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Biomedical subjects

R R Tuck

Publications and source records attributed to R R Tuck.

34 records · Page 2Linked to original sources

Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy.

Endoneurial hypoxia has been postulated to be important in the pathogenesis of diabetic peripheral neuropathy and may be due to reduced nerve blood flow. Neither blood flow nor oxygen tension have previously been measured in peripheral nerve in diabetic neuropathy. We have therefore measured both nerve blood flow and endoneurial oxygen tension in the sciatic nerves of 8 rats with streptozotocin-induced diabetes for four months, and in 8 age-matched controls. In 7 of the diabetic animals mean nerve blood flow was 8.7 +/- 1.3 ml X min-1 X 100 g-1 which is significantly less than mean nerve blood flow in the controls (13.08 +/- 0.8 ml X min-1 X 100 g-1; P less than 0.01). In one diabetic animal, nerve blood flow was too low to be accurately measured. The reduction in nerve blood flow in diabetic neuropathy is due to an increase in resistance to flow which may be due to microangiopathy and to blood hyperviscosity. Endoneurial oxygen tension was also significantly reduced in experimental diabetic neuropathy in which 60 per cent of the oxygen measurements were less than 25 mmHg, compared with 19 per cent in the controls. Nerve blood flow was also measured in rats with experimental galactose neuropathy in which there is more marked sugar-alcohol accumulation, endoneurial oedema and elevation of endoneurial fluid pressure than in experimental diabetic neuropathy. The results obtained in this neuropathy suggest that the reduction in nerve blood flow which occurs in experimental diabetic neuropathy is due largely to factors other than sugar-alcohol accumulation in nerve. We postulate that endoneurial hypoxia may produce many of the observed morphological and biochemical changes in experimental diabetic neuropathy.

Animals↗

Effects of changes of blood pressure, respiratory acidosis and hypoxia on blood flow in the sciatic nerve of the rat.

Using the hydrogen clearance technique, we have measured blood flow in the sciatic nerves of healthy, anaesthetized rats at rest, at various arterial blood pressures, and during respiratory acidosis and hypoxia. The majority of hydrogen clearance curves were bi-exponential. The slower component appears to reflect nerve blood flow more accurately than either the fast component or the composite value obtained from both components. Mean nerve blood flow estimated from the slow component of the seventeen bi-exponential hydrogen clearance curves and from the seven mono-exponential curves was 15.8 +/- 1.1 ml min-1 100 g-1 (+/- S.E. of the mean). The mean value of the fast component of the bi-exponential curves was 118 +/- 6 ml min-1 100 g-1 and that obtained from both components was 25.9 +/- 2.6 ml min-1 100 g-1. Sciatic nerve blood flow was measured over a range of arterial blood pressures of 60-160 mmHG. There is a curvilinear relationship between pressure and flow suggesting that the nerve vascular bed responds passively to changes in perfusion pressure. Respiratory acidosis resulted in no significant change in nerve blood flow. The mean flow was 15.5 +/- 1.9 ml min-1 100 g-1. During hypoxia, nerve blood flow decreased to 7.5 +/- 1.4 ml min-1 100 g-1 as a result of a reduction in arterial blood pressure and an increase in vascular resistance. These findings suggest that normal nerve blood flow is high in relation to metabolic activity, especially when compared with the brain.

Animals↗

Chronic polyneuropathy of undetermined cause.

The case histories of 519 patients with peripheral neuropathy on whom sural nerve biopsy had been performed were reviewed. In 67 patients (50 males, 17 females) (13%) who had symptoms of a symmetrical polyneuropathy for more than one year, the cause remained undiagnosed in spite of intensive investigation. Patients with inflammatory neuropathy were not included, but represented 17% of the whole series. The mean age of onset of symptoms was 50.6 years, and the median time from onset of symptoms to initial investigation was 2 years. Males were affected more commonly than females in a ratio of 3:1. The clinical features in 43 patients were those of a mixed motor and sensory neuropathy, in 17 patients a predominantly sensory neuropathy and in 7 patients a predominantly motor neuropathy. The mean CSF protein was 0.73 g/l and in only six patients was it greater than 1 g/l. Nerve conduction studies most commonly demonstrated mild slowing of motor conduction and impairment of sensory conduction. The usual pathological changes on sural nerve biopsy were those of chronic axonal degeneration. Forty seven patients (70%) were re-examined at intervals of time which ranged from 4 months to 12 years after their initial presentation and nerve biopsy (median, 3 years). As a group, they were only mildly disabled, the condition had a very slowly progressive course and there had been little change in their disability. A possible aetiological factor was found in 17 of the 47 patients (36%) and included malignancy, alcoholism, and benign paraproteinaemia. It is concluded that with intensive investigation the cause of chronic polyneuropathy of duration greater than one year remains undetermined in only about 13% of patients and that continued follow-up is worthwhile since a diagnosis may be established on re-examination.

Adult↗

Quantitative sudomotor axon reflex test in normal and neuropathic subjects.

We have quantified postganglionic sweat output in human subjects resulting from axon reflex stimulation using acetylcholine electrophoresis. Dehumidified nitrogen of controlled temperature and flow rate was passed through an acrylic plastic chamber placed over a defined area of skin. Sweat droplets were evaporated; humidity change was sensed by a narrow-range humidity sensor housed in a temperature-controlled compartment and was plotted on a chart recorder. The time integral (area under the curve) was continuously integrated and converted to absolute units using a derived equation. Because stimulation and recording were simultaneous, an accurate determination of the latency of the sweat response was also possible. Quantitative sudomotor axon reflex tests were performed on the left forearm and foot of 33 female and 29 male normal subjects aged 11 to 69 years. Acetylcholine, 10%, was electrophoresed for 5 mA-minutes in the forearm and 10 mA-minutes in the foot, and recording was continued for an additional 5 minutes. The mean sweat output in males was 2.7 and 3.0 times that in females in forearm and foot, respectively (p less than 0.0001). Studies in selected autonomic neuropathies confirm that quantitative sudomotor axon reflex tests will detect postganglionic sudomotor abnormalities sensitively and reproducibly.

Acetylcholine↗

Retinitis pigmentosa, ataxia, and peripheral neuropathy.

The clinical features of four patients with retinitis pigmentosa, ataxia and peripheral neuropathy but with no increase in serum phytanic acid are reported. Three patients also had sensorineural deafness and radiological evidence of cerebellar atrophy. Nerve conduction studies revealed abnormalities of sensory conduction and normal or only mild slowing of motor conduction velocity. Sural nerve biopsy demonstrated a reduction in the density of myelinated fibres. There were no onion bulb formations. These cases clinically resemble Refsum's disease, but differ in having no detectable biochemical abnormality, and a peripheral neuropathy which is not hypertrophic in type. They may represent unusual cases of spinocerebellar degeneration.

Adult↗

Familial spastic paraplegia with Kallmann's syndrome.

A sibship is reported in which two males have spastic paraparesis and Kallmann's syndrome (hypogonadotrophic hypogonadism and anosmia). One of the brothers also is color blind. The association of familial spastic paraplegia and Kallmann's syndrome has not been described previously.

Adult↗

Evaluation of skin vasomotor reflexes by using laser Doppler velocimetry.

We used a laser Doppler velocimeter for measurement of skin blood flow in 63 healthy control subjects and in patients with dysautonomias. We measured vasoconstrictor responses to inspiratory gasp, standing, Valsalva maneuver, and cold stimulus. An abnormal profile was defined in terms of the percentage of abnormal test results, the results of individual tests, and the alterations in the shape of the recorded response. These measurements of vasomotor function may permit the diagnosis of focal abnormalities of peripheral nerve sympathetic failure.

Adolescent↗

F-wave in experimental allergic neuritis.

The conduction velocity of volleys in motor fibres causing F waves, in addition to distal latency and to maximal motor conduction velocity of volleys in fibres causing the M response, were measured in the hindlimbs of control guinea pigs and rabbits and in those with experimental allergic neuritis (EAN). The spinal roots and sciatic nerves were examined histologically in the animals with EAN. The conduction time to the F wave was abnormal in the presence of normal maximal conduction velocity in fibres causing the M waves in 14% of the guinea pigs and 7% of the rabbits. However, conduction time to the F wave was prolonged in the presence of normal maximal motor conduction velocity in one case where no pathological abnormalities were found in the ventral roots and in some instances, F wave conduction time was within the normal range when ventral root and peripheral nerve demyelination was present. These findings highlight some of the problems in interpretation of F wave studies in man.

Animals↗

Autonomic neuropathy in experimental allergic neuritis: an electrophysiological and histological study.

Electrophysiological and histological studies have been performed on the vagus and splanchnic nerves of guinea pigs with experimental allergic neuritis. Slowing of conduction and dispersion of the compound action potential were consistent with the pathological changes of demyelination. In teased single fibre preparations, axonal degeneration was found more frequently than was expected and in the splanchnic nerves, the unmyelinated fibres appeared to have been indirectly involved. These findings in experimental allergic neuritis are relevant to the pathogenesis of autonomic dysfunction in the Landry-Guillain-Barré syndrome.

Animals↗

Autonomic dysfunction in Guillain-Barré syndrome.

The following tests of autonomic function were performed on seven patients with the Guillain-Barré syndrome and compared with controls: (1) measurement of heart rate and blood pressure in the supine and erect positions, (2) measurement of baroreflex sensitivity, (3) Valsalva's manoeuvre, (4) sweat test. In two patients the heart rates were fixed and greater than 100/min and in three there was postural hypotension. The baroflex sensitivity of four patients was abnormal and heart rate response to Valsalva's manoeuvre was impaired in two of the three patients who were able to perform the manoeuvre. Areas of anhidrosis were found in all seven patients. These abnormalities probably reflect pathological alterations of the sympathetic and parasympathetic components of the autonomic nervous system of patients with Guillain-Barré syndrome. The severity of autonomic involvement is not related to the degree of sensory and motor disturbance which is consistent with the patchy distribution of lesions throughout the peripheral and autonomic nervous systems.

Adult↗

Autonomic dysfunction in the Landry-Guillain-Barre syndrome.

Tests of autonomic function have been performed on 7 patients with the Landry-Guillain-Barre syndrome and 5 control subjects. These included a sweat test, and measurement of both postural hypotension and baroreflex sensitivity. Sweating was definitely abnormal in 5 patients. Postural hypotension was present in 4 patients. The baroreflex sensitivity was significantly reduced (p less than 0.01) in the patients when compared with the control group. The results demonstrate that both the sympathetic and parasympathetic nervous systems may be affected in the Landry-Guillain-Barre syndrome.

Adult↗