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Biomedical subjects

S Feldman

Publications and source records attributed to S Feldman.

At least 253 records · Page 14Linked to original sources

Interleukin-2 correction of defective in vitro T-cell mitogenesis in patients with common varied immunodeficiency.

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies, OKT3 and Pan T2, to induce interleukin-2 (IL2) production and proliferation in peripheral blood lymphocytes (PBL) from 14 patients with combined varied immunodeficiency (CVI). The median values of endogenous IL2 produced by mitogen-stimulated PBL was significantly lower in patients than controls irrespective of the mitogen used. The patients, taken as a group, had a significantly decreased in vitro PBL response to mitogen stimulation when compared to controls. With the addition of a highly purified human IL2 preparation, the proliferative response in the majority of patients was significantly improved with all mitogens. Three patient groups could be distinguished: Group A (3/14) had full restoration of proliferative response with the addition of IL2, Group B (5/14) had partial restoration, and Group C (6/14) had no significant response. The monoclonal antibody, Pan T2, recognized a T-cell proliferative defect in 5 of 14 patients which neither PHA nor OKT3 recognized. This was not significantly corrected by the addition of IL2. This T-cell proliferative defect correlated with the lack of B-cell proliferation and immunoglobulin production in response to B-cell mitogens in three-fourths of the patients assayed. These data show that CVI patients are a heterogeneous group but have in common a decreased in vitro production of IL2 resulting in a proliferative defect which is correctable at least in part, in vitro, in the majority by the addition of purified IL2.

Adolescent↗

Effect of central serotonin depletion on adrenocortical responses to neural stimuli.

In view of the possible role of serotonin in adrenocortical regulation, basal plasma corticosterone concentrations and the response to ether stress, photic, acoustic, or sciatic nerve stimulation, were studied in rats with 5,7-dihydroxytryptamine or vehicle injected into the raphe nuclei. The neurotoxin inhibited the response to photic stimulation without affecting the other modalities. This may suggest that the depletion of brain serotonin has a differential effect on the transmission of neural impulses which activate the adrenal cortex.

Acoustic Stimulation↗

Adrenocortical responses to ether stress and neural stimuli in rats following the injection of 6-hydroxydopamine into the medial forebrain bundle.

Adrenocortical responses, as expressed by changes in plasma corticosterone concentrations, after ether stress, or photic, acoustic, or sciatic nerve stimulation were studied in rats, with 6-hydroxydopamine or vehicle injected into the medial forebrain bundle (MFB). The neurotoxin partially inhibited the response to photic stimulation only, indicating the involvement of MFB catecholaminergic fibers in the transmission of this response which stimulates adrenocortical secretion.

Acoustic Stimulation↗

Balancing the failure modes in the electronic circuit of a cardiac pacemaker: a decision analysis.

Cardiac pacemaker malfunctions are of continuous concern to the medical profession as well as to the electronics industry. Certain failures in cardiac pacemaker performance are critical and can result in patient deaths. Cardiac pacemakers are vulnerable to certain malfunctions in the electrode, batteries and the electronic circuit. This paper focuses on failures and reliability of the electronic circuit and how they affect its choice and design. The paper discusses the issues of balancing the various failure modes by considering both failure rates and failure outcomes. As the choice of an appropriate pacemaker is a decision problem under conditions of uncertainty, we employ decision analysis as the analytical and conceptual framework. Use of utility theory enables a systematic quantitative evaluation of such seeming intangibles as the various failure outcomes. Probabilities are assessed using specific engineering and reliability literature. The method is demonstrated on a choice problem between two specific electronic circuit designs. The methodology can be useful in designing the electronic circuit to meet certain reliability specifications, deciding whether or not to introduce redundancy, decisions affecting components and technology, and establishing minimal reliability standards, with regard not only to cardiac pacemakers but to other electronics as well.

Electronics, Medical↗

Permanent cardiac pacing in congenital heart disease: a follow-up study of 20 patients.

Sinus nodal dysfunction (SND) and complete heart block (CHB) in congenital heart disease (CHD) are commonly associated with congestive heart failure, syncopal attacks, and sudden death. Permanent cardiac pacing (PCP) is required to avoid these manifestations which are frequently associated with a high rate of complications, particularly in the younger age group. Twenty patients with CHD aged 4 months to 46 years underwent pacemaker implantation. Twelve (60%) were less than 20 years of age. CHB was present in 15 patients: in 10 it developed 1 week to 11 years following surgery, in two it was congenital, and in three patients it developed spontaneously with previous conduction disturbances. SND was present in 5 patients: it was congenital in two patients and developed post-operatively in three. Seventeen patients are alive and no syncopal attacks or bradyarrhythmias were recorded 2.5 to 12.5 years following the initiation of PCP. Improvement in the cardiac output was noted in most patients with heart failure. The three patients who died had adequately functioning pacemakers. Only nine re-implantations were needed, seven of them in adult patients after closure of an atrial septal defect. Our experience indicates a favourable outcome for patients with CHD needing PCP.

Adolescent↗

A four-year experience with preoperative noninvasive carotid evaluation of two thousand twenty-six patients undergoing cardiac surgery.

From January 1979 through December 1982, 2026 patients scheduled to undergo open heart surgery were evaluated by a preoperative battery of noninvasive carotid tests including phonoangiography, oculopneumoplethysmography, pulse-timing oculoplethysmography, periorbital Doppler examination, and during the last 12 months, continuous-wave Doppler ultrasonography with spectral analysis. The incidence of hemispheric neurologic deficit following cardiac surgery in the 47 patients with carotid disease was 14.9%; the incidence in patients with no carotid disease was 1.9% (p less than 0.001). Fourteen of the 47 patients were not candidates for carotid surgery because of unilateral occlusion in 13 and bilateral occlusion in one. Three of the 14 (21.4%) had intraoperative strokes on the appropriate side. Thirty-three of the 47 had operable carotid disease. Four with unilateral stenosis had no carotid surgery; one had a postoperative deficit on the side referable to the nonstenotic artery. Eighteen with unilateral stenosis underwent simultaneous cardiac and carotid surgery; one (5.6%) had a transient deficit. Seven patients with bilateral stenosis underwent cardiac and unilateral carotid surgery; no deficits occurred. Four patients with unilateral stenosis and contralateral occlusion underwent combined surgery; one had a transient ischemic attack and one a fatal stroke, both referable to the hemisphere ipsilateral to the occlusion. It appears that the presence of carotid disease increased the risk of stroke during heart surgery. Proof that carotid endarterectomy lowers this risk awaits a prospective randomized trial.

Angiography↗

Mediobasal hypothalamic neurons are excited by the iontophoretic application of sodium.

In the course of studies on the responsiveness of mediobasal hypothalamic neurons to the iontophoretic application of cortisol, it was found that positive currents applied to a sodium chloride (1 M) barrel alone, but not to a choline chloride (1 M) barrel, frequently increased the firing of these neurons. Subsequently, systematic examination demonstrated that out of 102 MBH neurons 52 (51%) increased their firing by at least 30% with application of NaCl, using currents no greater than 10 nA. No such effect was obtained in response to Na application from a dilute solution (0.05 or 0.1 M). When glutamate was absent from the electrodes, the incidence of Na+ sensitivity fell to 17%, despite the routine use of backing currents to the glutamate barrel. K+ ions were more active than Na+ ions in producing excitation. When Na+ sensitivity was found, however, Na+ effects were produced by currents greater than K+ currents producing equivalent excitation. Like glutamate, K+ ions were capable of greatly enhancing responses to Na+. Comparison was made between cortisol and Na+ sensitivity in 70 MBH neurons; 28 cells responded to both, and 24 of them were inhibited by cortisol. Thus Na+ sensitivity is a frequent characteristic of MBH neurons inhibited by cortisol, and was present in 83% of cortisol-sensitive cells in this region. Iontophoresis of Na+ is commonly used as a control in pharmacological studies of the nervous system. Even more common is the case of concentrated NaCl solutions for recording. These procedures may not be as inert as previously thought, particularly in the hypothalamus.

Animals↗

The effects of iontophoretic application of putative neurotransmitters on the electrical activity of rat mediobasal hypothalamic neurons in relation to their steroid sensitivity.

In order to characterize the neurons responsible for ACTH release and the suppression produced by adrenocortical steroids, we have studied the pharmacological sensitivity of neurons in the region containing the highest concentration of corticotropin releasing factor (CRF) in the brain and probably responsible for most of these activities. The effects of 8 putative neurotransmitters applied iontophoretically to more than 400 mediobasal hypothalamic (MBH) neurons in the rat were examined, and compared with cortisol sensitivity of the same neurons. Glutamate was the only agent that produced excitation exclusively, while GABA, serotonin, glycine and dopamine were inhibitory in action. Mixed excitation and inhibition were produced by histamine, acetylcholine (ACh) and norepinephrine (NE). All 8 cells excited by ACh were inhibited by cortisol and constitute only about 10% of neurons sampled; these neurons are considered to be strong candidates for CRF-releasing cells. On 7 of these neurons histamine was strongly excitatory and its action greatly outlasted the iontophoretic application. Histamine, however, excited many other neurons, including those neither excited by ACh nor steroids.

Acetylcholine↗

The uptake and disposition of 1,1-dichloroethylene in rats during inhalation exposure.

The uptake, disposition, and respiratory elimination of 1,1-dichloroethylene (1,1-DCE) during inhalation exposure were evaluated to gain insight into the pharmacodynamics of the halocarbon. Anesthetized male Sprague-Dawley rats inhaled 25, 75, 150, or 300 ppm 1,1-DCE for 3 hr from an aluminized Mylar bag through a miniaturized one-way breathing valve inserted into the trachea. Periodic air samples were taken immediately adjacent to the valve from the separate inhaled air and exhaled breath streams concurrently with blood samples from a cannulated femoral vein and analyzed for 1,1-DCE content by gas chromatography. 1,1-DCE was absorbed very rapidly, in that substantial levels were present in the venous blood at the first sampling time (i.e., 2 min). Percentage systemic uptake decreased over time after initiation of exposure until equilibrium was established. Percentage uptake after reaching equilibrium varied inversely with the exposure concentration. 1,1-DCE venous whole-blood levels in animals exposed to 25, 75, and 150 ppm 1,1-DCE increased rapidly to near steady state within approximately 45 min, as did concentrations of 1,1-DCE in the exhaled breath and alveolar air. Calculation of the amount of 1,1-DCE taken up by the body over the course of the 3-hr exposures revealed that cumulative uptake of the inhaled chemical was statistically linear for the 25-, 75-, and 150-ppm exposures. Accumulation plots for 300-ppm exposed animals, however, were best fitted to a cubic curve form. Although trends toward the establishment of equilibrium were initially seen in the 300-ppm exposed animals, levels of 1,1-DCE in the blood and breath rose progressively during the latter hour of the 3-hr exposure period. Thus, despite increased exhalation of 1,1-DCE, these animals could not prevent systemic accumulation of the chemical.

Animals↗

Role of medial forebrain bundle catecholaminergic fibers in the modulation of glucocorticoid negative feedback effects.

The possible role of medial forebrain bundle (MFB) catecholaminergic fibers in the previously observed MFB-mediated modulation of hypothalamic sensitivity to glucocorticoid negative feedback effects has been investigated. MFB catecholaminergic fibers were destroyed by bilateral MFB injections of 6-hydroxydopamine (6-OHDA) to adult male rats. The inhibitory effect of dexamethasone (10 micrograms, i.p., 4 h) upon the adrenocortical secretory response to ether stress, as estimated by serum corticosterone levels, was enhanced in the 6-OHDA-treated animals, as compared to vehicle-injected controls. This study suggests that MFB noradrenergic neurons are at least partially responsible for the MFB-mediated modulation of hypothalamic sensitivity to glucocorticoid hormones.

Animals↗

Antacid effects on the gastrointestinal absorption of riboflavin.

The effect of aluminum hydroxide, magnesium hydroxide, and a combination of aluminum-magnesium hydroxide suspensions on the oral absorption of riboflavin was examined in five subjects. Coadministration of aluminum hydroxide or magnesium hydroxide suspension with riboflavin (30 mg) resulted in an increase in time of peak urinary excretion rate of riboflavin when compared with control studies. There was no increase in the peak excretion rate or total urinary excretion of riboflavin when the antacid-treated subjects were compared to the control studies. In vitro experiments indicated that significant binding of riboflavin to the aluminum hydroxide and magnesium hydroxide suspensions occurred. The results of the present investigation are consistent with the reported effect of aluminum ion on GI motility and the known influence of gastric emptying on the absorption of riboflavin from the GI tract.

Adult↗

Effect of 6-hydroxydopamine on in vitro hippocampal corticosterone binding capacity in the male rat.

Adult male rats were injected with 6-hydroxydopamine, either into the lateral brain ventricle or directly into the dorsal hippocampus. They were adrenalectomized 5-7 days later, and following an additional 24 hours, the specific in vitro 3H-corticosterone binding capacity of dorsal hippocampal slices was determined by estimation of uptake of radioactivity by the nuclear fraction. Specific corticosterone binding was reduced by 40-50% in both experimental groups, as compared to vehicle-treated controls. These results suggest that the maintenance of normal dorsal hippocampal corticosterone binding capacity is dependent upon the integrity of endogenous brain catecholaminergic neural systems.

Animals↗

Modifications in single cell activity in the rat midbrain during the iontophoretic application of cortisol.

In view of the modulatory role of the midbrain in the regulation of adrenocorticotrophic functions, the effects of iontophoretic application of cortisol to central gray and midbrain reticular formation units was studied. Two-thirds of the cells responded by a change in the rate of firing, mainly by inhibition, which in some cells lasted more than 1 min. These modifications in the excitability of midbrain neurons, produced by changing concentrations of glucocorticoids, may affect indirectly hypothalamic neuroendocrine mechanisms controlling ACTH secretion.

Animals↗

Single-cell and multiunit activity in freely moving rats after corticosterone administration.

With the purpose of correlating possible electrophysiologic changes in the brain with the negative feedback effect of glucocorticoids on neuroendocrine functions, the effects of corticosterone on multiunit (MUA) and single-cell activity in freely moving rats were studied in the hypothalamus, amygdala, and midbrain reticular formation. The hormone changed the MUA in all regions studied causing mainly an increase in the rate of firing. In the hypothalamus there was a predominance in overall inhibition, when the sensory responsiveness to acoustic stimulation was compared before and after corticosterone administration. No such effect was observed in the amygdala and midbrain reticular formation. The hormonally induced changes in MUA in the hypothalamus were confirmed by analysis of single-cell activity in the freely moving rats which showed also changes in the pattern of firing, as demonstrated by autocorrelations. These findings in the hypothalamus are significant and may represent the electrophysiologic correlates of changes in corticotrophin releasing factor in this region.

Amygdala↗

Episiotomy pain: efficacy and safety of fluproquazone compared to aspirin and placebo.

The analgesic efficacy of fluproquazone at 100 mg and 200 mg doses, was measured in 160 patients with episiotomy pain and was compared to that of aspirin (650 mg) and placebo. The 100-mg dose of fluproquazone was more effective in relieving episiotomy pain than the 200-mg dose of fluproquazone, aspirin or placebo in terms of mean pain intensity scores after 1 h. All active compounds were more effective than placebo by all criteria.

Adolescent↗