bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assesment of arsenic effects on cytosolic heme status using tryptophan pyrrolase as an index
Authors: Cebrián M. E. , Albores A. , Connelly J. C. , Bridges J. W. 
Published: October 2006

AbstractAcute arsenic (As) administration produced in rat liver a decrease in the heme saturation of tryptophan pyrrolase (TP), accompanied by dose‐related increases in 5‐aminolevulinate synthetase (ALAS) and heme oxygenase (HO) activities, along with a corresponding decrease in cytochrome P‐450 (P‐450) concentration. The relationship between heme synthesis and degradation was altered as a result of As treatment. The magnitude of these effects was related to the oxidation state of arsenic, sodium arsenite (AsIII) being more potent than sodium arsenate (AsV). These results support the contention that the heme saturation of TP is sensitive to treatments that modify liver heme concentration. The increase in HO activity produced by As appears to be mediated by a mechanism largely or entirely independent of heme. The main effects of continuous exposure to AsIII were an initial decrease in the heme saturation of TP, which remained constant during the period of treatment, and an initial increase in ALAS activity, which after ten days of exposure dropped somewhat but remained above control values. No significant effects on HO or P‐450 concentration were observed. These results were interpreted as indicative that a new balance between heme synthesis and degradation had been reached and that an adaptive response to the subchronic effects of AsIII was taking place.
Reaction of tobacco smoke aldehydes with human hemoglobin
Authors: Hoberman Henry D. , George Richard C. San 
Published: October 2006

AbstractFormaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, and acrolein, all of which are constituents of tobacco smoke, were reacted in 5 mM concentration with the purified major fraction of normal adult human hemoglobin (hemoglobin Ao) in 1 mM concentration. A cigarette smoke condensate, diluted to contain 5 mM total aldehydes, was also reacted with 1 mM hemoglobin Ao. Cationic exchange high‐performance liquid chromatography (HPLC) showed that the products formed from simple aliphatic aldehydes, with the exception of formaldehyde, were analogues of those formed from acetaldehyde, earlier shown by us to be imidazolidinone derivatives, that is, cyclic addition products of the N‐terminal aminoamide function of α and β chains. Formaldehyde and acrolein produced a heterogeneous mixture of derivatives including crosslinked hemoglobin dimers. The greater proportion of modified hemoglobins produced by condensate aldehydes resembled those formed from acetaldehyde, the most abundant aldehyde in the condensate. A smaller fraction consisted of crosslinked hemoglobin dimers, presumably due to the action of formaldehyde. Mass spectrometric and HPLC analyses of the 2,4‐dinitrophenylhydrazones precipitated from the condensate documented the presence of formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, furfsral, and methylfurfural. The toxicity of aldehydes is briefly discussed in the context of the findings of this study.
Expression profiling of BEN regulated genes in mouse embryonic fibroblasts
Authors: Chimge Nyam‐Osor , Mungunsukh Ognoon , Ruddle Frank , Bayarsaihan Dashzeveg 
Published: October 2006

AbstractBEN is a member of the TFII‐I family of helix–loop–helix transcription factors. Both TFII‐I and BEN are involved in gene regulation through interactions with tissue‐specific transcription factors and chromatin remodeling complexes. Identification of the downstream target genes of TFII‐I proteins is critical in delineating the regulatory effects of these proteins. In this study, we conducted a microarray analysis to determine gene expression alterations following the overexpression of BEN in primary mouse embryonic fibroblasts (MEFs). We found the BEN‐dependent modulation in the expression of large groups of genes representing a wide variety of functional categories including genes important in the immune response, cell cycle, transcriptional regulation and cell signaling. A set of genes identified by the microarray analysis was validated by independent real‐time PCR analysis. Among upregulated genes were Shrm, Tgfb2, Ube2l6, G1p2, Ccl7 while downregulated genes were Folr1, Tgfbr2, Csrp2, and Dlk1. These results support a versatile function of TFII‐I proteins in vertebrate physiology and lead to an increased understanding of the BEN‐dependent molecular events. J. Exp. Zool. (Mol. Dev. Evol.) 308B:209–224, 2007. © 2006 Wiley‐Liss, Inc.
Immunological characterization of a newly developed antibody for localization of a beta‐keratin in turtle epidermis
Authors: Alibardi Lorenzo , Toni Mattia 
Published: October 2006

AbstractTurtle scutes are made of hard (beta)‐keratins. In order to study size and localization of beta‐keratins in turtle shell, we produced a rat polyclonal antiserum against a turtle scute beta‐keratin of 13–16 kDa, which allowed the immunolocalization of the protein in the epidermis. In immunoblots the antiserum recognized turtle beta‐keratins but showed variable cross‐reactivity with lizard, snake, and avian beta‐keratins. The turtle antiserum appears less cross‐reactive than a chicken scale antiserum (Beta‐1). In bidimensional immunoblots, three main protein spots at 15–16 kDa with pI at 7.3, 6.8, 6.4, and an unresolved large spot at 40–45 kDa with pI around 5 were more constantly obtained. The latter may result from the aggregation of the smaller beta‐keratin protein. The corneous layer of the carapace and plastron of various species of chelonians appeared immunofluorescent. The ultrastructural immunolocalization showed sparse labeling over beta‐keratin filaments of cells of the horny layer of both carapace and plastron. The study for the first time shows that the isolated protein band derived from a component of the beta‐keratin filaments of the corneous layer of turtles. This antibody can be used for further studies on beta‐keratin expression and sequencing in chelonian shell. No labeling was present over other cell organelles or layers of turtle epidermis and it was absent in non‐epidermal cells. The specificity for turtle beta‐keratin suggests that the antiserum recognizes some epitope/s specific for chelonians beta‐keratins, and that it also variably recognizes other reptilian and avian beta‐keratins. J. Exp. Zool. (Mol. Dev. Evol.) 306B, 2006. © 2006 Wiley‐Liss, Inc.
Non‐steroidal anti‐inflammatory drugs and acute renal disease: A case control study
Authors: Beard Keith , Lawson David H. , MacFarlane Gary J. 
Published: October 2006

AbstractObjectives: To quantify the risk of acute renal disease in patients exposed to non‐steroidal anti‐inflammatory drugs (NSAIDs). Design: Matched case control study. Subjects: All patients who underwent renal biopsy in Glasgow Royal Infirmary and the Western Infirmary, Glasgow, in 1986 and 1987 were considered as possible cases. Patients with chronic disease, with disease that was clearly not drug‐related, and whose records could not be traced were excluded. For each case in the final group, two controls were matched for age, sex and general practice. All drug exposures in the year before the diagnosis of renal disease were obtained from the general practitioners' records. Results: 27 of the 88 cases (31%) and 38 of the 176 controls (22%) were exposed to NSAIDs (odds ratio (OR) = 1.6; 95% confidence interval (CI) = 0.9, 3.0). No difference in exposure to bronchodilators, tranquillizers, antihistamines or antacids was found between cases and controls. A significant increase in OR was found with histamine (H2) receptor blockers. Of cases where interstitial nephritis was part of the pathological appearance, two were thought to be definitely and six possibly related to NSAIDs. Conclusions: The present study shows that in previously healthy persons, the risk of clinically apparent acute renal disease caused by these commonly used drugs is likely to be extremely small. The attributable risk of acute renal disease is of the order of one case in 100,000 patients treated with NSAIDs.
Scientific and ethical standards in pharmaceutical medicine should be self‐regulated
Authors: Stonier Peter 
Published: October 2006

AbstractThis report summarizes a debate which was convened by the Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom at its first Annual Meeting on 10 December 1990, at the Royal College of Physicians, London, and moderated by Dr Richard Rondel, Registrar of the Faculty.
Sudden unexplained death in young persons with primary epilepsy
Authors: Jick S. S. , Cole T. B. , Mesher R. A. , Tennis P. , Jick H. 
Published: October 2006

AbstractA population based study was carried out at Group Health Cooperative of Puget Sound (GHC) to estimate the incidence of sudden unexplained death occurring in individuals 15–49 years of age with presumed chronic primary epilepsy. Eleven deaths, considered to be sudden and unexplained, occurred in an estimated 8460 person years at risk for an estimated rate of 1.3 per 1000 years at risk.
Unsuspected patterns of drug utilization revealed by interrogation of a regional general practitioner prescribing database
Authors: McGavock H. , Wilson‐Davis K. , Niblock R. W. F. 
Published: October 2006

AbstractThe classification of drugs according to the specificity of their use has been shown to reveal unsuspected patterns of GP prescribing (McGavock, 1988). The present aim was to define the frequency distribution of rate of issue and cost of prescriptions of (a) drugs used to treat proven pathology, (b) drugs used mainly to relieve symptoms, and (c) drugs like antibiotics, whose use should be specific, but which are often used presumptively. Prescribing data were retrieved from the GP prescription pricing database, specific for individual practices and at the level of the therapeutic group (e.g. hypnotics). A new microcomputer program sorted these data into categories (a), (b) and (c), and produced frequency distributions for all practices in Northern Ireland. The distributions in all three categories were unimodal, positively skewed. A seven–tenfold range in the rate of prescribing was seen in all three categories (cost showed a threefold range), between lowest and highest practices. For each practice, prescribing rate and cost in each category were displayed, with the Northern Ireland average for comparison. This revealed the emphasis placed by each practice on the use of symptomatic treatment and the doctors' tendency to use category (c) drugs. Above all, it revealed the frequency of prescribing of drugs for proven pathology (a) which, prima facie, should be directly related to the diagnoses of diseases such as diabetes, asthma and hypertension. The interpretation of these patterns for practice audit is discussed, together with problems and caveats.
Diuretic treatment in those dying from a myocardial infarction
Authors: Battersby Clare , Daymond Margot , Styles William M. , Struthers Allan D. , Rowley‐Jones David , Bulpitt Christopher J. 
Published: October 2006

AbstractThe relative risk of dying from a myocardial infarction according to diuretic therapy was estimated in a case control study for 189 cases, 144 dead controls and 349 living controls. The controls were matched for age (±2.5 years), sex and general practice. The study was community‐based; the cases were identified from death certificates and the death certificates of the dead controls had no mention of ischaemic heart disease. The relative risk was estimated from the odds ratio and was similar whether dead or living controls were considered. Against all controls combined, the odds ratio for dying while taking a potassium‐losing diuretic at 1 month prior to death (R1) was 1.5 (95 per cent CI 0.9, 2.4) and for a combined potassium‐losing + sparing diuretic (RL+S) was 2.0 (95 per cent CI 1.1, 3.4). Potassium‐sparing diuretics may be given more frequently to patients at greater risk of dying, thus masking a benefit, but the data could not provide evidence for a benefit from the addition of a potassium‐sparing diuretic.
The status and future of pharmacoepidemiology (part 1)
Authors: Jones Judith K. 
Published: October 2006

AbstractThe study of the effects and use of pharmaceuticals in populations, or pharmacoepidemiology, is in its formative years. The field is growing due to many factors, including access to large data resources. Current research is applied, emanating from the pharmaceutical industry and drug regulatory agencies, with limited presence in academia. Accomplishments include a growing use of many large population databases and an increased understanding and acceptance of drug risk, e.g. for agranulocytosis, which may explain the presence of certain drugs with defined risk remaining on the market. In the next decade, international consensus will be needed on acceptable methods and data standards, development of new data resources, and efforts made to assure database maintenance and quality. Further, the field must develop bases for a clear identity and scientific credibility to enable development of academic status. In the future, pharmacoepidemiology has considerable potential for applications in drug regulatory reform, drug development, risk management, pharmaceutical benefit and cost assessment, and drug utilization review, as well as for understanding drug‐associated disease.
Micturin and torsades de pointe — experience of a post‐marketing alert
Authors: Wild R. N. 
Published: October 2006

AbstractOn 13 September 1991 Micturin® (terodiline hydrochloride), was temporarily withdrawn worldwide after the discovery of an association with serious cardiac arrhythmias, notably a rare form of ventricular tachycardia known as torsades de pointe. This paper describes the events and actions leading up to the withdrawal and discusses the reasoning behind it.
Risk of death from human insulin
Authors: Suissa S. , Spitzer W. O. , Abenhaim L. , Downey W. , Gardiner R. J. , Fitzgerald D. 
Published: October 2006

AbstractIn response to growing concerns surrounding the risks of human insulin, we conducted a 13‐year historical cohort study of 4925 insulin users less than 40 years of age. This cohort was formed from the population of Saskatchewan, Canada, from 1978–90, using the computerized databases arising from the universal health insurance plan of this Province of 1.1 million inhabitants. Of 101 deaths, 53 occurred within the defined one‐month time window of effect. The cohort resulted in 14,600 person‐years of exposure to insulin use. The overall rate of death was 3.6 per 1000 person‐years of insulin use (95% CI: 2.7–4.6). This death rate remained stable throughout the 13‐year study period and did not increase after 1984, the year of introduction of human insulin in Saskatchewan. We found 46 deaths for animal insulin (4.0/1000/year) and 7 deaths for human insulin (2.3/1000/year). Among the latter 7 deaths, 1 death occurred in the group treated solely with human insulin (1.2/1000/year), and 6 deaths in those who were switched from animal to human insulin (2.8/1000/year). These observed differences are not statistically significant. The data from this rapid response pharmacoepidemiological study, which took 8 months to complete, do not support allegations that treatment with human insulin increases the risk of death. They do not however exclude the possibility that human insulin is associated with an elevated risk of fatal or non‐fatal hypoglycaemia.
Some patient experiences with drugs and adverse drug reactions in an African teaching hospital
Authors: Magunje S. , Simooya O. O. 
Published: October 2006

AbstractOne hundred and seventy patients regularly attending a general medical outpatients' clinic at the Parirenyatwa Central Hospital (PCH) in Harare, Zimbabwe were interviewed about their knowledge of their present drug therapy and possible adverse drug reactions (ADRs), history of previous ADRs and action taken on experiencing them, information source and satisfaction with their therapy. Sixty seven patients knew what drugs they were taking and this level of awareness was associated with age, occupation and level of education of the patient. Only 19 patients knew about the possible ADRs of their drugs and this knowledge was associated with language ability, disease knowledge and knowledge of what drugs they were taking. Seventy eight patients had experienced ADRs and this was linked to age and knowledge of ADRs. Eighty one patients said that they would continue their drug treatment on experiencing ADRs, and this behaviour was associated with knowledge of disease and ADRs. More than half of the patients were not satisfied with the information given about their drugs, and very few had read about this subject. These results suggest that overall knowledge of drugs and ADRs amongst patients at the PCH is low, and that there is a need to increase patient education regarding therapy. This training should take into account the patient's demographic and socioeconomic background. Knowledge of ADRs was shown to increase the potential for compliance.
Severe hypoglycaemia in Chinese patients with non‐insulin‐dependent diabetes treated with insulin or sulphonylureas
Authors: Chan Thomas Y. K. , Chan Juliana C. N. , Critchley Julian A. J. H. 
Published: October 2006

AbstractIn 2404 emergency admissions to two general medical wards over a 1‐year period, 41 (1.7 per cent) were due to insulin‐ or to sulphonylurea‐induced hypoglycaemia. Thirty‐six of the episodes involved 33 Chinese patients with non‐insulin‐dependent diabetes (NIDDM). Of these admissions, 75 per cent (n = 27) were related to sulphonylurea therapy. Compared to a control group of NIDDM patients attending the outpatient clinic [mean ± standard deviation age: 55 ± 13 years, median (range) plasma creatinine concentrations: 79 (49–1085) μmol/1], the hypoglycaemic patients were significantly older (71 ± 10 years; p < 0.001) and had higher plasma creatinine concentrations [120 (50–656) μmol/1; p < 0.001]. These risk factors applied both to patients treated with sulphonylureas and with insulin. Thus, particular caution is required when prescribing either sulphonylureas or insulin for elderly diabetic patients with renal impairment. Our findings may also reflect the preponderance of NIDDM in the Chinese population in Hong Kong and the high prevalence of renal impairment among Chinese diabetic patients.
Role and place of causality assessment
Authors: Venulet Jan 
Published: October 2006

AbstractFor biological reasons a drug has either caused or contributed to the development of an adverse reaction or it has not. All intermediary evaluations like possible, probable, etc. are only approximations of the unknown truth. Three practical approaches to assessment are possible — unstructured, based solely on knowledge and experience; semi‐structured, based on certain descriptive criteria; and standardized, based on an operational logic. Nowadays, causality assessment is understood as one of the signaling and sorting parameters and the many drug regulatory agencies assess causality, although rarely using a standardized assessment. The globalization of drug monitoring efforts speaks for a wider acceptance of one method as it would help to understand better how and why a particular assessment was reached.
Causality assessment of suspected adverse drug reactions: A transatlantic view
Authors: Jones Judith K. 
Published: October 2006

AbstractThe European Community's (EC) pending requirement for a standard assessment of the causal association between a drug product and a reported drug‐associated event prompts a review of this aspect of pharmaceutical safety evaluation. Pharmaceutical manufacturers who use various methods, or no methods, may need to consider these EC definitions and their interpretation for evaluating their current procedures and planning any future changes. This paper first describes the EC classifications and their basis as one statement on the status of causality assessment in Europe. Reflecting the rather different view of causality assessment in North America, this paper then briefly reviews the evolution and uses of causality assessment over the last two decades. The controversies over causality are next discussed, followed by examination of the diverse uses of assessment by a pharmaceutical manufacturer or a regulator. Finally, the paper concludes with thoughts on applying causality concepts as tools for enhancing drug‐risk assessment.
Drug safety alerts — a review of ‘current problems’
Authors: Mann R. D. 
Published: October 2006

AbstractA study of the ‘Current Problems’ publication of the Committee on Safety of Medicines in the UK has shown that many drug safety alerts or warnings are based upon a fairly small number of spontaneous adverse drug reaction reports. In terms of problems naming one drug and one serious reaction, or type of reaction, 24 (52%) of the 46 problems discussed in ‘Current Problems’ related to 10 or less yellow card reports. Nine (43%) of the 21 problems naming one drug and one non‐serious reaction, or type of reaction, were concerned with 10 or less reports. ‘Current Problems’ contain many entries other than this rather clear‐cut type of situation but, in respect of all other quantified entries in the publication that related to serious reactions, 13 (41%) of the 32 relevant problems were concerned with 10 or less yellow card reports. The situation seems to be different when non‐serious reactions are considered — as in general review articles or entries considering the whole range of reactions being reported in respect of a specific drug — when 9 (65%) of the 14 relevant ‘Current Problems’ entries were concerned with 51 or more yellow card reports.Of the problems that named one drug and one serious reaction, or type of reaction, 12 of the 24 relevant ‘Current Problems’ entries were concerned with 4 or less yellow card reports. The relevant alerts and warnings seem, in view of subsequent experience, to have been justified. Nevertheless, there would seem to be much merit in investigating health hazard signals on computerized databases before publication takes place that may lead to differential reporting and subsequently bias the relevant data.
Estimation of the frequency of warfarin‐associated necrosis in a large in‐patient record‐linked database
Authors: Jones Judith K. , Staffa Judy A. 
Published: October 2006

AbstractIn an effort to estimate the frequency of warfarin‐associated necrosis in hospital, a cohort of 20,556 patients who had received warfarin during hospitalization between July 1984 through June 1987 was identified retrospectively using the Medimetrik Hospital Diagnosis and Therapy Audit database. Case‐finding began with two broad screening efforts (using ICD‐9CM codes), followed by concurrent clinical and algorithmic evaluations and chart abstract reviews by a panel of three experts in the field. Those cases designated by one or more experts as possible or probable cases of warfarin‐associated necrosis constituted the numerator; the denominator was an estimate of the number of hospitalized patients administered warfarin who remained in the hospital for at least four days. A total of six possible cases (no probable cases were identified) of warfarin‐associated necrosis were found in this population, representing a frequency of 33.5 per 100,000 with a 95 per cent confidence interval of 12.3 per 100,000 to 73.06 per 100,000. To our knowledge, this is the first observational study to estimate the frequency of warfarin‐associated necrosis. The estimated should be interpreted with caution, however, due to the absence of probable cases and lack of complete information on the length of warfarin therapy. It demonstrates the need for automated databases which allow identification of drug therapy both inside and outside the hospital setting.