bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAims  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)
‘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

AbstractIn 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

SummaryBackground 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

SummaryBackground  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

SummaryBackground  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

SummaryAn 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

Abstract.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

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

AbstractObjective: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

ABSTRACT: 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

ABSTRACT: 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

AbstractOur 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.