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Biomedical subjects

L D Nelson

Publications and source records attributed to L D Nelson.

86 records · Page 5Linked to original sources

Oxygen consumption and optimum PEEP in acute respiratory failure.

The effect of PEEP on oxygen consumption (VO2) was observed in 3 groups of dogs. In addition to intermittent and indirect measurements using the expired gas collection and Fick methods, VO2 was measured continuously and directly using the "oxiconsumeter", a device utilizing a relatively simple feedback controlled gas replenishment technique which adapts to standard ventilator circuits. One group of dogs served as controls, while the other 2 groups developed acute respiratory failure (ARF) subsequent to an acute pulmonary injury (API) induced by iv administration of oleic acid. In animals without API, there were no PEEP-induced changes in gas exchange variables; whereas the 2 API groups showed graded improvement in arterial oxygen tension (PaO2), shunt fraction (Qsp/Qt), and alveolar-arterial oxygen tension gradient [P(A-a)O2] during mechanical ventilation with PEEP. In the absence of vascular volume loading, increasing PEEP was associated with decreased cardiac output in dogs with or without API. In contrast, when concurrently fluid resuscitated, the dogs receiving the most severe API showed all of the classic signs of progressive ARF but did not evidence decreased cardiac output with increasing PEEP. VO2 decreased at high PEEP when oxygen transport decreased. The following conclusions were reached: The oxiconsumeter provides a safe cost-effective means for VO2 monitoring, whose convenience and rapidity exceed those of expired gas collections and whose accuracy and reliability far exceeds those of Fick determinations. In general, PEEP has little effect on VO2 provided cardiac output is adequate; in particular, VO2 cannot be used to optimize PEEP via correlation with lung compliance or intrapulmonary shunt fraction. Decreased VO2 during PEEP therapy reflects a significant decrease in cardiac output, and is indication to support cardiac output, or reduce PEEP, or both.

Acute Disease↗

Influence of thiopental anesthesia on renal sodium and water excretion in the dog.

The influence of thiopental anesthesia on renal tubular sodium reabsorption was investigated in the well-trained dog. After administration of the anesthetic, renal sodium reabsorption was depressed, leading to the enhanced excretion of sodium and water. Associated with this response was a decrease in the plasma levels of epinephrine and norepinephrine. Neither renal hemodynamic functions nor the humoral factors, prostaglandin E, plasma renin activity, or arginine vasopressin appeared to be the major determinants of the natriuresis. These observations suggest that the administration of thiopental depresses renal sympathetic nerve activity, thereby diminishing the renal tubular transport of sodium.

Animals↗

Serum progesterone concentrations in cows receiving embryo transfers.

Progesterone concentrations in systemic blood were determined by radioimmunoassay in crossbred cattle used as recipients in an embryo transfer programme. An embryo was transferred surgically to the uterine horn of 528 females which were in oestrus within one half-day of the donor. Jugular blood was obtained at the time embryos were transferred (3-7 days after oestrus) and again from most females between Days 9 and 14. Pregnancy was determined by rectal palpation 45-65 days after oestrus. There were no significant differences between serum progesterone levels of females which remained pregnant and those which did not. Out of 177 pregnant recipients, none had serum progesterone levels less than 0.5 ng/ml on Days 10, 11, or 12 but in 8, values were less than 1.0 ng/ml. Blood samples were also taken on Days 20, 21, or 22 from 113 of these recipients. The mean +/- s.e.m. concentration of progesterone in the pregnant females (5.14 +/- 0.34 ng/ml) was significantly higher (P less than 0.001) than in the non-pregnant females (1.17 +/- 0.25 ng/ml). The correlation coefficients between progesterone levels on Days 3, 4, 5 or 6 and 10-12 ranged from 0.18 to 0.37 (all P less than 0.02). Progesterone levels were not related to length of the previous cycle, the time of day an animal was first noticed in oestrus or the side of the corpus luteum. However, cows with a short oestrus had higher progesterone levels on Days 3-7 (P less than 0.01) than those in oestrus for a longer time.

Animals↗

Kinetics of procainamide and N-acetylprocainamide in renal failure.

Four normal subjects and four functionally anephric patients were given 6.5 mg/kg of body wt of procainamide hydrochloride i.v., and plasma concentrations of procainamide (PA) and its major active metabolite N-acetylprocainamide (NAPA) were measured. Two individuals in each group were fast isonicotinic acid hydrazide (INH) and PA acetylators. The pharmacokinetics of PA and NAPA were analyzed with a computer program (SAAM 23). Volume of distribution (Vdss) and renal clearance of PA were similar in normal subjects regardless of acetylator phenotype. Nonrenal clearance was faster (383 vs. 244 ml/min), and PA elimination half-life (t 1/2) was shorter (2.6 vs. 3.5 hr) in fast acetylators. In the functionally anephric patients, Vdss was similar to that of normal subjects. Nonrenal clearence was faster (117.5 vs. 93.5 ml/min) and PA t 1/2 shorter (10.8 vs. 17.0 hr) in fast than in slow acetylators. In these patients, acetylation accounted for 56% of PA elimination, and NAPA concentrations reached 0.8 microgram/ml or more. The t 1/2 of NAPA in renal failure was 41.5 hr, in accord with predictions from studies in normal subjects, assuming no impairment in nonrenal NAPA elimination. PA metabolism, however, is severely impaired by renal failure, so PA t 1/2 was prolonged to an unpredictably greater extent than would be expected from studies in normal subjects.

Adult↗

Artificial kidneys and clearance calculations.

Clearance of solutes by artificial kidneys can be calculated using plasma flow and solute concentration, whole blood flow and plasma solute concentration, and midpoint of dialysis blood or plasma solute concentration and total amount of solute removed. Using these methods, the clearance of procainamide (PA) and N-acetylprocainamide (NAPA) was determined in 4 patients. In all but one case clearances using total amount recovered were greater than clearances using whole blood flow and plasma concentration. Without exception, clearance determined using amount recovered was substantially greater than clearance using plasma flow and plasma levels, suggesting that both PA and NAPA are removed not only from plasma but also from red blood cells. In vitro clearance of PA, NAPA, quinidine, and phenobarbital by 11 clinically available artificial kidneys and an XAD-4 hemoperfusion column was determined and differences were found.

Blood Flow Velocity↗

Adoptive transfer from interferon-alpha-fed mice is associated with inhibition of active experimental autoimmune encephalomyelitis by decreasing recipient tumor necrosis factor-alpha secretion.

Ingested type I interferon (IFN) suppresses clinical relapse in murine chronic experimental autoimmune encephalomyelitis (EAE), inhibits clinical attacks more effectively than subcutaneous doses, and decreases the adoptive transfer of EAE. To determine whether splenocytes from IFN-fed donors were "suppressor-like" populations, donor SJL/J mice were immunized and fed with mock IFN-alpha or with IFN-alpha every other day for at least 4 weeks after initial clinical attack. Recipients of adoptively transferred CD8+ T cells from mock IFN-alpha-fed donors showed no clinical improvement of clinical disease compared with actively immunized controls. In contrast, recipients of adoptively transferred CD8+ T cells from IFN-alpha-fed donors showed decreased clinical disease compared with recipients of mock IFN-alpha-fed CD8+ T cells. To evaluate the mechanism of protection by donor CD8+ T cells and to determine if ingested IFN-alpha activates natural immunomodulatory cell populations, the authors used the acute EAE model and naïve-fed donor animals as sources of T cells and CD8+ T cells. Con A-activated spleen T cells from naïve nonimmunized mock IFN-alpha-fed donors inhibited actively induced disease and showed decreased recipient TNF-alpha secretion compared with recipients of T cells from mock IFN-fed mice. Donor activated spleen CD8+ T cells from naïve nonimmunized IFN-alpha-fed animals suppressed actively induced EAE in recipients and showed decreased IFN-gamma and TNF-alpha proinflammatory secretion. Decreased recipient TNF-alpha secretion correlates best with the disease protection from IFN-fed T and CD8+ T cells.

Administration, Oral↗