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Biomedical subjects

L A Marco

Publications and source records attributed to L A Marco.

At least 19 recordsLinked to original sources
PubMed2000

Neuroleptic malignant syndrome and severe thrombocytopenia: case report and literature review.

We report an unusual case of thrombocytopenia associated with neuroleptic malignant syndrome (NMS). A 31-year-old Black male with a history of hypertension, partial seizures, and schizophrenia developed acute rigidity closely followed by severe hyperpyrexia (temperature 102 degree F), tachypnea, and tachycardia. His home medications at the time of presentation included propanolol 10 mg tid, haloperidol 10 mg bid, sodium valproate 500 mg bid, benztropine 1 mg bid, and haloperidol decanoate 100 mg i.m. every 3 weeks, from another psychiatric facility. Despite vigorous therapy for the hyperthermia, he rapidly developed significant hypoxia requiring mechanical ventilation. A diagnosis of neuroleptic malignant syndrome was made and the patient continued to receive aggressive supportive care. On hospital day 2 his platelet count dropped to 47,000/microl and bottomed out at 36,000/microl by day 3 with other blood cell counts remaining within normal limits. Over the next few days he showed rapid clinical improvement with normalization of his blood chemistries and he was discharged home after 5 days of hospitalization in good condition.

Adult↗
PubMed1991

Effects of MK-801, a non-competitive NMDA antagonist, on linguopharyngeal events in rats.

The effects of MK-801 at doses from 0.005 to 1 mg/kg IP on linguopharyngeal events (protrusions, retrusions and swallows) were determined in rats to find out whether MK-801 resembles ketamine in its capacity to increase the frequency of recurrence of such events that we have demonstrated in previous studies. All rats receiving a dose of 0.05 mg/kg or higher showed an increase in linguopharyngeal event frequency within 5 min and this enhancement (3-fold from baseline level) was maintained for longer than 1 h. At the lowest dose of 5 micrograms/kg the effect lasted only very briefly. A general increase in motor behavior was also observed within 10 min of drug administration. More complex patterns of motor behavior, consisting of stereotypical head bobbing, paw movements reminiscent of walking activity, nystagmus, and ataxia were observed with doses of 0.25 mg/kg and higher. All rats showed a marked startle response at early stages post-injection and hypersensitivity to external stimuli such as noise or movement in the room. However, there was an absolute lack of coordinated avoidance responses normally associated with such startle responses or arousing stimuli.

2-Amino-5-phosphonovalerate↗
PubMed1991

Unitary correlates of linguo-pharyngeal events in a dyskinetic rat model.

1. The hypoglossal nucleus unitary correlates of ketamine- and electrically induced tongue contractions and swallowing events were recorded and compared in stereotaxically mounted rats. 2. Very few of the units recorded could be identified as motoneurons by antidromic invasion through electrical stimulation of the hypoglossal nerve. 3. The sample consists of 109 units, 2/3 of which were located in the retrusor pool and 1/3 in the protrusor region. 4. Linguo-pharyngeal events were considered to be electrically induced if they followed consistently, and with a relatively fixed latency, a single electrical pulse delivered to the superior laryngeal nerve, and ketamine-induced if no such time-locked sequence existed or if they occurred in the absence of electrical stimulation. 5. No differences could be discovered between the two types of linguo-pharyngeal events whether they were compared at the polygraphic or the unitary level. 6. These findings suggest that pharmacologically (ketamine)-induced dyskinetic activity does not differ from comparable motor patterns induced by classical electrophysiological means.

Animals↗
PubMed1989

Effects of clozapine on ketamine-induced linguopharyngeal events in rats.

We tested the effects of clozapine (0.02-20 mg/kg i.p.) on ketamine-induced linguopharyngeal events in rats anesthetized with i.m. injections of ketamine hydrochloride (100 mg/kg) and mounted on a stereotaxic with the tip of the tongue tied to a force displacement transducer monitoring tongue protrusions, retrusions and swallows. Reduction began at the 0.04 mg/kg dose. At 4.8 mg/kg there was total suppression of events. At 20 mg/kg, suppression lasted for 1 h. Notably clozapine doses causing total suppression of events in our model were much lower than those usually reported to alter dopamine turnover.

Animals↗
PubMed1989

Serotonin-containing axon terminals in the hypoglossal nucleus of the rat. An immuno-electronmicroscopic study.

The morphology and distribution of serotonin-containing axon terminals in the rat hypoglossal nucleus (XII) was investigated immunocytochemically at the electron microscopic level. Serotonin-positive profiles were found throughout all regions of XII and included unmyelinated axons, varicosities and axon terminals. Most labeled profiles (68.1%) were nonsynaptic unmyelinated axons and varicosities, while synaptic profiles, ending on dendrites and somata, were seen less frequently (28.7%). The majority of labeled axon terminals (76.9%) ended on small-to-medium-sized dendrites. Most axodendritic terminals contained small, round agranular vesicles (20-55 microns), several large (60-100 microns) dense core vesicles, and were associated with a pronounced asymmetric postsynaptic specialization. By contrast, labeled axosomatic terminals were seen less often than those ending on dendrites (23.0%). Axosomatic terminals typically contained small, round, agranular and large dense core vesicles and were associated with a symmetric or no postsynaptic specialization. These results provide the structural substrates for elucidating the functional role of serotonin in tongue control.

Animals↗
PubMed1989

Ketamine-induced tongue protrusions in rats.

1. The purpose of this study was to demonstrate that ketamine anesthesia (100 mg/kg) induces tongue protrusions (P) in addition to retrusions (R) and swallows (S) in adult rats. 2. These linguo-pharyngeal events occur alone or combined in various sequential patterns. 3. The SPR sequence is not the predominant pattern in all preparations suggesting profound disruption of physiological linkages by ketamine. 4. Haloperidol administration suppresses these events for 1-120 min depending on the dose (0.75-2.5 mg/kg). 5. Swallows are the least vulnerable to haloperidol. 6. This and previous findings provide further evidence that ketamine induced linguo-pharyngeal activity can serve as a model for acute or tardive dyskinesia better than stereotypies.

Animals↗
PubMed1989

Cortical control of tongue contractility in the rat under ketamine anaesthesia.

1. Cortico-lingual and linguo-cortical interconnectivity was investigated in ketamine-anaesthetized rats mounted onto a stereotaxic apparatus. The tip of the tongue was tied to a force displacement transducer to monitor tongue retrusions. The tongue cortical area was exposed in one or both hemispheres to record evoked potentials or spontaneous electroencephalographic (EEG) activity, or to stimulate electrically with single square pulses of up to 50 V and 0.25 ms pulse width. 2. The results showed that (i) tongue retrusions elicited by electrical stimulation were identical to those induced by ketamine; (ii) ketamine-induced tongue contractions correlated in time with cortical EEG potentials which were easily distinguished from the background noise; (iii) haloperidol (2.5 mg/kg, i.m.) suppressed the cortically evoked tongue contractions as well as the ketamine-induced contractions. 3. These results suggest that ketamine-induced tongue retrusions may involve the cortex in their mediation if not their generation and that this may provide a basis for the suppression of dyskinetic activity during sleep or unconsciousness.

Anesthesia↗
PubMed1989

Metoclopramide fails to suppress linguopharyngeal events in a rat dyskinesia model.

The effects of metoclopramide on ketamine-induced linguopharyngeal events exemplified by tongue retrusions, protrusions, and swallowing acts were tested in ketamine-anesthetized rats mounted on a stereotaxic frame with the tip of the tongue tied to a force displacement transducer to monitor retrusion and protrusion and a pressure transducer inserted into the mouth at the level of the soft palate to monitor swallowing. Metoclopramide at doses ranging from 0.5 to 50 mg/kg im failed to decrease protrusions, retrusions, or swallowing. It rather increased all three events for up to 2.5 hours. The significance of these findings is discussed.

Animals↗
PubMed1988

Ketamine as a pharmacological model for tongue dyskinesia.

The purpose of this article is to document that ketamine hydrochloride, administered at an anesthetic dosage of about 100 mg/kg, produces tongue contractile activity in the rat. The methods for monitoring and quantitating ketamine-induced tongue contractions (KITCs) are described. We also found that neuroleptic agents consistently and readily abolish KITCs. On the basis of these observations and other pharmacological properties of ketamine, we propose that KITCs may be a useful model for studying neuroleptic-induced oral dyskinesia, e.g., tardive dyskinesia. Additional findings in support of this model are presented.

Animals↗
PubMed1988

Distribution of glutamic acid decarboxylase and gamma-aminobutyric acid in the hypoglossal nucleus in the rat.

Immunocytochemistry was used to investigate the distribution of glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in the hypoglossal nucleus (XII) of the adult rat. The distribution of GAD and GABA was found to be co-extensive throughout XII. Although immunoreactivity was moderately dense in all regions, the intensity of staining was greatest in the ventral district of XII particularly ventromedially in the caudal half of the nucleus. Immunoreactive terminal-like profiles were observed around motoneuron somata and dendrites. There also was evidence of sparse mediolaterally-oriented densities of immunoreactivity at the junction of XII and the dorsal vagal nucleus and between dorsal and ventral districts of XII. In addition, neurons staining positive for GABA were found scattered within XII laterally and immediately outside of XII in and around the Nucleus of Roller. These observations suggest a complex, differential distribution of GABA in XII and are discussed in relation to tongue motor behavior.

Animals↗
PubMed1988

Differential distribution of biogenic amines in the hypoglossal nucleus of the rat.

The distribution of biogenic amines in the rat hypoglossal nucleus (nXII) was investigated with immunocytochemical methods using antibodies to tyrosine hydroxylase (TH) as a marker for catecholamines, and to 5-hydroxytryptamine (5-HT), the principal indoleamine, at the light microscopic level. TH and 5-HT immunoreactivity were found throughout all regions of nXII. Although the innervations overlapped, clearly different patterns of distribution were observed. TH immunoreactivity was localized primarily in the ventromedial quadrant of the caudal half of nXII and appeared largely as perisomatic-like profiles. In contrast, 5-HT immunoreactivity was greatest dorsally along the caudal half of nXII, although secondary foci of staining were evident ventrolaterally and, to a lesser extent, ventromedially. A perisomatic-like pattern of termination was observed for 5-HT in both dorsal and ventral regions of nXII. Since ventral and dorsal districts of nXII contain motoneurons that innervate protrusor and retrusor tongue muscles, respectively, we propose that the overlapping, yet differential distributions of catecholamines and indoleamines are important in controlling the relationships between functionally related groups of nXII motoneurons. These findings are discussed in relation to oro-lingual motor dysfunction.

Animals↗
PubMed1988

Effects of cholinergic and anticholinergic drugs on ketamine-induced linguopharyngeal motor activity.

Benztropine mesylate (Cogentin) and physostigmine salicylate (Antilirium), were tested for changes in tongue protrusions, retrusions, and swallowing acts in rats anesthetized with a 100 mg/kg IM injection of ketamine hydrochloride. These ketamine-induced linguopharyngeal events were monitored by means of a force displacement transducer fed onto a polygraph. Benztropine (0.05-1 mg/kg) caused mild to moderate reductions in the rate of these events for a short period of time, up to about 30 min. With physostigmine (5-25 micrograms/kg), linguopharyngeal activity was markedly increased, up to 50-fold by the highest dose within 5 min and returned almost to the baseline within 60 min. With lower doses, more moderate responses were obtained. If methscopolamine (1.4, 3, 6 mg/kg IM) preceded physostigmine, the physostigmine enhancement was preserved.

Animals↗
PubMed1988

Catecholamine innervation of the rat hypoglossal nucleus.

The catecholamine innervation of the hypoglossal nucleus (XII) was investigated immunocytochemically by comparing the distribution patterns of tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the rat. Numerous TH- and DBH-positive profiles were found throughout XII, while only occasional PNMT immunoreactivity was observed. Significantly, the distribution patterns of TH and DBH immunoreactivity were coextensive with the most intense staining found ventromedially along the caudal half of XII. We conclude, therefore, that the catecholamine innervation of XII is largely noradrenergic, and that motoneurons innervating the genioglossi muscles, the principal protrusors of the tongue, are the primary targets of this input.

Animals↗
PubMed1988

Interconnections between substantia nigra reticulata and medullary reticular formation.

Injections of wheat germ agglutinin-HRP into the medullary reticular formation (MRf) or the substantia nigra reticulata (SNr) revealed the presence of reciprocating fiber connections between the two areas. Large injections in the MRf demonstrated the existence of labeled neurons in the lateral portions of the SNr. Isolated injections into the parvocellular nuclei of the MRf resulted in the presence of terminal fields in the SNr particularly its lateral portions. Injections in the SNr resulted in the presence of labeled cells in the parvocellular nuclei. The significance of these findings is discussed in terms of oro-facial dyskinesias.

Animals↗
PubMed1988

An electrographic characterization of ketamine-induced linguopharyngeal motor activity.

Ketamine-induced buccolinguopharyngeal motor activity was studied in rats visually and by means of force displacement transduction of tongue retrusions, electromyogram (EMG) of motor units of tongue muscles, and pressure transduction of swallowing acts. Each animal was anesthetized with an intramuscular injection of ketamine hydrochloride (100 mg/kg body weight). Through a tracheotomy the airway was intubated and the animal was mounted on a stereotaxic frame in a supine position for monitoring of the above parameters. Four varieties of events were demonstrated: (a) swallowing acts followed by tongue retrusion, (b) tongue retrusions in isolation, (c) tongue retrusions followed by swallowing events, and (d) swallowing events in isolation. All four types of events were vulnerable to intramuscular injection of haloperidol 0.75-2.5 mg/kg within 5 to 10 min and the suppression endured for at least several hours. We conclude that there is a parallel between ketamine-induced oral motor activity and neuroleptic-induced dyskinesia in that both are temporarily suppressed by neuroleptic drugs.

Animals↗