bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ELISA for recombinant Lepidoglyphus destructor, Lep d 2, and the monitoring of exposure to dust mite allergens in farming households
Authors: Parvaneh S. , Johansson E. , Elfman L. H. M. , Van Hage‐Hamsten M. 
Published: March 2003

Background Exposure to indoor allergens, such as dust mites, has been recognized as a risk factor for sensitization and symptoms.Objective To develop a two‐site ELISA for the determination of Lep d 2 in the reservoir, to measure dust mite allergen exposure (Lep d 2, Der p 1, Der f 1 and Der 2) in farm households, and to investigate whether exposure to these allergens is associated with sensitization, asthma and rhinoconjunctivitis.Methods Monoclonal antibodies to recombinant (r)Lep d 2 were produced with standard hybridoma technique. Dust samples from 393 households were analysed for allergen content by two‐site ELISA methods.Results A two‐site Lep d 2 ELISA was developed with a detection limit of 0.09 µg/g. The assay was highly reproducible and levels of Lep d 2 showed a strong correlation with the number of Lepidoglyphus mites (rs: 0.7; P = 0.0002). Lep d 2 was detected in 20% of the homes; levels ranged from 0.09 to 1.7 µg/g of dust. Der p 1 was recorded in 59% of the samples, ranging from 0.055 to 139 µg/g, and Der f 1 and Der 2 in 40% and 50% of the samples, ranging from 0.055 to 24.5 µg/g and 24.3 µg/g, respectively. Dermatophagoides allergens were significantly higher in mattresses than in carpets (P < 0.0001), but this difference was not observed with Lep d 2. A strong relationship between immunoglobulin (Ig)E to rLep d 2 and asthma (OR = 10.4) and rhinoconjunctivitis (OR = 7.5) was seen. Furthermore, sensitization to D. pteronyssinus was significantly associated with asthma (OR: 13.7) and rhinoconjunctivitis (OR: 5.7).Conclusion When assessing mite allergen exposure in rural homes, not only the Der p 1, Der f 1 and Der 2 allergens, but also the Lep d 2 allergen should be taken into consideration.
Empirically simulated study to compare and validate sampling methods used in aerial surveys of wildlife populations
Authors: Khaemba Wilson Mwale , Stein Alfred , Rasch Dieter , De Leeuw Jan , Georgiadis Nick 
Published: March 2003

AbstractThis paper compares the distribution, sampling and estimation of abundance for two animal species in an African ecosystem by means of an intensive simulation of the sampling process under a geographical information system (GIS) environment. It focuses on systematic and random sampling designs, commonly used in wildlife surveys, comparing their performance to an adaptive design at three increasing sampling intensities, using the root mean square errors (RMSE). It further assesses the impact of sampling designs and intensities on estimates of population parameters. The simulation is based on data collected during a prior survey, in which geographical locations of all observed animals were recorded. This provides more detailed data than that usually available from transect surveys. The results show precision of estimates to increase with increasing sampling intensity, while no significant differences are observed between estimates obtained under random and systematic designs. An increase in precision is observed for the adaptive design, thereby validating the use of this design for sampling clustered populations. The study illustrates the benefits of combining statistical methods with GIS techniques to increase insight into wildlife population dynamics.
Passage through bird guts causes interspecific differences in seed germination characteristics
Authors: Traveset A. , Riera N. , Mas R. E. 
Published: March 2003

Summary

Seed germination characteristics are often modified after seeds are ingested by frugivores. Factors that are intrinsic either to the plant or to the frugivore’s digestive tract are responsible for the great variation observed in germination response.
Our objectives were to determine whether and how the seed germination patterns of five common western Mediterranean plant species are affected by seed passage through the guts of their major dispersers, and to elucidate the mechanism by which such patterns are changed.
We used captive birds (Turdus merula and Sylvia melanocephala) to obtain ingested seeds and compared their germination rate (speed) and germinability (final percent germination) with those of controls (uningested, pulp‐removed seeds), controlling for seed age, size and source. Germination was monitored for 2 years in an experimental garden. We evaluated the possible changes in seed traits after ingestion by measuring weight and coat thickness, and by observing seed coat sculpture.
Rate of seed germination, but not germinability, changed in all species after gut treatment. The greatest effect was in Osyris, in which germination was much enhanced. A great acceleration of germination, which is likely to translate into a seedling size advantage, was also found in Asparagus. In the other three species tested, germination was slower for ingested than for control seeds.
For Rubus and Rubia seeds, we found a different germination response depending upon the frugivore species tested. A different degree of seed coat scarification caused by differences in gut retention time, chemical and/or mechanical abrasion probably account for such responses.
In three of the species (Osyris, Rubia and Phillyrea), seed weight decreased after gut treatment. Such weight loss was not caused by any change in coat thickness, but may have been because of the scarification and consequent alteration of the seed coat structure.
The five Mediterranean species studied germinate when rains are most likely to fall (mostly autumn and spring). The different speed of germination promoted by gut treatment within frugivores may increase the probability that seeds can recruit successfully at a given time and in a given place.
This study suggests that frugivores contribute to the heterogeneity in germination characteristics not only within plant populations but also within plant communities, each frugivore species having a particular effect on the seeds of each plant consumed.
Host recognition in a desert mistletoe: early stages of development are influenced by substrate and host origin
Authors: Rödl T. , Ward D. 
Published: March 2003

Summary  In many root parasites, chemical substances from the host are necessary for the successful initiation of germination and holdfast formation, and are the basis for host recognition and localization within the rhizosphere. In contrast, bird‐dispersed mistletoe seeds have no need for the chemical localization of a host, and possible mechanisms of host recognition are poorly understood. Many studies claim that mistletoes germinate readily in the absence of a host and independent of the substrate.  In this study, the possible occurrence of substrate dependence and host recognition in mistletoes during the establishment ofPlicosepalus acaciaeZucc. seeds onAcacia raddianaSavi was tested experimentally.  In a laboratory experiment, no influence of substrate on germination could be found, but a significantly higher proportion of the germinated seeds developed a holdfast on natural (bark) substrate than on artificial (plastic) substrate. Moreover, the origin of the bark had a significant influence on holdfast formation frequency.  Host influence was additionally tested in a reciprocal transplant experiment in two field sites with genetically different populations of the same host species. Those mistletoes of local origin germinated significantly more often than their non‐local counterparts.  These results suggest the existence of interactions between mistletoe seed and host branch on the basis of chemical cues that are active at an early stage of seedling development and are host‐specific at the level of populations.
No significant relationship exists between seedling relative growth rate under nutrient limitation and potential tissue toxicity
Authors: Almeida‐Cortez J. S. , Shipley W. 
Published: March 2003

Summary We asked two questions in this study: (i) is there is there a negative correlation between relative growth rate (RGR) among 19 species of herbaceous Asteraceae grown under nutrient limitation and potential tissue toxicity; and (ii) is the degree of toxicity of these species different than those measured in a previous study, in which the same species were grown under non‐limiting conditions? In the present study we grew 19 of the same species as previously in hydroponic sand culture for which the growth rate was limited by nutrient supply, and compared RGR and potential tissue toxicity due to secondary compounds. Under such conditions, RGR was reduced by 25%; specific leaf area was reduced by 32%; root : shoot ratios were increased by 320%; leaf nitrogen content was reduced by 69%; and potential toxicity was decreased by 46%. Although nutrient limitation clearly decreased both RGR and potential toxicity, we found no interspecific correlation between RGR and toxicity. We conclude that there was no detectable trade‐off between RGR and potential toxicity due to secondary compounds.
Men with acromegaly need higher doses of octreotide than women
Authors: Edén Engström Britt , Burman Pia , Karlsson F. Anders 
Published: March 2003

SummaryobjectiveTo investigate the effect of gender on the response of GH to short‐acting octreotide in patients with acromegaly, and on the GH and IGF‐1 levels during long‐term treatment with a slow‐release formulation of octreotide.study design and patientsTwenty‐one men (mean age 54 years; range 26–78) and 15 women (mean age 54 years; range 22–74) with acromegaly were treated with subcutaneous injections of 100 µg short‐acting octreotide twice daily. Serum samples for GH were taken before start of treatment, in the morning prior to the injection, and 1, 3, 5 and 7 h after the injection. Thirteen men (mean age 56 years; range 34–78) and 12 women (mean age 64 years; range 28–81) with acromegaly were switched from ongoing treatment with short‐acting octreotide to injections of the slow‐release formulation. A 4‐h GH‐profile and morning IGF‐1 were taken at start and after 3, 9, 15 and 21 months of treatment.resultsSubcutaneous injections of 100 µg octreotide reduced the mean level of GH during a 7‐h period to a similar extent in men and women compared to the GH levels prior to the injections. During long‐term treatment with similar doses of the depot formulation of octreotide, the mean IGF‐1 level remained significantly higher in the men than in the women, whereas there were no differences in the mean GH levels between the two groups.conclusionsThe responses to short‐ and long‐acting octreotide illustrate an effect of gender, due to different sensitivity to GH in the periphery. Furthermore, the results show that in the treatment of acromegaly, men will need higher doses of octreotide than women to normalize IGF‐1.
The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV‐1‐infected individuals
Authors: Koks C. H. W. , Crommentuyn K. M. L. , Hoetelmans R. M. W. , Burger D. M. , Koopmans P. P. , Mathôt R. A. A. , Mulder J. W. , Meenhorst P. L. , Beijnen J. H. 
Published: March 2003

Aims  To study the effect of fluconazole on the steady‐state pharmacokinetics of the protease inhibitors ritonavir and saquinavir in HIV‐1‐infected patients.Methods  Five subjects treated with saquinavir and three with ritonavir received the protease inhibitor alone (saquinavir 1200 mg three times daily, ritonavir 600 mg twice daily) on day 1, and the same protease inhibitor in combination with fluconazole (400 mg on day 2 and 200 mg on days 3 to 8). Pharmacokinetic parameters were determined on days 1 and 8.Results  In the saquinavir group, the median increase in the area under the plasma concentration vs time curve was 50% from 1800 µg l−1 h to 2700 µg l−1 h (P = 0.04, median increase: 900 µg l−1 h; 2.5 and 97.5 percentile: 500–1300), and 56% for the peak concentration in plasma (from 550 to 870 µg l−1, P = 0.04; median increase: 320 µg l−1 h, 2.5 and 97.5 percentile: 60–450 µg l−1). In the ritonavir group, there were no detectable changes in the pharmacokinetic parameters on addition of fluconazole.Conclusions  Because of the favourable safety profile of saquinavir, dose adjustments are probably not necessary with concomitant use of fluconazole, as is the case for ritonavir.
Evidence of impaired cisapride metabolism in neonates
Authors: Tréluyer Jean‐Marc , Rey E , Sonnier M. , Pons G , Cresteil T 
Published: March 2003

Aims  Cisapride has been shown to cause QTc prolongation in neonates in the absence of any of the known risk factors ascribed to children or adults (excessive dosage, drug–drug interactions). Our hypothesis was that the early neonatal liver may show defective elimination of cisapride resulting in its accumulation in the immature child. Owing to the difficulties associated with in vivo pharmacokinetic studies in a paediatric population, we explored the in vitro metabolism of cisapride by human cytochrome P450.
Methods
Experiments were conducted with recombinant CYPs stably expressed in mammalian cells and with liver microsomes obtained from human foetuses, neonates, infants and adults. Cisapride metabolites were measured by high performance liquid chromatography.
Results
The rate of biotransformation of cisapride was greater by recombinant CYP3A4 than by CYP3A7 (0.77 ± 0.5 and 0.01 ± 0.01 nmol metabolites formed in 24 h, respectively), whereas CYP1A1, 1A2, 2C8, 2C9 and 3A5 showed no activity. Norcisapride formation was significantly correlated with testosterone 6β‐hydroxylation, a CYP3A4 catalysed reaction (r = 0.71, P = 0.03) but not with the 16‐hydroxylation of dehydroepiandrosterone, catalysed by CYP3A7 (r = 0.30, P = 0.29) by microsomes from a panel of livers from foetuses, neonates and infants. No or negligible cisapride metabolic activity was observed in microsomes from either foetuses or neonates aged less than 7 days, which contained mostly CYP3A7 and no CYP3A4. The metabolism of cisapride steadily increased after the first week of life in parallel with CYP3A4 activity to reach levels exceeding adult values.
Conclusions

The low content of CYP3A4 in the human neonatal liver appears to be responsible for its inability to oxidize cisapride and could explain its accumulation in plasma leading to the cases of QTc prolongation reported in this paediatric population.
Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers
Authors: Kees F. , Färber L. , Bucher M. , Mair G. , Mörike K. , Grobecker H. 
Published: March 2003

Aims  To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously.Methods  Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash‐out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated.Results  The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml−1, tmax 2.6 h, t1/2 5.7 h and AUC(0,∞) 32.9 ng ml −1 h. After intravenous administration initial plasma concentration was 15.1 ng ml−1, t1/2 5.6 h, AUC(0,∞) 20.7 ng ml −1 h, V 678 l and CL 1800 ml min−1. An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27–0.99) of oral tropisetron.Conclusions  Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.
Randomized cross‐over clinical trial to study potential pharmacokinetic interactions between cisplatin or carboplatin and etoposide
Authors: Thomas Huw D. , Porter David J. , Bartelink Imke , Nobbs Joy R. , Cole Michael , Elliott Suzie , Newell David R. , Calvert A. Hilary , Highley Martin , Boddy Alan V. 
Published: March 2003

Aims  Cisplatin and carboplatin are often used in combination with etoposide. In a randomized cross‐over study, the potential interaction between the two platinum drugs and the metabolism of etoposide was explored. In vitro investigations using human liver microsomes were also performed.Methods  Etoposide was administered to 15 patients over 3 days, with the platinum drug administered on day 2. The alternate platinum drug was administered on the second course. The pharmacokinetics of etoposide were determined on all 3 days of each cycle. The effect of platinum drugs on etoposide metabolism by human liver enzymes was explored in vitro.Results  Neither cisplatin nor carboplatin coadministration affected the pharmacokinetics of etoposide during cycle 1. When carboplatin was administered on course 2, etoposide AUC was 8% higher on day 2 compared with day 1 or day 3 (for day 2 vs day 3, 95% CI: −0.72, −0.08 mg ml−1 min). In contrast, cisplatin on course 2 increased the AUC of etoposide (28%) on day 3 (day 3 vs day 1, 95% CI: 0.67, 2.09 mg ml−1 min), with no effect on day 2. In vitro carboplatin and cisplatin (10–100 µm) inhibited the metabolism of etoposide, if rat liver microsomes were preincubated (30 min) with NADPH and the platinum complexes. With human liver microsomes a small effect on etoposide metabolism, but not on catechol formation, was observed.Conclusions  The interaction between etoposide and platinum drugs is small and, given the pharmacokinetic variability seen with etoposide, the clinical impact is unlikely to be significant.
Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent
Authors: Hutchinson P. J. , . O'Connell M. T , Coles J. P. , Chatfield D. A. , Coleman M. R. , Al‐Rawi P. G. , Kett‐White C. R. , Gupta A. K. , Menon D. K. , Boniface S. J. , Heazell M. , Kirkpatrick P. J. , Pickard J. D. 
Published: March 2003

Aims  Promising pre‐clinical results from laboratory studies of neuro‐protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro‐protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain.Methods  Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head‐injured patients on the neuro‐intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min−1) intravenous loading infusion for 5 min followed by a slow (1 ml min−1) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi‐spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids.Results  Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients.Conclusions  Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro‐protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro‐protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end‐points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.
Dose–response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate
Authors: Fowler Stephen J. , Orr Linda C. , Wilson Andrew M. , Sims Erika J. , Lipworth Brian J. 
Published: March 2003

Aims  With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA‐beclomethasone dipropionate (BDP) vs HFA‐fluticasone propionate (FP).Methods  Sixteen healthy volunteers were randomised in placebo‐controlled single blind cross‐over fashion to receive 3 weeks with HFA‐FP or HFA‐BDP, given as 1 week cumulative doubling doses (nominal ex‐valve) of 500, 1000 and 2000 µg day−1, with a 1 week placebo run‐in and wash‐out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log‐transformed to normalize their distribution.
Results
Urine and serum cortisol were suppressed by 2000 µg FP and BDP vs placebo and by 1000 µg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 µg BDP vs 1000 µg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04–2.56). There were also more individual low values less than 3 nmol mmol−1 with BDP than FP at 1000 µg: n = 8/16 vs n = 2/16 (P < 0.05).
Conclusions
There was dose‐related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA‐BDP than HFA‐FP at 1000 µg. This suggests that the greater glucocorticoid potency of HFA‐FP may be offset by the greater lung bioavailability of HFA‐BDP
Hospital prescribing errors: epidemiological assessment of predictors
Authors: Fijn R. , Van den Bemt P. M. L. A. , Chow M , De Blaey C. J. , De Jong‐Van den Berg L. T. W. , Brouwers J. R. B. J. 
Published: March 2003

Aims  To demonstrate an epidemiological method to assess predictors of prescribing errors.Methods  A retrospective case‐control study, comparing prescriptions with and without errors.Results  Only prescriber and drug characteristics were associated with errors. Prescriber characteristics were medical specialty (e.g. orthopaedics: OR: 3.4, 95% CI 2.1, 5.4) and prescriber status (e.g. verbal orders transcribed by nursing staff: OR: 2.5, 95% CI 1.8, 3.6). Drug characteristics were dosage form (e.g. inhalation devices: OR: 4.1, 95% CI 2.6, 6.6), therapeutic area (e.g. gastrointestinal tract: OR: 1.7, 95% CI 1.2, 2.4) and continuation of preadmission treatment (Yes: OR: 1.7, 95% CI 1.3, 2.3).Conclusions Other hospitals could use our epidemiological framework to identify their own error predictors. Our findings suggest a focus on specific prescribers, dosage forms and therapeutic areas. We also found that prescriptions originating from general practitioners involved errors and therefore, these should be checked when patients are hospitalized.