PubMed Health⌕ Search

Biomedical subjects

E L Feldman

Publications and source records attributed to E L Feldman.

At least 109 records · Page 6Linked to original sources
PubMed1992

Complications: neuropathy, pathogenetic considerations.

The most common form of neuropathy associated with diabetes mellitus is distal symmetric sensorimotor polyneuropathy, often accompanied by autonomic neuropathy. This disorder is characterized by striking atrophy and loss of myelinated and unmyelinated fibers accompanied by Wallerian degeneration, segmental, and paranodal demyelination and blunted nerve fiber regeneration. In both humans and laboratory animals, this progressive nerve fiber damage and loss parallels the degree and/or duration of hyperglycemia. Several metabolic mechanisms have been proposed to explain the relationship between the extent and severity of hyperglycemia and the development of diabetic neuropathy. One mechanism, activation of the polyol pathway by glucose via AR, is a prominent metabolic feature of diabetic rat peripheral nerve, where it promotes sorbitol and fructose accumulation, myo-inositol depletion, and slowing of nerve conduction by alteration of neural Na(+)-K(+)-ATPase activity or perturbation of normal physiological osmoregulatory mechanisms. ARIs, which normalize nerve myo-inositol and nerve conduction slowing, are currently the focus of clinical trials. Other specific metabolic abnormalities that may play a role in the pathogenesis of diabetic neuropathy include abnormal lipid or amino acid metabolism, superoxide radical formation, protein glycation, or potential blunting of normal neurotrophic responses. Metabolic dysfunction in diabetic nerve is accompanied by vascular insufficiency and nerve hypoxia that may contribute to nerve fiber loss and damage. Although major questions about the pathogenesis of diabetic neuropathy remain unanswered and require further intense investigation, significant recent progress is pushing us into the future and likely constitutes only the first of many therapies directed against one or more elements of the complex pathogenetic process responsible for diabetic neuropathy.

Animals↗
PubMed1991

Mannose 6-phosphate potentiates insulin-like growth factor II effects in cultured human neuroblastoma cells.

Insulin-like growth factor II (IGF-II) and mannose 6-phosphate (man-6-P) bind to distinct sites on the same receptor. In the present study, we examined the effects of man-6-P on the growth promoting effects of IGF-II on SH-SY5Y cultured human neuroblastoma cells. Man-6-P alone increased cell number and neurite outgrowth by approximately 50%; as previously observed, IGF-II increased cell number and neurite outgrowth by approximately 110 and 30%, respectively. However, when cells were grown in the presence of both ligands, cell number increased by 330% and neurite outgrowth by 130%. These results suggest that man-6-P can potentiate the known growth promoting effects of IGF-II on human neuroblastoma cells. Furthermore, they indicate that the IGF-II/man-6-P receptor may serve as a means of integrating distinct growth promoting signals in neuronal cells.

Cell Division↗
PubMed1991

Immunosuppressive treatment in multifocal motor neuropathy.

We report the results of immunosuppressive treatments of 13 patients with multifocal motor neuropathy and elevated titers of serum antibodies to the GM1 ganglioside. All patients failed to respond to oral prednisone. There was no clinical response in 4 patients treated with plasma exchange. Nine patients received cyclophosphamide, with clinical improvement and fall in antibody titers in 8. In 3 patients, cyclophosphamide was discontinued with ensuing clinical relapse and rise in the titers of serum anti-GM1 antibodies. These patients provide further evidence for the efficacy of cyclophosphamide therapy in patients with multifocal motor neuropathy.

Adult↗
PubMed1991

Receptor-coupled phosphoinositide hydrolysis in human retinal pigment epithelium.

Carbachol and histamine stimulated phosphoinositide (PPI) hydrolysis in cultured human retinal pigment epithelium (RPE), as reflected by an accumulation of 3H-inositol phosphates in the presence of 10 mM Li+. Carbachol increased PPI hydrolysis to greater than 600% of basal with an EC50 of 60 microM; stimulation was linear up to 60 min. This activation likely occurred via the M3 muscarinic cholinergic receptor based on the IC50 values for 4-diphenylacetoxy-N-methylpiperidine methiodide (0.47 nM), pirenzepine (280 nM), and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11- dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (1.4 microM). Carbachol-mediated PPI hydrolysis was decreased by 80% in the absence of extracellular Ca2+. Histamine stimulated PPI turnover in a linear manner by 180% with an EC50 of 20 microM by the H1 histaminergic receptor. Serotonin, glutamate, norepinephrine, and dopamine were inactive. In human RPE, the resting cytoplasmic Ca2+ concentration, as determined by fura-2 fluorescence, was 138 +/- 24 nM. On the addition of carbachol, there was a 180% increase in peak intracellular Ca2+; addition of histamine increased intracellular Ca2+ by 187%. These results suggest receptor-mediated, inositol lipid hydrolysis is coupled to intracellular Ca2+ flux in human RPE.

Calcium↗
PubMed1991

Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein.

We studied a series of 64 patients with sensory +/- motor peripheral neuropathies by comparing clinical and physiologic features to serum antibody reactivity against compounds containing sulfated carbohydrate moieties. We determined antibody reactivity by an enzyme-linked immunosorbent assay (ELISA) using purified glycolipids and glycoproteins as antigens, and we used high-performance thin-layer chromatography and Western blotting to test the specificity of results. Twelve patients with high titers of IgM antibodies directed against the myelin-associated glycoprotein (MAG) had sensory-motor polyneuropathies with physiologic evidence of demyelination. IgM antibody reactivity to MAG was associated with an IgM serum M protein in five patients. Eight other patients, most with sensory greater than motor polyneuropathies, had high titers of antibody reactivity to sulfatide but not of IgM to MAG. Two had an associated IgM paraprotein. None of the patients with selective serum antisulfatide activity had predominantly demyelinating features on physiologic testing. We conclude that (1) high ELISA titers of antibodies to MAG may be more common than previously suspected in patients with chronic demyelinating sensory-motor neuropathies, and (2) the presence of high titers of antisulfatide antibodies in serum may provide clues to the pathogenesis of otherwise idiopathic, axonal, predominantly sensory neuropathies.

Adult↗
PubMed1991

Acute pandysautonomic neuropathy.

Acute pandysautonomic neuropathy is characterized by severe postganglionic sympathetic and parasympathetic dysfunction, with relative or complete sparing of motor and sensory function. Of four reported cases with sural nerve biopsies, two were normal and two abnormal, revealing loss of small myelinated and unmyelinated fibers. We present a patient with pandysautonomic neuropathy and elevated CSF protein whose sural nerve biopsy showed active axonal degeneration.

Acute Disease↗
PubMed1990

Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren's syndrome.

Thirteen patients, 11 women and 2 men, developed sensory and autonomic neuronopathies in association with features of primary Sjögren's syndrome. In 11, Sjögren's syndrome had not been previously diagnosed at the time of neurological presentation. All had prominent loss of kinesthesia and proprioception. Pain and thermal sensibility were less severely affected. Most had evidence of autonomic insufficiency. In some this was severe, with Adie's pupils, fixed tachycardia, and orthostatic hypotension. The course ranged from an abrupt, devastating onset to indolent progression over years. Stabilization or functional improvement occurred in 6 patients, 2 of whom received no drug therapy. Sensory nerve conduction studies and examination of nerve biopsy specimens demonstrated a wide spectrum in the severity of loss of large myelinated fibers. The cutaneous nerves of 6 patients had perivascular mononuclear infiltrates without necrotizing arteritis. Examination of biopsy specimens of dorsal root ganglia in 3 patients revealed lymphocytic (T-cell) infiltration in the dorsal roots and ganglia, with focal clusters around neurons. In the more mildly affected ganglia, individual sensory neurons were undergoing degeneration. In the most advanced case, very few neurons remained. The possibility of Sjögren's syndrome should be considered in patients, especially women, who develop acute, subacute, or chronic sensory and autonomic neuropathies, with ataxia and kinesthetic loss.

Adult↗
PubMed1990

Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies.

We studied 74 patients with progressive, asymmetrical lower motor neuron syndromes. Clinical features of these patients, including age, sex, disease duration, patterns of weakness, and reflex changes, were evaluated by review of records. In each patient the clinical features were compared to the type of nerve conduction abnormalities and to the specificities of high-titer serum antiglycolipid antibodies. Antibody specificities were determined by an enzyme-linked immunosorbent assay using purified glycolipids and carbohydrates as substrates. Our results show that high titers of antibodies to glycolipids are common in sera of patients with lower motor neuron syndromes. Selective patterns of reactivity indicate that specific carbohydrate epitopes on the glycolipids are the targets of the high-titer antibodies in individual patients with lower motor neuron syndromes. Several distinct lower motor neuron syndromes can be identified based on clinical, physiological, and antiglycolipid antibody characteristics. These syndromes include multifocal motor neuropathy with evidence of multifocal conduction block on motor, but not sensory, axons and frequent (84%) high titers of anti-GM1 ganglioside antibodies; a lower motor neuron syndrome with predominantly distal weakness early in the disease course, no conduction block, and a high incidence (64%) of anti-GM1 antibodies; and a lower motor neuron syndrome with predominant early weakness in proximal muscles and serum antibodies to asialo-GM1 that do not cross-react with GM1 ganglioside.

Adult↗
PubMed1983

Autosomal dominant exudative vitreoretinopathy.

Eight family members had familial exudative vitreoretinopathy. They exhibited a variety of clinical stages of the disease process. Some clinical findings included retinal detachment, fibrovascular masses with dragged disc and macula, neovascular fronds and intraretinal deposits. The fundus and angiographic findings were found to be similar to those in cases reported previously. Electroretinograms were normal. Of particular interest in this pedigree was the sole clinical finding of isolated intraretinal deposits in four family members. This characteristic may represent a mild expression of the disease and warrant appropriate genetic counseling. Our study confirms the variable clinical expression of the disease.

Adult↗
PubMed1981

Studies on the localization of newly added membrane in growing neurites.

Explant culture of the adult goldfish retina results in vigorous neuritic growth, provided that the optic nerve has been previously crushed in vivo. The site of new membrane addition in these growing neurites was studied with a a membrane-binding lectin Concanavalin A (Con A) in conjunction with a fluorescent indirect antibody method. Explant cultures were labeled with Con A followed by rabbit antibodies to Con A. This treatment was shown to immobilize Con A receptors while permitting growth. Twenty-four hours later, the washed preparation was treated with fluorescent goat antirabbit antibodies. The bound fluorescent antibodies appeared as a pattern of contiguous fluorescent speckles confined to the area of old growth while regions near the distal end of the neurite were not fluorescent. These results are compatible with the hypothesis that new membrane is added in the region of the growing tip of the neurite.

Animals↗
PubMed1980

Histological localization of binding sites of alpha-bungarotoxin and of antibodies specific to acetylcholine receptor in goldfish optic nerve and tectum.

Goldfish optic nerve as well as ganglion cell neurites grown in culture selectively bind rhodamine-labeled alpha-bungarotoxin following tissue fixation. Binding is competed for by unlabeled bungarotoxin, by carbamylcholine and tubocurarine, but not by atropine. In cross-sections, the label is seen confined to axonal bundles. The binding is not detectable without prior fixation and is very faint in brain sections, even after fixation. To further establish the nature of the binding, immunocytochemical studies were performed, taking advantage of a high cross-reactivity found between goldfish brain and antibodies against eel acetylcholine receptor (AChR). Antigenic sites were detected by an indirect unlabeled antibody complexed to horseradish peroxidase. Anti-AChR antibody binding to optic nerve and neurites in culture correlated with that seen with alpha-bungarotoxin. Binding of anti-AChR was observed in the brain, and was reduced in the denervated tectum following unilateral optic nerve crush or enucleation. The results are discussed in relation to functions of receptor proteins in the retinotectal system.

Acetylcholine↗
PubMedDate not supplied

Clinical practice guidelines on depression: awareness, attitudes, and content knowledge among family physicians in New York.

BACKGROUND: In 1989, the federal government mandated that the Agency for Health Care Policy and Research (AHCPR) appoint expert panels to develop clinical practice guidelines to define standards for the provision and quality of health care. There is uncertainty about physicians' awareness and attitudes concerning guidelines. METHODS: We surveyed 992 members of the New York State Academy of Family Physicians. In addition to demographic data, respondents were questioned about awareness of AHCPR guidelines for depression in primary care, urinary incontinence, and pressure ulcers in adults; knowledge of the diagnosis and treatment of depression; and general attitudes about guidelines. RESULTS: Three mailings produced a response rate of 53.2%. While 90.5% of respondents treat depression in their primary care practices, only 33.6% are aware of the existence of the guidelines on depression 1 year after publication. Only 13.1% of respondents have a copy of the guidelines. Physicians are slightly less aware of the guidelines on urinary incontinence and pressure ulcers (30.0%). Respondents are generally knowledgeable about the diagnosis and treatment of depression, and board certification is correlated with increased knowledge about the treatment of recurrent depression. Logistic regression analyses demonstrate that female family physicians, those living in larger communities, and physicians with 3 or more years of training are most likely to have positive attitudes toward guidelines. CONCLUSIONS: The AHCPR guidelines failed to reach their targeted audience. Specific strategies derived from survey data can identify physicians who may most benefit from educational interventions.

Adult↗
PubMedDate not supplied

Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose.

Diabetic autonomic neuropathy is a major cause of morbidity and mortality. However, its etiology and treatment remain obscure. Using the in vitro rat superior cervical ganglion model of diabetic neuropathy, we studied the neuroprotective effects of IGF-I on neurite growth and neuronal apoptosis in a high-glucose milieu. In the presence of elevated levels of glucose similar to those seen in poorly controlled diabetics (20 mM above control), there is inhibition of neurite growth, reduction in neurite caliber, beading of neurites, and retraction of the neurite growth cone. High glucose also induces apoptosis in ganglion neurons. In contrast, IGF-I prevented both glucose induced apoptosis and changes in neurites, even after 96 hours. The IGF-I receptor was uniformly distributed throughout the developing neurite and growth cone in control and IGF-I treated neurons, but not with high glucose alone. These findings suggest that high glucose inhibits neurite growth and initiates apoptosis in cultured sympathetic primary neurons, and IGF-I ameliorates these changes. Collectively, these observations suggest that many of the features of diabetic autonomic neuropathy can be reproduced in a tissue culture model using defined conditions, and may have important implications in defining the etiology and treatment of diabetic neuropathy.

Adrenergic Fibers↗