bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interaction between epiphytic algae, a parasitic fungus and Sphagnum as affected by N and P
Authors: Limpens Juul , Raymakers Jeffrey T. A. G. , Baar Jacqueline , Berendse Frank , Zijlstra Jantineke D. 
Published: October 2003

We report the effects of fertilisation with N and P on the infection of Sphagnum by its fungal parasite Lyophyllum palustre, the expansion of epiphytic algae and the interaction between the latter two from 1998 to 2001. We added 40 kg N ha−1 yr−1 or 3 kg P ha−1 yr−1 in a full factorial design at 4 field sites. In a greenhouse experiment we reinoculated Sphagnum to verify the identity of the fungus and its necrotic effect on Sphagnum. Lyophyllum palustre was responsible for the necrosis of Sphagnum in our experiments. Adding N induced complete necrosis of Sphagnum cuspidatum by L. palustre, whereas adding P decreased the area of necrotic tissue. Disease severity was related to the N concentration in the Sphagnum capitula. In Sphagnum magellanicum and S. papillosum, infection with L. palustre resulted in defoliation of stem sections. Adding N stimulated the expansion of algae at all sites, reducing the volume of photosynthetic tissue in Sphagnum. The density of the film of algae in the treatments receiving N was a function of the frequency of defoliated Sphagnum stems.We conclude that infection with parasitic fungi and, in humid environments, the expansion of epiphytic algae, may aggravate the impact of increased N deposition or of other ecosystem disturbances that affect nutrient availability.
Role of the Actin Cytoskeleton in Regulating Endothelial Permeability in Venules
Authors: VALESKI J. EDWARD , BALDWIN ANN L. 
Published: October 2003

ABSTRACTObjective: This study was performed to determine the effect of myosin light chain kinase (MLCK) inhibition on histamine‐ and thrombin‐induced venular permeability in the rat mesentery, coincidental with actin cytoskeleton changes.Methods: The mesenteric microvasculature of rats was perfused with a fluorescent tracer plus thrombin, histamine, or buffered saline, and the preparation was suffused with the MLCK inhibitor ML‐7. The microvasculature then was stained for actin.Results: The average (±SE) number of leaks per micrometer of venule length of the thrombin plus 5 µM ML‐7 treatment (35.3 ± 5.9 × 10−4; n = 224) was significantly lower than that for the thrombin‐only treatment (61.7 ± 5.6 × 10−4; n = 385; p < 0.001). The histamine preparations required higher concentrations of ML‐7 to significantly reduce the number of leaks. A concentration of 100 µM reduced the average leak number from 20.8 ± 3.9 × 10 4 (n = 140) to 2.5 ± 0.8 × 10−4 (n = 383; p < 0.001), but 20 µM ML‐7 had no effect. Although leaky areas of both the thrombin‐ and histamine‐treated preparations showed disruptions of the peripheral actin rim coincident with fluorescein isothiocyanate‐bovine serum albumin leaks, qualitative and quantitative differences were identified.Conclusions: The results suggest both similar and dissimilar mechanisms for thrombin and histamine regarding in situ endothelial gap formation.
The role of general practitioners’ working style and brief alcohol intervention activity
Authors: Aalto Mauri , Värre Tanja , Pekuri Petteri , Seppä Kaija 
Published: October 2003

ABSTRACTAims  To examine correlates of general practitioners’ (GP) activity delivery of brief alcohol interventions to patients with particular reference to their ‘working style’.Design  A postal questionnaire survey.Setting and participants  All 75 GPs in the Community Primary Health Care Centre of the City of Tampere, Finland.Measurements  Measures of working style classifying GPs into ‘problem solving’ versus ‘technological’, self‐reported brief advice activity and other demographic details.Findings and conclusions  Of the respondents (response rate 85%) 45% (29/64) reported carrying out brief alcohol interventions. Male GPs provided brief interventions more often than female GPs (71% versus 36%, P = 0.017). The respondents had mainly positive attitudes to brief interventions for excessive drinkers. The working style typology did not show any relationship with brief intervention activity.
Effects of cardiac output on disposition kinetics of sorbitol: recirculatory modelling
Authors: WEISS M. , HÜBNER G. H. , HÜBNER I. G. , TEICHMANN W. 
Published: October 2003

1 The purpose of this study was to determine the effects of cardiac output on distribution and elimination kinetics of the marker compound sorbitol. 2 The disposition kinetics of sorbitol were investigated after rapid intravenous injection and arterial sampling in nine patients who had undergone cardiac catheterization whereby the cardiac output was measured. 3 A minimal circulatory model consisting of pulmonary and systemic subsystems, both of which were characterized by an inverse Gaussian transit time density function, fitted the data very well. The method involves numerical inverse Laplace transform of the model equations. 4 The mixing clearance introduced as a novel non‐compartmental parameter of distribution dynamics was significantly correlated with cardiac output. The steady‐state volume of 14 l matched the extracellular volume. The systemic extraction ratio of 23% may reflect the fractional liver blood flow. 5 This pharmacokinetic model can be applied when an independent observation of cardiac output is available. In contrast to the conventional compartmental (or sum of exponential) approach it contains fewer adjustable parameters which can be more readily interpreted in physiological terms.
Are young adults with asthma treated sufficiently with inhaled steroids? A population‐based study of prescription data from 1991 and 1994
Authors: GAIST DAVID , HALLAS JESPER , HANSEN NIELS‐CHR. G. , GRAM LARS F. 
Published: October 2003

1 We conducted a descriptive cross‐sectional study of asthma therapy among young adults to assess to what extent the current guidelines for asthma therapy have been implemented. In particular, we examined the use of inhaled corticosteroids in heavy users of inhaled β‐adrenoceptor agonists. 2 Data were retrieved from a population‐based prescription database. For each of the years 1991 and 1994, all 20 to 44‐year‐olds who redeemed anti‐asthma medication in the Odense area (210 000 inhabitants) were studied. 3 We identified the number of users and total sales volume for specific anti‐asthma medications in defined daily doses (DDD) as well as the number of users and median annual doses of common regimens. Combined use of inhaled corticosteroids and inhaled β‐adrenoceptor agonists was also described. 4 The annual sales volume of anti‐asthma drugs increased by 23% to 927 636 DDD from 1991 to 1994. Inhaled corticosteroids were mainly responsible for this with a 52% increase in number of users and an 88% increase in DDD. Inhaled β‐adrenoceptor agonists used in monotherapy remained the most popular regimen in 1994 (1685 users=39%). Inhaled corticosteroids in combination with inhaled β‐adrenoceptor agonist were the second most popular regimen in 1994 (1308 users=30%), increasing by 64% as compared with 1991. However, among patients with an annual use of inhaled β‐adrenoceptor agonist of 200 DDD (1600 ‘puffs’) or more the percent of patients not receiving inhaled corticosteroids at all only fell from 37 to 33%. 5 Though the number of patients being treated with inhaled corticosteroids has increased, there is still evidence of a substantial underuse.
Pharmacodynamics and pharmacokinetics of BAY x 7195 aerosol, a new and selective receptor antagonist of cysteinyl‐leukotrienes, in normal volunteers
Authors: WENSING G. , HEINIG R. , KUHLMANN J. 
Published: October 2003

1The safety, tolerability and pharmacokinetics of BAY x 7195 aerosol, a new selective receptor antagonist of cysteinyl‐leukotrienes, were investigated in healthy male volunteers in two observational studies (1 and 2 mg; n=5 each) and two double blind, placebo‐controlled two way crossover studies (4 and 8 mg; n=6 each) using the commercially available Inhaler Ingelheim M.2The pharmacodynamic effect was assessed by testing the ability of BAY x 7195 aerosol to inhibit leukotriene‐D4 (LTD4) induced bronchoconstriction in healthy volunteers. Using a double‐blind, placebo‐controlled three way crossover design, volunteers received 2 and 4 mg of BAY x 7195 by means of a newly developed metered dose dry powder inhaler. Bronchoprovocation with nebulized LTD4 was performed 20 min and 8 h (n=6 each) after drug administration. Specific airways conductance (SGaw) served to assess the airway's response.3BAY x 7195 aerosol was safe and well tolerated. Inhalation of the aerosol had no effect on baseline lung function. Only one volunteer reported cough following the inhalation of the 8 mg dose.4The pharmacokinetics of unchanged drug following the administration of BAY x 7195 aerosol were linear in the investigated range of doses and in general very similar to a previously investigated tablet formulation. Plasma‐concentration vs time courses followed a two‐compartment body model. Compared with oral administration of the tablet formulation absorption tended to be more rapid with the aerosol formulation.5Compared with placebo, 2 and 4 mg BAY x 7195 increased the concentration of LTD4 needed to produce a 35% decrease in SGaw 20 min after drug administration by a mean (geometric) of 14.2 and 29.7 fold, respectively. For both doses only three volunteers showed a protective effect against LTD4 induced bronchoconstriction 8 h after drug administration. Individual shifts in the concentration‐response curve ranged between 0.4 and 7.2 fold.6In conclusion, the present results suggest that BAY x 7195 aerosol is a safe and potent but short acting receptor antagonist of cysteinyl leukotrienes in man.
The causes of essential hypertension
Authors: BROWN MORRIS J. 
Published: October 2003

1Confusion between the criteria for defining and diagnosing hypertension may have misled the search for the causes of hypertension. 2The systematic approach of molecular genetics appears to offer the best chance of explaining hypertension, but the attractions are partly offset by the large numbers required, and unproven record of the genetic techniques in finding functional mutations in complex human disorders. 3Part of the evidence for the polygenic nature of essential hypertension derives from the variable response to a large number of different anti‐hypertensive agents. Systematic investigation of this variability may provide a basis for dividing patients into genetically more homogeneous sub‐groups, within which smaller numbers will be required to detect the genes responsible for the susceptibility to hypertension. 4The proportion of hypertensive patients with affected siblings has been studied in 6000 patients from Addenbrookes Hospital and local general practices. A recurrence risk for hypertension of∼3.5 was found. 5Approximately two‐thirds of patients have no known affected siblings. The next largest group, about one third, is patients whose siblings are all hypertensive. In a small group, <10% of all patients, half the siblings are hypertensive. 6We conclude from these surprising findings that hypertension is not a continuous, multifactorial part of the normal blood pressure distribution. They suggest that several more single‐gene disorders causing hypertension will be found. The sibships where all members are hypertensive are inconsistent with the segregation of Mendelian genetics and suggest the selection of some genes linked to hypertension at the time of gamete maturation.
A randomized, double‐blind, placebo‐controlled trial comparing pethidine to metamizol for treatment of post‐anaesthetic shivering
Authors: MONSÓ A. , RIUDEUBAS J. , BARBAL F. , LAPORTE J‐R. , ARNAU J. M. 
Published: October 2003

1Shivering is frequent during the post‐anaesthetic recovery period, and there is no clear consensus about the best strategy for its treatment. We tested the efficacy of two commonly used analgesic drugs, pethidine and metamizol. 2A randomized, double‐blind, placebo‐controlled clinical trial was performed, including 104 adult patients who presented with post‐anaesthetic shivering during the recovery from general anaesthesia. They were randomized to receive placebo (n=32), metamizol 25 mg kg−1 (n=37), or pethidine 0.4 mg kg−1 (n=35). The response to treatment was assessed 5, 15 and 45 min after drug administration, and the main outcome variable was complete suppression of shivering. 3The efficacy at 5, 15 and 45 min was as follows: placebo 6%, 16% and 37%; metamizol 13.5%, 32% and 76%, and pethidine 89%, 91% and 89%. With both active drugs the efficacy at all three time intervals was significantly higher than that with placebo (P<0.05). The differences (at 5 and 15, but not at 45 min) between pethidine and metamizol were statistically significant (P<0.05). Both drugs were well tolerated. 4The persistence of shivering at 45 min in two thirds of placebo‐treated patients indicates that drug treatment is worthwhile; metamizol produces a better post‐anaesthetic shivering response than placebo, especially 15 and 45 min after drug administration; the efficacy of pethidine was the highest and the response to it appeared more quickly; however, at 45 min it was similar to that observed with metamizol. 5Both metamizol and pethidine suppress postanaesthetic shivering, but the latter induces a quicker and more reliable response.
Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N‐demethylation
Authors: SCHMIDER JÜRGEN , GREENBLATT DAVID J. , HARMATZ JEROLD S. , SHADER RICHARD I. 
Published: October 2003

1To determine kinetic parameters (Vmax, Km) for cytochrome P450 (CYP) mediated metabolic pathways, nonlinear least squares regression is commonly used to fit a model equation (e.g., Michaelis Menten [MM]) to sets of data points (reaction velocity vs substrate concentration). This method can also be utilized to determine the parameters for more complex mechanisms involving allosteric or multi‐enzyme systems. Akaike's Information Criterion (AIC), or an estimation of improvement of fit as successive parameters are introduced in the model (F‐test), can be used to determine whether application of more complex models is helpful. To evaluate these approaches, we have examined the complex enzyme kinetics of amitriptyline (AMI) N‐demethylation in vitro by human liver microsomes. 2For a 15‐point nortriptyline (NT) formation rate vs substrate (AMI) concentration curve, a two enzyme model, consisting of one enzyme with MM kinetics (Vmax=1.2 nmol min−1 mg−1, Km=24 μm) together with a sigmoidal component (described by an equation equivalent to the Hill equation for cooperative substrate binding; Vmax=2.1 nmol min−1 mg−1, K′=70 μm; Hill exponent n=2.34), was favoured according to AIC and the F‐test. 3Data generated by incubating AMI under the same conditions but in the presence of 10 μm ketoconazole (KET), a CYP3A3/4 inhibitor, were consistent with a single enzyme model with substrate inhibition (Vmax=0.74 nmol min−1 mg−1, Km=186 μm, K1=0.0028 μm−1). 4Sulphaphenazole (SPA), a CYP2C9 inhibitor, decreased the rate of NT formation in a concentration dependent manner, whereas a polyclonal rat liver CYP2C11 antibody, inhibitory for S‐mephenytoin 4′‐hydroxylation in humans, had no important effect on this reaction. 5Incubation of AMI with 50 μm SPA resulted in a curve consistent with a two enzyme model, one with MM kinetics (Vmax=0.72 nmol min−1 mg−1, Km=54 μm) the other with ‘Hill‐kinetics’ (Vmax=2.1 nmol min−1 mg−1, K′=195 μm; n=2.38). 6A fourth data‐set was generated by incubating AMI with 10 μm KET and 50 μm SPA. The proposed model of best fit describes two activities, one obeying MM‐kinetics (Vmax=0.048 nmol min−1 mg−1, Km=7 μm) and the other obeying MM kinetics but with substrate inhibition (Vmax=0.8 nmol min−1 mg−1, Km=443 μm, K1=0.0041 μm−1). 7The combination of kinetic modelling tools and biological data has permitted the discrimination of at least three CYP enzymes involved in AMI N‐demethylation. Two are identified as CYP3A3/4 and CYP2C9, although further work in several more livers is required to confirm the participation of the latter.
A cohort study of the ocular safety of anti‐ulcer drugs
Authors: GARCÍA RODRÍGUEZ LUIS A. , MANNINO SALVATORE , WALLANDER MARI‐ANN , LINDBLOM BERTIL 
Published: October 2003

1Recently, some cases have been reported where intravenous use of omeprazole was followed by loss of vision. We followed up a cohort of close to 140 000 persons during periods of treatment and non‐treatment with five anti‐ulcer drugs.2The relative risk of vascular disorders of the eye during use of omeprazole compared with non‐use was 1.8 (95% CI 0.5–6.0). Use of other anti‐ulcer drugs was associated with a similar risk of vascular disorders. The relative risk associated with current use of any anti‐ulcer drug was 1.9 (95% CI 1.1–3.4). We did not find a single case of optic inflammatory disorder during treatment with any of the five anti‐ulcer drugs.3These results do not suggest a major increased risk for vascular or inflammatory disorders of the eye associated with use of omeprazole or other anti‐ulcer drugs.
In vitro adrenaline and collagen‐induced mobilization of platelet calcium and its inhibition by naftopidil, doxazosin and nifedipine
Authors: Alarayyed N. A. , Cooper M. B. , Prichard B. N. C. , Betteridge D. J. , Smith C. C. T. 
Published: October 2003

Aims The aim of the study was to obtain further information regarding the modes of action of doxazosin, naftopidil and nifedipine on platelet function.
Methods We conducted an in vitro study of drug influences on adrenaline and collagen‐induced mobilization of platelet calcium.‘fn2\Results In the presence of fibrinogen (300 μg ml−1 ) both collagen (5 μg ml−1 ) and adrenaline (16 μm ) stimulated the aggregation of washed platelets. Collagen induced a transient rise (+4.97±0.63 μm ) in platelet Ca2+ concentration, [
Ca2+]i, as measured using the photoprotein aequorin, which coincided with the onset of aggregation. Adrenaline induced a smaller rise (+3.6±0.96 μm ) which, however, occurred after the onset of aggregation. Naftopidil, an α1‐adrenoreceptor antagonist produced a concentration‐dependent inhibition of collagen‐induced Ca2+ mobilization, maximum inhibition (22.9±4%, P<0.05) occurring with 40 μm naftopidil. The inhibition of Ca2+ mobilization was not reflected by a concentration‐dependent inhibition of platelet aggregation, although 40 μm naftopidil produced statistically significant inhibition (23.3±11.7%, P<0.05). The adrenaline‐induced rise in [Ca2+]i was inhibited dose dependently by naftopidil (e.g. 40 μm naftopidil, 100±0%, P<0.05), as was aggregation (40 μm naftopidil, 100±0%, P<0.05). Doxazosin, another α1‐adrenoreceptor blocker, inhibited Ca2+ mobilization induced by collagen to similar extents as for naftopidil (30 μm doxazosin, 17.4±2.5%, P<0.05), but did not inhibit platelet aggregation. It also inhibited the adrenaline‐induced rise in [Ca2+]i in a concentration‐dependent manner (30 μm doxazosin, 37.6±13.7%, P<0.05), significant inhibitions of platelet aggregation also being produced (30 μm, 49.6±17.2%, P<0.05). As expected, the calcium channel blocker nifedipine produced concentration‐dependent inhibitions of both collagen‐induced Ca2+ mobilization (e.g. 28 μm nifedipine, 47.8±2.7%, P<0.05) and aggregation (28 μm, 55.1±9.2%, P<0.05).
Conclusions These data indicate that the α1‐adrenoreceptor blockers, naftopidil and doxazosin, inhibit Ca2+ mobilization, this mechanism being possibly the means whereby these drugs inhibit platelet aggregation.
The acute effects of inhaled salbutamol on the beat‐to‐beat variability of heart rate and blood pressure assessed by spectral analysis
Authors: Jartti Tuomas , Kaila Timo , Tahvanainen Kari , Kuusela Tom , Vanto Timo , Välimäki Ilkka 
Published: October 2003

Aims We wanted to study the effects of a 600 μg inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma.
Methods In this randomized, double‐blind, placebo‐controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow‐volume spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R–R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross‐spectral analysis.
Results Salbutamol significantly decreased the total and low frequency (LF) variability of R–R intervals as well as the high frequency (HF) variability of R–R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R–R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation.
Conclusions We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.
Pharmacokinetics of thiopentone enantiomers following intravenous injection or prolonged infusion of rac‐thiopentone
Authors: Cordato D. J. , Gross A. S. , Herkes G. K. , Mather L. E. 
Published: October 2003

Aims Thiopentone is administered as a racemate (rac‐thiopentone) for induction of anaesthesia as well as for neurological and neurosurgical emergencies. The pharmacokinetics and pharmacodynamics of rac‐thiopentone have been extensively studied but the component R‐(+)‐ and S‐(−)‐ enantiomers, until very recently, have been largely ignored.
Methods The present study analyses the pharmacokinetics of R‐(+)‐ and S‐(−)‐thiopentone in 12 patients given rac‐thiopentone intravenously for induction of anaesthesia and five patients given a prolonged infusion of rac‐thiopentone used for treatment of intracranial hypertension.
Results The mean total body clearance (CLT ) and apparent volume of distribution at steady‐state (V
ss ) showed trends towards higher values for R‐(+)‐ than for S‐(−)‐thiopentone in both patient groups; CLT and V
ss of unbound fractions of R‐(+)‐ and S‐(−)‐thiopentone, however, did not show these trends. The time courses of R‐(+)‐ and S‐(−)‐ thiopentone serum concentrations were so similar that EEG effect could not be attributed to one or other enantiomer. Serum protein binding for S‐(−)‐thiopentone was greater than for R‐(+)‐thiopentone (P=0.02) and 24 h urinary excretion of R‐(+)‐thiopentone was greater than for S‐(−)thiopentone (P=0.03). In one patient, concomitant measurement of CSF and serum thiopentone concentrations found that serum: CSF equilibration of unbound fractions of both enantiomers was essentially complete.
Conclusions The study was unable to determine any pharmacokinetic difference of clinical significance between the R‐(+)‐ and S‐(−)‐thiopentone enantiomers and concludes that minor differences in CLT and V
ss could be explained by enantioselective difference found in serum protein binding.