bluuebunny/crossref_metadata_2025 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

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

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

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

objective 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.
Dose‐effect relationship for several coagulation markers during administration of the direct thrombin inhibitor S 18326 in healthy subjects
Authors: Gaussem P. , Dubar M. , le Bonniec B. , Richard‐Lordereau I. , Jochemsen R. , Aiach M.
Published: March 2003

Aims  We conducted a phase I placebo‐controlled trial with two i.v. doses (0.5 mg h−1 and 3 mg h−1) of S 18326, a selective thrombin inhibitor that interacts with the catalytic site of thrombin, with the aim to study the relationships between increasing plasma levels of S 18326 and changes in coagulation tests and thrombin generation markers.

Methods  Thirty‐six healthy male volunteers were divided into three groups. In each group, 10 volunteers were randomly assigned to receive S 18326 and two to receive a placebo. Following a bolus of 4.5 mg, doses were 0.5 mg h−1 in the first group and 3 mg h−1 in the two other groups, administered as an i.v. infusion for 24 h. Blood was drawn repeatedly up to 36 h after the bolus, and tested for the activated clotting time (ACT) and activated partial thromboplastin time (APTT). The APTT reagent was chosen among five commercial reagents to yield a linear increase in the clotting time among possible therapeutic S 18326 concentrations in vitro. To accurately measure the thrombin‐inhibiting effects of low doses of S 18326 (< 0.5 µm), we developed a specific chromogenic assay. We also measured F1 + 2 prothrombin fragment levels to assess the effect of S 18326 on thrombin generation in vivo.

Results  A two‐compartment pharmacokinetic model was fitted to the S 18326 plasma concentration vs time data by using population pharmacokinetic methods. Results of the pharmacodynamic‐pharmacokinetic relationships showed that both the ACT and APTT methods yielded a linear increase according to the S 18326 concentration measured using a highly sensitive analytical method. At the end of infusion, ACT was prolonged 1.20 and 1.95‐fold in the 0.5 mg h−1 and the 3 mg h−1 groups, respectively, and APTT was prolonged 1.27 and 2.75‐fold. Thrombin inhibition plateaued above 0.5 µm of S 18326 according to an Emax model, confirming that the test was highly sensitive. F1 + 2 levels fell significantly after the 24 h S 18326 infusion (0.83 nm to 0.6 nm and 0.80 nm to 0.44 nm in the 0.5 mg h−1 and the 3 mg h−1 groups, respectively), but remained stable after the placebo infusion.

Conclusions  Our results support specific monitoring of the thrombin inhibitor S 18326 with ACT and APTT to establish the safety range of the drug in further studies. Moreover, the fall in F1 + 2 prothrombin fragments suggests that S 18326 effectively reduces the retroactivation of factors V and VIII by thrombin.
Factors associated with discontinuing insulin therapy after diabetic ketoacidosis in adult diabetic patients
Authors: Hsin Yu E. , Guo H.‐R. , Wu Ta‐Jen
Published: March 2003

Aims  To assess the factors associated with successful discontinuation of insulin therapy after diabetic ketoacidosis (DKA) in adult patients.

Methods  Patients (≥ 18 years) attending the Endocrine and Metabolism Clinic at a major hospital in southern Taiwan were recruited. After recovery from the acute stage, those with no contraindications to oral antidiabetic agents, with adequate β cell reserve, and with no antiglutamic acid decarboxylase (GAD) antibody were treated with oral agents.

Results  Sixty‐six patients (38 males, 28 females, aged 18–76 years) were included, and 21 qualified for treatment with oral agents. These 21 patients were older at diagnosis of diabetes (45.5 ± 14.0 vs. 40.0 ± 13.8 years, P = 0.047), had shorter diabetes duration (median 0 vs. 5.5 months, P = 0.040), higher BMI (median 23.4 vs. 19.5 kg/m2, P < 0.001), higher serum osmolality during DKA (352.1 ± 40.7 vs. 318.0 ± 16.4 mmol/kg, P = 0.005), and lower insulin dose following recovery (median 0.49 vs. 0.83 unit/kg/d, P < 0.001) than those patients that had to continue insulin therapy. Thirteen patients (8 males, 5 females; 62%) successfully discontinued insulin for at least one year without recurrence of DKA. Multiple logistic regression analyses showed that ΒΜΙ ≥ 25 kg/m2 (adjusted relative risk (ARR) 8.85, 95% CI 1.05, 8.39), diabetes onset age ≥ 40 years (ARR 8.08, 95% CI 1.16, 6.95), and undiagnosed diabetes before DKA (ARR 8.90, 95% CI 1.19, 7.51) were significant factors associated with successful discontinuation of insulin therapy.

Conclusion  We identified three independent clinical factors associated with successful discontinuation of insulin therapy after DKA.

Diabet. Med. 18, 895–899 (2001)
Causes of spatially variable tectonic subsidence in the Miocene Bermejo Foreland Basin, Argentina
Authors: Cardozo N. , Jordan T.
Published: March 2003

ABSTRACT Tectonic subsidence in the 20–9 Ma Bermejo basin resulted from spatially variable crustal loading on a lithosphere of spatially variable strength (e.g. elastic thickness). Reconstruction of the crustal loads added between 20 and 9 Ma, and assessment of the effects of these loads on an elastic, isotropic lithosphere confirm this hypothesis. Elastic models effectively explain tectonic subsidence east of the Iglesia–Calingasta basin, but west of it crustal loads were locally compensated. Elastic models also prove that the 20–9 Ma Frontal Cordillera loading is of no importance in the mechanical system of the Bermejo basin. 2D and 3D elastic models of a uniformly strong lithosphere under 20–9 Ma crustal loads corrected for post‐9 Ma erosion successfully replicate the 9 Ma Bermejo basin's proximal palaeotopography. However, they fail to replicate the 9 Ma basin's medial and distal palaeotopography. A 3D finite element model of a lithosphere with bimodal strength (weak below the Bermejo basin and west of the Precordillera, and strong below the Precordillera and east of the Valle Fértil lineament) successfully replicates the 9 Ma basin's palaeotopography. That variable strength model introduces a southward decrease in the wavelength of flexural deformation, which results in a basin that narrows southward, consistent with the 9 Ma Bermejo basin. The preferred 9 Ma lithospheric strength distribution is similar to the present lithospheric strength field derived from gravity data, suggesting that the bimodal strength signature was retained throughout the entire basin's evolution. Late Miocene flattening of the subducting slab, tectonic change to a broken foreland, or deposition of a thick (∼8–10 km) sedimentary cover did not affect the strength of the lithosphere underlying the Bermejo basin. The long‐term bimodal strength field does not correlate with the documented thickness of the seismogenic crust.
‘Arm‐reaching’ neurons in the parietal area V6A of the macaque monkey
Authors: Fattori Patrizia , Gamberini Michela , Kutz Dieter F. , Galletti Claudio
Published: March 2003

In previous experiments we have found that several cells of area V6A in the macaque superior parietal lobule were activated by small and stereotyped movements of the arms (C. Galletti, P. Fattori, D. F. Kutz & P. P. Battaglini, Eur. J. Neurosci., 1997, 9, 410). This behaviour was not accounted for by retinal information, nor by somatosensory inputs from the arms. We now want to investigate whether V6A neurons are modulated by purposeful movements aimed at reaching visual targets or targets located outside the field of view. V6A neuronal activity was collected while monkeys performed arm movements during an instructed‐delay reaching task in darkness. The task required the animal to reach out for a visual target in the peripersonal space and to bring the hand back to its body. Quantitative analysis of neuronal activity carried out on 55 V6A neurons showed that: (i) the great majority of neurons (71%) was significantly modulated during the execution of arm movements; (ii) 30% of neurons were significantly modulated during preparation of reaching; and (iii) modulations during both execution and preparation of reaching occurred in the absence of any visual feedback and were not due to eye movements. V6A reach‐related neurons could be useful in guiding the hand to reach its target with or without visual feedback.
Proliferative effects of eosinophil lysates on cultured human airway smooth muscle cells
Authors: Masu K. , Ohno I. , Suzuki K. , Okada S. , Hattori T. , Shirato K.
Published: March 2003

Background The hypertrophy/hyperplasia of airway smooth muscle (ASM) cells is one of the characteristic features of bronchial asthma. This structural change leads to the thickening of airway walls resulting in the amplification of airway narrowing. However, the pathogenesis of this structural change has not yet been determined. Eosinophils, which play a pathogenic role in asthma, have been demonstrated to have proliferative effects on fibroblasts and vascular smooth muscle cells.

Objective We attempted to investigate the potential of eosinophils to induce the proliferation of ASM cells.

Methods We examined the effect of lysates of eosinophils purified from peripheral blood of healthy donors on cultured human ASM cell proliferation.

Results Eosinophil lysates significantly induced ASM cell proliferation in time‐ and dose‐dependent manners, reaching a maximum on day 6 at 50% of eosinophil lysates (6.0 ± 0.7 × 104[mean ± SD] /well, n = 5 vs. 4.5 ± 1.1 × 104/well, n = 5; P < 0.05). This proliferative activity was heat‐sensitive and recovered in the soluble fraction of the eosinophil lysates. Furthermore, the molecular weight of the mitogenic activity in the soluble fraction was identified as lower than 10 kDa. The inhibitory activity to ASM cell proliferation was also found in the insoluble fraction of the lysates.

Conclusion These results indicate that circulating eosinophils store mitogenic activity for ASM cells, suggesting that eosinophils might contribute to the development of the hyperplasia of ASM cells in asthmatics through the release of the stored mitogenic activity upon stimulation at the site of inflammation.
Hypertonic saline nasal provocation and acoustic rhinometry
Authors: Baraniuk J. N. , Ali M. , Naranch K.
Published: March 2003

Background  Hypertonic saline (HTS) acts as an airway irritant in human nasal mucosa by stimulating nociceptive nerves and glandular secretion. HTS does not change vascular permeability. In asthma, HTS causes airflow obstruction.

Objective  To determine the effect of HTS on mucosal swelling using acoustic rhinometry (AcRh). Potential vasodilator effects were controlled by maximally constricting mucosal vessels with oxymetazoline (Oxy).

Method  Normal subjects had AcRh before and 30 min after either 0.05% Oxy or saline (0.9% NaCl) nasal treatments. Nasal provocations followed immediately with five step‐wise incremental escalating doses of HTS administered at 6‐min intervals. AcRh was performed 1, 3 and 5 min after each HTS administration, and then after blowing the nose at 5 min. The minimum cross‐sectional area (Amin), volume of the anterior 6 cm of nasal cavity (V6) and incremental changes from pre‐drug treatment baseline levels (Δ, mean ± SEM) were calculated.

Results  Oxy increased Amin by 46% (Δ = 0.48 ± 0.07 cm2, P = 0.0001) and V6 by 53% (Δ = 9.9 ± 1.5 mL, P < 1 × 10−7) during the first 30 min. Saline (vehicle) treatment had no effect. The maximum HTS dose had no effect after 1 or 3 min. However, in the 4th and 5th minutes there were reductions in Amin (Δ = 0.07 ± 0.03 cm2, P = 0.035) and V6 (Δ = 1.57 ± 0.42 mL, P = 0.004) with an increase in the weight of secretions (Δ = 700 ± 100 mg, P < 0.05). Blowing the nose returned Amin and V6 towards baseline. Oxy had no effect on HTS‐induced changes in Amin, V6, pain, rhinorrhea or weight of secretions.

Conclusion  HTS induced nociceptive nerve stimulation and mucus secretion, and reduced V6 and Amin. Oxy caused vasoconstriction but did not alter HTS‐induced effects. HTS may stimulate neurogenic axon response‐mediated glandular secretion that contributes to perceptions of nasal obstruction in normal subjects.
Interleukin‐12 inhibits eosinophil differentiation from bone marrow stem cells in an interferon‐γ‐dependent manner in a mouse model of asthma
Authors: Rais M. , Wild J. S. , Choudhury B. K. , Alam R. , Stafford S. , Dharajiya N. , Sur S.
Published: March 2003

Background  Intrapulmonary administration of IL‐12 has been shown to inhibit the number of eosinophils in lung murine models of asthma, but the precise mechanism of this inhibition has not been reported. The purpose of this study was to examine whether IL‐12 treatment inhibits bone marrow eosinophilopoiesis, and to elucidate the role of IFN‐γ in this process.

Objective  To elucidate the in vivo and in vitro effects of IL‐12 on eosinophil differentiation from murine bone marrow (BM) stem cells, and to examine the mechanistic role of IFN‐γ in this process.

Methods  Allergen‐sensitized BALB/c mice were administered low doses of intranasal IL‐12 at the time of allergen challenge, and the number of eosinophils in BM was determined 3 days later. The direct actions of IL‐12 on eosinophil differentiation from BM cells were determined in vitro. The mechanistic role of IFN‐γ was assessed by measuring IFN‐γ induction by IL‐12 in BM cell cultures, and through the use of IFN‐γ KO mice.

Results  Treatment of allergic mice with intrapulmonary IL‐12 (1 ng or 10 ng) reduced eosinophils in BM by 43%. Culture of BM cells from allergen‐sensitized mice with IL‐3 + IL‐5 induced eosinophil differentiation in vitro. Addition of IL‐12 to these cultures inhibited eosinophil differentiation, with maximal inhibition (45%) occurring at 10 ng/mL IL‐12 concentration. IL‐12 induced IFN‐γ production from BM cultures, and failed to inhibit eosinophil differentiation in IFN‐γ‐knockout mice, indicating a critical mechanistic role for IFN‐γ.

Conclusion  This study demonstrates that IL‐12 selectively inhibits BM eosinophilopoiesis, and that this effect is mediated by IFN‐γ. Intrapulmonary IL‐12 has suppressive effects on BM eosinophilopoiesis that may represent a novel mechanism contributing to the anti‐eosinophilic effects of IL‐12 in allergic airway disease.
Site-specific strong ground motion prediction using 2.5-D modelling
Authors: Narayan J. P.
Published: March 2003

An algorithm was developed using the 2.5-D elastodynamic wave equation, based on the displacement–stress relation. One of the most significant advantages of the 2.5-D simulation is that the 3-D radiation pattern can be generated using double-couple point shear-dislocation sources in the 2-D numerical grid. A parsimonious staggered grid scheme was adopted instead of the standard staggered grid scheme, since this is the only scheme suitable for computing the dislocation. This new 2.5-D numerical modelling avoids the extensive computational cost of 3-D modelling. The significance of this exercise is that it makes it possible to simulate the strong ground motion (SGM), taking into account the energy released, 3-D radiation pattern, path effects and local site conditions at any location around the epicentre. The slowness vector (py) was used in the supersonic region for each layer, so that all the components of the inertia coefficient are positive.

The double-couple point shear-dislocation source was implemented in the numerical grid using the moment tensor components as the body-force couples. The moment per unit volume was used in both the 3-D and 2.5-D modelling. A good agreement in the 3-D and 2.5-D responses for different grid sizes was obtained when the moment per unit volume was further reduced by a factor equal to the finite-difference grid size in the case of the 2.5-D modelling. The components of the radiation pattern were computed in the xz-plane using 3-D and 2.5-D algorithms for various focal mechanisms, and the results were in good agreement. A comparative study of the amplitude behaviour of the 3-D and 2.5-D wavefronts in a layered medium reveals the spatial and temporal damped nature of the 2.5-D elastodynamic wave equation.

3-D and 2.5-D simulated responses at a site using a different strike direction reveal that strong ground motion (SGM) can be predicted just by rotating the strike of the fault counter-clockwise by the same amount as the azimuth of the site with respect to the epicentre. This adjustment is necessary since the response is computed keeping the epicentre, focus and the desired site in the same xz-plane, with the x-axis pointing in the north direction.
p21WAF1 is associated with CDK2 and CDK4 protein during HL‐60 cell differentiation by TPA treatment
Authors: Cho J.‐W. , Jeong Y.‐W. , Kim K.‐S. , Oh J.‐Y. , Park J.‐C. , Lee J.‐C. , Baek W.‐K. , Suh S.‐I. , Suh M.‐H.
Published: March 2003

TPA‐treated HL‐60 cells are mainly arrested in G1 by p21WAF1 accumulation. We investigate the downstream changes following such accumulation. Increased p21WAF1 is associated with CDK2 and CDK4. pRb is dephosphorylated in the presence of p21–CDK2/4 complexes, and the Rb–E2F1 complex increases after TPA treatment, whereas the Rb–HDAC1 complex decreases slightly. Our results suggest that increased p21WAF1 is associated with CDK2/4, and that these complexes induce pRb dephosphorylation. In turn, hypophosphorylated pRb are mainly complexed with E2F1, but HDAC1 appears not to be a key component in this process.
Laparoscopic port scar endometriosis: an unusual complication
Authors: Sizer Andrew R. , Bhal Preetkiron S. , Ladipo Oladapo A. , Shaw Robert W.
Published: March 2003

We report a case of an endometrioma in a laparoscopic port scar, an unusual possible complication of laparoscopic surgery. The patient presented with typical features of a scar endometrioma and the lesion was surgically excised. Laparoscopic laser treatment to pelvic endometriosis in this patient has resulted in her becoming pregnant. The aetiology of scar endometriosis is discussed.
What every emergency physician needs to know about childhood asthma
Authors: Browne Gary J , Phin Susan J , Chin Raymond
Published: March 2003

See Commentary, page 405.
The effect of the InterLink® cannula on fluid flow rates and haemolysis
Authors: Saw Sharon , Arendts Glenn
Published: March 2003

Objective:

To examine the effect of the InterLink cannula system (Becton Dickinson, New Jersey, NY, USA) on intravenous fluid flow rates and red blood cell haemolysis.

Methods:

An in vitro study was performed with crystalloid and packed red blood cells run through intravenous catheters of various sizes, with and without the InterLink cannula. Data recorded and analysed included fluid flow rates and plasma free haemoglobin concentration.

Results:

The InterLink cannula significantly reduced flow of crystalloid through a 14G catheter (reduction of median flow rate by 0.72 L/h, 12.3%, P  < 0.001). There was a reduction of flow of packed red blood cells through a 14G catheter (0.11 L/h) but this was not statistically significant. There was no significant reduction of flow through smaller catheters and no significant effect on red blood cell haemolysis.

Conclusions:

The InterLink cannula reduced flow rates through large diameter intravenous catheters. Because of other factors affecting fluid infusion in vivo this is of minor clinical significance. No increased haemolysis of red blood cells occured with the InterLink cannula.
HOSPITAL SEPARATIONS INDICATE INCREASING NEED FOR PREVENTION OF DIABETIC FOOT COMPLICATIONS IN CENTRAL AUSTRALIA
Authors: Ewald Dan , Patel Mahomed , Hall Gill
Published: March 2003

The aim of this study was to guide service provision for prevention of diabetic foot complications through the analysis of hospital separation data for those with diabetes in central Australia. We reviewed the hospital separation data for central Australia from 1992 to 1997 for adults known to be diabetic and those with diabetic foot complications. Foot complications were identified from International Classification of Diseases‐9th Revision (ICD‐9) codes. Additionally, we assessed the proportion of cases with diabetic foot, identified by ICD‐9 coding and confirmed by record review, that were identified by Australian National‐Diagnostic Related Group‐Version 3 (AN‐DRG‐3) coding. Separations with diabetes doubled from 352 in 1992 to 796 in 1997. This represents an increase from 1232 to 2521 separations per 100 000 people over 15 years of age. Separations with foot complications increased threefold from 28 in 1992 to 90 in 1997, a rate increase from 98 to 285 per 100 000 people over 15 years of age. The proportion of diabetes separations that had foot complications remained around 10% during the 6 year period. Aboriginal people made up 89% of the individuals with foot complications and 91% of separations for diabetic foot. Foot complications were predominantly of the more acute type (90%), amenable to early intervention. The AN‐DRG‐3 code for diabetic foot identified only 59% (37/63 in 1997) of the separations identified by the ICD‐9 codes, and admitted primarily for foot complications in Alice Springs Hospital. The known burden of hospital care for diabetes and diabetic foot complications has increased markedly in recent years. A combination of changes in prevalence, primary care utilisation, detection, hospital access or re‐admission rates may underlie the observed increases. As it is very unlikely that diabetes or diabetic foot complications are being over diagnosed, or that the hospitals are over utilised, this analysis shows there is an increasingly apparent need for improved prevention of diabetic foot complications. Therefore primary health care systems should ensure that they implement evidence‐based care for preventing foot complications among people with diabetes.
APPROACH TO SUSTAINABLE PRIMARY HEALTH CARE SERVICE DELIVERY FOR RURAL AND REMOTE SOUTH AUSTRALIA
Authors: Taylor Judy , Blue Ian , Misan Gary
Published: March 2003

We describe the operation of four University Teaching Practices established by the South Australian Centre for Rural and Remote Health (SACRRH) and the Adelaide University Department of General Practice. These practices were established in response to the acknowledged difficulty in recruiting and retaining GPs in rural South Australia. The practices are co‐located with a hospital or accident and emergency service and community based nurses and allied health professionals. They provide integrated health care and multidisciplinary health care student placements in a learning environment where students experience rural multidisciplinary practice and country life. The study found that although the sites differed in significant ways, they all provided integrated care and effective placements for students. This style of health care delivery is flexible and broadly applicable. Sustainability is achieved through financially viability, attracting and retaining health care professionals and the development of electronic information systems, to support integrated practice.
Ecological processes influencing mortality of juvenile pink salmon (Oncorhynchus gorbuscha) in Prince William Sound, Alaska
Authors: Willette T. M. , Cooney R. T. , Patrick V. , Mason D. M. , Thomas G. L. , Scheel D.
Published: March 2003

Our collaborative work focused on understanding the system of mechanisms influencing the mortality of juvenile pink salmon (Oncorhynchus gorbuscha) in Prince William Sound, Alaska. Coordinated field studies, data analysis and numerical modelling projects were used to identify and explain the mechanisms and their roles in juvenile mortality. In particular, project studies addressed the identification of major fish and bird predators consuming juvenile salmon and the evaluation of three hypotheses linking these losses to (i) alternative prey for predators (prey‐switching hypothesis); (ii) salmon foraging behaviour (refuge‐dispersion hypothesis); and (iii) salmon size and growth (size‐refuge hypothesis). Two facultative planktivorous fishes, Pacific herring (Clupea pallasi) and walleye pollock (Theragra chalcogramma), probably consumed the most juvenile pink salmon each year, although other gadids were also important. Our prey‐switching hypothesis was supported by data indicating that herring and pollock switched to alternative nekton prey, including juvenile salmon, when the biomass of large copepods declined below about 0.2 g m−3. Model simulations were consistent with these findings, but simulations suggested that a June pteropod bloom also sheltered juvenile salmon from predation. Our refuge‐dispersion hypothesis was supported by data indicating a five‐fold increase in predation losses of juvenile salmon when salmon dispersed from nearshore habitats as the biomass of large copepods declined. Our size‐refuge hypothesis was supported by data indicating that size‐ and growth‐dependent vulnerabilities of salmon to predators were a function of predator and prey sizes and the timing of predation events. Our model simulations offered support for the efficacy of representing ecological processes affecting juvenile fishes as systems of coupled evolution equations representing both spatial distribution and physiological status. Simulations wherein model dimensionality was limited through construction of composite trophic groups reproduced the dominant patterns in salmon survival data. In our study, these composite trophic groups were six key zooplankton taxonomic groups, two categories of adult pelagic fishes, and from six to 12 groups for tagged hatchery‐reared juvenile salmon. Model simulations also suggested the importance of salmon density and predator size as important factors modifying the predation process.