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Biomedical subjects

R Perkins

Publications and source records attributed to R Perkins.

At least 73 records · Page 4Linked to original sources
PubMed1981

Radiological techniques for small acoustic tumors--a re-evaluation.

Small acoustic neuromas are not detected on conventional, computed tomography (CT) brain scans. Eighteen patients with proven acoustic tumors and negative CT brain scans were studied retrospectively to re-evaluate current radiological techniques. We found that the conventional mastoid plain film or thin section tomography is an accurate, cost effective, screening test for acoustic tumors. When these screening studies are positive and agree with the clinical and audiometric examinations, a CT brain scan should then be performed. If the latter is negative, Pantopaque myelography or air-CT should follow. The decision to proceed to invasive studies has been helped by such tests as brain stem audiometry. Since no single, noninvasive X-ray test currently exists to diagnose the small acoustic tumor, screening X-ray studies are indicated before the use of invasive, expensive studies. A protocol for the radiological work-up of small acoustic tumors is suggested.

Adult↗
PubMed1979

Isolation of cholera toxin receptors from a mouse fibroblast and lymphoid cell line by immune precipitation.

Cholera toxin receptors have been isolated from both a mouse fibroblast (Balbc/3T3) and mouse lymphoid cell line labeled by the galactose oxidase borotritiide technique. Tritiated receptor-toxin complexes solubilized in NP40 were isolated by addition of toxin antibody followed by a protein A-containing strain of Staphylococcus aureus. In both cell types by far the major species of toxin receptor isolated was ganglioside in nature, although galactoproteins were also present in the immune complexes. Whether the galactoproteins form part of a toxin-receptor complex or are artifacts of the isolation procedure is presently unclear. The relative specificity of cholera toxin for a carbohydrate sequence in a glycolipid suggests that the toxin might prove a useful tool in establishing the function and organization of glycolipids in membranes. For example, interaction of cholera toxin with the mouse lymphoid cell line was shown to result in patching and capping of bound toxin, raising the possibility that the glycolipid receptor interacts indirectly with cytoskeletal elements. Cholera toxin might also be used to select for mutant fibroblasts lacking the toxin receptor and therefore having an altered glycolipid profile. Such mutants might prove useful in establishing the relationship (if any) between modified glycolipid pattern and other aspects of the transformed phenotype. Attempts to isolate mutants, based on the expectation that growth of cells containing the toxin receptor would be inhibited by the increase in cAMP levels normally induced by cholera toxin, proved unsuccessful. Cholera toxin failed to inhibit significantly the growth of either Balbc or Swiss 3T3 mouse fibroblasts although it markedly elevated cAMP levels.

Animals↗
PubMed1976

Tympanomastoid reconstruction: an operative procedure for anatomical and functional restoration of the radicalized ear.

A new operative procedure for the anatomical and functional restoration of both the middle ear and mastoid is described. The technique employs homograft tympanic membrane with ossicles en bloc for the middle ear reconstruction and a homograft dura form and autogenous bone pate is used to recreate the bony posterior ear canal wall. The reconstructed wall becomes hard viable bone in about one year. Results in terms of wall integrity, tympanic membrane survival and hearing are discussed. The mechanism of new bone formation is discussed with presentation of histologic findings.

Bone Regeneration↗
PubMed1975

Effect of caffeine upon maximal muscular endurance of females.

The effect of various dosages of caffeine upon maximal endurance capacity in females was studied. The effect of caffeine upon resting heart rate (RHR), submaximal heart rate (SHR), maximal heart rate (MHR), and ratings of perceived exertion (RPE) was also studied. Prior to undertaking a standarized progressive workload to exhaustion on an electric bicycle ergometer, each subject consumed either a placebo, small (4 mg/kg), medium (7 mg/kg) or large (10 mg/kg) dose of caffeine. A double-blind procedure was followed. Mean times to exhaustion for the placebo, small, medium and large dosages of caffeine were, respectively, 299.5, 312.1, 299.8, and 303.2 seconds. MHR were respectively, 183.4, 185.0, 185.4, and 184.4. Maximal RPE were 16.6, 17.0, 16.3, and 17.1. The analysis of variance revealed no significant differences between the drug trials for the above three variables; in addition, no significant differences were noted for the RHR, SHR, and submaximal RPE. Within the limitations of this study, the following conclusion appears warranted: A small, moderate, or large dose of caffeine exerted no significant effect upon maximal endurance time, RHR, SHR, MHR, or RPE at either submaximal or maximal workloads.

Adaptation, Physiological↗
PubMedDate not supplied

On a hiding to nothing? Assessing the corporate governance of hospital and health services in New Zealand 1993-1998.

In New Zealand the governance of public sector hospital and health services has changed significantly over the past decade. For most of the century hospitals had been funded by central government grants but run by locally elected boards. In 1989 a reforming Labour government restructured health services along managerialist lines, including changing governance structures so that some area health board members were government appointments, with the balance elected by the community. More market oriented reform under a new National government abolished this arrangement and introduced (1993) a corporate approach to the management of hospitals and related services. The hospitals were established as limited liability companies under the Companies Act. This was an explicitly corporate model and, although there was some modification of arrangements following the election of a more politically moderate centre-right coalition government in 1996, the corporate model was largely retained. Although significant changes occurred again after the election of a Labour government in 1999, the corporate governance experience in New Zealand health services is one from which lessons can, nevertheless, be learnt. This paper examines aspects of the performance and process of corporate governance arrangements for public sector health services in New Zealand, 1993-1998.

Governing Board↗
PubMedDate not supplied

The use of the bicipital groove for alignment of the humeral stem in shoulder arthroplasty.

Four hundred twenty humeri were measured to determine humeral head retroversion and its relation to the location of the bicipital groove. Average head retroversion was found to be 28.3 degrees (+/- 13.2 degrees), and the angular orientation of the bicipital groove referenced to the transepicondylar axis was 55.5 degrees (+/- 13.8 degrees). The average difference between these angular orientations was 27.3 degrees (+/- 14.2 degrees). This result implies that the bicipital groove can be used as a landmark for prosthetic stem positioning in shoulder arthroplasty if the center of the lateral aspect of the stem is posteriorly offset approximately 30 degrees from the center of the groove. However, because of the appreciable variation in these averages, the use of the bicipital groove as a reference can result in a significant error of humeral stem alignment, which should be considered when determining the retroversion for a particular patient.

Aged↗
PubMedDate not supplied

QSAR models using a large diverse set of estrogens.

Endocrine disruptors (EDs) have a variety of adverse effects in humans and animals. About 58,000 chemicals, most having little safety data, must be tested in a group of tiered assays. As assays will take years, it is important to develop rapid methods to help in priority setting. For application to large data sets, we have developed an integrated system that contains sequential four phases to predict the ability of chemicals to bind to the estrogen receptor (ER), a prevalent mechanism for estrogenic EDs. Here we report the results of evaluating two types of QSAR models for inclusion in phase III to quantitatively predict chemical binding to the ER. Our data set for the relative binding affinities (RBAs) to the ER consists of 130 chemicals covering a wide range of structural diversity and a 6 orders of magnitude spread of RBAs. CoMFA and HQSAR models were constructed and compared for performance. The CoMFA model had a r2 = 0.91 and a q2LOO = 0.66. HQSAR showed reduced performance compared to CoMFA with r2 = 0.76 and q2LOO = 0.59. A number of parameters were examined to improve the CoMFA model. Of these, a phenol indicator increased the q2LOO to 0.71. When up to 50% of the chemicals were left out in the leave-N-out cross-validation, the q2 remained significant. Finally, the models were tested by using two test sets; the q2pred for these were 0.71 and 0.62, a significant result which demonstrates the utility of the CoMFA model for predicting the RBAs of chemicals not included in the training set. If used in conjunction with phases I and II, which reduced the size of the data set dramatically by eliminating most inactive chemicals, the current CoMFA model (phase III) can be used to predict the RBA of chemicals with sufficient accuracy and to provide quantitative information for priority setting.

Animals↗
PubMedDate not supplied

Evaluation of quantitative structure-activity relationship methods for large-scale prediction of chemicals binding to the estrogen receptor.

Three different QSAR methods, Comparative Molecular Field Analysis (CoMFA), classical QSAR (utilizing the CODESSA program), and Hologram QSAR (HQSAR), are compared in terms of their potential for screening large data sets of chemicals as endocrine disrupting compounds (EDCs). While CoMFA and CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) have been commercially available for some time, HQSAR is a novel QSAR technique. HQSAR attempts to correlate molecular structure with biological activity for a series of compounds using molecular holograms constructed from counts of sub-structural molecular fragments. In addition to using r2 and q2 (cross-validated r2) in assessing the statistical quality of QSAR models, another statistical parameter was defined to be the ratio of the standard error to the activity range. The statistical quality of the QSAR models constructed using CoMFA and HQSAR techniques were comparable and were generally better than those produced with CODESSA. It is notable that only 2D-connectivity, bond and elemental atom-type information were considered in building HQSAR models. Since HQSAR requires no conformational analysis or structural alignment, it is straightforward to use and lends itself readily to the rapid screening of large numbers of compounds. Among the QSAR methods considered, HQSAR appears to offer many attractive features, such as speed, reproducibility and ease of use, which portend its utility for prioritizing large numbers of potential EDCs for subsequent toxicological testing and risk assessment.

Animals↗
PubMedDate not supplied

Comparative molecular field analysis (CoMFA) model using a large diverse set of natural, synthetic and environmental chemicals for binding to the androgen receptor.

A large number of natural, synthetic and environmental chemicals are capable of disrupting the endocrine systems of experimental animals, wildlife and humans. These so-called endocrine disrupting chemicals (EDCs), some mimic the functions of the endogenous androgens, have become a concern to the public health. Androgens play an important role in many physiological processes, including the development and maintenance of male sexual characteristics. A common mechanism for androgen to produce both normal and adverse effects is binding to the androgen receptor (AR). In this study, we used Comparative Molecular Field Analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) technique, to examine AR-ligand binding affinities. A CoMFA model with r2 = 0.902 and q2 = 0.571 was developed using a large training data set containing 146 structurally diverse natural, synthetic, and environmental chemicals with a 10(6)-fold range of relative binding affinity (RBA). By comparing the binding characteristics derived from the CoMFA contour map with these observed in a human AR crystal structure, we found that the steric and electrostatic properties encoded in this training data set are necessary and sufficient to describe the RBA of AR ligands. Finally, the CoMFA model was challenged with an external test data set; the predicted results were close to the actual values with average difference of 0.637 logRBA. This study demonstrates the utility of this CoMFA model for real-world use in predicting the AR binding affinities of structurally diverse chemicals over a wide RBA range.

Androgens↗