31). Pre‐incubation with latex C‐serum completely inhibited the reaction of pooled sera IgE from patients with C. japonica pollinosis and/or latex allergy to purified CJP‐4.Conclusion
We identified CJP‐4 as a novel and fourth C. japonica chitinase allergen with high IgE‐binding frequency. The competitive IgE‐binding profile between C. japonica chitinase and latex C‐serum indicated that C. japonica chitinase should be an important pan‐allergen in C. japonica pollen.