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Biomedical subjects

J Rothwell

Publications and source records attributed to J Rothwell.

At least 37 records · Page 2Linked to original sources
PubMed1996

Clinical and physiological features of epilepsia partialis continua. Cases ascertained in the UK.

Epilepsia partialis continua (EPC) is defined clinically as a syndrome of continuous focal jerking of a body part, usually localized to a distal limb, occurring over hours, days or even years. The anatomical and physiological origin of EPC has been the subject of much speculation. It has been argued that EPC is a form of focal cortical myoclonus, but subcortical mechanisms have also been proposed. We describe a series of 36 patients ascertained over a period of 1 year in the UK using the British Neurological Surveillance Unit. The commonest aetiologies identified were Rasmussen's syndrome (n = 7; 19%) and cerebrovascular disease (n = 5; 14%). Rasmussen's syndrome was the most common diagnosis in patients under 16 years. In seven patients the cause remained unknown. Eight patients (22%) had focal epileptiform scalp EEG abnormalities, and 56% had generalized background scalp EEG disturbances. Lesions on MRI or CT were found in 20 cases (56%), half of whom showed predominant cortical involvement. The muscle jerking resolved in four patients (with no treatment in one), with a partial response to treatment in seven (19%) patients. A cognitive or neurological decline had been noted retrospectively in 13 (36%) patients (and in all of the patients with Rasmussen's syndrome). We personally saw 16 patients who underwent detailed clinical and neurophysiological assessments. Only six of the patients had EEG and EMG evidence for a cortical origin of their jerks; five others had indirect evidence for a cortical origin, from EMG, magnetic stimulation, and other investigations. Two patients did not have myoclonus of cortical origin, but some other source (brainstem and basal ganglia). The origin in the remaining three patients was uncertain. The clinical appearance of the muscle jerks was similar in all patients despite the different origins. We propose that the definition of EPC is best restricted to "continuous muscle jerks of cortical origin'. Continuous muscle jerking that arises from other sites in the nervous system should be termed "myoclonia continua'.

Adolescent↗
PubMed1995

Neck muscle responses to abrupt free fall of the head: comparison of normal with labyrinthine-defective human subjects.

1. EMG responses from sternocleidomastoid (SCM) and orbicularis oculi were recorded in subjects who lay supine with their heads cradled in a sling. When the sling released abruptly, their heads fell freely. Normal and bilateral labyrinthine-defective subjects (LDs) were studied. 2. The normal response in SCM was a small burst of excitation at 22-25 ms latency, of 18 ms duration. This merged into a larger, later burst. The drop also produced eye blinks at 22-38 ms. 3. The onset of the SCM response in LDs was delayed (56-73 ms) even though the latency of their eye blinks was normal. 4. We conclude that the early response at approximately 22 ms in normal subjects is mediated by a vestibulocollic reflex. The delayed activity in LDs may be a stretch reflex. This is the first demonstration of the latency of the vestibulocollic pathway to natural stimulation in man.

Acceleration↗
PubMed1995

Clinical and electrophysiological findings in the Tullio phenomenon.

A 55 year old female with idiopathic Tullio phenomenon is presented. Binocular, scleral search eye coil recordings demonstrated a predominantly torsional left-beating and vertical down-beating nystagmus in response to sound intensities over 100 dB HL to the left ear, increasing in amplitude and slow phase velocity with sound intensity and removal of visual fixation. The vertical ocular movement was conjugate, i.e. without skew deviation. Neuro-imaging, all other neuro-otological features, including ipsilateral-contralateral stapedius muscle reflexes, and surgical exploration of the middle ear, were normal. Click-evoked vestibulo-collic potentials were normal from the right ear but showed low threshold (70 dB) and increased amplitude from the left. There was no evidence that the Tullio phenomenon in this patient arises from stapes footplate hypermobility. The findings suggest that some cases of the Tullio phenomenon may be due to a hyperexcitability of the normal vestibular response to sound.

Acoustic Stimulation↗
PubMed1994

Transcranial electrical stimulation of the motor cortex in man: further evidence for the site of activation.

1. The motor cortex was stimulated electrically (vertex anode; cathode 6 cm lateral) in neurologically normal subjects undergoing surgery for scoliosis, and the evoked corticospinal volleys were recorded from the spinal cord using epidural electrodes. 2. Stimuli > 330 V produced a complex D-wave volley containing three separate peaks, with high-threshold components, 0.8 ms (D2) and 1.6 ms (D3), in advance of the lowest-threshold component (D1). As stimuli increased up to 1500 V, D3 replaced the later components completely, but there was no further latency 'jump'. 3. Brainstem stimulation using electrodes over each mastoid process produced a descending volley that had the same latencies as D3. At threshold, stimulation of the brainstem or spinal cord attenuated the D wave evoked by simultaneous cortical stimulation. 4. It is concluded that transcranial electrical stimulation of the motor cortex at high intensities can access corticospinal neurones at the pyramidal decussation, and that stimulation of the brainstem (and the spinal cord) preferentially accesses corticospinal axons. At threshold, motor cortex stimulation probably activates corticospinal neurones at or near the cerebral cortex.

Adolescent↗
PubMed1994

The time constants of motor and sensory peripheral nerve fibers measured with the method of latent addition.

The time constants of motor and sensory fibers in the human ulnar, median and tibial nerves were determined using the method of latent addition. Two square-wave stimuli were applied: the first one was subthreshold and the second, at various delays relative to the first, was adjusted to achieve threshold activation. Strength-delay curves were obtained, from which the time constant was determined using a mathematical model. Sensory fibers had time constants that were about 3 times the time constant for motor fibers. The strength-delay curves gave similar time constants as those obtained from strength-duration curves.

Adolescent↗
PubMed1993

Effect of oral cyclosporin on renal function in Crohn's disease.

Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0, 6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m2; at six weeks: 100.9 ml/min/1.73 m2; mean ERPF at baseline: 497.3 ml/min/1.73 m2; at six weeks: 398.5 ml/min/1.73 m2). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m2), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m2). Serum creatinine rose significantly (median pretreatment 72 mumol/liter; median at four weeks 86 mumol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction.

Administration, Oral↗
PubMed1993

Carriage of adhesive Escherichia coli after restorative proctocolectomy and pouch anal anastomosis: relation with functional outcome and inflammation.

Restorative proctocolectomy with pelvic ileal reservoir is a well accepted option for the surgical treatment of ulcerative colitis. Acute pouchitis is a common complication and resembles acute ulcerative colitis. Patients with ulcerative colitis carry Escherichia coli that adhere to epithelial cells and thus this study examined whether acute pouchitis is associated with the carriage of adhesive E coli. E coli isolated from stool samples from 24 patients (median age 34 years, range 16-64; 13 men, 11 women) who had had restorative proctocolectomy with pelvic ileal reservoir were examined by means of the buccal epithelial cell adhesion assay. Patients were studied at a median of 12 months (range 7-21) after operation. Eight of 24 patients had acute pouchitis at the time of study. Adhesive E coli were detected in nine of 24 patients with a pelvic ileal reservoir compared with none of 12 controls (p < 0.05). The buccal epithelial cell adhesion index was inversely related to the degree of acute pouchitis (rs = 0.46, p = 0.024) and to the functional outcome (rs = -0.49, p = 0.022). Carriage of adhesive E coli was not related to the design of the reservoir. By contrast with ulcerative colitis, acute pouchitis is not associated with the carriage of adhesive E coli.

Adolescent↗
PubMed1991

Long-term treatment of Crohn's disease with cyclosporine: the effect of a very low dose on maintenance of remission.

Low-dose oral cyclosporine was used to maintain remission in patients with Crohn's disease. In seven patients, cyclosporine was used as a steroid-sparing agent; in 14 it was given for refractory active disease as an adjunct to conventional treatment, and then continued as maintenance treatment. Cyclosporine was given at an initial dose of 5 mg/kg reduced by 1 mg/kg at 2-month intervals until a maintenance dose of 2 mg/kg was reached. Of the seven patients in whom cyclosporine was used as a steroid-sparing agent, six had a relapse. Remission was achieved in seven of the refractory active group, but cyclosporine was withdrawn because of side effects in six of the patients in this group. Of the seven patients who had achieved remission, six subsequently had a relapse. Therefore, 12 of 14 patients (86%) in remission had a relapse despite cyclosporine maintenance. Ten of these (83%) had a relapse at a cyclosporine dose of 2 or 3 mg/kg. Cyclosporine levels at relapse (median, 74 ng/ml) were lower than the mean levels over the first 6 weeks of treatment (median, 130 ng/ml; p = 0.02). Our data do not support the use of cyclosporine to maintain remission in Crohn's disease.

Administration, Oral↗
PubMed1991

Physiological analysis of simple rapid movements in patients with cerebellar deficits.

Patients with cerebellar deficits made elbow flexion movements as rapidly as possible for three different angular distances. Electromyographic activity of biceps and triceps and the kinematics of the movements were analysed. Results were compared with those of normal subjects making both rapid and slow movements. In the patients, the first agonist burst of the biceps was frequently prolonged regardless of the distance or speed of the movement. The most striking kinematic abnormality was prolonged acceleration time. The pattern of acceleration time exceeding deceleration time was common in patients but uncommon in normal subjects. The best kinematic correlate of the duration of the first agonist burst was acceleration time. Altered production of appropriate acceleration may therefore be an important abnormality in cerebellar dysfunction for attempted rapid voluntary movements.

Adolescent↗
PubMed1990

Resuscitation skills among the general public in Dublin.

Evidence exists that many of the victims of cardiac arrest due to ischemic heart disease can be resuscitated if cardiopulmonary resuscitation (CPR) and defibrillation are made available in the minutes following collapse. In order to evaluate the ability of the general public in Dublin to perform CPR appropriately, 225 people were asked when CPR was indicated and how cardiac arrest was diagnosed and then asked to perform CPR on a mannequin. In the knowledge sections, 45% gave an appropriate indication for CPR and 34% gave appropriate criteria for diagnosing cardiac arrest. However, only eight participants were able to perform CPR correctly and only six (2.6%) had both the correct skills and knowledge. There is an urgent need to improve the public's knowledge of and ability to perform CPR as part of an overall strategy to decrease mortality from ischemic heart disease in Ireland.

Educational Status↗
PubMed1989

Lactulose/mannitol test: an ideal screen for celiac disease.

A lactulose/mannitol (La/Ma) test was compared with a standard cellobiose/mannitol test (Ce/Ma) in 17 patients with newly diagnosed celiac disease and 12 healthy controls. The mean La/Ma test was 0.163 (SEM 0.076) in celiacs and 0.016 (SEM 0.002) in controls. The mean Ce/Ma test was 0.132 (SEM 0.024) in celiacs and 0.014 (SEM 0.002) in controls (p less than 0.001). There is no significant difference between the new La/Ma test and the Ce/Ma test. Eighty-two patients referred to a general gastroenterology clinic with symptoms or signs of celiac disease performed a La/Ma test. A jejunal biopsy was indicated in 44 of these. In this selected group the sensitivity was 89%, specificity 54%, and negative predictive value of 95%. The La/Ma test fulfills the criteria of a screening test; it is sensitive, of low cost, and simple to perform, and it has the advantage of a simple enzyme assay and does not cause diarrhea in patients with hypolactasia. It can, therefore, be used in screening large patient populations.

Adolescent↗
PubMed1989

Cellobiose/mannitol sugar test--a sensitive tubeless test for coeliac disease: results on 1010 unselected patients.

The cellobiose/mannitol (Ce/Ma) test is a non-invasive technique for investigating intestinal permeability. In coeliac disease there is a decreased absorption of small molecules and paradoxically increased absorption of large molecules. The simultaneous administration of cellobiose and mannitol as two probe molecules allows the permeability of the small bowel mucosa to be studied, eliminating extraneous factors such as gastric emptying, and incomplete urine collection. One thousand and ten patients presenting to a gastroenterology clinic with symptoms, signs, or biochemical indices compatible with coeliac disease had a Ce/Ma test. Eight hundred and seventeen had a normal test and of these 197 had a jejunal biopsy showing 148 normal mucosa, two coeliac disease, 43 non-specific abnormalities, four giardiasis. One hundred and ninety three had an abnormal test; of these 132 had a jejunal biopsy showing 62 normal mucosa, 48 coeliac disease, and 22 other abnormalities. Considering those who had jejunal biopsies, the sensitivity of the test for coeliac disease is 96%, specificity 70%, the predictive value of the positive 36%, and predictive value of the negative 99%. Eleven per cent of the patients with a 'false positive' test had abnormalities in the jejunal biopsy or a diagnosis which could explain the abnormal permeability.

Celiac Disease↗
PubMed1987

Permeability of the rat small intestine to carbohydrate probe molecules.

1. Absorption of carbohydrate probe molecules from ligated loops of rat small intestine was studied. Absorption was determined by measuring recovery of molecules in the urine, corrected for incomplete recovery after intravenous injection, and was examined for correlation with several parameters of molecular dimension. 2. Absorption depended on molecular volume rather than relative molecular mass, molecular radius or molecular area. 3. Molecules with a molecular volume below 225 X 10(-3) nm3 were absorbed to a greater extent than larger molecules, and absorption was affected critically by molecular volume, small changes in volume producing considerable variation in absorption. 4. Absorption of larger molecules was not affected by changes in volume within the range 362 X 10(-3)-1128 X 10(-3) nm3. 5. These findings support the concept that there are at least two aqueous diffusion pathways across the intestinal mucosa. small molecules diffusing through a small channel of finite dimension, compatible with a transcellular aqueous pore, whilst large molecules diffuse through a less frequent pathway of considerably larger dimensions.

Animals↗
PubMed1986

p,p'-DDT-induced myoclonus in the rat and its application as an animal model of 5-HT-sensitive action myoclonus.

p,p'-DDT-induced myoclonus in mice has been proposed as a model of stimulus-sensitive action myoclonus responsive to L-5-HTP and clonazepam treatment. However, we have been unable to confirm the ability of clonazepam to reduce myoclonus induced by p,p'-DDT in the rat. A detailed pharmacological, biochemical, and physiological investigation in the latter species shows p,p'-DDT-induced myoclonus not to resemble stimulus-sensitive action myoclonus occurring in humans. Precursors of 5-HT (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists quipazine and Org 6582 did not. 5-HT antagonists (methergoline, methysergide, and cinanserin) did not potentiate myoclonus induced by p,p'-DDT. In contrast, administration of MAOIs (pargyline, nialamide, and tranylcypromine) markedly attenuated the myoclonus. No observable changes in cerebral 5-HT biochemical parameters occurred at the onset of myoclonus, although brain tryptophan and 5-HIAA were increased following periods of prolonged myoclonus. Electrophysiological analysis of p,p'-DDT-induced myoclonus in the rat revealed changes in EEG and EMG activity that were different from those observed in human reticular reflex myoclonus. In conclusion, in contrast to the mouse, myoclonus induced by p,p'-DDT in the rat does not appear to be a suitable model of 5-HT-sensitive action myoclonus in man.

5-Hydroxytryptophan↗
PubMed1986

Urea-induced stimulus-sensitive myoclonus in the rat.

Uremia in humans can cause spontaneous and stimulus-sensitive myoclonus that responds to clonazepam. Uremic myoclonus in humans resembles the reticular reflex form of postanoxic action myoclonus. Previous investigations have established that urea infusions in the cat can produce spontaneous and stimulus-sensitive myoclonus. This has been shown, electrophysiologically, to arise in the brainstem medullary reticular formation, and it does not require forebrain structures. Our own studies in the rat have shown that urea infusions also produce spontaneous and stimulus-sensitive myoclonus. Electrophysiologically, this resembles human reticular reflex myoclonus. It can be reduced by clonazepam. The myoclonus produced by urea infusions in the rat progresses very rapidly into uncontrollable tonic-clonic convulsions. Although the urea model in the rat mimics some forms of human myoclonus that arise in the brainstem, it is not suitable as a routine animal model for pharmacological investigations.

Animals↗
PubMed1985

Cellobiose/mannitol test: physiological properties of probe molecules and influence of extraneous factors.

The influence of gastric emptying, intestinal transit, renal and hepatic function, and variations in the timing of urine collections, on the cellobiose/mannitol test of intestinal permeability has been studied. None of these extraneous factors influences the cellobiose/mannitol recovery ratio, and there is only a modest effect of renal function on urinary mannitol recovery. Cellobiose is almost totally recovered in the urine within 10 h of intravenous injection, whilst mannitol is less completely recovered, perhaps due to hepatic metabolism. The simultaneous administration of two probe molecules in the cellobiose/mannitol test, and the use of a ratio to express results, thus achieves the desired object of minimising the effect of extraneous factors on the test result. The cellobiose/mannitol test is therefore not subject to the limitations of previous tests of intestinal permeability using orally administered probe molecules, and is widely applicable as a screening test for coeliac disease.

Celiac Disease↗