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J C Nelson

Publications and source records attributed to J C Nelson.

At least 91 records · Page 5Linked to original sources

Map of the synapses formed with the dendrites of spiny stellate neurons of cat visual cortex.

The synaptic input of six spiny stellate neurons in sublamina 4A of cat area 17 was assessed by electron microscopy. The neurons were physiologically characterized and filled with horseradish peroxidase in vivo. After processing the neurons were reconstructed at the light microscopic level using computer-assisted methods and analyzed quantitatively. The extensive branching of the dendritic tree about 50 microns from the soma meant that the distal branches constituted five times the length of proximal dendrite. Proximal and distal portions of a single dendrite from each neuron were examined in series of ultrathin sections (1,456 sections) in the electron microscope. The majority (79%) of the 263 synapses examined were asymmetric; the remainder (21%) were symmetric. Symmetric synapses formed 35% of synapses sampled on proximal dendrites and were usually located on the shaft. They formed only 4% of synapses sampled on distal dendrites. Spines accounted for less than half of the total asymmetric synapses (45%); the remainder were on shafts. Symmetric synapses formed with four of 92 spines. Nine spines formed no synapses. Spiny stellate neurons in cat visual cortex appear to differ considerably from pyramidal neurons in having a significant asymmetric (excitatory) synaptic input to the dendritic shaft.

Animals↗

Polyneuronal innervation of spiny stellate neurons in cat visual cortex.

Our hypothesis was that spiny stellate neurons in layer 4 of cat visual cortex receive polyneuronal innervation. We characterised the synapses of four likely sources of innervation by three simple criteria: the type of synapse, the target (spine, dendritic shaft), and the area of the presynaptic bouton. The layer 6 pyramids had the smallest boutons and formed asymmetric synapses mainly with the dendritic shaft. The thalamic afferents had the largest boutons and formed asymmetric synapses mainly with spines. The spiny stellates had medium-sized boutons and formed asymmetric synapses mainly with spines. We used these to make a "template" to match against the boutons forming synapses with the spiny stellate dendrite. Of the asymmetric synapses, 45% could have come from layer 6 pyramidal neurons, 28% from spiny stellate neurons, and 6% from thalamic afferents. The remaining 21% of asymmetric synapses could not be accounted for without assuming some additional selectivity of the presynaptic axons. Additional asymmetric synapses may come from a variety of sources, including other cortical neurons and subcortical nuclei such as the claustrum. Of the symmetric synapses, 84% could have been provided by clutch cells, which form large boutons. The remainder, formed by small boutons, probably come from other smooth neurons in layer 4, e.g., neurogliaform and bitufted neurons. Our analysis supports the hypothesis that the spiny stellate receives polyneuronal innervation, perhaps from all the sources of boutons in layer 4. Although layer 4 is the major recipient of thalamic afferents, our results show that they form only a few percent of the synapses of layer 4 spiny stellate neurons.

Animals↗

Comparison of the hormonal response after bidirectional Glenn and Fontan procedures.

Fluid retention is a frequent complication after the bidirectional Glenn and Fontan procedures. It was our hypothesis that this fluid retention may have a hormonal basis. To test this hypothesis, we made serial determinations of antidiuretic hormone, cortisol, aldosterone, angiotensin, and renin before and after operation in patients undergoing a bidirectional Glenn (n = 15) or Fontan (n = 18) procedure. Patients undergoing a bidirectional Glenn procedure had elevations in antidiuretic hormone, cortisol, and aldosterone immediately after operation. However, none of the hormonal elevations persisted by the fifth postoperative day. In contrast, patients undergoing a Fontan procedure had elevations in antidiuretic hormone, cortisol, aldosterone, renin, and angiotensin II in the immediate postoperative period. Five days postoperatively, the renin and angiotensin II levels remained elevated compared with the preoperative values. The data demonstrate that patients undergoing a bidirectional Glenn procedure and those undergoing a Fontan procedure have different patterns of hormonal response. These results suggest that hormonal factors may contribute to fluid retention after these operations.

Aldosterone↗

Suppression of the pituitary thyroid axis after cardiopulmonary bypass in the neonate.

Thyroid hormone has numerous effects on cardiovascular function in the adult. The present study was undertaken to evaluate the effects of cardiopulmonary bypass and deep hypothermia on thyroid function in the neonate. Ten newborns were studied preoperatively and postoperatively. The total and free triiodothyronine, total and free thyroxine, thyroid-stimulating hormone, and thyroglobulin levels were measured by immunoassays. The data demonstrated a transient rise in the free thyroxine level associated with and followed by significant reductions in the free and total triiodothyronine, total thyroxine, thyroid-stimulating hormone, and thyroglobulin levels in the early postoperative period. By the fifth postoperative day, the free and total triiodothyronine and total thyroxine levels were returning toward the preoperative levels under the influence of an elevated thyroid-stimulating hormone level. These results suggest that the combination of cardiopulmonary bypass and deep hypothermia can result in a transient suppression of the pituitary-thyroid axis in the neonate.

Cardiopulmonary Bypass↗

Reduction in triiodothyronine levels following modified Fontan procedure.

Diminished cardiac function is a common manifestation following the modified Fontan procedure. Since thyroid hormone has important effects on cardiovascular function, the present study was undertaken to evaluate changes in thyroid hormone levels following this operation. A control group consisting of children undergoing open heart procedures other than a Fontan procedure was also evaluated. Serum total and free triiodothyronine (T3), total and free thyroxine (T4), thyroid stimulating hormone (TSH), and thyroglobulin were measured by immunoassays. The Fontan group demonstrated an initial increase in free T4, while free T3, total T3, total T4, TSH, and thyroglobulin were reduced. Over the subsequent days, free T4 decreased to below the preoperative value. By the fifth and eighth postoperative days, free T3, total T3, free T4, and total T4 remained reduced, while TSH and thyroglobulin began increasing toward the preoperative levels. The control group also demonstrated decreases in free T3 and TSH. However, these values had returned to baseline by the fifth postoperative day. The results indicate that children undergoing open heart surgery have suppression of the pituitary-thyroid axis, and that this is prolonged in patients undergoing Fontan procedure. The decreased levels of T3 following Fontan procedure may have adverse effects on the recovery of patients undergoing this operation.

Atrial Function↗

Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.

Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.

Adult↗

Underestimates of serum free thyroxine (T4) concentrations by free T4 immunoassays.

Different free T4 (FT4) assays often give different FT4 measurements, and conflicting measurements have been striking in nonthyroidal illness. Because FT4 immunoassays depend upon serum protein-bound T4 (PBT4) dissociation to stabilize the FT4 concentration during assay perturbations, interassay differences in perturbations combined with variation in serum PBT4 concentrations could produce discordant FT4 measurements. This study examined the effects of PBT4 on FT4 measurements obtained by direct immunoassay methods. Standard solutions with constant FT4 levels and varying PBT4 concentrations were prepared and analyzed by direct equilibrium dialysis, two-step immunoextraction, one-step labeled T4 antibody, and one-step labeled T4 analog FT4 methods. Direct equilibrium dialysis results were independent of PBT4 concentrations and gave correct measurements of serum FT4 when the PBT4 concentration was above 8 nmol/L or 0.6 micrograms/dL, but were PBT4 dependent and underestimated serum FT4 at lower PBT4 concentrations. The other three methods were PBT4 dependent and variably underestimated serum FT4 at all levels of PBT4 up to 256 nmol/L (19.9 micrograms/dL), the highest level studied. Thus, PBT4-dependent underestimates of serum FT4 occurred with all four methods, whereas the measured FT4 level at each PBT4 concentration varied widely between methods. A serum PBT4 dependent bias causes discordant FT4 measurements and probably explains the observed underestimates of FT4 in nonthyroidal illness.

Blood Proteins↗

Variable underestimates by serum free thyroxine (T4) immunoassays of free T4 concentrations in simple solutions.

The immunoassays used to measure free T4 in serum frequently underestimate free T4 concentrations. These underestimates of serum free T4 are often greater than can be attributed to sample dilution. Unrecognized T4 sequestration by assay materials could cause such underestimates, but T4 sequestration during free T4 measurements has not been well studied. To study T4 sequestration, we used simple solutions containing gravimetrically determined quantities of T4 without T4 binding proteins. T4 sequestration was calculated as the differences between the actual quantities of free T4 required to obtain a specific free T4 measurement and the quantities that would, in theory, have been required, assuming zero T4 sequestration. Sequestration occurred in every serum free T4 assay studied, was often in the nanomolar range, and varied from 26-99+% of the actual amount of free T4 required to obtain free T4 measurements. We conclude that unrecognized T4 sequestration is a major confounding variable in free T4 assay performance, and that it explains the underestimates of serum free T4 concentrations by free T4 immunoassays which cannot be explained by sample dilution.

Humans↗

Heterogeneity in affinities of serum proteins for thyroxine among patients with non-thyroidal illness as indicated by the serum free thyroxine response to serum dilution.

UNLABELLED: Some patients with non-thyroidal illness (NTI) have sera with characteristics suggesting decreased functional affinity of thyroxine-binding globulin (TBG) for T4: increased T4 free fraction, decreased total T4 to TBG ratio, and a fall in free T4 with serum dilution greater than theoretical predictions assuming normal affinity. These studies aimed to further characterize this phenomenon. According to the law of mass action binding protein affinity for T4 can be estimated from the response of free T4 to progressive serum dilution. Free T4 responses in 25 normal controls and in 7 congenital TBG deficient controls resembled the predictions from the law of mass action. Among 25 of 38 medical intensive care unit patients, responses were intermediate between normals and TBG deficiency. Responses in the other 13 NTI were consistent with the presence of a dissociable inhibitor. In this subgroup, total T4 was depressed, both free T4 and TSH were elevated, and there was a positive correlation between TSH and free T4 (r2 = 0.41, p < 0.02). CONCLUSIONS: (i) decreased affinities of serum proteins for T4 consistent with binding inhibitor(s) are found in some patients with NTI; (ii) there is an association of these severely altered affinities with reversal of the expected free T4-TSH relationship.

Adult↗

Delirium associated with the combination of a neuroleptic, an SSRI, and benztropine.

BACKGROUND: On the basis of recent findings, the increased use of serotonin selective reuptake inhibitors (SSRIs) in combination with antipsychotics and concomitant benztropine is likely. METHOD: Five patients who developed delirium while receiving a neuroleptic, an SSRI, and benztropine are described. RESULTS: The timing of the delirium in relation to drug administration suggests the delirium was the result of an interaction of the SSRI and benztropine. CONCLUSION: Possible mechanisms are explored. Clinicians should be aware that patients receiving this combination may be at increased risk for delirium.

Aged↗

Characteristics of desipramine-refractory depression.

BACKGROUND: To determine the predictors of desipramine-refractory depression, the authors examined the outcome in patients with major depression who were admitted to a general hospital and treated with desipramine adjusted to an adequate blood level. METHOD: Sixty-eight consecutive inpatients with DSM-III nonpsychotic unipolar major depression who had failed to respond to 1 week of hospitalization without drug treatment were studied. Outcome was assessed with the Yale Depression Inventory after a 4-week desipramine trial in which 24-hour plasma concentrations were used to rapidly achieve a therapeutic desipramine level. RESULTS: Poor response to a therapeutic desipramine trial, which occurred in 15 of 50 patients, was significantly associated with definite personality disorder, prior treatment failure, near delusional status, age < or = 35 years, duration of depressive episode, recurrence of depression, dysthymia, and secondary depression. The first four items remained significantly correlated with poor response when the presence of the other items was accounted for using multiple regression. Drug response was not predicted by the diagnosis of melancholia (DSM-III and DSM-III-R) or initial severity of the depressive episode. CONCLUSION: The four strongest correlates of outcome were highly predictive of drug response. In patients with two or more predictors, only 25% (4 of 16) responded, while in those with one or no predictors, 91% (31 of 34) responded.

Adult↗

Plasma cortisol levels increase with age in obese subjects.

In order to assess the influence of age, sex, and body mass on plasma cortisol concentrations, we measured the 24-hour Integrated Concentration (IC) of cortisol (F) in 36 obese subjects (16 males, 20 females) aged 5.3-56.4 years, BMI = 35.5 +/- 7.3 kg/m2 and compared with 119 nonobese subjects, body mass indices (BMI) 21.2 +/- 2.7 kg/m2, aged 8.8-66.2 years (55 males, 64 females). Subjects were nondiabetic, normotensive, without history of psychiatric illness, and otherwise in good health. IC studies were performed using a continuous blood withdrawal methodology, and IC-F was assayed from the 24 hour pooled sample by a protein binding method. The effect of age and gender on IC-F was analyzed by multivariate regression. In the nonobese group there was no effect of age or sex on IC-cortisol levels, the mean IC-F = 173.8 +/- 44.1 nmol/L. A statistically significant but weak negative effect of BMI on IC-cortisol (r=-.18, p<0.05) was present. In the obese subjects there was a significant increase in IC-cortisol levels with age IC-F(nmol/L) = 2.76 x age(years) + 85.0 (r2=.36, p<0.0001). IC-cortisol levels tended to be lower in obese males than females when controlled for age (p<0.05). We conclude that in nonobese subjects IC-F levels are independent of age and gender. However, there is a significant increase of IC-cortisol levels with age in obese individuals. The observed increase of IC-cortisol with age may contribute to metabolic complications of obesity.

Adolescent↗

Age-related changes in serum free thyroxine during childhood and adolescence.

The purposes of this study were to reevaluate age-related changes in the concentration of serum free thyroxine (T4) between early infancy and adulthood, and to study the relationship of serum thyrotropin to these changes in free T4. Five hundred thirty-six healthy infants, children, adolescents, and adults between 1 day and 45 years of age were studied. Serum free T4 was determined by direct equilibrium dialysis, thyrotropin by a sensitive immunoassay, and total T4 by radioimmunoassay. Free T4 concentrations were age dependent and differed significantly (p < 0.001) at 1 to 4 days, 2 to 20 weeks, 5 to 24 months, 2 to 7 years, 8 to 20 years, and 21 to 45 years of age. Corresponding free T4 concentrations (mean +/- SEM) were 48.1 +/- 1.5, 20.3 +/- 0.6, 17.0 +/- 0.4, 19.9 +/- 0.4, and 21.2 +/- 0.4 pmol/L (3.74 +/- 0.12, 1.58 +/- 0.05, 1.32 +/- 0.03, 1.55 +/- 0.03, 1.32 +/- 0.03, and 1.65 +/- 0.03 ng/dl), respectively. Age-related reference ranges were determined. Changes in the relationship between serum thyrotropin and free T4 were complex, indicating age-related changes in pituitary thyroid regulation. No correlation existed between concentrations of free T4 and total T4 after the first 13 days of life (r2 < 0.01). We conclude that (1) pediatric free T4 concentrations and free T4-thyrotropin relationships differ from those in adults and (2) age-related changes in total T4 do not indicate age-related changes in either free T4 or thyroid function, after 13 days of age.

Adolescent↗

Combined treatment strategies in psychiatry.

Combination drug regimens are commonly employed in the treatment of psychiatric disorders. Virtually all classes of psychotropic medications have been used in combination and for a variety of indications. Some drug combinations are thought to be synergistic, and others are used to treat different target symptoms. Combination therapies are used as the primary treatment for certain disorders (antipsychotic-antidepressant combinations in psychotic depression); as adjunctive treatment for patients refractory to initial drug therapy (lithium augmentation in refractory depression); and as treatment for the emergence of a secondary disorder (depression in a schizophrenic patient). Since combination treatment may increase the risk of adverse reactions through either pharmacodynamic or pharmacokinetic interactions, knowledge of these interactions and their possible adverse effects is crucial.

Antidepressive Agents↗

The neurobiology of primate vision.

Studies of the visual system of the primate have taken two directions. One group of neurobiologists have studied the oculomotor system, while an entirely separate group have analysed sensory processing in the retinogeniculo-cortical circuits. However, the versatility and adaptability of the primate visual system is only possible because sensory and oculomotor processing are highly integrated. More than any other species, primates have exploited the advantages of extensive and coordinated binocular eye movements to improve their visuomotor performance. This chapter describes the basic apparatus of primate vision. The integrated nature of visuomotor function is illustrated by two examples: smooth pursuit eye movements and stereovision. Both of these tasks require huge amounts of sensory processing in many different visual centres and, simultaneously, very precise control of binocular eye position. These examples illustrate the difficulty and artificiality of assigning unique functions to any component part of the system. Each part of the visual system, from the retina through the brain to the oculomotoneurones that drive the eye muscles, is involved in many different functions. This integration within the system raises the problem of how we represent and recognize our visual world in the brain. The traditional view from sensory psychology is that single nerve cells in the visual cortex signal significant percepts. As this chapter shows, the activity of single cortical neurones is influenced by multiple factors, including the qualities of the visual stimulus, the position of the eyes, and the attention being paid to the stimulus. Thus, the activity of single neurones is an ambiguous indicator of both perceptual and motor events. Only the collective action of many nerve cells, it seems, represents unique percepts and actions. Given this indivisibility of function, patients with localized brain lesions will invariably present with multiple visuomotor deficits.

Animals↗

Seizures associated with antidepressants: a review.

BACKGROUND: Seizures are uncommon, but serious, adverse effects of antidepressant drugs. A better understanding of drug-related seizure risk, its predictors, and its neurophysiologic basis might help clinicians avoid this adverse event. A better understanding of the factors involved in the determination of seizure risk would be helpful for interpretation of seizure rates reported. METHOD: The authors review case reports, series of cases, and information from clinical trials of antidepressants to determine antidepressant-related seizure risk. Predisposing factors are identified. Effects of dose, blood levels, and duration of treatment on seizure risk are examined. Electrophysiologic and in vitro models of drug-related seizure induction are discussed. RESULTS: A significant proportion of drug-related seizures occurs in individuals with an identifiable predisposition, such as previous seizures, sedative or alcohol withdrawal, and multiple concomitant medications. Seizure risk for most antidepressants increases with dose (or blood level), and comparisons between drugs should consider seizure rates at the effective dose (or blood level) for each drug. For imipramine, the most frequently studied tricyclic, the literature indicates a seizure rate between 0.3% and 0.6% at effective doses. In unselected patients and at higher doses, these rates may be higher. Fluoxetine, sertraline, fluvoxamine, trazodone, nomifensine, and the monoamine oxidase inhibitors have a lower seizure risk. Estimates for recently marketed antidepressants with intermediate seizure risk are complicated by the fact that effective doses and blood levels are not well established. CONCLUSION: Assessment of seizure risk in individuals involves consideration of predisposing factors, the antidepressant selected, and the bioavailability of the drug. Future studies of seizure risk would benefit from the use of specified criteria for determination of probable seizure events, a priori definition of predisposing exclusions, samples sufficiently large to provide adequate power, blood level monitoring, and inclusion of duration of drug treatment in the calculation of risk.

Antidepressive Agents↗