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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 91 records · Page 5Linked to original sources

Establishment of a microbiological profile for an air-chilling poultry operation in the United States.

The microbiological profile of an air-chilling poultry process was investigated from the farm through the processing plant. Within a 1-year period, nine broiler flocks from four different farm sources were studied. Numbers of total aerobes, coliforms, psychrotrophic organisms, E. coli Biotype I (generic E. coli), Salmonella spp., and Campylobacter spp. were determined for multiple sampling sites on the farm as well as in the processing plant. Farm samples were collected the day before the chickens were slaughtered at the plant. The same flock was sampled at the plant on the day of slaughter. Sites located before evisceration (BE), after evisceration (AE), and after chilling (AC) were sampled. Results indicated a positive correlation between contamination of ceca with Salmonella on the farm and the presence Salmonella in carcass samples from the plant for all three types of sampling sites. The in-plant trend for total aerobes, coliforms, and generic E. coli revealed a significant decrease from counts obtained before evisceration to those obtained for the (AC) final product when flock variations were taken into account. The average coliform counts were 3.91, 3.27, and 2.59 log10 CFU/ml of rinse for BE, AE, and AC samples, respectively. Generic E. coli counts were 3.74, 3.08, and 2.20 log10 CFU/ml of rinse for BE, AE, and AC samples, respectively. No reductions in numbers of Campylobacter or Salmonella were observed during processing, which suggests that practical intervention strategies for lowering pathogen levels are critical on a multilevel basis at the farm and in the plant.

Animal Husbandry↗

The stethoscope: some preliminary investigations.

Textbooks, clinicians, and medical teachers differ as to whether the stethoscope bell or diaphragm should be used for auscultating respiratory sounds at the chest wall. Logic and our results suggest that stethoscope diaphragms are more appropriate.

Auscultation↗

Measurements of ultracold-neutron lifetimes in solid deuterium.

We present the first measurements of the survival time of ultracold neutrons (UCNs) in solid deuterium (SD2). This critical parameter provides a fundamental limitation to the effectiveness of superthermal UCN sources that utilize solid ortho-deuterium as the source material. These measurements are performed utilizing a SD2 source coupled to a spallation source of neutrons, providing a demonstration of UCN production in this geometry and permitting systematic studies of the influence of thermal up-scatter and contamination with para-deuterium on the UCN survival time.

Journal Article↗

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man.

AIMS/HYPOTHESIS: The role of glucose sensing cells in the human hepatic portal system in the initiation of the neuroendocrine responses to acute hypoglycaemia is not known. We investigated the effect of raising blood glucose concentrations in the hepatic-portal vein on neurohumoral responses during induction of systemic hypoglycaemia in nine healthy male volunteers. METHODS: Each subject received an insulin infusion (3 mU.kg(-1).min(-1)) on two occasions, in random order. Variable rate glucose infusion was used to maintain plasma glucose at 5 mmol/l for 60 min, then 3.2 mmol/l for 60 min. At 20 min prior to hypoglycaemia, subjects drank 20 g of glucose in water or water sweetened with saccharin. In five of the volunteers, the oral glucose was labelled with U-13C6 glucose, which showed peak systemic glucose absorption between 90 and 110 min. Five volunteers also repeated the study with a euglycaemic clamp. RESULTS: Oral glucose was associated with a reduction in the early adrenaline response to hypoglycaemia, the area under the curve from 90 to 110 min falling from 24.02+/-20.84 (means +/- SD) to 15.26+/-13.65 nmol/l per 20 min, p<0.05. Symptom scores (area under curve) decreased from 99.72+/-91.86 to 16.39+/-94.71, p=0.008 (total), 51.8+/-68.61 to 7.78+/-41.61, p=0.03 (autonomic) and 54.17+/-50.61 to 8.6+/-57.99 with oral glucose, p=0.001 (neuroglycopenic). Oral glucose did not influence symptoms during euglycaemia. CONCLUSION/INTERPRETATION: Our data are compatible with the hypothesis that centrally mediated symptomatic and neuroendocrine responses are attenuated by glucose detection in the hepatic portal vein in humans.

Adaptation, Physiological↗

Hypoglycaemia unawareness and the brain.

The intention of this paper is to critically review the current state of knowledge of the role of the brain in the syndrome of hypoglycaemia unawareness. Both the role of the brain in the detection of hypoglycaemia and initiation of the counterregulatory responses and the function of the cerebral cortex during acute hypoglycaemia are considered. The evidence for and against the brain as the primary site of mammalian hypoglycaemia sensing and the mechanisms whereby such sensing may occur and change in hypoglycaemia unawareness are discussed. Current evidence supports a major role for the central nervous system in hypoglycaemia sensing and there is increasing understanding of the mechanisms of counterregulatory failure and cognitive dysfunction in hypoglycaemia unawareness. More needs to be done to expand this understanding and translate it into therapeutic strategies to defend against severe hypoglycaemia in diabetes therapy.

Aging↗

Active fluidization of polymer networks through molecular motors.

Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations.

Actins↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗