bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics of intramuscular gentamicin administered to young infants with suspected severe sepsis in Kenya
Authors: Thomson Alison H. , Kokwaro Gilbert O. , Muchohi Simon N. , English Michael , Mohammed Shebbe , Edwards Geoffrey 
Published: July 2003

Aims  To determine the population pharmacokinetics of intramuscular (i.m.) gentamicin in African infants with suspected severe sepsis.Methods  Samples were withdrawn 1 h after a single i.m. injection of 8 mg kg−1 gentamicin and the next morning prior to any further dosing. Concentration‐time data were analysed with the population pharmacokinetic package NONMEM. Data were fitted using a one‐compartment model with a log‐normal model for interindividual variability and an additive residual error model. The influence of a range of clinical characteristics was tested on the pharmacokinetics of intramuscular gentamicin and the effect of incorporating interindividual variability on bioavailability was examined.Results  The data set comprised 107 patients and 203 concentrations. Peak concentrations ranged from 3.0 mg L−1 to 19.8 mg L−1 (median 10.6 mg L−1) and ‘next day’ samples from 0.3 mg L−1 to 6.2 mg L−1.The best models were clearance/bioavailability (CL) (L h−1) = 0.0913 × weight (kg) × (age (days) + 1)/11)0.130 and volume of distribution/bioavailability (V) = 2.02 × (1 + 0.277 × (weight −3)). Therefore, an infant with the median weight of 3 kg and age 10 days would have a predicted CL of 0.274 L h−1 and V of 2.02 L. Interindividual variability in CL was 40% and in V was 42%. This model required a term for covariance between CL and V. When variability in bioavailability was introduced as an alternative model, interindividual variability in CL was 22%, in V 18% and in relative bioavailability 36%.Conclusions  Intramuscular administration of 8 mg kg−1 gentamicin daily to infants gives mean 1 h peak concentration of 10.6 mg L−1 and a trough concentration of less than 2 mg L−1. Wide variability in the peak concentration may reflect variable absorption rate or bioavailability.
Development of a dosing strategy for enoxaparin in obese patients
Authors: Green Bruce , Duffull Stephen B. 
Published: July 2003

Aims  Enoxaparin dosing is currently based on total body weight. It is not known how to dose adjust for patients who are overweight or obese. This population pharmacokinetic pharmacodynamic (PKPD) study was undertaken to determine a suitable dosing strategy for such patients.Methods  Patients admitted to the Royal Brisbane Hospital and prescribed enoxaparin as part of their normal care were eligible for inclusion into the study. Approximately three blood samples were taken per patient to determine anti‐Xa concentrations. The occurrence of bruising was also recorded. A population pharmacokinetic–pharmacodynamic analysis using NONMEM was undertaken. Simulations were performed using MATLAB.Results  Ninety‐six patients were recruited in a prospective study. One‐third of patients had a body mass index < 24.9 kg m−2, one‐third from 25 to 29.9 kg m−2, and one‐third> 30 kg m−2. A two‐compartment linear model with additive error was fitted to the data. A covariate analysis showed clearance was best described by lean body weight and the central volume compartment by total body weight. The probability of bruising using a logistic regression model was best described by Cmax and age. Simulations suggest that patients over 50 years of age whose total body weight is> 90 kg, or under 50 years of age whose total body weight is> 120 kg are likely to have a smoother concentration–time profile and less bruising if a dose of 100 IU kg−1 (1 mg kg−1) based on lean body weight is administered every 8 h.Conclusions  Dose adjustments of enoxaparin in obese patients are likely to reduce the prevalence of bruising, although prospective validation of this is required.
Asylum, children's rights and social work
Authors: Cemlyn Sarah , Briskman Linda 
Published: July 2003

ABSTRACTAlthough it is only a minority of displaced and persecuted people globally who seek refuge in ‘Western’ countries, they meet an increasingly hostile reception. This paper focuses on the situation facing children seeking asylum with or without their families in Britain and Australia, and the implications for children's rights and for social work. The policy background and its racist foundations in both countries are outlined. Despite geopolitical differences, there are unnerving parallels. Legislative changes and policy complexity signal increasingly punitive attitudes towards asylum seekers. The situation of children and families in the community is discussed in terms of the exclusion of asylum seekers from basic rights, and specific issues for separated children. Even more damaging is the incarceration of children and families in detention centres, and the emerging research is explored. In both countries there is widespread flouting of children's rights, and children also feature as pawns in ideological contests. However, they also act autonomously and illustrate an inclusive model of citizenship. The role of social workers in the statutory and voluntary sectors is considered, and the paper concludes with a discussion of the challenges for social work of avoiding collusion with repressive policies and actively promoting human rights.
Social work with African refugee children and their families
Authors: Okitikpi Toyin , Aymer Cathy 
Published: July 2003

ABSTRACTThis article explores the issues and dilemmas that arise when social workers attempt to work with African refugee and asylum seeking children and their families. There is a complex interplay between social workers’ skills and knowledge in this area and the prevailing social attitudes towards these groups of service users. By initially setting the context of mass movement of peoples from situations of danger in their countries of origin, the discussion highlights the key issues and shows the tensions of practice intervention in this area. Drawing on a small‐scale research study with social workers and discussions with immigration officers and workers in voluntary agencies working with refugees and asylum seekers, the article draws some conclusions about the lessons that can be learnt in order to improve practice.
The social services response to unaccompanied children in England
Authors: Mitchell Fiona 
Published: July 2003

ABSTRACTIn England, social services departments have a duty to provide care and protection to unaccompanied asylum seeking children from the point they arrive in the country. In recent years, research studies have identified a number of practice and policy issues of concern regarding the social services response to unaccompanied children. This paper focuses on three broad issues that emerge from the literature. The paper explores research concerns associated with (i) the referral and assessment process, (ii) the use of the child welfare legislative framework, and (iii) a number of issues arising from the provision of placements and other support offered to unaccompanied children. The findings of the research reviewed demonstrate that there are indeed clear grounds for concern. However, this paper argues that the evidence base is relatively weak and that as a result we know very little about the nature and context of the social work response to this group of children and young people.
Serum lipids in fathers and sons at middle age: the study of sons to men born in 1913
Authors: Rosengren A. , Eriksson H. , Welin C. , Welin L. 
Published: July 2003

Abstract. Rosengren A, Eriksson H, Welin C, Welin L (Sahlgrenska University Hospital/Östra, Göteborg; and Lidköpng Hospital, Lidköping; Sweden). Serum lipids in fathers and sons at middle age: the study of sons to men born in 1913. J Intern Med 2003; 254: 126–131.Objective. To relate lipid levels in middle‐aged men to that of their fathers at 50 years of age measured 30 years earlier.Design and subjects. In 1963, 855 men born in 1913 took part in a cardiovascular risk factor survey when they were at 50 years of age. In 1993, 475 sons to these men, aged 44–56, were invited to another examination; 263 of these men were examined (response rate: 56%) and compared with their 217 fathers when they were examined at 50 years of age in 1963. In the 1993 survey, 798 men aged 50, were also examined, from a general population sample of men born in 1943 (response rate: 55%).Setting. City of Göteborg, Sweden.Main outcome measures. Serum lipids in sons as a function of lipids in their fathers.Results. Compared with the men born in 1913, both sons and men born in 1943 had lower mean serum cholesterol, but higher body mass index (BMI) and serum triglycerides. There was a significant relation between serum cholesterol in sons and their fathers (r = 0.25; P < 0.0001). Amongst sons to fathers in the highest cholesterol quartile (>6.9 mmol L−1), 37% had serum cholesterol above 6.5 mmol L−1, compared with 16% amongst sons to fathers in the lowest quartile (<5.7 mmol L−1) [adjusted odds ratio 3.73 (1.52–9.12)]. Sons to fathers with the highest serum cholesterol levels had slightly lower BMI; otherwise there was no relation between serum cholesterol in the father and any other lifestyle or biological risk factor in the sons. Serum triglyceride concentration in the father was unrelated to any variable in the son.Conclusions. There was a moderately strong association between serum cholesterol concentration in fathers and sons at middle age. However, secular trends were also important in determining serum cholesterol concentrations in those born at a later period, indicating a major role of environmental factors.
Circulating soluble cytochrome c in liver disease as a marker of apoptosis
Authors: Ben‐Ari Z. , Schmilovotz‐Weiss H. , Belinki A. , Pappo O. , Sulkes J. , Neuman M. G. , Kaganovsky E. , Kfir B. , Tur‐Kaspa R. , Klein T. 
Published: July 2003

Abstract. Ben‐Ari Z, Schmilovotz‐Weiss H, Belinki A, Pappo O, Sulkes J, Neuman MG, Kaganovsky E, Kfir B, Tur‐Kaspa R, Klein T (Beilinson and Golda Campuses, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and In Vitro Toxicology Laboratory, Sunnybrook Women's College, Toronto, Canada) Circulating soluble cytochrome c in liver disease as a marker of apoptosis. J Intern Med 2003; 254: 168–175.Objectives. To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity.Design. Laboratory research study with comparison group.Setting. Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada.Subjects. A total of 108 patients with liver disease and 30 healthy controls.Interventions. Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme‐linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick‐end‐labelling (TUNEL) assay.Main outcome measures. Soluble cytochrome c level by type of liver disease by clinical and histological findings.Results. Soluble cytochrome c concentration (mean 187.1 ± 219.5 ng mL−1) was significantly higher in patients with liver disease than in controls (39.8 ± 35.1 ng mL−1; P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 ± 2844.8 ng mL−1; P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 ± 297.0 ng mL−1) than the portal vein (mean 169.2 ± 143.3 ng mL−1), and it was highly detectable in bile (mean 2288.0 ±4596.0 ng mL−1) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 ±304.3 ng mL−1) than treated patients (77.9 ± 35.8 ng mL−1; P = 0.001).Conclusions. Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis.
Temporal responses of Arabidopsis root architecture to phosphate starvation: evidence for the involvement of auxin signalling
Authors: AL‐GHAZI Y. , MULLER B. , PINLOCHE S. , TRANBARGER T. J. , NACRY P. , ROSSIGNOL M. , TARDIEU F. , DOUMAS P. 
Published: July 2003

ABSTRACTThe ability of the root system architecture to respond to nutrient availability is a key adaptative behaviour allowing plants to cope with environmental conditions. On the basis of single time point comparisons, the response to phosphate deprivation was previously shown to involve both the primary and lateral roots of Arabidopsis. In this work, the temporal pattern of Arabidopsis root responses to phosphate starvation was investigated. Daily scanning of roots showed that changes in architecture were largely due to the alterations of time‐based growth parameters, namely a decrease in the elongation rate of the primary root opposed to an increase in the elongation rate of lateral roots and a decrease in the number of initiated lateral roots. In addition, another identified response was a decrease in the proportion of lateral roots showing early growth arrest. All these changes occurred within a short period of approximately 3 d. In addition, the root morphology comparison with the auxin‐resistant mutant axr4, the auxin‐treatment of phosphate‐starved plants and a limited transcriptome analysis supported the conclusion that auxin signalling was involved in the adaptive response of the root system architecture to phosphate deprivation.
A coupled model of stomatal conductance, photosynthesis and transpiration
Authors: TUZET A. , PERRIER A. , LEUNING R. 
Published: July 2003

ABSTRACTA model that couples stomatal conductance, photosynthesis, leaf energy balance and transport of water through the soil–plant–atmosphere continuum is presented. Stomatal conductance in the model depends on light, temperature and intercellular CO2concentration via photosynthesis and on leaf water potential, which in turn is a function of soil water potential, the rate of water flow through the soil and plant, and on xylem hydraulic resistance. Water transport from soil to roots is simulated through solution of Richards’ equation. The model captures the observed hysteresis in diurnal variations in stomatal conductance, assimilation rate and transpiration for plant canopies. Hysteresis arises because atmospheric demand for water from the leaves typically peaks in mid‐afternoon and because of uneven distribution of soil matric potentials with distance from the roots. Potentials at the root surfaces are lower than in the bulk soil, and once soil water supply starts to limit transpiration, root potentials are substantially less negative in the morning than in the afternoon. This leads to higher stomatal conductances, CO2assimilation and transpiration in the morning compared to later in the day. Stomatal conductance is sensitive to soil and plant hydraulic properties and to root length density only after approximately 10 d of soil drying, when supply of water by the soil to the roots becomes limiting. High atmospheric demand causes transpiration rates, LE, to decline at a slightly higher soil water content,θs, than at low atmospheric demand, but all curves ofLEversusθsfall on the same line when soil water supply limits transpiration. Stomatal conductance cannot be modelled in isolation, but must be fully coupled with models of photosynthesis/respiration and the transport of water from soil, through roots, stems and leaves to the atmosphere.
Light and temperature, but not UV radiation, affect chlorophylls and carotenoids in Norway spruce needles (Picea abies (L.) Karst.)
Authors: KIRCHGEßNER H.‐D. , REICHERT K. , HAUFF K. , STEINBRECHER R. , SCHNITZLER J.‐P. , PFÜNDEL E. E. 
Published: July 2003

ABSTRACTConcentrations of chlorophyll a/freshweight (Chl a FW) and photosynthetic pigments/chlorophyll a were studied during one growing season in the current year's (CYN) and last year's needles (LYN) from Norway spruce (Picea abies (L.) Karst.) grown under natural or close‐to‐natural climate. Climate regimes differed in photosynthetic active radiation (PAR), temperature (T) and UV‐B radiation. Pigments were not affected by UV‐B but most of the differences between climate regimes, and also seasonal variations within climate regimes, could be related to PAR and T. Generally, two types of response to climate were observed: firstly, pigments reacted primarily to PAR without marked sensitivity to T and exhibited slow response times (> 30 d), and, secondly, pigments were affected by the combined action of PAR and T and responded faster than 20 d. The Chl a FW and chlorophyll b/chloprophyll a ratio exhibited slow‐type response in CYN and fast‐type response in LYN. Higher amplitudes in CYN than in LYN were observed for the latter two parameters, which are known to be associated with levels of pigment–protein complexes. It is suggested that slow response in CYN ensures that the high investments in proteins in these needles occur only in response to longer‐lasting climate episodes.
The radish Rfo restorer gene of Ogura cytoplasmic male sterility encodes a protein with multiple pentatricopeptide repeats
Authors: Brown Gregory G. , Formanová Nataša , Jin Hua , Wargachuk Richard , Dendy Charles , Patil Prashant , Laforest Martin , Zhang Jinfa , Cheung Wing Y. , Landry Benoit S. 
Published: July 2003

SummaryA single radish nuclear gene, Rfo, restores Ogura (ogu) cytoplasmic male sterility (CMS) in Brassica napus. A map‐based cloning approach relying on synteny between radish and Arabidopsis was used to clone Rfo. A radish gene encoding a 687‐amino‐acid protein with a predicted mitochondrial targeting pre‐sequence was found to confer male fertility upon transformation into ogu CMS B. napus. This gene, like the recently described Petunia Rf gene, codes for a pentatricopeptide repeat (PPR)‐containing protein with multiple, in this case 16, PPR domains. Two similar genes that do not appear to function as Rfo flank this gene. Comparison of the Rfo region with the syntenic Arabidopsis region indicates that a PPR gene is not present at the Rfo‐equivalent site in Arabidopsis, although a smaller and related PPR gene is found about 40 kb from this site. The implications of these findings for the evolution of restorer genes and other PPR encoding genes are discussed.
Characterization of the Major Antigenic Protein 2 of
Ehrlichia canis
and
Ehrlichia chaffeensis
and Its Application for Serodiagnosis of Ehrlichiosis
Authors: Knowles Tamece T. , Alleman A. Rick , Sorenson Heather L. , Marciano David C. , Breitschwerdt Edward B. , Harrus Shimon , Barbet Anthony F. , Bélanger Myriam 
Published: July 2003

ABSTRACT

Canine monocytic ehrlichiosis, caused by
Ehrlichia canis
or
Ehrlichia chaffeensis
, can result in clinical disease in naturally infected animals. Coinfections with these agents may be common in certain areas of endemicity. Currently, a species-specific method for serological diagnosis of monocytic ehrlichiosis is not available. Previously, we developed two indirect enzyme-linked immunosorbent assays (ELISAs) using the major antigenic protein 2 (MAP2) of
E. chaffeensis
and
E. canis
. In this study, we further characterized the conservation of MAP2 among various geographic isolates of each organism and determined if the recombinant MAP2 (rMAP2) of
E. chaffeensis
would cross-react with
E. canis
-infected dog sera. Genomic Southern blot analysis using digoxigenin-labeled species-specific probes suggested that
map2
is a single-copy gene in both
Ehrlichia
species. Sequences of the single
map2
genes of seven geographically different isolates of
E. chaffeensis
and five isolates of
E. canis
are highly conserved among the various isolates of each respective ehrlichial species. ELISA and Western blot analysis confirmed that the
E. chaffeensis
rMAP2 failed to serologically differentiate between
E. canis
and
E. chaffeensis
infections.
Effect of Clarithromycin on Inflammatory Markers in Patients with Atherosclerosis
Authors: Berg Hans F. , Maraha Boulos , Scheffer Gert-Jan , Peeters Marcel F. , Kluytmans Jan A. J. W. 
Published: July 2003

ABSTRACTAtherosclerosis can to a certain extent be regarded as an inflammatory disease. Also, inflammatory markers may provide information about cardiovascular risk. Whether macrolide antibiotics, especially clarithromycin, have an anti-inflammatory effect in patients with atherosclerosis is not exactly known. To study this phenomenon, a placebo-controlled, randomized, double-blind study was performed. A total of 231 patients with documented coronary artery disease received a daily dose of either 500 mg of slow-release clarithromycin or placebo until the day of surgery. Levels of inflammatory markers (C-reactive protein, interleukin-2 receptor [IL-2R], IL-6, IL-8, and tumor necrosis factor alpha) were assessed during the preoperative outpatient visit, on the day of surgery, and 8 weeks after surgery. Also, changes in the levels of inflammatory markers between visits were determined by delta calculations. Baseline patient characteristics were balanced between the two treatment groups: the average age was 66 years (standard deviation [SD] = 9.0), 79% of the patients were male, and the average number of tablets used was 16 (SD = 9.3). The inflammatory markers of the groups as well as the delta calculations were not significantly changed. Treatment with clarithromycin did not influence the inflammatory markers in patients with atherosclerosis.
Comparison of a Dipstick Assay for Detection ofBrucella-Specific Immunoglobulin M Antibodies with Other Tests for Serodiagnosis of Human Brucellosis
Authors: Clavijo Encarnación , Díaz Ramón , Anguita Ángel , García Antonio , Pinedo Alfonso , Smits Henk L. 
Published: July 2003

ABSTRACTA dipstick assay for the detection ofBrucella-specific immunoglobulin M (IgM) antibodies was evaluated by studying the serological response of 133 cultures and or serologically confirmed patients with brucellosis in its different stages along with those of 34 healthy controls. As regards patients with illness less than 3 months in duration, 93.1% tested positive by the dipstick assay, a percentage similar to that obtained in the standard serum agglutination test (SAT) (92.0%), somewhat lower than that obtained by culture (100%) and higher than that obtained by IgM enzyme-linked immunosorbent assay (ELISA) (80.5%). SAT was the most sensitive test (87.0%) for patients with illness more than 3 months in duration, followed by culture (50%), the dipstick assay (28.3%), and IgM ELISA (7.5%). The results demonstrate that the dipstick assay could well be used in the serodiagnosis of patients with acute brucellosis, as well as to identify patients with a long history of the illness. Under laboratory conditions this test has the advantage of being quick and IgM antibody-specific.