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Biomedical subjects

S Nelson

Publications and source records attributed to S Nelson.

At least 325 records · Page 18Linked to original sources

Delayed effects of Soman: brain glucose use and pathology.

The [14C]-2-deoxyglucose (2-DG) technique was used to determine the delayed effects of Soman, a potent anticholinesterase inhibitor, on local cerebral glucose utilization (LCGU). Rats were given 100 micrograms/kg of Soman (0.9 LD50; i.m.) or saline and LCGU was assessed 24, 48 or 72 hours later. All Soman injected rats had strong, continuous seizures which persisted for at least one hour. At 24 hours post-Soman there was greater than a 2-fold reduction in LCGU in the frontal cortex, cingulate gyrus, anterior and ventral thalamic nuclei, lateral habenula, parietal cortex, lateral geniculate and medial geniculate. On the other hand, the hippocampal structures did not show a significant decrease in LCGU until 48 hours post-Soman exposure. Conspicuous neuropathology was obvious in a number of structures upon inspection of the frozen brain sections, hematoxylin and eosin stained sections or the 2-DG autoradiograms, 24 to 72 hours post soman-exposure. Damage was most severe in the piriform cortex and amygdala. The lateral and ventral thalamic nuclei, many cortical regions and variable segments of the hippocampus were also consistently damaged. We suggest that energy deprivation, inadequate perfusion and/or inadequate calcium sequestration may contribute to the delayed effects following Soman-induced seizures. The 2-deoxyglucose method provides information about the dynamic process of cerebral glucose utilization and serves as a "window" for identifying neuroanatomical structures affected by neurotoxins.

Animals↗

Attachment theory.

Maternal-infant attachment theory is another example of a theory borrowed from one discipline and adapted to another. Ethological observations of species-specific behavior exhibited by animals at the time of birth generated the hypothesis that perhaps humans also had species-specific behaviors which could have lasting effects on the relationship between mother and baby. While one cannot generalize the attachment theory, it has opened the way for a more humanistic approach to birthing.

Animals↗

The determinants of nursing home costs in Nebraska's proprietary nursing homes.

In the past few years nursing home care expenditures in Nebraska and the U.S. have been the fastest growing component of total health care expenditures. This rate of increase is particularly alarming in view of the fact that nursing home care is financed primarily by the Medicaid program or direct out-of-pocket payments. In fact, given the cutbacks in federal and state funds for this program, consumers will be forced to allocate a larger share of their income to meet the costs of nursing home care. Although nursing home expenditures have grown at an extremely rapid rate, relatively few empirical studies exist which analyze the cost function of nursing home providers. The purpose of this study is to identify factors which have directly influenced the cost of nursing home care in Nebraska and to evaluate the current Nebraska Medicaid reimbursement system in terms of its impact upon nursing home costs. The study was limited to a sample of 40 nursing homes in Nebraska which represents 42% of the total proprietary nursing homes in the state. The sample was limited to those facilities licensed only as an Intermediate Care Facility--I and they had to be receiving some Medicaid revenue. The data were averaged over the period of 1977-79, but the year of analysis corresponded to 1978. Multiple regression analysis was used to measure the effect of the hypothesized independent variables upon two different measures of cost--the average total cost per patient day and the average variable cost per patient day. In the first regression model 76% of the variance was explained and 71% was explained in the second equation. The results of this analysis are basically consistent with the findings of other studies and indicate that the number of staffing hours, patient mix, facility age, administrator experience and administrative intensity are significant determinants of nursing home costs. The most important finding from a policy perspective is that the current retrospective cost-related Medicaid reimbursement system does not provide incentives for minimizing costs. In fact, the present system encourages administrators to overutilize resources and charge higher prices. Considerable evidence exists which suggests that a prospective system would encourage a more efficient allocation of resources without adversely affecting the quality of care. Given the increase in the state's share of the total Medicaid budget, it would appear that a change to a prospective system is critical in order to maintain the financial accessibility to nursing home care by all Nebraska residents.

Costs and Cost Analysis↗

Mechanism of the pressor response to tetradecapeptide renin substrate in the rat.

The synthetic tetradecapeptide renin substrate (TDP; Asp-arg-val-tyr-ile-his-pro-phe-his-leu-leu-val-tyr-ser) has been employed frequently to elucidate the enzymatic action of renin in vitro and, to a lesser extent, in vivo. We assessed the utility of TDP as a renin substrate in vivo using conscious spontaneously hypertensive rats. Intravenous injection of TDP (1 and 3 micrograms/kg) increased diastolic pressure by 45 +r2 and 67 +/- 2 mmHg, respectively. The pressor response to TDP was significantly inhibited by captopril (3 mg/kg, po), indicating its dependence on conversion by ACE to some active molecule. Pressor responses to TDP also were less in animals subjected to bilateral nephrectomy 18-24 hr before study. However, responses to angiotensin I and II also were reduced, implying a non-specific effect of nephrectomy. Intravenous infusion of the renin inhibitor pepstatin (200 micrograms/min) inhibited pressor responses to hog renin by approximately 60%, but did not affect those to TDP. Intravenous infusion of the water soluble renin inhibitor, pepstatinyl-arginine-o-methyl ester (500 micrograms/min), also inhibited pressor responses to renin (approx. 80%) and did not affect those of TDP. Incubation to TDP (5 microM) with rabbit lung ACE resulted in generation of AI that was blocked by captopril (1 microM). These data suggest that TDP is a substrate for ACE and that the increase in blood pressure produced by TDP is due to its sequential cleavage by ACE to AII and can be independent of renin.

Angiotensin I↗

Captopril in primary pulmonary hypertension.

Seven women with primary pulmonary hypertension underwent hemodynamic evaluation, at rest and during exercise, before and after the oral administration of captopril. Dose-response curves were generated for the 25-, 50- and 100-mg doses. Captopril significantly reduced systemic blood pressure and systemic vascular resistance; these effects persisted at submaximal levels of exercise. Captopril did not alter pulmonary artery pressure or resistance, cardiac output or stroke volume at rest or during exercise. Exercise tolerance did not improve. Four of the patients also received captopril chronically for 12 weeks at doses of 75 and 100 mg every 8 hours. Resting and exercise hemodynamic evaluation was repeated at the end of the 12-week period. Except for a persistent reduction in mean systemic blood pressure at rest, chronic captopril administration did not elicit hemodynamic changes. Measured exercise duration did not change during continuous captopril treatment, although one patient reported mild subjective improvement in activity tolerance. In primary pulmonary hypertension, captopril exerts its major effect on systemic vasculature, with little or no effect on the pulmonary circuit. While an occasional patient may experience some clinical improvement with captopril therapy, the majority of adult patients with severe primary pulmonary hypertension will not benefit from its chronic administration.

Adult↗

Carney's triad: role of transthoracic needle biopsy.

A triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma, has been described in 7 patients, and a partial expression of this tumor complex consisting of 2 of the 3 tumors in at least 11 others. Sixteen of these 18 patients were female. The variable presentation and course of these patients warrants special attention. We present the nineteenth reported case: a 26-yr-old woman with a pulmonary chondroma and a gastric epithelioid leiomyosarcoma. It is suggested that in cases of this type thoracotomy may not be necessary for the diagnosis of the pulmonary chondroma, and extensive gastric resection of the leiomyosarcoma may be lifesaving.

Adult↗

In vitro effect of APF gel on three composite resins.

A laboratory study was conducted to determine effects of 1.23% APF gel on three composite resins. All composite resins immersed in APF gel lost significantly more weight than did their controls with significantly different weight losses among the APF-treated composites. Surfaces of all resins exposed to APF gel, as viewed in SEM's, exhibited degradation of filler particles.

Acidulated Phosphate Fluoride↗

Brain regional glucose use during Soman-induced seizures.

The (14C)-2-deoxyglucose procedure was used to determine the effects of the potent acetylcholinesterase inhibitor Soman on regional metabolism in the brain. Groups of rats were given 112 micrograms/kg Soman, 84 micrograms/kg Soman, or saline i.m., and 15 min later the (14C)-2-deoxyglucose mapping procedure was initiated. All animals given 112 micrograms/kg Soman and 2 of 6 given 84 micrograms/kg Soman developed seizures that continued throughout the mapping procedure. Very high rates of glucose use occurred in most of the brain regions studied during seizures. The most striking increases occurred in substantia nigra, septum, outer layer of dentate gyrus of the hippocampus, hippocampal body, frontal cortex, caudate, ventral thalamus, parietal cortex, medial geniculate and interpeduncular nucleus. Only the inferior colliculus, superior olivary nucleus and lateral habenula were unaffected by the seizures. The mid layers of cerebral cortex rostral to superior colliculus showed marked reductions in glucose use which may represent inhibition of neuronal activity or functional failure from depleted energy reserves. The animals given 84 micrograms/kg i.m. that did not have seizures had regional glucose use patterns similar to the controls. The results indicate that the brain damage observed by others in Soman treated rats may be in part due to the excessive neuronal stimulation that occurs during the prolonged Soman-induced seizure.

Animals↗

Soman-induced depression of brain activity in TAB-pretreated rats: 2-deoxyglucose study.

Administration of large doses of Soman (2xLD50) to rats protected with TAB, a mixture of trimedoxime (TMB-4), atropine and benactyzine, results in approximately 2-fold reductions of local cerebral glucose utilization (LCGU) in most brain regions. This is in contrast to the marked increase in LCGU that is observed in conjunction with the seizures associated with an LD50 dose of Soman given to unprotected rats. This study reveals that TAB is effective in protecting against Soman-induced seizures, but only at the expense of a severe decrease in LCGU after Soman exposure.

Animals↗

Heart rate responsiveness after sustained chronotropic stimulation with a beta 1-adrenergic receptor agonist.

Six normal male human subjects underwent two 72 hr infusions of saline (control) and butopamine, a beta-adrenergic agonist with strong positive chronotropic properties, in order to determine the chronotropic responsiveness of the human heart after sustained chronotropic stimulation. Chronotropic responsiveness was assessed by heart rate responses to intravenous isoproterenol and bicycle ergometry before and serially over 50 hr after discontinuation of the infusions. Chronotropic responsiveness to isoproterenol and exercise was reduced significantly in the butopamine group compared to control; this blunted chronotropic effect persisted beyond 48 hr. Positive inotropic responsiveness, assessed by echocardiography and systolic time intervals, was reduced modestly for the butopamine-treated group up to 24 hr after infusion. Although the precise mechanisms are not fully elucidated, continuous chronotropic stimulation of the human heart with the beta 1 agonist, butopamine, elicits a significant reduction in the heart rate response to isoproterenol and exercise challenges. In addition, the degree and time course of suppression of the chronotropic vs. inotropic responsiveness are disparate.

2-Hydroxyphenethylamine↗

Kainic acid alters cholinergic responses in the rat retina: a 2-deoxyglucose study.

Intraocular injections of the neuroexcitatory toxin, kainic acid, did not alter the output of the retinal ganglion cells, as determined by the rate of glucose use in the stratum griseum superficialis of the superior colliculus. However, significant differences were observed in cholinergic interactions of the ganglion cells after kainic acid treatment. Intraocular injection of kainic acid prevented the increase in the stratum griseum superficialis activity typically produced by systemic injection of the acetylcholinesterase inhibitor diisopropylfluorophosphate (DFP). In addition, the retinal ganglion cells were strikingly sensitive to intraocular injections of acetylcholine 1 week after exposure to kainic acid, as reflected in the marked increased glucose utilization in the stratum griseum superficialis. This responsiveness to acetylcholine may be entirely due to the 80% decrease in acetylcholinesterase in the retina observed 1 week after kainic acid exposure or in part to a supersensitivity of the ganglion cells following the period of acetylcholine depletion.

Acetylcholine↗

Intravenous pirbuterol.

Pirbuterol was given intravenously to nine normal men to determine the hemodynamic effects of intravenous injection of this rather selective beta 2-adrenoceptor agonist. Pirbuterol induced marked improvement of the echocardiographic (percent change in the dimension of the minor axis of the left ventricle during systole, ejection fraction, and velocity of left ventricular circumferential fiber shortening) and systolic time interval (preejection period interval, preejection period/left ventricular ejection time) indices of ventricular performance. The increase in stroke volume was indicated by elevation of systolic blood pressure and widening of pulse pressure. Vascular beta 2-receptor agonist effects were indicated by the fall in diastolic and mean systemic blood pressure and marked reduction in derived systemic vascular resistance. Dose-related positive chronotropic properties were observed without dysrhythmias. There was a good direct correlation between mean plasma pirbuterol concentration and dose. Because of the reported efficacy of oral doses, the direct relationship between plasma concentration and dosage, the positive inotropic properties, and the peripheral vasodilating effects of pirbuterol, investigation of the intravenous form of the drug in patients with severe decompensated low-output congestive heart failure seems warranted.

Adult↗

Influence of long-term infusions on lidocaine kinetics.

Lidocaine kinetics were examined during continuous infusions in five healthy subjects using stable isotope lidocaine labeled with two deuterium atoms. During phase 1, lidocaine and stable isotope lidocaine (50 mg IV each) were given as a bolus to confirm that the two species were kinetically identical. Phase 2 consisted of a long-term (30 hr) lidocaine infusion designed to produce a steady-state concentration equal to 1.5 microgram/ml. Twenty-four hours into the infusion, stable isotope lidocaine (50 mg) was given as an intravenous bolus and kinetic parameters were calculated. Phase 3 differed from phase 2 in that target steady-state lidocaine concentration was 4 microgram/ml and the stable isotope lidocaine dose was reduced to 40 mg. A gas chromatograph-mass spectrometer was used to determine lidocaine and stable isotope lidocaine serum concentrations. Compared to phase 1, clearance decreased (P less than 0.05) and half-life increased (P less than 0.025) during phases 2 and 3. The volume of distribution at steady-state remained constant during all three phases. Lidocaine cumulated in serum during long-term infusions in all five patients; repeated decreases in infusion rate were necessary to avoid exceeding desired target concentrations in phases 2 and 3.

Adult↗

Effects of hydralazine on coronary blood flow and myocardial energetics in congestive heart failure.

The acute effects of oral hydralazine, 1 mg/kg, on coronary vascular resistance, coronary blood flow (estimated using the coronary sinus thermodilution technique), and myocardial oxygen consumption were evaluated in 10 patients with chronic (New York Heart Association class III and IV) nonischemic congestive heart failure. Central hemodynamic responses demonstrated a modest decrease in mean arterial pressure, pulmonary capillary wedge pressure and systemic vascular resistance (12%, 15% and 29%, respectively), while the cardiac index increased from 2.3 +/- 0.1 to 3.1 +/- 0.3 and left ventricular stroke work index from 24 +/- 3.7 to 28 +/- 3.4 (p less than 0.01). Heart rate and diastolic filling time did not change. Coronary blood flow increased approximately 50%, from 144 +/- 17 to 218 +/- 30 ml/min, and coronary vascular resistance decreased from 0.55 +/- 0.09 to 0.36 +/- 0.08 mm Hg/ml/min (both p less than 0.01). Oral hydralazine increased myocardial oxygen consumption by 33%, from 15 +/- 1.6 to 20 +/- 2.7 ml/min. Despite this moderate augmentation in myocardial oxygen consumption, the arterial-coronary sinus oxygen difference decreased from 104 +/- 6.2 to 94 +/- 7.5 and the myocardial oxygen extraction ratio decreased from 71% to 64% (both p less than 0.05). The ratio of coronary vascular resistance to systemic vascular resistance decreased with hydralazine therapy, while coronary blood flow increased from 3.5% to 4.3 % of total cardiac output. In this group of patients with nonischemic cardiomyopathy, hydralazine had a favorable effect on the coronary circulation and improved the critical myocardial oxygen supply-demand ratio.

Adult↗