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Biomedical subjects

J Mathis

Publications and source records attributed to J Mathis.

At least 55 records · Page 3Linked to original sources
PubMed1993

Beneficial effects of combined thromboxane synthase inhibition/receptor blockade with CGS 22652 in a canine model of coronary thrombosis.

Various antiplatelet agents were examined for their effectiveness as adjuncts to thrombolytic therapy in a canine model of thrombin-induced coronary thrombosis. Aspirin (5 mg/kg i.v. bolus), CGS 15435A (thromboxane synthase inhibitor (TxSI), 0.1 mg/kg i.v. bolus +0.04 mg/kg per h) and BM 13.505 (thromboxane receptor antagonist (TxRA), 0.5 mg/kg i.v. bolus +0.2 mg/kg per h) administered concurrently with streptokinase (750,000 units/h) were examined for their effects on reperfusion and reocclusion, as were a combination therapy with CGS 15435A + BM 13.505 or the dual TxRA/TxSI inhibitor, CGS 22652 (1 mg/kg i.v. bolus +0.4 mg/kg per h). All dogs received heparin (150 U/kg bolus + 50 U/kg per h) throughout the experimental protocol. Survival analysis at reperfusion indicated that thrombolysis was significantly improved in dogs treated with CGS 15435A, BM 13.505, CGS 15435A+BM 13.505 or CGS 22652 over that of vehicle-treated animals. Both dual inhibitor groups and the BM 13.505 group were significantly different from aspirin. Aspirin-treated dogs were not different from vehicle. Otherwise, all treatments differed from the vehicle-treated group at reocclusion. Time and incidence of reocclusion for CGS 22652 was significantly improved over that of BM 13.505. Residual thrombus weight was significantly reduced in the CGS 22652-treated and BM 13.505 + CGS 15435A-treated animals. These findings demonstrate that streptokinase-induced thrombolysis is accompanied by TxA2/prostaglandin H2 synthesis and platelet activation and suggest a role for platelet activation during reocclusion following clot lysis. These studies also show it is possible to combine the beneficial effects of both a TxRA and TxSI into a single chemical entity, CGS 22652, which, when administered as adjunctive therapy to streptokinase, results in an apparent synergistic antithrombotic effect.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 5. Synthesis and evaluation of enantiomers of 8-[[(4-chlorophenyl)sulfonyl]amino]-4-(3-pyridinylalkyl)octanoic acid.

The enantiomers of 8-[[(4-chlorophenyl)sulfonyl]amino]-4-(3-pyridinylpropyl)octanoic acid (1) and its pyridinyl ether analog (2) were synthesized using the highly diastereoselective method of alkylation of acyloxazolidinone. These enantiomerically pure compounds were compared with the corresponding racemic compounds 1 and 2 for their in vitro activity. Compounds 1, 1R, and 1S and 2,2S, and 2R were equipotent as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) (IC50 = 2-30 nM). Upon oral administration to guinea pigs, the enantiomers inhibited the ex vivo U 46619-induced platelet aggregation with potency similar to that of the corresponding racemic compound. This indicates that the enantiomers have pharmacologic profile and bioavailability similar to that of the corresponding racemic compound.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Artifact reduction in magnetic stimulation.

A new biopotential amplifier is described in which the stimulus artifact from recordings of electrically or magnetically evoked biopotentials is minimized by a special active filter. The amplifier is tested in different experiments and the recordings are compared to standard EMG recordings.

Action Potentials↗
PubMed1992

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-(3-(3-pyridinyl) propyl)octanoic acid and analogs.

The title compound (10a) and its analogs were synthesized and found to possess two activities, the inhibition of the biosynthesis of thromboxane A2 and antagonism of its receptors. The in vitro and in vivo profile of these compounds as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) is described. 10a and its analogs displayed very potent TxRA activity in human washed platelets (IC50 approximately 10(-7)-10(-9) M) and dog saphenous vein (pA2 approximately 9) and also potent TxSI activity (IC50 approximately 10(-9) M). The good bioavailability and the long duration of action of some of these compounds was demonstrated using ex vivo measurement of the TxRA activity upon oral administration to guinea pigs. Compounds 10a, 20, and 33 potently inhibited arachidonic acid induced bronchoconstriction in guinea pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

[Current aspects in the diagnosis and therapy of narcolepsy].

Narcolepsy is a potentially invalidating disorder of the sleep and wakefulness structure, characterized by attacks of sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed night sleep. The diagnosis is mainly based on the history. Additional sophisticated examinations, such as nocturnal polysomnography, are primarily indicated to rule out other causes of excessive daytime somnolence. The recently detected high correlation between a certain HLA status and cataplexy has led to new pathogenetic concepts. The primary aim of the therapy is to keep the patient at work rather than attempting a symptom free state. Measures to organize his day with planned naps should precede the use of medication. Besides stimulants against daytime somnolence and tricyclic antidepressants to suppress cataplectic attacks, some new drugs have been administered successfully against the various symptoms of narcolepsy in recent years.

Antidepressive Agents, Tricyclic↗
PubMed1989

Variance analysis of excitatory postsynaptic potentials in cat spinal motoneurons during posttetanic potentiation.

1. Fluctuations in the peak amplitudes of composite excitatory postsynaptic potentials (EPSPs) in cat spinal motoneurons were analyzed during posttetanic potentiation (PTP). Each of a series of identical tetanic stimulus trains delivered to a muscle nerve was followed by 45 test stimuli applied at 2-s intervals. The mean peak amplitude and mean peak variance were calculated for EPSPs evoked by all those stimuli following a tetanus with the same time interval. It was assumed that the variance arises primarily from the probabilistic all-or-none behavior of single synaptic boutons and background noise due to spontaneous synaptic activity and thermal noise in the recording system. The variance was corrected for the contribution from additive Gaussian background noise. 2. If it is assumed that individual synaptic boutons behave independently, corrected mean peak variance and mean peak amplitude are related by a parabolic function. The expected parabolic relationship was seen in 9 of 31 cases studied, and the parameters of the best parabolic fit to the data allowed estimation of some synaptic properties. From these parameters, the mean amplitude of the unit EPSP (v) was estimated to be 102.1 +/- 57.4 (SD) microV. An average of 3.7 boutons comprised each Ia-motoneuron contact system. 3. On average, only 27% of all synaptic boutons given off by the stimulated Ia fibers to one motoneuron were active and releasing transmitter during unpotentiated reflex transmission. The remaining 73% of the synapse population was intermittently silent. The population of boutons which took part in synaptic transmission could be divided into two subpopulations, one with a release probability P = 1 and a second with a mean release probability P = 0.13 +/- 0.086. 4. We conclude that synaptic boutons connecting Ia afferents to motoneurons exist in two populations, one having a high and one a low probability of transmitter release. Transmitter release is quantal, resulting in a unit EPSP of approximately 100 microV measured at the motoneuron soma.

Analysis of Variance↗
PubMed1988

Comparison of radially sensitive and circumferentially sensitive microtransducer esophageal manometry probes in normal subjects.

Circumferentially sensitive microtransducer probes are commercially available for use in esophageal manometry, and may offer an advantage over radially sensitive microtransducer probes in sphincters with radial asymmetry. In order to compare performance of the two probes, we performed esophageal manometry in 30 healthy adult volunteers with both probes. In only three of 52 manometric parameters measured were differences between mean values for the two probes statistically significant. Intrasubject variability was significantly (p = less than 0.005) less with the circumferentially sensitive probe (coefficient of variation 37% vs. 53%).

Adult↗
PubMed1985

Structural and topographical influences on functional connectivity in spinal monosynaptic reflex arcs in the cat.

A greatly expanded version of spike-triggered averaging (Mendell & Henneman, 1971), performed off-line on tape-recorded signals, was utilized to determine the presence or absence of functional connexions between stretch-afferent fibres and homonymous motoneurones. As many as 264 possible connexions between eleven Ia or spindle group II fibres and twenty-four motoneurones were studied in each single, acute experiment. Morphological and topographical factors influencing functional connectivity were analysed with the aid of wiring diagrams and connectivity matrices. In all experiments the greater the conduction velocity (i.e. diameter) of a Ia or group II fibre, the higher was the probability of its having functional connexions with homonymous motoneurones. The greater the longitudinal distance between the spinal entry points of Ia fibres and the location of a motoneurone, the less was the same probability. The influence of axonal conduction velocity of motoneurones on functional connectivity was apparent in some experiments, but not in others. In pooled data large motoneurones received functional connexions from a higher percentage of group II fibres than did small cells. The projection percentage reached 100 only when both Ia fibres and motoneurones were large, suggesting that motoneurone size influences the probability of functional connexions from group Ia as well as group II fibres. On a cell-to-cell level, connectivity apparently does not follow strict, deterministic rules. The results raise the question of how probabilistic connexions between afferent fibres and motoneurones give rise to deterministic outputs from the whole pool.

Action Potentials↗
PubMed1984

Wiring diagrams of functional connectivity in monosynaptic reflex arcs of the spinal cord.

The direct functional connections between Ia and group II spindle afferent fibers from the cat medial gastrocnemius muscle and their homonymous motoneurons were examined in 10 acute experiments. Trains of stretch-evoked impulses from as many as 20 undivided sensory fibers were recorded simultaneously from 5 dorsal root filaments, as well as the corresponding excitatory postsynaptic potentials (EPSPs) they elicited in 10-20 motoneurons. Spike-triggered averaging [13] of these tape-recorded signals revealed the functional connections (or non-connections) between each Ia or group II afferent fiber and each motoneuron. Wiring diagrams constructed from these data indicate that the probability of a functional connection between an afferent fiber and a motoneuron decreases with the size of either and with the distance between the entry point of the afferent fiber and the motoneuron.

Afferent Pathways↗
PubMed1984

Simultaneously active and inactive synapses of single Ia fibres on cat spinal motoneurones.

A technique is described for recording large numbers of individual or single-fibre excitatory post-synaptic potentials (e.p.s.p.s) from single motoneurones by means of spike-triggered averaging. The cable properties of the motoneurones were calculated from the decay time course of a voltage transient in the motoneurone following a current pulse applied to the soma. From this response a theoretical shape index curve was calculated. Most individual or single-fibre e.p.s.p.s elicited by impulses in different Ia fibres had simple decay time courses and shape indices that fitted the theoretical shape index curve of the motoneurone from which they were recorded very well. This suggested that the active terminals of these afferent fibres were located within limited post-synaptic areas. In a few cases the original amplitude, latency and shape of individual e.p.s.p.s changed dramatically when they were re-averaged 40 min later after the membrane potential had decreased, but was still at an acceptable level. E.p.s.p.s with simple decay time courses changed to e.p.s.p.s with composite decay time courses, presumably due to activation of previously silent synapses. The results suggest that impulses conducted in a single afferent fibre from a muscle spindle do not necessarily activate all of the synapses which the fibre forms on a motoneurone, but may repeatedly fail to activate some endings during prolonged periods of spike-triggered averaging, while consistently activating others. Evidence regarding the site of transmission failure and the possible mechanism of its relief is discussed.

Action Potentials↗
PubMed1978

Propranolol rebound--a retrospective study.

To assess the effects of sudden withdrawal of propranolol on inpatients with coronary artery disease, 102 patients admitted for cardiac catheterization were evaluated. Criteria for inclusion in the study were angiographically documented coronary artery disease, propranolol therapy at a mean daily dose of at least 80 mg and abrupt discontinuation of propranolol therapy before catheterization. There were 55 patients (mean age 52.5) who discontinued propranolol therapy (mean daily dose 127 mg) and a control group of 47 patients (mean age 53) who continued to receive propranolol (mean daily dose 143 mg). The criteria for morbidity were death, myocardial infarction or change in pain pattern. In the withdrawal group there were no deaths, one myocardial infarction judged to be related to catheterization and only one instance of a change in pain pattern. Thus, propranolol rebound appears to occur infrequently among hospitalized patients with reduced activity.

Adult↗
PubMed1978

Angiography of intimal and intramural arterial injuries.

Fifteen patients with injuries disrupting the tunica intima and media are reviewed and 5 cases demonstrating the typical angiographic appearance of these injuries described. In all 15, the tunica adventitia remained intact and pulses were present on the initial physical examination. Injuries described include subintimal hemorrhages with and without an associated tear of the intima and a complete tear of both the tunica intima and media with the tunica adventitia intact. The authors conclude that angiography is the best preoperative diagnostic procedure for these injuries; it should be used whenever the trauma involves a site near a major vessel.

Adult↗