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Biomedical subjects

J C Nelson

Publications and source records attributed to J C Nelson.

At least 19 recordsLinked to original sources
PubMed1992

Synaptic connections of physiologically identified geniculocortical axons in kitten cortical area 17.

Single geniculocortical axons were recorded in the cortical white matter of kittens and adult cats by using micropipettes filled with horseradish peroxidase (HRP). Of 41 axons recovered in 4-5 week old kittens, three well-filled axons arborized in area 17; the remainder were incomplete or arborized in area 18. One axon had Y-like physiological properties, two were X-like. They were recovered from two 34-day-old kittens. All three axons formed clustered arborizations, mainly in layer 4A. Electron microscopic (EM) analysis of 50 boutons from kitten and 38 boutons from adult controls revealed that the boutons from kitten made synapses more frequently on spines (91% of targets) than did the boutons from the adult (71%). One X-like axon in kitten also had a collateral projection that made synapses in layer 1; this has not been seen in adult cats. In overall extent, the axons from kitten fell within the adult range.

Aging↗
PubMed1992

Lithium in combination with perphenazine: effect on plasma monoamine metabolites.

The addition of lithium to perphenazine altered the pattern of plasma homovanillic acid (HVA) during the course of treatment for acute psychosis. In the perphenazine-treated group plasma HVA declined significantly by days 7-9 of treatment, whereas in the perphenazine-plus-lithium group plasma HVA tended to increase. The pattern for plasma methoxyhydroxyphenethyl-glycol (MHPG) was not significantly different for the two groups. The addition of lithium to a neuroleptic may enhance the metabolism of dopamine.

Adult↗
PubMed1992

Drug-responsive symptoms during early neuroleptic treatment.

Identification of symptoms that are directly responsive to neuroleptic drugs at progressive phases of treatment is important for monitoring drug response and understanding the relationship between neurochemical mechanisms of drug action and disordered behavior. Using multiple regression analyses that controlled for pretreatment severity, we identified those symptoms that improved in direct relation to serum concentrations of perphenazine after 10 days of treatment. Improvement in two positive symptoms of psychosis--hallucinations and conceptual disorganization--appears to be related to perphenazine level and useful for assessment of early drug response.

Adult↗
PubMed1992

Thyroid stimulating hormone and prolactin responses to thyrotropin releasing hormone in nondepressed alcoholic inpatients.

Thyroid stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin releasing hormone (TRH) stimulation are sometimes blunted in alcoholic subjects; however, the mechanisms involved in these phenomena have not been established. We hypothesized that elevations in free thyroid concentrations might be related to these abnormal responses and then tested that hypothesis in a sample of nondepressed alcoholic inpatients (n = 21). Four alcoholic patients had delta max TSH responses that were < 7 mIU/l; three had PRL responses at or below 8 micrograms/l. Baseline TSH was the only significant predictor of peak TSH; however, free thyroxine (FT4) and baseline TSH both were significant predictors of peak PRL. The average baseline FT4 concentration in alcoholic patients was significantly higher than that in healthy control subjects (n = 10). Our data, thus, suggest that small elevations of FT4 play a role in the inhibition of TSH and PRL responses to TRH among nondepressed, abstinent alcoholic patients.

Adult↗
PubMed1992

Suicide attempts in elderly psychiatric inpatients.

OBJECTIVE: To describe the psychopathological characteristics of elderly suicide attempters admitted to an inpatient psychiatric unit. DESIGN: Retrospective chart review. PATIENTS: All 168 patients age 60 years and over treated on the adult psychiatric inpatient unit of Yale-New Haven Hospital from 1979 to 1984. Twenty-five made a suicide attempt. MAIN OUTCOME MEASURES: Presence and severity of suicide attempts were rated and compared with demographic, clinical, and functional data. RESULTS: (1) Eighty percent of the attempters had a major depressive syndrome; (2) among patients with affective disorders, presence of an attempt was significantly associated with a later age of onset; (3) patients who had made more severe attempts were more likely to be diagnosed as psychotic depression, although this trend was not significant; (4) substance abuse and dementia were uncommon diagnoses; (5) symptomatic and functional outcome of hospitalization was as favorable for the attempters as for the entire elderly cohort. CONCLUSIONS: Affective illness, especially late-onset major depression, was the major association with suicide attempts.

Affective Disorders, Psychotic↗
PubMed1992

Hypothalamic-pituitary-thyroidal function in eumenorrheic and amenorrheic athletes.

The impact of chronic high volume athletic training on thyroid hormone economy has not been defined. We investigated the status of the hypothalamic-pituitary-thyroid axis (H-P-T) in women athletes with regular menstrual cycles (CA) and with amenorrhea (AA). Their data were compared with each other and with those derived from cyclic sedentary women (CS) matched for a variety of confounding factors including the intensity of exercise, caloric intake, and body weight. Alterations of the H-P-T axis were observed in women athletes compared to CS. While serum levels of T4, T3, free T4, free T3 and rT3 were substantially reduced (P less than 0.01) in AA, only serum T4 levels were significantly decreased in CA. Further, remarkable differences were found between CA and AA in that serum levels of free T4 (P less than 0.01), free T3 (P less than 0.01), and rT3 (P less than 0.05) were significantly lower in AA than in CA. Thyroid binding globulin and sex-hormone binding globulin concentrations were within their normal ranges for all groups of subjects. Both 24-h mean TSH levels and the circadian rhythm of TSH secretion were also comparable. However, the TSH response to TRH stimulation was blunted (P less than 0.01) in AA when compared to CA, but not to CS. Whereas the underlying mechanism(s) to account for the "global" reduction of circulating thyroid hormone in the face of normal TSH levels in AA is presently unknown, these observations provide information of clinical significance: 1) chronic high volume athletic training in women athletes with menstrual cyclicity is accompanied by an isolated T4 reduction; 2) an impaired H-P-T axis occurs selectively in athletic women in whom chronic high volume athletic training is associated with compromised hypothalamic-pituitary-ovarian function and amenorrhea.

Adult↗
PubMed1992

Dependence of free thyroxine estimates obtained with equilibrium tracer dialysis on the concentration of thyroxine-binding globulin.

Some equilibrium dialysis determinations of free thyroxine (T4) vary directly with thyroxine-binding globulin (TBG) concentration. This apparent TBG dependence has been limited to methods involving radiolabeled T4 added to the dialysis system (tracer dialysis). In this study we compared tracer dialysis with direct dialysis for determining free T4 and obtained the following results (mean +/- SD) for patients with hypothyroxinemia of nonthyroidal illness (23.8 +/- 10.7 vs 24.2 +/- 10.9 pmol/L, P greater than 0.8), patients with congenital TBG deficiency (11.4 +/- 2.2 vs 16.2 +/- 7.1 pmol/L, P greater than 0.05), normal control subjects (32.7 +/- 6.5 vs 18.5 +/- 5.8 pmol/L, P less than 0.001), and pregnant women (31.2 +/- 8.7 vs 12.1 +/- 2.6 pmol/L, P less than 0.001). Direct dialysis determinations were independent of TBG and total T4. Tracer determinations were greater than direct determinations in normals, a discrepancy that increased in pregnancy. Tracer determinations correlated significantly with total T4 and TBG concentrations (P less than 0.001). TBG and total T4 dependence in the tracer method was attributable to small overestimations of the free fraction of T4. Similar overestimations multiplied by increasing total T4 concentrations resulted in greater errors. Relative to results for normal sera, the tracer method overestimated free T4 when total T4 was increased and underestimated free T4 when total T4 was decreased.

Adolescent↗
PubMed1991

Plasma free homovanillic acid (HVA) as a predictor of clinical response in acute psychosis.

The relationship of plasma free homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) to early clinical response was prospectively studied in a new series of acutely psychotic inpatients given a fixed dose of perphenazine elixir for 10 days. Elevated pretreatment plasma HVA but not MHPG was significantly associated with good response. Change in HVA was correlated with a favorable response and a significant decline in MHPG was found in responders. Results suggest that HVA can provide a useful clinical predictor of response, and that both dopamine metabolism and noradrenergic functioning, as measured by plasma HVA and MHPG, are reduced in effective neuroleptic treatment.

Acute Disease↗
PubMed1991

A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression.

Prompted by a recent study suggesting that the combination of desipramine hydrochloride and fluoxetine down-regulates beta-adrenergic receptors more rapidly than either drug alone, we administered both desipramine and fluoxetine to 14 inpatients with major depression in an open, 4-week trial. Desipramine plasma levels drawn 24 hours after an initial standardized dose were used to rapidly adjust desipramine dosage and compensate for the interactive effects of fluoxetine on desipramine levels in the blood. Responses were retrospectively compared with those of 52 inpatients who were descriptively similar and previously treated in the same setting with desipramine alone. Response was significantly more rapid in the group that received both drugs. One week after treatment began, the mean change in Hamilton Depression Rating Scale scores was 42% in the group that received both drugs and 20% in the group that received desipramine alone (Mann-Whitney U test, P = .007). Two weeks after administration of the drugs, the mean change in scores of the group that received both drugs was 60%, while a 30% change was noted in the patients treated with desipramine alone (P = .001). Ten (71%) of the 14 patients in the group that received both drugs completely remitted (change in Hamilton Depression Rating Scale score of greater than 75%, and final score of less than 7) within 4 weeks, while few patients treated with desipramine alone met these criteria within 4 weeks. This preliminary study suggests that treatment with both desipramine and fluoxetine is a rapid and effective strategy for treatment of major depression, and supports recent hypotheses of noradrenergic-serotonergic synergism.

Adult↗
PubMed1991

Sudden death in children receiving Norpramin: a review of three reported cases and commentary.

The 1990 "package insert" for Norpramin, the Merrell Dow Pharmaceuticals Inc., brand of desipramine, was changed to include the following statement in the Adverse Reactions section, "There has been a report of an 'acute collapse' and 'sudden death' in an eight-year-old (18 kg) male, treated for two years for hyperactivity. There have been additional reports of sudden death in children." The purpose of this commentary is to review what is known about the three reported cases of sudden death and to discuss the implications of these tragedies for children receiving treatment with tricyclic drugs.

Attention Deficit Disorder with Hyperactivity↗
PubMed1990

Examination of paralysis in Drosophila temperature-sensitive paralytic mutations affecting sodium channels; a proposed mechanism of paralysis.

We have used the identified cells of the Drosophila Giant Fiber System (GFS) to study the defects induced by the temperature-sensitive paralytic mutations no action potential (nap) and paralytic (para). These mutations paralyze at elevated temperatures, reported as due to a block of action potential propagation. We found, however, that the cells of the GFS still were able to respond to stimuli at 7-10 degrees C above the temperature causing mutant paralysis. Stimulus threshold and conduction time both decrease with increasing temperature in the mutants in a manner indistinguishable from wild-type. Since action potentials can propagate efficiently in the mutants at elevated temperatures, we looked for other neural defects that might be involved in producing paralysis. We did find reduced neuronal function at sites such as electrical synapses and axonal branch points where current may be limiting. These sites had weakened following frequency, occasional failures, and increased conduction times. We believe the non-temperature-dependent defects in nap and para uncover the normally temperature-sensitive traits latent within all neurons. Increasing temperature increases the rates of channel activation and inactivation. At higher temperatures, Na+ inactivation and K+ activation encroach upon the Na(+)-activation time, reducing inward sodium current. In addition to this normal temperature-dependent effect, the mutations decrease the number of sodium channels in neurons in a non-temperature-dependent manner. These two reductions in sodium current combine to prevent spiking threshold from being reached at current limited sites. The temperature at which a sufficient number of these sites block should be the temperature of paralysis.

Action Potentials↗
PubMed1990

Early protooncogene expression during hemin-induced differentiation of human erythroleukemic cells.

In situ hybridization was used to study the effects of hemin on the expression of the oncogenes c-myc, c-fos, and myb, and on the mRNA level of erythroid porphobilinogen deaminase (PBG-D) and alpha-globin in HEL cells during differentiation. The technique was effective in detecting changes in mRNA levels in small numbers of HEL cells. Hemin stimulation of HEL cells results in an early increase in myb and c-myc expression and a decrease in c-fos mRNA, while increased PBG-D and alpha-globin expression is not seen until 8 h after hemin treatment. Blast-like cells display expression of c-myc, alpha-globin and PBG-D, while the more differentiated cells give a positive response to both c-fos and myb. During HEL cell differentiation, the mechanism of hemin stimulation appears to be through the up regulation of myb and c-myc mRNA and down regulation of c-fos. The subsequent expression of PBG-D and alpha-globin may indicate that early increases in protooncogene expression are first required for the normal progression of erythropoiesis to occur.

Cell Differentiation↗