bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevation of serum triglyceride and cholesterol levels from isotretinoin therapy with concomitant oral contraceptives
Authors: Chen Yating , Xue Songlin , Dai Wanju , Labraico James 
Published: October 2006

AbstractThis is a matched case‐control study, using spontaneously reported data, to examine the effect of concomitant oral contraceptives on hypertriglyceridemia (HTG) and hypercholesterolemia (HCHL) among female patients who received isotretinoin therapy. Study subjects included all female isotretinoin users, aged 15 to 55, who experienced an adverse event following isotretinoin therapy and were reported to the manufacturer between January 1, 1982 and July 31, 1993. Cases were women who experienced HTG, HCHL, or both and were further classified into three groups ‘HTG only’, ‘HCHL only’, and ‘both HTG and HCHL’. Controls were women who experienced any adverse events other than HTG, HCHL, alopecia, diabetes mellitus, pancreatitis, and obesity. Two controls were randomly selected to match with each case by age (+/‐ 2 years) and by year of commencement of isotretinoin therapy. Statistically significant association was observed between concomitant OC use and HTG (OR = 3.36, 95 per cent CI = 1.30–8.65) as well as between concomitant OC use and HCHL (OR = 2.30, 95 per cent CI = 1.36–3.87) among female isotretinoin users. There was an unusual high frequency of concomitant OC use (OR = 12.0, 95 per cent CI = 3.12–45.36) among ‘both HTG and HCHL’ patients comparing to that of controls. These results suggest a possible interactive effect between oral contraceptives and isotretinoin on the elevation of serum triglyceride or cholesterol levels.
Adverse drug reactions in hospitalized patients: An operational procedure to improve reporting and investigate underreporting
Authors: Maistrello Italo , Morgutti Marina , Maltempi Maura , Dantes Marcello 
Published: October 2006

AbstractBackground — Adverse event (AE) underreporting is a serious obstacle to drug safety monitoring in hospitalized patients, and it is necessary to find new approaches for improving the situation. The aim of the present study was to try to improve reporting and to evaluate the difference between actual and expected reporting.Methods — The drug surveillance programme was implemented in a 72‐bed internal medicine ward. A simple algorithm was printed on each page of the progress notes of the patients' medical record, which the physicians were asked to use in choosing the AEs to be reported to the drug surveillance system. The actual reporting was evaluated for a period of 12 months (1203 patients). Using the same algorithm, two reviewing doctors evaluated expected reporting by analysing all of the AEs deduced from the records of 120 randomly selected patients.Results — Actual reporting: over a period of 12 months, the doctors reported 89 AEs (7.4 per 100 patients), whereas no event had been reported to the national drug surveillance system in the twelve months preceding the introduction of the project. Actual versus expected reporting: in 120 randomly selected patients, 22 AEs were considered by the reviewers as constituting the expected reporting; nine were actually reported.Conclusions — The described drug surveillance programme led to a substantial improvement in adverse event reporting, although a considerable difference still remains between expected and actual reporting.
Spontaneous reporting of adverse drug reactions in an Italian region: Six years of analysis and observations
Authors: Conforti A. , Leone R. , Moretti U. , Guglielmo L. , Velo G. P. 
Published: October 2006

AbstractPharmacovigilance started in Italy in 1965, and from 1987 reporting of ADRs has been mandatory. Doctors have to send the filled forms on suspected ADRs to the Local Health Districts which transmit biannually all the reports to the Health Department.In a Northern Italian Region (Veneto) spontaneous reporting of adverse drug reactions (ADRs) has been studied during the period 1988–1993. This Region contributes a substantial percentage of the total Italian reports. The total number of reports was 3700, most of these (54 per cent) coming from GPs. A great variability in the reporting rate among the 36 districts of Veneto Region (range: 0–8.8 per 10,000 inhabitants per year) and an important under‐reporting have been evident. Underreporting is also emphasized by the fact that in 1993 the Veneto doctors who sent at least one report were only 2.7 per cent. On the whole about 35 per cent of reports concerned minor reactions caused by drugs which have a well known toxicological profile. Comparison between reports coming from Veneto and the UK in some cases show a similar safety profile (omeprazole and simvastatin), whereas in other cases (e.g. terfenadine, glafenine, fluoxetine) no correspondence can be found. This article reveals the limits of the actual spontaneous reporting in Italy and suggests some possible measures for improving it.
Audit of care of acute inflammatory polyradiculoneuropathy in Italy
Authors: Beghi Ettore ,   The Italian Guillain‐Barré Study Group
Published: October 2006

AbstractA multicentre prospective investigation of the main treatment regimens for the Guillain‐Barré syndrome (GBS) was started in Italy to assess the quality of the care delivered for GBS in clinical practice. Between 14 April 1988 and 31 December 1993, 250 patients (157 males and 93 females aged 3 to 86 years) were recruited in 14 centres. The commonest treatments were plasma exchange (PE) (62 per cent), steroids (ST) (37 per cent) and immunoglobulins (IG) (19 per cent). Eighteen per cent of cases received ST and PE. These data contrast in part with reports on the treatment of GBS published between 1976 and 1993, which showed PE as an effective treatment, IG as a promising but still experimental drug, and ST as a failing therapeutic approach. The variables which seemed to affect the treatment choices most were centre, year of diagnosis, and disease severity. According to this survey, the treatment of GBS in Italy tends only partly to reflect the indications and recommendations in the main scientific reports. This not only indicates a suboptimal impact of the best available knowledge on the treatment of GBS, but also documents the need for more definite guidelines and further research through clinical trials.
Drug‐related problems as a cause of hospital admissions in Hong Kong
Authors: Chan Thomas Y. K. , Critchley Julian A. J. H. 
Published: October 2006

AbstractThe importance of drug‐related problems as a cause of hospital admissions in Hong Kong was studied in 925 patients admitted to two general medical wards at the Prince of Wales Hospital between November 1992 and February 1993. Drug‐related problems were judged to be the main reason for hospital admissions in 88 patients (9.5 per cent). These were adverse drug reactions (n = 57), drug poisoning (n = 22) and treatment failure consequent to noncompliance or inappropriate reduction in dosage (n = 9). The most important adverse drug reactions were gastrointestinal hemorrhage (36.8 per cent) and hypoglycemia (24.6 per cent), and the three drug classes that were most commonly involved were non‐steroidal anti‐inflammatory drugs (NSAIDs) (aspirin 12.3 per cent, non‐aspirin 28.1 per cent), sulphonylureas (19.3 per cent) and diuretics (12.3 per cent). Drug‐related problems are an important cause of hospital admissions, and much of the drug‐induced illnesses in Hong Kong could be preventable if particular attention was given to NSAID and sulphonylurea therapy. Patients should also be educated about the importance of good drug compliance.
Generic data
Authors: Walker Alexander M. 
Published: October 2006

AbstractIn an earlier issue of Pharmacoepidemiology and Drug Safety, I described an IMBRF/ISPE meeting on proposed European and British regulations on confidential medical data. ISPE members commonly deal in confidential medical data when they evaluate adverse drug reactions, when they make and respond to regulatory requests for population data on drug safety, and when they compare the health and economic consequences of treatment strategies! Here I would like to open a discussion of the first of the research areas that were raised by that meeting. This is the question of when data must be regarded as ‘personally identified’.
Infarct size estimated from peak creatine kinase is reduced in patients using beta‐blockers at the onset of chest pain
Authors: Landmark Knud , Abdelnoor Michael , Urdal Petter 
Published: October 2006

AbstractIn 418 patients (median 67 years) with acute myocardial infarction (AMI) we examined if ongoing β‐blocker treatment at the onset of AMI (n = 63) had beneficial effects on infarct size as judged from peak creatine kinase (CKmax) activity. The study had an observational exposed/non‐exposed design where we investigated the possible association between β‐blocker treatment and CKmax. Both crude and adjusted effects were looked for, in the latter adjusting for the effect of confounders such as thrombolytic treatment and age during AMI.Crude effects: β‐blocker treatment significantly (p = 0.003) reduced CKmax, from 1171 U/1 to 790 U/1 (median values). In the 25% of patients with the largest infarcts, β‐blockers reduced the incidence of large infarcts by 61% (odds ratio = 0.39) (p = 0.015). Previous coronary heart disease reduced CKmax (p = 0.0001), whereas thrombolytic treatment significantly increase CKmax (p = 0.0001), probably due to reperfusion.Adjusted effects: β‐blocker treatment significantly reduced CKmax (p = 0.03), and reduced the incidence of large infarcts by 54% (odds ratio = 0.46).Thus, when adjusting for confounders, β‐blocker treatment at the onset of AMI reduced infarct size as well as the incidence of large infarcts. These observational results suggest real myocardial salvage.
Prescription drug screening for subsequent carcinogenicity
Authors: van den Eeden Stephen K. , Friedman Gary D. 
Published: October 2006

AbstractCancer occurrence was determined through 1988 among a cohort of 143,574 Kaiser Permanente Medical Care Program members whose prescription records were computer‐stored between 1969–1973. Age‐ and gender‐adjusted standardized morbidity ratios (SMRs) were determined by dividing the number of cancers observed among one category of drug users by the number expected based on the cancer experience of the cohort as a whole. This hypothesis‐generating screening programme examined 215 drugs and 56 cancer sites. Although a large number of drug‐cancer associations were nominally statistically significant, many of these have been previously reported and the primary focus of this report is on new findings. Among the new findings considered intriguing were associations of indomethacin with stomach cancer (SMR = 1.51, p < 0.05), prednisone with myeloid leukemia (SMR = 2.27, p < 0.05) and lymphosarcoma (SMR = 2.22, p < 0.002), sulfamethoxazole with lymphosarcoma (SMR = 2.90, p < 0.01), thiazides (SMR = 1.80, p < 0.05) and isoniazid (SMR = 8.46, p < 0.05) with gallbladder cancer.Given the long follow‐up of this cohort, drug‐cancer relationships that are manifested only after latencies approaching two decades would have sufficient time to become apparent. However, since these data are based on pharmaceuticals dispensed over a short time period and because limited data on potential confounders were available, more definite investigations should follow‐up these results.
Pharmacovigilance education and certification report on a feasibility survey
Authors:   SIGAR
Published: October 2006

AbstractA survey conducted by the Special Interest Group on Adverse Reactions (SIGAR) identified an interest in developing a formal educational programme on pharmacovigilance. The majority of potential delegates had between 1 and 5 years of experience in pharmacovigilance and held higher qualifications. They were prepared to provide up to 6 hours of self‐study per week but only a minority would sponsor themselves.Managers envisaged providing at least one candidate for up to three modules per annum. Preferred modules included regulatory requirements and guidelines, spontaneous reporting, methodologies and company systems. As a result of this favourable response an academic partner has been appointed in the United Kingdom and the course will commence in 1996.
Plasminogen activator inhibitor type‐1 (PAI‐1) polymorphism 4G/5G is associated with prostate cancer among men with a positive family history
Authors: Jorgenson Eric , Deitcher Steven R. , Cicek Mine , Liu Xin , Plummer Sarah , Casey Graham , Witte John S. 
Published: October 2006

AbstractBACKGROUNDVariation in the expression of plasminogen activator inhibitor type‐1 (PAI‐1) is associated with many human diseases, including several types of cancer. In particular, tumor cell overexpression of PAI‐1 has been found to inhibit prostate cancer tumor growth, angiogenesis, and metastasis in mouse models. Normal host cell expression of PAI‐1 is influenced by the 4G/5G insertion/deletion polymorphism in the promoter region of the PAI‐1 gene. To evaluate the effect of PAI‐1 expression on cancer development, we examined the association of the 4G/5G polymorphism in a sibling‐based case‐control study of prostate cancer.METHODSOne thousand one hundred thirty seven subjects, 655 cases, and 482 sibling controls from 526 families, were recruited from the major medical institutions in the greater Cleveland, OH area and from the Henry Ford Health System, Detroit, MI. A Cox age‐of‐onset model with robust variance estimation was used to evaluate the association between the PAI‐1 4G/5G polymorphism and prostate cancer.RESULTSNo association was observed between the PAI‐1 4G/5G polymorphism and prostate cancer in the entire sample. We did, however, identify a statistically significant association between the PAI‐1 4G/5G polymorphism and prostate cancer in subjects with a family history of this disease (OR = 1.28, 95% CI 1.02–1.61, P‐value = 0.036). The PAI‐1 5G/5G genotype, associated with lower PAI‐1 expression, appears to drive this result as it was associated with an increased risk of prostate cancer and an earlier mean age of onset compared to those with the 4G/4G genotype (OR = 1.83, 95% CI 1.12–2.99) while the 4G/5G genotype group did not show a significant difference in prostate cancer risk compared to the 4G/4G genotype group (OR = 0.98, 95% CI 0.75–1.28).CONCLUSIONSThese observations suggest that the 4G/5G polymorphism in PAI‐1 may explain some of the increased risk and earlier mean age of onset of prostate cancer due to a positive family history. Prostate © 2006 Wiley‐Liss, Inc.
A Comparison by QSAR, Crystallography, and Computer Graphics of the Inhibition of Various Dihydrofolate Reductases by 5‐(X‐Benzyl)‐2,4‐diamino‐pyrimidines
Authors: Li Ren‐Li , Hansch Corwin , Matthews David , Blaney Jeffrey M. , Langridge Robert , Delcamp Tavner J. , Susten Sandra S. , Freisheim James H. 
Published: October 2006

AbstractThe QSAR for forty 2,4‐diamino‐5‐(X‐benzyl)‐pyrimidines inhibiting human lymphoblastoid dihydrofolate reductase is reported and compared with the QSAR for inhibition of dihydrofolate reductase from E. coli, L. casei, chicken, and bovine liver sources by the same inhibitors. A preliminary attempt to integrate the experimental QSAR results with the three‐dimensional X‐ray structures of E. coli and chicken dihydrofolate reductase, using interactive computer three‐dimensional color graphics molecular modeling methods, is described.
Quantitative Comparative Studies on Peripheral and Central Bradycardia Induced by Imidazolidines
Authors: Timmermans Pieter B. M. W. M. , De Jonge Adriaan , van Zwieten Pieter A. 
Published: October 2006

AbstractCentral hypotensive activity of α‐adrenoceptor agonists generally parallels bradycardic potency. This has led to the conclusion that bradycardia, like the induction of hypotension, is also initiated within the central nervous system by stimulation of α2‐adrenoceptors. However, bradycardia has still been found for a very hydrophilic α‐adrenoceptor agonist not showing central hypotensive activity following systemic application. In view of this inconsistency quantitative comparisons were made between central hypotensive activity and overall bradycardic potency in anaesthetized normotensive rats after intravenous administration within a series of phenyliminoimidazolidines. The log dose‐bradycardic response curves of the more lipophilic derivatives were monophasic, whereas those of the hydrophilic compounds were characterized by a bisigmoidal shape. As a result of the dual nature of this effect, the potency of the drugs to decrease heart rate was quantified at 10%, pC10(HR), as well as at 20%, pC20(HR), effect level. Linear regression analysis showed a highly significant correlation between pC20(HR) and hypotensive activity. Lipophilicity, log P′, had to be added to verify this relationship for pC10(HR). For the latter variable, however, a linear relationship was derived with the potency of the compounds to inhibit cardiac frequency via stimulation of presynaptic α2‐adrenoceptors in the heart itself. These results strongly suggest that overall bradycardia of α‐adrenoceptor agonists may consist of a peripheral and a central component. Both mechanisms are governed by the stimulation of α2‐adrenoceptors. The peripheral mechanism (presynaptic cardiac α2‐adrenoceptors) is triggered by hydrophilic as well as lipophilic compounds following systemic application. The induction of central bradycardia (central α2‐adrenoceptors) and hypotension is but limited to the more lipophilic drugs.
Rationalisations among Heterocyclic Partition Coefficients Part 1: The π‐Value of Phenyl
Authors: Lewis Susan J. , Mirrlees Margaret S. , Taylor Peter J. 
Published: October 2006

AbstractIt is shown that πPh has a minimum theoretical value of ca. 1.7 in aromatic rings. This value is attained whenever phenyl is forced into a highly non‐planar conformation, as may happen through peri‐interactions or the heavy solvation of sterically hindering neighbouring groups. In the absence of such hindrance πPh will be greater, and can attain values as high as ca. 2.6 when there is no steric hindrance to coplanarity and two hetero‐atoms can be shielded. These and a number of intermediate situations are delineated; estimates of πPh are provided for each distinct case. The effect of phenyl substitution at sp3‐carbon is discussed in similar terms. It is shown that these variations make qualitative chemical sense and can be used for predictive purposes.
BC(DEF) Coordinates 4. Correlations with General Anesthesia, Nerve Blockade, and Erythrocyte Stabilization
Authors: Cramer Richard D. 
Published: October 2006

AbstractThe abilities of structurally diverse compounds to induce general anesthesia, block neutral conduction, or stabilize erythrocytes against osmotic shock are highly correlated (r > 0.96) by the compounds BC(DEF) coordinates alone. Assuming that a compound whose effects are produced by a receptor‐mediated, structurally specific, mechanism would have a potency greater than that predicted by its BC(DEF) co‐ordinates, a “positive outlier exclusion” procedure for extracting such selectively acting compounds from a set of data was developed. However, its application to these three data sets yielded little evidence of specificity. These results are consistent with the view that these processes are non‐specifically mediated and mechanistically similar, except that anesthetic potency is favored by partitioning from vapor into lipid, rather than from water into lipid. The equations obtained resemble the property equation for octanol/water partitioning more than property equations for other partitioning systems. Long chain hydrocarbons are unusual, both in having unexpectedly low nerve blockade activity and in having highly negative C coordinates.
Structural Information and a Flexibility Index from the Molecular Connectivity 3χp Index
Authors: Kier Lemont B. , Hall Lowell H. 
Published: October 2006

AbstractThe molecular connectivity 3χp index has been evaluated for its structure information content. This index has been found to relate closely to a quantitation of the number of gauche‐trans rearrangements possible in the molecule. The count of the number of three‐path fragments, 3Np carries similar information. Both indexes are shown to relate closely to density and to the Mann estimate of the average number of gauche arrangements in a molecule, Zg. The 3χp and 3NP indexes are superior to the Zg index in relating to alkane density. On the basis of the quantitation of gauche‐trans folding a flexibility index, F = n/1 ‐ 3NP has been empirically derived to rank alkanes according to a perception of their kinetic flexibility.
BC(DEF) Coordinates 5. Shape‐Specific vs. Orientation‐Averaged Interactions of Neuroleptics and Other Centrally Acting Drugs: Correlation of Effects in Five in vitro Test Systems
Authors: Yunger Libby M. , Cramer Richard D. 
Published: October 2006

AbstractTo evaluate further a methodology proposed for determining whether the pharmacological actions of compounds are due to shape‐specific or orientation‐averaged molecular interactions with biological systems, the activities of neuroleptics and other centrally acting drugs in five in vitro test systems were correlated with the compounds' BCDEF coordinates. It is hypothesized that shape‐specific interactions will tend to enhance the activity of a compound in the test system and, thus, these compounds would be the positive outliers in such an analysis. These compounds were floated and the correlation repeated until all of the specifically‐acting compounds were identified. Inhibition of [3H]haloperidol, [3H]flupenthixol, and [3H]dopamine binding by neuroleptics and catecholamines appeared to be primarily due to shape‐specific molecular interactions with the receptor. In contrast, neuroleptic‐induced inhibition of synaptosomal GABA accumulation and of calmodulin‐mediated phosphodiesterase activity appeared to be due to non‐specific interactions, that is, these effects could be explained exclusively by the same orientation‐averaged interactions that determine the overall physicochemical properties of the test molecules. Although lipophilic in character, non‐specific interactions with these biological test systems are less selective against bulky and polar molecules than are common models of lipophilicity such as partitioning between water and immiscible organic solvents.
Theoretical Investigations on Interactions Between Pharmacon Molecules and Receptor Models V: Construction of a Model for the Ribosomal Binding Site of Chloramphenicol
Authors: Höltje Hans‐Dieter , Tintelnot Marina 
Published: October 2006

AbstractInteraction energies between the most stable conformations of chloramphenicol and Chloramphenicol derivatives and amino acids as binding site models were calculated using the multipol‐bond‐polarizability method. The resulting energies were correlated with the antibiotic activities of the drug molecules. A receptor model for the chloramphenicol molecule was constructed which consists of arginine and histidine as binding sites for the acyl sidechain and the substituted aromatic ring system, respectively.The significance of the hypothetical receptor was challenged by determination of low energy conformations of a fragment from the ribosomal chloramphenicol binding protein L16 which comprises the single histidine residue of this protein. The results of these ECEPP calculations and of experimental histidine blockade prove the receptor model to be realistic.