bluuebunny/crossref_metadata_2025_split huggingface dataset:
PEM report number 7. Itraconazole
Authors: Inman William , Kubota Kiyoshi , Pearce Gillian , Wilton Lynda 
Published: October 2006

AbstractPatients (13,645) who were prescribed the oral anti‐fungal drug itraconazole between April 1989 and April 1990 were studied by Prescription‐Event Monitoring (PEM).The pattern of events was compared with data obtained from PEM studies of fluconazole and 31 other drugs. Upper respiratory tract and genito‐urinary infections were reported more frequently than with other drugs but the relationship was with the disease being treated rather than with the drug itself. This pattern of events was virtually identical to that which had been encountered in an earlier study of fluconazole.Of doctors who offered an opinion, 83% considered that the drug had been effective.A total of 340 pregnancies were recorded in this study. Although pregnancy is a contra‐indication 53 had been exposed during the first trimester. There were 40 live births including one otherwise healthy infant with a minor abnormality of one ear.Fifty‐six of 66 deaths were successfully investigated. Cancer (27) and cardiac disease (12) were the most frequent causes of death. None was attributable to itraconazole.One group of 114 patients with onychomycosis had been treated daily for several months without ill‐effect, suggesting a very low order of toxicity. The overall conclusion after this study of more than 13,600 patients was that most events were attributable to the candidial infection rather than its treatment and that itraconazole was virtually free from recognizable side‐effects.
PEM report number 9. Omeprazole
Authors: Wilton Lynda , Inman William , Kubota Kiyoshi , Pearce Gillian , Skipp Marilyn 
Published: October 2006

AbstractPatients (16,204) who had been treated with omeprazole by general practitioners in England between June 1989 and June 1990 have been studied by Prescription‐Event Monitoring (PEM). The pattern of events recorded during the six months following each patient's initial prescription has been compared individually with four other drugs used for similar indications and studied by the same method — cisapride, misoprostol, famotidine and nizatidine — and with pooled data on these and other unrelated drugs.Omeprazole had been prescribed most frequently for oesophageal reflux, oesophagitis, hiatus hernia and peptic ulcer or its complications. Seventy per cent of patients used a daily dose of 20 mg and 26% used 40 mg. Where efficacy had been reported, 81% of the patients were said to have benefited.A comparison of events recorded during the first month with those recorded with other drugs produced no noteworthy ‘signals’. Diarrhoea and nausea or vomiting were the only events which produced a rate‐ratio of more than three when the rate during the first month was compared to that during months two to six. These events were probably more related to the indication than the treatment. No serious hazards were identified and no deaths were attributable to omeprazole.
The medical dictionary for drug regulatory affairs (MEDDRA) project
Authors: Wood K. L. 
Published: October 2006

AbstractElectronic transmission of information is a key component of the Future System for medicines regulation in the European Union (EU). Data sets and terminology will have to be standardized in order to ensure effective information exchange between organizations. The Medical Dictionary for Drug Regulatory Affairs (MEDDRA) is a medical terminology being prepared by an international Working Party for use by regulatory authorities, pharmaceutical companies and other relevant organizations. It incorporates terms relevant to all areas of drug regulation, including the marketing authorization (MA) process, MA maintenance/renewal and pharmacovigilance.
Medical events after a prescription for a benzodiazepine
Authors: Neutel C. Ineke , Downey Winanne , Senft Dwayne 
Published: October 2006

AbstractMuch controversy has surrounded triazolam since it was marketed in the late 1970s. In spite of ongoing debate no major pharmacoepidiomological study has been published, comparing triazolam to other benzodiazepines (BZD). The present study examines the occurrence of medical events after a prescription for one of five BZD. Data was obtained from the Saskatchewan Health Data Bases on all persons who received a prescription for one of triazolam, flurazepam, oxazepam, lorazepam or diazepam, not having had a prescription for any of these in the previous six months. These persons were monitored for eight types of medical events. (1. suicides and attempts, 2. depression, 3. other psychiatric condition, 4. traffic accident injury, 5. injury due to falls, 6. injury due to poisoning, 7. seizures, 8. allergic reactions) for three weeks after their prescription for the BZD. Rates for medical events were compared to those in an unexposed population sample. It was concluded that, on the whole, triazolam does not appear to show a record of hospitalization worse than the other five BZD tested. In general, BZD should be used cautiously, judiciously and at the lowest possible dose.
A prospective study of adverse drug reactions to anti tuberculous drugs
Authors: Thomas Molly , Seshadri M. S. , Cherian A. M. 
Published: October 2006

AbstractA study of adverse drug reactions to anti tuberculosis therapy in the medical outpatients showed that the overall incidence of adverse reactions was 26 per cent. Side‐effects to isoniazid and rifampicin were mainly hepatitis, nausea, vomiting. Ethambutol caused reversible optic neuritis in 7.9 per cent cases. Most adverse drug reactions occurred during the first 3 months of treatment.
Evolution of histamine H2‐receptor antagonist use in an ambulatory elderly population: A 14‐year overview
Authors: Stewart Ronald B. , Neal Carolyn , Padgett Phillip D. , Marks Ronald G. , Hale William E. 
Published: October 2006

AbstractThe purpose of this study was to determine the frequency and pattern of histamine H2‐receptor antagonist drug use in an ambulatory elderly population of individuals over 65 years of age from 1978 to 1992. A longitudinal health screening programme of ambulatory elderly participants was employed to conduct a series of cross‐sectional studies over a 14‐year period.Participants in the first period (1978–79) included 855 (37.1%) men and 1448 (62.9%) women. The use of histamine H2‐receptor antagonist increased from 0.8% of the population in the 1978–79 period to 7.0% in the 1991–92 period. There was no statistically significant correlation between drug use and age (p = 0.8114) or sex (p = 0.9229) at the 1991–92 time period. In the 1991–92 time period, cimetidine and ranitidine combined, accounted for 86.0% of all reported histamine H2‐receptor antagonist.Over the 14‐year period of study there has been a nearly constant increase of histamine H2‐receptor antagonist use in this elderly population.
Testing for clustering in record linkage databases
Authors: Hammerstrom Thomas 
Published: October 2006

AbstractOne way to identify an excess risk of an adverse event during drug exposure is to use administrative, medical, and pharmacy records data, such as Medicaid or HMO (Health Maintenance Organization) records, to compare the relative frequency of the suspect event in exposed and unexposed periods. Such estimates can be seriously biased if there is clustering in patient visits to physicians and pharmacies. This paper presents two simple tests for determining whether the patient visit dates in such a database are Poisson processes of visits or clustered processes. The paper shows that this test is quite powerful at detecting both clustered sequences and nearly regular sequences of visits. Finally, it gives a straightforward SAS program which will carry out the tests.
Use of insurance claims in epidemiologic research: Identification of peptic ulcers, gi bleeding, pancreatitis, hepatitis and renal disease
Authors: Lanza Lee L. , Dreyer Nancy A. , Schultz Nathan J. , Walker Alexander M. 
Published: October 2006

AbstractData bases that are created to administer health care benefits and to record financial aspects of medical care in the United States are useful for epidemiologic research in certain circumstances. Case finding and verification in such records is complex and rarely described in detail in research reports because of space limitations. This report describes portmarketing surveillance for peptic ulcer, upper gastrointestinal hemorrhage and hepatic dysfunction in 68, 180 people who took non‐steroidal anti‐inflammatory drugs (NSAIDs), by using an automated data base together with review of selected medical records. Cases included both mild diseases treated on an outpatient basis and more severe illnesses that required hospital admission. Using computer programs we identified 9642 subjects who had at least one insurance claim suggesting a possible case event. We manually reviewed chronological profiles of their insurance claims, to select 833 subjects for medical record reviews, of whom 152 were verified as cases. Our algorithms for case identification were sensitive, but not very specific. If we had restricted our manual review to people who had at least five relevant claims during the study period, we would have avoided 42% of the reviewing workload and lost only 5% of the cases.
Organic amendments affecting sorption, leaching and dissipation of fungicides in soils
Authors: Fernandes María C , Cox Lucía , Hermosín María C , Cornejo Juan 
Published: October 2006

AbstractMetalaxyl and tricyclazole are two fungicides widely used in Spain in vineyard and rice crops respectively. In this study an investigation has been made of the effect of three organic amendments [two commercial amendments, solid fertiormont (SF) and liquid fertiormont (LF), and a residue from the olive oil production industry, alperujo (OW)] on fungicide fate in soils. Changes in soil porosity on amendment were studied by mercury intrusion porosimetry, sorption–desorption studies were performed by the batch equilibration method, dissipation of metalaxyl and tricyclazole in the soil was studied at − 33 kPa moisture content and 20 °C and leaching was studied in hand‐packed soil columns. Amendments with SF and LF reduced soil porosity, while OW increased porosity through an increase in pore volume in the highest range studied. Tricyclazole sorbed to soils to a much higher extent than metalaxyl. With some exceptions, sorption of both fungicides increased on amendment, especially in the case of SF‐amended soils, which rendered the highestKocvalues. In soils amended with the liquid amendment LF, sorption either remained unaffected or decreased, and this decrease was much higher in the case of metalaxyl and a soil with 70% clay. In this clay soil, amendment with OW, of very high soluble organic matter content, also decreased metalaxyl sorption. Tricyclazole is more persistent in soil than metalaxyl, and both fungicides were found to be more persistent in amended soils than in unamended soils. Leaching of metalaxyl and tricyclazole in soil columns was inversely related to sorption capacity. The low recoveries of tricyclazole in leachates and in soil columns when compared with metalaxyl, a less persistent fungicide, were attributed to diffusion into micropores and to increase in sorption with residence time in the soil, both processes favoured by the low mobility of tricyclazole. Copyright © 2006 Society of Chemical Industry
Synthesis, characterization and conductivity measurements of polyaniline and polyaniline/fly‐ash composites
Authors: Narayan Himanshu , Alemu Hailemichael , Iwuoha Emmanuel 
Published: October 2006

AbstractPolyaniline (PANI) and polyaniline/fly ash (PANI/FA) composites with various concentrations of fly ash (20%, 40% and 50%) were synthesized by the process of in‐situ polymerization. The samples were characterized by powder X‐ray diffraction, thermogravimetric analysis, infrared spectroscopy, and scanning electron microscopy. Moreover, the dc conductivity of the samples was measured as a function of temperature in the range 80–290 K and it was found that the addition of FA decreases the conductivity. The temperature dependence of the dc conductivity for PANI and FA/PANI composites has been explained on the basis of the quasi one‐dimensional variable hopping model. A very good agreement was found between the experimental data and the theory. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Relationships between Octanol‐Water Partition Data, Chromatographic Indices and Their Dependence on pH in a Set of Nonsteroidal Anti‐Inflammatory Drugs
Authors: La Rotonda Maria Immacolata , Amato Gaetano , Barbato Francesco , Silipo Carlo , Vittoria Antonio 
Published: October 2006

AbstractOctanol/water partition and distribution coefficients of a set of nonsteroidal anti‐inflammatory drugs were measured. Relationships between partition data at different pH values and dissociation constants are discussed.Log k′ values were determined by reversed‐phase high‐performance liquid chromatography (HPLC) on bonded octyl and octadecylsilane supports at different pH values using various organic modifiers in the mobile phase.The log k′ values exhibited linear relationships with methanol concentration in the mobile phase. Octanol/water partition data correlated well with the extrapolated log k′ indices to zero methanol concentration (solvent regression equations) and with the corresponding Rm indices measured on octyl and octadecyl reversed phases thin layer chromatography (HPTLC). Nature of the slopes and the intercepts of the relationships is discussed.It is shown that the HPLC and HPTLC methods are useful alternatives for the determination of partition data.
A QSAR Study of the Ames Mutagenicity of 1‐(X‐Phenyl)‐3,3‐dialkyltriazenes Using Molecular Potential Energy Fields and Molecular Shape Analysis
Authors: Hopfinger A. J. 
Published: October 2006

AbstractA set of 18 1‐(X‐phenyl)‐3,3‐dialkyltriazenes whose mutagenic potencies have been measured were investigated in terms of their potential energy fields. Molecular shape analysis, MSA, was applied to the potential energy field data and a QSAR established. The MSA descriptor, common overlap steric volume between pairs of molecules, found to be a correlate in a previous study [1] is replaced in this study by what physically appears to be the difference in dispersion binding energy between pairs of molecules. A separate investigation of the interrelationship between molecular dielectric representation and corresponding potential energy field based MSA descriptors was carried out. Single molecule MSA descriptors derived from electrostatic energetics are quite dependent on dielectric form, while corresponding pairwise difference MSA features exhibit only a marginal relationship.
Biological Receptor Maps. 2 Steric Maps of Benzoate Antibody and Carbonic Anhydrase
Authors: Motoc Ioan 
Published: October 2006

AbstractSIBIS calculations for hapten‐antibody interactions (i.e., substituted benzoates in the anti‐p‐(p′‐azophenylazo)benzoate system) and sulfonamide binding to carbonic anhydrase are reported. The antibody active site steric map, supported by an excellent QSAR (n = 18, r = 0.99, s = 0.17, F = 156.25), demonstrates that the receptor consists of two regions with distinct steric features: one region exhibits stringent steric requirements and the other one is lax. The steric map of the carbonic anhydrase receptor (based on a very good correlation, n = 33, R = 0.96, s = 0.35, F = 126.64) is confirmed by pattern recognition calculations, and shows that the binding of sulfonamides depends mainly on steric effects.
Some Critical Remarks Concerning the Inductive Parameter σI Part III: Parametrization of the Ortho Effect in Benzoic Acids and Phenols
Authors: Bijloo Greetje J. , Rekker Roelof F. 
Published: October 2006

AbstractCorrelation analysis was applied to pKa values of a series of 63 benzoic acids and a series of 64 phenols in order to obtain more evidence for the correct rules of parametrization of orthosubstituents as suggested by Fujita and Nishioka in 1976.For the inductive effect parameter σI‐used in this type of equations ‐ again a σI = 0.00 parametrization for alkyl groups is applied. The results are in agreement with the findings for aliphatic amines and aliphatic carboxylic acids as discussed in previous papers in this series.Good correlation with r = 0.9982 for benzoic acids and r = 0.9987 for phenols could be made.
Specificities of Subtilisin BPN' and Intracellular Proteinase from Bacillus Amyloliquefaciens in Reaction with Organophosphorus Inhibitors
Authors: Aaviksaar Aavo , Peips Mart , Sikk Peeler , Strongin Alexander Y. A. , Markaryan Adham N. , Stepanov Valentin M. 
Published: October 2006

AbstractThe kinetics of irreversible inhibition of two proteinases from Bacillus amyloliquefaciens, i.e. an intracellular serine proteinase and subtilisin BPN', by O‐n‐alkyl‐p‐nitrophenyl methyl‐phosphonates, (n‐CnH2n+1O)(CH3)P(O)OC6H4NO2‐p, n from 2 to 8, have been studied. The inhibitory activity of these compounds significantly depended upon the length of the alkoxy group in their acid moieties. The dependence of the second‐order rate constant of the enzyme active site phosphorylation upon the Hansch hydrophobicity parameter π of the substituent ‐CnH2n+1 is described by the equation log ki = const. + φ, where φ is 1.1 for the intracellular proteinase and 0.7 for subtilisin BPN′. In subtilisin BPN′ the straight line holds up to n = 6, in the intracellular proteinase up to n = 5. The data point of a difference between the structures of nonpolar substrate‐binding areas in the active sites of the two enzymes.
Multivariate structure‐activity relationships between data from a battery of biological tests and an ensemble of structure descriptors: The PLS method
Authors: Dunn W. J. , Wold S. , Edlund U. , Hellberg S. , Gasteiger J. 
Published: October 2006

AbstractQuantitative structure‐activity relationships (QSAR) are discussed for the case when the chemical structure is characterised by a multitude of structure descriptors and the biological activity measured as the values of several tests.The use of the multivariate data analytical method PLS (partial least squares modelling with latent variables) in this type of problems is described. PLS has some advantages before regression methods, notably the ability to handle both multivariate activity and structure descriptor data and the ability to handle more variables (descriptors) than compounds.As an illustration, a battery of five measures of the mutagenicity of seven chlorinated aliphatic hydrocarbons is analysed in relation to eleven structure descriptors.
A Quantum Chemical QSAR Study of Carbonic Anhydrase Inhibition by Sulfonamides Sulfonamide Carbonic Anhydrase Inhibitors: Quantum Chemical QSAR
Authors: De Benedetti Pier G. , Menziani M. Cristina , Frassineti Chiara 
Published: October 2006

AbstractMolecular Orbital (MO) indices were computed (CNDO/2) for three series of sulfonamide carbonic anhydrase inhibitors, in their neutral and anionic forms.Linear regression analyses between the calculated indices and both physico‐chemical and enzyme inhibition data provide good correlations which enable us to test the predictive and diagnostic aspects of the quantitative structure‐activity relationships employing quantum chemical indices.In particular:

The molecular size affects the inhibitory power among the different sulfonamide derivatives (aliphatic, arylic and bridged diarylic) but not significantly within each molecular series;
the MO indices are good predictors of the various experimental molecular properties and suggest that the less electron‐rich the sulfamoyl group is, the more favoured are both the hydrophobic and hydrophilic steps leading to enzyme inhibition.
Topological Pharmacophores New Methods and Their Application to a Set of Antimalarials Part 2: Results from LOGANA
Authors: Franke Rainer , Streich W. Jürgen 
Published: October 2006

AbstractThe LOGANA procedure described in part 1 of this series is applied to a set of antimalarials as a test case. Its principle consists in the stepwise combination of binary descriptors characterizing the presence or absence of substructural features into conjunctions using the logical operator “and”, such that the structural patterns described by these conjunctions are typical of the class of high activity compounds. Clear substructural patterns for antimalarial activity are obtained which are consistent with corresponding Hansch equations taken from the literature.
Topological Pharmacophores New Methods and Their Application to a Set of Antimalarials Part 3: Results from LOCON
Authors: Franke Rainer , Streich W. Jürgen 
Published: October 2006

AbstractThe LOCON procedure described in the first part of this series is applied to a set of antimalarials as a test case. Its principle consists in the stepwise evaluation of conjunctions such that sets of compounds characterized by these conjunctions have high mean values of biological activity. The conjunctions are obtained from binary descriptors which characterize the presence or absence of predefined substructural features using the logical operator “and”. Clear substructural patterns typical of the highly active compounds are obtained which supplement the LOGANA results presented in Part 2 of this series. There is very good agreement with corresponding Hansch equations taken from the literature so that similar predictions result from both approaches.
The Prediction of Substituent Interactions in the Lipophilicity of Disubstituted Benzenes using RP‐HPLC
Authors: El Tayar Nabil , van De Waterbeemd Han , Testa Bernard 
Published: October 2006

AbstractA number of papers have recently appeared investigating interactions between substituents on aromatic rings, in particular their lack of additivity in terms of hydrophobic constants. In the present study, chromatographic capacity factors (log kw i.e. extrapolated to 100% water composition of the mobile phase) obtained from reversed‐phase high‐performance liquid chromatography (RP‐HPLC) are reported. For the exploration of functional group interactions these values provide a more consistent and precise data set than logP values collected in the literature. A series of 43 disubstituted benzenes was investigated. Substituent interactions are expressed in terms of a previously reported hydration factor ω and the general equation derived is log k = log k + mw · ω, where mw, is a multiplicity factor having an integer value. The physical background of the term mw · ω is discussed by considering the number of water molecules involved in the partitioning process.
Physical Factors Contributing to Hydrophobic Constant π
Authors: Yang Guang‐Zhong , Lien Eric J. , Guo Zong‐Ru 
Published: October 2006

AbstractThe hydrophobicity constants (μ) of different aromatic substituents have been factored into three major components, a volume factor (MW, or Vw), an electronic factor as represented by dipole moment (μ), and H‐bonding factor. The following general equation has been shown to be applicable to a wide range of nonpolar to polar substituents, with only a few notable outliers: π = a · MW (or Vw) ‐ b · HB ‐ c · μ + d.The usefulness and the limitations of such a general correlation are discussed.
Distribution Coefficients by Curve Fitting: Application to Ionogenic Nonsteroidal Antiinflammatory Drugs
Authors: Barbato F. , Caliendo G. , La Rotonda M. I. , Silipo C. , Toraldo G. , Vittoria A. 
Published: October 2006

AbstractA thorough investigation on the dependence of distribution coefficients of acidic drugs on pH and pKa values has been carried out. The results give evidence that the Henderson‐Hasselbach equation is an idealization and only an approximation for real systems.It is shown that a multiparametric curve‐fitting technique may constitute a useful alternative to the previously reported methods to describe the hydrophilic/lipophilic pH‐profiles of ionogenic substances. Calculated values at any given pH value are in very good agreement with the experimental partition (log P) and distribution coefficients determined by shake‐flask method and reversed‐phase high performance liquid chromatography.