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Biomedical subjects

S Feldman

Publications and source records attributed to S Feldman.

At least 217 records · Page 12Linked to original sources
PubMed1986

Inhibition by corticosterone of paraventricular nucleus multiple-unit activity responses to sensory stimuli in freely moving rats.

In order to determine possible electrophysiologic correlates of negative feedback influences of glucocorticoids upon neuroendocrine secretory activity, the effects of various doses of corticosterone on paraventricular nucleus multiple-unit activity responses to neural stimuli were examined in conscious, freely moving male rats. In control animals, photic and acoustic stimulation significantly increased multiple-unit activity of the paraventricular nucleus by increments of 75% and 117% (P less than 0.005), respectively. Doses between 0.1 and 5.0 mg of corticosterone produced a dose-dependent inhibition of responses to photic stimulation with a high correlation coefficient (r = -0.990). Corticosterone also caused an inhibition of paraventricular multiple-unit activity in response to acoustic stimulation, which was more effective than for photic stimulation, with complete blockade of response occurring with a dose of 1 mg corticosterone. These electrophysiologic findings, within a region of the hypothalamus known to contain corticotrophin-releasing factor cell bodies, may be related to reduced secretion of the hormone in response to the neurogenic stimuli employed, following glucocorticoid administration.

Acoustic Stimulation↗
PubMed1986

Electrophysiologic evidence for connections between the supraoptic and the arcuate/ventromedial hypothalamic nuclei in the rat.

Extracellular action potentials were recorded from 48 single units located in the hypothalamic arcuate and ventromedial nuclei. Fifteen percent of the cells were identified as projecting to the median eminence and some of these cells may have belonged to the tuberoinfundibular dopaminergic systems. Responses of all cells to stimulation of the ipsilateral supraoptic nucleus were recorded; 17% of ventromedial nucleus neurons were antidromically identified as projecting to the supraoptic nucleus. None of the latter cells was also identified as projecting to the median eminence. Three of six identified tuberoinfundibular and eight unidentified ventromedial nucleus cells were found to be excited by stimulation of the supraoptic nucleus. One arcuate cell identified as projecting to the median eminence was nonresponsive to supraoptic stimulation. Orthodromic inhibitory responses were recorded from 17% of all cells recorded but no inhibitory responses were recorded from cells identified as projecting to the median eminence. We suggest that these results may provide some neurophysiologic explanations for the observed interrelationships between oxytocin and prolactin secretion, and between vasopressin and growth hormone secretion.

Action Potentials↗
PubMed1986

Electrophysiology of limbic forebrain and paraventricular nucleus connections.

The connections of forebrain structures with the hypothalamic paraventricular nucleus (PVN) were examined electrophysiologically in anaesthetized male rats. Single unit recordings from 336 neurons were made within the cingulate cortex (CC, n = 78), lateral septum (LS, 114), bed nucleus of the stria terminalis (BST, 27). bed nucleus proprioris commissurae (BCA, 27) and preoptic area (POA, 90). Following PVN stimulation, some cells in all regions were identified as projecting to the PVN. Antidromic (24%), orthodromic excitatory (44%) and inhibitory (22%) responses recorded from CC units demonstrated the presence of reciprocal pathways between PVN and CC. Thirty-eight percent of LS units were antidromically identified as projecting to the PVN and these appeared to show some discrete topographic organization. Fifty-seven percent of LS units responded orthodromically to stimulation of the PVN, the majority of such responses being excitatory. Within the bed nuclei, 24% of units were antidromically identified as projecting to PVN and 70% of cells in these regions responded orthodromically following PVN stimulation, excitatory responses predominating within the BST and inhibitory responses within the BCA. Within the POA, 38% of units were identified as projecting to the PVN and the remaining units were approximately divided between orthodromic excitatory and inhibitory responses. A small proportion of antidromically identified units (less than 20%) in all regions also exhibited responses suggesting the presence of reciprocal connections with the PVN.

Animals↗
PubMed1986

Immunity to influenza A virus infection in young children: a comparison of natural infection, live cold-adapted vaccine, and inactivated vaccine.

Live attenuated, cold-adapted (ca) influenza A vaccines administered intranasally have been well characterized as safe and immunogenic, but comparative data on protective efficacy are required for further development. In this study, 59 young children were divided into the following four groups based on prior exposure to influenza A (H3N2) virus: natural infection, live ca vaccine given intranasally, inactivated vaccine given im, and no previous exposure. Virus challenge with homologous live ca vaccine occurred 12 months after vaccination or natural infection. Prior natural infection and live ca vaccine significantly reduced ca virus shedding after challenge compared with inactivated vaccine or no prior exposure to influenza A virus. Prechallenge nasal IgA, detected almost exclusively in subjects naturally infected or vaccinated with live ca virus, was associated with protection. Although inactivated vaccine failed to produce significant local IgA during the primary response, it seemed to prime for secondary local antibody responses after challenge with live ca virus.

Administration, Intranasal↗
PubMed1986

Pharmacokinetics of cefoperazone in the parturient.

Limited pharmacokinetic data for cefoperazone are available from the parturient. Because cefoperazone has a dual excretory pattern, primarily via the biliary system and secondarily via the kidney, pregnancy-induced physiologic alterations can influence its deposition and clearance. Twelve term parturients receiving cefoperazone prophylaxis after cesarean section were selected for study. After 2 g of cefoperazone was administered for 1 h intravenously, serial blood samples were assayed by high-pressure liquid chromatography. Plasma protein binding of cefoperazone was studied in vitro. The mean peak cefoperazone concentration +/- standard deviation was 169.9 +/- 60.4 micrograms/ml. The mean half-life was 152 min. Total serum clearance was 80.8 +/- 30.8 ml/min. The steady-state volume of distribution was 14.2 +/- 6.0 liters. All subjects had detectable trough levels at the end of the dosage interval, with a mean value of 6.5 +/- 5.2 micrograms/ml. Protein binding of cefoperazone for parturients was 74.3 +/- 10.9%, compared with 87.7 +/- 3.2% in nonpregnant controls (P less than 0.05). These data suggest that cefoperazone deposition can be greatly influenced by pregnancy. However, unlike several other new antimicrobial agents whose excretions are mainly renal, the cefoperazone half-life and thus trough concentration for the parturient more closely resemble that for the nonpregnant subject.

Adult↗
PubMed1986

Effects of stimulation of the preoptic area on hypothalamic paraventricular nucleus unit activity and corticosterone secretion in freely moving rats.

Recordings were made of single unit activity through chronically implanted electrodes within the hypothalamic paraventricular nucleus of freely moving male rats also bearing chronically implanted stimulating electrodes in the preoptic area (POA) and indwelling jugular cannulae. High frequency electrical stimulation of the POA evoked increases in the rate of electrical discharge in 58% of the units tested. Increases were recorded during each period of stimulation and were subsequently followed by a significant decrease in the rate of firing. In a substantial proportion of these neurones, bursting patterns of electrical discharge were observed before, during, and following stimulation of POA. When simultaneous removal of blood samples from these animals was performed, a significant increase in plasma corticosterone concentration, immediately following POA stimulation, was observed. The data obtained have provided a possible neurophysiological correlate of hypothalamic electrical activity that may be directly related to the neural control of adrenocortical secretion.

Animals↗
PubMed1986

Toxicokinetics and bioavailability of oral and intravenous 1,1-dichloroethylene.

Although aliphatic halocarbons have been identified as contaminants of drinking water supplies, little definitive information is available on their gastrointestinal (G.I) absorption and toxicokinetics. Therefore, a study of a representative halocarbon, 1,1-dichloroethylene (1,1-DCE), was undertaken to contrast the kinetics of the chemical following iv injection with that following oral administration. Four dosage-levels of 1,1-DCE (10, 25, 50, and 100 mg/kg BW) in 50% aqueous polyethylene glycol 400 were given iv and po to fasted and nonfasted male Sprague-Dawley rats. Serial blood samples were taken from the tail artery of the lightly etherized animals for up to 490 min after dosing. 1,1-DCE concentrations in the whole blood were determined by gas chromatographic head-space analysis. Evaluation of the iv data revealed that disappearance of 1,1-DCE from the systemic circulation followed a triexponential pattern. Light ether anesthesia did not appear to alter the pharmacokinetics of iv-injected 1,1-DCE. There was no difference between nonfasted and fasted iv rats in biological half-life (t1/2) or in any other pharmacokinetic parameter. Total body clearance, t1/2, apparent volume of distribution and volume of distribution in the central compartment did show increases with increasing dose in these animals. Oral dosing experiments revealed that 1,1-DCE was absorbed very rapidly and completely from the G.I. tract. Peak blood levels were reached 2 to 8 min following oral administration of 1,1-DCE as an aqueous suspension. The t1/2 of 1,1-DCE in orally dosed rats was somewhat longer than in their iv counterparts. The t1/2 values for nonfasted, orally dosed rats were longer than for their fasted counterparts, suggesting delayed absorption due to the presence of food in the G.I. tract. Bioavailability of 1,1-DCE, as determined by comparing areas under blood concentration versus time curves (AUCs), was equivalent in animals given the same dose of 1,1-DCE iv and po. AUCs increased with increasing dose in iv and po groups, but the increases were not proportional to dose.

Administration, Oral↗
PubMed1985

Involvement of the sensory cortex in adrenocortical responses following photic and acoustic stimulation in the rat.

In order to examine the possibility that the sensory cortex participates in the mediation of adrenocortical responses following sensory stimuli, the effects of photic and acoustic stimuli on plasma corticosterone were studied in rats with either visual or auditory cortex ablation. In animals with visual cortex ablation, the adrenocortical response to acoustic stimuli was intact; however, it was significantly reduced following photic stimulation. On the other hand, in animals with auditory cortex ablation, the response to acoustic stimulation was significantly reduced, but the response to photic stimulation remained intact. These data demonstrate the participation of the specific sensory cortex in adrenocortical responses following the stimulation of the corresponding sensory modality. The possible mechanisms involved may be either a tonic facilitatory effect of the specific cortex on subcortical mechanisms or the transmission of the specific stimuli in the primary sensory pathways, to achieve a full adrenocortical discharge.

Adrenal Cortex↗
PubMed1985

Comparison of long-term systemic and secretory antibody responses in children given live, attenuated, or inactivated influenza A vaccine.

A comparison of inactivated intramuscular and live intranasal influenza A vaccines in young children undergoing primary immunization might be expected to show differences in serum and local mucosal antibody responses. To demonstrate such differences, serum and local respiratory tract antibody responses of young children vaccinated with intranasal live, attenuated, cold-adapted (H3N2 or H1N1), or intramuscular inactivated (H3N2) influenza A vaccines were examined for one year after vaccination. Antibody responses were measured by hemagglutination-inhibition (HAI) and class-specific enzyme-linked immunosorbent assay (ELISA). One year after vaccination, live intranasal vaccinees had significantly less decay of serum HAI (p = 0.025) and IgG antibody (p = 0.01) directed against the influenza hemagglutinin and neuraminidase than did intramuscular inactivated vaccinees. Nasal secretory IgA developed almost exclusively in live vaccinees and persisted for up to one year. Persistent nasal secretory IgG was detected in both live and inactivated vaccinees. Live vaccination not only stimulates a more durable serum antibody response, but also induces long-lasting local respiratory tract IgA antibody that may play an important role in host protection.

Antibodies, Viral↗
PubMed1985

Pneumococcal vaccination in children with acute lymphocytic leukemia.

Sixty-three children with ALL in CCR and treated according to a standard therapy protocol were immunized with the 14-valent pneumococcal vaccine. Forty-six children were vaccinated 1, 3, or 6 months following initial induction remission; 15 were vaccinated 4-6 weeks following successful completion of 30 months of antileukemia therapy; and two were vaccinated at the time of diagnosis. Response to the vaccine was suboptimal and by the 6-month follow-up there were only two serotypes for which more than half the patients tested had greater than or equal to 300 ng antibodies N/ml.

Adolescent↗
PubMed1985

Effects of extrahypothalamic structures on the hypothalamic cell nuclear binding of corticosterone.

Hypothalamic or hippocampal slices were taken from adrenolectomized male rats either sham operated or with anterior (AHD) of posterior (PHD) hypothalamic deafferentations and from rats with dorsal hippocampectomy (DHIPP). The slices were incubated in Krebs-Ringer bicarbonate buffer in the presence of 10-60 nM 3H-corticosterone (CS) with or without 500 fold excess of unlabeled CS for 30 min. The cell nuclear binding in the hypothalami from either PHD of DHIPP rats were markedly reduced (by 50-70%) as compared to control or AHD rats. The binding of 3H-CS in hippocampi from AHD or PHD rats was not affected. These results suggest that extrahypothalamic structures can modulate the binding of CS in the hypothalamus by neural inputs entering the medio-basal hypothalamus from the caudal direction; such modulation may explain previously observed influences upon hypothalamic sensitivity to the feedback action of glucocorticoids by extrahypothalamic structures.

Animals↗
PubMed1985

Pharmacokinetics of acetohydroxamic acid in patients with staghorn renal calculi.

Acetohydroxamic acid (AHA), a bacterial urease inhibitor, has been recently approved by the United States Food and Drug Administration as a potential drug for the successful treatment of patients with infection induced staghorn renal calculi. The present study was designed to evaluate the disposition of 14C-AHA following oral administration to patients. The results of the study, while in a limited number of patients, indicate that upon oral administration, AHA is very rapidly absorbed from the gastrointestinal tract. Evaluation of urinary excretion data suggests that patients with compromised renal function have low recoveries of AHA in the urine. These data are supported by a strong linear correlation between creatinine clearance and AHA elimination. Acetamide and CO2 are identified as the two major metabolites of AHA in man. CO2 is eliminated in the breath and accounts for 20-45% of the administered dose, while acetamide is eliminated in the urine and accounts for only 9-14% of the administered dose. The remaining dose is eliminated as intact AHA in the urine (19-48%). Saliva concentrations of total radioactivity depict a strong positive correlation with their respective plasma concentrations. Parameter estimates from 14CO2 concentrations in breath as a function of time data closely correspond to the pharmacokinetic parameters of AHA in patients indicating that CO2 may be a primary metabolite derived directly from AHA rather than a secondary metabolite formed by the metabolism of an intermediate product. Upon multiple dose administration of AHA, there is the potential for significant accumulation of acetamide due to its relatively long half-life.

Acetamides↗
PubMed1985

Electrophysiologic evidence for neural connections between the paraventricular nucleus and neurons of the supraoptic nucleus in the rat.

These experiments were part of a study to examine the extrahypothalamic projections of the paraventricular nucleus in the rat. Thirty-nine cells, histologically identified as situated within the supraoptic nucleus, were recorded. Nine of those cells were classified as secreting vasopressin by their phasic patterns of electrical discharge. Six of the phasically firing cells were excited after electrical stimulation of the paraventricular nucleus and the other three were inhibited. Eight cells were antidromically identified as projecting to the paraventricular nucleus; most of these were not spontaneously active. Of the remaining 22 cells, the majority were spontaneously active, showing continuous patterns of firing, and most were inhibited after stimulation of the paraventricular nucleus. The data supply evidence for the presence of functional neural connections between the two major nuclei of the tuberohypophyseal neurosecretory system.

Animals↗
PubMed1985

The control of peritendinous adhesions using topical beta-aminopropionitrile base.

The Lindsay chicken foot tendon model was utilized to test the effect of topically applied beta-aminopropionitrile base upon the tensile strength of peritendinous adhesions following tenolysis of a scarified flexor tendon. The agent reduced by one-third the force required to effect tendon gliding and flexion of the joints in the involved digit. The results show that topical beta-aminopropionitrile is effective in the control of peritendinous adhesions and, therefore, achieves sufficient depth of penetration topically to affect the peritendinous location. No adverse effects of the topically applied agent were demonstrated. The principle of topical therapeutics that may have significant benefits to patients with tendon injuries is demonstrated.

Administration, Topical↗
PubMed1985

Modifications of adrenocortical responses following frontal cortex simulation in rats with hypothalamic deafferentations and medial forebrain bundle lesions.

With the purpose of delineating the neural pathways in the rat which mediate adrenocortical responses following frontal cortex stimulation, the effects of partial hypothalamic deafferentations and medial forebrain bundle lesion were studied. In intact and sham-operated animals, cortical stimulation through permanently implanted electrodes caused a significant increase in plasma corticosterone levels. In rats with anterior hypothalamic deafferentation and bilateral medial forebrain bundle lesions the adrenal response to cortical stimulation was blocked completely, while in animals with posterior hypothalamic deafferentation there occurred a normal rise in plasma corticosterone. These studies demonstrate that the frontal cortex effects on adrenocortical secretion are neurally mediated and involve an anterior hypothalamic input, more specifically the medial forebrain bundle.

Adrenal Cortex↗