Search PubMed⌕ Search

Biomedical subjects

D Burke

Publications and source records attributed to D Burke.

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

Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.

The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings have been measured directly, using the polar angle dependence of the polarized cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their semileptonic decays. Both the electron and muon analyses take advantage of new multivariate techniques to increase the analyzing power. Based on the 1993-1998 SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams, we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/-0.055(stat)+/-0.055(syst).

Journal Article↗
PubMed2002

Sustained contractions produced by plateau-like behaviour in human motoneurones.

Electrical stimulation over human muscle can generate force directly by activation of motor axons and indirectly by 'reflex' recruitment of spinal motoneurones. These experiments were designed to define the properties of the centrally generated 'reflex' force, including the optimal stimulus conditions for producing it in tibialis anterior (TA) and triceps surae (TS), and its interaction with volition. Subjects (n = 21) were seated with their foot strapped to an isometric myograph. Surface EMG was recorded from TS and TA. High-frequency electrical stimulation (100 Hz) of TS and TA with wide pulse widths (1 ms) was most effective to evoke the sustained centrally generated forces. The maximal force evoked by this mechanism during stimulation of TA for 40 s was approximately 42 % of that produced by a maximal voluntary contraction. For both muscle groups, ramp increases and decreases in stimulus frequency (from approximately 4 to 100 Hz and back to 4 Hz over 6 s) resulted in marked hysteresis in the force-frequency plot. After a single 'burst' of 100 Hz stimulation during prolonged stimulation at 25 Hz, force remained elevated. Repeated bursts often generated progressively larger force increments. These behaviours were abolished by an anaesthetic nerve block proximal to the stimulation site, confirming the central origin for the 'extra' force. After a brief voluntary contraction was performed during 25 Hz stimulation, force remained elevated, and this showed some gradation with voluntary contraction amplitude. Sometimes voluntary contractions alone initiated the sustained central motor output. Involuntary contractions often persisted for many seconds after electrical stimulation ceased. These were not terminated by brief inhibitory inputs to the active motoneurones but could be stopped by the voluntary command to 'relax completely'. Overall, these centrally generated contractions are consistent with activation of plateau potentials in motoneurones innervating the ankle dorsiflexors and plantarflexors. Large forces can be produced through this mechanism. The interaction with volitional drives suggests that plateau behaviour may contribute significantly to the normal output of human motoneurones.

Adult↗
PubMed2002

Chirality: a blueprint for the future.

The chirality that is inherent in the enzyme systems of living organisms results in an abundance of enantiopure organic molecules in the living world. In addition to the optical properties first noticed by Pasteur, stereospecific interactions at recognition sites result in differences in both biological and toxicological effects. This fact underlies the continuing growth in chiral chemistry, rooted as it is in fundamental biochemistry. The pharmaceutical industry has undergone a strategic shift and embraced the wide spectrum of asymmetrical synthetic methods now available. The use of these processes in developmental synthesis and large-scale manufacturing has provided new challenges in drug discovery, motivated by a desire to improve industrial efficacy and decrease the time from the conception of a new drug to the market. The economic impact of the industrial production of chiral drugs is now huge--more than 50% of the 500 top-selling drugs were single-enantiomers in 1997. Sales have continued to increase by more than 20% for the past 6 yr and worldwide annual sales of enantiomeric drugs exceeded US$100 billion for the first time in the year 2000, chiral drugs representing close to one-third of all sales worldwide. While some 'chiral switches' may be of less apparent benefit, or indeed detrimental in some cases, encouragement by the regulatory agencies and the ability to extend the life cycle of a drug coming off patent promotes the trend. However, it may turn out to be the ability to provide chiral templates, and thereby attack the key targets of selectivity and specificity, that will lead to the greatest benefits. Research into new chemical entities that can interact specifically with enzyme families may potentially lead to new therapies for complex disease processes. As Richards has stated, the approach is designed to create a made to measure product, rather than one off the peg.

Analgesics↗
PubMed2001

Continuous angiotensin II infusion increases tumour: normal blood flow ratio in colo-rectal liver metastases.

Insufficient blood flow within colo-rectal hepatic metastases is a factor which may limit drug delivery to, and thus the response of, these tumours to regional chemotherapy. Loco-regional flow may be manipulated pharmacologically to enhance the tumour blood flow relative to that of the normal liver. However, as yet, only transient effects have been studied. Patients receiving regional chemotherapy for unresectable hepatic disease were given a 45 min regional infusion of the vasoconstrictor Angiotensin II. Intrahepatic blood flow distribution was assessed serially by Positron Emission Tomography (PET) imaging together with the trapping tracer copper(II) pyruvaldehyde bis(N-4-methylthiosemicarbazone) (Cu-PTSM) labelled using copper-62. Eleven lesions in nine patients were studied, with no adverse effects. Prior to Angiotensin II administration tumour blood flow was generally found to be greater than that of liver (10/11 lesions; 8/9 patients; median TNR 1.3, iqr 0.9-2.5). A significant increase in relative flow to tumour was seen in response to 10 min Angiotensin II infusion in most cases (7/11 lesions; 7/9 patients; median TNR 2.1, iqr 1.4-4.1; P = 0.008), which appeared to be sustained throughout the 45 min infusion period (median TNR 1.85, iqr 1.3-3.8; P = 0.03). These effects were accompanied by transient elevation of mean arterial pressure, but no change in pulse rate. These observations suggest that prolonged regional vasoconstrictor administration could prove useful in the management of unresectable colo-rectal hepatic metastases, and that further development of vascular manipulation to enhance tumour targeting and drug delivery is warranted.

Angiotensin II↗
PubMed2001

Corticospinal excitation of presumed cervical propriospinal neurones and its reversal to inhibition in humans.

1. This study addresses whether in human subjects indirect corticospinal excitation of upper limb motoneurones (MNs) relayed through presumed cervical propriospinal neurones (PNs) is paralleled by corticospinal activation of inhibitory projections to these premotoneurones. 2. The responses to transcranial magnetic stimulation (TMS), whether assessed as the compound motor-evoked potential (MEP) or the peak of corticospinal excitation elicited in the post-stimulus time histograms (PSTHs) of single motor units, were conditioned by weak volleys to musculo-cutaneous, ulnar and superficial radial nerves. 3. Afferent volleys, which hardly modified the H reflex, significantly facilitated the corticospinal response produced by weak TMS. In PSTHs, the central delay of the peripheral facilitation of the peak of corticospinal excitation in MNs located at either end of the cervical enlargement was longer the more caudal the MN pool, suggesting an interaction in premotoneurones located rostral to the tested MNs. 4. Small increases in the strength of TMS (approximately 2--5 % of the maximal stimulator output) caused the facilitation to disappear and then to be reversed to inhibition. The facilitatory and inhibitory effects had the same latencies and spared the initial 0.5--1 ms of the corticospinal excitatory response. Both effects were more readily demonstrable when there was a co-contraction of the target muscle and the muscle innervated by nerve used for the conditioning stimulus. 5. The above features suggest that the inhibition resulted from disfacilitation due to suppression of corticospinal excitation passing through the presumed premotoneuronal relay. The reversal of the facilitation to inhibition by stronger corticospinal volleys is consistent with a well-developed system of 'feedback inhibitory interneurones' activated by corticospinal and afferent inputs inhibiting the presumed propriospinal excitatory premotoneurones. 6. It is argued that these findings might explain why simply stimulating the pyramidal tract or the motor cortex would fail to demonstrate this indirect corticospinal projection in the macaque monkey and in humans.

Adult↗
PubMed2001

Large involuntary forces consistent with plateau-like behavior of human motoneurons.

When electrical stimulation is applied over human muscle, the evoked force is generally considered to be of peripheral origin. However, in relaxed humans, stimulation (1 msec pulses, 100 Hz) over the muscles that plantarflex the ankle produced more than five times more force than could be accounted for by peripheral properties. This additional force was superimposed on the direct response to motor axon stimulation, produced up to 40% of the force generated during a maximal voluntary contraction, and was abolished during anesthesia of the tibial nerve proximal to the stimulation site. It therefore must have resulted from the activation of motoneurons within the spinal cord. The additional force could be initiated by stimulation of low-threshold afferents, distorted the classical relationship between force and stimulus frequency, and often outlasted the stimulation. The mean firing rate of 27 soleus motor units recorded during the sustained involuntary activity after the stimulation was 5.8 +/- 0.2 Hz. The additional force increments were not attributable to voluntary intervention because they were present in three sleeping subjects and in two subjects with lesions of the thoracic spinal cord. The phenomenon is consistent with activation of plateau potentials within motoneurons and, if so, the present findings imply that plateau potentials can make a large contribution to forces produced by the human nervous system.

Adult↗
PubMed2001

Voluntary contraction impairs the refractory period of transmission in healthy human axons.

1. Voluntary contraction of a muscle causes substantial hyperpolarization of the active motor axons due to activation of the electrogenic Na+-K+ pump. The present study was undertaken to determine whether voluntary effort produces a significant impairment in impulse transmission in normal axons and whether mechanisms other than membrane hyperpolarization contribute to the changes in axonal excitability. 2. The compound muscle action potential (CMAP) was recorded after median nerve stimulation at the wrist using sub- and supramaximal stimuli, delivered singly and in pairs at conditioning-test intervals of 2-15 ms. Axonal excitability parameters (threshold, refractoriness, supernormality, and strength-duration time constant (tauSD)) were measured using threshold tracking. Impulse transmission was assessed using supramaximal stimuli. 3. Maximal voluntary contractions of the abductor pollicis brevis for 1 min produced a substantial increase in threshold, an increase in supernormality and a decrease in tauSD, all of which lasted approximately 10 min and indicate axonal hyperpolarization. However, immediately after the contraction there was an unexpected increase in refractoriness. The post-contraction increase in refractoriness could not be mimicked by an imposed ramp of hyperpolarization that produced changes in the other indices to an extent that was similar to voluntary contraction. 4. The contraction had relatively little effect on the size of the unconditioned maximal CMAP. However, there was failure of transmission of supramaximal conditioned volleys when the conditioning-test interval was short. 5. The relationships between axonal excitability and supernormality and tauSD following voluntary contraction differed significantly from those recorded during the hyperpolarization produced by DC current. It is argued that these differences probably result from extra-axonal K+ accumulation with the voluntary contraction but not with the DC polarization. I6. It is concluded that, following maximal voluntary contraction of a normal muscle, the refractory period of transmission is impaired distal to the stimulus site sufficient to cause transmission failure of the second of a pair of closely spaced impulses. The site of transmission failure is likely to be the terminal axon, presumably at branch points, possibly in the unmyelinated pre-terminal segment.

Action Potentials↗
PubMed2001

Improved direct measurement of leptonic coupling asymmetries with polarized Z bosons.

We present final measurements of the Z boson-lepton coupling asymmetry parameters A(e), A(mu), and A(tau) with the complete sample of polarized Z bosons collected by the SLD detector at the SLAC Linear Collider. From the left-right production and decay polar angle asymmetries in leptonic Z decays we measure A(e) = 0.1544+/-0.0060, A(mu) = 0.142+/-0.015, and A(tau) = 0.136+/-0.015. Combined with our left-right asymmetry measured from hadronic decays, we find A(e) = 0.1516+/-0.0021. Assuming lepton universality, we obtain a combined effective weak mixing angle of sin (2)theta(eff)(W) = 0.230 98+/-0.000 26.

Journal Article↗
PubMed2001

First symmetry tests in polarized Z0 decays to bbg.

We have made the first direct symmetry tests in the decays of polarized Z0 bosons into fully identified bbg states, collected in the SLD experiment at SLAC. We searched for evidence of parity violation at the bbg vertex by studying the asymmetries in the b-quark polar- and azimuthal-angle distributions, and for evidence of T-odd, CP-even or CP-odd, final-state interactions by measuring angular correlations between the three-jet plane and the Z0 polarization. We found results consistent with standard model expectations and set 95% C. limits on anomalous contributions.

Journal Article↗
PubMed2001

Differences in responses of cutaneous afferents in the human median and sural nerves to ischemia.

Recent evidence suggests that two conductances responsible for accommodation to changes in membrane potential (a slow K(+) conductance and inward rectification [I(H)]) are less active on cutaneous afferents in the sural nerve than on those in the median nerve, and it has been suggested that these axons would therefore respond differently to stress, whether natural or due to disease. The present study was undertaken in eight healthy volunteers to determine whether these afferents respond differently to the depolarizing and hyperpolarizing stresses that accompany ischemia for 13 min and subsequent recovery. During ischemia, the decrease in threshold was quantitatively less for the sural afferents, as were the changes in the other indices of axonal excitability, presumably because the ischemic depolarization was less for sural afferents. Following release of ischemia, there was, as predicted, a divergence in the pattern of threshold change. With median afferents there was evidence of a transient depolarization, believed to be due to inward rectification, superimposed on a long-lasting hyperpolarization. The response of sural afferents lacked this transient depolarizing threshold change. Cutaneous afferents in the median and sural nerves behave differently in response to ischemic and postischemic stresses, and it is likely that they will also respond differently to disease processes. In a number of respects the differences between sural and median afferents are analogous to differences between diabetic and normal nerves.

Humans↗
PubMed2001

Image processing used to harness blinking as a channel of communication and control for physically disabled people.

Sophisticated mathematical algorithms (such as differencing, thresholding, aggregation and statistical analysis of skin colours) are used to compare successive frames of computer-captured images of the face. From these, changes in state of the eyes are determined and are used to detect blinks. A recognition performance of 83.74 +/- 0.03% is achieved over five subjects with a low rate of false positives 2.71 +/- 0.01%. A logical decision rule identifies purposeful blinks and applies them to control either a custom-designed communication package or an external device.

Adult↗
PubMed2001

62Cu-PTSM and PET used for the assessment of angiotensin II-induced blood flow changes in patients with colorectal liver metastases.

The aim of this study was to establish a quantitative positron emission tomography (PET) method for investigating angiotensin II (AII)-induced changes in blood flow distribution in the liver. This was in order to evaluate the role of vascular manipulation applied to locoregional chemotherapy treatment in patients with colorectal liver metastases. The tracer selected was copper-62 (II) pyruvaldehyde bis-(N4-methyl)thiosemicarbazone (62Cu-PTSM), which exhibits high first-pass extraction and tissue retention following intra-arterial administration. The short half-life of the tracer and its availability from a 62Zn/62Cu generator enabled short-interval repeat PET scans on patients in a single imaging session. Distribution of tracer within the liver was imaged in a single view using a PET camera with rotating large-area detectors. By optimisation of the acquisition protocol, it was possible to acquire sufficient data to produce good-quality images and to quantify tracer uptake with an accuracy of <10%. Reproducibility of the imaging method was assessed in a single patient in whom three consecutive 62Cu-PTSM PET scans were obtained, and in whom no vascular manipulation was performed. Sets of scans (before, during and immediately after a 45-min AII infusion) were obtained in nine patients to assess blood flow changes associated with prolonged vascular manipulation. Significant individual responses, varying in both the magnitude and the duration of flow change, were observed in the majority of cases (7/11 lesions; 7/9 patients). These findings illustrate the potential of 62Cu-PTSM and PET for pharmacological studies. The wide range of individual patient responses to AII infusion suggests that PET blood flow assessment would be of value for selecting patients in whom this procedure may be effective.

Algorithms↗
PubMed2001

Excitability of human axons.

The excitability of human axons can be studied reliably using the technique of threshold tracking, which allows the strength of a test stimulus to be adjusted by computer to activate a defined fraction of the maximal nerve or muscle action potential. The stimulus current that just evokes the target response is considered the "threshold" for that response. More useful than the resting threshold are other indices of axonal excitability derived from pairs of threshold measurements, such as refractoriness, supernormality, strength-duration time constant and "threshold electrotonus" (i.e. the changes in threshold produced by long-lasting depolarizing or hyperpolarizing current pulses). Each of these measurements depends on membrane potential and on other biophysical properties of the axons. Together they can provide new information about the pathophysiology underlying abnormalities in excitability in neuropathy.

Action Potentials↗
PubMed2001

Scientific perspectives on regulating the safety of genetically modified foods.

Regulation is often seen as the dull end of science. The recent storm over the introduction of genetically modified foods and the calls to regulate their consumption have had a negative effect on development of the science. Assuring the safety of genetically modified foods might raise questions where existing scientific data is limited and underline the need for further research.

DNA↗
PubMed2001

Levobupivacaine.

Regional anaesthesia has seen the development of a new local anaesthetic: levobupivacaine. This review aims to outline the rationale underlying the development of levobupivacaine and to consider its place in modern regional anaesthesia.

Anesthesia, Conduction↗
PubMed2001

Transvaginal repair of pouch-vaginal fistula.

BACKGROUND: The results of surgery for ileoanal pouch-vaginal fistula have been disappointing. Intra-anal procedures result in fistula healing in, at best, approximately 50 per cent of patients. A transvaginal approach was developed to achieve direct access to the internal opening, enabling closure without damage to the anal sphincter. METHODS: Fourteen patients were treated between January 1992 and December 1998. All had had restorative proctocolectomy for ulcerative colitis and all were defunctioned. Histological review confirmed the diagnosis in all patients. RESULTS: Median age was 40 (range 25-52) years. Median follow-up was 18 (range 6-60) months. The operation was successful in 11 of the 14 patients, after one attempt in six patients, after two attempts in four, and after three attempts in one patient. The operation failed in three patients, who had a permanent ileostomy. The number of bowel actions in the patients who had successful closure ranged from 2 to 10 (median 6) in 24 h, with no faecal incontinence reported. CONCLUSION: This simple technique achieved healing in 11 of 14 patients. This compares favourably with the poor results in 28 patients treated by other procedures in the same hospital, with certain healing in five and definite failure in 20.

Adult↗
PubMed2001

Improving community-based services for older patients with depression: the benefits of an educational and service initiative.

OBJECTIVE: The objective of this study was to report a quality improvement project for older patients with depression. The initiative focused on both clinical practice changes (improvement of medical, neurocognitive and behavioural assessment) and service development (greater continuity of care). METHOD: After initial identification of key deficits, implementation of a service and educational initiative took place within a district mental health service. The service consisted of an inpatient unit, a specialized psychogeriatric service and two adult community mental health services. Mental health staff received education regarding the specific needs of older patients with depression and were provided with assessment materials, patient education and treatment aids. General practitioners participated in shared long-term management. RESULTS: Following graded implementation, the management of 44 subjects (mean age = 65.4 years, 91% female) recruited over an 8-month period was reviewed. Compared with 99 subjects (mean age = 68.9 years, 69% female) from the earlier 12-month assessment phase, there were significant improvements in medical (43% to 92%), neurocognitive (37% to 84%) and behavioural (e.g. suicidal ideation: 78% to 100%) assessments. Similarly, relevant laboratory investigations (neuroimaging: 21% to 67%) and communication with general practitioners (73% to 97%) improved. The most change occurred in the adult community-based treatment services. CONCLUSIONS: A coordinated management and educational initiative resulted in marked improvement in basic medical and psychiatric assessment and more integrated care. These changes did not require expansion of specialist services.

Aged↗