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Biomedical subjects

S H Roth

Publications and source records attributed to S H Roth.

At least 109 records · Page 6Linked to original sources
PubMed1987

Cholinergic theta rhythm in transected hippocampal slices: independent CA1 and dentate generators.

The controversy concerning intrahippocampal theta (theta) generators, arising as a result of in vivo investigations, prompted us to record theta-activity from isolated populations of CA1 pyramidal or dentate granule neurons in vitro. In the present study, transected slices (trans-slices) of the hippocampal formation were used to isolate the CA1 area from the dentate gyrus, providing a method for testing the 'two generator' hypothesis. We demonstrated that neurons in both the CA1 area and dentate gyrus could independently generate carbachol-induced (type 2) electroencephalogram (EEG) theta-activity. This activity could be completely blocked by the muscarinic receptor antagonist atropine sulfate but was unaffected by the nicotinic blocker, (+)-tubocurarine. These in vitro results provide the first direct evidence for the two-generator hypothesis and confirm the cholinergic-muscarinic nature of type 2 slow wave theta.

Animals↗
PubMed1987

Endoscopy-controlled study of the safety of nabumetone compared with naproxen in arthritis therapy.

Nonsteroidal anti-inflammatory drug (NSAID) gastropathy is now a commonly recognized and reported complication of such arthritis therapy. Significant gastric lesions develop in up to 40 percent of arthritic patients treated with long-term anti-inflammatory doses of NSAIDs, 20 percent of which represents actual ulcer crater disease. This 12-week endoscopy-controlled, double-blind study was constructed to evaluate the safety and efficacy of nabumetone 1,000 mg at bedtime compared with naproxen 250 mg twice daily. A total of 37 patients completed the study, including 29 patients with a diagnosis of osteoarthritis and eight with a diagnosis of rheumatoid arthritis. By posttreatment endoscopy, nabumetone was significantly less toxic to the gastrointestinal tract than was naproxen. The nabumetone-treated group also showed greater improvement in all efficacy variables, with significant improvement noted in three of these five variables in both rheumatoid and osteoarthritic patients.

Adult↗
PubMed1987

Sucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage.

In a randomized, double-blind trial, sucralfate therapy, 1 g four times daily, was compared with placebo in 143 symptomatic patients to assess the treatment of gastrointestinal symptoms and gastric mucosal damage associated with nonsteroidal anti-inflammatory drugs (NSAIDs). All patients followed a fixed regimen of NSAIDs, were assigned to one of two groups based on the presence or absence of gastric erosions at baseline endoscopy, and were then assigned randomly to receive sucralfate or placebo for four weeks. Patients were then followed for up to six months while receiving open-label sucralfate 1 g twice daily to up to 1 g four times daily. After four weeks of double-blind therapy, patients taking either nonsalicylate NSAIDs or long half-life NSAIDs and who were treated with sucralfate experienced a significant reduction in both peptic symptom frequency and intensity (p less than 0.03) as compared with patients receiving placebo. Sucralfate-treated patients with baseline endoscopic lesions showed a significant reduction in lesion scores (p less than 0.005) at four weeks as compared with baseline, whereas no improvement was observed in gastric mucosal lesions of patients given placebo. Long-term sucralfate therapy resulted in continued improvement in gastrointestinal symptoms and gastric lesion scores in patients receiving all types of NSAIDs. The results indicate that sucralfate used in conjunction with NSAIDs may allow patients to continue therapy by relieving gastrointestinal symptoms and mucosal damage associated with NSAID therapy.

Aged↗
PubMed1987

Anesthetics produce differential actions on membrane responses of the crayfish stretch receptor neuron.

The actions of ethanol, halothane and pentobarbital on the membrane electrical properties and synaptic transmission of isolated crayfish stretch receptor neurons were studied to determine possible sites of action contributing to differential effects previously described on physiological discharge activity. The three agents depressed GABA-mediated transmission and altered postsynaptic membrane electrical properties. Both pre- and postsynaptic sites of action appeared to contribute to the anesthetic-induced alteration of neuronal function. The agents studied produced different, concentration-dependent, membrane effects which included biphasic actions on membrane resistance and spike threshold. The results suggest that multiple-sites of action are involved and different anesthetics may not act via the same mechanism(s) at these sites.

Anesthetics↗
PubMed1987

The effect of chlorpromazine on monoamine levels in the rat cerebellum and hippocampus: a developmental study.

Acute and chronic alterations of the monoamine levels in the rat cerebellum and hippocampus after late prenatal and early postnatal administration of chlorpromazine, were examined using high performance liquid chromatography with electrochemical detection. During a critical phase of development (one week postnatal), chlorpromazine produced increased levels of both serotonin and dopamine in both brain regions. At 24 weeks postnatal, or 21 weeks after cessation of drug administration, the levels of all 3 monoamines were decreased in the cerebellum and increased in the hippocampus. The early disruption in the normal monoamine levels may be related to abnormal growth patterns observed in previous studies.

Animals↗
PubMed1987

Phase shifting of CA1 and dentate EEG theta rhythms in hippocampal formation slices.

Carbachol-induced hippocampal EEG theta-rhythms were recorded simultaneously from the CA1 and dentate areas in rat hippocampal brain slices. Phase shifts ranging from 0 to 180 degrees between the CA1 and dentate theta generators were observed. The differences in slow wave theta phase relations between in vitro and in vivo preparations were interpreted as resulting from deafferentation of the hippocampal slices.

Animals↗
PubMed1987

Anesthetics produce differential actions on the discharge activity of a single neuron.

The effects of 26 anesthetic agents were studied on the rhythmical discharge activity of a single isolated neuron (crayfish stretch receptor). Many of these agents produced concentration-dependent biphasic responses (excitation and depression), and some also induced altered discharge patterns (burst activity). The dominant effect of a few of the anesthetics was excitation (e.g. alphaxolone); depression (e.g. decanol); or burst activity (e.g. benzocaine). A correlation was found to exist between equieffective concentrations in the perfusate and membrane/buffer partition coefficients; however, this general phenomenon does not provide an explanation for the biphasic or differential responses. These results demonstrate that selective interactions occur at the level of the single neuron, and suggest the existence of recognition sites in neuronal membranes which can discriminate structural differences of anesthetics.

Action Potentials↗
PubMed1987

Carbachol-induced EEG 'theta' activity in hippocampal brain slices.

Application of the cholinergic agonist carbachol (50 microM) produced theta-like rhythmical waveforms, recorded in the stratum moleculare of the dentate gyrus. Atropine sulfate (50 microM) antagonized the carbachol-induced theta-like activity, consistent with this action of atropine in vivo. These results provide the first direct evidence that hippocampal neurons are capable of producing synchronized slow-wave activity when isolated from pulsed rhythmic inputs of the medial septum and other brain regions.

Animals↗
PubMed1987

Theta in hippocampal slices: relation to synaptic responses of dentate neurons.

The effects of cholinergic agents on isolated dentate neurons were studied to characterize cellular mechanisms underlying carbachol-induced 'theta' EEG activity. Carbachol, eserine, and acetylcholine produced a synchronization of slow wave activity (theta) accompanied by depression of perforant path to dentate field potentials. These effects were antagonized by atropine but not d-tubocurarine. The results suggest that muscarinic receptors mediate theta activity resulting from a depolarization of dentate neurons.

Acetylcholine↗
PubMed1987

Enflurane-induced burst firing of hippocampal CA 1 neurones. In vitro studies using a brain slice preparation.

Enflurane can produce seizure activity in the cortical EEG, in vivo, at concentrations associated with surgical anaesthesia. The present study was designed to determine whether this seizure-like burst activity could occur in isolated cortical neurones. Enflurane altered synaptic transmission in the in vitro rat hippocampal slice preparation and produced seizure-like burst discharges of CA 1 neurones, at vapour concentrations equivalent to those obtained during anaesthesia (2-6 vol%; 0.5-1.5 mmol litre-1). Burst discharges occurred both spontaneously and in response to stimulation of stratum radiatum fibres in the CA 1 pyramidal region, but not in the dentate area. Low concentrations of enflurane (approx. 0.75 mmol litre-1), decreased the field potential responses of CA 1 neurones; however, dentate granule neurone responses were increased. Input/output analyses of field excitatory post-synaptic potential (EPSP) and population spike amplitudes revealed that the enflurane-induced depression of field potential responses was associated with decreases in synaptic input, whereas burst activity resulted from a decrease in the threshold of CA 1 neurones.

Action Potentials↗
PubMed1987

Barbiturate effects on hippocampal excitatory synaptic responses are selective and pathway specific.

Barbiturate actions on excitatory synaptic responses in CA 1 and dentate regions of hippocampal slices were studied to determine whether different effects occur on anatomically distinct synaptic pathways. Pentobarbital facilitated transmission between stratum radiatum inputs and CA 1 neurons at low concentrations (0.02-0.08 mM) and produced postsynaptic depression at higher concentrations. Only depression was observed for stratum oriens inputs to CA 1 and perforant path inputs to dentate granulae neurons. The (+) isomer of pentobarbital was approximately four times more potent than the (-) isomer of racemic mixture. Phenobarbital (0.04-0.12 mM) produced only depression of synaptic responses in CA 1 and dentate pathways. Comparison of effect on field excitatory postsynaptic potentials and population spike responses indicated that the barbiturates act at selective and pathway-specific sites. The results provide further evidence for specific cellular and membrane recognition sites for barbiturate action.

Action Potentials↗
PubMed1987

Effect of chlorpromazine on Purkinje cell growth patterns.

The phenothiazine, chlorpromazine, when administered perinatally to rats is implicated in the production of both motor and behavioural deficits. In this study the effects of chlorpromazine on dendritic growth of cerebellar Purkinje cells were examined after administering the drug to litters of Long-Evans hooded rats from 18 days postcoitus to 21 days postnatum. Various parameters of Purkinje cell growth were analysed at specific times after treatment utilizing Golgi-prepared specimens. Granule cell density was used as an estimate of parallel fibre numbers. When compared with control Purkinje cells the treated cells at 7 weeks postnatum had established longer segments and increased mean vertex path length. The total number of segments was also increased and the distribution of segments of different orders was abnormal. In addition, the spines on terminal dendritic branches were both longer and of increased density in the chlorpromazine-treated group. These observations confirm that chlorpromazine produces distinct morphological alterations in mature Purkinje cells.

Animals↗
PubMed1987

Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy. Double-blind long-term evaluation.

To assess the efficacy of cimetidine in treating and preventing gastric mucosal lesions associated with nonsteroidal anti-inflammatory drug (NSAID) therapy (NSAID gastropathy), we endoscopically studied 104 patients taking NSAIDs for a variety of rheumatic diseases. Fifty-six percent (22/43) of patients randomized to cimetidine 300 mg four times a day and 52% (22/42) of those randomized to placebo showed progression of endoscopic lesions during the eight-week short-term phase. Thirty-nine patients whose endoscopic lesions improved were then randomized to a ten-month maintenance regimen of either cimetidine 400 mg at bedtime or placebo. Fifty percent (7/14) of placebo-treated and 42% (5/12) of cimetidine-treated patients showed progression of lesions during the maintenance phase. The failure of cimetidine to offer any significant benefit under these protocol conditions reflects the fundamental difference in pathophysiologic features between classic acid-mediated ulcer disease and NSAID gastropathy.

Adolescent↗
PubMed1987

Nonsteroidal anti-inflammatory drug gastropathy. Recognition and response.

Gastropathy, recognized as gastric lesional disease ranging from erosions to actual ulcer craters, represents the most ubiquitous significant complication of common nonsteroidal anti-inflammatory drug (salicylate and nonsalicylate) use. Recently, this association has been established as distinct from classic peptic ulcer disease, which is primarily acid-mediated, duodenal, and more prevalent in a younger, often male, population. Nonsteroidal anti-inflammatory drug gastropathy is usually antral/prepyloric disease, and research indicates it is mediated through blockade of cyclooxygenase with reduction in cytoprotective gastric prostaglandins. The previous literature has been confounded with short-term studies on healthy volunteers and animals that emphasize the resiliency of normal gastric adaptation to heal such gastropathy. Newer long-term studies in patients with arthritis undergoing anti-inflammatory therapy on a sustained basis indicate fatigue of normal adaptation, with persisting gastropathy leading to bleeding and even death. In addition, silent lesions are more common as symptomatology is not synchronous with lesional disease. Since endoscopy is an expensive, not always utilized procedure, it is important to identify the population most at risk for appropriate cytoprotective management as well as modification of the anti-inflammatory therapy program.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Disability in rheumatoid arthritis: comparison of prognostic factors across three populations.

We previously identified variables that predict functional disability in rheumatoid arthritis (RA). Because of potential instabilities in the statistical model, we sought to determine whether these predictors were consistent across populations: 2,448 consecutive patients with (RA) were followed prospectively at ARAMIS centers in Phoenix, AZ, Wichita, KS, and Saskatoon, SK. Average followup was 1.7 years in Phoenix, 3.4 years in Wichita, and 12 years in Saskatoon. Twenty-four potentially predictive variables were analyzed by stepwise linear regression. Common predictors were age, sex, and duration of illness, suggesting that these variables are important predictors of disease regardless of the population being studied. In addition, the initial level of disability and radiographic variables are good predictors of disability. Elevated erythrocyte sedimentation rate and latex titers also were associated with future functional disability but do not have a linear relationship and predict less well.

Adolescent↗