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Biomedical subjects

D Noble

Publications and source records attributed to D Noble.

At least 127 records · Page 7Linked to original sources
PubMed1981

150 bicycle injuries in children: a comparison with accidents due to other causes.

One hundred and fifty bicycle accidents seen at the Children's Hospital Sheffield over a 6-month period from mid-August 1979 were analysed and 9.3 per cent of the cases were admitted. Twenty-two per cent had fractures, 20 per cent had soft tissue injuries of face or scalp, 8 children having damaged their teeth. Of the accidents 17.3 per cent were due to hitting an obstruction, 30.7 per cent were due to loss of control on a hill or corner and 8 per cent were of mechanical origin. Eighty-eight per cent had cycling experience of a year or more, and 32.7 per cent had had previous cycling accidents. Comparison with other types of accidents previously studied at the hospital, involving skateboards, playground equipment or road traffic accidents affecting child pedestrians, showed that by far the most serious were those involving child pedestrians. The injuries from bicycle accidents were similar in severity to those involving skateboards.

Accidents↗
PubMed1980

The contribution of potassium accumulation to outward currents in frog atrium.

1. Voltage-clamp experiments on frog atrial muscle were designed to distinguish effects due to K accumulation in extracellular spaces from those due to activation of K conductance mechanisms in the membrane. 2. The set of instantaneous current-voltage relations obtained at various external K concentrations following depolarization to about -10 mV for several seconds was found to be quite different from that obtained before the depolarization. Hence the process of increasing the extracellular K concentration cannot account for all the time-dependent changes in outward current during depolarization. 3. Although the instantaneous current-voltage relations obtained at different values of external K concentration before prolonged depolarization show the cross-over phenomenon (Noble, 1965), those obtained at the end of the depolarization did not show this feature. It is concluded that the current-voltage relations for the channels conducting the time-dependent K current do not show cross-over. 4. These results were used to construct a model involving both K activation and K accumulation. This model successfully reproduces the appearance of a very slow component in outward current decay tails which, when subtracted by semi-exponential curve-stripping leaves a component with the real time constant of conductance change. The model does not however reproduce the appearance of a fast decaying component without adding a second conductance mechanism, or assuming non-exponential decay of a single conductance mechanism. 5. It is therefore suggested that i chi, fast is not a perturbation of i chi, slow or of iK1 by the process of K accumulation. This conclusion is reinforced by the results of experiments showing that the relative magnitude of i chi, fast is not greatly changed by substantially increasing the external K concentration in order to reduce the proportionate effect of K accumulation on the K concentration.

Animals↗
PubMed1980

The time course of potassium current following potassium accumulation in frog atrium: analytical solutions using a linear approximation.

1. Regular perturbation theory was used to obtain analytical solutions for the time course of membrane current decay following voltage-clamp depolarizing pulses when both time-dependent K conductance mechanisms and the process of K accumulation in extracellular spaces are present. These solutions apply when the current and K concentration changes are small enough for linear relations to be assumed between current and K concentration. 2. In the case of a single Hodgkin-Huxley type conductance variable with time constant tau chi the presence of an accumulation process which, by itself, would produce a current decay with time constant tau alpha, induces the appearance of two infinite sets of components with decreasing time constants (1/(n+1/tau chi) and 1/(1/tau alpha + n/tau chi), where n is integer), and decreasing magnitudes. 3. The analytical solutions are used to investigate the range of conditions over which semi-exponential (curve-stripping) analysis of current decay tails may give useful information on the kinetics of current change. It is shown that, except at very large decay tail amplitudes, the method may give a good estimate of the true time constants of conductance decay even when the currents are assumed to be strongly dependent on external K concentration. 4. The method introduces error in current amplitude, but over the range in which curve-stripping gives useful results, the direct distortion of activation curves by variations in external K concentration is fairly small. However, as the current decay becomes grossly distorted in its time course by accumulation, so does the activation curve. The effects are very similar both to those obtained using numerical computation without linearization, and to those obtained experimentally. 5. Even with a large dependence of current on external K concentration the linear model does not reproduce i chi, fast as a perturbation of i chi, slow by K accumulation.

Animals↗
PubMed1980

Successful renal transplantation in polyarteritis nodosa.

Hemodialysis and renal transplantation were performed in a patient with end stage renal disease caused by polyarteritis nodosa. Severe peripheral neuropathy developed during hemodialysis. Five years after transplantation, marked improvement of the neuropathy associated with adequate function of the allograft has been noted. There has been no detectable clinical or pathologic signs of recurrent disease. These observations favor the consideration of renal transplantation in patients with polyarteritis nodosa and renal failure, particularly in the absence of extensive organ involvement.

Follow-Up Studies↗
PubMed1980

[Excitation-contraction coupling: role of ionic currents and of ionic pumps (author's transl)].

The processes of excitation-contraction coupling in skeletal and cardiac muscles show some very important differences. In skeletal muscle, the action potential is primarily a trigger mechanism for mechanical events which are much slower, whereas in cardiac muscle the electrical activity continues to control the mechanical response even after the initial triggering has occurred. To some extent the control is dependent on a calcium-sodium current which is activated during the action potential plateau. However, this is not the only process by which the force of cardiac contraction may be controlled, since there is evidence that changes in intracellular calcium may also be produced as a secondary consequence of the activity of the sodium-potassium exchange pump. Experiments with cardiac glycosides cast doubt on whether this effect is necessarily linked with a sodium gradient change. In particular, therapeutic levels of the glycosides may increase rather than decrease the Na+ and K+ gradients. The mechanism of the therapeutic action of the cardiac glycosides is therefore still unknown.

Action Potentials↗
PubMed1979

Action of salicylate ions on the electrical properties of sheep cardiac Purkinje fibres.

1. In sheep Purkinje fibre preparations, salicylate ions produce reversible changes in resting potential and in action potential duration. In most preparations these effects resemble those produced by -ow extracellular K concentration: the resting potential first increases and then decreases, the action potential is prolonged and eventually, low potential oscillations occur in the plateau range. In a few preparations, action potential shortening occurs. 2. The threshold current for initiating action potentials by an intracellular electrode is reversibly increased by salicylate. 3. The activation curve, soo(Em), for the pace-maker K current, iK2, shifted in a hyperpolarizing direction. The magnitude of the shift is about -5 mV in 5 mM-salicylate and -30 mV in 50 mM-salicylate. 4. The apparent reversal potential for iK2 is shifted in a negative direction. The magnitude of this shift at a given salicylate concent;ation varies with the K concentration. In an extracellular K concentration of 2.7 mM an average shift of -18 mV occurs in 10 mM-salicylate; in 8 mM, the average shift is only -1 mV. 5. It is proposed that most of these effects may be produced by an increase in surface negative potential produced by the binding of salicylate to the cell membrane. This would produce the hyperpolarizing shift of activation curves for ionic current and, by increasing surface K activity, may lead to stimulation of the Na-K pump to produce an increase in the K gradient across the cell membrane.

Action Potentials↗
PubMed1979

The interaction of ouabain and salicylate on sheep cardiac muscle.

1. The action potential duration in sheep ventricular fibres is rapidly diminished on exposure to 10(-6) M-ouabain. However, if 10--20 mM-sodium salicylate is added to the ouabain solution, glycoside-induced shortening is prevented, and a substantial increase in duration then occurs. Sodium salicylate also reverses the shortening effect of ouabain if applied after the glycoside has been allowed to act alone. 2. Sodium salicylate alone produces a much smaller prolongation than in the presence of ouabain. Alone and in the presence of ouabain it eventually increases the threshold and produces inexcitability. 3. Three other surface charge agents have been compared with salicylate: aminonaphthalene sulphonate, sodium dodecylsulphate and salicylamide, were unable to counter the actions of ouabain at the concentrations used. Since they also produced no changes in excitability it is likely that they did not bind significantly to the cell membrane. 4. In Purkinje fibres the reversal potential for the pacemaker current, iK2, is initially shifted in a negative direction in the presence of 10(-6) M-ouabain and 10 mM-salicylate instead of the positive shift expected with ouabain alone at this concentration. 5. In guinea-pig ventricle, salicylate alone reduces the duration of the action potential. This effect is rapidly reversible. Toxic levels of ouabain also reduce the action potential duration but this effect takes several hours to reverse. By contrast, the effects of salicylate and ouabain applied together are readily reversible. 6. It is suggested that the mechanism of these effects may depend on the ability of a surface negative charge agent like salicylate to increase the surface K+ concentration at the membrane and so protect the sodium-potassium pump from inhibition by large doses of ouabain.

Action Potentials↗
PubMed1979

Electrocardiographic changes resembling myocardial ischaemia in asymptomatic men with normal coronary arteriograms.

T wave and ST segment abnormalities in 20 asymptomatic men aged 18 to 55 were investigated because they were identical with myocardial ischaemic changes, and the professional livelihood of the subjects was jeopardised. Coronary arteriograms showed unobstructed arteries in all except one in whom a 50 per cent lesion of the left anterior descending artery was present. Left ventricular angiograms showed a normal contraction pattern, Ejection fractions were normal in 12 and increased in 8. Three characteristic electrocardiographic patterns were observed: flat or inverted T waves in leads II, III, aVF, and V4 to 6 designated type 1; deep T inversion particularly evident in leads V2 to 5 designated type 2, and minor ST segment depression in the inferior and lateral leads without T changes designated type 3. Characteristically, type 1 changes were temporarily suppressed by either beta-blockade or an overnight rest and were more abnormal in the standing position. Type 2 and 3 changes were relatively uninfluenced by these manoeuvres. Maximal treadmill exercise tests were positive in 6 and borderline or negative in 14. When repeated after oxprenolol all tests were negative. Echocardiograms showed asymmetric septal hypertrophy in 3 subjects (ratio of greater than 1.5 between ventricular septum and posterior left ventricular wall). After normalisation by an overnight rest, type 1 T wave abnormalities were reproduced by intravenous adrenaline infusion (0.024 to 0.18 microgram/kg/min) but not by noradrenaline or by adrenaline after prior administration of oxprenolol. When the T waves had remained deeply inverted before infusion despite rest (type 2) adrenaline infusion normalised them and again noradrenaline was without effect. This effect was also prevented by oxprenolol. Type 3 changes were uninfluenced by catecholamine infusion. Plasma catecholamine estimations suggest that catecholamine hypersecretion and hypersensitivity may both be relevant, particularly the latter. The apparent bimodal response of the ventricular myocardium to adrenaline infusion is not surprising since in vitro experiments suggest that reversal of T wave polarity in either direction may result from summation of changes in action potential duration in different parts of the heart. Such changes may be unimodal, that is both areas involved show lengthening or shortening of action potential duration, but by occurring at different rates may lead to a bimodal change in the differences in duration which generate the T wave.

Adolescent↗
PubMed1979

G1549, a new cyclic hydroxamic acid antibiotic, isolated from culture broth of Pseudomonas alcaligenes.

Antibiotic G1549, isolated from culture broth of Pseudomonas alcaligenes, is a new cyclic hydroxamic acid with a 1-hydroxy-2(1H)-pyridinone structure that complexes with metals. The structure of G1549 is suggested to be 1-hydroxy-5-methoxy-6-methyl-2(1H)-pyridinone. In vitro, G1549 and its copper and ferric complexes show moderate activity against Gram-positive bacteria, fungi and Trichomonas vaginalis. Topical application of G1549 and its copper and ferric complexes protect guinea pigs against cutaneous infection with Microsporum canis. The compounds, however, have some systemic toxicity in mice.

Animals↗
PubMed1978

The action of adrenaline on pace-maker activity in cardiac Purkinje fibres.

1. Adrenaline is known to shift the activation curve for iK2 (s infinite curve) in a positive direction on the voltage axis. This should cause an increase in the slope of diastolic depolarization, but cannot account for the experimentally observed increase in the maximum diastolic potential (MDP). 2. On application of adrenaline, in voltage clamp studies on short sheep cardiac Purkinje fibres there is a consistent 5-15 mV negative shift of the reversal potential for the pace-maker current, iK2. This shift is not reversed on application of the beta-blockers sotalol or propranolol, or on washout for up to one hour. 3. A computer simulation, including this effect of adrenaline, shows that it can shift the maximum diastolic potential in the hyperpolarizing or depolarizing direction depending on the initial value of [K+]o. In both cases it will add to the increase in rate caused by the positive shift of the activation curve for iK2 (the s infinite shift). 4. Studies of the effects of adrenaline on the MDP and rate in long sheep Purkinje fibres show a slower reversibility of the MDP than the rate, consistent with a slower reversal of the shift in the iK2 reversal potential than the shift in s infinite. 5. Possible mechanisms of the shift in reversal potential are discussed with respect to K+ balance in the intercellular clefts of the Purkinje fibre, including a a stimulation of the Na+- K+ pump. The possible sources of voltage clamp artifact are also discussed.

Action Potentials↗
PubMed1978

Displacement of activator thresholds in cardiac muscle by protons and calcium ions.

1. The Na current threshold in sheep cardiac Purkinje fibres and in frog atrium is shifted in a positive direction by protons and Ca2+ ions. The titration curves for Purkinje fibres are consistent with a surface potential of -18 mV at pH 7.4 and 1.8 mM-Ca. 2. In Purkinje fibres, the pacemaker K current activation curve, s infinity, is shifted in a positive direction by Ca2+ ions. The results are consistent with a surface potential of -16 mV in normal physiological solutions. 3. The results on s inifinity during pH changes are unexpected. As also shown by Van Bogaert, Vereecke & Carmeliet (1975) the voltage shifts are usually in the opposite direction to that expected from titration of external surface negative charges. 4. Acid solutions reduce the magnitude of iK2 when fully activated. Alkalinity has little effect on iK2. 5. Acidification and alkalinization are both capable of arresting spontaneous activity in Purkinje fibres. The effects of acidity are usually irreversible. The effects of alkalinity are reversible.

Action Potentials↗
PubMed1978

The interactions of protons, calcium and potassium ions on cardiac Purkinje fibres.

1. In sheep Purkinje fibres, acidosis shifts the steady-state current-voltage relation in an inward direction over a wide range of negative potentials. The reversal potential for iK2 is shifted in a positive direction. These changes are consistent with K+ accumulation in the extracellular spaces of the Purkinje fibre. 2. These effects of acidosis are completely prevented by increasing [K]0 from the normal range (2.7--5.4 mM) to 10.8 mM. 3. Increasing [Ca]0 from 2 to 6 mM also produces an inward shift in the steady-state current-voltage relation and a positive shift of the iK2 reversal potential. 4. In 10.8 mM-[K]0 these effects are absent even when [Ca]0 is increased to 20 mM. 5. One possible explanation is that K+ ions may protect the Na pump from inhibition by protons and Ca2+ ions. Alternative explanations are also discussed.

Animals↗
PubMed1978

225 skateboard injuries in children.

Among 225 skateboard accidents treated at the Children's Hospital, Sheffield, in 8 months from August 1977, there were 92 fractures (40.9 per cent), of which 19 required manipulation under general anesthetic. Most involved the upper limb. Next most frequent were lacerations, bruises, abrasions, and injuries of joints and soft tissues. Four children had concussions (one with a fractured skull), 8 others had minor head injury, and 23 had soft tissue injuries of the head and neck. As for the reasons for the accidents, 20 per cent were due to hitting a stone, 10 per cent to a hole or bump in the pavement, 8 per cent to collisions, and three accidents to faults in the skateboards. Sixteen of the children were injured on the first day of their skateboarding. The role of protective clothing was uncertain. The city has no skateboard parks. Injuries due to skateboards were compared to injuries due to playground equipment.

Adolescent↗