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Biomedical subjects

A J Windebank

Publications and source records attributed to A J Windebank.

At least 109 records · Page 6Linked to original sources
PubMed1990

How frequently does classic amyotrophic lateral sclerosis develop in survivors of poliomyelitis?

There is a paucity of reports of classic amyotrophic lateral sclerosis (ALS) developing in survivors of paralytic poliomyelitis. We describe a patient with classic ALS and an antecedent paralytic disease thought to have been poliomyelitis from which she recovered completely. If the paucity of ALS preceded by true poliomyelitis is not merely a matter of underreporting, antecedent paralytic poliomyelitis may have a protective role against the development of ALS. This has implications relevant to pathogenesis and to projected secular trends of ALS incidence since the introduction of poliomyelitis vaccines. There is a need to establish the incidence of cases of classic ALS in patients with antecedent poliomyelitis.

Aged↗
PubMed1990

The syndrome of acute sensory neuropathy: clinical features and electrophysiologic and pathologic changes.

We followed 42 patients with clinically defined pure sensory neuropathy of acute or subacute onset for 2 to 35 years. The symptoms began in the upper limbs in 23 patients, in the lower limbs in 13, symmetrically in all 4 limbs in 4, and the face was 1st affected in 2. For 19 patients, the symptoms began asymmetrically. Electrophysiologic testing typically showed absence of sensory potentials. Spinal fluid was usually acellular with a normal protein level. Sural nerve biopsy in 22 patients showed loss of large myelinated fibers and axonal atrophy without inflammation. Six of the patients died: 4 of unrelated causes and 2 of subdural hemorrhages. Only 2 patients had severe functional impairment. Twenty-two had significant sensory deficit but were able to carry out most of their usual activities. In 8, the symptoms had resolved completely. The acute, often focal onset suggests an immune-mediated or vascular process at the level of the posterior root or dorsal root ganglion.

Aged↗
PubMed1989

3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction, which result from impaired release of acetylcholine from cholinergic nerve terminals. It is frequently associated with cancer, it is autoimmune-mediated, and treatment has been unsatisfactory. 3,4-Diaminopyridine enhances the release of acetylcholine. In this prospective, double-blind, placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome (7 of whom had cancer), 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome. Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities, and from 45 to 65 percent of normal in the lower extremities. The amplitudes of compound-muscle-action potentials nearly doubled, increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg. Autonomic symptoms were relieved. One patient had a seizure after 10 months of treatment, but other side effects from the drug were minimal and dose-related. We conclude that 3,4-diaminopyridine, either alone or in conjunction with other therapies, may be useful in the treatment of Lambert-Eaton myasthenic syndrome.

4-Aminopyridine↗
PubMed1989

Biological activity of a new neuronal growth factor from injured peripheral nerve.

In response to transection injury, the distal nerve segment produces a soluble neurite promoting factor (SN). In this study, the ability to support neuronal survival and differentiation have been studied. Embryonic rat dorsal root ganglion (DRG) neurons were plated out on collagen substrates and incubated in medium containing either SN or nerve growth factor (NGF). The number of surviving neurons was counted after 1, 2, 4, 7, and 15 days in vitro. After fixation and staining, the diameter of the surviving neurons was measured. During the period of observation, 60.8 +/- 5.8% of plated neurons survived in the presence of NGF and 90.5 +/- 12.9% survived with SN (P less than 0.05). The mean of median neuronal cell diameter was 28 +/- 2.7 microns with NGF and 34.2 +/- 3.7 microns with SN, (P less than 0.01). This increased diameter was due to enhanced survival of 30-50 microns diameter neurons. In parallel experiments, the degree of myelination of DRG neurons by Schwann cells was assessed morphometrically. In the presence of SN there was an 86% increased in myelination compared with NGF which indicates that not only is the survival of neurons increased but they are able to become fully differentiated in the presence of SN.

Animals↗
PubMed1989

Residual ethylene oxide in hollow fiber hemodialysis units is neurotoxic in vitro.

Ethylene oxide gas is used to sterilize plastic medical equipment including capillary flow dialysis membranes. To test whether ethylene oxide retained in the dialyzers might be neurotoxic, tissue culture medium was incubated in the blood compartment of dialyzers. Embryonic rat dorsal root ganglion neurons were then incubated in this medium for up to 5 days. During the first 24 hours axonal growth was normal. During the next 24-hour period varicosities appeared on axons, and after 4 days neuron cell bodies died. The pattern of degeneration was identical to that observed when cultures were exposed to an atmosphere containing 1 ppm ethylene oxide gas. Culture medium introduced into dialyzers after routine prerinsing still caused degeneration, which was not completely abolished even by a 10-liter rinse. When medium was exposed to identical dialyzers sterilized by gamma irradiation, no changes were seen in culture. Identical morphological changes were produced by using dialysis patient serum in the culture medium in place of the usual calf bovine serum. Such changes were never seen with control human serum. Since ethylene oxide is toxic to the human peripheral nervous system, it is proposed that ethylene oxide in dialyzers may contribute to the progressive neuropathy observed in patients on long-term hemodialysis.

Animals↗
PubMed1987

Nonsystemic vasculitic neuropathy.

Among 65 patients with necrotizing vasculitis, 45 had systemic and 20 had nonsystemic vasculitic neuropathy. In nonsystemic vasculitic neuropathy, clinically only nerves are affected; there are no, or few, constitutional symptoms or serological abnormalities. The clinical and pathological features are those of an ischaemic neuropathy caused by a necrotizing vasculitis of small arterioles. These 20 patients had neuropathic symptoms for a median time of 11.5 yrs (range 1-35 yrs). The clinical pattern of neuropathy was that of multiple mononeuropathy in 13, asymmetric neuropathy in 4, distal polyneuropathy in 3, and sensory polyneuropathy in 1. As compared with their initial evaluation, 8 are now worse, 5 are better, 4 are approximately the same, and 3 are dead from unrelated causes. Prednisone was thought to prevent the development of new lesions in some cases. By contrast, of the 41 patients with systemic necrotizing vasculitis whose outcome is known, 12 are dead (median time, 1.5 yrs, range 3 months-8 yrs) and 29 are alive (median time, 6 yrs, range 6 months-22 yrs).

Adult↗
PubMed1986

Neuronal growth factors produced by adult peripheral nerve after injury.

Dorsal root ganglion neurons from embryonic rats, co-cultured with endoneurial explants from transected, adult rat sciatic nerve, extended neurites in the absence of exogenous nerve growth factor (NGF). The effect was seen with endoneurial explants from normal adult sciatic nerves or from nerves which had been permanently transected up to 51 days prior to explantation. The rate of outgrowth decreased at 5 and 7 days and reached a minimum at 14 days after transection. A second phase of increased neurite-promoting activity appeared in 28-, 35-, 41- and 51-day posttransection tissue. The early phase, but not the late phase, was partially inhibited by antisera to NGF.

Animals↗
PubMed1986

Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy.

Plasma exchange has been reported to be efficacious in chronic inflammatory demyelinating polyradiculoneuropathy. We performed a prospective double-blind trial in which patients with static or worsening disease were randomly assigned to plasma exchange (n = 15) or to sham exchange (n = 14) for three weeks. After three weeks, we observed statistically significant differences in combined measurements of nerve conduction (total, motor, proximal, velocity, and amplitude) favoring patients who had received plasma exchange. Improvement to a greater degree than for any patient receiving sham exchange was detected in the neurologic-disability score in five patients (P = 0.025) and in subset scores for weakness and reflex in four patients (P less than 0.057). We conclude that for some patients with chronic inflammatory demyelinating polyradiculoneuropathy, plasma exchange has an ameliorating effect on neurologic dysfunction and nerve conduction, but in others no improvement is observed. Because plasma was replaced with normal serum albumin, a humoral factor or factors may have a role in the neurologic deficit of this disorder.

Chronic Disease↗
PubMed1986

Specific inhibition of myelination by lead in vitro; comparison with arsenic, thallium, and mercury.

Lead induces peripheral nerve segmental demyelination in rats. Arsenic and thallium produce a peripheral neuropathy characterized by axonal degeneration in humans. Mercury and thallium appear to damage both the peripheral and the central nervous system. It is not known whether this difference in effect is due to different molecular forms of the elements, to differential access to various compartments of the nervous system, or to intrinsically different properties of the elements. Using an in vitro model system of dorsal root ganglion neurons and morphometry of neurite outgrowth and myelination, we demonstrated that mercury and arsenic produce 50% inhibition of neurite outgrowth at 3.9 and 9.6 X 10(-6) M, respectively, whereas the same degree of inhibition is produced by 1.3 X 10(-4) M thallium and 3.3 X 10(-4) M lead. Lead also produces complete inhibition of myelination at 1 X 10(-6) M, suggesting that a primary effect on myelination is present in this model system as well as in the intact rodent.

Animals↗
PubMed1986

Characteristics of neurite outgrowth from rat spinal ganglia: effects of serum and segmental level.

The outgrowth of neurites from spinal ganglia in tissue culture may be affected by many variables including medium constituents and the age of ganglia. If E15 rats were used, the rate of outgrowth from ganglion explants in response to nerve growth factor was independent of the cranial-caudal position from which the ganglia were derived. This contrasts with the cranial-to-caudal gradient present during embryonic development. The effect of serum on this outgrowth was also studied and ten of 17 lots of human placental serum, two of three lots of pooled human placental serum, and one of two lots of fetal calf serum significantly inhibited the outgrowth of neurites. This has relevance to the design of tissue culture studies and may be important in the interpretation of in vitro studies of disease mechanisms.

Animals↗
PubMed1985

Localization of lead in rat peripheral nerve by electron microscopy.

Lead intoxication in rats reliably produces segmental demyelination. Following a single intravenous injection of radioactive lead, localization of tracer was observed sequentially by quantitative electron microscopical autoradiography. The animals injected had been on a lead-containing diet for 70 days; as a result, the blood-nerve barrier was broken down and demyelination was proceeding. Six hours after a single dose, the lead was localized to the endoneurial space of the peroneal nerve, and 72 hours later, to the myelin membrane. Lead may exert a direct effect on the membrane and alter its stability both by altering the lipid content of the membrane and by directly interfering with the lamellar structure.

Animals↗
PubMed1985

Neurotoxicity of pyridoxine analogs is related to coenzyme structure.

In very high doses, pyridoxine is neurotoxic in humans and other animals. Using morphometry and a model system of dorsal root ganglion neurons in culture, we found that several analogs of pyridoxine were neurotoxic in vitro. Those that may be converted into active coenzymes--pyridoxal, pyridoxine, and pyridoxamine--were almost equal in toxicity. Pyridoxic acid, which is not active, was nontoxic. Pyridoxamine 5-phosphate, which cannot enter cells, also was nontoxic. Several hypotheses that link coenzyme function to toxic effect are described.

Animals↗
PubMed1985

Differentiation-specific regulation of Schwann cell expression of the major myelin glycoprotein.

Previous experiments demonstrated that Schwann cells from permanently transected sciatic nerves of adult rats synthesize basal levels of the major myelin glycoprotein (P0). This denervated preparation at 35 days after transection was characterized by the absence of both axons and myelin assembly. The present investigation demonstrates that production of P0 continues after culture of the Schwann cells as endoneurial slices for 14 days. Thus, the level of differentiation is unchanged in culture even though only basal levels of P0 are produced and post-translational processing is incomplete. In contrast, Schwann cells from 4-day-old rat sciatic nerves actively synthesized P0 and assembled myelin membrane; however, after only 4 days in culture biosynthesis of P0 ceased. Because the same culture conditions and precursor incorporation procedures were used for both neonatal and transected nerves, it is proposed that neonatal Schwann cells in culture return to a progenitor state that is not capable of P0 gene expression. This comparison, both before and after culture, of neonatal Schwann cells that are programmed to myelinate and Schwann cells from the adult transected nerve that were in a myelin-maintaining mode provides a useful model for investigating the mechanisms by which differential gene expression is controlled. These results confirm that axons are not necessary for specifying P0 gene expression by Schwann cells from the adult transected nerves. The role that axons play in controlling P0 gene expression by neonatal Schwann cells in culture, however, has yet to be determined. It is concluded that the differentiation and maturation of Schwann cells is multistage process that allows the sequential production of specific gene products.

Animals↗
PubMed1985

Pyridoxine neuropathy in rats: specific degeneration of sensory axons.

When rats received pyridoxine in doses large enough to cause neuropathy in humans, the animals developed gait ataxia that subsided after the toxin was withdrawn. By using quantitative histologic techniques, we found axonal degeneration of sensory system fibers and that the fibers derived from the ventral root were spared. Although the degeneration approached the dorsal root ganglion, neurons in the ganglion did not degenerate. We found no early decrease in oxygen consumption of nerve, suggesting that impaired oxidative metabolism was not the primary event.

Animals↗
PubMed1985

Myelination determines the caliber of dorsal root ganglion neurons in culture.

In order to understand the relationship of supporting cells to the differentiation of neurons in culture, we have used morphometry to study myelination of dorsal root ganglion (DRG) neurons by central or peripheral supporting cells. Dissociated DRG cultures from 15-day rat embryos, free of Schwann cells and fibroblasts, were prepared, and supporting cells were added from spinal cord or DRG; myelination commenced after 2 weeks. Control cultures received no supporting cells. At 7, 14, and 24 days, a total of 22 cultures were processed for electron microscopy. Three fascicles from defined points were sampled from each culture. In cultures containing glial cells, smaller fibers (p less than 0.001) were myelinated (mean of median diameter, 1.13 +/- 0.13 (SD) micron) than in cultures containing Schwann cells (1.67 +/- 0.17 micron), although there was no difference (p greater than 0.1) in the degree of myelination expressed as number of myelin lamellae/fiber. A new finding concerned the relationship of axonal diameter to the presence or absence of myelinating cells. In control cultures without supporting cells or in areas where supporting cells were absent, the range of neurite diameter (0.05 to 1.25 micron) and the median diameter (mean of median, 0.24 +/- 0.03 micron) were similar at different times (7, 14, and 24 days), demonstrating a stable population of neurite diameters throughout the period. In myelinated fascicles, a different distribution of neurite diameters was present. Myelinated neurites had a greater median diameter (measured to inner border of myelin) and a different range of fiber diameters compared to bare neurites. For Schwann cells, this range was 0.7 to 3.4 micron, and the mean of median diameters was 1.67 +/- 0.17 micron; for glial cells, the range was 0.6 to 2.4 micron, and the mean of median diameters 1.13 +/- 0.13 micron. Differences between myelinated and bare fibers were all highly significant (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗