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Biomedical subjects

M Leon

Publications and source records attributed to M Leon.

At least 19 recordsLinked to original sources

The function relating the subjective magnitude of brain stimulation reward to stimulation strength varies with site of stimulation.

A two-lever choice paradigm with concurrent variable interval schedules of reward was used to measure the growth in the subjective magnitude of reward as a function of current, by finding the adjustment in the stimulating current required to offset a given difference in the rates at which two rewards were received. Increasing current by a factor of 2 increased subjective reward magnitude by a factor ranging from as little as 3 to as much as 4,000. This range was about as great between electrodes within one rat as between electrodes and rats. In the light of earlier findings regarding the equivalent effects of increments is current and pulse frequency, these large differences cannot readily be explained by differing fiber densities at the site of stimulation. It is suggested that the medial forebrain bundle terminates in more than one spatio-temporal integration mechanism. The magnitude of the spatio-temporally integrated effect of a barrage of action potentials in the reward-relevant axons depends on which subset of reward-relevant axons is excited by the stimulation.

Action Potentials

Neuroethology of olfactory preference development.

Young mammals come to approach the odor of their mother, a response that facilitates their survival during early life. Young rats induce a cascade of events in their mother to induce the emission of her odor. The pups increase circulating prolactin levels, which increases food intake and the emission of large quantities of cecotrophe containing the maternal odor. This odor is synthesized by the action of cecal microorganisms and changes with maternal diet. The diet-dependence of the odor requires the pups to acquire their attraction to the odor postnatally. The acquisition of this preference occurs when an odor is paired with the tactile stimulation that pups receive during maternal care. The action of the tactile stimulation appears to be mediated by noradrenaline. The development of this type of olfactory attraction is accompanied by changes in the regions of the olfactory bulb that are responsive to the attractive odor. Metabolic, anatomical, and neurophysiological changes in response to the attractive odor emerge in such regions of the bulb after early olfactory preference training.

Animals

The combination of liquid crystal thermography and duplex scanning in the diagnosis of deep vein thrombosis.

One hundred patients with clinically suspected deep vein thrombosis (DVT) were studied by liquid crystal thermography (LCT), duplex scanning and venography. Liquid crystal thermography was found to have a negative predictive value of 97% if performed within 1 week of the onset of symptoms. Duplex scanning had a sensitivity of 93% and specificity of 91% for all thrombi (proximal and calf). On the basis of these results a plan of investigation has been formulated that would avoid duplex scanning and venography in 39 of the 100 patients. Duplex scanning alone would be appropriate in 56 of the remaining 61 patients. Only six patients would be unsuitable for duplex scanning because of a very tense tender leg and require venography. The plan would miss one calf thrombus and result in treating three patients unnecessarily. This policy would be not only effective but also cost-effective.

Female

Popliteal vein entrapment in the normal population.

The aim of this study was to determine the incidence and severity of popliteal vein compression by full knee extension in the normal population. The popliteal veins in 100 healthy volunteers (200 limbs) with no history of previous deep vein thrombosis (DVT) or venous obstruction were examined using duplex scanning with the knee slightly flexed and then fully extended. Knee extension produced complete obstruction in 17 subjects and severe obstruction (< 50% decrease in diameter) in a further 10 subjects. Thirteen subjects had unilateral compression and 14 bilateral. The 27 subjects were tested for functional venous outflow obstruction with air plethysmography. In flexion, the outflow fraction was normal (> 40%) in all subjects. With the knee fully extended, severe or complete venous obstruction (outflow fraction < 10%) was found in eight subjects. Moderate obstruction (outflow fraction 10-40%) was found in all the remaining 19 subjects. When digital compression of the long saphenous vein was performed, these subjects also demonstrated severe outflow obstruction. Although the incidence of symptoms of functional venous obstruction is rare in the general population, these findings have important implications for venous stasis for patients on the operating table and in those having prolonged bed rest. Studies investigating the association between popliteal vein compression and postoperative deep venous thrombosis are needed.

Adult

The neurobiology of filial learning.

Early filial learning evokes clear neural changes in the developing brain. Anatomy and function in the developing olfactory, auditory, and visual systems change following early learning. Since this type of learning seems critical for the survival of the young, the mechanisms of such plasticity should be clear and reliable. In each sensory modality examined, both distinct changes in the brain and the reliable nature of learning through early experience have become evident with experimental analysis.

Animals

Restenosis after placement of Palmaz-Schatz stents in native coronary arteries. Initial results of a multicenter experience.

BACKGROUND: Several metallic intracoronary stents are currently undergoing preliminary evaluation to ascertain potential benefit as means to reduce the 30-40% incidence of restenosis after balloon angioplasty. METHODS AND RESULTS: To determine the incidence and correlates of restenosis after placement of Palmaz-Schatz stents in native coronary arteries in the first group of patients selected for this procedure, clinical and quantitative angiographic data from 206 consecutive patients (221 stenoses) with successful stent placement (diameter stenosis < 50%) were analyzed. Six patients (2.9%) had thrombosis-mediated stent closure within 1 month after stent placement and were excluded from long-term angiographic follow-up. One hundred eighty-one (91%) of the remaining 200 patients had angiography at 5.8 +/- 2.1 months. Patients with and without follow-up did not differ in any baseline characteristic; in particular, history of restenosis at the site stented (73% versus 65%), placement of multiple overlapping stents (17% versus 20%), and mean poststent diameter stenosis (16 +/- 12% versus 14 +/- 12%). The overall incidence of restenosis (diameter stenosis > or = 50% at follow-up) in this group at high risk for restenosis was 36% (95% confidence interval, 29-43%) on a per-stenosis basis. The incidence of restenosis when a single stent was placed was 30% (95% confidence interval, 23-37%). Risk was dependent upon a history of restenosis (present versus absent 36% versus 16%, p = 0.02) and upon whether or not a poststent stenosis < or = 0% was achieved (6% versus 33%, p = 0.02). When multiple overlapping stents were placed, restenosis occurred at 64% of sites, and placement of multiple stents was discouraged during the later phases of this study as these results became apparent. CONCLUSIONS: Although multiple stents appear to yield a poor long-term result, placement of single stents may offer a benefit compared with standard coronary angioplasty, particularly if an excellent angiographic result can be obtained in patients without prior restenosis. Further randomized trials in such patients are needed.

Coronary Angiography

Skin flow the venoarteriolar response and capillary filtration in diabetics. A 3-year follow-up.

Resting skin blood flow (RF) and the venoarteriolar response (VAR = the vasoconstrictor response on standing) have been studied in 100 patients with diabetic neuropathy, in 100 diabetics without neuropathy, and in 100 normal subjects by laser Doppler flowmetry. Capillary filtration was also studied with strain gauge plethysmography. The authors followed up these patients by evaluating their microcirculation again after three years. At the beginning of the study in patients with neuropathy, RF and capillary filtration were increased. The VAR and the microangiopathy index (MI = VAR/RF) were reduced in all diabetics, to a greater extent to those with neuropathy. After three years the authors observed an increase in capillary filtration associated with a further impairment in VAR and MI, suggesting progression of microangiopathy in both groups of diabetics. These results suggest that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in neuropathics. Increased skin blood flow and capillary filtration and the impaired venoarteriolar response cause edema and may contribute to the thickening of capillary basement membranes and the progressive evolution of diabetic microangiopathy.

Adult

Veno-arterial carbon dioxide gradient in human septic shock.

Recent reports have shown that venous hypercarbia, resulting in a widening of the veno-arterial difference in PCO2 (dPCO2), is related to systemic hypoperfusion in various forms of low-flow state. Although septic shock usually is a hyperdynamic state, other factors can influence the CO2 production and elimination, and thus dPCO2 in septic shock This study examined the dPCO2 and acid-base balance together with cardiac output measurements and oxygen-derived variables in 64 adult patients with documented septic shock. For a total of 191 observations, a significant exponential relation between dPCO2 and CO was found. At time of first measurement, 15 patients had an increased dPCO2 (above 6 mm Hg) and a higher mixed venous PCO2 (PvCO2) (47.2 +/- 10.0 vs 35.9 +/- 7.3 mm Hg, p less than 0.001). These patients had a lower cardiac index (2.9 +/- 1.3 vs 3.8 +/- 2.0 L/min.m2, p less than 0.01), a higher oxygen extraction ratio, but a similar VO2 than patients with normal dPCO2. The higher dPCO2 could also be related to an impaired CO2 elimination as indicated by a higher PaCO2 and a lower PaO2/FIO2 in these patients. Nonsurvivors had a significantly higher dPCO2 than survivors (5.9 +/- 3.4 vs 4.4 +/- 2.3 mm Hg, p less than 0.05) in the presence of similar cardiac output. The higher dPCO2 in these patients was probably related to the higher blood lactate levels (7.7 +/- 5.3 mmol/L vs 4.5 +/- 2.8 mmol/L, p less than 0.01) and the more severe pulmonary impairment (SaO2 90 +/- 8 percent vs 95 +/- 4 percent, p less than 0.001). Arteriovenous oxygen content difference (dAVO2) and VO2 were similar in survivors and nonsurvivors. In conclusion, dPCO2 patients with septic shock is related principally to cardiac output but apparently also to the degree of pulmonary impairment. Although dPCO2 is larger in nonsurvivors, its prognostic value is modest.

Adult

Acute effects of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy (a dose comparison study).

The acute effects of hydroxyethylrutosides on capillary filtration were studied in 12 normal subjects, 25 patients with venous hypertension and 22 diabetics with microangiopathy. The two groups of patients randomly received a single oral dose (500 or 1000 mg) of hydroxyethylrutosides. A single dose of 500 mg was used for normal volunteers. In the following 6 hours capillary filtration was studied with straingauge plethysmography. The decrease in capillary filtration was evident within the first hour and was at its peak between the second and fourth hour. After 6 hours it was still significantly below baseline values in patients. The 1000 mg dose was significantly more effective in both groups of patients. This study confirms the efficacy of hydroxyethylrutosides in decreasing capillary filtration. It suggests that the effect of one dose lasts at least 6 hours and also that the higher dose is more effective.

Adult

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

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

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

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

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

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

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

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