bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consumption of non‐steroidal anti‐inflammatory drugs and the development of functional renal impairment in elderly subjects. Results of a case‐control study
Authors: Henry David , Page John , Whyte Ian , Nanra Ranjit , Hall Christopher 
Published: October 2003

Aims The aim of the present study was to explore the level of risk associated with community use of non‐steroidal anti‐inflammatory drugs (NSAIDs). Methods We carried out a matched case‐control study of the relationship between recent use of NSAIDs and the presence of functional renal impairment present at the time of hospitalisation with a range of clinical problems. Cases (n=110) were consecutive patients admitted acutely to hospital who had serum creatinine levels greater than or equal to 0.15 mmol l−1, which improved by 20% or more within the next 14 days, or prior to discharge from hospital. Controls (n=189) were subjects of the same sex and age (to within 5 years) as the cases, who were admitted to the same hospital, who had normal serum creatinine levels (<0.12 mmol l−1 ) throughout their hospital stay. Information on a number of study factors, including recent use of aspirin and other NSAIDs, was obtained by structured interview. Results Overall, there was a weak association between consumption of NSAIDs (including non‐prophylactic aspirin) and the development of functional renal impairment—adjusted odds ratios (OR) with use of NSAIDs in the previous week or in the previous month: OR 1.5 (95% CI 0.80, 2.9) and 1.8 (95% CI 0.97, 3.4) respectively. In subjects with a previous history of renal disease the adjusted OR was 6.6 (0.75, 57.8) and in those with a history of gout or hyperuricaemia the OR was 7.2 (1.3, 40.2). There was a weak positive relationship between the dose of drug consumed in the previous week and the odds of functional renal impairment. The relationship between risk and published figures for drug half‐lives (t½ ) was stronger. The odds ratio increased from 1.2 (95% CI 0.61, 2.4) with a t½≤4 h, to 4.8 (1.5, 15.8) with a t½ of ≤12 h (P=0.012, test for trend). This relationship remained statistically significant after adjustment for a number of clinical variables and the dose of drug ingested. Conclusions NSAIDs are an important cause of functional renal impairment in subjects with renal disease or a history of gout or hyperuricemia. The half‐life of the drug is more important than the ingested dose in determining the risk of this outcome. Long half‐life drugs should be avoided in individuals who are at risk of developing renal impairment.
Cyclosporin pharmacokinetics following administration of capsules and Neoral in paediatric patients with lupus nephritis
Authors: Fu L. W. , Yang L. Y. , Chen W. P. , Lin C. Y. 
Published: October 2003

Aims Neoral is a new microemulsion form of cyclosporin. Pharmacokinetic reports in children are scarce. Therefore, we performed a pharmacokinetic study between Cyclosporin A (CsA) capsules and Neoral in paediatric patients with lupus nephritis.Methods A single 5 mg kg−1 dose orally of either CsA capsules or Neoral was given to 10 paediatric patients (serum creatinine<1.5 mg dl−1 ). CsA whole blood levels were measured for 24 h post‐dose by h.p.l.c.Results Neoral had a higher Cmax and AUC(Cmax: 943±176 ng ml−1; AUC: 4612±785 ng ml−1 h) than those of the CsA capsules (Cmax: 697±187 ng ml−1; AUC: 3483±873 ng ml−1 h; P<0.05). There was no difference in tmax and t1/2,z between the two groups.Conclusions CsA Neoral had improved absorption and bioavailability, which is similar to what is reported in adults. However, interpatient variability still existed. Careful drug monitoring and dose adjustment should be performed during treatment to avoid nephrotoxicity, especially in lupus nephritis.
A comparison of the effects of aspirin on bleeding time measured using the Simplate™ method and closure time measured using the PFA‐100™, in healthy volunteers
Authors: Marshall P. W. , Williams A. J. , Dixon R. M. , Growcott J. W. , Warburton S. , Armstrong J. , Moores J. 
Published: October 2003

Aims The aim of this study was to compare the effects of aspirin on platelet function as measured by the ‘classical’ template bleeding time with a new ex vivo method measuring closure times using the PFA‐100™ machine. Platelet aggregation in response to arachidonic acid was also measured ex vivo.Methods The trial was a randomized, double‐blind, placebo‐controlled crossover design, with each volunteer taking 750 mg aspirin (BP) or placebo, three times a day for 5 days, with an 18 day wash‐out period between treatments. Bleeding times and closure times were measured before the first dose on the first day and 0.5 h after the last dose on the fifth day of each treatment period. They were also measured 2 weeks after the last day of the trial.Results Baseline bleeding times (pre‐placebo) were 415 s using the Simplate, whilst baseline closure times were 115 s using the PFA‐100™. Aspirin treatment caused an increase of both the template bleeding time (61%) and the closure time of the PFA‐100™ (79%) when compared with the effects of placebo. The platelet aggregatory response to arachidonic acid was completely inhibited following aspirin treatment and was unaffected following placebo. Two weeks after the end of the trial, all values had returned to pre‐treatment levels. The template bleeding time was unaltered in 1 of the 12 volunteers during aspirin treatment and was significantly prolonged in 3 of the 12 volunteers during placebo treatment. The PFA‐100™ closure time was unaltered in 1 of the 12 volunteers during aspirin treatment and was prolonged in 1 subject during placebo treatment.Conclusions The change in closure time using the PFA‐100™ is as sensitive and reproducible to the effects of aspirin on platelet function as is the template bleeding time test. However, the PFA‐100™ produced less variable effects with fewer false positive results.
Non‐puerperal lactation associated with antidepressant drug use
Authors: Egberts Antoine C. G. , Meyboom Ronald H. B. , De Koning Fred H. P. , Bakker Albert , Leufkens Hubert G. M. 
Published: October 2003

Aims The aim of the present study was to estimate the relative risk of non‐puerperal lactation in patients using antidepressants in general, and specifically for serotonergic (selective serotonin reuptake inhibitors (SSRIs) and clomipramine) and non‐serotonergic antidepressants. Methods All suspected adverse drug reactions in women and reported from January 1986 until August 1996 to the Netherlands Pharmacovigilance Foundation, a spontaneous adverse drug reaction reporting programme, were analysed. Adverse drug reaction (ADR) reporting odds ratios, defined as the ratio of the exposure odds among reported cases of non‐puerperal lactation to the exposure odds of reported other ADRs, were calculated adjusted for age and year of reporting. Results Thirty‐eight cases of non‐puerperal lactation were reported, of which 15 were associated with the use of antidepressant drugs. In general, antidepressants were associated with a higher risk of non‐puerperal lactation in comparison with other drugs (ADR reporting odds ratio 8.3 [ 95%CI: 4.3–16.1]). Serotonergic antidepressants (selective serotonin reuptake inhibitors (SSRIs) and clomipramine) were associated with a higher risk (OR 12.7 [95%CI: 6.4–25.4]), whereas other antidepressants were not (OR 1.6 [95%CI: 0.2–11.6]), compared with all other drugs. Conclusions Our results indicate that serotonergic antidepressants are associated with an approximately eight times higher risk of non‐puerperal lactation compared with other antidepressants. This effect is probably mediated by an indirect inhibition effect of serotonin on the dopaminergic transmission. This finding is in line with the occurrence of other antidopaminergic effects, such as extrapyramidal symptoms, in patients using serotonergic antidepressants.
A pharmacokinetic and pharmacodynamic interaction study between nebivolol and the H2‐receptor antagonists cimetidine and ranitidine
Authors: Kamali F. , Howes A. , Thomas S. H. L. , Ford G. A. , Snoeck E. 
Published: October 2003

Aims The study was designed to investigate the effects of the H2‐receptor antagonists, cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of nebivolol in healthy volunteers. Methods Twelve healthy volunteers took part in a randomized placebo‐controlled cross‐over study. Each subject received on three separate occasions placebo, cimetidine (400 mg twice daily) or ranitidine (150 mg twice daily) for 24 h before and 48 h after a single oral dose of nebivolol (5 mg). Nebivolol and its individual (+) and (−) enantiomers were determined tby h.p.l.c. Results Ranitidine had no significant effect on nebivolol pharmacokinetics. Cimetidine, however, resulted in a 21–23% increase in Cmax of unchanged nebivolol and of each enantiomer plus its hydroxylated metabolites. Cimetidine significantly (P<0.05) increased the AUC [mean±s.d. (95% C.I. of differences in mean)] for unchanged (±)‐nebivolol [7.76±3.07 ng ml−1h with placebo; 11.50±5.40 (1.75, 8.76) ng ml−1h with cimetidine], (+)‐nebivolol plus its hydroxylated metabolites [73.0±18.0 ng ml−1h with placebo; 91.5±25.7 (1.0, 23.1) ng ml−1h with cimetidine] and (−)‐nebivolol plus its hydroxylated metabolites [101±32 ng ml−1h with placebo; 123±38 (3.3, 27.0) ng ml−1h with cimetidine]. Statistical analysis of the resting blood pressure and heart rate and exercise data did not suggest any consistent effects of ranitidine or cimetidine upon the pharmacodynamic effects of nebivolol. Conclusions There was no interaction between ranitidine and nebivolol. Although cimetidine inhibited nebivolol metabolism, it did not have a significant influence on the pharmacodynamics of the drug.
Excretion of citalopram in breast milk
Authors: Spigset Olav , Carleborg Lena , Öhman Robert , Norström Åke 
Published: October 2003

Aims The objective of this study was to measure the secretion of the selective serotonin uptake inhibitor citalopram in breast milk. Methods The excretion of citalopram in breast milk was studied at steady‐state conditions in two patients with depression and in one healthy volunteer after ingestion of a single dose citalopram. Results Milk/serum concentration ratios based on single pairs of samples from the two patients ranged from 1.16 to 1.88. Based on milk concentration data from the patients, the absolute dose ingested by a suckling infant would be 4.3–17.6 &mu;g kg−1 day−1, and the relative dose 0.7–5.9% of the weight‐adjusted maternal dose. Based on area‐under‐the‐time‐concentration curves from the healthy volunteer, the milk/serum ratio was 1.00, the absolute dose to the infant during steady‐state conditions would be 11.2 &mu;g kg−1 day−1 and the relative dose 1.8% of the weight‐adjusted maternal dose. Conclusion The study shows that the relative dose to a suckling infant is close to that reported for fluoxetine, and higher than reported for fluvoxamine, paroxetine and sertraline.
Effects of prostacyclin on renal haemodynamics, renal tubular function and vasoactive hormones in healthy humans. A placebo‐controlled dose–response study
Authors: Nielsen C. B. , Bech J. N. , Pedersen E. B. 
Published: October 2003

Aims To investigate the acute effects of prostacyclin (Flolan® ) on renal haemodynamics, renal tubular function, plasma concentration of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), arginine vasopressin (AVP), mean arterial blood pressure (MBP), and heart rate (HR). Methods Thirteen healthy control subjects were investigated on two separate occasions in a placebo controlled, randomized, dose–response study of the effect of intravenous infusion of prostacyclin (PGI2, Flolan®, 2, 4 and 8 ng kg−1min−1 ). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the use of constant infusion of []>
51Cr]‐EDTA and [125I]‐hippurane. Urinary output, urinary sodium excretion, fractional sodium excretion, fractional lithium excretion were measured and hormones were measured using radioimmunoassay. Results During prostacyclin (PGI2 ) infusion we observed a significant increase in RPF (PGI2: 4.8%; 6.1% and 5.2%vs Plac: −1.5%; −1.9% and −5.8% for 2,4 and 8 ng kg−1min−1 respectively; P≤0.05 for 4 and 8 ng kg−1min−1 ) in Ang II (PGI2: 20.0%; 42.9% and 88.9%vs Plac: 0.1%; 8.0% and 0.0%, P≤0.01 for 4 and 8 ng kg−1 min−1 ) in ANP (PGI2: 13.6%; 12.7% and 37.5%vs Plac: −10.2%; −6.6% and −2.4%, P≤0.05 for 2 ng kg−1min−1 and P≤0.01 for 4 and 8 ng kg−1min−1 ), and in HR (PGI2: 8.8%; 17.6% and 32.7%vs Plac: 0.8%; 4.1% and 3.5%, P≤0.05 for 2 and P≤0.01 for 4 and 8 ng kg−1min−1.). A significant decrease was observed in MBP (MBP:PGI2: −1.7%; −1.9% and −5.6%vs Plac: −0.4%; −1.6% and +2.1%, P≤0.01 for 8 ng kg−1min−1 ). No significant changes were seen in the other effect variables. Conclusions Infusion of prostacyclin in healthy control subjects increases renal plasma flow, angiotensin II, atrial natriuretic peptide, and heart rate and decreases mean blood pressure. Furthermore prostacyclin infusion does not change net sodium excretion in healthy controls.
The role of plasma D‐dimer concentration in the exclusion of pulmonary embolism
Authors: Van Beek Edwin J. R. , Schenk B. Ed , Michel Bowine C. , Van Den Ende Bram , Brandjes Dees P. M. , Van Der Heide Yvonne T. , Bossuyt Patrick M. M. , Büller Harry R. 
Published: October 2003

Objective. To determine the role of four ELISA D‐dimer assays in the exclusion of pulmonary embolism. Design. Blinded comparison using pulmonary angiography and/or lung scintigraphy as a reference method. Setting. A secondary and tertiary referral centre. Patients and methods. Consecutive patients with suspected pulmonary embolism underwent lung scintigraphy, followed by angiography if a non‐diagnostic result was obtained. Comorbid conditions resulting in elevated plasma D‐dimer levels were defined a priori. Cut‐off levels for 100% sensitivity were determined. A decision‐analytic model was used to determine effectiveness and costs in the management pulmonary embolism. Main outcome measures. The exclusion efficacy of the various assays at a sensitivity of 100%, and cost‐effectiveness. Results. A total of 179 patients were included (78 inpatients and 101 outpatients; 74 patients had comorbid conditions). Pulmonary embolism could be adequately excluded in between 8% and 18% of all patients, and in between 3% and 7% and 11% and 27% of inpatients and outpatients, respectively, depending on the assay used. D‐dimer assays could exclude pulmonary embolism in <5% of patients with comorbid conditions, whereas this increased to 14–32% in outpatients without comorbid conditions. A cost‐effectiveness analysis showed a cost reduction of 10% at a specificity of 30%, largely due to a 28% decrease in angiography requirements. Furthermore, for every 2% decrease in sensitivity, one per 1000 evaluated patients would die as a result of inadequately treated pulmonary embolism. Conclusion. D‐dimer ELISA assays may have a role in the exclusion of pulmonary embolism in symptomatic outpatients, where the application may reduce angiography by 30% and costs by 10%.
Deletions of the long arm of chromosome 7 in myeloid disorders: loss of band 7q32 implies worst prognosis
Authors: Velloso Elvira Rodrigues Pereira , Michaux Lucienne , Ferrant Augustin , Hernandez Jesus Maria , Meeus Peter , Dierlamm Judith , Criel Arnold , Louwagie Andries , Verhoef Gregor , Boogaerts Marc , Michaux Jean‐Louis , Bosly André , Mecucci Cristina , Berghe Herman Vanden 
Published: October 2003

Clinical and cytogenetic data were analysed in 54 patients with acute non‐lymphocytic leukaemias (ANLL) or MDS (myelodysplastic syndromes) and deletion of the long arm of chromosome 7 (7q−), in order to determine if there is a commonly deleted region in 7q and to establish possible correlations between karyotypic features, such as karyotype pattern, karyotype complexity, associated anomalies, and/or the type of deleted segments, and outcome of patients with these disorders.The median follow‐up of our patients was 4 months (range 1–89), as was the median survival. In 30% of the cases there was a history of preceding MDS or previous chemotherapy. Clinical and cytogenetic remission was obtained in 7/36 patients treated with chemotherapy (CT). At the time of 7q− detection, three patients previously treated with CT for ANLL were in clinical remission. 5q− was the most recurrent associated abnormality. Complex karyotypes were observed in 68% of the cases. In univariate analysis, statistical differences in survival were observed according to diagnosis (therapy‐related and secondary diseases had a worse prognosis than primary disorders), the chromosomal segments deleted (the loss of band 7q32 was of poor prognostic value), the karyotype complexity (patients with single anomalies did better than patients with complex anomalies) and the response to therapy (patients who achieved complete remission had a better survival probability). In multivariate analysis, the loss of band 7q32 was found to be significantly related to very poor prognosis. This finding suggests that band 7q32 may contain critical genes that should be explored at the molecular level.
Stem cells in normal breast development and breast cancer
Authors: Dontu Gabriela , Al‐Hajj Muhammad , Abdallah Wissam M. , Clarke Michael F. , Wicha Max S. 
Published: October 2003

Abstract.  The main focus of this review is the role of mammary stem cells in normal breast development and carcinogenesis. We have developed a new in vitro culture system that permits, for the first time, the propagation of mammary stem and progenitor cells in an undifferentiated state, which should facilitate the elucidation of pathways that regulate normal mammary stem‐cell self‐renewal and differentiation. Furthermore, we propose a model in which transformation of stem cells, or early progenitor cells, results in carcinogenesis. A key event in this process is the deregulation of normal self‐renewal in these cells. Transformed mammary stem or progenitor cells undergo aberrant differentiation processes that result in generation of the phenotypic heterogeneity found in human and rodent breast cancers. This phenotypic diversity is driven by a small subset of mammary tumour stem cells. We will discuss the important implications of this mammary tumour stem‐cell model.
Risk factors for atopic dermatitis in infants at high risk of allergy: the PIAMA study
Authors: Kerkhof M. , Koopman L. P. , Van Strien R. T. , Wijga A. , Smit H. A. , Aalberse R. C. , Neijens H. J. , Brunekreef B. , Postma D. S. , Gerritsen J. ,   the PIAMA study group
Published: October 2003

SummaryBackground
It has been suggested that the period immediately after birth is a sensitive period for the development of atopic disease.Objective
We investigated whether birth characteristics and environmental factors are associated with the development of atopic dermatitis in the first year of life.Methods
Seventy‐six children with and 228 without atopic dermatitis, all children of mothers with respiratory allergy or asthma (PIAMA birth cohort study) were included in the study. Atopic dermatitis was defined as a positive history of an itchy skin condition with at least two of the following characteristics: visible dermatitis, history of outer arms/leg involvement, or general dry skin. Multiple logistic regression analysis was performed to study the independent effects of various risk factors.Results
A birth weight 4000 g compared to 3000–4000 g was a significant risk factor for atopic dermatitis (odds ratio (OR)=2.4; 95% CI: 1.1–5.1) as was day care attendance (OR=2.9; 95% CI: 1.5–5.9). Exclusive breastfeeding in the first 3 months was negatively associated with atopic dermatitis (OR=0.6; 95% CI: 0.3–1.2), especially with visible dermatitis (OR=0.4; 95% CI: 0.2–1.0). Gender, gestational age, the presence of siblings or pets, and parental smoking were not significantly associated with atopic dermatitis.Conclusion
This study shows that a high birth weight and day care attendance increase the risk of atopic dermatitis in the first year of life, while exclusive breastfeeding is a protective factor when dermatitis is found on inspection.
Allergen sensitization and bronchial hyper‐responsiveness to adenosine monophosphate in asthmatic patients
Authors: Currie G. P. , Jackson C. M. , Lee D. K. C. , Lipworth B. J. 
Published: October 2003

SummaryBackground
Indirect bronchoprovocation using adenosine monophosphate (AMP) is related to atopic phenotype expression.Objective
To evaluate the putative relationship between skin prick allergen sensitization and bronchial hyper‐responsiveness to AMP in a retrospective cross‐sectional database analysis.Methods
We retrospectively evaluated two groups of non‐smoking asthmatics (forced expiratory volume in 1 s (FEV)160% predicted) who were reactive (responders) or unreactive (controls) to inhaled AMP. The main outcome measure was the difference in sensitization to individual allergens and the total atopic load according to the presence or absence of bronchial hyper‐responsiveness.Results
We initially identified 180 (44%) non‐smoking asthmatics with PC20200 mg/mL, while 233 (56%) had PC201600 mg/mL. For those who had a skin prick test, the responders (n=151) and controls (n=151) were found to be matched for age, sex, inhaled corticosteroid dose and number of patients using inhaled corticosteroids. There were significant differences in the number of responders vs. controls in terms of sensitization to house dust mite (77% vs. 62%, P=0.004), aspergillus (19% vs. 9%, P=0.014), cat (61% vs. 48%, P=0.028), total atopic load (493 vs. 380 positive tests, P<0.001) and forced mid‐expiratory flow (60% vs. 68% predicted, P<0.001).Conclusion
Sensitization to common aeroallergens increased the likelihood of bronchial inflammation as reflected by bronchial hyper‐responsiveness to inhaled AMP, independently of both FEV1 or inhaled corticosteroid use. This in turn suggests an association between allergen exposure and AMP responsiveness in asthmatics. Further prospective long‐term evaluation is indicated to assess whether allergen avoidance strategies can modify the airway response.
Health visitors’ understandings of domestic violence
Authors: Peckover Sue 
Published: October 2003

Background. Feminist work has made visible the extent and nature of domestic violence and the problems women face in having their experiences recognized by health and welfare professionals. Research has demonstrated that many health care professionals, including nurses, midwives and health visitors have little working knowledge about this issue. This impacts on their ability to recognize and respond to domestic violence within their practice.Aim. This paper is based upon a study of British health visitors, which explored their practice in relation to domestic violence. Drawing upon empirical data from interviews with health visitors, it explores their understandings of the extent and nature of domestic violence in the context of their work.Methods. Semi‐structured interviews were undertaken with 24 health visitors selected by convenience and purposive sampling. Data collection took place during 1997–1998. The research draws on the theoretical perspectives of feminist poststructuralism.Findings. The findings demonstrate considerable differences between health visitors in their understandings of the extent of domestic violence in their caseloads and their recognition of different types of abuse experienced by women. There were also differences between participants in their willingness to name situations other than physical violence as abusive, as well as the extent to which they recognized domestic violence within different social groups.Conclusions. A feminist perspective provides critical insight into the professional knowledge base in relation to domestic violence, demonstrating the need for health visitors to develop their understandings further in order to respond appropriately to women and children experiencing domestic violence. This is discussed in the context of ongoing struggles for professional identity within an ever‐changing arena of health and welfare provision.