Biomedical subjects
Publications and source records attributed to W Saunders.
This paper highlights one aspect of a presentation to be given at the BDA Conference and is written in the context of dentistry in primary care. Careful oral health assessment as a foundation to good treatment planning and quality dentistry is not new, but there are a number of important new perspectives emerging across countries and healthcare systems in terms of the content and role of such an assessment in modern dental practice.
GermOnline provides information and microarray expression data for genes involved in mitosis and meiosis, gamete formation and germ line development across species. The database has been developed, and is being curated and updated, by life scientists in cooperation with bioinformaticists. Information is contributed through an online form using free text, images and the controlled vocabulary developed by the GeneOntology Consortium. Authors provide up to three references in support of their contribution. The database is governed by an international board of scientists to ensure a standardized data format and the highest quality of GermOnline's information content. Release 2.0 provides exclusive access to microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus, as well as curated information on approximately 700 genes from various organisms. The locus report pages include links to external databases that contain relevant annotation, microarray expression and proteome data. Conversely, the Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to the budding yeast section of GermOnline from their respective locus pages. GermOnline, a fully operational prototype subject-oriented knowledgebase designed for community annotation and array data visualization, is accessible at http://www.germonline.org. The target audience includes researchers who work on mitotic cell division, meiosis, gametogenesis, germ line development, human reproductive health and comparative genomics.
Pooled data from multiple clinical trials can provide information for medical decision-making that typically cannot be derived from a single clinical trial. By increasing the sample size beyond that achievable in a single clinical trial, pooling individual-patient data from multiple trials provides additional statistical power to detect possible effects of study medication, confers the ability to detect rare outcomes, and facilitates evaluation of effects among subsets of patients. Data from pharmaceutical company-sponsored clinical trials lend themselves to data-pooling, meta-analysis, and data mining initiatives. Pharmaceutical company-sponsored clinical trials are arguably among the most rigorously designed and conducted of studies involving human subjects as a result of multidisciplinary collaboration involving clinical, academic and/or governmental investigators as well as the input and review of medical institutional bodies and regulatory authorities. This paper describes the aggregation, validation and initial analysis of data from the sumatriptan/naratriptan aggregate patient (SNAP) database, which to date comprises pooled individual-patient data from 128 clinical trials conducted from 1987 to 1998 with the migraine medications sumatriptan and naratriptan. With an extremely large sample size (>28000 migraineurs, >140000 treated migraine attacks), the SNAP database allows exploration of questions about migraine and the efficacy and safety of migraine medications that cannot be answered in single clinical trials enrolling smaller numbers of patients. Besides providing the adequate sample size to address specific questions, the SNAP database allows for subgroup analyses that are not possible in individual trial analyses due to small sample size. The SNAP database exemplifies how the wealth of data from pharmaceutical company-sponsored clinical trials can be re-used to continue to provide benefit.
Dentists attempt to overcome patients' fears by using various oral, intramuscular, intravenous, and inhalational anxiolytic agents. This article discusses the use of oral midazolam as an alternative to oral diazepam in the management of the pediatric patient.
The Saccharomyces cerevisiae kinesin-related motor Kar3p, though known to be required for karyogamy, plays a poorly defined, nonessential role during vegetative growth. We have found evidence suggesting that Kar3p functions to limit the number and length of cytoplasmic microtubules in a cell cycle-specific manner. Deletion of KAR3 leads to a dramatic increase in cytoplasmic microtubules, a phenotype which is most pronounced from START through the onset of anaphase but less so during late anaphase in synchronized cultures. We have immunolocalized HA-tagged Kar3p to the spindle pole body region, and fittingly, Kar3p was not detected by late anaphase. A microtubule depolymerizing activity may be the major vegetative role for Kar3p. Addition of the microtubule polymerization inhibitors nocodazol or benomyl to the medium or deletion of the nonessential alpha-tubulin TUB3 gene can mostly correct the abnormal microtubule arrays and other growth defects of kar3 mutants, suggesting that these phenotypes result from excessive microtubule polymerization. Microtubule depolymerization may also be the mechanism by which Kar3p acts in opposition to the anaphase B motors Cin8p and Kip1p. A preanaphase spindle collapse phenotype of cin8 kip1 mutants, previously shown to involve Kar3p, is markedly delayed when microtubule depolymerization is inhibited by the tub2-150 mutation. These results suggest that the Kar3p motor may act to regulate the length and number of microtubules in the preanaphase spindle.
Two Saccharomyces cerevisiae kinesin-related motors, Cin8p and Kip1p, perform an essential role in the separation of spindle poles during spindle assembly and a major role in spindle elongation. Cin8p and Kip1p are also required to prevent an inward spindle collapse prior to anaphase. A third kinesin-related motor, Kar3p, may act antagonistically to Cin8p and Kip1p since loss of Kar3p partially suppresses the spindle collapse in cin8 kip1 mutants. We have tested the relationship between Cin8p and Kar3p by overexpressing both motors using the inducible GAL1 promoter. Overexpression of KAR3 results in a shrinkage of spindle size and a temperature-dependent inhibition of the growth of wild-type cells. Excess Kar3p has a stronger inhibitory effect on the growth of cin8 kip1 mutants and can completely block anaphase spindle elongation in these cells. In contrast, overexpression of CIN8 leads to premature spindle elongation in all cells tested. This is the first direct demonstration of antagonistic motors acting on the intact spindle and suggests that spindle length is determined by the relative activity of Kar3p-like and Cin8p/Kip1p-like motors.
Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF beta), a fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state TGF beta mRNA expression as shown by whole lung northern blot assay paralleled the TGF beta protein expression in BAL fluid. The peak of TGF beta protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In conclusion. TGF beta and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.
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A 42-month experience with 100 patients with fatal head injuries was analyzed to identify areas of organ procurement failure. Thirty-six patients were ineligible for organ donation. Reasons for exclusion included advanced age (7), sepsis (16), hepatitis (1), systemic illnesses (3), and HIV infection or risk (9). Resuscitation failure (17 patients) and late deaths from failed support (16 patients) left 31 potential donors. Of the 30 families asked to donate, 17 consented (56.7%). Annual consent rates were 25%, 71%, 75%, and 67%. Efforts to improve organ procurement should focus on resuscitation and physiologic support of potential donors. To assess the impact of HIV infection or risk on organ procurement, a 3-year experience of the regional transplantation center (RTP) was reviewed. Of 1,714 referrals to the RTP from 102 hospitals, 1,120 were from trauma centers. The incidence of rejection because of HIV risk or infection was significantly higher in the trauma center group than in the group from non-trauma centers, 17.2% versus 10.2% (p less than 0.004). A similar difference was noted between metropolitan and suburban hospitals (p less than 0.0001). Hepatitis risk was comparable, 3.9% vs. 3.2%. The risk of HIV infection is emerging as a factor limiting organ donation at urban trauma centers.
1. Fast feedback regulation of ACTH by cortisol has not been well studied in humans. The authors studied the existence and characteristics of fast feedback regulation in normal humans. 2. Hydrocortisone hemisuccinate was infused at two different rates: 6 mg/hour and 12 mg/hour for two hours. 3. The studies did not demonstrate the existence of fast feedback regulation of basal ACTH concentration by cortisol in man. Further, the response was variable and the rate sensitive character was difficult to demonstrate.
Methodological issues relating to multi-site studies of inpatient geriatric evaluation and management units were the focus of this working group's deliberations. The group favored a randomized clinical trial in which the inpatient geriatric evaluation and management unit was coupled with outpatient geriatric care. Inclusion of a broad spectrum of patients stratified according to risk for poor hospital outcomes was proposed in order to obtain information on the types of patients that would be most likely to benefit. The need for a detailed definition and description of care in the unit and of "usual care" was emphasized. Serious concerns were raised about including both VA medical centers and private hospitals in the same trial due to differences in the implementation of such a program. Furthermore, fears of contamination of the control group suggested that hospitals could be randomized either to provide usual care or have a GEM unit. However, this strategy would necessitate that hospitals that have already developed inpatient GEM units would be excluded from the trial and could be costly because of the number of hospitals that would be required.
It is well established that the adrenocorticotropic hormone (ACTH) stimulates the synthesis and release of cortisol from the adrenal cortex, but the role of ACTH in the physiological regulation of basal cortisol secretion has received surprisingly little study. The authors studied the nocturnal and early morning secretory pulses of cortisol and ACTH in normal subjects. A pulse detection algorithm was developed. The relationship between ACTH and cortisol pulses in terms of temporal and proportional relationship is described. Pulse concomitance for ACTH with cortisol was 47% and for cortisol with ACTH pulses it was 60%. The first description of the relationship between concomitant ACTH and cortisol pulse magnitudes in humans is presented. A highly significant linear relationship between the magnitudes of ACTH and cortisol pulses is shown. Putative reasons for dissociated pulses and the potential implication of these findings are discussed.
The purpose of this study was to evaluate the internal consistency of the content scales of the Child Assessment Schedule (CAS). A total of 116 psychiatric patients with a mean age of 10 years were administered the interview, and 92 parents were administered the parent version. Coefficient alpha was calculated for each of the 11 content scales. High internal consistency was demonstrated for school, friends, worries, mood, physical complaints, and expression of anger. More moderate but acceptable alphas were observed for the family, fears, and self-image scales. The same general pattern of results was observed for both the child and parent interviews. Additional analyses revealed that the number of items in the CAS could be reduced up to 30% without sacrificing internal consistency. These results indicate that 9 of the scales yield reliable scores.
The results of current pediatric surgical texts suggest that the damage sustained by solid abdominal viscera after blunt trauma is best treated expectantly. Therefore, a child with significant intra-abdominal pathology is managed nonoperatively. For this reason, missed or unexpected pathology may be inappropriately treated. This is the major problem faced by the surgeon caring for these children. A review of 56 patients seen after blunt abdominal trauma is reported; ten of this group had hollow viscus ruptures. It was found that special investigations were of no aid in guiding management policy. This decision remained a clinical one, which stresses the importance of the interpretation of abdominal signs made by the surgeon who is caring for the patient and the role he or she plays in the treatment of children with blunt trauma.
The purpose of this study was to evaluate existing X-ray CT methods for determining water-equivalent path length from body surface to a tumour site. In the method, the CT numbers are used to obtain linear attenuation coefficients which provide a measure of the electron density. These numbers are averaged over the energy spectrum of the diagnostic X-ray beam and other parameters which have a dependence on energy. From range measurements with heavy charged particles, it is also possible to obtain an independent and direct measure of electron density along the beam path. In the results reported here, the beam path electron density or water-equivalent path length was measured with charged particle beams, using radiation sensitive diodes as target markers. To minimise error which would be introduced by motion of the target volume, a frozen dog cadaver was used. Comparison was made between the water-equivalent path length measured with high energy particle beams, and the water-equivalent path length estimated from an X-ray CT image of the same target volume by the methods presently used in charged particle therapy (Chen et al. 1979). There was good agreement between the values determined directly with neon or helium ion beams, but when these values were compared with estimated path lengths derived from X-ray CT data, it was observed that the CT range could be in error by as much as 11% for adverse conditions of marked inhomogeneity and the presence of high atomic number bone. Under the best conditions of moderate inhomogeneity and absence of bone, the derived CT range values agreed reasonably well with the direct measurements.
We report on the first decade of the helium-ion radiotherapy clinical trial being carried out at the Lawrence Berkeley Laboratory. Over 500 patients have now been treated. We have had very good results to date in treating patients with small tumors critically located near a radiation-sensitive organ which would preclude delivering a curative dose with conventional radiotherapy. On the other hand, patients with larger tumors where the tumor dose cannot be increased more than 10% over conventional radiotherapy have not responded well to helium ion radiotherapy. This is illustrated by discussing selected patient groups in detail, namely those with uveal melanoma, small, low-grade tumors near the central nervous system, carcinoma of the pancreas, and carcinoma of the esophagus.
Experiments were conducted to determine the anorexigenic effects of ventromedial (VMH) and lateral hypothalamic (LH) injections of the mu-opiate receptor antagonists, naloxone and naltrexone, on food-deprived (20 h) rats. Lever pressing to obtain food pellets was measured in groups of hungry, male Sprague-Dawley rats following VMH, LH or subcutaneous (SC) injections of saline, naloxone or naltrexone. VMH injections of either narcotic antagonist (5 and 10 micrograms/microliter) and LH injections of naloxone (5 and 10 micrograms/microliter) decreased the total 90-min food intake, compared to saline controls, due to suppressed feeding especially during the initial 30-min interval. Rats given SC injections of naloxone (10 mg/kg) also decreased their food intake compared to amounts eaten after SC saline was given. Decrements in food consumption relative to saline controls were similar following VMH or LH administration of naloxone. Moreover, the anorexia observed following VMH naloxone administration was similar to that found after VMH injections of equal doses of naltrexone.