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Biomedical subjects

G M Anderson

Publications and source records attributed to G M Anderson.

At least 199 records · Page 11Linked to original sources

Effect of a meal on human whole blood serotonin.

Levels of whole blood serotonin and tryptophan were measured in 11 human subjects after the consumption of a meal. Blood samples were obtained at 30 and 15 min before the meal and at 15, 30, and 60 min postcibal. One-hour urine specimens were collected for 5 subjects at 0, 60, and 120 min. Whole blood serotonin and tryptophan and urinary 5-hydroxyindoleacetic acid were measured using specific high-performance liquid chromatographic methods. A precibal mean (+/- SEM) serotonin level of 136 +/- 8 ng/ml (n = 22) was observed; means at 15, 30, and 60 min after the meal were 138 +/- 20 ng/ml (n = 9), 145 +/- 18 ng/ml (n = 11), and 138 +/- 16 ng/ml (n = 11), respectively. At no time were postcibal levels of whole blood serotonin significantly higher than baseline levels (paired t-test). Urinary excretion of 5-hydroxyindoleacetic acid also was unchanged; mean hourly rates were 230 +/- 23 micrograms/h before the meal, and 196 +/- 17 micrograms/h and 190 +/- 33 micrograms/h (n = 5) during the first and second hour postcibal, respectively. The absence of a postcibal increase of serotonin in circulating whole blood indicates that serotonin is probably not a human gastrointestinal hormone in the usual sense.

Adult↗

Neurotransmitter precursors and metabolites in CSF of human neonates.

The amino-acid precursors tryptophan and tyrosine, and the major metabolites 5-hydroxyindoleacetic acid, indoleacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenethyleneglycol, related to the central neurotransmitters serotonin, dopamine and norepinephrine, were measured in 62 samples of cerebrospinal fluid from human neonates. Means are reported for the samples from 17 medically uncomplicated infants and for the larger group (42 to 45) of infants with medical complications. The latter group was divided according to diagnosis and medication. All groups had significantly higher levels of all compounds in comparison with older children and adults. There were few significant subgroup differences in the group with complications. In both the normal and complicated groups a number of significant correlations were observed between the compounds themselves and with other physiological measures.

Female↗

Liquid-chromatographic determination of vanillylmandelic acid in urine.

Urinary vanillylmandelic acid (VMA) was determined by "high-performance" liquid chromatography with fluorometric (LC-F) and amperometric (LC-EC) detection. Urine samples were first purified on a small, open-bed, reversed-phase preparatory column. VMA and the internal standard (iso-VMA) were then separated by reversed-phase ion-pair liquid chromatography. Analytical recovery of VMA was high (98.3%, SD 3.3%, n = 8), and concentrations measured by LC-F and LC-EC were in excellent agreement (r = 0.996). The LC-F chromatograms of urine samples had fewer late peaks; however, detection limits were lower (15 vs 120 micrograms/L) for the LC-EC method. Typical concentrations of 1-10 mg/L in urine can be measured easily with either method.

Chromatography, High Pressure Liquid↗

Whole blood serotonin and tryptophan levels in Tourette's disorder: effects of acute and chronic clonidine treatment.

Whole blood serotonin (WB5HT) and tryptophan (WBTRP) levels were studied in 20 patients (aged 8 to 45 years) with Tourette's disorder under medication-free baseline conditions and following acute and chronic clonidine treatment. Compared to 87 normal controls, Tourette's disorder patients had lower mean baseline WBTRP levels (mean +/- SEM: Tourette's, 5993 +/- 304 ng/ml vs. 6822 +/- 169 ng/ml; p less than .03). No significant differences in mean baseline WB5HT levels were found. Three hours after an acute dose of clonidine (2.5 - 5.1 micrograms/kg, p.o. at 9:00 A.M.), no mean differences were observed (baseline vs. post 3 hours) in WB5HT or WBTRP levels. However, following chronic treatment (greater than 3 weeks) with clonidine (3-8 micrograms/kg/day, p.o.), WB5HT levels were increased in 9 of 14 Tourette's disorder patients. The mean increases in WB5HT levels following chronic clonidine treatment were significant when WB5HT levels were expressed per 10(9) platelets. (mean +/- SEM: baseline, 471 +/- 45 ng/10(9) platelets vs. chronic, 697 +/- 82 ng/10(9) platelets, p = .02). No mean differences in WBTRP levels were observed after chronic clonidine treatment. These findings are discussed in light of a proposed intermediary role of 5HT systems in the mode of action of clonidine in the treatment of Tourette's disorder.

Adolescent↗

Determinants of the increasing cesarean birth rate. Ontario data 1979 to 1982.

We analyzed the records of 454,668 births in Ontario in the years 1979 to 1982 and found that the cesarean birth rate increased from 16.5 per hundred deliveries in 1979 to 18.7 in 1982. Cesarean births were classified according to four indications: previous cesarean birth, breech presentation, dystocia, and fetal distress. The increase in the cesarean rate for each indication from 1979 to 1982 was calculated and expressed as a percentage of the total rate increase. Previous cesarean births accounted for 68 per cent of the increase, breech presentation for 14 per cent, dystocia for 4 per cent, and fetal distress for 14 per cent. The impact of previous cesarean births was indicated by an increase in the number of women presenting with this indication--from 5.8 to 7.8 per cent of all deliveries. Although the incidence of breech presentation remained stable, the cesarean birth rate increased from 54.8 to 65 per cent for this indication. There were no marked changes in either the incidence of or cesarean rates for dystocia. The incidence of fetal distress doubled (2.4 to 4.7 per cent of deliveries), but the rate of cesarean births in these cases fell from 50.5 to 32.7 per cent. These findings suggest that physicians may have begun to respond to rising professional and public concern over the increasing cesarean birth rate, but major advances in controlling this rate can be achieved only by addressing the question of vaginal deliveries for some patients who have previously had cesarean section.

Breech Presentation↗

Radial arm maze performance in rats following neonatal dopamine depletion.

Neonatal dopamine (DA) depletion produces learning impairments both during development and throughout adulthood in the rat. The present experiment further investigated the memory capabilities of the dopamine-depleted rat by assessing performance in the radial arm maze. Results showed that, following neonatal injection of 6-hydroxydopamine and desmethylimipramine, lesioned rats per-performed more accurately than controls. In this paradigm, DA-depleted rats tended to enter each arm to obtain a food pellet and not enter unbaited, incorrect arms. The difference in performance of control and treated rats could not be accounted for by differences in locomotor activity, body weights, or motivational factors. A computer analysis of the data revealed that DA-depleted animals adopted a strategy of choosing adjacent arms consecutively, which probably accounted for their superior performance. Results are discussed in terms using algorithms versus extra-maze cues to complete the maze following early brain injury.

Animals↗

Dopaminergic but not noradrenergic mediation of hyperactivity and performance deficits in the developing rat pup.

The relative contribution of dopamine (DA) and norepinephrine (NE) in behavioral arousal was examined in developing rat pups using intracisternal 6-hydroxydopamine (6-OHDA) either alone or following pretreatment with desmethylimipramine (DMI). Such treatments were designed to examine the effects of preferential reduction of DA (DA depletion), NE (NE depletion), or both catecholamines (CA depletion) in the development of motor activity and escape performance. General motor activity increased with age and, over all ages, DA-depleted pups tended to exhibit greater activity. This was most apparent at 15 days of age, where DA-depleted pups were significantly more active than controls, NE-depleted, or CA-depleted pups. DA-depleted pups failed to exhibit the steep decline in activity over time (habituation of activity) demonstrated by the control and NE-depleted pups, while pups depleted of both CA fell into an intermediate position in habituation. Escape latency in a T-maze at 20 days and shuttle box at 26 days of age indicated comparable performance to controls for NE-depleted pups, while those animals in DA-depleted and CA-depleted groups appeared unable to perform the task. Brain CA concentrations (determined by a radioenzymatic assay) indicated preferential reduction of DA in the DA-depleted group to concentrations 25% of controls, reduction of NE to 62% of controls in the NE-depleted group, and reductions of DA to 42% and NE to 60% in the CA-depleted group. These results suggest that preferential reduction of brain DA in the developing rat pup increases motor activity and impairs habituation of activity during the stage of behavioral arousal in week 3 of postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Sympathetic control of sexual reflexes: peripheral 6-hydroxydopamine administration facilitates the onset of penile reflexes in male rats.

The latency to display penile reflexes was significantly reduced in male rats tested one day following treatment with 6-hydroxydopamine (6-OHDA; 75 mg/kg, administered via acute tail vein injection). Eight days following treatment the latency to the first reflex in 6-OHDA treated males did not differ significantly from saline treated control subjects. There were no significant differences in the mean number of erections or flips displayed by 6-OHDA subjects when compared to saline treated control subjects. On tests one day after 6-OHDA administration, treated subjects displayed significantly fewer cups than control subjects on the corresponding tests. Chemical sympathectomy was verified by extreme reduction of peripheral norepinephrine levels. Results of this study are consistant with those reported for spinally transected rats tested under similar conditions (that is, one day following spinal transection), and suggest sympathetic inhibition of the onset of penile reflexes.

Animals↗

Platelet imipramine binding in autistic subjects.

Previous reports of elevated platelet serotonin (5-HT) concentrations in autistic subjects suggest that platelet 5-HT uptake might be altered in autism. Parameters of 3H-imipramine (IMI) binding were measured in 11 drug-free autistic subjects and 10 normal volunteers. Similar means (+/- SD) for Bmax (autistics, 1350 +/- fmole/mg protein; normals, 1590 +/- 206 fmole/mg protein) and Kd (autistics, 0.98 +/- 0.10 nM; normals, 0.94 +/- 0.13 nM) were found in the two groups. The normal number (Bmax) and affinity (Kd) of the IMI binding site in autistic subjects suggest that the regulation of 5-HT uptake is not different in autism.

Adolescent↗

Neurochemical correlates of attention deficit disorder.

Evidence from both epidemiologic and pharmacologic investigations into the biology of attention deficit disorder suggests that abnormalities in neurotransmitter function exist in children with attention deficit disorder. This article reviews this evidence and discusses the limitations imposed upon such clinical investigations.

Attention Deficit Disorder with Hyperactivity↗

CSF neurochemistry of women with anorexia nervosa and normal women.

CSF tyrosine, tryptophan, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), gamma-aminobutyric acid, choline, and calcium were compared in 33 anorexic and 14 normal women. The only significant difference between groups was a lower tyrosine level in the anorexic patients; their MHPG level was nonsignificantly higher. No significant group differences in body weight or depressive subgroup were found. HVA levels were positively related to body weight, and choline was negatively correlated with anorexia severity. The role of tyrosine requires further research, but these findings do suggest that HVA and choline increase with some recovery measures and MHPG is increased with this illness.

Adolescent↗

CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls.

A total of 114 subjects (41 depressed, 20 schizophrenic, 15 manic, and 38 normal controls) underwent lumbar puncture and their CSF was analyzed for levels of tyrosine, tryptophan, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), choline, gamma-aminobutyric acid (GABA), and calcium. Results showed that depressed patients, particularly those over 40 years of age, had lower levels of GABA than did controls, and that their level of HVA increased with age, while controls' decreased. Schizophrenic subjects tended to have higher levels of 5-HIAA and manic subjects tended to have higher levels of HVA and MHPG. Age-associated changes were found in HVA, 5-HIAA, MHPG, GABA, and choline concentrations.

Adolescent↗

Central tryptamine turnover in depression, schizophrenia, and anorexia: measurement of indoleacetic acid in cerebrospinal fluid.

There has been a continuing interest in the possible role of the trace amine tryptamine in the etiology of neuropsychiatric disorders. We have therefore examined cerebrospinal fluid (CSF) levels of indole-3-acetic acid (IAA), the major metabolite of tryptamine, in a large group of normals and in several patient populations. No differences in CSF IAA levels (ng/ml, mean +/- SEM) were observed between normals (4.39 +/- 0.37, n = 36), anorectics (4.40 +/- 0.42, n = 35), schizophrenics (4.06 +/- 0.05, n = 17), manics (4.32 +/- 0.63, n = 10), or depressives (5.23 +/- 0.49, n = 39). A significant elevation (p = 0.05) was found in the subgroup of retarded depressives (RDC) where levels of 5.90 +/- 0.80 (n = 19) were observed. An age effect (r = 0.39, p = 0.02, n = 36) was observed in normals; however IAA was not reduced to either height or weight. IAA tended to be higher (but not significantly) in females in all groups studied; this difference also was not significant when all diagnostic groups (except anorectics) were combined (female: 4.95 +/- 0.44, n = 45; male: 4.46 +/- 0.30, n = 66). In general, the results indicate that tryptamine turnover is not altered in the disorders studied. The functional significance of the slight elevation seen in retarded depressives is not clear.

Adult↗

Differential effects of selective dopamine, norepinephrine or catecholamine depletion on activity and learning in the developing rat.

The present experiment investigated the behavioral changes which occurred following neonatal depletion of central catecholamine systems in the rat. The behavioral effects which resulted from selective dopamine (DA) depletion were compared with those resulting from selective norepinephrine (NE) depletion as well as depletion of both catecholamines (CA). Neonatal 6-hydroxydopamine (6-OHDA) was administered intracisternally at 5 days of age following pretreatment with desmethylimipramine in order to selectively deplete DA. NE levels were reduced by intraperitoneal injections of 6-OHDA at 1 and 2 days of age. Depletion of both catecholamines was effected by combining the procedures used for selective depletion of both DA and NE. Activity was time sampled during an hour at 3 preweanling ages. Avoidance and escape learning were measured in a T maze when pups were 20 days of age and in a Shuttlebox apparatus on day 28. Results revealed that DA and CA depleted animals were hyperactive in comparison to controls and displayed severe learning impairments in both T maze and Shuttlebox performance. In contrast, NE depleted animals showed activity levels which were similar to controls but were significantly impaired on both learning paradigms. These results suggest that selective lesions of DA and NE in infancy lead to a constellation of behaviors which are distinctly unique. The implications of these findings is discussed in terms of clinical research into the Attentional Deficit Disorder of childhood.

Animals↗