bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacokinetic effect of discontinuation of mesalazine on mercaptopurine metabolite levels in inflammatory bowel disease patients
Authors: GILISSEN L. P. L. , BIERAU J. , DERIJKS L. J. J. , BOS L. P. , HOOYMANS P. M. , VAN GENNIP A. , STOCKBRÜGGER R. W. , ENGELS L. G. J. B. 
Published: September 2005

SummaryBackground : In vitro studies suggest interactions between mesalazine (mesalamine) and thiopurines by thiopurine S‐methyltransferase (TPMT) inhibition, influencing the balance of hepatotoxic 6‐methylmercaptopurine ribonucleotide and immunosuppressive tioguanine (thioguanine) metabolites.Aim : To examine the in vivo pharmacokinetic interaction between mesalazine and mercaptopurine.Methods : A prospective study was performed in quiescent inflammatory bowel disease patients using the combination of mercaptopurine and mesalazine. Laboratory parameters, 6‐methylmercaptopurine ribonucleotide and tioguanine levels and thiopurine S‐methyltransferase activity in erythrocytes were measured at stable medication, after mesalazine discontinuation and mesalazine reintroduction, further mercaptopurine was continued.Results : Seventeen patients were participated. Mean mercaptopurine dose was 0.78 mg/kg/day and median of mesalazine dose was 3000 mg/day. After mesalazine discontinuation, mean tioguanine levels changed significantly from 262 to 209 pmol/8 × 108 red blood cell, increasing to 270 after reintroduction. Mean 6‐methylmercaptopurine ribonucleotide levels were 1422, 2149 and 1503 pmol/8 × 108 red blood cell respectively. Mean 6‐methylmercaptopurine ribonucleotide/tioguanine ratio increased significantly from 6.3 at baseline to 11.2. Mean baseline thiopurine S‐methyltransferase activity was 0.58 pmol/106 red blood cell/h and stable. All patients had wild‐type thiopurine S‐methyltransferase genotypes however, leucocyte counts were stable.Discussion : A significantly higher tioguanine levels and improving 6‐methylmercaptopurine ribonucleotide/tioguanine ratio were found during mesalazine/mercaptopurine combination. Theoretically, mesalazine inhibits thiopurine S‐methyltransferase activity. In vivo thiopurine S‐methyltransferase activity did not change, however.Conclusion : Mesalazine has synergistic effects on mercaptopurine therapy, but the mechanism is unclear. Combining these drugs may be further indication for mesalazine in inflammatory bowel disease treatment.
Polymorphisms in apoptosis genes predict response to infliximab therapy in luminal and fistulizing Crohn's disease
Authors: HLAVATY T. , PIERIK M. , HENCKAERTS L. , FERRANTE M. , JOOSSENS S. , VAN SCHUERBEEK N. , NOMAN M. , RUTGEERTS P. , VERMEIRE S. 
Published: September 2005

SummaryBackground : Infliximab treatment is effective in 70–80% of patients with refractory luminal and fistulizing Crohn's disease. The effect of infliximab is ascribed to induction of apoptosis.Aim : To study whether polymorphisms in apoptosis genes predict the response to infliximab and whether they interact with clinical predictors.Methods : Cohort of 287 consecutive patients treated with infliximab for refractory luminal (n = 204) or fistulizing (n = 83) Crohn's disease was genotyped for 21 polymorphisms in apoptosis genes. Short‐term clinical response was assessed at week 4 (luminal Crohn's disease) or 10 (fistulizing Crohn's disease) after the first infliximab infusion.Results : The response rate was 69% in luminal and 80% in fistulizing Crohn's disease. In luminal Crohn's disease, two genetic predictors were identified: (i) patients with the Fas ligand −843 CC/CT genotype (n = 135) responded in 75%, with the TT genotype (n = 21) in 38% only (P = 0.002; OR = 0.11; 95% CI: 0.08–0.56). (ii) Patients with the caspase‐9 93 TT (n = 9) genotype all responded, in contrast with 67% (n = 147) with the CC and CT genotype (P = 0.04; OR = 1.50; 95% CI: 1.34–1.68). Concomitant azathioprine/mercaptopurine therapy overcame the effect of unfavourable genotypes. In the fistulizing Crohn's disease cohort, the same Fas ligand −843 CC/CT genotype was the only predictor of response (P = 0.002; OR = 1.66; 95% CI: 1.21–2.29), interacting with caspase‐9 93 polymorphism but not with azathioprine/mercaptopurine.Conclusion : We observed that polymorphisms in FasL/Fas system and caspase‐9 influence the response to infliximab in luminal and fistulizing Crohn's disease. The strongest association was seen between the Fas ligand −843 TT genotype and non‐response. Concomitant mercaptopurine/azathioprine therapy, however, was able to overcome the effect of unfavourable genotypes in luminal disease.
Treatment of patients with heartburn without endoscopic evaluation: on‐demand treatment after effective continuous administration of lansoprazole 15 mg
Authors: BIGARD M. A. , GENESTIN E. 
Published: September 2005

SummaryBackground : Relapse is frequent after initial treatment for gastro‐oesophageal reflux. An alternative strategy to intermittent or continuous therapy may be on‐demand treatment.Aim : To compare the efficacy and safety of on‐demand lansoprazole 15 mg and placebo treatment in patients with gastro‐oesophageal reflux.Methods : This was a multicentre, randomized, double‐blind study in two parallel groups of patients. In the acute study phase, all included patients (n = 203) were treated with lansoprazole 15 mg (once per day) for 4 weeks. At week 4, asymptomatic patients entered the 6‐month, on‐demand, follow‐up phase and were randomized to receive either lansoprazole 15 mg (once per day) or placebo.Results : A higher percentage of patients in the lansoprazole group completed the 6‐month follow‐up than in the placebo group [81% vs. 61% (P = 0.003)]. Only 16% of patients in the lansoprazole group discontinued the study for insufficient control of heartburn vs. 28% in the placebo group (P = 0.046). The mean daily intake in patients who completed the study was 1–5 capsules/day in the lansoprazole 15 mg group.Conclusions : On‐demand treatment with lansoprazole 15 mg in symptomatic patients after short‐term, continuous treatment is a promising therapeutic alternative to intermittent and continuous treatment to maintain heartburn control in patients with gastro‐oesophageal reflux.
The association between admission for poisoning with paracetamol or other weak analgesics and subsequent admission for psychiatric disorder: a Danish nationwide case–control study
Authors: JEPSEN P. , QIN P. , NØRGÅRD B. , AGERBO E. , MORTENSEN P. B. , VILSTRUP H. , SØRENSEN H. T. 
Published: September 2005

SummaryBackground : Many cases of paracetamol poisoning are with suicidal intent, but the association between paracetamol poisoning and subsequent psychiatric disorder is unknown.Aim : To examine the association between poisoning with paracetamol or other weak analgesics and subsequent psychiatric disorder.Methods : The study was set in a nested case–control design and based on nationwide Danish registers. We identified all patients diagnosed with schizophrenia, affective disorder or eating disorder in 1994–1998 and matched population controls. We estimated the relative risk of these psychiatric disorders after admission for paracetamol or nonparacetamol poisoning, adjusting for income, employment and marital status.Results : We included 12 603 cases with psychiatric disorder, and 1.2% had a diagnosis of poisoning compared with 0.2% of the 252 060 matched population controls. Compared with those with no diagnoses of weak analgesic poisoning, the risk of schizophrenia increased 3.9‐fold after paracetamol poisoning, and 2.0‐fold after nonparacetamol poisoning. The risk of affective disorder increased 12.2‐fold after paracetamol poisoning and 2.6‐fold after nonparacetamol poisoning. The risk of eating disorder increased 5.0‐fold after paracetamol poisoning, and 2.2‐fold after nonparacetamol poisoning. The risk of a diagnosis of psychiatric disorder was very high immediately after poisoning and remained increased for more than 10 years.Conclusions : Paracetamol poisoning is a strong risk marker for psychiatric disorder, particularly affective disorders.
Haematopoietic stem cell transplantation for Shwachman–Diamond disease: a study from the European Group for blood and marrow transplantation
Authors: Cesaro Simone , Oneto Rosi , Messina Chiara , Gibson Brenda E. , Buzyn Agnes , Steward Colin , Gluckman Eliane , Breddius Robbert , Boogaerts Marc , Vermylen Christiane , Veys Paul , Marsh Judith , Badell Isabel , Michel Gerard , Güngör Tayfun , Niethammer Dietrich , Bordigoni Pierre , Oswald Cecilia , Favre Claudio , Passweg Jakob , Dini Giorgio ,   the EBMT Severe Aplastic Anaemia and Paediatric Diseases Working Party
Published: September 2005

SummaryThis report assessed the results of allogeneic stem cell transplantation (allo‐SCT) in 26 patients with Shwachman–Diamond disease (SDS) and severe bone marrow abnormalities. The conditioning regimen was based on busulphan (54%), total body irradiation (23%), fludarabine (15%) or other chemotherapy combinations (8%). Standard prevention of graft versus host disease (GVHD) with ciclosporin ± methotrexate was adopted in 54% of the patients whilst in vivo or in vitro T‐cell depletion was used in 17 and four patients respectively. Neutrophil and platelet engraftment were achieved in 21 (81%) and 17 (65%) of 26 patients after a median time of 18 days and 29 days respectively. The incidence of grade III and IV acute GVHD was 24% and of chronic GVHD 29%. Nine patients died after a median time of 70 d, post‐SCT. After a median follow‐up of 1·1 years, the transplant‐related mortality was 35·5% (95% CI 17–54) whilst the overall survival was 64·5% (95% CI 45·7–83·2). Allo‐SCT was found to be successful in more than half of SDS patients with severe bone marrow dysfunction. Further improvements would be anticipated by a better definition of the optimum time in the course of disease to transplant and by the adoption of less toxic conditioning regimens.
Epidemiology and outcome of infections due to Aspergillus terreus: 10‐year single centre experience
Authors: Lass‐Flörl Cornelia , Griff Katharina , Mayr Astrid , Petzer Andreas , Gastl Günter , Bonatti Hugo , Freund Martin , Kropshofer Gabriele , Dierich Manfred P. , Nachbaur David 
Published: September 2005

Summary Aspergillus terreus, a less common pathogen, appears to be an emerging cause of infection at our institution, the Medical University Hospital of Innsbruck. Thus the epidemiology and outcome of A. terreus infections over the past 10 years was assessed. We analysed 67 cases of proven invasive aspergillosis (IA) according to the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria, investigated antifungal susceptibility of amphotericin B (AMB), voriconazole and caspofungin and performed molecular typing of A. terreus. Patients with proven IA caused by A. terreus (n = 32) and non‐A. terreus (n = 35) were evaluated. The two groups were comparable in terms of age, gender, underlying disease, antifungal prophylaxis and duration of neutropenia (P > 0·05). Leukaemia was the most common underlying malignancy. Fungal dissemination occurred in 63% of the patients. Aspergillus terreus infections were associated with a lower response rate to AMB therapy (20%), compared with 47% for patients with non‐A. terreus infections (P < 0·05). In vitro, A. terreus was found to be resistant to AMB and molecular typing discriminated between patients isolates, showing a high strain diversity with 26 distinct types (I‐XXVI) identified by combination of three primers. Aspergillus terreus infections displayed evidence of AMB resistance in vitro and in vivo and were associated with a high rate of dissemination and poor outcome; A. terreus causes systemic infections of endemic character in Tyrol, Austria. The onset of A. terreus infection depends not on the degree of immunosuppression but on environmental Aspergillus spp. exposure.
A comparison of computerised strain gauge plethysmography with D‐dimer testing in screening for deep‐vein thrombosis
Authors: Williams D. , Lee A. J. , Clark H. , Webster J. , Watson H. G. 
Published: September 2005

SummaryThere has been a significant increase in the amount of diagnostic testing performed to confirm or refute a diagnosis of deep‐vein thrombosis (DVT), often in low‐risk patients. d‐dimer testing and computer‐assisted strain gauge plethysmography (SGP) are rapid, inexpensive methods of excluding DVT and, in combination with a clinical probability score for DVT, both have been used to accurately exclude DVT. d‐dimer testing, SGP and a combination of both in excluding DVT were compared in 243 ambulant outpatients who followed a prespecified investigation protocol. The negative‐predictive value of d‐dimer testing alone was 100%, 93·9% (95% CI 93·6–94·1) and 80% (95% CI 73·7–86·3) in patients with a low, moderate and high pretest probability (PTP) score for DVT respectively. The corresponding results for SGP were 95·6% (95% CI 95·5–95·7), 86·1% (95% CI 85·9–86·4) and 77·8% (95% CI 75·9–79·7) in patients with a low, moderate and high PTP score for DVT respectively. d‐dimer testing provided a rapid, cost‐effective method for excluding DVT in low‐risk ambulant patients, which was superior to SGP. Combined use of the modalities did not improve any aspect of clinical decision making.
Ontogenetic shifts in the functional response and interference interactions ofRhyacophila dorsalislarvae (Trichoptera)
Authors: ELLIOTT J. M. 
Published: September 2005

Summary1. Ontogenetic shifts in predator behaviour can affect the assessment of food‐web structure and the development of predator–prey models. Therefore, it is important to establish if the functional response and interference interactions differ between life‐stages. These hypotheses were tested by (i) comparing the functional response of second, third, fourth and fifth larval instars ofRhyacophila dorsalis, using three stream tanks with oneRhyacophilalarva per tank and one of 10 prey densities between 20 and 200 larvae ofChironomussp.; (ii) using other experiments to assess interference within instars (two to five larvae of the same instar per tank), and between pairs of different instars (one, two or three larvae per instar; total predator densities of two, four or six larvae per tank).2. The first hypothesis was supported. The number of prey eaten by each instar increased with prey density, the relationship being described by a type II model. The curvilinear response was stronger for fourth and fifth instars than for second and third instars. Mean handling time did not change significantly with prey density, and increased with decreasing instar number from 169 s for fifth instars to 200 s for second instars. Attack rate decreased progressively with decreasing instar number. Handling time varied considerably for each predator–prey encounter, but was normally distributed for each predator instar. Variations in attack rate and handling time were related to differences in activity between instars, fourth and fifth instars being more active and aggressive than second and third instars, and having a higher food intake.3. The second hypothesis was partially supported. In the interference experiments between larvae of the same instar or different instars, mean handling time did not change significantly with increasing predator density, and attack rate did not change for second and third instars but decreased curvilinearly for fourth and fifth instars. Interference between some instars could not be studied because insufficient second instars were available at the same time as fourth and fifth instars, and most third instars were eaten by fourth and fifth instars in the experiments. Prey capture always decreased with decreasing attack rate. Therefore, interference reduced prey consumption in fourth and fifth instars, but not in second and third instars. The varying feeding responses of different instars should be taken into account when assessing their role in predator–prey relationships in the field.
Increased growth and recruitment of piscivorous perch, Perca fluviatilis, during a transient phase of expanding submerged vegetation in a shallow lake
Authors: HARGEBY ANDERS , BLOM HENRIK , BLINDOW IRMGARD , ANDERSSON GUNNAR 
Published: September 2005

Summary1. In this study, we examine how a 7‐year period of expanding submerged stonewort (Chara spp.) vegetation during a shift from turbid to clear water in a shallow lake influenced individual growth and population size structure of perch (Perca fluviatilis). We expected that a shift from phytoplankton to macrophyte dominance and clear water would improve feeding conditions for perch during a critical benthivorous ontogenetic stage, and enhance the recruitment of piscivorous perch.2. Growth analysis based on opercula showed that growth during the second year of life was significantly higher in years with abundant vegetation than in years with turbid water and sparse vegetation. Growth was not affected during the first, third and fourth year of life. Stable isotope analyses on opercula from 2‐year‐old perch showed that the increase in growth coincided with a change in carbon source in the diet. Stable nitrogen ratio did not change, indicating that the increased growth was not an effect of any change in trophic position.3. Following the expansion of submerged vegetation, perch size range and abundance of piscivorous perch increased in central, unvegetated areas of the lake. In stands of stoneworts, however, mainly benthivorous perch were caught, and size range did not change with time.4. Our findings provide empirical support for the notion that establishment of submerged vegetation may lead to increased recruitment of piscivorous perch, because of improved competitive conditions for perch during the benthivorous stage. This is likely to constitute a benthic‐pelagic feedback coupling, in which submerged vegetation and clear water promote the recruitment of piscivorous perch, which, in turn, may increase water clarity through top‐down effects in the pelagic.
Effects of cold‐girdling on flows in the transport phloem in Ricinus communis: is mass flow inhibited?
Authors: PEUKE ANDREAS D. , WINDT CAREL , VAN AS HENK 
Published: September 2005

ABSTRACTThe effects of cold girdling of the transport phloem at the hypocotyl of Ricinus communis on solute and water transport were investigated. Effects on the chemical composition of saps of phloem and xylem as well as of stem tissue were studied by conventional techniques and the water flow in the phloem was investigated by NMR imaging. Cold girdling reduced the concentration of sucrose but not that of inorganic solutes or amino acids in phloem saps. The possibility that cold treatment inhibited the retrieval of sucrose into the phloem, following leaching from the sieve tubes along a chemical gradient is discussed. Leaching of other solutes did not occur, as a result of missing promoting gradients in stem tissue. Following 3 d of cold girdling, sugar concentration increased and starch was synthesized and accumulated in stem tissue above the cold girdling region and along the cold‐treated phloem pathway due to leaching of sugars from the phloem. Only in the very first period of cold girdling (< 15–30 min) was mass flow inhibited, but recovered in the rest of cold treatment period to values similar to the control period before and the recovery period after the cold treatment. It is concluded that cold treatment affected phloem transport through two independent and reversible processes: (1) a permanent leaching of sucrose from the phloem stem without normal retrieval during cold treatment, and (2) a short‐term inhibition of mass flow at the beginning of cold treatment, possibly involving P proteins. Possible further mechanisms for reversible inhibition of water flow are discussed.
Contributions of evaporation, isotopic non‐steady state transpiration and atmospheric mixing on the δ18O of water vapour in Pacific Northwest coniferous forests
Authors: LAI CHUN‐TA , EHLERINGER JAMES R. , BOND BARBARA J. , PAW U KYAW THA 
Published: September 2005

ABSTRACTChanges in the 2H and 18O of atmospheric water vapour provide information for integrating aspects of gas exchange within forest canopies. In this study, we show that diurnal fluctuations in the oxygen isotope ratio (δ18O) as high as 4‰ were observed for water vapour (δ18Ovp) above and within an old‐growth coniferous forest in the Pacific Northwest region of the United States. Values of δ18Ovp decreased in the morning, reached a minimum at midday, and recovered to early‐morning values in the late afternoon, creating a nearly symmetrical diurnal pattern for two consecutive summer days. A mass balance budget was derived and assessed for the 18O of canopy water vapour over a 2‐d period by considering the 18O‐isoflux of canopy transpiration, soil evaporation and the air entering the canopy column. The budget was used to address two questions: (1) do δ18O values of canopy water vapour reflect the biospheric influence, or are such signals swamped by atmospheric mixing? and (2) what mechanisms drive temporal variations of δ18Ovp? Model calculations show that the entry of air into the canopy column resulted in an isotopically depleted 18O‐isoflux in the morning of day 1, causing values of δ18Ovp to decrease. An isotopically enriched 18O‐isoflux resulting from transpiration then offset this decreased δ18Ovp later during the day. Contributions of 18O‐isoflux from soil evaporation were relatively small on day 1 but were more significant on day 2, despite the small H216O fluxes. From measurements of leaf water volume and sapflux, we determined the turnover time of leaf water in the needles of Douglas‐fir trees as ≈ 11 h at midday. Such an extended turnover time suggests that transpiration may not have occurred at the commonly assumed isotopic steady state. We tested a non‐steady state model for predicting δ18O of leaf water. Our model calculations show that assuming isotopic steady state increased isoflux of transpiration. The impact of this increase on the modelled δ 18Ovp was clearly detectable, suggesting the importance of considering isotopic non‐steady state of transpiration in studies of forest 18O water balance.
Identification of QTL controlling root growth response to phosphate starvation in Arabidopsis thaliana
Authors: REYMOND MATTHIEU , SVISTOONOFF SERGIO , LOUDET OLIVIER , NUSSAUME LAURENT , DESNOS THIERRY 
Published: September 2005

ABSTRACTOne of the responses of plants to low sources of external phosphorus (P) is to modify root architecture. In Arabidopsis thaliana plantlets grown on low P, the primary root length (PRL) is reduced whereas lateral root growth is promoted. By using the Bay‐0 × Shahdara recombinant inbred line (RIL) population, we have mapped three quantitative trait loci (QTL) involved in the root growth response to low P. The Shahdara alleles at these three QTL promote the response of the primary root to low P (i.e. root length reduction). One of these QTL, LPR1, located in a 2.8 Mb region at the top of chromosome 1, explains 52% of the variance of the PRL. We also detected a single QTL associated with primary root cell elongation in response to low P which colocalizes with LPR1. LPR1 does not seem to be involved in other typical P‐starvation responses such as growth and density of root hairs, excretion of acid phosphatases, anthocyanin accumulation or the transcriptional induction of the P transporter Pht1;4. LPR1 might highlight new aspects of root growth that are revealed specifically under low P conditions.