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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 37 records · Page 2Linked to original sources
PubMed2002

Reduced oviposition of Boophilus microplus feeding on sheep vaccinated with vitellin.

The most abundant protein present in Boophilus microplus eggs, vitellin, was isolated and purified as a non-covalent complex of six glyco-polypeptides of Mr 44-107kDa. The protein complex bound haem. Immuno-blots demonstrated that antibodies raised to vitellin recognised a 200kDa polypeptide in the haemolymph of adult female ticks. This is consistent with the general proposal that in arthropods vitellin is derived by proteolytic processing from a large precursor protein, vitellogenin. In parallel with this study, an 80kDa glycoprotein (GP80) was independently purified from larvae of B. microplus using efficacy in vaccination trials as an assay. Antibodies to GP80 also recognised a 200kDa protein in the haemolymph of ticks and a major 87kDa polypeptide present in the vitellin complex. Conversely, antibodies to purified vitellin recognised GP80. The amino-terminal amino acid sequences of the 87kDa vitellin polypeptide and GP80 were identical for at least the first 11 residues and internal peptide sequences from both polypeptides were co-located in a single but incomplete deduced amino sequence of B. microplus vitellogenin. Thus, GP80 is a processed product from vitellogenin and highly related to but not completely identical with the 87kDa vitellin polypeptide. Vaccination trials in the model host sheep were performed with purified vitellin and GP80. Sheep vaccinated with either purified vitellin or GP80 returned significantly reduced numbers of engorged female ticks with decreased weights and reduced oviposition. In contrast, sheep vaccinated with recombinant hexahis-GP80, which was incorrectly folded and not glycosylated showed no significant effects on ticks. It was concluded that vitellin and GP80 could induce immune responses that partially protect sheep from the tick, B. microplus. However, critical protective epitopes are associated with the folding of the protein and/or the oligosaccharides attached to it.

Animals↗
PubMed2002

Use of three-dimensional computer graphic animation to illustrate cleft lip and palate surgery.

OBJECTIVE: Three-dimensional (3D) computer animation is not commonly used to illustrate surgical techniques. This article describes the surgery-specific processes that were required to produce animations to teach cleft lip and palate surgery. MATERIALS AND METHODS: Three-dimensional models were created using CT scans of two Chinese children with unrepaired clefts (one unilateral and one bilateral). We programmed several custom software tools, including an incision tool, a forceps tool, and a fat tool. RESULTS: Three-dimensional animation was found to be particularly useful for illustrating surgical concepts. Positioning the virtual "camera" made it possible to view the anatomy from angles that are impossible to obtain with a real camera. Transparency allows the underlying anatomy to be seen during surgical repair while maintaining a view of the overlaying tissue relationships. Finally, the representation of motion allows modeling of anatomical mechanics that cannot be done with static illustrations. The animations presented in this article can be viewed on-line at http://www.smiletrain.org/programs/virtual_surgery2.htm. CONCLUSIONS: Sophisticated surgical procedures are clarified with the use of 3D animation software and customized software tools. The next step in the development of this technology is the creation of interactive simulators that recreate the experience of surgery in a safe, digital environment.

Child↗
PubMed2002

Human AML cells in NOD/SCID mice: engraftment potential and gene expression.

Most cases of human acute myeloid leukemia (AML) engraft in irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Intravenous transfer of as few as 10(5) human AML cells resulted in engraftment. Cases with poor prognosis clinical features, including FLT3 mutations, tended to engraft efficiently. Nevertheless, AML cells obtained from patients at relapse did not engraft more efficiently than cells obtained from the same patients at initial diagnosis. One passage of human AML cells in NOD/SCID mice did not appear to select for increased virulence, as measured by serial transplantation efficiency. Finally, cDNA microarray analyses indicated that approximately 95% of genes were expressed at similar levels in human AML cells immunopurified after growth in mice, as compared to cells assessed directly from patients. Thus, the growth of human AML cells in NOD/SCID mice could yield large numbers of human AML cells for direct experimental use and could also function as a renewable, potentially unlimited source of leukemia cells, via serial transplantation.

Acute Disease↗
PubMed2002

Equid herpesvirus 1 infection of endothelial cells requires activation of putative adhesion molecules: an in vitro model.

Antisera to activated equine endothelial cells, which detected surface molecules of 116 kD, 97 kD, 42 kD and 38 kD, were made to investigate the role of endothelial adhesion molecules in equid herpes virus 1 infection. These putative adhesion molecules could be induced by 17-beta oestradiol, chorionic gonadotrophin, or IL-2, as well as by LPS and PWM. In an in vitro flow system, using equine veins or arteries, equid herpesvirus 1 in leucocytes was only transferred to infect endothelial cells if both leucocytes and endothelial cells expressed these surface molecules. Blocking of the membrane molecules with polyclonal antibodies prevented transfer of virus to the endothelial cells, indicating that the adhesion molecules had a key role in effecting transfer of virus. These in vitro observations give particular insight into the reports that in the natural course of infection in horses infection of endothelial cells is restricted to certain tissues, and in a wider context the results illustrate the complexity of factors that may direct tissue tropism.

Animals↗
PubMed2002

Phenotypic degeneration occurs during sector formation in Metarhizium anisopliae.

AIMS: The formation of sectors was observed during subculturing of an isolate of the entomopathogenic fungus Metarhizium anisopliae, a fungus used for biological control of insect pests. The aim of the investigation was to establish whether sector formation was accompanied by changes in physiological characters. METHODS AND RESULTS: Four degenerative morphological states, with reduced sporulation capacity, were characterized. Subcultures were taken from each sector and four new culture lines established. The new lines were further subcultured every 21 d. A physiological assessment of each line was undertaken after 42 d using TLC of secondary metabolites and fluorogenic enzyme tests. Full sporulation capacity was not regained on subculture, although some cultures recovered partially. Changes in secondary metabolite profiles and the loss in detection of activity of specific enzymes were observed. CONCLUSIONS: Sector formation was frequently accompanied by changes in the ability to produce secondary metabolites and enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results illustrate the importance of maintaining the stability of important cultures during routine subculture. The consequences could have significant implications if degenerate cultures are used as inocula for liquid fermentation cultures or industrial scale production.

Enzymes↗
PubMed2002

An immunocytochemical investigation of human trigeminal nucleus caudalis: CGRP, substance P and 5-HT1D-receptor immunoreactivities are expressed by trigeminal sensory fibres.

5-HT1D (but not 5-HT1B)-receptor immunoreactivity (i.r.) can be detected on trigeminal fibres within the spinal trigeminal tract of the human brainstem. The present study used immunohistochemical and morphometric techniques to determine the proportions of trigeminal fibres expressing substance P, CGRP or 5-HT1D-receptor immunoreactivities. Co-localization studies between 5-HT1D-receptor and substance P- or CGRP-i.r. were also performed. Brainstem material was obtained with consent (four donors) and the total number of immunoreactive fibres within the trigeminal tract was estimated using random field sampling. A greater proportion of fibres (>1 microm diameter) expressed CGRP-i.r. (80 +/- 6%) compared with substance P-i.r. (46 +/- 7%) or 5-HT1D-receptor-i.r. (25 +/- 1%). 5-HT1D-receptor-i.r. was co-localized on some CGRP- or substance P-i.r. fibres. This suggests that 5-HT1D-receptors can regulate the release of CGRP and substance P and may be relevant to the clinical effectiveness of 5-HT1B/1D-receptor agonists in the treatment of migraine and other cranial pain syndromes.

Calcitonin Gene-Related Peptide↗
PubMed2002

Coronary angioplasty versus medical therapy for angina. Health service costs based on the second Randomized Intervention Treatment of Angina (RITA-2) trial.

AIMS: The second Randomized Intervention Treatment of Angina (RITA-2) trial compares an initial strategy of PTCA with continued medical management in patients with arteriographically proven coronary artery disease. This paper employs resource use data collected in the trial to compare the health service costs of the two strategies over 3 years follow-up. METHODS AND RESULTS: 1018 patients were randomized, 504 to PTCA and 514 to continued medical management. Health service resource use data were collected prospectively on all patients. Hospital unit costs were estimated in collaboration with five U.K. centres. PTCA patients underwent more subsequent coronary arteriograms, but subsequent (non-randomized) PTCAs were more common in patients randomized to medical management (118 procedures in 102 patients) compared to those randomized to PTCA (73 procedures in 62 patients). The likelihood of undergoing CABG was similar in the two groups. The use of antianginal medications was higher in patients randomized to an initial strategy of medical management. There was an overall mean additional cost per patient over 3 years in patients randomized to PTCA of pound 2685 (95% CI pound 2074- pound 3322). CONCLUSIONS: In RITA-2, the cost of an initial strategy of PTCA exceeded the cost of an initial strategy of medical management by 74% over 3 years.

Angina Pectoris↗
PubMed2002

Intensive interventional maternity care reduces infant morbidity and hospital costs.

OBJECTIVE: The purpose of this study was to introduce an intensive interventional maternity care program, called the Temple Infant and Parent Support Services (TIPSS) program, and to determine whether comprehensive maternal and infant care would reduce the high rate of infant morbidity and mortality. METHODS: The TIPSS program was comprehensive, offering multidisciplinary services that were family focused and community based. Program services included community outreach, health education, as well as clinical care for the entire family. The effect of this program was evaluated among a very high-risk group of women who were recruited into care versus a control group of high-risk patients from the same neighborhood who voluntarily sought care at the Temple University School of Medicine. Outcome parameters evaluated included gestational age at delivery, birth weight, neonatal intensive care admission, infant death and cost of infant care. RESULTS: Among the TIPSS study group, 5.2% of infants were below 2500 g versus 11% in the control group (p < 0.05). Similarly, preterm deliveries occurred in 4.2% and 12% of the study and control groups, respectively (p < 0.005). Other significant differences observed included the number of prenatal visits (p < 0.001), maternal weight gain (p < 0.05) and admission to the neonatal intensive care unit (2% vs. 6.6%; p < 0.05). The reduced admission rate among neonates from the TIPSS program resulted in significant cost savings: $2849 for neonates in the study group versus $8499 for those in the control group. This corresponds to a $5560 savings per infant born to mothers cared for in the TIPSS study group. CONCLUSIONS: The Temple Infant and Parent Support Services program demonstrated that infant morbidity could be reduced when a comprehensive prenatal program was made available to indigent patients, even if there were multiple factors that placed the mother and her infant at high risk for complications.

Female↗
PubMed2002

Spatiotemporal analysis of epizootic raccoon rabies propagation in Connecticut, 1991-1995.

The quantitative analysis of pathogen transmission within its specific spatial context should improve our ability to predict and control the epizootic spread of that disease. We compared two methods for calibrating the effect of local, spatially distributed environmental heterogeneities on disease spread. Using the time-of-first-appearance of raccoon rabies across the 169 townships in Connecticut, we estimated local spatial variation in township-to-township transmission rate using Trend Surface Analysis (TSA) and then compared these estimates with those based on an earlier probabilistic simulation using the same data. Both the probabilistic simulation and the TSA reveal significant reduction in transmission when local spatial domains are separated by rivers. The probabilistic simulation suggested that township-to-township transmission was reduced sevenfold for townships separated by a river. The global effect of this sevenfold reduction is to increase the time-to-first-appearance in the eastern townships of Connecticut by approximately 29.7% (spread was from west to east). TSA revealed a similar effect of rivers with an overall reduction in rate of local propagation due to rivers of approximately 22%. The 7.7% difference in these two estimates reveals slightly different aspects of the spatial dynamics of this epizootic. Together, these two methods can be used to construct an overall picture of the combined effects of local spatial variation in township-to-township transmission on patterns of local rate of propagation at scales larger than the immediate nearest neighboring townships.

Animals↗
PubMed2002

The New Zealand Blood Donors' Health Study: baseline findings of a large prospective cohort study of injury.

INTRODUCTION: Cohort studies have contributed important scientific knowledge regarding the determinants of chronic diseases. Despite the need for etiologic investigations, this design has been infrequently used in injury prevention research. OBJECTIVES: To describe the baseline findings of the New Zealand Blood Donors' Health Study, a large prospective study designed to investigate relationships between lifestyle, psychosocial factors, and serious injury due to road crashes, falls, self harm, assault, work, sport, and recreation. METHODS: Participants were recruited from fixed and mobile collection sites of a voluntary non-profit blood donor program. Baseline exposure data (for example risk taking behaviors, alcohol and marijuana use, sleep habits, and depression) were collected using a self administered questionnaire. Outcome data regarding serious injury will be collected prospectively through computerized record linkage of participants' unique identifiers to national morbidity and mortality databases. RESULTS: In total, 22 389 participants enrolled in the study (81% response rate). The diverse study population included 36% aged 16-24 years, 20% rural residents, and large variability in exposures of interest. For example, in the 12 months before recruitment, 21% had driven a motor vehicle when they considered themselves over the legal limit for alcohol, and 11% had been convicted of traffic violations (excluding parking infringements). Twelve per cent had seriously considered attempting suicide sometime in their life. CONCLUSIONS: This is the first, large scale cohort study investigating determinants of serious injury in New Zealand and among the largest worldwide. Preliminary findings from prospective analyses that can inform injury prevention policy are expected within five years.

Adolescent↗
PubMed2002

Baroregulation of vasopressin release in adipsic diabetes insipidus.

Adipsic diabetes insipidus (ADI) occurs in association with a heterogeneous group of conditions. We report vasopressin (AVP) responses to hypotension in nine patients with ADI and nine controls. Hypertonic saline infusion produced absent thirst (1.7 +/- 1.7 to 1.5 +/- 1.7 cm, P = 0.99) and AVP responses (0.3 +/- 0.1 to 0.4 +/- 0.1 pmol/liter, P = 0.99) in the ADI group, who also drank less than the control group (258 +/- 200 ml vs. 1544 +/- 306 ml, P < 0.001). Intravenous infusion of trimetaphan camsylate produced a fall in mean arterial pressure of 31.6% +/- 8.9% in patients and 29.4% +/- 6.1% in controls. Plasma AVP concentrations rose from 1.4 +/- 0.8 to 340.3 +/- 497.4 pmol/liter (P < 0.001) in the control group. In three patients with craniopharyngioma, there was no rise in plasma AVP concentrations (0.3 +/- 0.1 to 0.3 +/- 0.1 pmol/liter, P = 0.96), but plasma AVP rose significantly in response to hypotension in the other six patients (0.4 +/- 0.2 to 204.5 +/- 223.2 pmol/liter, P < 0.001). We concluded that the AVP responses to hypotension in ADI are heterogeneous and reflect the site of the lesion causing the diabetes insipidus.

Adolescent↗
PubMed2002

Fully automated radioligand binding filtration assay for membrane-bound receptors.

Here we describe a fully automated, hands-free radioligand filtration binding assay for dopamine D3 receptors. Three separate instruments were linked in tandem to perform the following operations: The Genmate and Genesis were linked to perform liquid handling, incubation, and the scheduling operations, while an automated harvester was used to perform rapid filtration. To minimize carryover of compounds, disposable tips were used for diluting and dispensing the compounds. A custom-designed tip holder was used to handle loading and pipetting by the Genmate 96-well pipettor. The assay for 84 compounds with six concentrations that spans six logs can be completed within 4 h. The reproducibility of the individual data point (cv < 10% between duplicates) and Ki (cv < 20%) is superior to that determined by manual procedures. Ki values of various dopamine ligands determined by the hands-free procedure are similar to published values. This technology reduces hands-on time (at least 70%), minimizes exposure to radioligands (up to 95%), and improves the reproducibility of results. The technology is applicablefor high-throughput screening and rapid determination of structure-activity relationship of compounds for many other membrane-bound receptors.

Animals↗
PubMed2002

A Monte-Carlo estimation of effect size distortion due to significance testing.

A Monte-Carlo study was done with true effect sizes in deviation units ranging from 0 to 2 and a variety of sample sizes. The purpose was to assess the amount of bias created by considering only effect sizes that passed a statistical cut-off criterion of alpha = .05. The deviation values obtained at the .05 level jointly determined by the set effect sizes and sample sizes are presented. This table is useful when summarizing sets of studies to judge whether published results reflect an accurate appraisal of an underlying effect or a distorted estimate expected because significant studies are published and nonsignificant results are not. The table shows that the magnitudes of error are substantial with small sample sizes and inherently small effect sizes. Thus, reviews based on published literature could be misleading and especially so if true effect sizes were close to zero. A researcher should be particularly cautious of small sample sizes showing large effect sizes when larger samples indicate diminishing smaller effects.

Humans↗
PubMed2002

Estimation of pedigree errors in the UK dairy population using microsatellite markers and the impact on selection.

The proportion of cows in the UK dairy herd whose sires were misidentified was estimated using DNA markers. Genetic marker genotypes were determined on 568 cows (from 168 milk samples and 400 hair samples) and 96 putative sires (from semen samples). The estimated pedigree error rate from the hair samples was 8.8%, and from the milk samples, 13.1%, giving an overall estimate of the error rate of 10%. This level of pedigree errors will have a relatively large impact on the efficiency of progeny testing and the accuracy of cow predicted breeding values. We predict a loss of response to selection of approximately 2 to 3% given this error rate.

Animals↗
PubMed2002

The establishment of a hospital clinical ethics committee.

In the Republic of Ireland the establishment of Clinical Ethics Committees (CECs) are relatively new. The need for such committees has occurred due to the fact that the consideration of ethical issues in healthcare has become an important and frequent part of discussions by individuals and institutions. A number of factors have contributed to this growth of ethical considerations. The Bon Secours Health System (BSHS) decided to establish a CEC and appointed a co-ordinating team to draw up terms of reference for such a committee. During this process the co-ordinating team drew on the experience of other countries and of its own staff. Potential criticisms of how such a committee would function were examined. A representative membership of the CEC was also arrived at. The following functions were identified for a CEC: the need to provide a mechanism for the identification, discussion and resolution of medical ethical issues; the need to identify medical ethical issues which may create challenges to the health system and to monitor the responses of the health system to these areas, and the provision of education. Policy development was seen as a primary function of the CEC. Ethical case review also emerged as one area of potential involvement by the CEC. During the staff consultation a large number of ethical issues emerged which the staff requested the CEC to address. A methodology necessary for coping with the differences within the BSHS was developed by the CEC. It is evident that CECs are here to stay and how they develop and function will have an impact on the quality of healthcare.

Ethics Committees, Clinical↗