Arthur F. Battista

Studies of amines in the striatum in monkeys with nigral lesions. The disposition, biosynthesis and metabolites of [3H]dopamine and [14C]serotonin in the striatum.

The effects of ventromedial tegmental lesions on the biosynthesis and disposition of biogenic amines in the striatum of monkeys were investigated. The concentrations of endogenous dopamine and of the intraventricularly injected [3H]dopamine were distinctly lower in the striatum on the lesion side than on the intact side.

Studies on the antiparkinsonian efficacy of lergotrile

The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigated in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinsons disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients.

Mapping of central monoamine neurons in the monkey

Verteilung und Morphologie von Katecholamin-(KA) 5-Hydroxytryptamin-Neuronen im Affengehirn stimmt mit früheren Befunden über das Rattengehirn gut überein. Die Zahl der KA-Zellkörper in Area Subceorulea ist jedoch bedeutend grösser bei Affen, und eine neue Art terminaler KA-Nervenfasern von starker Fluoreszenzintensität und im Durchmesser variierender Varikosität wurde aufgefunden.

The effects of ventromedial tegmental lesions on the biosynthesis of catecholamines in the striatum

Abstract Following ventromedial tegmental lesions in the brain stem of monkeys, tyrosine hydroxylase activity is significantly lower on the lesion side of the caudate nucleus and putamen. The in vivo formation of dopamine-C 14 from tyrosine-C 14 is impaired on the lesion side in these two regions of the CNS. The present findings support the idea that ventromedial tegmental lesions produce a degeneration of dopamine neurons in the ipsilateral caudate nucleus and putamen.

The antiparkinsonian efficacy of bromocriptine

The antiparkinsonian activity of bromocriptine, a presumed dopaminergic receptor agonist, was investigated in monkeys with surgically induced tremor and in a group of parkinsonian patients. A single administration of bromocriptine resulted in a dose-dependent relief of tremor in monkeys. Repeated administration enhanced this effect. Only mild abnormal involuntary movements were observed and only after repeated administration. Eleven patients with Parkinsons disease were treated with bromocriptine (mean dose, 26.4 mg a day). Clinically obvious improvement was noted in one or more of the cardinal signs of the disease in six patients (responders). No obvious improvement in any of the cardinal signs was noted in the remaining five patients (nonresponders). Clinically, the responders were older and more severely affected and had been on a higher dose of levodopa. However, they had had the disease for a shorter period. It is suggested that failure to respond to bromocriptine may be related to a decrease in the sensitivity of postsynaptic dopaminergic receptors.

Neuroma Formation and Prevention by Fascicle Ligation in the Rat

Light and electron microscopic studies of the cut sciatic nerve in the rat showed typical neuroma formation. If the nerve was cut and the proximal segment was ligated as a whole, the neuromatous process appeared to be even more severe than that in the simply cut nerve. When the perineurium of the cut nerve was kept intact by fascicle ligation, the axonal regenerative process seemed to be altered significantly, and less neuroma formation occurred. The mechanism by which fascicle ligation limits axonal regeneration is unknown, but could involve peripheral as well as central mechanisms. Such a limitation of neuroma formation by fascicle ligation as was found in the rat might also apply to painful human neuromas.

Painful neuroma: changes produced in peripheral nerve after fascicle ligation.

Sixteen months after resection of a painful neuroma and fascicle ligation of the proximal nerve segments, the fascicle ligated neural tissue was examined by light and electron microscopy. No significant neuroma formation was found in the fascicle-ligated regions. The distal portion consisted mainly of connective tissue fibroblasts with an absence of neural elements. Maintaining the perineurium intact by fascicle ligation seems to alter significantly axonal regeneration in humans, as is indicated by minimal neuroma formation. Similar findings after fascicle ligation in animals have also been reported. This lack of neuroma formation after resection of a painful neuroma and fascicle ligation may play a significant role in relieving pain in patients with painful neuromas.

CEREBRAL ULTRASONIC TOMOGRAPHY.

Ultrasonic acoustic waves have been used in recent years to delineate the structure of biological tissues. The principles are similar to those of marine sonar equipment for ocean depth determination and the location of submarines (3, 17, 18). In 1950 French and his co-workers (6, 7) attempted to delineate cerebral structures by ultrasound technics. Wild and Reid in 1952 then devised methods for differentiating mass lesions in other parts of the body (17, 18), which required immersion of the body part in a liquid. Modifications of this immersion technic have subsequently been employed by others (4, 10). The pulse echo method to locate the position of the midline structures of the brain in living patients was described by Leksell (14) in 1956, and later by others (2, 5, 8, 12, 15, 16). Kikuchi and Tanaka employing the method first described by French, Wild, and Neil in 1951, went a step further and tried to identify the structures observed with an ultrasonic pulse (13). This attempt was made on the living h...

Effect of harmaline in monkeys with central nervous system lesions.

Abstract Harmaline produced shivering in normal monkeys and intensified the resting tremor or evoked a resting tremor in monkeys with ventromedial tegmental lesions. In monkeys with such lesions, thalamic or globus pallidus destruction abolished the spontaneous tremor, blocked the harmaline-evoked tremor, but did not prevent the shivering induced by harmaline.

The therapeutic potential of centrally acting dopamine agonists

Much interest has been stimulated by epidemiological evidence which suggests that abortion, foetal abnormality, haemo- poietic disorders and neuropathy occur- ring in operating theatre staff might be due to chronic exposure to waste anaes- thetic gases. The interaction of nitrous oxide and vitamin B~2 can explain each of these disorders. In contrast, there is no theoretical or experimental basis for believing that they could be caused by exposure to trace concentrations of halothane or other currently used volatile anaesthetic agents. The lowest level at which nitrous oxide has been shown to cause signifi- cant inhibition of methionine synthase is 1 000 p.p.m. 9 which is also the lowest concentration at which foetotoxicity has been observed in rodents. 450 p.p.m, is the highest concentration demonstrated to be without effect on hepatic meth- ionine synthase activity in rats dur- ing prolonged exposure 9. Comparable measurements cannot easily be made in man but the data from rats suggest that the maximum safe concentration lies between 450 p.p.m, and 1 000 p.p.m. and allowance for a two-fold safety mar- gin would then suggest that prolonged exposure to 200 p.p.m, should be safe. Levels in excess of 200 p.p.m, com- monly occur in unscavenged operating theatres and the interaction of nitrous oxide and vitamin Bl2 pro~4des an unanswerable case for scavenging waste gases in any area in which aaaesthetics are administered. Levels of 25 p.p.m. can certainly be attained with the use of a cuffed tracheal tube and an efficient scavenging system.