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Concentrated organic residues extracted from 5 blended aliquots of commercial beers were evaluated for their ability to induce sister chromatid exchange (SCE), chromosomal aberrations and forward mutation in Chinese hamster ovary (CHO) cells. Each extract was prepared by blending 4 commercial beers of similar ingredients and brewing method, passing the beer pool over XAD-2 resin, extracting the resin and concentrating the extract. Studies were performed both with and without metabolic activation using variable amounts of reconstituted residues from 225-fold concentrates of the blended samples. CHO cultures were treated with 0.75 microliters/ml through 10.0 microliters/ml of the concentrates in the SCE assays, 1.0 microliters/ml through 10.0 microliters/ml of the extracts in the aberration assays and 2.5 microliters/ml up to 20 microliters/ml for forward mutation assays. In preliminary screening for SCE as an indicator of potential DNA damage, a significant increase was observed for 3 of 5 concentrated samples; however, no increase in SCE was induced by any of the 5 samples when S9 was added as a source of exogenous metabolic activation. More definitive tests for induction of genetic events, i.e., chromosome aberrations and forward HGPRT mutations, were negative for all 5 extracts whether or not S9 mix was present. Since SCE were not induced in tests with metabolic activation and since there was no concordant aberration or point mutation induction, the preliminary indication of potential DNA damage shown by elevated SCE under conditions without metabolic activation appears to have little biological significance.

Perfluoro-n-decanoic acid (PFDA) is a perfluorinated fatty acid that produces hepatomegaly and increased peroxisomal beta-oxidation when administered to rodents. Chlorotrifluoroethylene (CTFE) trimer acid and CTFE tetramer acid are metabolites of the six- and eight-carbon oligomers of CTFE, respectively. They are structurally related to PFDA, and CTFE tetramer acid has caused toxic effects in rodents that are similar to those observed following PFDA administration. Because of the correlation between peroxisome proliferation and hepatocarcinogenesis, CTFE trimer acid, CTFE tetramer acid, and PFDA were evaluated in in vitro and in vivo/in vitro bioassays to assess their potential genotoxic activity. The assays conducted were the Ames Salmonella/microsomal mutagenicity assay, the hypoxanthineguanine phosphoribosyltransferase (HGPRT) locus Chinese hamster ovary gene mutation assay, the sister chromatid exchange (SCE) assay, chromosomal aberration assay, and an in vivo/in vitro unscheduled DNA synthesis (UDS) and S-phase DNA synthesis assay. All test articles were negative in the Ames assay, the HGPRT assay, and the SCE assay. In the chromosomal aberration assay CTFE trimer acid and CTFE tetramer acid were negative in cultures with and without S9 metabolic activation. PFDA was also negative in the absence of metabolic activation, but chromosomal aberrations were observed when PFDA was incubated in the presence of S9 fraction. All test articles were negative for inducing UDS but all induced S-phase replicative DNA synthesis 16 hr after administration of the test article to the test animals; only CTFE tetramer acid and PFDA induced S-phase synthesis 48 hr after dosing: the usual timepoint examined for this response.

We established the occurrence of headache in a group of 20 patients with traumatic transections of the cervical spinal cord. All but two patients had complete sensory lesions at levels varying from C2-3 to C7-8. Only three patients claimed to have no headaches at all although one of them had nuchal pains with fever. Twelve patients had "bladder" or "bowel headaches" or had had them in the past. These headaches were mostly generalized, throbbing or pounding in nature and severe in intensity. They were caused by obstruction of urinary flow and fecal impaction, respectively, and were associated with autonomic dysreflexia. Otherwise the headaches reported by the patients were mild although frequent in four, i.e once per week or more. These headaches were also mostly bilateral and lasted a relatively short time, i.e. less than one or two hours. The causes of these headaches were nonspecific for the group studied except for stimulation of the body which, however, probably depended on a mechanism similar to that of the bladder and bowel headaches. Migraine, either classic or common, was not reported by any of the patients.

Disease of the spinal cord or cauda equina may cause pain, motor abnormalities, sensory disturbance, alteration of reflexes and muscle tone, and bladder dysfunction. These five neurologic abnormalities occur in various combinations, evolve rapidly or slowly, and result in one of eight possible spinal cord syndromes. When a particular syndrome is defined by neurologic history and examination, differential diagnosis is limited to only a few possible disorders. An appropriate neuroradiologic or electrophysiologic procedure done at this point will usually provide the correct diagnosis.

Fast isometric elbow flexor muscle contractions of specified amplitude in six normal subjects were compared with those of 11 patients with Parkinson's disease. Despite treatment, all patients exhibited deficits in this motor task. Three patients were able to produce rapid force pulses with normal contraction times, but the variability of their force responses was increased in comparison with the highly stereotyped responses produced by normal subjects. The other eight patients had prolonged contraction times and segmentation of the force profiles. The integrated area of the first agonist EMG burst and the rate of development of force (dF/dt) were less at any target level than what was needed to produce a fast response. The area of the EMG burst, however, did increase with target amplitude, and the relative increase of dF/dt, with target amplitude, was normal. It is concluded that the motor program subserving fast muscle contraction is preserved in Parkinson's disease, but its execution is characterised by improper scaling of motor output.

Motor points (areas of maximal sensitivity to electrical stimulation) were found in constant locations over orbicularis oculi when measured in both eyes of six normal subjects. All subjects had a motor point at the lateral terminus of the upper lid crease and the medial extent of the lower lid crease. A study of the innervation zone [distribution of neuromuscular junctions (NMJ)] was conducted on strips of pretarsal and preseptal portions of the upper eyelid orbicularis that had been removed routinely during involutional ptosis surgery. There was no significant difference in NMJ concentration between the medial and lateral sections, as determined by cholinesterase staining. Therefore, we concluded that the innervation zone is diffuse for the orbicularis muscle within this portion of the upper eyelid. Single-point injections of botulinum toxin were then compared to the conventional multiple injection sites on separate eyes in 10 patients with benign essential blepharospasm. Eight of the 10 patients reported greater relief on the side given injections into multiple points; the other two patients experienced no difference between the two methods. Both histologic data and clinical observation of response to botulinum toxin injection suggest the innervation zone for the upper orbicularis is diffuse. Thus, we conclude that multiple injections are superior to the injection of a single motor point.

A study of 10 patients with brachial plexus trauma was performed to determine whether the diagnostic accuracy of sensory evoked potentials (SEPs) may be improved by using stimulation of multiple peripheral nerves (median, radial, musculocutaneous and ulnar). In addition, the relative advantages of SEPs and peripheral electrophysiological studies were considered. SEP patterns following most common brachial plexus lesions were predictable. Injuries to the upper trunk affected the musculocutaneous and radial SEPs predominantly. Lower trunk or medial cord lesions primarily affected ulnar SEPs. Diffuse brachial plexus lesions affected SEPs from all stimulation sites. In the majority of cases, the necessary information was obtainable from conventional EMG: however, for lesions involving the upper segments only, SEP techniques were more useful. It is suggested that selective SEPs from appropriate peripheral nerves when interpreted in combination with conventional EMG may add useful additional information.

Physiologic evidence of peripheral neuropathy has been described previously in children undergoing hemodialysis. In order to detect early or subclinical evidence of peripheral neuropathy, several newer electrophysiologic techniques, including latencies of late responses (H reflex and F response) and sural nerve sensory studies, were evaluated in addition to routine motor and sensory conduction in 17 randomly selected children (mean age 14.2 years) undergoing hemodialysis (12 of whom had no clinical evidence of peripheral neuropathy) and 20 age-matched normal control subjects. Conventional motor and sensory conduction studies of median and ulnar nerves and motor conduction of peroneal and tibial nerves showed abnormalities of motor conduction in 5 (29%) and abnormalities of sensory conduction in 2 (12%). Sural nerve sensory potentials were abnormal in 10 (59%) patients. Late response were significantly abnormal in 10 (59%) patients, 5 (29%) of whom had normal routine motor conduction studies in the same nerve distribution. The abnormalities of late responses and motor and sensory conduction were more evident in lower limbs. Studies of late responses and sural sensory conduction provide a method of detecting subclinical neuropathy in this patient population at a time when results of conventional motor and sensory conduction tests are within normal limits. Effects of dialysis may then be followed quantitatively in patients whose neuropathy would otherwise be undetectable.

EEG was monitored at bilateral scalp sites outside the operative field during hypotensive aneurysm surgery in 21 patients. Mean arterial blood pressure at axillary level was 50-60 mm Hg (average 55 mm) for 1.9-5.3 hours (average 3.6). Four new deficits were noted immediately post-operatively, all related to the operated site: these were attributable to intra-operative rupture with forced vascular clipping, vasospasm, or edema. In no instance was hypotension solely responsible for a new deficit. EEG showed persistent slowing in relation to surgery in only 1 patient, where aneurysmal rupture led to severe hypotension, forced clipping of 1 posterior cerebral artery, and subsequent brain stem infarction. In the 3 other patients with fresh focal postoperative deficits, no persistent intraoperative EEG changes were observed. EEG monitoring did not detect ischemia in these 3 patients because 1) hypotension was moderate and did not per se cause new deficit, and 2) EEG electrodes did not survey the area at maximal risk, namely the operative field. EEG scalp electrodes near but outside the operative site do not seem useful for monitoring cerebral function in the region of aneurysm surgery. Epidural or cortical electrodes in the operative field may prove to be more useful.

Synchronization between pairs of single motor units simultaneously recorded from wrist extensor muscles was quantitated in 3 normal subjects during physiologic tremor (PT), beta-adrenergically enhanced physiologic tremor (EPT), and fast voluntary wrist flexion-extension movements mimicking tremor (VT). Cross-correlation histograms generated from the two spike trains of each motor unit pair demonstrated central or paracentral peaks in 13/19 recordings during PT, 22/36 during EPT, and 6/7 during VT. Relative peak area was used as a quantitative index of synchronization between the two motor units of each pair. It was lowest in PT, progressively increased in EPT as tremor amplitude increased, and highest in VT. In PT and lower amplitude EPT, the synchronization indexes were higher between motor units that discharged at the same or nearly the same frequency. In contrast, in higher amplitude EPT and VT, motor units with different firing frequencies were sometimes strongly synchronized as a consequence of double discharges in faster-firing motor units that had burst repetition rates in the range of slower-firing motor units discharging as singlets. Greater motor unit synchronization with increasing tremor amplitude in EPT may be secondary to a simultaneous increase in muscle spindle afferent activity from the tremulous muscle. Greatest synchronization in VT presumably reflects near maximal supraspinal and segmental common synaptic input onto motoneurons that generate VT. These results support a longstanding hypothesis that synchronization of motor units is the physiological basis for higher amplitude tremor.

Nocturnal enuresis, a common childhood problem, has several plausible etiologies: adverse environmental circumstances, psychologic disturbances and physiologic mechanisms. A wait-and-see approach is commonly adopted, since spontaneous resolution occurs in many children. Moderate success has been reported with the use of tricyclic antidepressants. Two behavioral conditioning approaches are reported to be highly successful in ameliorating enuretic episodes.

A technique is described for the recovery of infective larvae of strongyloid nematodes from sediment resulting from the washing of pasture and soil samples. The process of recovery and counting of larvae is described by a model based on the binomial distribution. Tests of the technique have shown that it will recover approximately 50% of the larvae present in samples of pasture sediment of either 7.5 or 12.5 ml in volume after centrifugation. The efficiency of the technique was independent of the number of larvae present in samples of pasture sediment. The technique was shown to be less efficient and more variable in recovery of larvae from samples of soil sediment. Estimations in efficiency of recovery from soil sediment ranged from 64 to 110.2% and a significant effect of volume of sediment on recovery was detected.

A delayed gamma distribution satisfactorily described the distribution of times to hatching of Ostertagia circumcincta eggs incubated in 0.1% saline at temperatures between 6 and 20 degrees C. Below 6 degree C hatching of eggs was extremely variable. The relationship between rates of development and temperature within the range 10 to 20 degrees C was more closely described by a non-linear function than a linear one. The non-linear function was incorporated into a temperature summation equation which satisfactorily predicted the hatching of eggs incubated under conditions of alternating temperatures.

Clinical, electrophysiological, and myelographic findings were correlated in 57 patients with the clinical diagnosis of lumbosacral root disease. Conventional motor and sensory (including sural nerve) conduction studies were normal in all patients. Electromyography, late response studies in different muscles of the lower extremity, the myelogram, or combinations of these tests were abnormal in 44 patients (77%). Of 36 patients (63%) with abnormal myelograms, 14 had normal electrophysiological studies. Twenty-nine (51%) had an abnormal electrophysiological or myelographic finding; although 8 patients in this group had a normal myelogram, 2 had an abnormal discogram and 1 an abnormal epidurogram. Electrophysiological or myelographic findings, in some cases both, correlated well with clinical signs and symptoms in 41 patients (72%). H-reflex and F response studies, when abnormal, helped in localizing a lesion in the appropriate root distribution.

The "suppressive" effect of vibration on the H-reflex was studied in 18 patients with motor system deficits due to cerebrovascular lesions of less than 3 weeks duration. No meaningful difference was found in the degree of H-reflex suppression between clinically involved and uninvolved sides in the patients, several of whom had increased deep tendon reflexes at the time of examination. It is concluded that hyperreflexia of "spasticity" cannot be explained purely on the basis of lack of presynaptic inhibition, even if it were one of the underlying mechanisms responsible for the suppression of the H-reflex by vibration, as previously claimed. Not only specific lesions themselves but also changes with the passage of time after CNS damage are important for understanding and treatment of motor system abnormalities.

A prospective study was made of changes in the electroencephalogram after the use of metrizamide for myelography and posterior fossa cisternography in 61 patients (62 studies). The EEG changed in 21 patients (34%); 3 of these had had previously abnormal records, and the abnormalities were accentuated on the second recording. Eight developed paroxysmal activity, including spike and wave in 1. EEG changes appeared 24 to 48 hours after the use of metrizamide in 6 patients whose intervening EEGs were normal. The percentage of records that changed tended to increase as metrizamide was brought to more rostral levels. Symptoms following the use of metrizamide were reviewed in 58 patients. Although there were no seizures in the present series, seizures did occur with subsequent use of metrizamide in 3 other patients at our institution. Previous reports may have underestimated the frequency of EEG changes after metrizamide since these may require 24 to 48 hours to develop. The appearance of such activity suggests that the use of metrizamide in patients with known seizure disorders, the anatomical level to which metrizamide is brought during radiography, removal of contrast medium, and further investigation of premedication with anticonvulsants all require careful consideration when use of metrizamide is being contemplated.

EMGs from biceps and triceps were recorded during stereotyped elbow flexion tasks performed by 20 patients fulfilling clinical criteria for 'cerebellar deficits' and the data were compared with previously established normal standards. In a fast flexion task, 15 of 18 patients showed prolongation of the initial biceps and/or triceps components, and it is suggested that this abnormality might be an elemental feature of dysmetria. Ten of 14 patients showed the normal pattern of smooth flexion indicating that, with cerebellar deficits, smooth movements are better preserved than fast movements. The timing of the cessation of triceps activity before the initiation of biceps activity in an alternating movement was abnormal in 12 of 16 patients; this abnormality might be an elemental feature of dysdiadochokinesia.

The usefulness of performing late response studies for the detection of peripheral nerve dysfunction has been demonstrated. It has been shown that significant prolongation of the minimal latencies of the H reflex and the F response is present at a time when conventional methods of motor and sensory conduction do not show an abnormality in individual patients. Abnormalities of late responses have been shown to occur in a variety of peripheral neuropathies with "axonal" as well as "segmental demyelination" type of underlying pathology.

Possible underlying neurophysiological mechanisms of spinal cord stimulation in the modification of motor disorders were discussed by scientists working in research on motor control mechanisms. Changes of motor unit properties in upper motoneuron lesions were reviewed, the role of proprioceptive input and long-loop reflexes in motor control was discussed, analysis of ramp and ballistic movements in motor control was presented, and some aspects of neural control of locomotion were reviewed. Some physiological considerations of the influence of electrical stimulation on various neural functions were given and the conclusion was reached that, at present, no definitive models of the action of spinal cord stimulation are available.

One year after bilateral lumbar sympathectomy for Raynaud's syndrome, a young woman underwent fascicular biopsy of the sural nerve to help elucidate the cause of lower limb pain. The morphological features, density, and diameter spectrum of unmyelinated fibers were normal. The sympathetic nervous system appears to contribute few, if any, axons to the total population of unmyelinated axons in this cutaneous nerve.

The patient described in this report appears to have had a unique, severe, pure pan-dysautonomia, and has been investigated in sufficient detail to specify precisely the disorders of functions subserved by the autonomic nervous system. Though we cannot rule out the possibility of an unknown autonomic toxin, we have no evidence for it and suggest that our patient's disorder be considered an acute polyneuritis, restricted to the autonomic system. Comment is made on tests of autonomic dysfunction and on the reliance which can be placed upon the results.

Three hundred sixty-seven carotid endarterectomies were monitored using routine electroencephalographic (EEG) techniques. In 9.8%, changes in the EEG followed clamping of the internal carotid artery and could roughly be grouped into 6 patterns. The most common (47%) was rapid unilateral or bilateral attenuation of background anesthetic-induced fast EEG activity. Conclusions drawn from studies of the 9 patients who had immediate postoperative neurological deficits of varying degrees are presented as they illustrate monitoring techniques that are useful for early recognition of cerebral ischemia. Thirty-five patients were monitored with both routine and computerized techniques--the latter proved more useful than the former on all counts.

The development of the free-living stages of Ostertagia ostertagi incubated at constant temperatures from 5 to 27 degrees C and in dung pats in the field was observed. The death rates were adequately described by a single exponential functional and the distribution of times for development by a delayed gamma density function. The times of appearance of selected development stages such as maximum numbers of embryonated eggs and half the maximum number of infective larvae, were highly dependent on temperature. The relationships between these times and temperature were adequately described by the Arrhenius equation. The parameters of this equation and mean hourly temperature recorded in dung pats in the field were used to predict development times in the field. A comparison of predicted and observed times showed that an initial delay accounted for a large proportion of the time required for development in dung pats, particularly the embryonation of eggs. This delay was attributed to lack of aeration associated with high moisture content of the dung pat.

Thirty-five patients who met all clinical criteria for brain death and 53 patients who did not were tested with brainstem auditory (BAER) and short-latency somatosensory (SER) evoked responses. Of the brain-dead patients, 77% had no waves present in the BAER, including wave I, whereas 69% had medullary components present in the SER. These data suggest that the SER has greater clinical utility in the brain-death setting, because it is important to have a wave present that established that the input signal has reached the central nervous system. No brain-dead patients had subsequent waves in either test. These results are correlated with neuropathologic findings and contrasted with data obtained in the comatose but not brain-dead patients.

The serotonin precursor L-5-hydroxytryptophan is useful therapy for patients with posthypoxic intention myoclonus. L-5-hydroxytryptophan plus carbidopa was administered to eight patients with this disorder or other syndromes in which myoclonus is prominent. This treatment (1) decreased the frequency of occurrence and amplitude of intention myoclonus in two patients with posthypoxic intention myoclonus and in one with idiopathic myoclonus, (2) had no effect in one patient with congenital encephalopathy and myoclonus, and (3) increased the frequency of occurrence and amplitude of myoclonus in two patients with lipid storage disease, one with myoclonic epilepsy, and in an additional patient with idiopathic myoclonus. Therefore, L-5-hydroxytryptophan does not effect improvement in all forms of myoclonus; it should be given with caution because it produces a high incidence of side effects. A patient's response to L-5-hydroxytryptophan therapy may be important in a diagnostic classification of myoclonic syndromes based on differences in indoleamine neurotransmitter function.

Brain stem auditory evoked responses (BAERs) were recorded in 50 normal adult subjects at various click rates. Attention was paid to absolute latencies, interwave latencies, interear interwave latencies, absolute amplitudes, and various amplitude ratios. The variability of waves VI and VII suggests that the clinical utility of these waves is restricted-their absence is not necessarily due to a CNS lesion. The wave IV-V complex appears with six different patterns. These variations must therefore be considered normal; none should be misconstrued as indicative of disease of the CNS. Repeated studies over a period of two to nine months showed no statistically significant changes in amplitude or latency measurements with the passage of time. Knowledge of these normal values and their variations, as a precondition for establishing criteria for abnormality, is essential to the interpretation of BAERs in clinical situations.

The term spasticity is used to describe many relatively unrelated syndromes and, because they share few common pathophysiologic mechanisms, it is not possible to define the physiology or pharmacology of spasticity. In patients with spastic paresis, it is the latter negative symptom (rather than the spasticity) that accounts for almost all the functional disability. Clinical neurophysiologic techniques are useful for categorization of patients with clinically identical syndromes into subgroups which respond to different therapies. Fusimotor or spindle primary afferent hyperactivity have not been demonstrated in spastic patients; reduction in central inhibitory mechanisms probably accounts for spastic hyper-reflexia. Increased passive muscle stiffness may also be clinically significant. Therapies for spasticity include elimination of causative or enhancing factors, frequent muscle stretching, surgical approaches and chemotherapy. The latter includes dantrolene (which weakens muscles), baclofen (particularly useful for reduction of flexor spasms and flexor dystonia in patients with spinal lesions) and diazepam.

EMG activity was recorded in biceps and triceps while subjects voluntarily flexed their elbows during a visual matching task. With fast flexion, the initial EMG was characterized by a triphasic pattern with a burst of activity first in biceps, then in triceps with a silent period in biceps, and finally in biceps again; these components were analysed quantitatively. Smooth flexion was characterized by continuous activity in biceps. Inhibition of tonic activity of triceps in relation to a fast flexion occurred in the 50 ms before the initiation of biceps activity. A patients with a severe pansensory neuropathy performed normally on these tasks. Physiological mechanisms underlying these patterns are analysed; an important conclusion is that the triphasic activity with fast flexion is 'centrally programmed'.