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Biomedical subjects

R D White

Publications and source records attributed to R D White.

At least 55 records · Page 3Linked to original sources

Electrocardiographic evaluation of defibrillation shocks delivered to out-of-hospital sudden cardiac arrest patients.

OBJECTIVE: Following out-of-hospital defibrillation attempts, electrocardiographic instability challenges accurate assessment of defibrillation efficacy and post-shock rhythm. Presently, there is no precise definition of defibrillation efficacy in the out-of-hospital setting that is consistently used. The objective of this study was to characterize out-of-hospital cardiac arrest rhythms following low-energy biphasic and high-energy monophasic shocks in order to precisely define defibrillation efficacy and establish uniform criteria for the evaluation of shock performance. METHODS: Automatic external defibrillators (AEDs) delivering 150 J impedance-compensating biphasic or 200-360 J monophasic damped sine waveform shocks were observed in a combined police and paramedic program. ECGs from 29 biphasic patients and 87 monophasic patients were classified as organized, asystole or VF at post-shock times of 3, 5, 10, 20 and 60 s. RESULTS: Post-shock time (P<0.0001) and shock waveform type (P = 0.02) affected the classification of post-shock rhythm. At each analysis time, there were more patients in VF following high-energy monophasic shocks than following 150 J biphasic shocks (P<0.0001). The percentage of patients in VF increased with post-shock time. The rate of VF recurrence was not a function of shock type, indicating that refibrillation is largely a function of the patient's underlying cardiac disease. CONCLUSION: Defibrillation should uniformly be defined as termination of VF for a minimum of 5-s after shock delivery. Rhythms should be reported at 5-s after shock delivery to assess early effects of the defibrillation shock and at 60-s after shock delivery to assess the interaction of the defibrillation therapy and factors such as post-shock myocardial dysfunction and the patient's underlying cardiac disease.

Adolescent↗

RT-PCR quantification of AHR, ARNT, GR, and CYP1A1 mRNA in craniofacial tissues of embryonic mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone.

C57BL/6N mouse embryos exposed to hydrocortisone (HC) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) develop cleft palate. An interaction between these agents produces clefts at doses which alone are not teratogenic. The glucocorticoid receptor (GR) and dioxin receptor (AhR) mediated these responses and their gene expression was altered by TCDD and/or HC in palates examined on gestation day (GD) 14 by Northern blot analysis and in situ hybridization. The present study quantifies AhR, AhR nuclear translocator (ARNT), and GR mRNA at 4, 12, 24, and 48 h after exposure (time 0 = dose administration at 8 A.M. on gestation day 12) on GD12 to TCDD (24 micrograms/kg), HC (100 mg/kg) or HC (25 mg/kg) + TCDD (3 micrograms/kg). The induction of CYP1A1 mRNA was also quantified at 2, 4, 6, 12, 24, and 48 h for control and TCDD-exposed samples. Total RNA was prepared from midfacial tissue of 4-6 embryos/litter at each time and dose. An RNA internal standard (IS) for each gene was synthesized, which included the gene's primer sequences separated by a pUC19 plasmid sequence. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on total RNA + IS using a range of 5-7 IS concentrations across a constant level of total RNA. PCR products were separated in gels (mRNA and IS-amplified sequences differed by 30-50 bases), ethidium bromide-stained, imaged (Hamamatsu Photonics Systems, Bridgewater, NJ), and quantified with NIH Image. CYP1A1 mRNA was significantly induced in the TCDD-exposed samples at all time points examined (p = 0.005 at 2 h and 0.001 after 2 h). During palatal shelf outgrowth on GD12, AhR mRNA levels increased significantly and this was not affected by treatment with TCDD or HC + TCDD. A significant increase in GR was detected at 24 h (p < 0.05) and this was unaffected by any of the exposures. Expression of ARNT increased at 12 h (p < 0.001); however, treatment with HC or HC + TCDD blocked this increase (p < 0.05). At 24 h, the TCDD-treated embryos had significantly lower ARNT mRNA compared with controls (p < 0.001). The relative overall expression level of the genes was AhR > ARNT > GR. Within individuals, expression of AhR and/or ARNT was highly correlated with GR level. In conclusion, CYP1A1 mRNA was expressed in developing craniofacial tissue and was highly induced by TCDD exposure. AhR, ARNT, and GR mRNA are upregulated in early palatogenesis, although not on the same schedule. The TCDD-induced decrease in ARNT at 24 h after dosing and the HC and HC + TCDD-induced delay in upregulation of ARNT may affect the dynamics of heterodimer formation between AhR and ARNT. The changes in ARNT mRNA level could also affect availability of this transcriptional regulator to interact with other potential partners, and these effects, separately or in combination, may be involved in disruption of normal embryonic development.

Animals↗

Charged-particle transport in gases in electric and magnetic fields crossed at arbitrary angles: Multiterm solution of Boltzmann's equation.

A multiterm solution of the Boltzmann equation has been developed and used to calculate transport coefficients of charged-particle swarms in gases under the influence of electric and magnetic fields crossed at arbitrary angles psi. The hierarchy resulting from a spherical harmonic decomposition of the Boltzmann equation in the hydrodynamic regime [Ness, Phys. Rev. A 47, 327 (1993)] is solved numerically by representing the speed dependence of the phase-space distribution function in terms of an expansion in Sonine polynomials about a weighted sum of Maxwellian distributions at different temperatures. Results are given for charged-particle swarms in certain model gases over a range of psi and field strengths. The variation of the transport coefficients with psi is addressed using physical arguments. The errors associated with the two-term approximation and inadequacies of Legendre polynomial expansions are highlighted.

Journal Article↗

Nonconservative charged-particle swarms in ac electric fields.

A time-dependent multi-term technique has been developed and employed to solve the space- and time-dependent Boltzmann equation for charged-particle swarms in ac electric fields. This technique allows for the accurate calculation of both the full set of transport coefficients and the phase-space distribution function. This technique avoids restrictions on the field amplitude and frequency and/or the charged-particle to neutral molecule mass ratio traditionally associated with many contemporary investigations. To our knowledge, it represents the first rigorous treatment of the explicit effects of nonconservative processes on transport coefficients in ac electric fields. The phenomena associated with these explicit effects of nonconservative processes are striking (e.g., negative phase lags in the drift velocity for an attaching gas), and the errors associated with traditional treatments of ionization and attachment on the transport coefficients are highlighted.

Journal Article↗

Oxidative inactivation of cytochrome P-450 1A (CYP1A) stimulated by 3,3',4,4'-tetrachlorobiphenyl: production of reactive oxygen by vertebrate CYP1As.

Microsomal cytochrome P-450 1A (CYP1A) in a vertebrate model (the teleost fish scup) is inactivated by the aryl hydrocarbon receptor agonist 3,3',4,4'-tetrachlorobiphenyl (TCB). Here, the mechanism of CYP1A inactivation and its relationship to reactive oxygen species (ROS) formation were examined by using liver microsomes from scup and rat and expressed human CYP1As. In vitro inactivation of scup CYP1A activity 7-ethoxyresorufin O-deethylation by TCB was time dependent, NADPH dependent, oxygen dependent, and irreversible. TCB increased microsomal NADPH oxidation rates, and CYP1A inactivation was lessened by adding cytochrome c. CYP1A inactivation was accompanied by loss of spectral P-450, a variable loss of heme and a variable appearance of P-420. Rates of scup liver microsomal metabolism of TCB were < 0.5 pmol/min/mg, 25-fold less than the rate of P-450 loss. Non-heme iron chelators, antioxidant enzymes, and ROS scavengers had no influence on inactivation. Inactivation was accelerated by H(2)O(2) and azide but not by hydroxylamine or aminotriazole. TCB also inactivated rat liver microsomal CYP1A, apparently CYP1A1. Adding TCB to scup or rat liver microsomes containing induced levels of CYP1A, but not control microsomes, stimulated formation of ROS; formation rates correlated with native CYP1A1 content. TCB stimulated ROS formation by baculovirus-expressed human CYP1A1 but not CYP1A2. The results indicate that TCB uncouples the catalytic cycle of CYP1A, ostensibly CYP1A1, resulting in formation of ROS within the active site. These ROS may inactivate CYP1A or escape from the enzyme. ROS formed by CYP1A1 may contribute to the toxicity of planar halogenated aromatic hydrocarbons.

Animals↗

Refining and blending of aviation turbine fuels.

Aviation turbine fuels (jet fuels) are similar to other petroleum products that have a boiling range of approximately 300F to 550F. Kerosene and No.1 grades of fuel oil, diesel fuel, and gas turbine oil share many similar physical and chemical properties with jet fuel. The similarity among these products should allow toxicology data on one material to be extrapolated to the others. Refineries in the USA manufacture jet fuel to meet industry standard specifications. Civilian aircraft primarily use Jet A or Jet A-1 fuel as defined by ASTM D 1655. Military aircraft use JP-5 or JP-8 fuel as defined by MIL-T-5624R or MIL-T-83133D respectively. The freezing point and flash point are the principle differences between the finished fuels. Common refinery processes that produce jet fuel include distillation, caustic treatment, hydrotreating, and hydrocracking. Each of these refining processes may be the final step to produce jet fuel. Sometimes blending of two or more of these refinery process streams are needed to produce jet fuel that meets the desired specifications. Chemical additives allowed for use in jet fuel are also defined in the product specifications. In many cases, the customer rather than the refinery will put additives into the fuel to meet their specific storage or flight condition requirements.

Aviation↗

The clinical application of 'edema-weighted' magnetic resonance imaging in the assessment of Takayasu's arteritis.

Takayasu's arteritis is an inflammatory process affecting medium to large arteries. In about half of cases, constitutional symptoms and laboratory studies do not correlate with disease activity, confounding therapeutic decision making. We present six representative cases of Takayasu's arteritis in which new magnetic resonance imaging sequences for improved morphological and tissue characterization were useful in identifying aortic wall thickening and acute inflammatory changes, respectively. Specifically, fast spin-echo sequences designed to enhance detection of vessel wall edema were included. This information proved useful in guiding clinical decision making, particularly in regard to initiation and monitoring of therapy in our patients.

Adolescent↗

Potential cost-effectiveness of public access defibrillation in the United States.

BACKGROUND: Approximately 360,000 Americans experience sudden cardiac arrest each year; current treatments are expensive and not very effective. Public access defibrillation (PAD) is a novel treatment for out-of-hospital sudden cardiac arrest that refers to use of automated external defibrillators by the lay public or by nonmedical personnel such as police. A clinical trial has been proposed to evaluate the effectiveness of public access defibrillation, but it is unclear whether such early defibrillation will offer sufficient value for money. Our objective was to estimate the potential cost-effectiveness of public access defibrillation by use of decision analysis. METHODS AND RESULTS: A decision model compared the potential cost-effectiveness of standard emergency medical services (EMS) systems with that of EMS supplemented by PAD. We considered defibrillation by lay responders or police, using an analysis with a US health-care perspective. Input data were derived from published data or fiscal databases. Future costs and effects were discounted at 3%. Monte Carlo simulation was performed to estimate the variability in the costs and effects of each program. Sensitivity analyses assessed the robustness of the results to changes in input data. A standard EMS system had a median cost of $5900 per cardiac arrest patient (interquartile range, IQR, $3200 to $10,900) and yielded a median of 0.25 quality-adjusted life years (IQR, 0.20 to 0.30). PAD by lay responders had a median incremental cost of $44,000 per additional quality-adjusted life year (IQR, $29,000 to $68,900). PAD by police had a median incremental cost of $27,200 per additional quality-adjusted life year (IQR, $15,700 to $47,800). The results were sensitive to changes in the cost and relative survival benefit of PAD. CONCLUSIONS: Although more expensive than standard EMS for sudden cardiac arrest, PAD may be economically attractive. The effectiveness and cost-effectiveness of PAD should be assessed in a randomized, controlled trial.

Cost-Benefit Analysis↗

Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of a distillate from light alkylate naphtha.

A distillate of light alkylate naphtha (CAS number 64741-66-8; LAN distillate) was administered via inhalation, 6 h/d, 7 d/wk to 4 groups of Sprague-Dawley rats (10/sex/dose) at target concentrations of 0 (filtered air control), 5, 12.5, or 25 g/m3 with the highest dose exceeding 60% of the lower explosive limit of LAND. Exposure began 2 wk prior to mating and continued throughout gestation until postnatal d 4 for females or for 8 consecutive weeks for males. No apparent clinical signs indicative of systemic toxicity were observed in the F0 and F1 animals of either sex. Inhalation exposure to LAND up to and including the 25 g/m3 dose level had no effect on parental food consumption, body weights, absolute and relative organ weights, and reproductive indices. All groups had comparable delivery data and a fertility index > or 80%. Pups in all groups showed comparable birth weights, weight gain, a viability index (postnatal d 4) for all groups of > or = 97%, and no histopathological changes. In the dams, there were no significant differences in the mean numbers of corpora lutea, implantation sites, and resorptions recorded at necropsy. In the males, the only remarkable findings at necropsy were a small right epididymis and testis seen in one mid-dose male and an abscess on the right epididymis of a high-dose male. In both cases, the dams that had been bred to these males produced normal litters. There were no test material-related microscopic changes observed in the testes and epididymis of the F0 male rats or ovaries of the F0 female rats exposed to LAND. Under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for LAND via inhalation in rats is established at greater than 24.7 g/m3 (analytical concentration).

Administration, Inhalation↗

Right-left asymmetry of cell proliferation predominates in mouse embryos undergoing clockwise axial rotation.

BACKGROUND: Differential growth is fundamental to most mechanisms proposed for axial rotation in amniotes. Other mechanisms such as changes in cell shape are not consistently suggested by ultrastructure. Lateral asymmetries in cell proliferation exist in mouse and chick embryos undergoing normal, anticlockwise axial rotation, but there has been no investigation of inverse clockwise rotation that could test the correlation. METHODS: We used the BALB/cHu-iv/iv, situs inversus mouse to test the apparent correlation of lateral asymmetries with morphogenesis that we saw in cell division patterns of normally rotating mice. Proliferation indices were collected from tritium autoradiograms. RESULTS: Asymmetry of cell proliferation in inverse axial rotation is a mirror image of the pattern seen for normal axial rotation: right predominates over left. This asymmetry is statistically significant and correlates with morphology. Patterns of proliferation in constraining extraembryonic membranes, particularly visceral yolk sac, suggest that rotation could be pushed by uneven lateral growth as body and gut tubes form, for they are attached to these membranes. CONCLUSIONS: Data from iv/iv mice provide additional evidence that differential growth, constrained by contiguous extraembryonic membranes, may drive closure of body and gut walls and contribute to axial rotation. Asymmetries of cell proliferation are likely consequences of genetic cascades, and will need to be incorporated with in situ information on gene activity.

Animals↗

Seven years' experience with early defibrillation by police and paramedics in an emergency medical services system.

PRIMARY OBJECTIVE: To assess the outcome of patients with out-of-hospital cardiac arrest with ventricular fibrillation as the presenting rhythm in an emergency medical services system utilizing a combined police/paramedic response to provide early defibrillation. MATERIALS AND METHODS: Police and paramedics were dispatched from law enforcement and ambulance communications centers, respectively. First-arriving personnel delivered initial shocks, all using automated external defibrillators. Patients were classified according to response to initial shocks: restoration of pulses with shocks only or in need of advanced life support, including epinephrine. Discharge survival was defined as return to home without disabling neurologic injury. RESULTS: Over the 7-year period of study 131 patients presented with ventricular fibrillation: 58 were first treated by police and 73 by paramedics. Restoration of pulses with shocks only and discharge survival were not different in police and paramedic groups, with overall survival of 40% (53 of 131 patients). Among the survivors, 19% (18/95 patients) obtained a spontaneous circulation only after administration of epinephrine and other ALS interventions. CONCLUSION: Both restoration of a functional circulation, without need for advanced life support interventions, and discharge survival without neurologic disability are very dependent upon the rapidity with which defibrillation is accomplished, regardless of who delivers the shocks. In addition, a smaller but significant number of patients who require ALS interventions, including epinephrine, for restoration of a spontaneous circulation survive to discharge. Short time differences, on the order of 1 min, are significant determinants of both immediate response to shocks and discharge survival.

Adolescent↗

Right ventricular arrhythmia in the absence of arrhythmogenic dysplasia: MR imaging of myocardial abnormalities.

PURPOSE: To evaluate right ventricular abnormalities with magnetic resonance (MR) imaging in patients with arrhythmia but without arrhythmogenic dysplasia. MATERIALS AND METHODS: In 53 patients being evaluated for right ventricular arrhythmia and 15 control subjects, MR imaging was performed to evaluate fixed thinning, fatty replacement, or reduced systolic wall thickening or motion. A diagnosis of idiopathic right ventricular outflow tract tachycardia or indeterminate was assigned for each patient, and the severity of arrhythmia was categorized. RESULTS: Right ventricular abnormalities were revealed in 32 (60%) of the 53 patients: fixed thinning in 27 (84%), fatty replacement in eight (25%), and reduced wall thickening or motion in 31 (97%). Right ventricular abnormalities were found in 35 (76%) of 46 patients with idiopathic right ventricular outflow tract tachycardia and in seven (39%) of 18 patients with indeterminate diagnoses (P = .022). CONCLUSION: Mild right ventricular abnormalities are likely sources for arrhythmias, even in the absence of arrhythmogenic right ventricular dysplasia.

Adolescent↗

Localization of the prostatic apex for radiotherapy treatment planning using urethroscopy.

PURPOSE: To assess the ability of computed tomography (CT) scans and retrograde urethrograms to accurately define the prostatic apex in the craniocaudad dimension, using urethroscopy as a reference. METHODS AND MATERIALS: Plain film radiographs of the pelvis were obtained in 15 patients with early-stage adenocarcinoma of the prostate, with the tip of a urethroscope held in place at the external sphincter, which most closely approximates the prostatic apex. The scope was then withdrawn, and a retrograde urethrogram was performed. Immediately afterwards, a CT scan of the pelvis was obtained. Because differential filling of the bladder and rectum affects the position of the prostatic apex, patients voided prior to rather than in between the three consecutive studies. RESULTS: The urethroscopy-defined prostatic apex was located 4 +/- 8 mm (mean +/- SD) superior to the CT-defined apex, 13 +/- 3 mm (mean +/- SD) superior to the urethrogram tip and 30 +/- 7 mm (mean +/- SD) superior to the ischial tuberosities. There was significant interobserver variability in the location of the prostatic apex as determined by CT scans. Placement of the inferior border of the radiation portals at the ischial tuberosities would have resulted in irradiation of > or = 20 mm bulbar urethra, as defined by the dye column of the retrograde urethrogram, in 6 out of 15 (40%) of the patients and irradiation of < 10 mm bulbar urethra in 2 out of 15 (13%) of the patients. CONCLUSION: Because the prostate blends inferiorly with the urogenital diaphragm, CT scans do not allow one to precisely localize the prostatic apex. Due to anatomic variability, the ischial tuberosities do not allow one to accurately localize the prostatic apex. Retrograde urethrograms provide helpful supplemental information regarding the position of the prostatic apex for radiotherapy treatment planning.

Endoscopy↗

Induction and post-transcriptional suppression of hepatic cytochrome P450 1A1 by 3,3',4,4'-tetrachlorobiphenyl.

3,3',4,4'-Tetrachlorobiphenyl (TCB) can induce and inhibit cytochrome P450 1A1 (CYP1A1) in vertebrates. TCB may also suppress CYP1A1 protein levels, but the mechanism is unknown. This study examined transcriptional and translational aspects of hepatic CYP1A1 regulation in the fish scup (Stenotomus chrysops) given single intraperitoneal injections of low (0.1 mg/kg) or high (5 mg/kg) doses of TCB, and sampled over 16 days. The low dose strongly induced hepatic CYP1A1 mRNA (25-fold), protein (12-fold), and activity [ethoxyresorufin O-deethylase (EROD)] (15-fold). The high dose also strongly induced CYP1A1 mRNA (29-fold), in a pattern like that at the low dose, but microsomal CYP1A1 protein content was induced only 4-fold and EROD rates were near control levels. Both TCB doses caused similar increases in microsomal cytochrome b5 content, and in rates of NADPH-cytochrome c (P450) reductase and UDP-glucuronosyltransferase (with p-nitrophenol). The contents of CYP forms other than CYP1A1 (putative CYP2B or CYP3A) were only weakly affected by TCB at either dose. The strong and largely specific post-transcriptional suppression of CYP1A1 content was associated with high concentrations of TCB measured in the liver. Incubation of scup hepatic microsomes with TCB plus NADPH led to a time-dependent inactivation of CYP1A1 that was distinct from catalytic inhibition, and appeared not to involve reactive metabolites of TCB. This in vitro result suggests that TCB may inactivate CYP1A1 in vivo, which could account for the apparent antagonistic effect of TCB on CYP1A1 induction.

Animals↗

Automatic external defibrillators for public access defibrillation: recommendations for specifying and reporting arrhythmia analysis algorithm performance, incorporating new waveforms, and enhancing safety. A statement for health professionals from the American Heart Association Task Force on Automatic External Defibrillation, Subcommittee on AED Safety and Efficacy.

These recommendations are presented to enhance the safety and efficacy of AEDs intended for public access. The task force recommends that manufacturers present developmental and validation data on their own devices, emphasizing high sensitivity for shockable rhythms and high specificity for nonshockable rhythms. Alternative defibrillation waveforms may reduce energy requirements, reducing the size and weight of the device. The highest levels of safety for public access defibrillation are needed. Safe and effective use of AEDs that are widely available and easily handled by nonmedical personnel has the potential to dramatically increase survival from cardiac arrest.

Algorithms↗