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Biomedical subjects

S W Smith

Publications and source records attributed to S W Smith.

At least 55 records · Page 3Linked to original sources

Subjective assessment of fever by parents: comparison with measurement by noncontact tympanic thermometer and calibrated rectal glass mercury thermometer.

STUDY OBJECTIVE: To assess the ability of parents to subjectively evaluate their children for fever and to compare their assessments with temperature measurements made with the use of a noncontact tympanic (NCT) or rectal glass mercury thermometer. A secondary goal was to assess how well a recently developed definition of fever for NCT thermometers, when used in the ear-equivalent mode (temperature of 37.7 degrees C or more), performed in a clinical situation. METHODS: This 6-month prospective observational study employed a convenience sample of 180 children, aged birth to 4 years, who presented to the emergency department of a tertiary care children's hospital. Parents were asked to subjectively assess whether their child had a fever. The child's temperature was then measured with an NCT thermometer (three times in the rectal-equivalent mode and three times in the actual-ear mode). Both the subjective assessment and the NCT temperatures were compared with the rectal temperature measured by a rectal glass mercury thermometer. RESULTS: The mean age of participants was 14.6 +/- 11.8 months (range, 2 days to 48 months); 56% were boys. The sensitivity of parental detection of fever by subjective means was 81.8% and the specificity 76.5%. The parent and the rectal glass thermometer agreed 79% of the time (95% confidence interval [CI], 73% to 85%). The sensitivity of the first temperature reading obtained with the NCT thermometer in rectal-equivalent mode was 74.7%, and the specificity was 96.3%. The NCT thermometer and the rectal glass thermometer agreed 84% of the time (95% CI, 78% to 89%). Use of the proposed definition of fever for NCT thermometers, when used in the ear-equivalent mode, caused sensitivity of a single measurement for fever to drop to 53.5%. CONCLUSION: Parental subjective assessment of fever agreed with the presence of fever as measured by rectal glass thermometer in 79% of cases. Specificity was improved with the use of the NCT thermometer. The recently proposed definition for fever for NCT thermometers, when they are used in the ear-equivalent mode, does not appear to be validated by the current data.

Child, Preschool↗

Novel azole derivatives are antagonists at the inhibitory GABA receptor on the somatic muscle cells of the parasitic nematode Ascaris suum.

The somatic muscle cells of the parasitic nematode Ascaris suum possess GABA receptors that gate chloride conductances in a similar fashion to the mammalian GABAA receptor subtype. These receptors mediate muscle relaxation and are the site of action of the anthelmintic piperazine. The properties of this receptor differ from the properties of the GABA-gated chloride receptors in the mammalian host, in particular they are not as sensitive to mammalian GABA receptor antagonists such as bicuculline and picrotoxin. Using two-electrode intracellular electrophysiological recording techniques from Ascaris muscle cells, we have tested the potency of a series of azole derivatives for their ability to block the chloride-dependent GABA response. The lead compound, SN606078, 2-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazo l-2-yl)-2H- 1,2,3-triazole, and 4 structurally related compounds reversibly blocked the conductance increase elicited by 30 microM GABA with IC50s of less than 10 microM. SN606078 (10 microM) decreased the slope of the dose-response curve for GABA, suggesting a non-competitive mechanism of action. In two-electrode voltage clamp experiments, 10 microM SN606078 blocked the outward current elicited by 20 microM GABA in a voltage-dependent manner with 72 +/- 2% inhibition at -20 mV and 49 +/- 6% inhibition at -40 mV. These observations indicate that SN606078 may act as an open-channel blocker of the GABA-gated chloride channel in A. suum.

Animals↗

Interobserver reliability and intraobserver reproducibility of the modified Ficat classification system of osteonecrosis of the femoral head.

Anteroposterior and lateral plain radiographs of 116 osteonecrotic femoral heads were reviewed to assess the interobserver reliability and intraobserver reproducibility of the modified Ficat classification system. The radiographs were reviewed initially and then again six months later by three adult reconstructive surgeons, two general orthopaedic surgeons, two orthopaedic residents, and one musculoskeletal radiologist. All eight observers agreed on the classification of twenty hips (17 per cent) at both the first and the second review of the radiographs. Paired comparisons revealed a mean interobserver kappa reliability coefficient of 0.46 (range, 0.30 to 0.67) for the first review and 0.45 (range, 0.30 to 0.66) for the second. For all observers, the mean rate of perfect agreement between the first and the second review was 68 per cent (range, 56 to 80 per cent). The mean kappa value for intraobserver reproducibility was 0.59 (range, 0.44 [one of the residents] to 0.73 [one of the general orthopaedic surgeons]). No observer or pair of observers had excellent reproducibility or reliability (kappa > 0.75). The poor interobserver reliability and fair intraobserver reproducibility diminishes any meaningful comparison of studies in which the modified Ficat classification system has been used and illuminates the need for a more reliable and reproducible classification system.

Femur Head Necrosis↗

Human skin permeability enhancement by lauric acid under equilibrium aqueous conditions.

An in vitro method was developed to investigate the enhancement of hydrocortisone transport across human stratum corneum (SC) by a model enhancer, lauric acid, in aqueous solutions under equilibrium conditions with respect to the enhancer. In contrast to classical (i.e., nonequilibrium) loading techniques, in which the enhancer is applied only to the donor side of SC either in pure form or in an organic solvent while enhancer-free aqueous buffers are placed in the receptor phase, this method allowed the investigation of pH effects, concentration effects, and reversibility of both enhancer uptake and enhancement of drug transport under thermodynamically well-defined conditions. The SC-buffer partition coefficients for lauric acid were linear with concentration and sigmoidal with pH, suggesting that both the neutral species and laurate anion partition into SC. Comparisons of partition coefficients in delipidized and untreated SC as a function of pH indicated that the uptake of lauric acid in neutral form is governed primarily by the lipid domain, whereas the protein domain accounts for anion uptake. The effects of lauric acid on skin permeability were > 80% reversible upon extraction of the enhancer from the membrane. However, the degree of enhancement of hydrocortisone permeability was nonlinearly dependent on the equilibrium concentration of lauric acid in either the aqueous buffer or the membrane, exhibiting thresholds in the appearance of enhancement with concentration. The enhancer concentration necessary to achieve isoenhancement of about 6-fold varied from approximately 1 x 10(-5) M at pH < pKa to approximately 1 x 10(-2) M at high pH (pH > 8) demonstrating the higher influence of the free acid species.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Cardiac ultrasound phantom using a porcine heart model.

A beating cardiac phantom has been developed using an excised porcine heart for use as a training tool in echocardiography. The heart is fixed with a formalin-based preservation method, housed in an optically transparent Lexan chamber, and undergoes hydraulic pumping to circulate a blood-mimicking fluid. The cardiac phantom has been used for a period of four months to produce images of excellent quality with ventricular wall motion typical of human subjects.

Animals↗

Physiologic responses of cardiac patients to supine, recumbent, and upright cycle ergometry.

Physiological responses were compared in nine stable male cardiac patients (mean +/- standard error (SE): age, 68.3 +/- 8.1 years; height, 172.7 +/- 3.9cm; weight, 72.8 +/- 14.5kg) during stationary cycling in the supine, recumbent, and upright positions. A discontinuous exercise protocol was performed in which each stage included 3 minutes of exercise and 1 minute of recovery. Each subject's workload started at 150kgm.min-1 and increased by 150kgm.min-1 per stage until volitional fatigue. Testing sessions were randomized and performed 1 week apart. Subjects continued their normal medication regimen. All subjects were participants in a community-based cardiac rehabilitation program. Dependent variables were assessed at two different intensities; submaximal (300kgm.min +/- 1) and maximal. A two-way repeated measures ANOVA found no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), minute ventilation (VE), respiratory exchange ratio (R), rate pressure product (RPP), and rating of perceived exertion (RPE) at submaximal (300kgm.min +/- 1) and maximal exercise efforts. Heart rate (HR) was significantly lower (p < or = .05) in the supine position compared with either the upright or recumbent positions during the submaximal workload. In addition, oxygen uptake (VO2) was significantly lower in the supine position at the submaximal workload (p < or = .05) compared with both upright and recumbent. No difference in HR or VO2 was observed at maximal exercise. Regressions of HR on VO2 showed similar slopes and intercepts for supine, recumbent, and upright ergometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Transient transfection assays to examine the requirement of putative cell death genes.

In conclusion, this chapter provides a convenient and efficient method for the detection and analysis of transiently transfected cells. Such strategies allow a fast and simple analysis of the requirement for particular genes that have been identified as being induced during apoptosis. Our experience has been that, when screening for "cell death genes," it is easy to isolate genes induced during apoptosis but far more difficult to determine the requirement for any given gene. These protocols have rendered such determinations much simpler to perform.

Antigens, CD↗

An evaluation of the safety and efficacy of fluconazole in the treatment of onychomycosis.

Sixteen subjects were enrolled in this open-label noncomparative study to evaluate the safety and efficacy of fluconazole as a single daily dose for a period of 6 months. Liver function enzymes were monitored to assess safety. An adverse function questionnaire was used on a monthly basis to assess patient tolerance. A visual analogue scale was used to assess efficacy of treatment. After 6 months of fluconazole, all subjects experienced improvement in the appearance of their nails. None of the subjects evidenced any elevation in liver function enzymes. Adverse reactions were limited and consistent with other studies involving fluconazole. Fluconazole proved to be safe and efficacious in the treatment of onychomycosis. Further studies are needed to determine a cost-effective dosing regimen for the treatment of onychomycosis with fluconazole.

Adult↗

Optimization of signal-to-noise ratio for multilayer PZT transducers.

In medical ultrasound imaging, two-dimensional (2-D) array transducers are desirable to implement dynamic focusing and phase aberration correction in two dimensions as well as volumetric imaging. Unfortunately, the small size of a 2-D array element results in a small clamped capacitance and a large electrical impedance near the resonance frequency. This results in poor signal-to-noise ratio (SNR) of the array elements. It has previously been demonstrated that transducers made from multilayer PZT ceramics have lower electrical impedance and greater SNR than comparable single layer elements. A simplified circuit model has been developed to optimize the SNR for multilayer ceramic (MLC) transducers. In this model, an electronic transmitter excites the array element and in the receive mode, the element drives a coaxial cable load terminated by a high impedance preamplifier. The transducer impedance is Zt/N2, where N is the number of piezoelectric layers. Maximum transmit signal is obtained when N = Ntx such that the transducer impedance, Zt/Ntx2, is matched to the source impedance. Maximum receive signal is obtained when N = Nrx such that the transducer impedance, Zt/Nrx2, is matched to the coaxial cable reactance. For maximum pulse-echo signal, the transducer should be designed with N = square root of Ntx Nrx, the geometric mean of Ntx and Nrx. Using this optimization technique, a 1.5-D array was designed with 3 layers for maximum pulse-echo SNR. Results of simulations from the simplified circuit analysis were consistent with those of the KLM model. The 3 layer array was fabricated as well as a single layer control array. The measured transmit signal and receive signal agreed with the simulation results.

Ceramics↗

Phase aberration correction in two dimensions using a deformable array transducer.

Phase aberrations due to tissue inhomogeneities degrade medical ultrasound images by disrupting the ultrasound beam focus. Currently, phase correction algorithms are implemented by adjusting the electronic phase delays uses to steer and focus the ultrasound beam. This means that a two-dimensional array is necessary to completely correct two-dimensional aberrations in tissue. However, two-dimensional arrays are a complex option due to their large number of elements and poor sensitivity. Instead of using a full two-dimensional array, a new technique is proposed, similar to one used in adaptive optics, which used a deformable transducer of significantly fewer channels for two-dimensional phase correction. Phase correction in azimuth is achieved by altering the electronic phase delay of the element. However, phase correction in elevation is achieved by tilting the element in elevation with a piezoelectric actuator. Comparison of simulations of the new phase correction transducer versus the conventional phase correction technique have shown that a deformable 1 x N or 2 x N transducer can approach the image quality of a 4 x N two-dimensional array or greater. A prototype 1 x 32 array with eight low frequency piezoelectric actuators has been constructed such that every four ultrasonic transducer elements in azimuth are mounted on one independently controlled actuator. This prototype transducer was used to test the ability of a deformable array to produce real time phased array scans and to simulate on-line phase correction by tilting the elements in the elevation direction.

Algorithms↗

Core decompression of the osteonecrotic femoral head.

The results in 114 hips of ninety-two patients who had osteonecrosis of the femoral head were assessed after treatment with core decompression. The average duration of follow-up was three years and four months (range, two years to six years and six months). The average age of the patients was forty-one years (range, fifteen to sixty-seven years). The presumed risk factors were the use of corticosteroids (thirty-seven hips), excessive use of alcohol (thirty-two hips), trauma (seven hips), and various other factors (seven hips). No specific risk factor was identified for thirty-one hips, and the osteonecrosis was considered to be idiopathic. The preoperative evaluation consisted of clinical assessment, magnetic resonance imaging, and radiographic staging according to a modification of the system of Ficat. Thirty-two hips were in stage I; thirty-eight, in stage IIA; twenty-five, in stage IIB (transition stage, with a crescent sign); and nineteen, in stage III. Clinical failure was defined as the performance of a subsequent operation. Over-all, sixty-four hips (56 percent) failed clinically. Fifty-seven were treated with a hip replacement; four, with a femoral osteotomy; and three, with a vascularized fibular graft. Clinical failure was seen in five (16 percent) of the thirty-two hips in stage I, twenty (53 percent) of the thirty-eight hips in stage IIA, twenty (80 percent) of the twenty-five hips in stage IIB, and in all nineteen of the hips in stage III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77.

Engagement of the T-cell antigen receptor (TCR) on immature thymic T cells induces death by apoptosis. Although several lines of evidence indicate that apoptosis requires de novo gene expression, little is known about the molecular pathways that mediate this response. Here we show that nur77 (refs 4-7), a zinc-finger transcription factor, is expressed in response to TCR engagement in immature T cells and T-cell hybrids. Antisense inhibition of nur77 expression prevents apoptosis in TCR-stimulated cells. nur77 is also expressed in response to mitogens, but in this case transcription is regulated by 5' upstream elements that are distinct from those used for induction of apoptosis. In addition, polyadenylation is only observed on nur77 transcripts found in condemned cells. These data support a role for nur77 in cell death that may be distinct from that of activation.

Animals↗

The genetic data environment an expandable GUI for multiple sequence analysis.

An X-Windows-based graphic user interface is presented which allows the seamless integration of numerous existing biomolecular programs into a single analysis environment. This environment is based on a core multiple sequence editor that is linked to external programs by a user-expandable menu system and is supported on Sun and DEC workstations. There is no limitation to the number of external functions that can be linked to the interface. The length and number of sequences that can be handled are limited only by the size of virtual memory present on the workstation. The sequence data itself is used as the reference point from which analysis is done, and scalable graphic views are supported. It is suggested that future software development utilizing this expandable, user-defined menu system and the I/O linkage of external programs will allow biologists to easily integrate expertise from disparate fields into a single environment.

Algorithms↗

Two-dimensional random arrays for real time volumetric imaging.

Two-dimensional arrays are necessary for a variety of ultrasonic imaging techniques, including elevation focusing, 2-D phase aberration correction, and real time volumetric imaging. In order to reduce system cost and complexity, sparse 2-D arrays have been considered with element geometries selected ad hoc, by algorithm, or by random process. Two random sparse array geometries and a sparse array with a Mills cross receive pattern were simulated and compared to a fully sampled aperture with the same overall dimensions. The sparse arrays were designed to the constraints of the Duke University real time volumetric imaging system, which employs a wide transmit beam and receive mode parallel processing to increase image frame rate. Depth-of-field comparisons were made from simulated on-axis and off-axis beamplots at ranges from 30 to 160 mm for both coaxial and offset transmit and receive beams. A random array with Gaussian distribution of transmitters and uniform distribution of receivers was found to have better resolution and depth-of-field than both a Mills cross array and a random array with uniform distribution of both transmit and receive elements. The Gaussian random array was constructed and experimental system response measurements were made at several ranges. Comparisons of B-scan images of a tissue mimicking phantom show improvement in resolution and depth-of-field consistent with simulation results.

Ultrasonography↗

Improved cardiac anthropomorphic phantom.

An improved cardiac sonographic phantom is described that simulates the anatomy of the human heart for applications as a low cost quality assurance and training tool in echocardiography. The major new feature in the phantom is the development of a polyurethane sponge left ventricle, which mimics the myocardium during sonographic imaging while undergoing hydraulic pumping. The left ventricle, including prosthetic mechanical mitral and aortic valves, is housed in an optically transparent Lexan chamber or in a tissue mimicking polyurethane rubber torso. Additional new features include a port for transesophageal imaging, and an adjustable calibrated stroke volume on the piston pump, which can serve as a standard for echocardiographic stroke volume measurement. B-scans of the phantom show excellent image quality in all three standard echocardiographic views as well as in transesophageal scanning.

Echocardiography↗

p53 is required for radiation-induced apoptosis in mouse thymocytes.

The p53 tumour suppressor gene is the most widely mutated gene in human tumorigenesis. p53 encodes a transcriptional activator whose targets may include genes that regulate genomic stability, the cellular response to DNA damage, and cell-cycle progression. Introduction of wild-type p53 into cell lines that have lost endogenous p53 function can cause growth arrest or induce a process of cell death known as apoptosis. During normal development, self-reactive thymocytes undergo negative selection by apoptosis, which can also be induced in immature thymocytes by other stimuli, including exposure to glucocorticoids and ionizing radiation. Although normal negative selection involves signalling through the T-cell receptor, the induction of apoptosis by other stimuli is poorly understood. We have investigated the requirement for p53 during apoptosis in mouse thymocytes. We report here that immature thymocytes lacking p53 die normally when exposed to compounds that may mimic T-cell receptor engagement and to glucocorticoids but are resistant to the lethal effects of ionizing radiation. These results demonstrate that p53 is required for radiation-induced cell death in the thymus but is not necessary for all forms of apoptosis.

Animals↗