Unit-based quality assurance projects Glenrose Rehabilitation Hospital.
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Adult↗
Biomedical subjects
S Love
Publications and source records attributed to S Love.
Giant axonal neuropathy: correlation of clinical findings with postmortem neuropathology.
We report the clinical and postmortem neuropathological findings in a case of long-standing giant axonal neuropathy. The patient, a caucasian male with kinky hair, was first seen at 4 years of age because of increasing unsteadiness of gait. Clinical examination showed nystagmus, cerebellar ataxia, distal sensory loss, and weakness. A sural nerve biopsy at 8 years of age revealed giant axonal neuropathy. The patient became increasingly demented and was incapacitated by weakness and ataxia; he died at 18 years of age. Histological examination of the brain and spinal cord showed numerous Rosenthal fibers, a distal axonopathy that most severely affected the corticospinal tracts, middle cerebellar peduncles, and posterior columns, and olivocerebellar degeneration.
Adolescent↗
Infantile neurodegenerative disease with neuronal accumulation of phosphorylated neurofilaments.
A caucasian male with a history of mental retardation and intractable epilepsy since birth, developed progressive wasting and weakness of skeletal muscles, leading to death at 4 years of age. A biopsy of gastrocnemius muscle at 2 years of age revealed severe neurogenic atrophy. Sural nerve biopsies at 2 and 3 years showed progressive atrophy and loss of large myelinated nerve fibers with a paucity of neurofilaments in remaining nerve fibers. Postmortem immunohistochemical and ultrastructural examination showed that neurons were markedly distended by phosphorylated neurofilaments. Whereas large lower motor neurons were most severely involved, dorsal root ganglia and neurons in the cerebral cortex and deep gray nuclei were also affected. It is suggested that this disease is caused by a disorder of neurofilament phosphorylation and transport.
Amyotrophic Lateral Sclerosis↗
Distribution of Theiler's virus in the CNS of athymic nude mice: effect of varying the route of inoculation.
Immunohistochemical and ultrastructural techniques were used to map the distribution of Theiler's virus in the central nervous system (CNS) of the nude mouse, after intracerebral (i.c.), intravenous (i.v.) or intraocular (i.o.) inoculation. Expression of viral antigen was largely restricted to the subthalamus, substantia nigra, ventral tegmental tract and the grey and white matter of the spinal cord. Electron microscopy showed paracrystalline arrays of viral particles within neurons in the substantia nigra and spinal cord. Inoculation of virus i.v. or i.o. rather than i.c. delayed the onset of neurological signs but did not affect the distribution of virus within the CNS. In particular, there was no evidence of spread along the optic pathways after i.o. inoculation. The localization of Theiler's virus within certain regions of the CNS seems to depend on differential susceptibility to infection or differential restriction of replication rather than on the route of inoculation.
Animals↗
Effects of regional spinal X-irradiation on demyelinating disease caused by Theiler's virus, mouse hepatitis virus or experimental allergic encephalomyelitis.
The effects of X-irradiation on the course of chronic demyelinating disease were examined in mice with experimental allergic encephalitis (EAE), mouse hepatitis virus (MHV) or Theiler's virus (DAV) infection. One month after the induction of EAE or 2-16 months after inoculation of DAV, exposure of the cervical spinal cord to 20 Gy X-rays caused local exacerbation of disease activity but spinal irradiation did not affect MHV-induced demyelination. In EAE, there was a significant increase in the number of inflammatory cells in the irradiated part of the cord. Mice infected with DAV showed locally increased demyelination and axonal degeneration but no change in the titer of infectious virus within the cord. Thus in DAV infection, as in EAE, the exacerbation of disease seemed to be due to vascular or immunological factors rather than viral reactivation.
Animals↗
Environmental enrichment and recovery from contralateral sensory neglect in rats with large unilateral neocortical lesions.
Previous investigations of the potential value of postoperative environmental enrichment in enhancing functional recovery in brain-lesioned rats have yielded contradictory results. The present study sought to resolve some of the contradictions by drawing a clear distinction between the contribution of environmental enrichment to the processes of compensation for sensory loss and recovery per se. By using unilateral lesions, thus avoiding total loss in any sensory modality, and examining a behavioural deficit not anyway thought to be, primarily, a consequence of sensory loss, it was hoped to arrive at an experimental test in which reinstatement of preoperative performance would necessarily reflect recovery rather than compensation. Recovery from the effects of large unilateral neocortical removals on performance on the 'bracelets' test, recently proposed by Schallert and Whishaw, Behavioural Neuroscience, 1984, 98: 518-540, as a model of simultaneous extinction in humans, was investigated. Lesions significantly impaired bracelet removal from the contralateral paw and a degree of recovery from this impairment was observed. However, recovery was not enhanced by postoperative environmental enrichment. The reasons for this were discussed and possible explanations of the recovery that did occur were considered. Implications for Schallert and Whishaw's model were also discussed. It was concluded that the present results were consistent with the view that any restorative value that postoperative environmental enrichment may have lies in facilitating compensation rather than recovery.
Animals↗
The relative antihistaminic and psychomotor effects of hydroxyzine and cetirizine.
Twelve healthy subjects with atopy received single doses of hydroxyzine, 25 mg, its metabolite cetirizine, 10 and 20 mg, and placebo in a four-way crossover study randomized by Latin square design. Skin wheal response to histamine, psychomotor effects, and serum concentrations of each drug were measured for 36 hours after each dose. Central nervous system (CNS) effects were measured with critical flicker frequency, Stroop word testing, and visual analog scales. All three active treatments (cetirizine, 10 mg, cetirizine, 20 mg, and hydroxyzine) produced an equivalent suppression of skin wheal response to histamine that was significantly greater than placebo (P less than 0.01). Hydroxyzine produced a significant change compared with placebo in all three CNS parameters. Neither cetirizine, 10 mg, nor cetirizine, 20 mg, produced any significant change in CNS parameters. Both the intensity and time course of CNS effects were related significantly (P less than 0.05) to hydroxyzine concentrations. The CNS changes measured after oral hydroxyzine are the result of the parent drug, whereas its metabolite cetirizine when administered alone produced significant antihistaminic effects without CNS changes.
Adult↗
Induction of demyelination by a temperature-sensitive mutant of the coronavirus MHV-A59 is associated with restriction of viral replication in the brain.
The neurovirulence of eight temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59 in 4-week-old BALB/c mice was investigated. Whereas a dose of 100 p.f.u. of wild-type virus killed mice within a week, a 1000-fold higher dose of ts mutants did not. Three ts mutants induced demyelinating disease in the central nervous system (CNS). The pathology of the demyelinating disease caused by one mutant, designated ts-342, was studied in detail. Pathological changes, starting 3 days post-inoculation (p.i.), were characterized by inflammation and demyelination in the CNS. Antibody responses directed against all virus-specific structural proteins were present at 7 days p.i. No virus particles were observed by electron microscopy at 14 days p.i. However, macrophages and lymphocytes were abundant in the areas of demyelination. The growth kinetics in vivo of wild-type virus, ts-342 and a revertant of ts-342 were compared. Wild-type virus and the revertant replicated rapidly in the brain and spread to the liver causing a lethal hepatitis. Ts-342, however, replicated to a much lesser extent within the brain and could not be detected in the blood or liver. The ts lesion in the genome of ts-342 seems, therefore, to determine the outcome of the infection.
Animals↗
Independent expression in serum of three tumour-associated antigens: CA 125, placental alkaline phosphatase and HMFG2 in ovarian carcinoma.
Circulating levels of CA 125, the HMFG2 antigen and placental alkaline phosphatase were measured in patients with epithelial ovarian cancer. In 37 patients the antigens were assayed before operation and 161 follow-up samples from 41 patients were assayed at different times during treatment. These three human tumour-associated antigens were expressed independently of each other. Measurement of all three antigens, compared with measurement of CA 125 alone, resulted in a statistically significant improvement in the detection rate of patients with localized disease from 18% to 69%.
Alkaline Phosphatase↗
Acute swelling of nodes of Ranvier caused by venoms which slow inactivation of sodium channels.
The venoms of the spider Phoneutria nigriventer and the scorpions Leiurus quinquestriatus and Centruroides sculpturatus cause acute, transient swelling of axons at nodes of Ranvier. The changes in the morphology of the node and paranode were studied in the mouse. Venom was injected into the sciatic nerve by means of a glass micropipette. After survival times ranging from 15 min to 3 weeks the nerves were examined by light and electron microscopy. The increase in nodal axoplasmic volume led within an hour to disruption of neurofilaments and microtubules, swelling of the paranodes and displacement of the terminal loops of myelin away from the node. Axonal calibre recovered within a few hours, but restoration of nodal width took several days and seemed to be accomplished by elongation and remodelling of the paranodal myelin. Occasional internodes were interrupted by node-like discontinuities in the myelin sheath. These developed within a few hours and persisted for the duration of the study.
Animals↗
Chronic demyelination in mouse peripheral nerve produced by lysophosphatidyl choline and X-irradiation: ultrastructural observations.
The effects of X-irradiation on demyelination and remyelination were studied in the peripheral nerve of the mouse. Three days after injection of lysophosphatidyl choline into one sciatic nerve, a 20 Gy dose of X-rays was administered to the hind limb. At survival times ranging from 4 days to 6 months after injection, the nerves were examined by light and electron microscopy. Removal of myelin debris was retarded and remyelination delayed or prevented. The myelin sheaths which did form were thin and the configuration of Schmidt-Lanterman incisures and nodes of Ranvier was abnormal. Some of the chronically demyelinated fibres formed focal node-like complexes: patches of finely granular material coated the inner aspect of the axolemma, the external surface was covered by slender processes of Schwann cell cytoplasm, and an electron-dense lamina was present in the enlarged periaxonal space. Elsewhere demyelinated axons and their ensheathing Schwann cells were separated by gap junctions or transverse bands. The present findings indicate that the morphological differentiation of structures thought to be characteristic of nodes of Ranvier can take place in the absence of remyelination.
Animals↗
X-irradiation impairs regeneration of peripheral nerve across a gap.
The effects of X-irradiation on the regeneration of peripheral nerve across a gap were studied in the mouse. The right sciatic nerve was transected and 3 days later a 20-Gy dose of X-rays was administered to the hind limb, which was shielded so that the irradiation affected either the proximal, the distal or both parts of the nerve. Within a few hours of irradiation, the proximal and distal nerve stumps were inserted into a polythene tube within which they were separated by a 5-mm gap. After 1 or 2 months the sciatic nerves were processed for examination by light and electron microscopy. Irradiation affected axonal growth, differentiation of Schwann cells and formation of a perineurium. These effects were most marked when both the proximal and distal stumps had been exposed to X-rays. At 2 months there were fewer axons in the irradiated than in control nerves (P less than 0.01), but all of the larger axons which had regenerated were myelinated, albeit more thinly than in the controls. The changes in the pattern of regeneration in the irradiated nerves are interpreted as being largely due to radiation damage to Schwann cells.
Animals↗
Differential reinforcement effects in rats reared in enriched and impoverished environments.
Comparison of the effects of environmental enrichment (EC) and impoverishment (IC) on learning in the rat is hindered by difficulty in distinguishing, experimentally, EC/IC differences in learning capacity per se from differences in performance-related variables such as sensory or motor ability, activity and motivation. Experiments are described which analyse EC/IC performance differences in a simple lever-press training procedure. In particular the hypothesis that EC and IC rats may be differentially reinforced by the same response-contingent events is examined. The data firmly support this hypothesis and possible explanations of the differential reinforcement effect are examined.
Animals↗
Morphological abnormalities in myelinated nerve fibres caused by Leiurus, Centruroides and Phoneutria venoms and their prevention by tetrodotoxin.
Morphological changes in peripheral nerve caused by the venoms of the scorpions Leiurus quinquestriatus and Centruroides sculpturatus were compared with those caused by Phoneutria nigriventer spider venom. Both scorpion venoms are known to delay the inactivation of sodium currents, Centruroides venom also altering the voltage dependence of sodium gating. Venom was injected by means of a glass micropipette into the sciatic nerves of anaesthetized mice. After survival times ranging from 15 min to 24 h the nerves were examined by light and electron microscopy. The two scorpion venoms caused alterations virtually identical to those produced by Phoneutria venom, which included swelling of the nodal axoplasm and accumulation of fluid in the periaxonal space of myelinated fibres. These alterations were most marked after 1 to 2 h and had largely disappeared by 24 h. Pre-treatment of the nerves with tetrodotoxin, which specifically blocks sodium channels, completely prevented both the nodal axoplasmic swelling and the periaxonal oedema. It seems likely that these effects result from an action common to the three venoms and that this is probably a delay in the inactivation of sodium current at the node of Ranvier.
Animals↗
Conservative surgery and radiation therapy for early breast cancer: results, controversies, and unsolved problems.
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Antineoplastic Agents↗
Encephalomyeloneuropathy in the absence of a detectable neoplasm. Clinical and postmortem findings in three cases.
The clinical and postmortem findings in three cases of encephalomyeloneuropathy are reported. Two patients presented with subacute sensory neuropathy and one with amnesia and confusion. In none of these cases was a tumour detected clinically or at autopsy. Neuropathological examination showed inflammatory lesions in the brain, spinal cord and posterior root ganglia indistinguishable from encephalomyeloneuropathy occurring as a remote effect of carcinoma.
Aged↗
Doppler shift radar monitoring of activity of rats in a behavioural test situation.
The present study investigates the use of an activity monitoring system based upon Doppler shift radar for monitoring general activity of rats in a standard open field test situation. Significant positive correlations were found between the radar activity counts and the conventional lines crossed measure of activity. On the basis of these correlations it is suggested that this method of activity monitoring might be used in conjunction with other behavioural test situations. Further potential benefits of this activity monitoring system are discussed.
Animals↗
Qualitative and quantitative morphology of human sural nerve at different ages.
A qualitative and quantitative study was made of 27 sural nerves obtained within 24 hours of death from human subjects without history of disease or ingestion of drugs known to affect peripheral nerve. Parameters studied included fascicular area, internodal length and diameter of teased fibres, density of myelinated and unmyelinated axons, and axonal and fibre diameter. The slope of internodal length-fibre diameter regression lines increased progressively during the first decade but thereafter remained relatively constant until about the age of 60 years, after which degeneration and regeneration, and demyelination and remyelination caused increasing variation in internodal length. Densities of myelinated and unmyelinated axons decreased markedly from birth to the end of the eighth decade, due to increasing size and separation of fibres during the first decade, and axonal degeneration and an increase in endoneurial collagen in the older age groups. Except during the first year of life, the diameter distribution of myelinated fibres was bimodal, the lower mode occurring at 3-5 microns in all age groups and the upper shifting progressively from 5-6 microns at 1 year to 9-12 microns after the first decade. g ratios were generally higher in small than in large fibres and showed increasing scatter with age. The distribution of unmyelinated axons was unimodal until the fifth decade; thereafter the number of fine calibre axons increased. Ageing was associated with reduplication of vascular, and thickening of perineurial, basement membranes.
Adolescent↗