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Biomedical subjects

D J Swanson

Publications and source records attributed to D J Swanson.

30 records · Page 2Linked to original sources
PubMed1991

Ultrastructural distribution of glutamate immunoreactivity within neurosecretory endings and pituicytes of the rat neurohypophysis.

An ultrastructural analysis of post-embedding glutamate immunocytochemistry within the neural lobe of the pituitary was used to explore the possible role of glutamate within the magnocellular neuroendocrine cells. Relative densities of a colloidal gold marker associated with various cellular and subcellular compartments of the neural lobe were quantified by computer analysis of electron micrographs. Robust glutamate immunoreactivity was observed in both pituicytes (cytoplasm, mitochondria and nucleus) and neurosecretory endings. Within the neurosecretory endings, glutamate staining was specifically localized to the microvesicles with no overlap into the neurosecretory granule population. Stimulation of the vasopressin/oxytocin neurosecretory system by water deprivation increased glutamate content in pituicytes and mitochondria within neurosecretory endings but had little influence on microvesicle glutamate content. The results are consistent with the existence of multiple functional pools of immunoreactive glutamate in both pituicytes and neurosecretory endings. Microvesicles within the neurosecretory endings exhibit many properties of secretory vesicles, appear to be functionally independent of the neurosecretory granules, and have sufficient glutamate immunoreactivity to suggest that this amino acid may be compartmentalized for release in the neural lobe.

Animals↗
PubMed1989

Light and electron microscopic localization of glutamate immunoreactivity in the supraoptic nucleus of the rat hypothalamus.

The distribution of glutamate immunoreactivity was mapped within the supraoptic nucleus of the rat hypothalamus utilizing a specific anti-glutamate antibody. Magnocellular neuroendocrine cells of the supraoptic nucleus showed intense immunoreactivity for glutamate which varied with the conditions of fixation. Within the perikarya, reaction product was found associated with the endoplasmic reticulum but not the mitochondria, Golgi, dense bodies or neurosecretory granules. A relatively high density of glutamate-immunoreactive terminals was found in the supraoptic nucleus. These terminals were less affected by fixation condition and were generally found contacting large, glutamate-immunoreactive processes within the ventral dendritic neuropil of the supraoptic nucleus. The pattern and characteristics of glutamate immunoreactivity in the supraoptic nucleus suggested the presence of two distinct glutamate pools. The magnocellular neuroendocrine cells may contain a large, labile metabolic pool of glutamate. These cells, in turn, appear to receive glutamate synaptic input from a more stable pool consistent with suggestions that glutamate may be used as a transmitter within this system.

Animals↗
PubMed1988

Local synaptic organization of cholinergic neurons in the basolateral hypothalamus.

A monoclonal antibody to choline acetyltransferase (ChAT) was utilized for immunocytochemical identification of cholinergic neurons in the basolateral hypothalamus. Light and electron microscopic examination revealed a network of cell bodies, dendrites, and axonal processes dorsolateral to the supraoptic nucleus. Within this region the cells immunoreactive for ChAT receive numerous unlabeled terminals which contact dendrites, cell soma, axons and occasional somatic spines. In a few cases, small ChAT-immunoreactive terminals were observed contacting a cholinergic cell soma or large dendrite. Many ChAT-immunoreactive fibers were directed toward the supraoptic nucleus forming a dense local network but very few of these fibers penetrated deeper than approximately 20 micron into the supraoptic nucleus. A total of 63 ChAT-immunoreactive terminals were mapped within the basal hypothalamus, of which the vast majority contacted unlabeled dendrites immediately dorsolateral to the supraoptic nucleus. Labeled terminals were rare or nonexistent in the medial portions of the hypothalamus or deep within the supraoptic nucleus. This pattern of ChAT terminal densities correlates with the distribution of binding for the muscarinic cholinergic probe, [3H]quinuclidinylbenzilate, but not the binding of the putative nicotinic cholinergic probe, [125I]alpha-bungarotoxin, which is high within the supraoptic nucleus. Thus, the cholinergic neurons of the basal hypothalamus appear to form a network of intrinsic connections which probably represent input to muscarinic cholinergic receptors. No evidence was found to suggest that cholinergic presynaptic terminals were colocalized with the alpha-bungarotoxin binding protein within the supraoptic nucleus.

Animals↗
PubMed1988

The influence of laminin on the initial differentiation of cultured neural tube neurons.

Portions of the metencephalic neural tube containing the trigeminal (V) motor nucleus from 40-hr chick embryos were excised and held freely floating in culture medium for 36-40 hr, so that neuronal generation within motor V could be completed, but precluding neuronal differentiation. The explants were then dissociated and plated either on 1) glass coverslips that had been coated with the extracellular matrix (ECM) glycoprotein, laminin, and subsequently irradiated to produce a grid pattern; or 2) coverslips, one-half of which had been coated with laminin, and the other one-half with collagen, another component of the ECM. The purpose of these studies was to assess possible laminin influences on neuronal adhesion and nerve fiber expression and extension during these periods of initial neuronal differentiation. The early neural tube neurons selectively adhered to the established laminin grid pattern; neuronal survival, elaboration of neurites, and extent of neurites were significantly enhanced on the laminin side of the laminin/collagen preparations. These latter effects were specifically blocked by the application of anti-laminin. In demonstrating these influences during stages of initial neuronal differentiation, the results support the hypothesis that laminin may play a role in normal neurogenesis, presumably by providing an adhesive surface for outgrowing growth cones.

Animals↗
PubMed1985

Treatment with aztreonam or tobramycin in critical care patients with nosocomial gram-negative pneumonia.

During the course of one year, 47 critical care patients with gram-negative bacillary pneumonia at Millard Fillmore Hospital were randomly assigned to aztreonam or tobramycin therapy (two to one). Of these, 40 were fully evaluable for microbiologic and clinical response. All evaluable patients had gram-negative organisms in tracheal aspirate culture specimens and confirmed susceptibility of the organism to both study drugs. There was no difference between the two groups with respect to the percentage of patients who received concurrent antibiotics for gram-positive organisms. More than 60 percent of the patients received mechanical ventilation. Essentially, all had new lung infiltrates as shown by chest radiography, leukocytosis, recent onset of fever, and increased volume of purulent secretions. Half had multilobar pulmonary infiltrates. Their mean age was 73 years, with none under age 50. Most had chronic obstructive pulmonary disease, congestive heart failure, or both. By the prognostic nutritional index criteria, over 70 percent were nutritionally deficient at entry. The majority of infections were caused by Pseudomonas, Enterobacter, Klebsiella, and Escherichia coli. Aztreonam eradicated 92 percent of the causative gram-negative organisms, compared with 57 percent for tobramycin (p less than 0.05). Aztreonam produced a favorable clinical response (cure or improvement) in 93 percent of patients, compared with 50 percent for tobramycin (p less than 0.05). There were no differences in the minor adverse effects observed in the two treatment groups. Overall, aztreonam was superior to tobramycin for treatment of pneumonia due to susceptible gram-negative bacteria in these critical care patients.

Aged↗
PubMed1984

Role for dual individualization with cefmenoxime.

Cefmenoxime concentration/effect relationships were retrospectively explored for gram-negative bacteria isolated from 14 critical care patients treated for nosocomial pneumonia. The effects of cefmenoxime concentrations on in vitro growth kinetics of 21 isolated pathogens were studied using the Abbott MS-2 Research System, from which a dynamic response concentration was derived. Serum pharmacokinetic profiles were obtained in each patient. These data were used to calculate the in vivo total area under the curve over dynamic response concentration and the time that cefmenoxime concentrations exceeded the dynamic response concentration for each bacteria. The same determinations were made in 18 patients prospectively treated, except that dosage was optimized on the basis of previous mathematical relations to achieve bacterial eradication in four days. This method of dosage optimization is termed dual individualization. Serial cultures of infected tissues were evaluated to determine the number of days to the eradication of bacteria, and the pharmacokinetic and pharmacodynamic variables were used to describe the bacteriologic response of the original pathogen isolated in pretreatment culture. Bacterial eradication rates could be described from cefmenoxime pharmacokinetics in the patient and from the relation between concentration and bacterial inhibition. Patients who were prospectively treated using these retrospectively derived relationships had a predictable day of bacterial eradication. This, in turn, was associated with a shorter duration of treatment (p less than 0.05). The success of prospective dual individualization is encouraging and suggests that more precise optimization of antibiotic dosage can yield a predictable rate of bacterial eradication from the infection site.

Aged↗
PubMed1983

Steady-state moxalactam pharmacokinetics in patients: noncompartmental versus two-compartmental analysis.

Moxalactam pharmacokinetics at steady state was examined in a group of 40 patients with presumed or proven abdominal sepsis. Mean steady-state serum concentrations ranged from 27.0 to 211.0 mcg/ml and correlated inversely with creatinine clearance (r = 0.91, p less than 0.0001). Terminal half-life ranged from 1.27 to 8.27 hr and reflected the varying renal function of the patients. Moxalactam total body clearance (CL) displayed excellent correlation with creatinine clearance as 92% (r2 x 100) of the variance in clearance could be accounted for by renal function (p less than 0.0001). Pharmacokinetic parameters were estimated using noncompartmental analysis based on statistical moment theory. Noncompartmentally determined CL was in agreement with CL determined by nonlinear least squares regression (r = 0.99, p less than 0.0001). Moxalactam total body clearance is best predicted from creatinine clearance corrected for body surface area.

Biological Assay↗
PubMedDate not supplied

Ethanol exposure affects trophic factor activity and responsiveness in chick embryo.

Chick embryos were chronically exposed to either ethanol (approximately 30 mg/d) or saline, from E4-E13. Homogenate extract was prepared from forebrain tissue from E16 experimental and control embryos and was applied to cultured dorsal root ganglia (DRG). Neurotrophic activity in the forebrain extract (FBX) was significantly reduced in the ethanol-treated embryos compared to saline controls, both in terms of influences on neuronal survival and process elaboration. In addition, E8-9 DRGs from embryos exposed to ethanol from E4 were less viable in the presence of NGF than were those from controls. DRG survival in the presence of E16 FBX (from untreated embryos) was not different following ethanol treatment, but neurite production was significantly reduced. These results suggest that neurotrophic factor content and responsiveness may be appreciably altered following chronic prenatal ethanol exposure. Such alteration could underlie certain CNS anomalies seen in the fetal alcohol syndrome.

Animals↗
PubMedDate not supplied

Chronic ethanol alters CNS cholinergic and cerebellar development in chick embryos.

Chick embryos were given daily injections of ethanol (approximately 30 mg/day) either chronically from embryonic days 4 to 15 (E4-E15) or E18, or acutely from E15 to E18. Untreated and saline-injected embryos served as controls. Although morphological indicators of developmental age were not different among groups, chronic ethanol reduced weights of several brain regions. Similar to rodent models of prenatal ethanol exposure, chronic ethanol treatment reduced cerebellar Purkinje cell numbers compared to controls. Chronic but not acute ethanol exposure resulted in a significant reduction in choline acetyltransferase activity in the optic tectum (OT) and forebrain (FB) compared with controls. This study demonstrates that the chick embryo is a viable model to investigate the effects of ethanol exposure on CNS development. Unlike the mammalian fetus, the avian embryo is isolated from maternal interactions and may prove more useful in investigating the mechanisms by which ethanol directly influences brain development.

Animals↗
PubMedDate not supplied

Pharmacokinetics and extravascular penetration of aztreonam in patients with abdominal sepsis.

Patients with abdominal sepsis were enrolled in a clinical trial of aztreonam vs. tobramycin. All were given clindamycin concomitantly. The pharmacokinetics of aztreonam in 21 patients randomly assigned to receive treatment with aztreonam are reported. The mean age of these patients was 68 years; most had underlying disorders such as malnutrition and cardiac or pulmonary disease. Creatinine clearance (Clcr) ranged from 11.2 to 133.1 ml/min. The usual dose of aztreonam was 2.0 g every 8-12 hr. A single pharmacokinetic study was performed over one dosing interval after steady-state conditions were achieved. In approximately one-half of the patients, peritoneal fluid was collected during the interval between doses. Penetration of aztreonam, as expressed as the ratio of concentration in the peritoneal fluid to that in serum, was higher for aztreonam (0.95:1) than for tobramycin (0.46:1). The ratio of the concentration in peritoneal fluid to the minimum inhibitory concentration (MIC) of the infecting bacteria was also higher for aztreonam. Serum pharmacokinetic data were analyzed by both two-compartment and moment analysis. For both the steady-state volume of distribution (Vdss) and total body clearance (TBC), the values determined by both methods were highly correlated (r = .96, .99, respectively). Average values for Vdss and TBC were 0.28 liters/kg and 80 ml/min. TBC for aztreonam correlated strongly with CLcr and was described by the regression equation TBC = 1.1 (Clcr) + 1.6, r = .87, P less than .01.

Abdomen↗