Search PubMed⌕ Search

Biomedical subjects

H S Singer

Publications and source records attributed to H S Singer.

At least 109 records · Page 6Linked to original sources

Clinical symptomatology, CSF neurotransmitter metabolites, and serum haloperidol levels in Tourette syndrome.

Our studies have demonstrated that TS patients show a high degree of sensitivity to butyrophenone blockade of dopaminergic receptors. The clinical response to extremely low serum levels of haloperidol includes sedating side effects, as well as therapeutic effects. These clinical changes are associated with significant increases in CSF HVA levels, which were abnormally decreased before treatment. CSF HIAA levels tended to be normal and did not change with haloperidol treatment. These results lend additional support to the hypothesis that TS is related to supersensitivity of dopaminergic receptors.

Adolescent↗

Effects of spinal transection on presynaptic markers for glutamatergic neurons in the rat.

To evaluate the hypothesis that glutamic acid may be the neurotransmitter of descending, excitatory supraspinal pathways, the uptake and release of L-[3H] glutamate and the levels of endogenous glutamate were measured in preparations from rat lumbar spinal cord following complete mid-thoracic transection. Following transection, the activity of the synaptosomal high-affinity glutamate uptake process was increased in both dorsal and ventral halves of lumbar cord between 1 and 14 days after transection and returned to control levels by 21 days posttransection. At 7 days, the increased activity of the uptake process for L-[3H]glutamate resulted in elevation of Vmax with no significant alteration in KT as compared to age-matched controls. Depolarization-induced release of L-[3H]glutamate from prelabeled slices did not differ significantly from control in the lesioned rat except at 21 days after lesion when the amount of tritium release was significantly greater in the transected preparations than in control. Amino acid analysis of the lumbar cord from control and transected rats indicated only a 10% decrease in the level of endogenous glutamate and no alterations in the concentration of GABA and glycine 7 days after lesion. These findings do not support the hypothesis that glutamate serves as a major excitatory neurotransmitter in supraspinal pathways innervating the lumbar cord of the rat.

Animals↗

The development of catecholaminergic innervation in chick spinal cord.

This combined biochemical and histofluorescent study of the embryonic chick was designed to investigate the temporal and spatial development of noradrenergic pathways in the spinal cord. The sequence of catecholaminergic innervation was analyzed by measuring the specific uptake of [3H]norepinephrine, the levels of endogenous norepinephrine, and the distribution of catecholamine histofluorescence. Uptake studies showed early axons present in all levels of spinal cord by 10 days incubation with subsequent increases of uptake activity appearing in a rostrocaudal fashion. Endogenous norepinephrine values were low until day 14, at which time transmitter levels began to increase, approaching hatched values on incubation day 17. Morphologic studies demonstrated catecholaminergic terminals first in the intermediate gray matter and later concentrated in the ventral and dorsal horns. These observations were interpreted to indicate that: (1) noradrenergic axons are an early descending supraspinal pathway; (2) arborization of this system occurs in a rostral-caudal sequence; and (3) monoaminergic uptake mechanisms develop prior to and independent of neurotransmitter synthesis and storage. The development of this noradrenergic system parallels alteration in spinal cord physiology and refinements in the motility of the embryo.

Animals↗

Hypersomnia with simultaneous waking and sleep patterns in the electroencephalogram. A case report with neurotransmitter studies.

A mildly dyslexic boy of 11 years, with no neurological deficit or history of epileptic seizures, had marked hypersomnia for 2 years, which was most pronounced in the morning hours. Repeated EEG studies and power spectral analysis revealed simultaneous posterior alpha rhythm and sleep patterns (spindles, vertex waves, K complexes) over vertex and frontocentral regions, while the patient was behaviorally awake. Bilateral synchronous anterior spikes were frequently noted in association with sleep patterns. A polysomnogram over 24 h confirmed excessive sleep, night and day (especially morning hours) and there was evidence of a large REM sleep percentage (on EMG and EOG basis) while the EEG had predominantly non-REM sleep patterns. Special neurotransmitter studies were performed in view of a presumed disturbance affecting the neurobiochemical sleep regulation. These studies were based on CSF metabolite levels and provided evidence for a high serotonin metabolite (5HIAA) level. It is tempting to hypothesize that the biochemical disturbance has led to encroachment of non-REM sleep patterns on both wakefulness and REM sleep. Further discussion deals with the bilateral-synchronous spike activity and its relationship to arousal patterns in sleep.

Child↗

Biogenic amine metabolism in Tourette syndrome.

Biogenic amine metabolism in the central nervous system of 9 children with Tourette syndrome was evaluated by quantitation of their metabolites in cerebrospinal fluid by a gas chromatographic/mass spectrometric method. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in CSF before and after oral administration of probenecid. Dopamine metabolism appeared defective, as both baseline and accumulated levels of HVA after probenecid were decreased. Serotonin metabolism also appeared defective in some patients with low baseline and low accumulated levels of 5-HIAA after probenecid. Taken together with other clinical features of this disease, the results suggest an underlying disorder of dopamine and serotonin metabolism in Tourette syndrome.

Biogenic Amines↗

The development of intersegmental connections in embryonic spinal cord: an anatomic substrate for early embryonic motility.

This ultrastructural study of the embryonic chick spinal cord was designed to determine whether intersegmental inputs are formed before the closure of the reflex arc. Lesions were made in the thoracic cord of chick embryos at five days of incubation, when synapses are present in the ventral half of the cord, but before dorsal root afferents have made contacts in the central nervous system. Axons degenerating were observed in the upper brachial and lower lumbar regions of embryos sacrificed two days later. Synapses exhibiting degenerative changes were present up to six segments above and below the lesion. These observations were interpreted to indicate that: (1) intersegmental fibers connect the thoracic cord to brachial and lumbar areas by the fifth day of incubation; (2) early synapses contain both segmental and intersegmental connections; and (3) some intersegmental connections occur prior to the closure of the reflex arc. These morphologic studies, in conjunction with behavioral and electrophysiological data, strongly suggest that the early intersegmental connections are part of the propriospinal system. The development of these intersegmental tracts coincides with the onset of movement and thus provides an anatomical substrate for understanding embryonic motility.

Age Factors↗

Gilles de la Tourette syndrome: further studies and thoughts.

A possible association between the Gilles de la Tourette and Lesch-Nyhan syndromes has recently been postulated. Fourteen patients with Tourette syndrome demonstrated no similarity to Lesch-Nyhan based upon patterns of inheritance, behavioral changes, or alterations of purine metabolism. Despite a strong male predominance, a sex-linked pattern of inheritance could not be confirmed. Self-mutilating behavior was found in 4 male patients but was readily differentiated from that characteristic of the Lesch-Nyhan syndrome. Quantitation of hypoxanthine-guanine phosphoribosyltransferase and isoelectric focusing of its isoenzymes produced results that were indistinguishable from those in controls. We speculate that, pathophysiologically, Tourette syndrome represents an imbalance between the central neurotransmitters dopamine and serotonin rather than an alteration in purine metabolism.

Child↗

Progressive focal deficit with porencephaly.

The association of porencephalic cysts with hydrocephalus was first cited in 1939. Subsequent descriptions of this combination in terms of fixed, nonprogressive neurological problems have been reported. We describe four patients with hydrocephalus who had progressive focal motor deficits secondary to porencephalic diverticulation of the lateral ventricle. Symptoms of increased intracranial pressure were not a consistent finding in all patients. Enlargement of the porencephalic cyst is related to either a generalized increase in intraventricular pressure or to "hydrostatic" forces that may act independently. Computerized axial tomography has provided a noninvasive technique that allows definition of the abnormality and its progression. Neurosurgical intervention has resulted in clinical improvement in all patients studied.

Brain Diseases↗

Seizures in adolescents.

The management of a patient with seizures involves proper classification, etiologic evaluation, and administration of appropriate therapy. With proper evaluation and management, control of seizures can be expected in the majority of patients. The physician must realize that an epileptic adolescent has intrinsic anxieties and faces social, educational, and vocational restrictions. Failure to deal with these psychosocial problems may result in a greater handicap to the patient than the seizures themselves.

Adolescent↗