Biomedical subjects

M Leon

Publications and source records attributed to M Leon.

At least 109 records · Page 6Linked to original sources

PubMed1992

Myocardial depression characterizes the fatal course of septic shock.

The relationship between cardiac and vascular abnormalities was studied in 68 patients with established septic shock. At time of hemodynamic evaluation, after initial resuscitation, there was no significant difference in arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac index between the 38 survivors of shock and the 30 patients who died of shock, but the left ventricular stroke work index and the right ventricular (RV) stroke work index were higher in survivors than in those who died (mean +/- SD: 25.0 +/- 9.1 vs 20.1 +/- 9.4 gm/m2 [p less than 0.05] and 6.6 +/- 3.6 vs 4.8 +/- 2.8 gm/m2 [p less than 0.05], respectively). Survivors had also higher thermodilution RV ejection fraction and lower RV end-diastolic volumes than had those who died (43.9% +/- 16.3% vs 31.1% +/- 13.7% [p less than 0.01] and 82 +/- 30 vs 99 +/- 31 ml/m2 [p less than 0.05], respectively). Calculated systemic vascular resistance was similar in the two groups, but vasopressors had been required in 22 (58%) of 38 survivors and 25 (83%) of 30 patients who died (p less than 0.01). Moreover, when the patients were separated into two groups according to their cardiac output, higher or lower than 3 L/min/m2, in both subgroups patients who died had lower blood pressure than had survivors. Blood lactate levels were significantly lower in survivors than in nonsurvivors (5.1 +/- 2.1 vs 8.1 +/- 4.7 mEq/L, p less than 0.01). Final data obtained before recovery of shock or death indicated that the survivors had higher arterial pressure, lower pulmonary artery pressure and right atrial pressure, higher stroke volume, and higher RV ejection fraction than had the patients who died. No survivors but all patients who died had been treated with vasopressors. These data therefore indicate that death as a result of septic shock is characterized by both myocardial depression and altered vascular tone and both are probably interrelated.

Female↗

PubMed1991

Neurobehavioral responses of neonatal rats to previously experienced odors of different concentrations.

Neonatal rats acquire an olfactory preference following daily exposure to an odor that is accompanied by tactile stimulation. In the present study, we determined the neurobehavioral responses of pups trained and tested with odors of either the same or different concentration. On postnatal day (PND) 1-18, all animals were exposed for 10 min/day to either peppermint or air while receiving perineal tactile stimulation. On PND 19, pups trained with a low odor concentration preferred that odor to air, regardless of its concentration and showed equal preference between odor concentrations. These results suggest both that pups can learn to prefer a specific odor concentration and that they can learn to recognize odor quality across concentrations. To determine the neural responses to such stimuli, trained and control pups were exposed to either low or high peppermint odor concentrations following an injection of 14C-labelled 2-deoxyglucose (2-DG). Early experience with the high odor concentration resulted in the 2-DG uptake response to both test odor concentrations which was higher than that of pups that had previous experience with either the low odor concentration or with clean air. Though the 2-DG density did not increase with test odor concentration, the size of the 2-DG foci did, regardless of previous experience. The 2-DG response to odor concentration is, therefore, influenced by both previous experience and immediate odor stimulus characteristics that are revealed in parallel responses within the olfactory bulb.

Air↗

PubMed1991

Extracellular dopamine increases in the neonatal olfactory bulb during odor preference training.

Young rats learn to approach an odor that has been paired with tactile stimulation. This attraction is accompanied by changes in the metabolism and anatomy within the olfactory bulb glomerular layer. In this study, we examined the changes that occur in the olfactory bulb during early olfactory learning, rather than after such pairings have occurred. Specifically, we determined whether the pairing of an odor with tactile stimulation would produce a modified response by olfactory bulb glomerular-layer neurons. To monitor one large subgroup of these neurons during early learning, we used in vivo microdialysis to assess the activity of dopaminergic neurons in the olfactory bulb of postnatal day (PND) 3 rats during simultaneous presentation of odor and tactile stimulation, tactile stimulation alone, odor alone, or clean air alone. Clean air evokes no change in extracellular dopamine (DA), while both odor alone and stroking alone induce prolonged increases in DA peaking at about 200% of baseline. The combination of odor and tactile stimulation, which allows an olfactory preference to be formed, induces a prolonged increase in DA which peaks at about 400% of baseline. The level of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) increases only in pups receiving both odor and tactile stimulation and peaks at about 200% of baseline. With the exception of the pups exposed to clean air, all groups show an increase in homovanillic acid (HVA) of between 150-200% following stimulation. The large and prolonged increase in DA may be linked to the longer term anatomical and physiological changes in the glomerular layer of the bulb that form as a consequence of early olfactory preference training.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Norepinephrine-induced plasticity and one-trial olfactory learning in neonatal rats.

The influence of norepinephrine (NE) on the acquisition of a conditioned odor preference and enhanced focal uptake of [14C]2-deoxyglucose (2-DG) within the olfactory bulb was assessed in neonatal rat pups. On postnatal day (PN) 6, pups were injected with either an NE receptor agonist (isoproterenol), NE receptor antagonist (propranolol or timolol), or saline before one-trial odor conditioning. The experimental conditioning group received a 10-min exposure to an odor (peppermint) and reinforcing tactile stimulation similar to that received from the dam. Control groups received only the odor, only the tactile stimulation, backwards presentation of the odor and tactile stimulation or neither of these stimuli. The next day, pups were either tested for an olfactory preference (Expts. 1 and 2) or assessed for differential olfactory bulb activity using the 2-DG technique (Expt. 3). The results indicate that early odor experience with either tactile stimulation or isoproterenol is sufficient to produce a learned behavioral preference and enhanced focal 2-DG uptake within the olfactory bulb. Moreover, an NE receptor blocker injected prior to training with odor and tactile stimulation blocks the acquisition of both behavioral preference and the enhanced 2-DG uptake. In Expt. 4, the effects of tactile stimulation and isoproterenol were further assessed. An odor paired with a moderate level of either of these stimuli produces learning. However, the simultaneous presentation of a moderate level of these stimuli paired with an odor does not result in an odor preference. An odor preference may be reinstated by simultaneous presentation of these stimuli, provided the level of each of these stimuli is too low to produce an odor preference when presented alone with an odor. These data suggest that exogenous NE and tactile stimulation are additive in their effect on learning. These results are discussed in terms of the neural mechanisms underlying reinforcement in infant rats.

Animals↗

PubMed1991

Glutathione levels in olfactory and non-olfactory neural structures of rats.

Olfactory receptor neurons are a CNS entry point for a wide variety of airborne substances. Therefore, it is probable that detoxification mechanisms are present in these neurons to neutralize such agents. Glutathione (GSH) is an essential component of several detoxification schemes, and in this study we examined the distribution and levels of GSH in the olfactory epithelium, olfactory bulb, cortex, hippocampus and cerebellum in neonatal, weanling, adult and aged rats. We report that GSH is primarily localized to the olfactory receptor neurons and their oxons within the olfactory epithelium. It is also localized within the glomerular neuropil and granule cells of the olfactory bulb. Levels of GSH in the olfactory epithelium and hippocampus do not change as a function of age, although GSH levels decrease in several brain regions, including the olfactory bulb, cerebellum and cortex.

Aging↗

PubMed1991

Increase in a focal population of juxtaglomerular cells in the olfactory bulb associated with early learning.

Young rats learn to approach an odor that had been experienced in the presence of reinforcing tactile stimulation. Subsequent presentation of the conditioned odor also evokes an enhanced focal uptake of 2-deoxyglucose (2-DG) in the glomerular layer of the olfactory bulb, and the glomerular-layer width of such foci increases in conditioned pups. In the present study, we determined whether an increase in the glomerular-layer cell population contributes to this structural and functional change. We therefore counted and measured glomerular-layer cells in Nissl-stained sections from focal regions of radiolabeled 2-DG uptake. While cell size did not differ between groups, conditioned pups had a 19% increase in the number of glomerular-layer cells associated with the 2-DG foci compared to controls. The increase in cell number may contribute to the enhanced 2-DG uptake in glomerular-layer foci.

Animals↗

PubMed1991

Olfactory deprivation increases dopamine D2 receptor density in the rat olfactory bulb.

Unilateral olfactory deprivation during postnatal development results in significant anatomical and neurochemical changes in the deprived olfactory bulb. Perhaps the most dramatic neurochemical change is the loss of dopaminergic expression by neurons of the glomerular region. We describe here the effects of early olfactory deprivation on other elements of the bulb dopaminergic system, namely the dopamine receptors of the olfactory bulb. Rat pups had a single naris occluded on postnatal day 2 (PN2). On PN20 or PN60, animals were sacrificed and the bulbs were examined for catecholamine levels or D2 and D1 dopamine receptor binding. Receptor densities were quantified by in vitro autoradiography using the tritiated antagonists spiperone (D2) and SCH23390 (D1). Dopamine uptake sites were similarly examined using tritiated mazindol. No significant specific labeling of D1 or mazindol sites was observed in the olfactory bulbs of control or experimental animals at either age. Normal animals displayed prominent labeling of D2 sites in the glomerular and nerve layers. After 60 days of deprivation, deprived bulbs exhibited an average increase in D2 receptor density of 32%. As determined by Scatchard analysis, the mean values for Kd and Bmax were 0.134 nM and 293 fmol/mg protein in normal bulbs, and 0.136 nM and 403 fmol/mg protein in deprived bulbs. The results suggest that, as in the neostriatum, dopamine depletion in the olfactory bulb leads to an upregulation of D2 receptor sites. This change may represent an attempt by the system to adapt neurochemically to reduced dopaminergic activity and thereby maintain bulb function.

Aging↗

PubMed1991

Biochemical quantitation and histochemical localization of glucose-6-phosphate dehydrogenase activity in the olfactory system of adult and aged rats.

The activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate shunt, was examined in olfactory epithelium, respiratory epithelium, olfactory bulb, and occipital cortex in Fisher 344 rats aged 4 and 24 months. Marked differences in this enzyme were found in olfactory compared to nonolfactory tissues. Olfactory epithelium and olfactory bulb have much greater glucose-6-phosphate dehydrogenase activity than respiratory epithelium and occipital cortex at both ages. Glucose-6-phosphate dehydrogenase remains fairly constant between adulthood and senescence in respiratory epithelium and occipital cortex. However, glucose-6-phosphate dehydrogenase activity decreases during the same time in both of the olfactory tissues examined. Previous studies of changes in this enzyme with aging have shown increases in enzyme activity in some brain regions, but never the decreases that we describe in olfactory tissues. Glucose-6-phosphate dehydrogenase histochemistry revealed intense staining of both the apical layer of olfactory epithelium and of Bowman's glands along with their ducts. Histochemistry of the olfactory bulb showed strongest staining in the nerve and glomerular layers of the bulb. The functional implications of these findings are discussed.

Aging↗

PubMed1991

Clinical experience with the Palmaz-Schatz coronary stent.

Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent. Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with "suboptimal" angioplasty results (dis-section) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received a single stent. Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to those of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients.

Adult↗

PubMed1991

Clinical experience with the Palmaz-Schatz coronary stent. Initial results of a multicenter study.

Stenting of native coronary arteries with a balloon-expandable stent was attempted in 226 patients after elective angioplasty. Delivery of the device was successful in 213 (94%) of the patients. Of these, 39 received aspirin and dipyridamole only (group 1) and 174 received aspirin, dipyridamole, and warfarin for 1-3 months (group 2). There was no abrupt closure (less than or equal to 1 day) or perioperative death in either group. In-hospital or perioperative complications in group 1 compared with group 2 were as follows: subacute closure (1-14 days), seven (18%) patients versus one (0.6%) patient, respectively, p less than 0.0001; myocardial infarction, five (13%) patients versus one (0.6%) patient, respectively; condition requiring urgent bypass surgery, one (2.5%) patient versus no patients, respectively. Thus, the incidence of major complications such as death, myocardial infarction, or a condition requiring urgent bypass surgery was 15% in group 1 and 0.6% in group 2. Clinical follow-up revealed that 92% of the patients were asymptomatic at 3 months after stenting compared with 6% before stenting (p less than 0.0001). Of the 13 patients who were symptomatic, nine underwent cardiac catheterization and, ultimately, successful elective coronary angioplasty or bypass surgery. We conclude that a high delivery success rate can be expected with this device and that clinical thrombosis is less frequent in anticoagulated patients than in nonanticoagulated patients. Furthermore, in this selected patient population, coronary stenting results in a low incidence of in-hospital and perioperative complications. Clinical success, defined by absence of symptoms, appears to be sustained at 3 months.

Angioplasty, Balloon, Coronary↗

PubMed1991

Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock.

Recent reports have shown that oxygen delivery (Do2) and oxygen uptake (Vo2) could be related to outcome of critically ill patients. In this study, we examined measurements of cardiac output, oxygen-derived variables, and blood lactate levels in 48 patients with documented septic shock. There were 27 survivors and 21 nonsurvivors from the shock episode. For all 174 observations, there was a significant linear relationship between Vo2 and Do2 (Vo2 = 79 + 0.17 x Do2, r = 0.64, p less than 0.001). There were no significant differences in Do2 between survivors and nonsurvivors at the onset of septic shock (mean +/- SD, 540 +/- 219 vs 484 +/- 222 ml/min.m2, NS) or in the final phase of septic shock (506 +/- 163 vs 443 +/- 187 ml/min.m2, NS). Also, no significant differences were found in Vo2 and oxygen extraction between survivors and nonsurvivors. However, survivors had significantly lower blood lactate levels both initially (5.1 +/- 2.7 vs 8.2 +/- 5.4 mmol/L, p less than 0.05) and in the final phase of septic shock (2.6 +/- 1.9 vs 7.7 +/- 5.6 mmol/L, p less than 0.001). Only the survivors had a significant decrease in blood lactate levels during the course of septic shock (p less than 0.001). We conclude that the oxygen-derived variables, Do2 and Vo2, cannot be used as prognostic indicators in human septic shock. In contrast, blood lactate levels are closely related to ultimate survival from septic shock. Furthermore, decreases in blood lactate levels during the course of septic shock could indicate a favorable outcome. Therefore, blood lactate levels can serve as a reliable clinical guide to therapy.

Cardiac Output↗

PubMed1991

Effect of current on the maximum possible reward.

Using a 2-lever choice paradigm with concurrent variable interval schedules of reward, it was found that when pulse frequency is increased, the preference-determining rewarding effect of 0.5-s trains of brief cathodal pulses delivered to the medial forebrain bundle of the rat saturates (stops increasing) at values ranging from 200 to 631 pulses/s (pps). Raising the current lowered the saturation frequency, which confirms earlier, more extensive findings showing that the rewarding effect of short trains saturates at pulse frequencies that vary from less than 100 pps to more than 800 pps, depending on the current. It was also found that the maximum possible reward--the magnitude of the reward at or beyond the saturation pulse frequency--increases with increasing current. Thus, increasing the current reduces the saturation frequency but increases the subjective magnitude of the maximum possible reward.

Animals↗

PubMed1991

Measuring the subjective magnitude of brain stimulation reward by titration with rate of reward.

The magnitude of experienced reward as a function of the pulse frequency and current in trains of fixed duration delivered to the medial forebrain bundle of the rat was measured using a new psychophysical method in which the parameters of the brain stimulation reward on one lever are adjusted to offset the effect of changing the rate of reward on a competing lever. Subjective reward magnitude is a steep sigmoidal function of both pulse frequency and current. The growth of reward to its half-maximal level was approximated by a power function with an exponent that varied from 2 to 10. Within a subject, the exponent was the same for both current and pulse frequency, which supports the hypothesis that the magnitude of reward from a train of fixed duration is determined by the rate at which action potentials are generated in the population of reward-relevant axons (the counter hypothesis). This rate is proportional to Current x Pulse Frequency.

Animals↗

PubMed1991

Olfactory classical conditioning in neonates.

One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unconditioned stimulus (a stimulus with positive properties). Control babies received only the odor, only the stroking, or the stroking followed by the odor presentation. The next day, all infants, in either the awake or sleep state, were given five 30-second presentations of the odor. Results were analyzed from video tapes scored by an observer unaware of the infants' training condition. The results indicate that only those infants who received the forward pairings of the odor and stroking exhibited conditioned responding (head turning toward the odor) to the citrus odor. The performance of the conditioned response was not affected by the state of the baby during testing, because both awake and sleeping infants exhibited conditioned responses. Furthermore, the expression of the conditioned response was odor specific; a novel floral odor presented during testing did not elicit conditioned responses in the experimental babies. These results suggest that complex associative olfactory learning is seen in newborns within the first 48 hours of life. These baseline findings may serve as normative data against which observation from neonates at risk for neurological sequelae may be compared.

Conditioning, Classical↗

PubMed1990

Modification of olfactory bulb synaptic inhibition by early unilateral olfactory deprivation.

Early unilateral olfactory deprivation produces large structural and neurochemical changes in the olfactory bulb, the first central relay for olfactory information. The functioning of deprived bulbs was examined in the present report by using paired-pulse stimulation of the lateral olfactory tract. Paired-pulse stimulation reflects interactions between mitral/tufted cells and granule cells, as well as the modulatory effects of centrifugal and intra-bulbar association fibers. Paired-pulse stimulation produced inhibition of mitral/tufted cells in control animals at PN20-PN22. This inhibition was significantly enhanced in littermates deprived of olfactory input from PN1 to PN20-PN22. Suppression of mitral/tufted cell single-unit spontaneous activity following single-pulse stimulation of the lateral olfactory tract (LOT) was similarly enhanced in deprived bulbs. These results suggest that early olfactory deprivation significantly modifies subsequent olfactory system function.

Animals↗

PubMed1990

Modified behavioral and olfactory bulb responses to maternal odors in preweanling rats.

Rat pups acquire an attraction for maternal odors, which can vary with maternal diet. In the two experiments reported here, maternal diet was modified and both pup behavioral responses and pup olfactory bulb neural responses [( 14C]2-DG uptake) to maternal odors were examined. In experiment 1, pups were reared from birth to postnatal day 19 with either a dam fed normal rat chow or a dam fed a sucrose-based diet which suppressed her normal maternal odor. In experiment 2, pups were raised from birth to postnatal day 19 with either a dam fed the sucrose-based diet adulterated with peppermint, or the non-scented sucrose-based diet. Pups selectively expressed both a behavioral attraction and an enhanced olfactory bulb neural response to odors that they experienced in the nest.

Action Potentials↗

PubMed1990

Early unilateral deprivation modifies olfactory bulb function.

Unilateral olfactory deprivation during postnatal development produces significant structural and neurochemical modifications of the olfactory bulb. In the present report, we describe the functional consequences of such deprivation. Rat pups had a single naris occluded on postnatal day 2 (PN2) to deprive them of early olfactory stimulation. On PN20-22, the occluded naris was reopened, the previously open naris was sealed, and responses of the deprived olfactory bulb to odors were assessed using both single-unit recording from mitral/tufted cells and quantitative 14C-2-deoxyglucose (2-DG) autoradiography. While the response properties of individual odor-stimulated mitral/tufted cells were not altered by early deprivation, spontaneous activity was depressed, and there was a significantly higher incidence of odor-responsive mitral/tufted cells in deprived compared to nondeprived bulbs. In addition, odor-stimulated deprived bulbs demonstrated greater uptake of 2-DG than did non-deprived bulbs. Together, these data indicate that the olfactory system demonstrates an increased responsiveness to sensory cues following early deprivation.

Animals↗

PubMed1989

Glucose-6-phosphate dehydrogenase activity in the olfactory system of the young rat: an enzyme histochemical study using computerized image analysis.

An understanding of olfactory system glucose metabolism is necessary for the interpretation of radiolabeled 2-deoxyglucose studies of odor processing since the relationship between glucose uptake and neural activity is based on assumptions regarding cellular glucose utilization. As part of an ongoing study examining divergent pathways of glucose metabolism in the olfactory system, the relative activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate shunt, was examined among cells of the rat olfactory bulb and anterior olfactory nucleus, by using enzyme histochemistry on fresh frozen tissue. Optical density measurement of formazan reaction product in stained tissue were quantified by computerized image analysis. To aid in the identification of histochemically stained neurons, alternate sections were Nissl-stained. The highest olfactory bulb dehydrogenase levels were found in the olfactory nerve and glomerular layers. Individual mitral and tufted cells also showed high dehydrogenase activity. In most stained neurons, formazan reaction product filled the cytoplasm and sometimes extended into the proximal part of dendrites and axons. The external plexiform and granule cell layers had low enzyme activity. High activity also was seen in pyramidal cells of pars dorsalis and pars lateralis of the anterior olfactory nucleus, one of the first, and most rostral of the olfactory bulb projection sites. High glucose-6-phosphate dehydrogenase activity in the olfactory system indicates that a significant amount of glucose can be channeled through the hexose monophosphate shunt in these neurons, with a concomitant production of NADPH. This may reflect high activity of cellular detoxification enzymes that rely on NADPH for reducing power. Such detoxification processes may be engaged in response to the potential entry and transsynaptic movement of airborne chemicals into the brain via the olfactory system.

Animals↗