bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate change in the Arctic: using plant functional types in a meta‐analysis of field experiments
Authors: Dormann C. F. , Woodin S. J. 
Published: March 2003

Summary

The effects of global climate change are predicted to be strongest in the Arctic. This, as well as the suitability of tundra as a simple model ecosystem, has led to many field experiments investigating consequences of simulated environmental change.
On the basis of 36 experiments reviewed here, minor light attenuation by clouds, small changes in precipitation, and increases in UV‐B radiation and atmospheric CO2 concentrations will not affect arctic plants in the short term. However, temperature elevation, increases in nutrient availability and major decreases in light availability will cause an immediate plant‐growth response and alter nutrient cycling, possibly creating positive feedbacks on plant biomass. The driver of future change in arctic vegetation is likely to be increased nutrient availability, arising for example from temperature‐induced increases in mineralization.
Arctic plant species differ widely in their response to environmental manipulations. Classification into plant functional types proved largely unsatisfactory for generalization of responses and predictions of effects.
Nevertheless, a few generalizations and consistent differences between PFTs were detected. Responses to fertilization were the strongest, particularly in grasses. Shrubs and grasses were most responsive to elevated temperature.
Future studies should focus on interactive effects of environmental factors, investigate long‐term responses to manipulations, and incorporate interactions with other trophic levels. With respect to plant functional types, a new approach is advocated, which groups species according to their responses to environmental manipulations.
Offspring size–number strategies: experimental manipulation of offspring size in a viviparous lizard (Lacerta vivipara)
Authors: Olsson M. , Wapstra E. , Olofsson C. 
Published: March 2003

Summary  Aspects of female ‘offspring sizevsnumber’ strategies were studied in the viviparous Common Lizard,Lacerta viviparaJacquin, by surgical yolk extraction from ovarian follicles and ovulated eggs in the oviduct (‘allometric engineering’).  This method has previously been applied exclusively to oviparous lizards but here it is applied to a viviparous taxon.  There was a strong negative relationship between the amount of yolk removed and the size of offspring at birth, and yolk‐removed young were smaller and in poorer condition at birth than their control counterparts from within the same litters.  In yolk‐removed young physiological performance was positively correlated with body mass.  Maternal resource provisioning thus influences offspring physiological performance, which suggests ongoing selection on female optimization of the offspring size–number trade‐off.
Antisymmetry in male fiddler crabs and the decision to feed or breed
Authors: Pratt A. E. , Mclain D. K. 
Published: March 2003

Summary In male Sand Fiddler Crabs,Uca pugilator, a major cheliped (with claw), used in intersexual displays and intrasexual contests, develops opposite a minor cheliped used for feeding. Cheliped size demonstrates antisymmetry because greater development is equally likely on the right or left side. The side with the major cheliped (major side) also has longer walking legs which may facilitate use of the claw. In contrast, eye stalk asymmetry is equally due to antisymmetry and fluctuating asymmetry. Fluctuating asymmetry is a subtle, non‐adaptive departure from the population‐level trajectory relating growth on major and minor sides. In a South Carolina (USA) marsh, cheliped and leg antisymmetries are greater and eye stalk asymmetry is less among males able to defer feeding in favour of breeding. However, the composition of up‐slope breeding and down‐slope feeding subpopulations changes across the lunar cycle. The number of mates sequestered in breeding burrows is positively correlated with cheliped and leg antisymmetry and negatively correlated with eye stalk asymmetry. Male fitness is a function of the product of time spent breeding and the number of mates per unit time while breeding. Both fitness components are predicted by relative cheliped antisymmetry and eye stalk fluctuating asymmetry, which are themselves significantly negatively correlated.
Fracture risk is increased in patients with GH deficiency or untreated prolactinomas – a case‐control study
Authors: Vestergaard Peter , Jørgensen Jens Otto L. , Hagen Claus , Hoeck Hans Christian , Laurberg Peter , Rejnmark Lars , Brixen Kim , Weeke Jørgen , Andersen Marianne , Conceicao Flavia L. , Nielsen Torben Leo , Mosekilde Leif 
Published: March 2003

Summaryobjective The pituitary secretes many hormones of significance to bone turnover and thus skeletal integrity. The aim of this study was to examine fracture risk in patients with pituitary disorders with special reference to GH deficiency and hyperprolactinaemia.design Case‐control study.measurements Fracture occurrence.patients A self‐administered questionnaire was issued to 537 consecutive patients with pituitary disorders excluding Cushing’s disease. A total of 426 (79%) returned the questionnaire and 422 of these could be analysed. Each respondent was compared to three age‐ and gender‐matched control respondents to the same questionnaire drawn randomly from the background population.results The patients had a mean age of 51·4 ± 14·8 years. One hundred and eight patients had acromegaly, 86 had prolactinomas, 136 had non‐functioning pituitary adenomas (NFPA), 23 had craniopharyngiomas, and 73 had other types of pituitary disorders. For the total group the fracture risk was not elevated either before or after confirmed diagnosis compared to controls. However, among the patients with prolactinomas, the fracture risk was significantly increased before (relative risk, RR = 1·6, 95% CI: 1·1–2·3) but not after diagnosis. In patients with NFPA, fracture risk was borderline significantly elevated following diagnosis (RR = 1·6, 95% CI: 1·0–2·6). Patients with subnormal stimulated peak GH values suggestive of GH deficiency had a significantly higher risk of fractures after diagnosis than patients who had normal stimulated peak GH values (odds ratio, OR = 4·90, 95% CI: 1·10–21·88).conclusions Untreated prolactinomas were associated with a significant increase in fracture risk. Growth hormone deficiency was also associated with a higher fracture risk.
Onset and duration of action of sildenafil for the treatment of erectile dysfunction
Authors: Eardley Ian , Ellis Peter , Boolell Mitradev , Wulff Maria 
Published: March 2003

Aims  To determine the onset and duration of action of sildenafil in patients with erectile dysfunction (ED).Methods  Two randomised, double‐blind, placebo‐controlled, two‐way crossover studies were conducted in men with ED of no known organic cause. Study I: The time to onset of erections after sildenafil (50 mg) or placebo dosing following visual sexual stimulation (VSS) was assessed in 17 patients. Patients not achieving >60% penile rigidity by 70 min postdose as measured by a RigiScan® monitoring device were assigned an onset time of 70 min. Study II: The duration of grade 3 (hard enough for penetration) and grade 4 (fully hard) erections, determined by self‐assessment during 60 min of VSS starting 2 and 4 h after sildenafil (100 mg) or placebo dosing, was measured in 16 patients.Results  Study I: The median time (range) to onset of erections was 27 min (in a range of 12–70) after receiving sildenafil 50 mg. In the sildenafil group, 71% of patients experienced onset of erections within 30 min of dosing, and 82% responded within 45 min. Of the patients who achieved >60% penile rigidity after sildenafil, 86% had done so by 30 min after dosing. Study II: When VSS began 2 h postdose, the median duration of grade 3 or 4 erections was 19.5 min (0–55) for sildenafil vs 0 min (0–23) for placebo. When VSS began 4 h postdose, the median duration was 5 min (0–45) for sildenafil compared with 0 min for placebo (0–27).Conclusions  Sildenafil is an effective oral treatment for ED that produces a penetrative erection as early as 12 min and for most patients, within 30 min after dosing, and a duration of action lasting at least 4 h.
Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration?
Authors: Martin Jennifer H. , Begg Evan J. , Kennedy Martin A. , Roberts Rebecca , Barclay Murray L. 
Published: March 2003

Aims  The aim of this study was to explore whether genetic variation of cytochrome P450 2C9 (CYP2C9) contributes to NSAID‐associated gastric ulceration. The hypothesis tested was that CYP2C9 poor metabolizer genotype would predict higher risk of gastric ulceration in patients on NSAIDs that are metabolized by CYP2C9, due to higher plasma NSAID concentrations.Methods  Peripheral blood DNA samples from 23 people with a history of gastric ulceration attributed to NSAIDs metabolized by CYP2C9, and from 32 people on NSAIDs without gastropathy, were analysed to determine CYP2C9 genotype.Results  The following genotypes were found: *1/*1 (wild type) in 70% of cases and 58% of controls, *1/*2 in 17% of cases and 29% of controls, *1/*3 in 13% of cases and 13% of controls. The difference between case and control nonwild‐type genotype frequency was 11.5% (95% CI −14,37%), with the direction of the difference being against the hypothesis. No individuals with homozygote poor metaboliser genotype were identified. The differences in genotype frequencies between the two groups were not significant and the frequencies were similar to those in a large published population study. Ninety‐five percent binomial confidence interval analysis confirms that there is no apparent clinically significant relationship between CYP2C9 genotype and risk of gastric ulceration although a small difference in risk in poor metabolizers cannot be excluded.Conclusions  These results do not support the hypothesis that gastric ulceration resulting from NSAID usage is linked to the poor metabolizing genotypes of CYP2C9.
Seasonal differences in finger skin temperature and microvascular blood flow in healthy men and women are exaggerated in women with primary Raynaud's phenomenon
Authors: Gardner–medwin J. M. , Macdonald I. A. , Taylor J. Y. , Riley P. H. , Powell R. J. 
Published: March 2003

Aims  Patients with primary Raynaud's phenomenon (PRP) have more severe symptoms in the winter. The aetiology of this is more complex than simply increased vasoconstriction in response to the immediate ambient temperature. The aim of this study was to investigate differences in skin temperature (Tsk), microvascular blood flow and responses to endothelium‐dependent and independent vasodilators in healthy controls, and women with PRP under identical environmental temperatures but in different seasons.Methods  Ten women with PRP were compared with age matched women (10) and men (10). Finger skin responses were recorded immediately on arrival, after stabilizing in a temperature regulated laboratory at 22–24 ° C, and at matched warm (35 ° C) and cold (15 ° C) Tsk in the winter and summer. Baseline red blood cell flux (r.b.c. flux), and the change in flux in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) were recorded by laser Doppler fluxmetry at the warm and cold Tsk.Results  Arrival Tsk were significantly cooler for all subjects during the winter (mean seasonal difference −2.6 ° C, P < 0.0001), and markedly colder in subjects with PRP (mean seasonal difference −3.5 ° C, P < 0.0005). Statistically significant seasonal differences persisted in all subjects at stable Tsk despite an identical laboratory temperature (mean difference 1.3 ° C, P < 0.0001). To achieve comparable controlled finger Tsk a significantly colder local environment was required for male controls (mean of −2.1 ° C, P < 0.0001), and a significantly warmer environment for subjects with PRP (mean of + 2.4 ° C, P < 0.0001) compared with female controls. This needed to be warmer in the winter, by a mean of 2.4 ° C, than the summer for all subjects. Vasodilatation in response to ACh, but not SNP, was significantly smaller (P < 0.0001) in the PRP group compared with the female controls for all visits, with most of this difference arising in the winter visits (P < 0.01).Conclusions  There is a seasonal and persistent influence on finger Tsk, and microvascular blood flow in healthy men and women, which modifies the observed responses to immediate changes in finger Tsk. The seasonal differences are greater in women than men, and are further exaggerated in women with PRP, in whom this is associated with reduced endothelium‐dependent vasodilatation.
Nature, frequency and determinants of prescription modifications in Dutch community pharmacies
Authors: Buurma Henk , De Smet Peter A. G. M. , Van Den Hoff Olga P. , Egberts Antoine C. G. 
Published: March 2003

Aims  To examine the nature, frequency and determinants of prescription modifications in Dutch community pharmacies.Methods  A prospective case‐control study comparing modified prescriptions with nonmodified prescriptions was carried out in 141 Dutch community pharmacies. 2014 modified prescriptions (cases), collected in the selected pharmacies on a predetermined day in a specific period (25th February until 12th March 1999) and 2581 nonmodified prescriptions (controls) randomly selected on the same day were studied. The nature and frequency of prescription modifications and patient, drug and prescriber related determinants for a modified prescription were assessed.Results  The overall incidence of prescription modifications was 4.3%, with a mean of 14.3 modifications per pharmacy per day. For prescription only medicines (POM) the incidence was 4.9%. The majority of POM modifications concerned a clarification (71.8%). In 22.2% a prescription could potentially have had clinical consequences when not altered; in more than half of the latter it concerned a dose error (13.7% of all cases). POM prescriptions of patients of 40–65 years had a significantly lower chance of modification compared with those of younger people (OR = 0.74 [0.64–0.86]). With respect to medication‐class, we found a higher chance of POM modifications in the respiratory domain (OR = 1.48 [1.23‐1.79]) and a decreased chance for nervous system POMs (OR = 0.71 [0.61–0.83]). With regard to prescriber‐related determinants modifications were found three times more often in non printed prescriptions than in printed ones (OR = 3.30 [2.90‐3.75]). Compared with prescriptions by the patient's own GP, prescriptions of specialists (OR = 1.82 [1.57‐2.11]), other GP's (OR = 1.49 [1.02‐2.17]) and other prescribers such as dentists and midwives (OR = 1.95 [1.06‐3.57]) gave a higher probability of prescription modifications. When a GP had no on‐line access to the computer of the pharmacy the chance of a modification was also higher (OR = 1.61 [1.33‐1.94]). Multivariate analysis revealed that a nonprinted prescription was the strongest independent determinant of prescription modifications (OR = 3.32 [2.87‐3.84]), remaining so after adjustment for GP computer link to the pharmacy and for type of prescriber.Conclusions  At least 30% of Dutch community pharmacies corrected 2.8 POM prescriptions per pharmacy per working day, which could potentially have had clinical consequences if not altered. If the study sample is representative for The Netherlands, Dutch community pharmacies correct a total of approximately 4400 of these prescriptions per working day. Using computerized systems to generate prescriptions is an important strategy to reduce the incidence of prescription errors.
Effect of acid secretion blockade by omeprazole on the relative bioavailability of orally administered furazolidone in healthy volunteers
Authors: Calafatti Silvana A. , Ortiz Rodrigo A. M. , Deguer Maristela , Martinez Márcio , Pedrazzoli José 
Published: March 2003

Aims  The administration of omeprazole may interfere with the absorption of orally administered drugs by reducing gastric pH and hence tablet dissolution. The aim of this study was to investigate the effects of a 5 day administration of omeprazole on the pharmacokinetics of furazolidone.Methods  Eighteen healthy (nine male and nine female) volunteers were selected. The study had an open randomized two‐period crossover design with a 21 day washout period between the phases. Serum concentrations of furazolidone were measured by reversed‐phase h.p.l.c. with ultraviolet detection.Results  Administration of omeprazole caused a significant reduction of Cmax[0.34 µg ml−1 (range 0.25–0.43) vs 0.24 µg ml−1 (range 0.15–0.34)] with no significant delay in absorption tmax[2.5 h (range 1.85–3.0) vs 2.4 h (range 2.06–2.71)].Conclusions  Furazolidone was rapidly absorbed after oral administration. Short‐term treatment with omeprazole did alter the relative bioavailability of this drug, probably through an effect on absorption kinetics or first‐pass metabolism.
Determinants of signal selection in a spontaneous reporting system for adverse drug reactions
Authors: Van Puijenbroek Eugène P. , Van Grootheest Kees , Diemont Willem L , Leufkens Hubert G. M. , Egberts Antoine C. G. 
Published: March 2003

Aims  Detection of new adverse drug reactions (ADR) after marketing is often based on a manual review of reports sent to a Spontaneous Reporting System (SRS). Among the many potential signals that are identified, only a limited number are important enough to require further attention. The goal of this study is to gain insight into factors contributing to the selection and dissemination of possible signals originating from the SRS maintained by the Netherlands Pharmacovigilance Foundation.Methods  In a case control design, all signals (n = 42) disseminated to the Medicines Evaluation Board from the second quarter of 1997 until the third quarter of 2000, which could be expressed as a combination of a single ATC code and a single WHO preferred term, were included. For each case, four controls were matched in time. Logistic regression analysis was used to investigate the influence of various factors, such as the fact whether the ADR or drug is new, the strength of the association, the seriousness of the reaction and the documentation of the reports.Results  Multivariate analysis showed that the presence of a ‘serious report’ (Odds Ratio 3.8, 95% CI 1.3, 11.0), a WHO ‘critical term’ (OR 4.7, 95% CI 1.8, 13), the ADR being unlabelled (OR 6.1, 95% CI 2.3, 16) and the presence of a disproportionate association (OR 3.5, 95% CI 1.4, 8) were all independently associated with signal selection. The number of reports and the time after marketing of the drug had no influence.Conclusions  This study showed that selection of signals is based on both qualitative and quantitative aspects. Knowledge of these factors may improve the efficiency of the underlying signal selection process.
Excretion of low molecular weight heparin in human milk
Authors: Richter Christiane , Sitzmann Jörg , Lang Pierre , Weitzel Hans , Huch Albert , Huch Renate 
Published: March 2003

Aims  The excretion of low molecular weight heparin (LMWH) in breast milk was investigated in 15 lactating mothers after Caesarean section.Methods  Blood and milk samples were collected before and 3–4 h after once daily routine subcutaneous injection of 2500 IU dalteparin. Anti‐Xa activity was measured by an assay utilizing prolonged clotting times in plasma or breast milk as an index of LMWH activity.Results  Plasma anti‐Xa activities ranged from 0.074 to 0.308 IU ml−1 of plasma. Anti‐Xa activities in breast milk ranged from < 0.005–0.037 IU ml−1 of milk. This is equivalent to a milk/plasma ratio of < 0.025–0.224.Conclusions  Therefore, it appears highly unlikely that puerperal thromboprophylaxis with LMWH has any clinically relevant effect on the nursing infant.
Distribution of venlafaxine and its O‐desmethyl metabolite in human milk and their effects in breastfed infants
Authors: Ilett Kenneth F. , Kristensen Judith H. , Hackett L. Peter , Paech Michael , Kohan Rolland , Rampono Jonathan 
Published: March 2003

Aims  To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine (V) and its O‐desmethyl metabolite (ODV), in breastfeeding women taking venlafaxine for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants.Methods  Six women (mean age 34.5 years, mean weight 84.3 kg) taking venlafaxine (median dose 244 mg day−1, range 225–300 mg day−1) and their seven infants (mean age 7.0 months, mean weight 7.3 kg) were studied. V and ODV in plasma and milk were measured by high‐performance liquid chromatography over a 12 h dose interval at steady‐state. Infant exposure was estimated as the product of estimated milk production rate (0.15 l kg−1day−1) and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight‐adjusted maternal dose.Results  Mean M/PAUC values of 2.5 (range 2.0–3.2) and 2.7 (range 2.3–3.2) were calculated for V and ODV, respectively. The mean maximum concentrations (95% CI) of V and ODV in milk were 1161 (95% CI, 588, 1734) µg l−1 and 796 (362, 1230) µg l−1. Mean infant exposure was 3.2% (1.7, 4.7%) for V and 3.2% (1.9, 4.9%) for ODV (as V equivalents). V was detected in the plasma of one out of seven infants studied (5 µg l−1), while ODV was detected in four of the infants, at concentrations ranging from 3 to 38 µg l−1. All of the infants in the study were healthy, as reported by their mothers and/or by clinical examination on the study day.Conclusions  The concentrations of V and ODV in breast milk were 2.5 and 2.7 times those in maternal plasma. The mean total drug exposure (as venlafaxine equivalents) of the breastfed infants was 6.4% (5.5–7.3%), which is below the 10% notional level of concern. There were no adverse effects in any of the infants. The data support the use of V in breastfeeding. Nevertheless, since low concentrations of ODV were detected in the plasma of four out of the seven infants studied, we recommend breastfed infants should be monitored closely. Each decision to breast feed should be made as an individual risk:benefit analysis.