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Biomedical subjects

H Powell

Publications and source records attributed to H Powell.

At least 73 records · Page 4Linked to original sources

Nerve compression injury and increased endoneurial fluid pressure: a "miniature compartment syndrome".

An inflatable miniature cuff was used to apply local compression of 80 mm Hg or 30 mm Hg to a segment of rat sciatic nerve for time periods varying from two to eight hours. The endoneurial fluid pressure was measured by direct micropipette measurement techniques at one or 24 hours after removal of the cuff, and the nerves were subjected to histological analysis. Endoneurial oedema, associated with a four-fold increase in endoneurial fluid pressure, was observed after compression at 80 mm Hg for four hours, and a three-fold increase was found after compression at 30 or 80 mm Hg for eight hours. Such an increase in endoneurial fluid pressure may interfere with intrafascicular capillary flow, and thereby constitute an important pathophysiological mechanism in nerve compression injuries.

Animals↗

Demyelination in allergic and Marek's disease virus induced neuritis. Comparative electron microscopic studies.

Patterns of demyelination were studied in sciatic nerves, spinal roots and ganglia of chickens afflicted with either Marek's disease (MD) or experimental allergic neuritis (EAN). MD was induced in susceptible chicks after hatching by inoculation of the JM strain of MD Herpes virus. Tissues from these chickens were examined 7-83 days after infection. EAN was studied 10-21 days after sensitization of 4 week old chickens to emulsions containing human peripheral nerve with complete Freund's adjuvant. In both conditions lesions were encountered which consisted of perivenular infiltrates of mononuclear cells that penetrated the basal lamina of the neurolemmal sheath, displaced Schwann cells, lysed and stripped myelin lamellae without damage to axons. Other lesions in MD were characterized by lymphomatous infiltrates that contained necrotic cells and disintegrating axons. The similarity of the demyelinating process in MD to that seen in EAN suggests that MD virus infection activates lymphocytes sensitized to peripheral nerve myelin. The findings are discussed with reference to acute idiopathic polyneuritis (Guillain-Barré syndrome) in patients with preceding or concurrent Herpes virus infections including those known to cause lymphoproliferative disorders.

Animals↗

Alloxan diabetic neuropathy: electron microscopic studies.

Peripheral nerves of diabetic rats were studied 2 years after alloxan injection. We observed demyelination and remyelination, axonal degeneration and regeneration, reduplication of basal laminae around vessels and Schwann's cells, as well as onion bulb formation by proliferated Schwann's cells. Crystalline deposits composed of aggregates of fibrillary electron dense material often occurred in vessel walls and endoneurium of diabetic animals but rarely were seen in nerves from age-matched control animals. Glycogen accumulated in myelinated and unmyelinated axons within mitochondria. Axoplasmic inclusions resembling Lafora's bodies and the inclusions of glycogenosis type IV were frequent and often were accompanied by deposits of particulate glycogen. The findings suggest that the neuropathy in alloxan diabetes is caused by metabolic impairment of anxons, Schwann's cells, and vessels, leading to segmental demyelination and axonal degeneration.

Animals↗

Perfluoro carbon bromides as contrast media in radiography of the central nervous system. A preliminary experimental report.

A preliminary investigation of the properties of perfluorooctyl bromide in the subarachnoid space revealed this compound to have suitable attenuation capacity and advantageous physical and biologic properties for demonstration of the brain and spinal cord. No acute or chronic neurotoxicity was encountered. Microscopy demonstrated evidence of chronic inflammatory changes subsequent to long term exposure to the compound. It was concluded that the medium was superior to iodophendylate in several respects and that it may provide an alternative to water-soluble contrast media. Perfluorohexyl bromide proved unsuitable for neuroradiologic use because of formation of excessive amounts of non-absorbable gas, leading to high subarachnoid pressure and severe neurologic deficits.

Animals↗

Adrenoleukodystrophy. Electron microscopic findings.

Ultrastructural and neurochemical studies were done on three male patients with adrenoleukodystrophy. In each case, the affected white matter contained enlarged glial cells filled with pathognomic intracytoplasmic inclusions consisting of electron-lucent spicules bounded by 25-Angstrom wide membranes. Similar inclusions were present in adrenocortical cells. These findings and a review of 47 reported cases indicate that adrenoleukodystrophy is a storage disorder caused by a sex-linked recessive error of metabolism.

Adrenal Cortex↗

Use of pre-coated immunoplates and freeze-dried reagents for the diagnosis of foot-and-mouth disease and swine vesicular disease by enzyme-linked immunosorbent assay (ELISA).

An indirect sandwich ELISA is used by the World Reference Laboratory for Foot-and-Mouth Disease for the diagnosis of foot-and-mouth disease virus and swine vesicular disease virus. The potential for supplying ELISA 'kits' for diagnosis to other laboratories has been assessed by evaluating the reactivity of (a) immunoplates pre-coated with rabbit antisera to FMDV and SVDV and (b) freeze-dried diluted reference antisera. Immunoplates pre-coated using a sodium carbonate/hydrogen carbonate buffer retained 100% sensitivity at temperatures of 4 degrees C and -20 degrees C over the experimental storage period of 140 days but elevated storage temperatures, 18-24 degrees C and 37 degrees C, produced declining reactivity. There was a marked improvement in retention of reactivity upon storage at 37 degrees C when employing an alternative coating buffer, ammonium hydrogen carbonate. The reactivity of the rabbit antisera diluted in sodium carbonate/hydrogen carbonate solution and freeze-dried was high, as was the freeze-dried guinea pig antisera which had been diluted in each of the test solutions investigated. ELISA 'kits' for diagnosis, therefore, could be supplied using pre-coated immunoplates, with freeze-dried antiserum reagents or a combination of the two.

Animals↗

Myopathy in an infant with a fatal peroxisomal disorder.

An infant with neonatal adrenoleukodystrophy experienced extreme hypotonia and virtually continuous convulsions at four months of age and died. Light and electron microscopic examination revealed evidence of myopathy and the presence of mitochondrial inclusions. Concentrations of very long-chain fatty acids were elevated in blood and fibroblasts and the oxidation of 14C-labeled fatty acids was defective. Urinary pipecolic acid content was increased. Activity of the peroxisomal dihydroxyacetone phosphate acyltransferase, which catalyzes the first step in plasmalogen synthesis, was decreased.

Acyltransferases↗

Control of virtual environments for young people with learning difficulties.

PURPOSE: The objective of this research is to identify the requirements for the selection or development of usable virtual environment (VE) interface devices for young people with learning disabilities. METHOD: A user-centred design methodology was employed, to produce a design specification for usable VE interface devices. Details of the users' cognitive, physical and perceptual abilities were obtained through observation and normative assessment tests. CONCLUSIONS: A review of computer interface technology, including virtual reality and assistive devices, was conducted. As there were no devices identified that met all the requirements of the design specification, it was concluded that there is a need for the design and development of new concepts. Future research will involve concept and prototype development and user-based evaluation of the prototypes.

Adolescent↗

Safety assessment of encapsulated morphine delivered epidurally in a sustained-release multivesicular liposome preparation in dogs.

We have shown that the epidural (EPI) delivery of morphine encapsulated in multivesicular liposomes (DepoFoam drug delivery system) produces a sustained clearance of morphine and a prolonged analgesia. We have sought to subsequently determine the likelihood of deleterious effects on local tissue of repetitive epidural injections of this encapsulated morphine preparation (C0401). Beagle dogs were prepared according to protocol approved by the Institutional Animal Care and Use Committee under volatile general anesthesia with chronic lumbar EPI catheters and subcutaneous injection ports. Male and female dogs (three groups) received a total of 4 EPI injections at 8-day intervals of 3 mL of C0401 (10 mg/mL morphine) (N = 6), DepoFoam vehicle (N = 6), or 0.9% sodium chloride (N = 6). Following EPI-C0401, but not saline or DepoFoam vehicle, there were transient (< 72 hr) decreases in food consumption, arousal, hindlimb muscle tone, and body temperature. Heart rate was unaltered, but there were modest decreases in blood pressure and respiratory rate, which persisted for 24-72 hr after C0401. No persistent changes in sensory/motor function, body weight, or stool/urine production were observed. Cerebrospinal fluid, blood chemistry, and urinalysis performed at surgery and on the day of sacrifice (24 hr after the last dose) were within normal ranges. Gross pathology at necropsy was unremarkable. Spinal histopathology findings were judged to be minimal (e.g., modest pericatheter inflammation and fibrosis) and present in all dogs. However, a statistical trend in the rank order of pathology scores was noted (Saline < DepoFoam vehicle < C0401). Repeated EPI injection of C0401 at the maximum dose that could be administered (30 mg) resulted in moderate, transient behavioral and physiological effects after each injection, consistent with morphine administration, and a modest effect on cord histopathology. This level of pathology is reflected in the lack of change observed in cerebrospinal fluid and lack of neurological findings. These results suggest that C0401 is without significant pathological effects at this dose after repeated epidural delivery in dogs.

Analgesia, Epidural↗

Grafts of genetically modified Schwann cells to the spinal cord: survival, axon growth, and myelination.

Schwann cells naturally support axonal regeneration after injury in the peripheral nervous system, and have also shown a significant, albeit limited, ability to support axonal growth and remyelination after grafting to the central nervous system (CNS). It is possible that Schwann cell-induced axonal growth in the CNS could be substantially increased by genetic manipulation to secrete augmented amounts of neurotrophic factors. To test this hypothesis, cultured primary adult rat Schwann cells were genetically modified using retroviral vectors to produce and secrete high levels of human nerve growth factor (NGF). These cells were then grafted to the midthoracic spinal cords of adult rats. Findings were compared to animals that received grafts of nontransduced Schwann cells. Spinal cord lesions were not placed prior to grafting because the primary aim of this study was to examine features of grafted Schwann cell survival, growth, and effects on host axons. In vitro prior to grafting, Schwann cells secreted 1.5+/-0.1 ng human NGF/ml/10(6) cells/day. Schwann cell transplants readily survived for 2 wk to 1 yr after in vivo placement. Some NGF-transduced grafts slowly increased in size over time compared to nontransduced grafts; the latter remained stable in size. NGF-transduced transplants were densely penetrated by primary sensory nociceptive axons originating from the dorsolateral fasciculus of the spinal cord, whereas control grafts showed significantly fewer penetrating sensory axons. Over time, Schwann cell grafts also became penetrated by TH- and DBH-labeled axons of putative coerulospinal origin, unlike control cell grafts. Ultrastructurally, axons in both graft types were extensively myelinated by Schwann cells. Grafted animals showed no changes in gross locomotor function. In vivo expression of the human NGF transgene was demonstrated for periods of at least 6 m. These findings demonstrate that primary adult Schwann cells 1) can be transduced to secrete augmented levels of neurotrophic factors, 2) survive grafting to the CNS for prolonged time periods, 3) elicit robust growth of host neurotrophin-responsive axons, 4) myelinate CNS axons, and 5) express the transgene for prolonged time periods in vivo. Some grafts slowly enlarge over time, a feature that may be attributable to the propensity of Schwann cells to immortalize after multiple passages. Transduced Schwann cells merit further study as tools for promoting CNS regeneration.

Animals↗

Mother's pride.

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Humans↗