Search PubMed⌕ Search

Biomedical subjects

C J Mathias

Publications and source records attributed to C J Mathias.

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

The prevalence and association of neck (coat-hanger) pain and orthostatic (postural) hypotension in human spinal cord injury.

OBJECTIVE: To investigate the prevalence of orthostatic (postural) hypotension (OH) and neck pain in a 'coat-hanger' occipito-cervical distribution in subjects with spinal cord injury (SCI), and their association. METHOD: Blood pressure was measured during head-up tilt to 60 degrees (to determine OH) and neck pain was assessed in 28 subjects with SCI (cervical, thoracic and lumbar level) with McGill Pain Questionnaire, visual analogue scale for pain intensity and Orthostatic Intolerance Symptoms Questionnaire for pain frequency. RESULTS: Neck pain was reported by 53.6% of subjects. Orthostatic hypotension was present in 57.1% of subjects. Neck pain was reported by 75% of subjects with OH and 25% of subjects without OH (P<0.03, Chi-square). Features of such pain included positive correlation to upright posture and exercise, and relief when lying flat. CONCLUSION: There is a high prevalence of neck pain and OH in SCI, with a positive association similar to that reported in primary autonomic failure with OH.

Adolescent↗
PubMed2002

Organisation of the sympathetic skin response in spinal cord injury.

OBJECTIVES: The sympathetic skin response (SSR) is a technique to assess the sympathetic cholinergic pathways, and it can be used to study the central sympathetic pathways in spinal cord injury (SCI). This study investigated the capacity of the isolated spinal cord to generate an SSR, and determined the relation between SSR, levels of spinal cord lesion, and supraspinal connections. METHODS: Palmar and plantar SSR to peripheral nerve electrical stimulation (median or supraorbital nerve above the lesion, and peroneal nerve below the lesion) were recorded in 29 patients with SCI at various neurological levels and in 10 healthy control subjects. RESULTS: In complete SCI at any neurological level, SSR was absent below the lesion. Palmar SSR to median nerve stimuli was absent in complete SCI with level of lesion above T6. Plantar SSR was absent in all patients with complete SCI at the cervical and thoracic level. In incomplete SCI, the occurrence of SSR was dependent on the preservation of supraspinal connections. For all stimulated nerves, there was no difference between recording from ipsilateral and contralateral limbs. CONCLUSIONS: No evidence was found to support the hypothesis that the spinal cord isolated from the brain stem could generate an SSR. The results indicate that supraspinal connections are necessary for the SSR, together with integrity of central sympathetic pathways of the upper thoracic segments for palmar SSR, and possibly all thoracic segments for plantar SSR.

Adult↗
PubMed2002

Cardiovascular autonomic function in systemic lupus erythematosus.

AIM: To determine whether cardiovascular autonomic function is impaired in systemic lupus erythematosus (SLE). METHODS: A case-control study of 23 patients with SLE was performed. Autonomic symptoms were assessed using a standard questionnaire. Cardiovascular autonomic function was measured using 10 non-invasive investigations. There were significant differences between patients and controls in three out of 24 parameters measured during the different tests (P < 0.002). These were reduction in systolic blood pressure at 5 min on head-up tilt, and heart rate responses to isometric exercise and cutaneous cold. Eleven out of 23 patients had an abnormal heart rate, blood pressure or Valsalva response (value below the age corrected 5th centile) while testing compared with six of the controls. Plasma adrenaline and noradrenaline levels were significantly lower in patients vs controls in both the supine (P < 0.05) and tilt position (P < 0.01). Twenty-one of the 23 patients had one or more symptoms that may be attributable to abnormalities in autonomic function. There was no significant association between the number of symptoms and presence of autonomic dysfunction. Cardiovascular autonomic impairment may be demonstrated in some patients with SLE. Symptoms attributable to autonomic dysfunction are common in SLE and autonomic assessment may be required.

Adult↗
PubMed2001

Observations on recurrent syncope and presyncope in 641 patients.

BACKGROUND: Syncope is a common disorder that is potentially disabling and affects both young and old. Once neurological, cardiological, and metabolic causes have been excluded, there remains a group in which diagnosis is unclear; some may have an autonomic basis. We therefore did a retrospective study on consecutive patients referred to our tertiary referral autonomic centres between 1992 and 1998 with recurrent syncope and presyncope, in whom non-autonomic causes, before referral, had been sought and excluded. The object was to find out whether autonomic investigation helped diagnosis. METHODS: Data from case notes and from the autonomic database on 641 patients were analysed. Syncopal patients with a known or provisional diagnosis of autonomic failure were excluded from analysis. The role of screening tests in establishing or excluding an autonomic cause was assessed. Response to additional autonomic tests (such as head-up tilt with or without venepuncture, and food challenge and exercise) was documented. Some patients underwent further testing if non-autonomic neurological, psychiatric, and other disorders were considered. FINDINGS: Screening autonomic function tests indicated orthostatic hypotension and confirmed chronic autonomic failure in 31 (4.8%) patients. Neurally mediated syncope was diagnosed in 279 (43.5%) on the basis of clinical features and autonomic testing. Most had vasovagal syncope (227 [35%]); other causes included carotid sinus hypersensitivity (37 [5.8%]), and a group of 15 (2.3%) were associated with rarer causes such as micturition and swallowing. Miscellaneous cardiovascular causes (systemic hypotension, arrhythmias), or drugs, contributed to syncope in 53 (8.3%). Non-autonomic neurological causes included vestibular dysfunction (32 [5%]) and epilepsy (11 [1.7%]). In 56 (8.7%) a psychiatric cause was thought to be contributory. In 179 (27.9%), syncope was of unknown cause. INTERPRETATION: In recurrent syncope and presyncope, when cardiac, neurological, and metabolic causes have been excluded, autonomic investigation can aid management by making, confirming, or excluding various factors or diagnoses.

Adolescent↗
PubMed2001

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Adolescent↗
PubMed2001

The metabolic, catecholamine and cardiovascular effects of exercise in human sympathetic denervation.

The cardiovascular and metabolic responses to supine leg exercise were measured in 9 healthy subjects (controls) and in 19 subjects with two primary forms of autonomic failure (11 with peripheral sympathetic denervation [pure autonomic failure; PAF], 8 with central sympathetic failure [multiple system atrophy; MSA]). With exercise, blood pressure increased in controls and fell markedly in subjects with PAF and MSA. Blood pressure returned to baseline in controls, but remained low in the PAF and MSA groups. With exercise, heart rate increased more in controls than the PAF and MSA groups. Resting plasma noradrenaline concentrations in controls and in subjects with MSA were similar, but were lower in subjects with PAF. With exercise, plasma noradrenaline concentrations increased in controls and were unchanged in subjects with PAF; there was no significant increase in the MSA group. Resting plasma lactate, pyruvate and lactate/pyruvate ratios were similar in all three groups. With exercise, lactate concentrations increased until 2 minutes post exercise in all groups. Pyruvate concentrations after 9 minutes' exercise were higher in controls than in the PAF group but were similar to the MSA group; thereafter, concentrations increased similarly in all groups. The lactate/pyruvate ratio increased until 2 minutes post exercise in all groups. Resting plasma free fatty acids, and beta-hydroxybutyrate were similar in all groups. Plasma glycerol concentrations in control and MSA subjects were similar; concentrations were lower in PAF subjects. With exercise, plasma free fatty acids and glycerol concentrations remained unchanged in all groups; beta-hydroxybutyrate concentrations decreased less in control subjects than in PAF and MSA subjects. In conclusion, there were similar concentrations of plasma free fatty acids, glycerol and beta-hydroxybutyrate in control, PAF and MSA subjects; this could indicate up-regulation of beta-receptors in AF, or that sympathetic activity plays a smaller role in lipolysis. Plasma lactate and pyruvate concentrations increased similarly in all groups, despite marked differences in BP; this suggested an impairment of production or clearance of lactate in AF. A role for lactate-induced vasodilatation, not compensated for by sympathetic vasoconstriction, remains speculative.

3-Hydroxybutyric Acid↗
PubMed2001

Cardiovascular and neurohormonal responses to i. v. l-arginine in two groups with primary autonomic failure.

Nitric oxide (NO) is synthesised from the amino-acid l-arginine by the enzyme nitric oxide synthetase (NOS) and modulates a wide variety of neural, cardiovascular and hormonal processes. Cardiovascular autonomic dysfunction and impaired neurohormonal secretion characterise patients with primary chronic autonomic failure (AF). To investigate the role of NO, we studied the cardiovascular and neurohormonal effects of intravenous (i. v.) l-arginine (0.5 g/kg) in 20 patients with AF: [10 with multiple system atrophy (MSA) and 10 patients with pure autonomic failure (PAF)] and compared them with age-matched healthy normal subjects. Basal mean arterial pressure (MAP) was higher in MSA and PAF than controls (p < 0.02). Following l-arginine, MAP fell in MSA (mean: -39 +/- 8 mmHg, 95 % CI -21 to -57, p < 0.05) and PAF (-37 +/- 5,95 % CI -26 to -58, p < 0.05) but not in controls. There were no significant changes in HR between the groups. Basal plasma noradrenaline (NA) was similar in controls and MSA, but lower in PAF (p < 0.05). Following l-arginine the percentage rise in plasma NA was similar in controls and MSA, but not in PAF (p < 0.05). Plasma insulin rose similarly in controls and MSA, but was higher in PAF (p < 0.05). Plasma glucose rose to a similar level in all groups. In conclusion, l-arginine, lowered BP in both MSA and PAF. In PAF a contributory factor may be increased insulin release, without a compensatory increase in sympatho-neural activity to counter its potential vasodilator effects. These studies suggest that reducing NO levels, as with NOS inhibitors, may be of benefit in the treatment of postural hypotension and possibly post-prandial hypotension in chronic primary AF.

Adult↗
PubMed2001

Neural activity in the human brain relating to uncertainty and arousal during anticipation.

We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.

Adult↗
PubMed2001

Characteristics of habituation of the sympathetic skin response to repeated electrical stimuli in man.

OBJECTIVES: To study the effect of repeating electrical peripheral nerve stimulation on latency, duration and amplitude of the sympathetic skin response (SSR). METHODS: SSRs were elicited in all limbs by median and peroneal nerves stimuli. In 10 subjects, 20 stimuli were applied at random time intervals (15-20 s). Another test was performed in 7 subjects using the same protocol, but switching the stimulation site every 5 or 10 stimuli without warning. RESULTS: The mean amplitude of right palmar response to right peroneal nerve stimulation decreased from 5.05+/-0.76 (SEM) mV at the first stimulus to 1.23+/-0.42 mV at the 20th stimulus (P<0.001). The latency did not change significantly (1473+/-82 to 1550+/-90 ms, P>0.1), while the duration increased (1872+/-356 to 3170+/-681 ms, P<0.001). Stimulation and recording at other sites showed similar trends. Changing the stimulation site failed to alter the adaptation process in terms of amplitude, latency or duration. CONCLUSIONS: Changes in amplitude and duration of the SSRs to repeated electrical stimuli can occur in presence of constant latency and appear to be independent of the source of sensory input. Peripheral sweat gland mechanisms may be involved in the loss of amplitude and increase in duration of the SSR during habituation.

Adult↗
PubMed2001

Neuroanatomical basis for first- and second-order representations of bodily states.

Changes in bodily states, particularly those mediated by the autonomic nervous system, are crucial to ongoing emotional experience. A theoretical model proposes a first-order autoregulatory representation of bodily state at the level of dorsal pons, and a second-order experience-dependent re-mapping of changes in bodily state within structures such as cingulate and medial parietal cortices. We tested these anatomical predictions using positron emission tomography and a human neurological model (pure autonomic failure), in which peripheral autonomic denervation prevents the emergence of autonomic responses. Compared to controls, we observed task-independent differences in activity of dorsal pons and context-induced differences in cingulate and medial parietal activity in PAF patients. An absence of afferent feedback concerning autonomically generated bodily states was associated with subtle impairments of emotional responses in PAF patients. Our findings provide empirical support for a theory proposing a hierarchical representation of bodily states.

Aged↗
PubMed2001

Age- and gender-related growth hormone responses to intravenous clonidine in healthy adults.

The alpha(2)-adrenoceptor agonist clonidine stimulates growth hormone (GH) release in both animals and humans. It has been used to test for GH deficiency in children, to assess central alpha(2)-adrenoceptor function in adults and to determine the pathophysiological basis and to confirm diagnosis in neurological diseases with autonomic failure. The dose and mode of administration, however, may be important, as in some studies in adults oral clonidine has minimal effects on GH. We report our experience following intravenous (i.v.) clonidine (2 microg/kg) in 98 normal adults on the neuroendocrine (GH, insulin, glucose and catecholamine) and cardiovascular (blood pressure) responses. In males between 25 and 89 years and females between 25 and 64 years there was a significant rise in GH secretion (P < 0.05) after clonidine. Males showed an age-sensitive secretory pattern, with the greatest response between 25 and 35 years (P < 0.02). Younger males (< 45 years) had significantly higher peak GH levels post-clonidine than younger females < 45 years (P < 0.03). No sex-related change was observed in older subjects (< 45 years). Clonidine caused a significant fall in plasma noradrenalin and adrenalin in all age-sex groups (P< 0.001). There were no significant changes in glucose or insulin. There were no effects of age on the fall in blood pressure induced by clonidine. In conclusion, i.v. clonidine stimulated GH in all age groups and there was a marked sexually dimorphic pattern in adults < 45 years. The results overall suggest that i.v. clonidine-GH testing provides a reliable method for investigation of central alpha(2)-adrenergic function in adult humans.

Adrenergic alpha-Agonists↗
PubMed2001

Brain activity during biofeedback relaxation: a functional neuroimaging investigation.

The mechanisms by which cognitive processes influence states of bodily arousal are important for understanding the pathogenesis and maintenance of stress-related morbidity. We used PET to investigate cerebral activity relating to the cognitively driven modulation of sympathetic activity. Subjects were trained to perform a biofeedback relaxation exercise that reflected electrodermal activity and were subsequently scanned performing repetitions of four tasks: biofeedback relaxation, relaxation without biofeedback and two corresponding control conditions in which the subjects were instructed not to relax. Relaxation was associated with significant increases in left anterior cingulate and globus pallidus activity, whereas no significant increases in activity were associated with biofeedback compared with random feedback. The interaction between biofeedback and relaxation, highlighting activity unique to biofeedback relaxation, was associated with enhanced anterior cingulate and cerebellar vermal activity. These data implicate the anterior cingulate cortex in the intentional modulation of bodily arousal and suggest a functional neuroanatomy of how cognitive states are integrated with bodily responses. The findings have potential implications for a mechanistic account of how therapeutic interventions, such as relaxation training in stress-related disorders, mediate their effects.

Adult↗
PubMed2001

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension.

OBJECTIVES: To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy. METHODS: Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital. RESULTS: Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication. CONCLUSIONS: Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.

Aged↗
PubMed2001

A novel TRK A (NTRK1) mutation associated with hereditary sensory and autonomic neuropathy type V.

A boy with recurrent pyrexial episodes from early life sustained a painless ankle injury and was found to have a calcaneus fracture and, later, neuropathic joint degeneration of the tarsus. Examination revealed distal loss of pain and temperature sensation and widespread anhidrosis. Sural nerve biopsy demonstrated severe reduction in small-caliber myelinated fiber density but only modest reduction in unmyelinated axons, the pattern of type V hereditary sensory and autonomic neuropathy (HSAN V). DNA analysis showed that he was homozygous for a mutation in the NTRK1/high-affinity nerve growth factor (TrkA) gene, his parents being heterozygous. Mutations in this gene are known to be responsible for HSAN IV (congenital insensitivity to pain with anhidrosis). The two disorders are therefore likely to be allelic.

Biopsy↗
PubMed2001

Haemodynamics of the pressor effect of oral water in human sympathetic denervation due to autonomic failure.

Oral water ingestion increases blood pressure in normal elderly subjects and in patients suffering from autonomic failure, but the time course of the haemodynamic changes is not known. We therefore studied 14 subjects with documented sympathetic denervation due to pure autonomic failure, with continuous haemodynamic recordings obtained before and after ingestion of 500 ml of distilled water at room temperature. The time course of changes in values of systolic and diastolic beat-by-beat finger blood pressure, heart rate, stroke volume, cardiac output, ejection fraction and total peripheral resistance were analysed. Systolic blood pressure rose from 115+/-8 mmHg (mean+/-S.E.M.) to 133+/-8 mmHg (P<0.001), and diastolic blood pressure from 64+/-4 to 73+/-4 mmHg (P<0.001), with the pressor response beginning a few minutes after water ingestion, plateauing between 10 and 35 min (peak at 14 min), and returning to baseline at 50 min. Heart rate fell from 71+/-2.5 to 67+/-2 beats/min (P<0.001), and total peripheral resistance increased from 1.31+/-0.19 to 1.61+/-0.24 m-units (P<0.001). There were no significant changes in ejection fraction, stroke volume or cardiac output. This study confirmed a pressor response to oral water in subjects with sympathetic denervation. The temporal profile of the response did not favour reflexly mediated sympathetic activation. As subjects with autonomic failure are prone to salt and water depletion, and since blood pressure is exquisitely sensitive to such changes, it may be that the observed response is due to repletion or restoration of intravascular and extravascular fluid volume.

Adult↗
PubMed2000

Neural activity relating to generation and representation of galvanic skin conductance responses: a functional magnetic resonance imaging study.

Central feedback of peripheral states of arousal influences motivational behavior and decision making. The sympathetic skin conductance response (SCR) is one index of autonomic arousal. The precise functional neuroanatomy underlying generation and representation of SCR during motivational behavior is undetermined, although it is impaired by discrete brain lesions to ventromedial prefrontal cortex, anterior cingulate, and parietal lobe. We used functional magnetic resonance imaging to study brain activity associated with spontaneous fluctuations in amplitude of SCR, and activity corresponding to generation and afferent representation of discrete SCR events. Regions that covaried with increased SCR included right orbitofrontal cortex, right anterior insula, left lingual gyrus, right fusiform gyrus, and left cerebellum. At a less stringent level of significance, predicted areas in bilateral medial prefrontal cortex and right inferior parietal lobule covaried with SCR. Generation of discrete SCR events was associated with significant activity in left medial prefrontal cortex, bilateral extrastriate visual cortices, and cerebellum. Activity in right medial prefrontal cortex related to afferent representation of SCR events. Activity in bilateral medial prefrontal lobe, right orbitofrontal cortex, and bilateral extrastriate visual cortices was common to both generation and afferent representation of discrete SCR events identified in a conjunction analysis. Our results suggest that areas implicated in emotion and attention are differentially involved in generation and representation of peripheral SCR responses. We propose that this functional arrangement enables integration of adaptive bodily responses with ongoing emotional and attentional states of the organism.

Adult↗