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Biomedical subjects

I Ziv

Publications and source records attributed to I Ziv.

At least 73 records · Page 4Linked to original sources
PubMed1994

Can nimodipine affect progression of motor neuron disease? A double-blind pilot study.

Recently, there has been some evidence suggesting that exposure to neuroexcitotoxic amino acids, culminating in excessive neuronal calcium influx, may cause nerve cell destruction in motor neuron disease (MND). We therefore hypothesized that central calcium channel blockade with nimodipine might slow-down progression of MND. Two patients with sporadic MND were treated in a double-blind placebo controlled cross-over study with oral nimodipine (120 mg/day) for 5 months. Disease progression was assessed by repeated computerized measurements of isometric force from 20 muscle groups, and calculation of global force score. Global force deterioration slopes during the 5-month periods of nimodipine or placebo therapy were highly linear and almost identical. Nimodipine therefore does not seem to be effective in changing the course of MND. The observed remarkable linearity of disease course also confirms that cross-over methodology and serial measurements of muscle force are constructive tools in the clinical evaluation of novel therapeutic strategies for this devastating disease.

Administration, Oral↗
PubMed1994

Intravenous gammaglobulin treatment in multiple sclerosis and experimental autoimmune encephalomyelitis: delineation of usage and mode of action.

Multiple sclerosis (MS) is a central nervous system demyelinating disease of implicated autoimmune aetiology. The effect was evaluated of intravenous gammaglobulin (IVIg), a successful therapy in various autoimmune diseases, in relapsing-remitting MS patients treated for three years. IVIg treatment significantly reduced the number and severity of acute exacerbations and resulted in a lesser neurological disability. There were no significant short or long-term adverse effects to IVIg treatment. To clarify the putative therapeutic effects of IVIg, this treatment was examined in the animal model of experimental autoimmune encephalomyelitis (EAE) in the rat. IVIg suppressed active EAE in relation to disease severity and duration, despite the presence of T-cell reactivity to specific antigens, while the treatment had no effect on passive EAE induced by adoptive transfer of myelin basic protein specific CD4 + T-cells. It is concluded that IVIg treatment may be a promising treatment in relapsing-remitting MS as it can alter the natural course of the disease.

Adult↗
PubMed1994

Simulator for neural networks and action potentials: description and application.

1. We describe a simulator for neural networks and action potentials (SNNAP) that can simulate up to 30 neurons, each with up to 30 voltage-dependent conductances, 30 electrical synapses, and 30 multicomponent chemical synapses. Voltage-dependent conductances are described by Hodgkin-Huxley type equations, and the contributions of time-dependent synaptic conductances are described by second-order differential equations. The program also incorporates equations for simulating different types of neural modulation and synaptic plasticity. 2. Parameters, initial conditions, and output options for SNNAP are passed to the program through a number of modular ASCII files. These modules can be modified by commonly available text editors that use a conventional (i.e., character based) interface or by an editor incorporated into SNNAP that uses a graphical interface. The modular design facilitates the incorporation of existing modules into new simulations. Thus libraries can be developed of files describing distinctive cell types and files describing distinctive neural networks. 3. Several different types of neurons with distinct biophysical properties and firing properties were simulated by incorporating different combinations of voltage-dependent Na+, Ca2+, and K+ channels as well as Ca(2+)-activated and Ca(2+)-inactivated channels. Simulated cells included those that respond to depolarization with tonic firing, adaptive firing, or plateau potentials as well as endogenous pacemaker and bursting cells. 4. Several types of simple neural networks were simulated that included feed-forward excitatory and inhibitory chemical synaptic connections, a network of electrically coupled cells, and a network with feedback chemical synaptic connections that simulated rhythmic neural activity. In addition, with the use of the equations describing electrical coupling, current flow in a branched neuron with 18 compartments was simulated. 5. Enhancement of excitability and enhancement of transmitter release, produced by modulatory transmitters, were simulated by second-messenger-induced modulation of K+ currents. A depletion model for synaptic depression was also simulated. 6. We also attempted to simulate the features of a more complicated central pattern generator, inspired by the properties of neurons in the buccal ganglia of Aplysia. Dynamic changes in the activity of this central pattern generator were produced by a second-messenger-induced modulation of a slow inward current in one of the neurons.

Action Potentials↗
PubMed1993

Detection and measurement of an endogenous clonidine-displacing substance in human cerebrospinal fluid.

Clonidine-displacing substance (CDS) is a novel endogenous ligand for clonidine receptors previously detected in bovine brain and human serum. We examined for the first time whether CDS can be detected and measured in human cerebrospinal fluid (CSF). Using the [3H]clonidine displacement assay, we found that CDS could be identified and quantified in each of the CSF samples obtained from 81 patients with various neurological disorders. Mean level of CDS in CSF was 4.66 units/ml. Exceedingly high levels were observed in the CSF of patients with neoplastic meningitis (mean, 36.75 units/ml) and stroke (mean, 19.5 units/ml) (P < 0.0001). No correlation was found between CDS levels in CSF and age, gender, CSF protein or number of cells. CDS levels in CSF were higher than those in the serum (P < 0.01). We conclude that CDS is present and can be measured in human CSF. High CDS levels in CSF from patients with leptomeningeal metastases may serve as a tumor marker for malignant infiltration of the meninges. Additional studies in stroke patients will determine whether this endogenous ligand plays a role in the pathogenesis of cerebral ischemia.

Adolescent↗
PubMed1993

Spastic paraparesis associated with human T-lymphotropic virus type I: a clinical, serological, and genomic study in Iranian-born Mashhadi Jews.

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intrafamilial marriage among its members. A high risk of infection by human T-lymphotropic virus type I (HTLV-I) and of adult T-cell leukemia associated with such infection was found in this population. HTLV-I is also associated with a syndrome of progressive spastic paraparesis. We therefore evaluated the occurrence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews who immigrated to Israel. We examined 83 Mashhadi-born subjects (52 women, 31 men; mean age, 61 +/- 15.5 years) and 73 age-matched non-Mashhadi Iranian-born Jews. Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. Fifteen Mashhadi-born Jews (18%) were both seropositive and PCR-positive for HTLV-I. Four HTLV-I-seronegative subjects were found to be positive for HTLV-I proviral DNA by PCR. Of the 19 HTLV-I-infected subjects (11 women, 8 men; mean age, 59 +/- 16 years), 13 (68%) had spastic paraparesis of varying severity. There were no signs of myelopathy in the Mashhadi-born subjects who were negative for HTLV-I proviral DNA by PCR. None of the non-Mashhadi Iranian Jews was seropositive or PCR-positive for HTLV-I proviral DNA, or had clinical signs of spastic paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Primary progressive freezing gait.

Freezing gait is an incapacitating symptom often observed in patients with Parkinson's disease. It has been less frequently described in association with multi-infarct state, multisystem atrophies, and normotensive hydrocephalus. In our movement disorder clinic, we have diagnosed (and followed up to 3 years; median, 16 months), 18 patients in whom progressive freezing gait was the sole neurological dysfunction. These 15 men and 3 women (aged 60-82 years; 74 +/- 6) were subjected to an extensive neurological workup that included clinical evaluation, videotaping for grading of gait disability, comprehensive blood and cerebrospinal fluid (CSF) analysis, and brain computed tomography (CT) and magnetic resonance imaging (MRI). Mean disease duration was 2.5 +/- 1.9 years (range, 0.5-6). Neurological examination disclosed freezing gait, often associated with varying degrees of postural instability. The degree of freezing gait ranged from sudden motor blocks only when confronted with obstacles to severe disability with total inability to start walking requiring a walker, massive assistance, or a wheelchair. However, patients could mimic gait movements with absolutely no freezing when seated or lying prone, and most of them could overcome arrests by the "walking-over-lines" maneuver. Otherwise, neurological examination was normal with no signs of bradykinesia, rigidity, or tremor. Blood chemistry and CSF analysis were normal. Brain CT and MRI were normal or showed mild cortical atrophy in 12 and putative lacunes in 6 patients. Therapy with levodopa or dopamine agonists was ineffective. During the follow-up period, a gradual progression of the freezing gait was observed. However, it remained unaccompanied by any other neurological findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Short-term beneficial effect of deprenyl monotherapy in early Parkinson's disease: a quantitative assessment.

It was recently shown that early treatment with deprenyl in patients with Parkinson's disease can delay the need for initiation of levodopa therapy. It was therefore suggested that deprenyl may slow down disease progression. Alternatively, the observed stabilization of clinical disability may merely reflect drug-induced symptomatic benefit. We therefore examined a possible short-term beneficial effect of deprenyl (10 mg/day) as the first and only drug in 15 consecutive de novo patients. Bradykinesia was quantitatively assessed by computerized analysis of isometric force/time curves of biceps and triceps bilaterally and by calculation of simple reaction time (RT) and maximal muscle contraction rate (MMCR). We also measured maximal muscle force, evaluated clinical status by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score, and recorded patients' subjective reports. All tests were carried out before and at 1 and 2 months of treatment. Only one patient reported a beneficial effect. No significant changes in the UPDRS or score or muscle force were observed. In contrast, MMCR and RT improved at 1 month by an average of 12.1 and 7.2%, respectively (p < 0.01, paired t test). This improvement persisted after 2 months of treatment. Study shows that deprenyl monotherapy exerts a short-term beneficial effect in de novo parkinsonian patients. This effect, however, appears to be small, subclinical, and probably cannot account for the observed delay in the need to start levodopa therapy.

Aged↗
PubMed1993

Human facet cartilage: swelling and some physicochemical characteristics as a function of age. Part 2: Age changes in some biophysical parameters of human facet joint cartilage.

This study was aimed at investigating, in relating to aging, some of the biochemical and biophysical characteristics of the facet cartilage that determine the functional behavior of this tissue. In addition, facets and discs from the same segment were graded according to their macroscopic appearance. The proportion of severely degenerate discs was low in young subjects and increased with age; by contrast, the proportion of coarsely fibrillated and/or ulcerated facets was high in spines from young adults and remained constant throughout adulthood. Unlike discs, facets do not show an age-related loss of proteoglycans or a consequent decrease in the resistance to a compressive load. However, even in relatively young age groups (30-50 years) a high hydration was observed more often in facet joints than in cartilage from other joints studied. These characteristics are known to accompany damage of the collagen network and cartilage degeneration. Unlike normal femoral head cartilage, facet cartilage does not show a rise in fixed charge density with age. The cartilage from the superior processes (concave) is thicker than that from the inferior processes (convex) and has a higher fixed charge density. At the same time it has a higher water content, which indicates that damage occurs more frequently.

Adolescent↗
PubMed1993

The role of interneurons in controlling the tail-withdrawal reflex in Aplysia: a network model.

1. The contributions of monosynaptic and polysynaptic circuitry to the tail-withdrawal reflex in the marine mollusk Aplysia californica were assessed by the use of physiologically based neural network models. Effects of monosynaptic circuitry were examined by the use of a two-layer network model with four sensory neurons in the input layer and one motor neuron in the output layer. Results of these simulations indicated that the monosynaptic circuit could not account fully for long-duration responses of tail motor neurons elicited by tail stimulation. 2. A three-layer network model was constructed by interposing a layer of two excitatory interneurons between the input and output layers of the two-layer network model. These interneurons had properties mimicking those of the recently described interneuron LP117, receiving excitatory input from pleural sensory neurons and evoking a biphasic excitatory postsynaptic potential (EPSP) in pedal motor neurons (Cleary and Byrne 1993). The three-layer model could account for long-duration responses in motor neurons. 3. Sensory neurons are a known site of plasticity in Aplysia. Synaptic plasticity was incorporated into the three-layer model by altering the magnitudes of conductance changes evoked in motor neurons and interneurons by presynaptic sensory neurons. In these simulations the excitatory interneurons converted an amplitude-coded input into an amplitude- and duration-coded output, allowing the three-layer network to support a large range of output amplitudes and durations. 4. Synaptic plasticity at more than one locus modified dramatically the input-output relationship of the three-layer network model. This feature gave the model redundancy in its plastic properties and points to the possibility of distributed memory in the circuitry mediating withdrawal reflexes in Aplysia. Multiple sites of control over the response of the network would likely allow a more diverse repertoire of responses.

Animals↗
PubMed1993

Interdependence of lumbar disc and subdiscal bone properties: a report of the normal and degenerated spine.

A nondestructive mechanical testing technique was used to assess midsagittal plane variations in the mechanical properties of human lumbar vertebral bone adjacent to the intervertebral discs of normal and degenerated spines. Bone mechanical properties were compared with midsagittal plane measurements of intervertebral disc (IVD) physical-chemical properties. In the normal spine a heterogeneous midsagittal plane distribution of subdiscal bone stiffness, IVD hydration and fixed charge density was found. Segments with degenerated discs exhibited a lower amount of midsagittal variation in subdiscal bone and IVD properties. A positive linear correlation between subdiscal bone stiffness and IVD fixed charge density was also found, suggesting that an interdependence of IVD and bone properties exists. These results support previous findings and are hypothesized to be an adaptive response to changes in the stress environment in the IVD.

Adult↗
PubMed1992

Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis.

Ten patients with relapsing-remitting multiple sclerosis were treated with intravenous immune globulin, 0.4 g/kg per day for 5 consecutive days, and then with additional booster doses of immune globulin of 0.4 g/kg, once every 2 months, for the next 12 months. Ten untreated patients with relapsing-remitting multiple sclerosis who were matched with the study patients for age, disease duration, and number of attacks per year served as controls. Immune globulin treatment was well tolerated, with no side effects. The exacerbation rate decreased from 3.7 +/- 1.2 exacerbations per year before treatment to 1.0 +/- 0.7 exacerbations per year during the treatment in the immune globulin-treated patients, while it remained unaltered in the controls. The posttreatment Kurtzke Expanded Disability Status Scale score decreased from a mean of 4.45 to 4.15, whereas in controls it increased from 3.55 to 3.75. The results suggest that immune globulin suppresses the ongoing pathologic process in multiple sclerosis and may be a promising treatment to prevent disease exacerbations.

Adult↗
PubMed1992

Physicochemical properties of the aging and diabetic sand rat intervertebral disc.

Hydration, fixed charge density, (FCD) and hydration under various osmotic pressures were compared in young, old, and young diabetic sand rats. This rat is a desert animal that may develop diabetes when fed a regular diet; it is also known to have radiographic and histologic evidence of intervertebral disc (IVD) disease. Forty-five rats and 180 IVD were used in this study; they were divided into three equal groups: young healthy, old healthy, and young diabetics. IVD, cancellous bone, and muscle were sampled from distal lumbar spines. The young diabetic rats (YD) were considerably heavier than the age-matched controls, had higher insulin and glucose levels, and all YD had cataracts. The discs of the young diabetic animals demonstrated decreased hydration, FCD and ability to resist compression under osmotic pressures as compared with the young and healthy discs and were more similar to the discs from old rats. The IVD is the most affected musculoskeletal connective tissue in sand rats with aging and diabetes. The aged and diabetic discs in the sand rat demonstrated changes similar to human changes with regard to lower hydration, FCD, and ability to resist osmotic pressure. Therefore, the sand rat may be a suitable animal model for studying the pathogenesis of disc degeneration.

Aging↗
PubMed1992

Prevention of peripheral side-effects of transdermal hyoscine by adjunctive therapy with low dosage of pyridostigmine.

1. The value of low dosage of pyridostigmine (30 mg three times daily) in preventing peripheral anti-muscarinic side effects of a transdermal controlled-release formulation of hyoscine, was tested in a double-blind placebo-controlled study, involving 47 healthy subjects. 2. Salivary excretion was repeatedly measured during 48 h of combined therapy of two transdermal hyoscine patches with pyridostigmine and 14 h after its cessation. Blood acetylcholinesterase activity was also measured, serving as an index of pyridostigmine bioavailability. 3. The adjunctive therapy with pyridostigmine was highly effective in preventing the substantial impairment in salivary flow caused by the transdermal formulation. An associated 23% inhibition of blood acetylcholinesterase activity was observed. 4. Small doses of pyridostigmine may therefore have a role in increasing the tolerability of transdermal hyoscine therapy. In some patients this drug combination might also allow some increment of the hyoscine dose.

Acetylcholinesterase↗
PubMed1992

Increased plasma endothelin-1 in acute ischemic stroke.

BACKGROUND AND PURPOSE: Endothelins are a recently discovered group of most powerful vasoconstrictor peptides. Endothelin-1 is produced by endothelial cells, and endothelin-3 is derived from neuronal tissue. Theoretically, endothelin-mediated vasoconstriction may enhance ischemic neuronal damage. This study aimed to measure plasma levels of both endothelins in patients with acute nonhemorrhagic cerebral infarction. SUMMARY OF REPORT: Plasma levels of endothelin-1 and endothelin-3 were measured by radioimmunoassay in 16 consecutive patients within the first 72 hours after the onset of nonhemorrhagic cerebral infarct, as diagnosed clinically and by computed tomography. There was a marked (fourfold) elevation in plasma endothelin-1 levels in the patients (median, 11.7 pg/ml; 25th and 75th centiles, 5.4 and 13.2 pg/ml) compared with those in a control group of 13 age-matched subjects (median, 2.56 pg/ml; 25th and 75th centiles, 2.4 and 3.0 pg/ml; p less than 0.0001). The first 24 hours after stroke onset were associated with higher endothelin-1 levels, and there was a trend to elevated levels with more severe neurological deficits. In all patients and controls endothelin-3 levels were below 0.5 pg/ml. CONCLUSIONS: Ischemic stroke is associated with acute and marked increases in plasma levels of endothelin-1. This may reflect enhanced production by damaged endothelial cells within the infarcted tissue. Local leakage of endothelin-1 may induce severe and prolonged constriction of collateral vessels and may therefore have a deleterious role in the pathogenesis and final outcome of cerebral infarction.

Acute Disease↗
PubMed1992

Aphasia in multiple sclerosis: clinical and radiologic correlations.

Aphasia is not commonly reported in multiple sclerosis (MS). We report on two clinically definite MS patients, with a remitting-relapsing course, who presented with acute onset of aphasia. MRI demonstrated giant plaques in the left frontal region in one and in the left centrum semiovale in the other. These lesions were not evident in MRI performed several months previously, and may account for the aphasia. In both patients, language functions markedly improved within several weeks. In one patient, follow-up MRI 3 months later revealed a moderate reduction in the size of the plaque.

Adult↗