The dopaminergic response in multiple system atrophy. Fifteen of 23 pathologically confirmed cases of multiple system atrophy (MSA) showed some initial response to levodopa and eight of these remained at least partially responsive at the time of death. Eleven developed motor oscillations, and drug-induced dyskinesias, often involving the face and jaw, were also seen in 11 cases. Acute levodopa and apomorphine challenges were administered to 11 patients with clinical MSA who were considered levodopa responsive. A short duration relatively small amplitude response with associated dyskinesias occurred in six and a further three developed dyskinesias without any motor response. Following levodopa withdrawal, a delayed deterioration occurred after three to six days in six patients, five of whom had shown no short duration motor response to the acute challenges. The occurrence of levodopa-induced dyskinesias without a concomitant motor response and delayed deterioration several days after levodopa withdrawal may be more typical of patients with MSA than Parkinson's disease.


Impaired joint mobility in Guillain-Barré syndrome: a primary or a secondary phenomenon? Three patients with Guillain-Barré syndrome had significant residual impairment of joint mobility. Pain in the limbs and axial skeleton was a prominent early feature, as were autonomic disturbances and bulbar involvement resulting in prolonged mechanical ventilation. All three patients developed marked joint stiffness and contractures despite having physiotherapy from the outset. The skeletal problems and complications became major components of disability despite improving neurological status.


Reduced regional cerebral blood flow in Huntington's disease studied by SPECT. Regional cerebral blood flow (rCBF) was studied in 18 patients with Huntington's disease (HD) and 19 age- and sex-matched controls with high resolution single photon emission computerised tomography (SPECT), using Tc-99m-HMPAO. Significant reductions in tracer uptake were found in the caudate and lentiform nuclei (20 and 8%) and in the cerebral cortex, especially in the frontal and parietal areas (11-13%). No significant reductions were found in the thalamus, mesial temporal cortex, and occipital cortex. Fourteen patients had neuropsychological testing. Relationship between rCBF and cognitive function was tested by regression analysis. A linear relationship was found between test scores of Wisconsin Card Sorting Test, Picture Arrangement Test and blood flow in the caudate nucleus. Other tests of cognitive function (Block Design Test, Face and Word Recognition Test, Street Fragmented Pictures Test, and Similarities Test) correlated better with flow in the cortical regions believed to be involved in solving those particular tests. These findings indicate, that blood flow is reduced in both cortical and subcortical structures in symptomatic HD, and that both reductions in cortical and subcortical blood flow may be related to cognitive function in HD.


Beginning-of-dose motor deterioration following the acute administration of levodopa and apomorphine in Parkinson's disease. Six Parkinsonian patients on long term levodopa therapy complained of short-lived deterioration of Parkinsonian symptoms immediately after levodopa intake. After withdrawal of the drug overnight, and following an oral challenge with levodopa/carbidopa (250/25) in all six cases, and with subcutaneous apomorphine (3 mg) in two, deterioration below base line levels of disability were observed which would not be explained by loss of sleep benefit. This occurred 10-20 minutes after levodopa challenge and lasted for 10-20 minutes. The latency and duration of this phenomenon were shorter with apomorphine but the characteristics were similar. This phenomenon may be due to an inhibitory effect of levodopa acting via presynaptic dopamine receptors.


F response and somatosensory and brainstem auditory evoked potential studies in HMSN type I and II. To evaluate conduction along the proximal and distal segments of motor and sensory long limb nerves, as well as along the very short acoustic nerve, F response and somatosensory and brainstem auditory evoked potential were studied in a series of patients with hereditary motor and sensory neuropathy (HMSN) types I and II. A diffuse and comparable slowing of conduction in proximal and distal nerve segments, as well as along the acoustic nerve, seems to favour a primary myelin defect in HMSN I. F response and motor conduction velocity showed a similar derangement in both proximal and distal motor segments. Latencies of somatosensory evoked potentials were symmetrically prolonged and correlated with motor nerve impairment. Central conduction times were normal. Studies of brainstem auditory evoked potentials showed a high incidence of acoustic nerve involvement, the most evident abnormality being a statistically significant increase in the latency of the I wave. Our data seem to support the presence of primary myelinopathic damage in HMSN I.


Prevalence of sleep apnoea in patients over 40 years of age with spinal cord lesions. Twenty two patients over the age of 40 with stable spinal cord damage underwent overnight sleep studies to investigate the prevalence of sleep apnoea. Ten patients had some evidence of obstructive sleep apnoea (OSA). Hypoxic events were scored as number of dips of SaO2 more than 4% below the preceding 10 minute average (> 4% SaO2 dip rate). All the patients had more than five such dips per hour and six had clearly abnormal dip rates of more than 15 per hour. Two other patients had dip rates above 10 per hour without apnoeas but periods of central hypoventilation mainly during rapid eye movement (REM) sleep. OSA appears to be more common in older patients with spinal cord injury than in the general population. Possible relevant factors include patient selection, reduced ventilatory function secondary to spinal cord damage, sleep posture and medication.


Cerebral cavernous angioma: a potentially benign condition? Successful treatment in 16 cases. Cerebral cavernous angioma (cavernoma) has previously been treated by resection for all presentations when surgically resectable. In this retrospective series of 16 cases, it is demonstrated that, for those patients presenting with epilepsy alone, surgery is often unnecessary. Diagnosis can be made radiologically and excellent seizure control can be obtained with medications. In the authors' experience, those cavernomas symptomatic as epilepsy rarely cause major haemorrhage and the need for surgery as prophylaxis against bleeding in this group is unproven.


Hysteria following brain injury.

Hysteria following brain injury. Of 167 patients referred to a unit treating severe behaviour disorders after brain injury, 54 showed clinical features closely resembling those of gross hysteria as described by Charcot. Close correlation was found with very diffuse insults (hypoxia and hypoglycaemia), but not with severity of injury or with family or personal history of hysterical or other psychiatric disorder. The findings may have implications for the understanding of the nature of hysteria.


Fluctuating cognitive abnormalities and cerebral glucose metabolism in neuropsychiatric systemic lupus erythematosus. Brain imaging techniques such as MRI and PET have the potential for identifying central nervous system involvement in SLE. They may also help elucidate the mechanisms giving rise to the widely diverging manifestations of CNS involvement in SLE. This report documents an intensive longitudinal study of three women with neuropsychiatric SLE. PET and neuropsychological evaluation were both used to examine the co-occurrence of behavioural/cognitive deficits with alterations in regional brain glucose metabolism. In all three patients, FDG uptake indicated abnormalities which were not identified on CT scan, but corresponded well with localisable cognitive deficits. Changes in each patient's cognitive profile on reassessment paralleled changes on PET. These findings support the suggestion that cognitive deficits in SLE patients reflect primary CNS involvement.


Visuo-spatial neglect: qualitative differences and laterality of cerebral lesion. From a large sample of patients who sustained a first stroke, 98 patients were selected with unilateral left brain damage and 92 with unilateral right brain damage. Examined on a visual search task (Star Cancellation) approximately four years after onset, we found a comparable incidence of visual inattention in the two groups. Despite this quantitative similarity, the qualitative pattern of performance was different in the two impaired samples. Patients with right brain damage showed a distinctive linear relationship whereby omission errors increased from right to left across the stimulus page. Within the left brain damaged sample, two subgroups could be discerned. As expected, one subgroup showed more contralesional than ipsilesional errors, but the other subgroup was comparable to the sample with right hemisphere damage. The reasons are discussed for these qualitative differences, drawing particular attention to the importance of motor/manual factors in the determination of performance on visual search tasks.


Transient musical hallucinosis of central origin: a review and clinical study. A 52 year old, right handed, hearing impaired woman was admitted with headache and neck stiffness. The only neuropsychological symptom was transient auditory perceptions in the left ear, which were musical, seemed familiar and were not influenced by verbal communication. CT and MRI showed a right subarachnoid haemorrhage, while brainstem auditory evoked potentials failed to reveal a brainstem lesion. In patients with organic cerebral disease, unilateral auditory hallucinations (AHs) may indicate a lesion in the contralateral hemisphere. However, according to this review the type of AHs (verbal versus musical) is not consistently associated with a cerebral lesion on either side.


Acetylcholinesterase and butyrylcholinesterase activities in cerebrospinal fluid from different levels of the neuraxis of patients with dementia of the Alzheimer type. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities of cerebrospinal fluid (CSF) collected post mortem from the lateral ventricles, cisterna magna, and lumbar regions of the spinal cord of patients with a histologically confirmed diagnosis of Alzheimer's disease were compared with those of normal, age matched control patients, patients with dementia of non-Alzheimer aetiology, and patients with non-dementing neurological disorders. The AChE activity of the ventricular CSF of patients with Alzheimer's disease was 48% lower (p < 0.005) than that of age matched controls or patients with other types of dementia, and the AChE activity of CSF sampled from the basal cistern was 40% lower (p < 0.005) in patients with Alzheimer's disease. There were no significant differences between the AChE activity in Alzheimer's disease and control patients in CSF collected from the lumbar cistern. AChE activity was lower in CSF sampled from the basal and lumbar cistern of patients with dementia of non-Alzheimer aetiology, while ventricular activity was in the normal range. BuChE activity in ventricular CSF of Alzheimer's disease patients was 41% lower than normal (p < 0.05) and in the normal range in all other samples. The secretion of AChE from forebrain and hindbrain regions is reduced in Alzheimer's disease patients, leading to decreased ventricular and cisternal levels of the enzyme. Secretion from more caudal regions of the central nervous system seems to be unaffected by the disease, resulting in AChE in the lumbar CSF of patients with Alzheimer's disease being in the control range. Such altered secretion of AChE in the brain could have profound implications not only for cholinergic transmission in these patients but also for the proposed noncholinergic modulatory actions of AChE.


Pseudoaxonal Guillain-Barré syndrome: severe demyelination mimicking axonopathy. A case with pupillary involvement. A patient with fulminant Guillain-Barré syndrome developed pupillary denervation, loss of all brain stem reflexes and a complete flaccid quadriparesis. Pathological studies confirmed this was due to a primarily demyelinating process and not an axonal form of Guillain-Barré syndrome.


Diagnosis by axilla skin biopsy in an early case of Lafora's disease. Myoclonus, seizures and progressive dementia are the main clinical features in Lafora's disease. This is the first reported case in which the diagnosis has been made by axillary skin biopsy in a patient with myoclonus but no other neurological symptoms.


Propriospinal myoclonus in multiple sclerosis. The clinical and electrophysiological features of segmental myoclonus affecting the right arm and upper trunk are described in a patient with multiple sclerosis. Electrophysiological studies suggested that the myoclonus was propagated from a generator site in the cervical cord, where lesions were found using MRI. The spread of electromyographic activity in each myoclonic jerk was slow and variable. These findings are characteristic of propriospinal myoclonus, which has not been associated with multiple sclerosis previously.


"Isolated" postinfectious myoclonus.

"Isolated" postinfectious myoclonus. Two cases are reported who developed myoclonus as the only manifestation of a post-infectious syndrome without evidence of encephalitis or the opsoclonus-myoclonus syndrome. Case 1 had generalised myoclonus following an influenza-like illness, while case 2 had right upper limb segmental myoclonus following uncomplicated chicken pox. Neither had any localising neurological signs or abnormality on investigation. Both recovered completely within six months of the onset. Similar cases are reviewed from the literature and it is suggested that such cases be called "isolated" post-infectious myoclonus.


Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin: a second case. A 44 year old female presented with a progressive cerebellar disturbance approximately 13 years after receiving human pituitary derived gonadotrophin injections as a treatment for infertility. The patient died approximately nine months later. Creutzfeldt-Jakob disease was confirmed at necropsy. This is the second reported case of Creutzfeldt-Jakob disease in a recipient of human derived gonadotrophin.


Treatment of lower urinary tract dysfunction in patients with multiple sclerosis. Committee of the European Study Group of SUDIMS (Sexual and Urological Disorders in Multiple Sclerosis). Bladder symptoms in patients with multiple sclerosis (MS) are common and usually arise as a result of spinal lesions which interrupt the neural pathways connecting the pontine micturition centre to the sacral spinal cord. Thus these symptoms are particularly likely to occur in those with lower limb neurological deficits. Fortunately bladder dysfunction in MS is rarely associated with serious upper tract disease so that the problem is usually one of symptomatic management. Lower urinary tract symptoms may be both "irritative" or "obstructive" in nature and can be explained in terms of underlying detrusor hyperreflexia and incomplete bladder emptying. Treatment is aimed at minimising both these effects. Oral anticholinergic medication can be effective in reducing detrusor hyperreflexia and intermittent catheterisation is used to reduce abnormally high post micturition residual volumes. With this simple treatment, often used in combination, many less severely affected patients with MS can gain considerable improvement in controlling urinary continence.


Motor recovery after acute ischaemic stroke: a metabolic study. The metabolic changes occurring after ischaemic stroke were measured to investigate the functional anatomy of clinical motor recovery. Positron emission tomography (PET) and the steady-state 15O technique was used to compare resting relative metabolic distributions at the onset of functional deficit with those following recovery. Ten patients were studied with repeat scans. Motor recovery was associated in some patients with an increase of relative oxygen metabolism in anatomical structures normally involved in motor function in the affected hemisphere, particularly in the cortical motor areas. In those patients without such metabolic changes in the cortex of the diseased hemisphere, relative increases in cortical metabolism in the contralateral hemisphere were associated with better motor recovery than in patients with no relative cortical metabolic increase in either hemisphere. There was no correlation between the degree of improvement in motor function and the severity of motor deficit at onset, the size and site of the lesion and the metabolic changes in the infarcted zone. No particular pattern of global metabolic changes was observed after recovery. Thus different relative patterns of metabolic recovery were seen in patients with different lesions and evidence was found for the participation of contralateral structures in the recovery process in some patients.


Striatal dysfunction in Rolling mouse Nagoya: an electrophysiological study. To elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling, genotype rol/rol), an experimental neurologic mutant mouse, we studied the physiological characteristics of neurons of the globus pallidus (GP) in rolling, comparing them with those of the behaviorally normal heterozygotes (+/rol) and normal controls (+/+). Forty-nine units in rolling, 41 in heterozygotes and 48 in controls were recorded under urethane anesthesia. The group mean of the interspike interval (ISI) of the spontaneous unit discharges was significantly shorter in rolling (42.2 +/- 2.6 msec, mean +/- SEM) than that of controls and of heterozygotes (55.4 +/- 2.4 msec, P < 0.001 and 50.4 +/- 2.6 msec, P < 0.05, respectively), indicating a significantly higher rate of spontaneous unit activity in the GP of rolling. In the controls and heterozygotes, about 60% of the GP neurons responded to striatal (ST) electrical stimulation with a predominantly inhibitory response, whereas a significantly smaller number of the GP neurons (22%, P < 0.001) exhibited inhibitory responses in rolling. The positive field potentials recorded in the GP evoked by ST stimulation were significantly smaller in amplitude in rolling (1.04 +/- 0.10 mV, mean +/- SEM) than that of the controls and heterozygotes (1.78 +/- 0.15 mV, P < 0.001 and 1.97 +/- 0.17 mV, P < 0.001, respectively). These results are in agreement with our previously reported findings of increased glucose metabolism and reduced concentration of GABA in the GP and substantia nigra pars reticula (SNr) in rolling.(ABSTRACT TRUNCATED AT 250 WORDS)


Somatic motor efferents in multiple system atrophy with autonomic failure: a clinico-pathological study. The myelinated fibers in the corticospinal tracts, ventral spinal roots, and the neurons in the ventral spinal horns were quantitatively examined in 8 autopsied cases of multiple system atrophy associated with autonomic failure. In these structures consisting of the somatic motor efferents, the main pathological feature was the size dependent-involvement of predominantly small-sized fibers and neurons. The small myelinated fibers were significantly depopulated, while the large myelinated fibers were well populated in the corticospinal tract. Neurons in the ventral horns were also involved, but those with a small diameter and located in the intermediate zone (Rexed's lamina VII, VIII) were markedly diminished. In the ventral spinal roots, in the fourth lumbar segments containing essentially no autonomic efferents, small myelinated fibers were also preferentially involved. These pathological changes in the small-sized fiber and neuron loss were examined in relation to the somatic and autonomic motor symptoms, particularly of pyramidal signs.


Characterisation of the distribution of choline acetyltransferase messenger RNA in human spinal cord and its depletion in motor neurone disease. We have characterised the distribution of choline acetyltransferase (ChAT) mRNA in spinal cord from normal and motor neurone disease/amyotrophic lateral sclerosis (MND) subjects by in situ hybridisation. High concentrations of ChAT-mRNA were detected in 4 main regions of spinal cord, layer IX of the ventral horn, layer III of the dorsal horn, the intermediate grey matter and layer X around the central canal. ChAT mRNA was most highly concentrated in layers IX and III. Substantial decreases in ChAT mRNA were detected in ventral grey matter (layer IX) of cervical and lumbar cord in all cases of MND. Smaller and more variable changes in ChAT mRNA were seen in MND in other regions of spinal cord which indicates that these changes may arise as secondary processes. The value of this technique in understanding the pathophysiology of MND is discussed.


Analysis of the CAG repeat region of the androgen receptor gene in a kindred with X-linked spinal and bulbar muscular atrophy. Herein we describe a family with X-linked spinal and bulbar muscular atrophy (SBMA or Kennedy's disease), an adult onset neuromuscular disease characterized by slow progression, predominant proximal and bulbar muscle weakness. One frequent association is the appearance of gynecomastia. This disorder was previously shown to be linked to the locus DXYS1 on the proximal long arm of the X chromosome. Recently, a report implicated a mutation at the N-terminus of the androgen receptor gene involving amplification of CAG repeats as the cause of X-linked SBMA. We studied this region of the androgen receptor in a kindred clinically suspected but not confirmed of having X-linked SBMA by the polymerase chain reaction (PCR) followed by Southern analysis and DNA sequencing. The mutated allele was found to have an increased number of 51 CAG repeats confirming the clinical diagnosis of SBMA. Normal individuals revealed 23 repeat numbers within the normal range, while another unrelated X-linked SBMA patient had an enlarged CAG repeat region. The carrier or disease status could be established or confirmed in 12 individuals of this family on the basis of detecting normal and disease alleles reflected by the number of CAG repeats.


Somatosensory and motor evoked potentials in the assessment of cerebrotendinous xanthomatosis before and after treatment with chenodeoxycholic acid: a preliminary study. We studied two unrelated patients with cerebrotendinous xanthomatosis, in whom clinical examination revealed central nervous system long tract involvement. Brain and spinal cord magnetic resonance imaging showed no signs supporting the involvement of the long pathways. Somatosensory and motor evoked potentials demonstrated central sensory and motor conduction abnormalities, which suggested distal degeneration of longer fibers, rather than scattered focal lesions in the CNS. In one of the patients the neurophysiological study was repeated 6 and 12 months after the beginning of treatment with chenodeoxycholic acid, showing a progressive improvement. Therefore, our data suggest that central motor and sensory conduction studies may be useful in the assessment of the disease and in monitoring treatment.


TRH analogue, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) enhances neurite outgrowth in rat embryo ventral spinal cord in vitro. We have studied effects of TRH analogue, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) (from Tanabe, Osaka, Japan) on explanted ventral and dorsal spinal cord cultures from 13- and 14-day-old rat embryos. TA-0910-treated cultures had significantly increased neurite outgrowth with cultures of ventral spinal cord, but not with cultures of dorsal spinal cord. The effect was dose-dependent. A possible role for TRH in amyotrophic lateral sclerosis remains to be defined.


Electron microscopic features of skin in neurometabolic disorders. Skin biopsy may contribute to the clinical diagnosis of neurometabolic disorders. It is an easy and much less traumatic procedure than brain, rectal, peripheral nerve and skeletal muscle biopsies. The method is informative and not too time-consuming for an experienced examiner. Differential diagnosis is possible in most storage disorders since the ultrastructure of the storage is virtually typical in lysosomal and in nonlysosomal diseases. The storage has a particular distribution with characteristic ultrastructural patterns in the various cell types. Skin biopsy plays a major diagnostic role when clinical features are atypical for a storage disorder, to discover new phenotypic variants of known enzymatic deficiencies or when the biochemical defect has not yet been determined. It can be used as a screening procedure to orientate the investigations, to suggest specific biochemical assays on cultured fibroblasts or other tissues or body fluids. It can be applied to detect "presymptomatic" patients in affected families. Other disorders of the nervous system should be investigated in the future to ascertain whether skin biopsies could possibly be used for diagnostic purposes. Thorough knowledge of the morphological features of these disorders may also improve the understanding of their pathogenesis, shed some light on the underlying basic defects and control the results of therapy.


Anti-sulfatide antibodies in neurological disease: binding to rat dorsal root ganglia neurons. Increased titers of anti-sulfatide antibodies were detected by ELISA in 5 of 200 patients and control subjects. All 5 patients had sensory impairment; 4 had neuropathy, and one had multiple sclerosis. Of the patients with neuropathy, 2 had a clinical syndrome of small fiber sensory neuropathy with normal electrophysiological or nerve biopsy studies, 1 had a sensorimotor axonal neuropathy associated with IgM monoclonal gammopathy, and 1 had sensorimotor neuropathy with multifocal motor conduction block and anti-GM1 antibodies. The anti-sulfatide antibodies bound to the surface of unfixed rat dorsal root ganglia neurons and human neuroblastoma cells, and to fixed sections of central and peripheral myelin. No binding was detected following intraneural injection into rat sciatic nerves. Pre-absorption with sulfatide but not with galactocerebroside eliminated the tissue binding activity. These findings indicate that increased titers of anti-sulfatide antibodies are found in patients with sensory impairment but are not restricted to a particular neurological syndrome or type of neuropathy. The significance of anti-sulfatide antibodies is uncertain although sulfatide on dorsal root ganglia neurons may be a target antigen.


Immunosuppression in nerve allografting: is it desirable? Immunologically incompatible sciatic nerve grafts were inserted into the severed sciatic nerves of Wistar rats. In an attempt to induce graft tolerance, low-dose cyclosporin A (CsA) was administered to some animals for 20 weeks, then gradually withdrawn. Behavioural, electrophysiological and histological studies indicated that some degree of regeneration took place in all animals regardless of treatment. Neither a daily dose of 5 mg/kg nor 10 mg/kg was sufficient to prevent the rejection and subsequent disruption of allograft structure, and as a consequence reinnervation of the distal stump was limited. This was manifest both in the poor functional recovery of the denervated foot, and in the large number of regenerated axons found outside of the perineurial membranes of the transplanted fascicles. Therefore, tolerance was not induced at these doses. Furthermore, the significant decrease in the amplitude of electromyographs recorded from experimental and unoperated (control) animals suggests CsA may have a deleterious effect on unlesioned nerve even at these low doses. It would be prudent, therefore, to exercise caution in the combined use of nerve allografts and CsA immunosuppression, until the neurotoxicity of CsA has been investigated further. This is particularly important since CsA is sometimes used in the treatment of certain neuropathic autoimmune diseases.


Alterations in the contractile properties of motor units within the ageing rat medial gastrocnemius. The decline in muscle force accompanying senescence is associated with a loss of motor nerves which provides some opportunity for collateral reinnervation and alterations in the mechanical properties of surviving motor units. The contribution of the different motor unit types to this neuromuscular reorganization was investigated by determining the isometric contractile properties of single motor units within the medial gastrocnemius of rats aged 791 +/- 39 days. These were compared with a group of similarly isolated and classified units within young adult rats aged between four and five months. The estimated number of units decreased significantly from 93 +/- 28 in young adults to 66 +/- 19 in senescent animals. There was a preferential loss of fast motor units and a significant loss of myelinated axons within the muscle nerve. The maximum tetanic force developed by FF motor units decreased with age while that of the more fatigue resistant FI and FR motor units increased. Other contractile properties were unaltered and there was no change in any contractile parameter for S unit types. Alterations in the cross-sectional areas and proportions of histochemically classified muscle fibres reflected these changes. The proportion of FG fibres declined with age and there was evidence of denervation, particularly within the peripheral rim of fast type fibres. The number of muscle fibres within the medial gastrocnemius decreased with age. These results indicate that fast motor units are most severely affected during the early stages of senescence. Within this population the FF motor units which have the largest innervation ratios in the young adult may suffer preferential degeneration.


Effect of partial denervation on motor units in the ageing rat medial gastrocnemius. The ageing neuromuscular system is thought to undergo a continual process of reorganization as motoneurones are lost and surviving motor nerves reinnervate neighbouring denervated muscle fibres. However, the extent to which collateral reinnervation is able to compensate for neural deficits in the ageing individual is unknown. The ability of the senescent motoneurone to increase the size of its peripheral field was therefore investigated following transection of the right L5 ventral root in male Sprague Dawley rats aged 775 +/- 50 days. This procedure resulted in an extensive partial denervation of the right medial gastrocnemius muscle. After a recovery period of between 28 and 31 days the isometric contractile properties of surviving motor units were compared to control motor units from both the contralateral muscle and a group of unoperated control animals aged 791 +/- 39 days. Motor unit force was found to be unchanged after partial denervation and the absence of any alteration in motor unit size was confirmed by histological analysis. However, the time course of the isometric twitch was significantly longer for both fast and slow motor unit types and the conduction velocity of motoneurones innervating fast units was decreased following partial denervation. These results demonstrate that senescent motor nerves are unable to substantially increase the size of their peripheral fields by extensive collateral reinnervation.


Effects of leukaemia inhibitory factor and other cytokines on murine and human myoblast proliferation. It has been shown previously that leukaemia inhibitory factor (LIF) and transforming growth factor-alpha (TGF-alpha) stimulate proliferation of primary cultures of murine myoblasts. We now show that human myoblasts respond in a similar manner to LIF and TGF-alpha. These responses occur over a range of growth conditions. There are total additive effects in both human and murine myoblasts between LIF and TGF-alpha and LIF and fibroblast growth factor-beta (FGF-beta), but not between LIF and interleukin-6 (IL-6) or insulin-like growth factor 1 (IGF-1). The LIF response is initiated by a short exposure to the cytokine and is maintained for prolonged periods in its absence.


Multifocal motor nerve conduction abnormalities in amyotrophic lateral sclerosis. Motor nerve conduction in motor neuron disease is considered normal until the terminal stages of the disease, a notable exception being lower motor neuron syndrome associated with anti-glycolipid antibodies. We reviewed the electrophysiological findings in all our patients who were diagnosed as having amyotrophic lateral sclerosis (ALS) during the last 6 years. Six patients, clinically indistinguishable from "classical" ALS patients, out of 31 (19%) displayed motor nerve conduction abnormalities. The most consistent finding, occurring in all 6, was prolonged distal latency or reduced conduction velocity in the distal segment of the median nerve, with normal sensory conduction, suggesting possible pressure proneness of motor nerve fibers in ALS. Additional abnormalities included multifocal motor conduction slowing (3 patients), and conduction blocks (4 patients). None of the patients had paraproteinemia and anti-GM1 and anti-GD1a antibodies were not detected. Thus, a subgroup of clinically indistinguishable ALS patients may have multifocal motor nerve conduction abnormalities, indicating motor nerve fiber involvement. The etiology and pathogenesis of the peripheral nerve involvement are presently unknown.


Enhanced proliferative response of myasthenic thymus cells in mixed lymphocyte reaction. To determine the functional diversity of thymic lymphoid cells in patients with myasthenia gravis (MG), we evaluated mixed lymphocyte reactions (MLR) using thymus cells in 7 MG patients and 8 controls. In the MLR, we used thymus cells as responder cells and mitomycin C-treated peripheral non-T cells as stimulator cells. In an autologous MLR test, a low proliferative response was observed in both the MG patients and controls. In an allogeneic MLR test, in which thymus cells were co-cultured with allogeneic non-T cells, the thymus cells from MG patients showed an increased proliferative response to stimulator cells, whether they were from MG patients or the controls. However, thymus cells from the controls showed a low proliferative response to any allogeneic stimulator cells. The enhanced allo-reactivity of thymus cells from MG patients thus suggests that there is an increase in the number of functionally mature T lineage cells in the MG thymus.


Suppression of experimental autoimmune myasthenia gravis with new immunosuppressants: 15-deoxyspergualin and actinobolin. In the search for a new drug to treat myasthenia gravis, we studied the efficacy of new immunosuppressants on experimental autoimmune myasthenia gravis (EAMG). 15-Deoxyspergualin (15-DSP), bactobolin and actinobolin were administered to some groups at the time of immunization and to other groups 10 days after. The most effective results were achieved with doses of 2.5 mg/kg daily of 15-DSP and 30 mg/kg daily of actinobolin administered from day 1. In both groups, the body weights of the rats increased as normally as those of controls and signs of myasthenia were mild. Immunoelectron microscopic examination of the neuromuscular junctions in rats treated with 2.5 mg/kg of 15-DSP appeared normal, even in the chronic phase (induced by a booster at week 4). Levels of anti-acetylcholine receptor antibodies were almost completely suppressed. Although the effects of these drugs were more remarkable when administered from day 1 than from day 10, the results suggest that they may prove useful in treating myasthenic patients.


Effects of Guillain-Barré sera containing antibodies against glycolipids in cultures of rat Schwann cells and sensory neurons. Serum samples from 52 patients with the acute Guillain-Barré syndrome (GBS), 19 patients with other neurological disorders, and 18 healthy volunteers were tested for cytotoxicity in cultures of rat Schwann cells and dorsal root ganglion neurons. The samples were also examined by enzyme-linked immunosorbent assay for IgG and IgM antibodies against various acidic and neutral glycolipids. Samples from 16 of the 52 (31%) acute GBS patients and from 1 of the 6 patients with chronic inflammatory demyelinating polyneuropathy produced myelin breakdown in culture. Although 10 of the 16 cytotoxic acute GBS serum samples contained anti-glycolipid immunoglobulins, there was no correlation in individual samples between cytotoxic activity and the presence of antibodies against specific glycolipids. While our results do not exclude a role for anti-glycolipid antibodies in the pathogenesis of the acute GBS, the cytotoxic effects of acute GBS serum in cultures of Schwann cells and sensory neurons are probably not due to these antibodies alone.


Serum levels of zinc and copper in patients with Parkinson's disease. Several recent studies have shown decreased copper and increased zinc concentrations in the substantia nigra and increased copper concentrations in the cerebrospinal fluid of Parkinson's disease patients. To elucidate whether changes in serum levels of these trace elements may increase the risk of developing Parkinson's disease (PD), we assessed serum levels of zinc and copper by flame atomic absorption spectrophotometry, and albumin and ceruloplasmin, in 32 (Zn) and 39 PD patients (Cu), respectively, with their spouses as the control group. Serum zinc, albumin, copper and ceruloplasmin levels and the zinc/albumin and copper/ceruloplasmin ratios, did not differ significantly between the two groups and were not influenced by antiparkinsonian therapy in the PD patients. Serum zinc/albumin ratio (r = 0.43), ceruloplasmin (r = -0.36) and copper/ceruloplasmin ratio (r = 0.36) correlated significantly with age, but not with age of onset, duration of the disease, scores of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr staging in PD patients. These values did not correlate with age in the control group. These results suggest that serum levels of zinc and copper do not play any role as risk factors for PD.


Treatment with triiodothyronine decreases the abundance of the alpha-subunits of Gi1 and Gi2 in the cerebral cortex. Treatment of rats for 3 days with T3 halved the abundance of the alpha-subunits of Gi1 and Gi2 in synaptosomal membranes isolated from the cerebral cortex. It is suggested that these changes could contribute to behavioural abnormalities in hyperthyroidism. Similar T3 treatment did not alter abundance of Gi1 alpha or Gi2 alpha in the medulla oblongata nor did it alter abundance of G(o) alpha-subunits in three tested brain regions.


Experimental superficial siderosis of the central nervous system: biochemical correlates. The pathogenesis of superficial siderosis of the central nervous system (CNS) may be examined by the repeated intracisternal injection of washed autologous red blood cells (RBC). In rabbits, the injections cause the accumulation of iron in the cytoplasm of microglial cells and astrocytes of cerebellar and cerebral cortices. Immunocytochemistry for ferritin reveals enhanced reaction product mainly in microglia but hemosiderin occurs only after extending the injections to 6 months. In an effort to determine the biochemical correlates of these morphological changes, iron, ferritin, ferritin subunits and the ferritin repressor protein (FRP) were quantitated. There was no increase of total iron or ferritin in the exposed cortical areas. However, the injections of RBC caused dramatic shifts of the relative contributions by heavy (H-) and light (L-) ferritin subunits. The initial response was a prompt increase of the H/L ratio to over 4.0 from the normal ratio near 1.0. Extended injections caused the ratio to drop to below unity, and the predominance of L-ferritin at 6 months coincided with the appearance of granular hemosiderin. This investigation also confirmed the presence of FRP in rabbit brain cytosols but the induction of experimental superficial siderosis did not change its levels or in vitro affinity for the iron-responsive element in ferritin messenger ribonucleic acid. It is proposed that the incrustation by hemosiderin which characterizes superficial siderosis of the CNS in humans occurs when prolonged exposure to hemoglobin produces persistent shifts of the H/L-ratios by accumulation of L-ferritin.


DNA repair mechanisms in neurological diseases: facts and hypotheses. DNA repair mechanisms usually consist of a complex network of enzymatic reactions catalyzed by a large family of mutually interacting gene products. Thus deficiency, alteration or low levels of a single enzyme and/or of auxiliary proteins might impair a repair process. There are several indications suggesting that some enzymes involved both in DNA replication and repair are less abundant if not completely absent in stationary and non replicating cells. Postmitotic brain cell does not replicate its genome and has lower levels of several DNA repair enzymes. This could impair the DNA repair capacity and render the nervous system prone to the accumulation of DNA lesions. Some human diseases clearly characterized by a DNA repair deficiency, such as xeroderma pigmentosum, ataxia-telangiectasia and Cockayne syndrome, show neurodegeneration as one of the main clinical and pathological features. On the other hand there is evidence that some diseases characterized by primary neuronal degeneration (such as amyotrophic lateral sclerosis and Alzheimer disease) may have alterations in the DNA repair systems as well. DNA repair thus appears important to maintain the functional integrity of the nervous system and an accumulation of DNA damages in neurons as a result of impaired DNA repair mechanisms may lead to neuronal degenerations.


Relationship between corpus callosum atrophy and cerebral metabolic asymmetries in multiple sclerosis. Corpus callosum (CC) atrophy by magnetic resonance imaging (MRI) is a common finding in multiple sclerosis (MS). In order to examine the relationship between CC atrophy and cortical brain metabolism, we compared the cerebral metabolic rates for glucose (CMRglc), measured by positron emission tomography (PET), of 8 MS patients with evidence of CC atrophy on midsagittal MRI, 8 MS patients without CC atrophy and 10 healthy controls. Results showed no significant differences in supratentorial CMRglc absolute values between the three groups, although a slight metabolic reduction was observed in both MS groups compared with normal controls. By contrast, only patients with CC atrophy showed greater directional metabolic asymmetry than normals, the left frontal, temporal and parietal association cortices being significantly lower than the right. Predominant left hemispheric metabolic reductions were not accompanied by a corresponding left-sided predominance in the extent of MRI-detected demyelinating lesions. Therefore our data suggest that CC atrophy interfers more with left than with right metabolic function.


Familial Creutzfeldt-Jakob disease in Chile is associated with the codon 200 mutation of the PRNP amyloid precursor gene on chromosome 20. We have found the codon 200Lys mutation in 6 Chilean CJD families, including a family in the rural case cluster in Chillán. Thus, all 3 of the known clusters of CJD, in Slovakia, Libyan-born Israeli Jews, and Chile, are linked to the presence of the same mutation. The phenotypic features of the disease in these families are similar to those reported for other clustered or individual families elsewhere in the world. The heterogeneous genetic composition of the Chilean population interpreted in light of historical migration patterns suggests that the mutation may have entered Chile by Jewish emigration from Spain.


Astrocytosis, beta A4-protein deposition and paired helical filament formation in Alzheimer's disease. Alzheimer's disease (AD) temporal cortex (Brodmann area 22) was investigated using stains for astrocytes (GFAP immunohistochemistry), paired helical filaments (Gallyas silver impregnation) and beta A4-protein deposition (beta A4-protein immunohistochemistry). Paired helical filament formation (PHF), as demonstrated by neurofibrillary tangle (NFT) and neuritic plaque (NP) density, was greatest in the pyramidal cell layers III and V. beta A4-protein deposition was greatest in layer III but was present in all neocortical layers. In a regression analysis, astrocyte density was significantly correlated with beta A4-protein deposition (R2 = 0.35, P = 0.02). Astrocyte density was also positively correlated with PHF formation as measured by NFT (R2 = 0.16, P = 0.14) and NP (R2 = 0.25, P = 0.06) density, but this was less significant. This quantitative study demonstrates that both beta A4-protein deposits and PHF formation are positively correlated with the severity of astrocytosis and that damage to the brain parenchyma in temporal cortex in AD may be slightly more strongly associated with beta A4-protein deposition than paired helical filament formation. These results demonstrate the close association of astrocytes with beta A4-protein deposition and neuritic change in AD.


Magnetic stimulation of motor cortex in relation to fastest voluntary motor activity in neurologically asymptomatic HIV-positive patients. Forty-two HIV-positive patients of various CDC stages without clinically evident neurological deficits were examined with transcranial magnetoelectrical stimulation (TMS). Cortical as well as cervical and lumbar root stimulation was performed after excluding peripheral neuropathies in comparison to an age- and sex-matched control group. Whereas central conduction times were normal, conduction between cervical or lumbar roots and muscle was prolonged. Results were correlated to those of a motor test battery, which revealed slowing of fast alternating movements similar to findings in extrapyramidal disorders. Data indicate that proximal parts of the peripheral nervous system and extrapyramidal structures are subclinically involved in early HIV infection whereas the fastest corticospinal projections remain intact.


Smooth-pursuit eye movements: alterations in Alzheimer's disease. Smooth-pursuit eye movements induced by targets moving at constant velocities (from 5 to 100 deg/sec) were recorded from 13 patients with Alzheimer's disease (AD) and from 11 healthy subjects. Four variables were evaluated to quantify the patients' response to the eye movement tests: (1) average peak velocity of smooth-pursuit; (2) percent target matching index after saccade removal (percent ratio between the area of the velocity curve of smooth-pursuit eye movement after saccade removal and the area of target velocity) which is related to the eye performance for each value of target velocity; (3) total amplitude of anticipatory saccades; (4) total number of anticipatory saccades. Compared to the controls, AD patients were found to have significantly lower values of average peak velocity of smooth pursuit and of percent target matching index and a significantly increased number and amplitude of anticipatory saccades. A discriminant stepwise analysis indicated that 5 oculographic variables were significantly associated with the patient's clinical condition (healthy volunteer or AD patient). These statistics yielded an equation for predicting the patient's status according to which the percentage of cases classified correctly was 82.6% in the overall group (n = 23). The predictive performance was similar between the healthy volunteers subgroup (81.8%, n = 11) and the AD subgroup (83.3%, n = 12). The discriminant score was significantly correlated with the score resulting from the MiniMental test (r = 0.67). A significant correlation was also found between the MiniMental score and the number of anticipatory saccades (r = -0.61). No significant correlation was present between the gain of smooth pursuit and the patients' cognitive decline.(ABSTRACT TRUNCATED AT 250 WORDS)


Dopa-responsive dystonia with depigmentation of the substantia nigra and formation of Lewy bodies. The patient, who died at 23 years of age, was first diagnosed when she was 12 year old as having a dopa-responsive dystonia with decreased concentrations of monoamine metabolites in the cerebrospinal fluid. Also the concentrations of other neurotransmitters including somatostatin, substance P and metenkefalin were lowered indicating a more widespread damage of the cerebral neurotransmitter systems. At autopsy the brain was essentially intact except for pronounced gliosis and extreme loss of melanotic nerve cells in the substantia nigra. Several remaining nerve cells showed the presence of Lewy bodies.


Convulsive action and toxicity of uremic guanidino compounds: behavioral assessment and relation to brain concentration in adult mice. Four guanidino compounds that are known to accumulate in uremia, namely creatinine, guanidine, guanidinosuccinic acid and methylguanidine, were administered intraperitoneally and intracerebroventricularly to adult albino mice and the compounds epileptogenic and toxic properties were behaviorally assessed. After intraperitoneal injection, brain concentration of the compounds as a function of injected dose was monitored additionally. Guanidino compound brain concentration was determined by cation exchange chromatography with fluorescence ninhydrin detection. After systemic administration, especially guanidinosuccinic acid and methylguanidine induced long-lasting generalized convulsions which gradually increased in severity. Increasing the dose injected intraperitoneally resulted in linear increase in brain concentration of the injected compounds, in parallel with increase in proportion of animals presenting with convulsions and/or severity of convulsions. Guanidinosuccinic acid brain concentration increased more slowly than that of the other 3 compounds and guanidinosuccinic acid also exerted its effect later than the others. Since none of the other metabolically related guanidino compounds determined was significantly increased in the brains of the injected animals, the observed behavior was most certainly induced by the compounds injected and not by some secondary metabolite. Epileptogenic properties of the four compounds were markedly and qualitatively different in systemic administration, but rather similar in intracerebral administration. A tentative epileptogenic potency order was inferred from the combined behavioral and biochemical results. All 4 of the compounds tested displayed the ability to induce full-blown clonic-tonic convulsions and they did so in a dose-related manner. Guanidinosuccinic acid appeared to be slightly more potent than methylguanidine, but both guanidinosuccinic acid and methylguanidine were considerably more potent than guanidine. Creatinine was many times less potent than the other 3 guanidino compounds. Revised epileptogenic potency order on the basis of guanidino compound brain concentration after systemic administration as well as potency order after intracerebral administration paralleled the potency order of these compounds in their GABA antagonism reported earlier. It was therefore postulated that the GABA antagonism of uremic guanidino compounds could underlie their epileptogenic character. Moreover, these compounds could very likely be at the basis of the neurological complications including epilepsy of uremic patients in whom they accumulate in physiological fluids and brain.


A 31P-NMR study of muscle exercise metabolism in mdx mice: evidence for abnormal pH regulation. We have studied exercise metabolism in vivo in the mdx mouse model of Duchenne muscular dystrophy with 31P-nuclear magnetic resonance spectroscopy. Intracellular pH, ratios of phosphocreatine (PCr) to ATP and PCr to inorganic phosphate (P(i)) expressed as PCr/ATP and PCr/(PCr+P(i)) as well as tension generated at the Achilles tendon were measured during sciatic nerve stimulation. Tension was similar between the mdx and control strain C57Bl/10ScSn at 10 Hz stimulation but slightly higher than the control at 100 Hz. The PCr/ATP and PCr/(PCr+P(i)) ratios were significantly reduced in mdx vs. control muscle during exercise. Although resting muscle pH in mdx mice is more alkaline than normal muscle, the pH of mdx muscle during exercise is reduced relative to controls, as is the rate of pH recovery. Total lactate is not elevated in the cells and so it is argued that there is a reduction in the capacity to export proton equivalents in muscles of mdx mice which could be caused by an elevation in intracellular sodium. This provides more evidence of impaired ionic regulation in dystrophic muscle and could be used as an index for the evaluation in vivo of therapeutic interventions such as myoblast transfer or gene replacement therapy.


Experimental simvastatin-induced myopathy in rabbits. We induced experimental myopathy in rabbits by giving simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. After oral administration of simvastatin (50 mg/kg/day) for 2 weeks, serum CK was elevated in 5 of 7 rabbits; degenerating or necrotic fibers were seen in 3 rabbits. Using electromyography, myotonic discharges were found in the 2 rabbits examined. The combination of myotonic discharges, necrosis and raised serum CK levels suggests that the myopathy was induced by lesions of the muscle surface membrane.


Hereditary motor and sensory neuropathy with calf muscle enlargement. We report three related patients with autosomal dominant hereditary motor and sensory neuropathy (HMSN). An unusual and characteristic feature was calf enlargement, caused by muscle fiber hypertrophy predominantly of type 1 fibers. None of the family members showed atrophy of the legs. Sural nerve pathology disclosed marked loss of myelinated fibers and numerous onion bulb formations. While cases of HMSN with calf muscle hypertrophy have been reported, the present pedigree was different from that in any of the previous cases in that no family member showed clinically apparent leg atrophy.


Oculomotor and vestibular anomalies in Pelizaeus-Merzbacher disease: a study on a kindred with 2 affected and 3 normal males, 3 obligate and 8 possible carriers. Two males suffering from Pelizaeus-Merzbacher disease were examined, one at the age of 1 year 4 months and at the age of 7 years, and the other at the age of 7 years 8 months. The former had spontaneous vertical pendular nystagmus. He also showed horizontal "micronystagmus", present only at the age of 1 year, which might be similar to "voluntary nystagmus". Both males had jerky bilateral gaze-evoked nystagmus, defective smooth pursuit and optokinetic responses and a hyporeactive vestibulo-ocular reflex (VOR). All three obligate carriers exhibited typical VOR disinhibition in the two horizontal nystagmus directions, which may be a distinctive feature. This feature was also found in one of the 7 possible carriers examined and was not observed in the 3 non-affected males, who had normal oculomotor responses.


HLA-DR2 negative narcolepsy in Australian Caucasians: clinical features, serology and sequence specific oligonucleotide typing. An almost invariable association with HLA-DR2 and DQw1 has previously been reported in Japanese and caucasian narcoleptics. We performed HLA typing in 18 Australian narcoleptics using serological techniques and sequence specific oligonucleotide probes. HLA-DQw1 was present in 15 patients and DR2 in 12; 3 patients with cataplectic narcolepsy were DR2-negative. The serological haplotype most strongly associated with narcolepsy was DRw15 (a subtype of DR2), DQw1. DRw15-positive patients were positive for the alleles DRB1*1501 and DQB1*0602 defined with oligonucleotide probes. We conclude that the association of narcolepsy with DR2 and DQw1 is not as strong as previously reported and the absence of DR2 or DQw1 does not preclude the diagnosis of classical narcolepsy, at least in caucasians. Secondly, DR2-positive narcoleptics possess characteristic serological subtypes and alleles defined with oligonucleotide probes that are also found in normals. Thirdly, the occurrence of DR2-negative cataplectic narcoleptics points to the existence of more than one narcolepsy susceptibility gene.


Are medium and long latency reflexes a screening tool for early Parkinson's disease? We have studied whether assessment of medium latency (ML) and long latency (LL) reflex amplitudes may serve as a marker for early Parkinson's disease. Twenty-three patients with idiopathic Parkinson's disease (Hoehn and Yahr stage 1 to 4) and 24 controls received 20 4 degrees toe-up rotations of a platform upon which they were standing. All antiparkinsonian medication was withheld for at least 12 h before the study. ML reflexes in the stretched gastrocnemius muscle and LL reflexes in the shortened tibialis anterior muscle were recorded from both legs. ML responses were significantly enhanced in patients compared to controls. In contrast to previous studies which studied patients who continued their usual treatment, we observed that LL responses were significantly reduced in patients compared to controls. For the purpose of individual analysis, we subsequently determined the optimal specificity and sensitivity using various criteria for abnormality. The presence of either enhanced ML responses or reduced LL responses (or both) in at least one leg yielded a maximum sensitivity of 65.2% with a specificity of 75.0% (positive likelihood ratio 2.6; negative likelihood ratio 0.5). Abnormal reflexes were almost exclusively present in patients with advanced and long-standing Parkinson's disease. These results show abnormalities of ML and LL responses in advanced Parkinson's disease, but render it unlikely that these abnormalities are a suitable screening tool for early stages of the disease. The fact that LL responses were reduced in patients taken off antiparkinsonian medication raises the possibility that this reflex is under supraspinal dopaminergic control.


Is early onset cerebellar ataxia with retained tendon reflexes identifiable by electrophysiologic and histologic profile? A comparison with Friedreich's ataxia. An electrophysiologic and histologic study was performed on 18 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Sensory and motor conduction velocity (SCV, MCV) was measured along peripheral nerves in all patients, somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) were recorded in 13; cortical stimulation (CS) in 12, and sural nerve biopsy in 4 patients were also performed. The results as a whole allow a division of EOCA patients into 2 groups: with (7 patients) and without (11 patients) peripheral neuropathy. Among EOCA patients with neuropathy a differential diagnosis with Friedreich's disease patients was not possible according to BAEPs and CS, while SSEPs could differentiate 2 out 5 patients in whom they were performed.


Evaluation of IL-2, sIL2R, IL-6, TNF-alpha, and IL-1 beta levels in serum and CSF of patients with optic neuritis. Optic neuritis (ON) is characterized by immune-mediated demyelination of the optic nerve. In this study we addressed the question of cytokine signalling as part of activation of the immune system. 20 patients with first episode of acute idiopathic unilateral ON, prolonged visual evoked potentials, but normal 1.5 tesla MRI of the brain, and normal somatosensory evoked potentials were included into the study. Paired cerebrospinal fluid (CSF) and serum samples of these patients were analyzed for the presence of interleukin (IL-)-2, soluble IL-2R (sIL2R), IL-6, tumor necrosis factor (TNF)-alpha, and IL-1 beta by an enzyme-linked immunosorbent assay (IL-2, sIL2R, TNF-alpha, IL-1 beta) or a bioassay (IL-6). IL-2 was significantly elevated in the CSF (P < 0.01), whereas sIL2R (P < 0.01) and IL-6 (P < 0.01) were significantly increased in serum. TNF-alpha could not be detected in CSF or serum, and IL-1 beta was negative in serum in all but one sample and positive in only low amount (mean 9 pg/ml) in the CSF of 6/20 patients. This cytokine pattern in ON indicates an activation of the immune system within and outside the central nervous system with a predominance of T-cell activation.


Hereditary spastic dystonia with Leber's hereditary optic neuropathy: neuropathological findings. Neuropathological findings in a 59-year-old male case of hereditary spastic dystonia with Leber's hereditary optic atrophy included: marked depletion of myelinated nerve fibres in the posterior funiculi, corticopontine tracts and striatum; practically complete neuronal depletion in the putamen and lateral part of the caudate, and mild cell loss in the substantia nigra. The putamina had changed into a spongy fibrillary scar, the pallidal fibres and laminae were practically all degenerated. Moreover, there was generalised mild fibre degeneration of the white matter. The optic nerve showed marked, predominantly central, loss of nerve fibres with demyelination.


Pupillary constriction in response to light in rodents, which does not depend on central neural pathways. We show here that the widely held belief that reflex constriction of the mammalian pupil in response to light depends exclusively upon neural pathways between eye and brain is in need of revision. We investigated the response of the pupil to light in dark-adapted rodents (golden hamsters; hooded rats; albino rats) subjected to a variety of surgical and pharmacological interventions designed to destroy or block all of the neural pathways and structures through which the reflex could be mediated. The interventions included bilateral intraorbital optic nerve section, or unilateral intracranial optic nerve section with enucleation of the contralateral eye, combined in some cases with bilateral removal of the superior cervical ganglia and/or pinealectomy; topical application of atropine; intraocular injection of tetrodotoxin (TTX). Golden hamsters and hooded rats, but not albino rats, retained an effective constriction of the pupil in response to light after all of these interventions, although the constriction was less and slower than in normal animals. These findings show that hamsters and hooded rats have both a neurally mediated fast light reflex that can be eliminated by severing connections between eye and brain, by blockade of cholinergic transmission to iris smooth muscle, and by blockade of action potentials by TTX; and a local, slower constriction in response to light, which remains after all these procedures. We have also confirmed previous observations of Bito and Turansky (1975) that pupillary constriction in response to light occurs in isolated in vitro anterior chamber preparations of hamster and hooded rat eyes.(ABSTRACT TRUNCATED AT 250 WORDS)


Neuropathologic and morphometric effects of aminoguanidine on rat nerves. Aminoguanidine prevents some pathophysiologic changes typical of streptozocin diabetes and, therefore, might be efficacious in prevention or treatment of human diabetic polyneuropathy. In order to evaluate the possible toxicity of aminoguanidine on peripheral nerves, Sprague-Dawley rats received aminoguanidine intraperitoneally in dosages of 0, 50, 100, and 300 mg/kg per day for 3 months. Only rats receiving the highest dosages developed acute and chronic behavioral changes and had decreased weight gain. Minor hepatic dysfunction also was observed in this group. Teased-fiber abnormalities were not significantly more frequent in the highest dosage group than in controls. Likewise, a significant morphometric abnormality was not found for the peroneal nerve. Mild changes were found in the highest dosage group compared to the control group in the sural nerve (increased fiber density, decreased myelin area). We interpret the small morphometric differences for the sural nerve as due to maldevelopment. We found no evidence that aminoguanidine at a high dosage (300 mg/kg per day) caused fiber degeneration or demyelination.


Reciprocal inhibition of forearm flexor muscles in spasmodic torticollis. Reciprocal inhibition between forearm extensor and flexor muscles was tested by means of an H-reflex technique in patients with spasmodic torticollis and normal controls. In both, patients and controls three different phases of reciprocal inhibition could be demonstrated with maximal inhibition at conditioning test intervals of 0 ms, 15 ms and 100 ms, respectively. However, the quantitative amount of this inhibition was different for the patients and the controls. Significantly less inhibition was found for the second and the third phase of reciprocal inhibition in the patient group. Discriminant analysis showed a clear separation between normal subjects and patients if the amount of reciprocal inhibition of the second and third phase were taken into account. We were not able to detect any side differences neither for the patients nor for the controls. The findings demonstrate a functional disturbance of motor control mechanisms of a clinically unaffected extremity in spasmodic torticollis. This is believed to reflect a bilateral disturbance most likely within the basal ganglia or their outflow. Therefore, our data support the idea, that spasmodic torticollis is associated with or even due to a generalized rather than a focal disturbance of motor control mechanisms.


Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: effect of ageing. The analysis of human skeletal muscle mitochondria revealed a progressive decline in mitochondrial respiratory chain function with age. The activities affected to the greatest extent were those of complexes I and IV which were decreased by 59% and 47% respectively between the ages of 20-30 years and 60-90 years of age. Quantitation of the 5 kb 'common' deletion of mtDNA using PCR revealed a progressive accumulation with age, from approximately 1 in 100,000 at 21 years to 1 in 10,000 at 56 years and 1 in 5000 at 78 years of age. The low absolute levels of this mutation are unlikely to contribute significantly to the observed mitochondrial dysfunction.


Bidirectional signals between Trypanosoma brucei brucei and dorsal root ganglion neurons. The extracellular haemoflagellate Trypanosoma brucei brucei releases a factor, which can induce CD8+ T-cells to produce interferon-gamma. Interferon-gamma derived from these cells promotes proliferation of the trypanosomes. We now report that these trypanosomes can interact with small neurons in cultures of rat dorsal root ganglia, which contain an interferon-gamma like immunoreactive molecule. Cultures of dorsal root ganglia were able to promote the proliferation and survival of the trypanosomes and this growth promoting effect was blocked by monoclonal antibodies against the trypanosome-derived lymphocyte triggering factor, interferon-gamma and CD8+ and by Fab-fragments of these antibodies. Living trypanosomes and the factor induced an increase in expression of major histocompatibility complex class I antigens in the cultures; this induction was blocked by Fab fragments of the interferon-gamma antibody, indicating that it is mediated by release of the neuronal interferon-gamma-like immunoreactive molecule. These data suggest, that the interferon-gamma-like immunoreactive molecule in small dorsal root ganglion neurons mimics certain physiological effects of lymphocyte derived interferon-gamma. Furthermore, the trypanosomes and small sensory neurons seem to interact bidirectionally by release of the trypanosome-derived lymphocyte triggering factor and the neuronally derived interferon-gamma-like molecule, whereby, perhaps, neuronal disturbances may be elicited and trypanosome proliferation regulated.


Immunolocalization of B-50 (GAP-43) in the mouse olfactory bulb: predominant presence in preterminal axons. Because the growth-associated protein B-50 (GAP-43) has been implicated in neurite outgrowth as well as in synaptic plasticity, we studied its light and electron microscopical distribution in the mouse olfactory bulb, an area of the nervous system which exhibits a high degree of synaptic plasticity. Immunofluorescent staining with monospecific affinity-purified anti-B-50 antibodies revealed that B-50 is most abundantly expressed in the olfactory nerve fibre layer and the granule cell layer neuropil, while little staining was observed in the external plexiform layer and in cell bodies. B-50 is absent from dendrites and myelinated axons as indicated by double labelling with monoclonal antibodies against microtubule-associated protein 2 and the large neurofilament protein, respectively. Using post-embedding immunogold labelling on ultrathin Lowicryl sections, B-50 was found to be highly concentrated in presumed growth cones in the olfactory nerve fibre layer and in thin unmyelinated axons and presynaptic terminals in the granule cell layer neuropil. Near background immunolabelling was seen in perikarya, dendrites and myelinated axons. In view of the implication of B-50 in plasticity-related phenomena, its abundance in the thin unmyelinated preterminal axons suggests that these are potential sites of extrasynaptic plasticity.


The taiep rat: a myelin mutant with an associated oligodendrocyte microtubular defect. This report describes a new inherited disorder of myelination in the rat, named taiep, in which failure of normal myelination of the CNS and subsequent demyelination result in a progressive neurological disturbance. At two months of age, myelin is present throughout the spinal cord, but is immature in the fasciculus gracilis and corticospinal tracts despite the presence of abundant oligodendrocytes. By 12 months, myelin has largely been lost in these spinal cord tracts and also in more rostral parts of the CNS, such as the cerebellum and optic nerves. Other funiculi of the spinal cord show a more diffuse lack of myelin. Oligodendrocytes develop a unique cellular abnormality, most obviously in older rats, which is characterized by the accumulation of microtubules throughout their cytoplasm. As the mutant rats age, there is a continued protracted breakdown of myelin throughout the CNS, with evidence suggesting either persistent hypomyelination or attempts at remyelination of affected axons. It is proposed that the microtubular defect in oligodendrocytes results in a disruption of the normal myelination process in certain areas of the CNS of this mutant, and eventually leads to failure of maintenance of the myelin sheath.


Childhood brain tumors that occupy more than one compartment at presentation. Multiple compartment tumors. Children whose brain tumor involves two or more compartments at presentation differ clinically and pathologically from children whose brain tumor is confined to one compartment. In this study of 3,291 children with a brain tumor, at least 10% had a tumor that occupied two or three compartments at first hospitalization. Infratentorial tumors occupying multiple compartments were 1.7 times more likely to involve the cervicomedullary junction than the mesodiencephalic junction. Younger children (1-3 years) were more likely to have had multiple compartment tumors than older children. Children whose tumor was limited to the infratentorial compartment had a longer survival than children whose tumor also occupied other compartments. Ependymoma, anaplastic ependymoma, and astrocytoma (nos) were over represented among infratentorial multiple compartment tumors. Pilocytic astrocytoma, primitive neuroectodermal tumor (medulloblastoma), and desmoplastic medulloblastoma were less likely to have occupied multiple compartments at the time of the first surgical exploration. The distributions of histologic features in tumors at the cervicomedullary junction differed from those in tumors limited to the posterior fossa or to the spinal canal. Seizures were more likely if the tumor was confined to the supratentorial compartment, whereas nausea or vomiting and headache were more likely if the tumor was confined to the infratentorial compartment. Children whose tumor was confined to the spinal canal were significantly more likely to have bladder symptoms and back and/or abdominal pain than those whose tumor also involved compartments above the foramen magnum. We conclude that brain tumors apparently confined to one compartment at presentation are biologically and structurally different from tumors evident in two or more compartments.


Therapy-related myelodysplastic syndrome in children with medulloblastoma following MOPP chemotherapy. Between 1978 and 1988, 20 children with medulloblastoma (MB) of the brain were treated postoperatively with MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine). All but one received post-operative radiation prior to MOPP. Eight of 20 patients remained in continuous complete remission from MB, two of whom eventually developed myelodysplastic syndrome (MDS). Following resection of MB at age 12 months, one patient was treated with 24 courses of MOPP over 2 years without radiation therapy. She developed pancytopenia, and MDS was diagnosed 19 months after the completion of MOPP. Analysis of unstimulated bone marrow (BM) chromosomes showed structural abnormalities involving chromosomes 7, 10, 17, and 21. Eight months later, MDS evolved into acute myeloid leukemia. The second patient was diagnosed with MB at age 7 years and received postoperative craniospinal radiation followed by 12 courses of MOPP over one year. Five months after completion of MOPP, she developed MDS with monosomy 7 on chromosome analysis of bone marrow cells. Therapy-related MDS may be a complication of MOPP chemotherapy for MB in young children.


Combined intra-arterial chemotherapy followed by radiation in astrocytomas. Seventy-five patients harboring astrocytomas received 4 cycles of infra-ophthalmic carotid injections of BCNU, combined with vincristine intravenously and procarbazine orally. All of the patients thereafter, received radiation therapy. The five year survival was 73% for all patients. The age of the patients had no significant impact on survival. The treatment results were compared with the results of 57 patients with astrocytomas who were treated with surgery followed by radiation in the same period. These 57 patients had a 5 year survival of 45% with a five year survival in patients < or = 40 years and patients > 40 years of 70% and 22%, respectively (p < 0.05). In multivariate survival analysis of the BCNU group and radiation group together, treatment group and corticosteroid dependency were the only prognostic factors. No leukoencephalopathy was seen during the treatment or in the follow-up of the patients. We conclude that pre-radiation intra-arterial chemotherapy can be given without significant morbidity and produces an improvement in survival in patients older than 40 years.


Metabolic changes of glioma following chemotherapy: an experimental study using four PET tracers. To shed light on the metabolic changes in glioma following therapy, uptake changes among 18F-fluoro-2'-deoxyuridine (18FUdR), 14C-thymidine (dThd), 14C-methionine (Met) and 3H-deoxyglucose (DG) in glioma model after chemotherapy were studied, as a means for interpreting clinical PET results, together with the changes in the bromodeoxyuridine (BUdR) labeling index. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(-2chloroethyl)-3-nitro sourea hydrochloride (ACNU) was administered intraperitoneally in the tumor-bearing rats and uptake of the tracers or BUdR labeling index in tumor tissue were measured. The metabolic response following chemotherapy was a sharp fall immediately for 14C-dThd and 18FUdR and a moderate fall for 14C-Met whereas there was a fall in 3H-DG from 1 week after chemotherapy. The changes of BUdR labeling index paralleled that in the uptake for dThd and FUdR. These result indicate that PET scans using a variety of tracers in conjunction could be used for clinical diagnosis and evaluation of therapy in glioma cases. 18FUdR is a promising tracer of nucleic acid metabolism to evaluate the proliferative potential of brain gliomas.


Intraneoplastic application of metrizamide-containing liposomes: kinetic studies with computed tomography. Liposomes may serve as drug carriers not only for systemic chemotherapy but also for intraneoplastic drug therapy because they show a sustained drug release. In the present study, the in vivo kinetics of intraneoplastic deposits of large multilamellar vesicles containing metrizamide was followed up in a rat tumor model with computed tomography. The influence of four different lipid compositions on the retardation capacity of large multilamellar liposomes was investigated. By comparing the dynamic data of X-ray attenuation and volume of liposome deposits, a rank order for the in vivo stability of metrizamide containing multilamellar vesicles could be established: the least stable liposomes were made of pure dimyristoyl-phosphatidyl-choline, the most stable type was made of equimolar parts of stearoyl-palmitoyl-phosphatidyl-choline and cholesterol. Of intermediate stability were liposomes made of equimolar parts of dimyristoyl-phosphatidyl-choline and cholesterol, and those made of pure stearoyl-palmitoyl-phosphatidyl-choline. The addition of 50% cholesterol increased the membrane stability of both dimyristoyl-phosphatidyl-choline and stearoyl-palmitoyl-phosphatidyl-choline liposomes. No diffusion of large multilamellar liposomes away from the injection site was observed. The in vivo stability of the liposomes was considerably less than that observed in vitro, suggesting active degradation processes. It is concluded that large, multilamellar liposomes may be suitable carriers for intraneoplastic chemotherapy. The present model is easily adaptable to be transferred into clinical conditions, and may allow direct monitoring of intraneoplastic liposome-mediated chemotherapy in human brain tumors.


Lumbar root compression by a gas-containing cyst in the extradural space. Case report. The case report describes a patient with acute sciatica of three months duration, resulting from lumbar root compression by a gas containing cyst in the extradura space. This condition is related to vacuum disc phenomenon, because the gas appears to have originated from within the adjacent disc space.


Isolated oculomotor nerve palsy following apoplexy of a pituitary adenoma. An isolated oculomotor nerve palsy is very rarely the presenting sign of a pituitary adenoma. It may occur slowly due to mechanical compression or rapidly, secondary to pituitary apoplexy. Magnetic resonance imaging (MRI) with and without gadolinium DTPA enhancement provides excellent anatomical detail and is useful in the planning of the operative procedure. When correctly diagnosed and treated, the third nerve dysfunction appears to be reversible. We report a case of a pituitary adenoma presenting with an isolated, partial oculomotor nerve palsy in the setting of apoplexy. The pathophysiology, prognostic factors and MRI findings of this entity are discussed.


Extra-foraminal prolapsed lumbar disc: a possible cause of recurrent sciatica in failed low-back surgery patient. Case report. The present report describes the case of a 48 year-old woman who had undergone two separate lumbar laminectomies for a L4-L5 disc. She was admitted for a recurrent sciatica of 6-months duration, which failed to respond to conservative treatment. Myelogram on admission was negative. However CT showed a far laterally placed bulging L4-L5 disc. The patient was successfully reoperated on using a paramedian posterolateral approach on the side of the lesion. The rationale for this approach is discussed.


Isolated aspergillosis of the sphenoid sinus. Case report. The Authors report a rare case of isolated sphenoid sinus aspergillosis in a 69-year-old man. The patient had a complete recovery. The preoperative CT-scans and the preoperative and postoperative MRI are shown. The incidence, the pathology, the various clinical presentations, the prognosis and the management of this disease are debated.


Spontaneous cervical epidural hematoma with Brown-Séquard syndrome and spontaneous resolution. Case report. Spontaneous spinal epidural hematoma (SSEH) is an un common cause of cord compression. It is non-traumatic in origin and usually produces a severe neurological deficit. We report a case of SSEH that caused a Brown-Séquard syndrome and resolved spontaneously following myelography.


Cervical epidural abscess: approaches to diagnosis. We report on two cases of cervical epidural abscess (CEA). Their clinical presentation included fever, neck pain and symptoms of neural compression, and the presence of epidural abscess was documented by surgery. Several imaging methods were used to establish a prompt diagnosis of CEA in both patients. Magnetic Resonance image provided a noninvasive means of visualize both extent in the spinal canal and paravertebral locations. None of the other currently used imaging modalities could provide the same information alone. The role of these techniques in diagnosing this condition is discussed.


Nurse administrators in job transition: stories from the front. Nurse executives continually experience legal and ethical dilemmas that affect their personal and professional lives. An issue facing increasing numbers of nurse executives is turnover, whether voluntary or involuntary. The next several columns will explore the nurse administrator in job transition, with the goal of increasing their understanding of their legal rights and responsibilities when dealing with this aspect of their professional practice.


The role of real time B-mode ultrasonography in the follow-up of patients submitted to carotid endarterectomy. Sixty-eight patients submitted to carotid endarterectomy for carotid stenosis have been studied periodically by B-mode real time ultrasonography. This non-invasive investigation allows to detect not only a recurrent stenosis, but also minor changes following endarterectomy, including suture, lesions from clamps, myointimal proliferation, and intimal flaps. We think that all patients submitted to carotid endarterectomy must be explored periodically by duplex scanning, in order to follow-up the normal and pathological changes of the arterial wall.


Optic nerve injury in children. A prospective study of 35 patients. Thirty-five children under 15 years of age with optic nerve injury are prospectively studies for their clinical presentation, radiological findings, visual evoked potentials and outcome. Over 50% were under 10 years of age. In half of the children, injury was due to fall from a height. Fracture of the skull was recorded in a third of the patients, and optic canal fracture was seen only in three children. Visual Evoked Potentials (VEP) were record in 30 children and were repeated several times in first three weeks. All the patients received corticosteroids and optic canal decompression was not carried out routinely. Overall spontaneous visual recovery was observed in 12 patients. Among the 30 children in whom Veps were recorded, 17 children had repeatedly absent VEP, and none of the children showed wave formation, 10 (77%) had visual recovery. Only in 5 patients an optic canal decompression was carried out several weeks after injury. This study brings out the role of VEP in children with optic nerve injury.


Different systems, different costs? An examination of the comparability of workload measurement systems. This study examines the equivalence of the hours of care estimates of four patient classification/workload measurement systems. Although the hours of care estimates of the systems were similar, differences between the estimates could be as great as 4.53 hours per day for the same patient. The researchers developed relational statements that made hours of care estimates equivalent for all systems studied. System differences can have a profound impact on nursing unit and department budgets, if not adjusted.


A new prospect on the approach to open, complex, craniofacial trauma. Complex craniofacial trauma has been traditionally managed in three stages: urgent craniotomy, secondary orbitofacial repair and delayed cranioplasty. Departing from this conventional approach, we employ an early single-stage neuro and plastic-surgical reconstruction for patients presenting open cranial wounds of the frontobasilar region coexisting with orbitofacial fractures. Neurological outcome does not seem to be affected by the additional operating time, nor is the incidence of infection raised, although bone fragments are repositioned, primary bone grafting is employed, and metallic material is used for fixation. Adequate direct exposure followed by reduction and rigid internal fixation results in primary bone healing and permits to avoid the difficult complications related to soft tissue contracture over misaligned bone. Compared with the conventional staged approach, immediate reconstruction appears functionally and aesthetically preferable, as well as technically easier.


Public health service administration and academia. A joint venture. Joint ventures between service and academia are designed to enhance the quality of client services, enrich faculty teaching experiences and skills, and strengthen communication channels. The joint venture described in this article is an example of how public health nursing services and academia can be united through faculty participation in administration. Included in the discussion are the impetus for the project, the contract negotiations, the positive outcomes and disadvantages of the venture, and questions that should be raised when a similar venture is considered.


A registered nurse-licensed vocational nurse partnership model for critical care nursing. The development, implementation, and evaluation of a program that incorporates a registered nurse and licensed vocational nurse partnership model into the critical care practice setting is described. This model can be used by nurse executives to alleviate some of the immediate consequences of the nursing shortage and potentially to achieve a longer-range solution by expanding the pool of registered nurses. Evaluation of the program revealed statistically significant increases in nurse job satisfaction; perceptions of reduced workload and stress; a perception by registered nurses and physicians of increased nursing care quality; decreased registered nurse turnover and sick time; and a positive perception of the role of the licensed vocational nurse in the critical care unit.


Referral sources in home healthcare.

Referral sources in home healthcare. Home health agencies are dependent on referrals for survival, and sources for referrals are limitless. It is imperative that administrators have systems in place to accept referrals, including all data that are pertinent to the care of the patient, collect and maintain referral source data to use as one aspect of the agency's internal evaluation process, and target its marketing efforts. A home health agency must have approved policies and procedures available that address criteria for admission, continuation, and discharge from service. These must be shared with the personnel of the referral sources. The admission criteria should state the types of referrals that are not appropriate for service and how these referrals will be handled. As part of the overall management of the agency, administrators must also be aware of seasonal trends and how they may affect staffing and total budget. A positive relationship between the staff of the home health agency and the referral source is one way to generate needed referrals. The end result will benefit the patient, the agency, and the referring source.


Unit-based shared governance. Nurturing the vision. Once a unit-based shared governance counselor model is established, the evolution from establishing the structure of shared governance toward the process of initiating goal-oriented activities begins. Nurturing staff participation, empowerment, and effective communication patterns are vital. The author shares strategies to address these issues and accelerate development of the transformational vision of shared governance.


Implementation issues in home healthcare universal precautions. Universal precautions in home healthcare are essential, yet cost and compliance monitoring are major barriers to their implementation. To help administrators ensure adherence to universal precautions, the authors present specific strategies, including management commitment, a comprehensive training program sensitive to the educational level of the employee, and participation of employees in the continuing implementation and evaluation of the universal precautions policy.


Non operative management of acute extradural hematomas in children. The Authors have reported a series of 15 patients with acute epidural hematomas (EDHs) that were not evacuated surgically. These EDHs were diagnosed 6 hours after injury and were followed by serial CT scanning. All patients showed resolution of the hematoma on CT scanning over a period of 2 to 5 weeks. Factors that influence outcome of medical treatment have been discussed.


Autonomous staff selection teams.

Autonomous staff selection teams. Although some other organizations encourage staff input into employee selection, the advanced care department at Bellin Hospital in Green Bay, Wisconsin has taken this concept to a new level by implementing an autonomous interview team. This team is empowered to make hiring decisions for all positions within the department without management influence or interference.


The 'temporomandibular pain dysfunction syndrome' personality: fact or fiction? It is widely accepted that abnormal personality traits are important factors in the aetiology and maintenance of the temporomandibular pain and dysfunction syndrome (TMPDS). However, the foundation upon which this paradigm rests is largely based on clinical lore rather than evidence. The continued belief in the stress theory has onerous implications. First of all, clinicians could be lulled into a false sense of security about the efficacy of traditionally sanctioned treatments. Second, and potentially more important is the chilling effect on research that results from the premature and unsupported conclusions voiced by many, that certain issues regarding the diagnosis and treatment of TMPDS are solved. Such conclusions will lead not only to problems of patient care but may forge an unstable foundation for future research. Three theories are examined for convergent evidence in support of the putative relationship between personality and TMPDS. They are the 1) psychosomatic 2) coping and 3) psychophysiological theories. Currently evidence lacks for all three theories although there is partial support for the latter. It has not been demonstrated that TMPDS cases are characterized by a specific premorbid personality.


Filler particle size and composite resin classification systems. The currently used composite resin classification systems need review if they are to continue to serve as descriptives and quantitative parameters denoting the filler particle content of these materials. Examination of the particles in 12 composite resins using a technique of washing the filler particles from the matrix of the composite resin was presented as yet another method of grouping composites according to filler particle content. Light microscopic examination of the filler particles that remained provided a separation of the 12 materials into four easily distinguished groups based on filler particle sizes. The wear of the 12 composite resins determined in a previous study was examined in relation to the classification of the materials by the currently available systems. The wear values were also examined using the groupings of the materials according to their filler particle sizes as determined by separating the particles from the matrix by the washing technique. Grouping composites on the basis of the filler particle sizes found after washing was easily correlated with wear and supported the suggestion that composites with smaller filler particles wear less.


Longitudinal study on occlusal force distribution in lower distal-extension removable partial dentures with circumferential clasps. In this study, longitudinal changes of the occlusal force distribution ratio were examined in lower distal extension removable partial dentures with cast circumferential clasps. Occlusal force applied to the denture base and forces transmitted to the retainers were measured on several separate occasions from the insertion of new dentures to about 4 months after. Two rates of loading were chosen. One was simulated mastication (fast loading rate) and the other was 10 Ns-1 (slow loading rate). Location of the loading points were first premolar (P1), second premolar (P2) and first molar (P3) of the denture. The occlusal force distribution ratio to the retainers was calculated when a load of 20N was applied to the loading point. The results are summarized as follows: (1) The occlusal force distribution ratio at fast loading rate on P1 and P2 was changed until 1 or 1 1/2 months after the insertion of the new dentures, and then became constant. This constant value was 30% on P1, 20% on P2 and 10% on P3. (2) Slow loading rate produced a greater ratio than the fast loading rate on P2 and P3 while there were no remarkable differences in the ratio between both loading rates on P1.


The recording and analysis of EMG and jaw tracking. I. The recording procedure. A computer-based system is described which records and analyses electromyographic (EMG) signals and tracking data for mandibular movements during function. EMG signals were obtained bilaterally from six muscles and a Sirognathograph monitored the position of the lower incisor teeth in three dimensions. Directed jaw movement tasks by subjects were monitored. These data were continuously sampled at a rate of 1 KHz per channel over an operator controlled period. Analysis of the data was performed off-line following the experiment. Individual chewing cycles associated with masticatory function were identified and the timing and dimensions of each chewing envelope established. Corresponding EMG values were also determined and displays of EMG and jaw movement were plotted on a common time base. An average chewing cycle and correlated EMG activity could also be displayed on a high resolution monitor and plotted for a hard copy to enable a comparison to be made between subjects with and without jaw dysfunction.


Bending strength of Fuji and Ketac glass ionomers after sonication. Glass ionomer cements mixed by conventional methods contain voids that can decrease their overall strength. This study evaluated the effect of sonication on the reduction of air entrapment by measuring the bending strength in glass ionomer cements (Fujj-II and Ketac-fil). Glass ionomer cement was placed in identical-test vials and sonicated for 45s, 10s, or 0s. The bending strengths were measured (0.005 in min-1) after setting times of 1 or 2 weeks. Mean bending strengths (MPa +/- SD) for the 12 treatment both cements (P < 0.001) and sonication times (P < 0.001). The effect of setting time produced minimal increases in bending strength (P < 0.218). The sonication of freshly mixed glass ionomer cements is a possible solution for reducing voids to increase bending strength.


Physics and the sounds produced by the temporomandibular joints. Part II. In clinical dentistry, the solidborne vibrations (tissue pressure waves) produced by the temporomandibular joints (TMJ) may signify dysfunction or disease of the mandibular locomotor system. This article discusses aspects of the applied mathematics and electronic recording of solidborne vibrations of the TMJ (electrovibratography).


An in vitro study of the influence of X-ray beam angulation on the radiographic images of the amelocemental junction and simulated alveolar crest. The aim of this in vitro study was to determine the effect of X-ray beam angulation on the radiographic images and relative positions of the amelocemental junction and alveolar crest. Using an artificial model to represent the tooth/bone relationship, radiographs were taken of a total of 15 extracted premolar teeth which had been divided into three distinct groups on the basis of the contour (configuration) of their approximal amelocemental junction. Radiographs of the tooth/bone units were taken at baseline and with a range of horizontal and vertical X-ray beam angulations from 5 degrees to 20 degrees. Analysis of the radiographs revealed that when using the ideal horizontal angulation the radiographic image of the amelocemental junction was dependent upon its contour and was not always represented by its mid-point bucco-lingually. Changing the horizontal angulation of the X-ray beam altered substantially that part of the junction visible on the film regardless of contour. Variation in the vertical angulation of the X-ray beam had little influence on the distance between the radiographic images of the amelocemental junction and a point representative of the approximal crest of the alveolar bone. It is concluded that the contour of the approximal amelocemental junction has an influence on its radiographic appearance and that films taken with an inappropriate horizontal angulation never provide an image of its mid-point bucco-lingually.


Bite-force endurance in patients with temporomandibular joint osteoarthrosis and internal derangement. The aim of this study was to investigate the potential clinical relevance of testing bite force endurance in patients with articular temporomandibular disorders. The endurance of a 50 N bite force was measured in 51 patients with painful temporomandibular joint disorders. The results were compared to those of a control group of 20 subjects. The force exerted was sustained until this task could not be continued because of intolerable pain or fatigue. The endurance test was repeated following therapy. Testing bite force endurance could be reliably carried out (paired t-test not significant, product-moment correlation coefficient 0.87). The mean endurance time in the patient group was significantly different from that of the control group (t = 7.43, df = 69, P < 0.01). The 95% confidence intervals for patients and controls did not show any overlap. No difference in endurance time between diagnostic subgroups could be detected (F = 1.30, df = 4,46, P < 0.28). Following treatment, all patients showed a significant increase of endurance time (t = 8.09, df = 50, P < 0.01) and reported a decrease in post-test pain. The mean difference between pre- and post-treatment endurance was 60s. Subjects of the control group stopped the biting effort predominantly because of muscle fatigue. By contrast, the main reason of the patients to cease the effort was TMJ pain. The results of this study indicate that the discriminatory power of the test is sufficient to justify its utility as a complementary tool in assessing the functional capacity of the masticatory system.