Search PubMed⌕ Search

Biomedical subjects

C Birkett

Publications and source records attributed to C Birkett.

11 recordsLinked to original sources
PubMed2001

Generation of a high-density rat EST map.

We have developed a high-density EST map of the rat, consisting of >11,000 ESTs. These ESTs were placed on a radiation hybrid framework map of genetic markers spanning all 20 rat autosomes, plus the X chromosome. The framework maps have a total size of approximately 12,400 cR, giving an average correspondence of 240 kb/cR. The frameworks are all LOD 3 chromosomal maps consisting of 775 radiation-hybrid-mapped genetic markers and ESTs. To date, we have generated radiation-hybrid-mapping data for >14,000 novel ESTs identified by our Rat Gene Discovery and Mapping Project (http://ratEST.uiowa.edu), from which we have placed >11,000 on our framework maps. To minimize mapping errors, ESTs were mapped in duplicate and consensus RH vectors produced for use in the placement procedure. This EST map was then used to construct high-density comparative maps between rat and human and rat and mouse. These maps will be a useful resource for positional cloning of genes for rat models of human diseases and in the creation and verification of a tiling set of map order for the upcoming rat-genome sequencing.

Animals↗
PubMed1998

Central vagotonic effects of atropine modulate spectral oscillations of sympathetic nerve activity.

BACKGROUND: Low-dose atropine causes bradycardia either by acting on the sinoatrial node or by its effects on central muscarinic receptors increasing vagal activity. Any central muscarinic effects of high-dose atropine on RR interval are masked by peripheral muscarinic blockade at the sinoatrial node, which causes tachycardia. Effects of central parasympathetic activation on sympathetic activity are not known. METHODS AND RESULTS: Using power spectral analysis of RR interval, intra-arterial blood pressure, respiration, and muscle sympathetic nerve activity (MSNA), we examined the effects of both low (2 microgram/kg IV) and high (15 microgram/kg IV) doses of atropine. After low-dose atropine, RR increased by 9+/-1% (P<0.0001), the low-frequency (LF) component (in normalized units, NU) of RR variability decreased by -32+/-8%, and the high-frequency (HF)NU component increased (+74+/-19%); hence, LF/HF of RR variability fell by 52+/-10% (all P<0.01). Although overall MSNA did not change, LFNU of MSNA decreased (-15+/-5%), HFNU of MSNA increased (+31+/-3%), and LF/HF of MSNA fell (-41+/-8%) (all P<0.01). After high-dose atropine, LFNU of MSNA decreased (-17+/-12%), HFNU of MSNA increased (+22+/-3%), and LF/HF of MSNA fell (-51+/-21%) (all P<0.02). CONCLUSIONS: Increasing central parasympathetic activity with low-dose atropine is associated with an increase in the HF and a decrease in the LF oscillations of both RR interval and MSNA variability. High-dose atropine similarly induces an increase in the HF and a decrease in the LF components of MSNA variability. Thus, central parasympathetic activation is able to modulate the oscillatory characteristics of sympathetic nerve traffic to peripheral blood vessels.

Adult↗
PubMed1997

Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent.

There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species. This BSE 'signature' has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt-Jakob disease (CJD), referred to as 'new variant' CJD (vCJD), have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

Animals↗
PubMed1997

Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans.

BACKGROUND: Spectral analysis of RR interval and systolic arterial pressure variabilities may provide indirect markers of the balance between sympathetic and vagal cardiovascular control. METHODS AND RESULTS: We examined the relationship between power spectral measurements of variabilities in RR interval, systolic arterial pressure, and muscle sympathetic nerve activity (MSNA) obtained by microneurography over a range of blood pressures. In eight healthy human volunteers, MSNA, RR interval, intra-arterial pressure, and respiration were measured during blood pressure reductions induced by nitroprusside and during blood pressure increases induced by phenylephrine. Both low-frequency (LF; 0.10 +/- 0.01 Hz) and high-frequency (HF; 0.23 +/- 0.01 Hz) components were detected in MSNA variability. Increasing levels of MSNA were associated with a shift of the spectral power toward its LF component. Decreasing levels of MSNA were associated with a shift of MSNA spectral power toward the HF component. Over the range of pressure changes, the LF component of MSNA variability was positively and tightly correlated with LF components of RR interval (in normalized units; P < 10(-6)) and of systolic arterial pressure variability (both in millimeters of mercury squared and normalized units; P < 5 x 10(-5) and P < 5 x 10(-6), respectively). The HF component of MSNA variability was positively and tightly correlated with the HF component (in normalized units) of RR-interval variability (P < 3 x 10(-4)) and of systolic arterial pressure variability (P < .01). CONCLUSIONS: During sympathetic activation in normal humans, there is a predominance in the LF oscillation of blood pressure, RR interval, and sympathetic nerve activity. During sympathetic inhibition, the HF component of cardiovascular variability predominates. This relationship is best seen when power spectral components are normalized for total power. Synchronous changes in the LF and HF rhythms of both RR interval and MSNA during different levels of sympathetic drive are suggestive of common central mechanisms governing both parasympathetic and sympathetic cardiovascular modulation.

Blood Pressure↗
PubMed1996

Transthoracic defibrillation: importance of avoiding electrode placement directly on the female breast.

OBJECTIVES: This study sought to determine the effect on transthoracic impedance of placement of defibrillation electrodes on the female breast versus adjacent to or under the breast. BACKGROUND: Transthoracic impedance is a major determinant of transthoracic current flow in defibrillation. For a given energy setting, a high transthoracic impedance reduces current flow and may adversely affect the ability of electric shocks to accomplish defibrillation. We hypothesized that the increased interelectrode tissue associated with placement of the apex defibrillation electrode on the female breast would result in increased transthoracic impedance compared with electrode placement lateral to or under the breast. METHOD: Transthoracic impedance was measured noninvasively by passing a 5-V, 31.25-kHz square wave current through the chest and comparing the low level current flow to known references. We measured transthoracic impedance associated with three different apex defibrillation electrode positions--on the breast, under the breast and lateral to the breast--in 25 women (brassiere size 34A to 48C, 25 to 75 years old, body weight 128 to 328 lb [58 to 148 kg] and 2 men. The measurements were taken with a modified defibrillator that accurately predicts transthoracic impedance without delivering an actual shock. The measurement sequence was random. RESULTS: The average measured transthoracic impedance with placement of the apex defibrillation electrode on the breast was 95 +/- 25 ohms (mean +/- SD), under the breast 84 +/- 17* ohms and lateral to the breast 83 +/- 20* ohms (asterisk indicates p < 0.01 vs. on the breast by analysis of variance). The study cohort was also classified into two groups: large breasted (brassiere size > or = 40) and small breasted (brassiere size < or = 39). The measured transthoracic impedances for the large-breasted group were 112 +/- 20 ohms for on the breast, 94 +/- 13* ohms for under the breast and 98 +/- 19* ohms for lateral to the breast. For the small breasted group, the similar transthoracic impedance measurements were 81 +/- 21, 77 +/- 16 and 71 +/- 13* ohms, respectively. CONCLUSIONS: In women, placement of the apex defibrillation electrode on the breast results in higher transthoracic impedance, which will reduce current flow. We recommend placing the apex electrode lateral to or underneath the breast.

Adult↗
PubMed1994

Overlapping sequential pulses. A new waveform for transthoracic defibrillation.

BACKGROUND: A directionally changing shock electrical vector could facilitate defibrillation by depolarizing myocytes with different orientations vis-à-vis the shock field. Such a changing vector can be achieved by a new waveform for transthoracic defibrillation: overlapping sequential pulses. Our purpose was to evaluate this waveform. METHODS AND RESULTS: Ventricular fibrillation was induced in closed-chest dogs. Single and overlapping truncated exponential waveform pulse shocks were then administered from self-adhesive chest electrodes. Single pulse (control) shocks were 7.5-millisecond duration, while the sequential overlapping pulse shocks, using two different pathways, consisted of two pulses, each 5.0-millisecond duration; the second pulse began 2.5 milliseconds after the start of the first pulse and ended 2.5 milliseconds after the end of the first pulse. Thus, the total duration of the sequential overlapping shock was 7.5 milliseconds. During the overlap phase (2.5 milliseconds), the electrical vector orientation is the summation of the individual vectors. Two different electrode placements and corresponding electrical vector orientations were studied: group 1 (n = 14), left lower chest to right upper chest (pulse 1), overlapped by right lower chest to left upper chest (pulse 2), with the sequence then reversed; and group 2 (n = 11), left chest to right chest (pulse 1) overlapped by dorsal (vertebral column) to ventral (sternum) (pulse 2) with the sequence then reversed. At voltages equivalent to energies of 50, 100, and 150 J, the sequential overlapping pulse shocks achieve higher success rates than the single pulse shocks: At the low energy, 50 J, single pulse shock success rates were 0% (group 2) and 14% (group 1), while the overlapping pulse shocks achieved success rates of 39% (group 2) and 55% (group 1) (P < .05). Similarly, at the highest energy tested, 150 J, single pulse shock success rates were 45% (group 2) and 61% (group 1), while the overlapping pulse shock success was 91% (group 2) and 95% (group 1) (P < .05). In a third group of dogs (n = 3), intracardiac plunge electrodes placed orthogonally in the septum showed that the orthogonal components of intracardiac voltage gradient change varied markedly during the three phases of the sequential overlapping shocks, demonstrating the changing direction of the net electrical vector as the shock proceeded. In a fourth group of dogs (n = 5), short-duration (2.5-millisecond) single pulse shocks were compared with longer 7.5-millisecond single pulse shocks and with the sequential overlapping pulse shocks, all at equivalent energies. Despite substantially higher current flow, the 2.5-millisecond-duration single pulse shocks were not more effective than 7.5-millisecond single pulse shocks, and both 2.5- and 7.5-millisecond duration single pulse shocks had markedly inferior success rates compared with the sequential overlapping pulse shocks. CONCLUSIONS: Sequential overlapping pulse shock waveforms facilitate defibrillation compared with single pulse shocks of the same total energy. This is due at least in part to the changing orientation of the electrical vector during the multiple pulse shock.

Animals↗
PubMed1993

Transthoracic defibrillation: effect of dual-pathway sequential pulse shocks and single-pathway biphasic pulse shocks in a canine model.

To determine whether dual-pathway sequential shocks and single-pathway biphasic shocks improved the efficacy of transthoracic defibrillation, we delivered single or sequential truncated waveform shocks of variable duration, voltage, and direction (polarity) to three groups of closed-chest dogs. Dual-pathway sequential shocks were assessed in group 1 (eight animals), biphasic shocks with a single pathway were compared in 11 dogs (group 2), and the effect of varying the duration of the biphasic shocks was assessed in group 3 (four animals). There was no improvement in success rates of the intervention shocks compared with a standard single "control" shock at any energy level. In this experimental model unidirectional or biphasic sequential shocks given over single or dual pathways were not superior to standard single-pulse transthoracic defibrillation.

Analysis of Variance↗
PubMed1992

Problems in measuring heart rate variability of patients with congestive heart failure.

Heart rate variability (HRV) has become an important noninvasive measure of the integrity of the autonomic nervous system in various disease states. The power spectrum of HRV is a means to separate the instability oscillations of the various feedback mechanisms that contribute to cardiovascular homeostasis. The reliability of HRV data is largely unexplored. The day-to-day correlations in the low and mid-frequency components of HRV spectra average 91%, and that of the high-frequency component averages 81%. The correlations among spectral and nonspectral measures of HRV (SD) for the same data segment average 50-60%, suggesting that they encode similar information. Heart rate variability spectra exhibit diurnal variation consistent with physiologic expectation: respiratory sinus arrhythmia (thought to be mediated by parasympathetic tone) and to a lesser extent, the low-frequency spectral component (thought to be of mixed sympathetic-parasympathetic origin) are higher at night than in the daytime; the mid-frequency component (associated with the baroreflex, which is more excited when the patient is upright) is slightly higher during the daytime. Increased frequency of ectopic beats, such as occurs in congestive heart failure, reduces the reliability of the power spectrum since the number of usable data segments falls off rapidly with even small increases in rate of ectopy, and the variance of the estimate (in the method of averaged periodograms) is inversely proportional to the square root of the number of data segments. Using shorter data segments increases the number of segments available, but reduces resolution. Interpolation over ectopic beats (by either linear or cubic splint interpolation) increases the apparent power in low frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗
PubMed1990

Transthoracic defibrillation using sequential and simultaneous dual shock pathways: experimental studies.

Dual pathway sequential DC shocks reduce energy requirements for internal defibrillation. Our purpose was to determine if dual pathway shocks similarly reduce energy requirements or improve shock success in transthoracic (external) defibrillation. We studied 39 closed-chest anesthetized mongrel dogs. The dual pathways used were left chest to right chest and left chest to posterior. In eight dogs we also assessed dual shock pathways oriented orthogonally, left lower chest to right upper chest and left upper chest to right lower chest. Four different dual pathway groups were studied: group 1: simultaneous shocks, sinusoidal waveform; group 2: sequential shocks, sinusoidal waveform, 100-msec shock separation, orthogonal shock pathways; group 3: sequential shocks, sinusoidal waveform, 100 msec shock separation; and group 4: sequential shocks, rectangular waveform (sequential shocks: 2 pulses, 2.5 msec each, 0.1-msec separation; single shock: 1 pulse, 5 msec). Shocks were given at 50 (J) joules, 100 J and 150 J and curves of energy versus success compared for dual pathway shocks versus single shocks. We found that the highest mean success rates (96 +/- SD 9%) were achieved by simultaneous sinusoidal waveform dual pathway shocks at 100 J; this was identical to results achieved by the single pathway sinusoidal waveform comparison shocks at 100 J. Sequential dual pathway sinusoidal shocks separated by 100 msec achieved a mean success rate of 79 +/- 31% at 150 J; the comparison single pathway mean success rate was similar: 81 +/- 22% at 150 J. Thus, dual pathway sequential or simultaneous transthoracic shocks did not demonstrate clear superiority over single pathway shocks.

Animals↗