Education is not enough to reduce the adverse consequences of pharmaceutical drug use.
Explore the source record for details and available documents.
Drug Information Services↗
Biomedical subjects
R Harvey
Publications and source records attributed to R Harvey.
Linking prescription and patient-identifying data: a pilot study.
OBJECTIVE: To link a Pharmaceutical Benefits Scheme (PBS) prescription data set with patient-identifying data held by the Health Insurance Commission (HIC) and to then determine the prevalence of prescribing of cardiovascular drugs, non-steroidal anti-inflammatory drugs, hypnotics and minor tranquillizers, and diuretics (prescribed without other cardiovascular drugs) by age and sex in two defined populations. DESIGN: Prescription data for a three-month period in 1985 were matched with patient-identifying information to obtain a database which included the patient's age, sex and an identifying number, for each prescription record. The percentages of the population taking a drug from each of the drug categories mentioned above were then determined and the effect of age, sex and region of residence on prescribing prevalence was investigated using logistic regression analysis. SETTING: Two rural regions of Australia with a total population of 65,087 residents. MEASUREMENTS AND MAIN RESULTS: Of the 101,383 prescriptions dispensed over the period 96% could be matched with HIC information. In the two regions combined, the percentages of the population taking a cardiovascular drug, non-steroidal anti-inflammatory drug, hypnotic or minor tranquilizer, or diuretic (without other cardiovascular drugs) were 10.4%, 5.8%, 3.5% and 2.5%, respectively. Prescribing rates were higher for females than males, increased with age and varied between the two regions. Approximately 5% of women aged 30-39 years were taking diuretics without other cardiovascular drugs, compared with only 0.2% of men in the same age group. CONCLUSIONS: This pilot study illustrates the use of a patient-identified prescription database for drug utilisation review, therapeutic audit and hypothesis generation.
Adult↗
The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization.
The vav proto-oncogene encodes a protein of unknown function that is rendered oncogenic by loss of a short N-terminal domain. A correction reported here to the vav sequence reveals that a central domain of some 230 amino acids is similar to the products of three genes: the human dbl oncogene, now known to encode a GDP-GTP exchange factor for the Ras-like polypeptide CDC42Hs; the CDC24 gene of Saccharomyces cerevisiae, which participates with CDC42Sc in organization of the cytoskeleton for budding; and the human bcr gene, which recombines with the abl oncogene in certain forms of leukemia. Furthermore, the N-terminal portion of Vav (and of CDC24) is similar to that of certain proteins that associate with filamentous structures. These similarities suggest that Vav, and perhaps also Bcr, may function as a GDP-GTP exchange factor for a Ras-like molecule such as CDC42Hs, and that its action may coordinate cytoplasmic architecture with the cell cycle. Reported evidence that the vav proto-oncogene is widely expressed in hematopoietic cells but not other cell types is extended here by detection of vav mRNA in 49 of 50 murine hematopoietic cell lines representing diverse hematopoietic lineages, and by in situ hybridization in embryos showing expression confined to the only hematopoietic tissue, fetal liver. Thus, like Dbl in other cell types, Vav may function throughout the hematopoietic compartment to govern a Ras-like signal transduction pathway.
Amino Acid Sequence↗
SCL is coexpressed with GATA-1 in hemopoietic cells but is also expressed in developing brain.
The SCL gene encodes a putative transcription factor with a basic helix-loop-helix (B-HLH) motif and is known to be predominantly expressed in erythroid cells. Here we also demonstrate expression of SCL mRNA in normal mast cells, mast cell lines and megakaryocytic cell lines. SCL is therefore expressed in the same three lineages as GATA-1, a well-recognized hemopoietic transcription factor. SCL and GATA-1 mRNA were also co-expressed in interleukin 3-dependent primitive myeloid lines. In murine erythroleukemia (MEL) cells SCL and GATA-1 underwent coordinated biphasic modulation during hexamethylene bisacetamide (HMBA)-induced erythroid differentiation. The kinetics of SCL and GATA-1 mRNA expression was inversely correlated with changes in ID, a negative regulator of B-HLH proteins, and was distinct from changes in MYC, MYB and erythropoietin receptor transcripts. During myeloid differentiation of K562 cells, SCL and GATA-1 mRNA levels also underwent biphasic modulation. Thus SCL and GATA-1 are coordinately expressed in multiple hemopoietic lineages and coordinately regulated during induced erythroid and myeloid differentiation. In nonhemopoietic tissues SCL was only detected in adult and developing brain where GATA-1 is reportedly not expressed. In day 14.5 embryos analysed by in situ hybridization, SCL transcripts were detected in post-mitotic neurons in the metencephalon and roof of the mesencephalon. This suggests a previously unexpected role for SCL in neural differentiation.
Animals↗
Rapid detection of chromosome aneuploidies in uncultured amniocytes by using fluorescence in situ hybridization (FISH).
Herein we report the results of the first major prospective study directly comparing aneuploidy detection by fluorescence in situ hybridization of interphase nuclei with the results obtained by cytogenetic analysis. We constructed probes derived from specific subregions of human chromosomes 21, 18, 13, X, and Y that give a single copy-like signal when used in conjunction with suppression hybridization. A total of 526 independent amniotic fluid samples were analyzed in a blind fashion. All five probes were analyzed on 117 samples, while subsets of these five probes were used on the remaining samples (because of insufficient sample size), for a total of over 900 autosomal hybridization reactions and over 400 sex chromosome hybridization reactions. In this blind series, 21 of 21 abnormal samples were correctly identified. The remaining samples were correctly classified as disomic for these five chromosomes. The combination of chromosome-specific probe sets composed primarily of cosmid contigs and optimized hybridization/detection allowed accurate chromosome enumeration in uncultured human amniotic fluid cells, consistent with the results obtained by traditional cytogenetic analysis.
Amniocentesis↗
Bilateral tibial fractures in properly restrained toddlers involved in motor vehicle collisions: case reports.
It is well documented that the use of child restraints, specifically child safety seats, can reduce morbidity and mortality in young victims of motor vehicle crashes. Literature review reveals few extremity fractures in properly restrained toddlers. Of 10 restrained infants involved in car crashes admitted to our hospital, 4 had leg fractures. We report 2 cases of bilateral tibial fractures in restrained toddlers in which the usual clinical signs of fracture were minimal or lacking. A high index of suspicion must be maintained in evaluating even properly restrained toddlers in motor vehicle crashes.
Accidents, Traffic↗
Structural elements that regulate pp59c-fyn catalytic activity, transforming potential, and ability to associate with polyomavirus middle-T antigen.
Except for its unique amino-terminal region (residues 1 through 83), which possibly dictates substrate recognition, pp59c-fyn bears a high degree of homology with other members of the src family of tyrosine kinases. Here we show that the carboxy terminus of pp59c-fyn is necessary for stable middle-T-antigen association, that pp59c-fyn is normally phosphorylated on both serine and tyrosine residues, and that Tyr-531 and Tyr-420 are phosphorylation sites in vivo and in vitro, respectively. Analysis of a spontaneously generated mutant encoding a truncated form of pp59c-fyn and of variants specifically mutated at the Tyr-531 and Tyr-420 phosphorylation sites indicates that pp59c-fyn has regulatory elements analogous to those that have already been identified for other src-like tyrosine kinases. However, further examination of the pp59c-fyn variants suggests the likelihood of additional means by which its activities might be regulated. Although alteration of Tyr-531 to phenylalanine (531F) in pp59c-fyn results in a protein which is more active enzymatically that the wild type, the enhancement is much less than that for the analogous variant of pp60c-src. Furthermore, contrary to results of similar experiments on other src-like proto-oncogene products, 531F did not induce transformation of NIH 3T3 cells. Studies involving pp59c-fyn-pp60c-src chimeras in which the unique amino-terminal sequences (residues 1 through 83) of the two kinases were precisely interchanged implied that the inability of 531F to induce transformation is probably not caused by the absence of substrates for pp59c-fyn in NIH 3T3 cells but rather by the insufficient enhancement of pp59c-fyn kinase activity. It is therefore probable that the kinase and transforming activities of pp59c-fyn are repressed by additional regulatory elements possibly located in the amino-terminal half of the molecule.
Amino Acid Sequence↗
Cloning of the t(11;14)(q13;q32) translocation breakpoints from two human leukemia cell lines.
The t(11;14)(q13;q32) translocation has been associated with several subtypes of human leukemia and lymphoma. It has been proposed that this translocation activates a proto-oncogene designated BCL1. In an effort to better understand the mechanism by which this translocation leads to malignancy, we have studied this translocation in two human cell lines. MO1094 and MO2058 were derived from patients with prolymphocytic variants of chronic lymphocytic leukemia. Southern blotting of the MO2058 cell line documented that the translocation linked the Jh region in the immunoglobulin heavy chain gene to the previously described BCL1 major translocation cluster (MTC). Using the polymerase chain reaction, we cloned this translocation and showed that the chromosome 11 breakpoint was within 7 bp of two other samples reported previously. Southern blotting of the MO1094 cell line suggested that the translocation in this cell line might link Jh sequences to a new region in the BCL1 locus on chromosome 11. Therefore, the MO1094 breakpoint was cloned from a genomic library. Comparison with normal cloned DNA from the BCL1 locus showed that the chromosome 11 breakpoint occurred 24 kb telomeric of the MTC. This work reinforces the concept that translocation breakpoints in the BCL1 locus are scattered over at least 63 kb.
Base Sequence↗
From Medibank to Medicare: trends in Australian medical care costs and use from 1976 to 1986.
Private medical care costs and service use in Australia from 1976 to 1986 are compared. In each of these years Australia had a compulsory, universal, fee-for-service, national health insurance scheme - Medibank in 1976 and Medicare in 1986. Over the period of 1976 to 1986, the number of private medical services per capita, in the 6 month period 1 April to 30 September, increased from 2.79 to 3.95, an increase of 3.54 per cent per year. The cost of services per capita, adjusted for increases in schedule fees for each item-group of services (the 'fee-adjusted cost'), grew at a rate of 3.91 per cent per year. The results are reported by subsets of age, sex and item-group of service. It is found that very little of the large increases in use and cost of services can be attributed to demographic changes or population growth. Rather, they represent rapid increases in age and sex-specific rates of use, primarily among the very young, the very old and, for some types of service, women of child-bearing age. The most dramatic increases in service use are found in pathology, radiotherapy and miscellaneous procedures.
Adolescent↗
Stoichiometry of cellular and viral components in the polyomavirus middle-T antigen-tyrosine kinase complex.
Our results indicate that only one type of tyrosine kinase is present within each middle-T antigen-tyrosine kinase complex, suggesting that middle-T antigen forms separate complexes with different tyrosine kinases. Furthermore, we determined that there is only one molecule of middle-T antigen within any one of these complexes. We interpret this to mean that in any given cell, polyomavirus transformation involves, at least in part, the simultaneous deregulation of a number of separate pathways controlling cellular proliferation. Finally, we also demonstrate that the separate middle-T:pp60c-src and middle-T:pp59c-fyn complexes are each able to interact with the same cellular p81/85-kDa phosphoprotein, a possible component of the phosphatidylinositol kinase.
1-Phosphatidylinositol 4-Kinase↗
The amino-terminal region of pp60c-src has a modulatory role and contains multiple sites of tyrosine phosphorylation.
The c-src gene product from either platelet-derived growth factor treated cells or from polyomavirus-infected cells migrates anomalously on gels, displays enhanced kinase activity, and contains additional sites of tyrosine phosphorylation within its amino-terminus. To probe the importance of these post-translational modifications, each of the five amino-terminal tyrosine residues (residues 90, 92, 131, 136, and 149) was altered to phenylalanine using site-directed mutagenesis. Except for the 136F variant, the mutants displayed enhanced kinase activity, albeit at a low level shown insufficient to induce focus formation in NIH3T3 cells. Mutagenesis of residues adjacent to tyrosines 90 and 92 also resulted in variants with enhanced kinase activity indicating that the region and not the tyrosines per se, may be involved in regulating this activity. Fingerprinting analysis demonstrated that the enhanced kinase activity brought about by these mutations occurred through a mechanism which appears to be independent of the phosphorylation state of Tyr 416 and possibly Tyr 527. Upon treatment of cells with vanadate both amino-terminal variants and transforming mutants of pp60c-src displayed a slower migrating form, designated p60+. Hence, the appearance of these p60+ proteins may be elicited either by mutations that enhance the transforming activity of pp60c-src or by perturbations within the amino-terminal region of the enzyme. The retarded mobility of p60+ was shown to be due in part to additional tyrosine phosphorylations residing at its amino-terminus. The demonstration that p60+ could be resolved into multiple bands and that amino-terminal fragments containing phosphorylated tyrosine residues were obtained regardless of which of the five tyrosines in the region was altered to phenylalanine indicates that there are multiple sites of tyrosine phosphorylation within the amino-terminal region of pp60c-src.
Amino Acid Sequence↗
Cloned genes for ligand-operated ion channels and their expression in vitro.
Explore the source record for details and available documents.
Acetylcholine↗
Quality assurance in Australian hospitals: who does it and how?
OBJECTIVE: To seek information on the type, method and extent of quality assurance being undertaken in all public and private hospitals within Australia. METHOD: Mailed questionnaire. RESULTS: There was a predominance of two types of review being undertaken. Some important deficiencies in the quality assurance process were identified. Far more private than public hospitals reviewed medical records and surveyed patient satisfaction.
Australia↗
Immunoscintigraphy with monoclonal antibodies.
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
Death from drug-induced hemolytic anemia.
Fatal hemolytic anemia occurred in a 71-year-old man after trimethoprim-sulfamethoxazole was given for presumed cystitis. Administration of this combination has previously caused multiple hematologic reactions by affecting folic acid metabolism. Megaloblastic anemia and neutropenia have been produced by both of these agents, while sulfamethoxazole alone has induced acute hemolytic anemia in patients with hereditary deficiency of glucose-6-phosphate dehydrogenase. Although hematologic complications of trimethoprim-sulfamethoxazole treatment usually follow long-term or high-dose therapy, acute reactions apparently may occur at lower doses as well.
Aged↗
Mechanism of activation of complexed pp60c-src by the middle T antigen of polyomavirus.
Explore the source record for details and available documents.
Animals↗