Biomedical subjects
Publications and source records attributed to P Leonard.
The technique of biopsy of the vertebral body through a posterior approach passing through the pedicle was first reported in 1963. A description of the technique is given. The importance of good radiological control is stressed. Biopsy can be made with a curette once the approach has been made with a drill. The results were positive in 46 cases out of 47. A false negative was found on only one occasion.
Sympathetic nervous system function was studied in patients with primary depressive illness. Tritiated norepinephrine was used to measure the rate of entry to plasma of norepinephrine released from sympathetic nerves ("norepinephrine spillover rate"), and to assess the neuronal uptake of norepinephrine by studying the removal of norepinephrine from plasma. Norepinephrine spillover was elevated in five of 11 patients. This abnormality, which was unrelated to the presence of individual vegetative symptoms, occurred exclusively in patients with endogenous depression. The rapid-removal phase of the disappearance of tritiated norepinephrine from plasma, which seemed to correspond with neuronal uptake of norepinephrine, was accelerated in patients with depressive illness, providing presumptive evidence of increased neuronal uptake. If norepinephrine uptake is also accentuated within the brain, a functional deficiency of the transmitter at adrenergic receptor sites might result.
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Adjustments to sympathetic nervous system activity may regulate constant body weight despite wide variations in energy intake. To test this six normal weight subjects were studied at three different energy intakes (low, weight maintaining and high). Noradrenaline turnover was measured on the tenth day of each diet. Both noradrenaline appearance rate and noradrenaline clearance increased significantly with increasing energy intake and were a more sensitive indices than the plasma noradrenaline concentrations which rose, but not significantly. Fasting triiodothyronine (T3) rose and reverse T3 fell with increasing energy intake, while thyroxine (T4) concentrations did not change. Systolic blood pressure also rose significantly. Underfeeding resulted in reductions in noradrenaline appearance and clearance rates and in the T3 level. These results demonstrate that sympathetic nervous system activity, as determined by noradrenaline turnover in plasma, varies in response to short-term changes in energy intake in normal weight subjects. These changes may partly explain why some individuals maintain body weight constant despite large differences in food intake. The present findings may also be relevant to the variability in susceptibility to become obese.
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We have developed radiotracer techniques for studying noradrenaline kinetics, to assess better sympathetic nervous system function in humans. Tritiated l-noradrenaline was infused intravenously (0.35 microCi/m2/min) to plateau plasma concentration. Noradrenaline plasma clearance was calculated from plasma tritiated noradrenaline concentration at steady state, and the rate of spillover of noradrenaline to plasma derived from plasma noradrenaline specific radioactivity. Mean noradrenaline spillover at rest in 34 normal subjects was 0.33 micrograms/m2/min (range 0.17-0.61 micrograms/m2/min). Predictably, noradrenaline spillover was reduced in patients with subnormal sympathetic nervous system activity, 0.16 +/- 0.09 micrograms/m2/min in eight patients with idiopathic peripheral autonomic insufficiency, and 0.11 +/- 0.07 micrograms/m2/min (mean +/- SD) in six patients with essential hypertension treated with clonidine (0.45 mg daily). Noradrenaline line plasma clearance in normal subjects was 1.32 +/- 0.28 L/m2/min. Clearance fell with age, causing the previously described rise in plasma noradrenaline concentration with aging. Unexpected effects of drugs were encountered, for example chronic beta-adrenergic blockade in patients with essential hypertension reduced noradrenaline clearance. Plasma noradrenaline concentration measurements were not in agreement with noradrenaline release rate values, and do not reliably indicate sympathetic nervous system activity, in instances such as these where noradrenaline clearance is abnormal.
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The incidence of sister chromatid exchanges (SCE) in the lymphocytes of patients with aplastic anemia (AA) was determined before and after exposure to mitomycin C (MMC). The "baseline" SCE rate was significantly higher in AA, but MMC-induced SCE rate was not different compared to controls. It is suggested that some patients with AA may have an underlying DNA damage.
We studied the effect of a single oral dose of the neuronal norepinephrine uptake blocker, desipramine 125 mg, on norepinephrine kinetics. Desipramine reduced the plasma norepinephrine clearance by approximately 20%, from 1.33 +/- 0.22 to 1.08 +/- 0.19 l/m2/min (p less than 0.01). Similarly, plasma norepinephrine clearance was slowed in patients with sympathetic nerves damaged by disease (idiopathic peripheral autonomic insufficiency). Desipramine also reduced the rate of spillover of norepinephrine to plasma, 0.27 +/- 0.07 to 0.15 +/- 0.04 micrograms/m2/min, leaving the plasma norepinephrine concentration unchanged. Disappearance of tritiated norepinephrine from plasma, after infusion to steady state, was biexponential, with half-time of the rapid-removal phase (t1 1/2) = 2.0 +/- 0.4 min and half-time of the second exponential (t2 1/2) = 34 +/- 10 min. The rapid-removal phase was sensitive to disturbances in the neuronal uptake of norepinephrine, the t1 1/2 being prolonged by desipramine and lengthened in the patients with peripheral autonomic insufficiency. In contrast, the selective extraneuronal norepinephrine uptake blocker, cortisol, 500 mg intravenously, had no effect in normal subjects on either plasma norepinephrine clearance or the t1 1/2 value. Neuronal uptake of norepinephrine contributes to the overall removal of norepinephrine from plasma. Extraneuronal uptake of norepinephrine could not be demonstrated at existing plasma norepinephrine concentrations.
1. The influence of age on the rate of spillover of noradrenaline into plasma, clearance of noradrenaline from plasma, and plasma noradrenaline concentration at rest was studied in 34 healthy subjects aged 20--69 years. 2. The plasma concentration of noradrenaline was dependent on age, values being higher in older subjects. 3. This age-dependence of plasma noradrenaline concentration was due principally to a reduced clearance of noradrenaline from the circulation in older subjects. 4. The rate of spillover of noradrenaline into plasma was little influenced by age. The higher plasma noradrenaline values found in older subjects do not seem to be due to an increase in sympathetic nervous system tone with aging.
1 The rates of noradrenaline spillover to, and removal from, plasma were measured in ten patients with essential hypertension treated with propranolol, to ascertain if long-term administration of this drug reduces sympathetic nervous system tone. 2 The plasma clearance of noradrenaline fell with propranolol, leading to a small rise in the mean plasma noradrenaline concentration. Sympathetic nervous activity in treated patients cannot be reliably gauged from plasma noradrenaline values because these are distorted by the reduction in noradrenaline clearance. 3 There was no consistent effect on noradrenaline spillover rates, which fell in six patients, but rose in the remaining four. The magnitude of the antihypertensive response was unrelated to these changes in noradrenaline release. During propranolol treatment, noradrenaline spillover rates were in every case within the normal range, much higher than in patients treated with the known sympathetic nervous systems suppressant, clonidine. 4 The principal mode of antihypertensive action of propranolol is something often than central suppression of sympathetic tone or pre-synaptic inhibition of noradrenaline release.
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A patient with propranolol-induced mental status changes was studied during and after the period of propranolol intoxication. While intoxicated he manifested the syndrome of "non-aphasic misnaming," did poorly on the nonverbal portions of the WAIS, and exhibited perseveration and variability of performance. Our observations clarify the nature of the neurobehavioral disturbances in toxic-metabolic encephalopathies.
1. The rates of entry of noradrenaline to plasma and of removal of noradrenaline from plasma, and plasma noradrenaline concentration, were determined in normal subjects and in patients with essential hypertension. Neuronal uptake of noradrenaline was assessed from the plasma tritiated noradrenaline disappearance curve, after infusion to steady state. 2. Noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed if neuronal noradrenaline uptake was reduced, either by desipramine in normal subjects, or in patients with sympathetic nerve dysfunction (autonomic insufficiency). 3. In 10 of 41 hypertensive patients the t 1 1/2 similarly was prolonged, presumptive evidence of a defect in neuronal noradrenaline uptake. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, and plasma noradrenaline concentration, were increased in these patients. 4. Defective neuronal uptake of noradrenaline, by exposing adrenoreceptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.
Noradrenaline uptake was studied in normal subjects, and in patients with essential hypertension. Uptake of noradrenaline by blood platelets was low-affinity in type. Platelets do not provide a satisfactory in vitro model of neuronal noradrenaline uptake. Study of disappearance of tritiated noradrenaline from the circulation was more helpful. Plasma disappearance was biexponential. The rapid removal component was slowed if neuronal noradrenaline uptake was reduced, either by desipramine in normal subjects, or in patients with idiopathic peripheral autonomic insufficiency, who have sympathetic nerve dysfunction. The t1 1/2 similarly was prolonged in a proportion of patients with essential hypertension, providing presumptive evidence of a defect in neuronal noradrenaline uptake. Spillover of endogenous noradrenaline to plasma, of transmitter escaping uptake after release, and plasma noradrenaline concentration, were increased in these patients. Defective neuronal uptake of noradrenaline, by exposing adrenergic receptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.
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