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Biomedical subjects

C M Smith

Publications and source records attributed to C M Smith.

At least 235 records · Page 13Linked to original sources

Recognition memory in Alzheimer's disease.

Recognition memory for several types of stimulus material was examined in patients clinically diagnosed as having early Alzheimer's disease and in normal elderly controls. Although performance deficits were demonstrated for verbal and abstract stimuli (geometric shapes and histology slides), memory for faces was relatively intact in the patient group. Patients made more false positive responses than controls, but this could not be accounted for by a general disinhibition of responding. It is suggested that a contextual processing deficit may explain the pattern of false positive responding and this is discussed in relation to previous findings of drug studies in Alzheimer's disease.

Alzheimer Disease↗

Halothane anesthesia does not exacerbate hepatic dysfunction in cirrhotic rats.

The authors have refined a model of cirrhosis in the rat and used it to determine whether the administration of halothane anesthesia adversely affects preexisting liver disease. Male Wistar rats were placed on phenobarbital water and were assigned randomly to two groups. Group 1 rats were exposed by inhalation to carbon tetrachloride (CC14) at weekly intervals for 12 exposures while Group 2 rats received only air. All treatment including phenobarbital then was withdrawn for 4 weeks. Rats then were bled for SGOT and SGPT determinations and 24 h later were exposed to 1.8% halothane in oxygen for 3 h (HAL); the remaining rats from each group were exposed to 100% oxygen for 3 h (O2). Twenty-four hours later, rats were killed and blood was obtained for SGOT and SGPT by cardiac puncture. Light microscopic histologic examination was performed blind on liver sections for cirrhosis and scored for superimposed acute focal necrosis. The weekly sublethal CCl4 exposure resulted in histologically demonstrable cirrhosis in all surviving Group 1 animals. The mean (+/- SD) SGOT (128 +/- 32 IU/1) and SGPT (86 +/- 24 IU/1) values for the Group 1 rats were significantly greater (P less than 0.01) than those for Group 2 rats (98 +/- 18 IU/1 and 57 +/- 12 IU/1, respectively). Cirrhotic animals showed neither deterioration in liver function nor acute liver cell necrosis after Hal compared with O2. However, Group 2 rats showed a modest but significant increase in SGOT (P less than 0.05) after HAL, while this change was not noted after O2. Thus, 1.8% halothane anesthesia in oxygen did not result in superimposition of acute liver cell injury in already cirrhotic rats.

Alanine Transaminase↗

Chemically defined medium for oral microorganisms.

We formulated a chemically defined medium consisting of 14 inorganic salts, 23 amino acids, 23 vitamins and other factors, seven purines and pyrimidines, and glucose which would successfully support the growth of a wide variety of oral microorganisms. Of 204 oral isolates representing 20 genera and 60 species, 197 maintained viability through six serial transfers.

Bacteria↗

Estimation of ventilation-perfusion inequality by inert gas elimination without arterial sampling.

Estimation of ventilation-perfusion (VA/Q) inequality by the multiple inert gas elimination technique requires knowledge of arterial, mixed venous, and mixed expired concentrations of six gases. Until now, arterial concentrations have been directly measured and mixed venous levels either measured or calculated by mass balance if cardiac output was known. Because potential applications of the method involve measurements over several days, we wished to determine whether inert gas levels in peripheral venous blood ever reached those in arterial blood, thus providing an essentially noninvasive approach to measuring VA/Q mismatch that could be frequently repeated. In 10 outpatients with chronic obstructive pulmonary disease, we compared radial artery (Pa) and peripheral vein (Pven) levels of the six gases over a 90-min period of infusion of the gases into a contralateral forearm vein. We found Pven reached 90% of Pa by approximately 50 min and 95% of Pa by 90 min. More importantly, the coefficient of variation at 50 min was approximately 10% and at 90 min 5%, demonstrating acceptable intersubject agreement by 90 min. Since cardiac output is not available without arterial access, we also examined the consequences of assuming values for this variable in calculating mixed venous levels. We conclude that VA/Q features of considerable clinical interest can be reliably identified by this essentially noninvasive approach under resting conditions stable over a period of 1.5 h.

Arteries↗

Regulation of purine metabolism in lymphocytes.

Three general questions regarding nucleosides and lymphocytes are discussed: (a) Why are so many measurements being made of adenosine deaminase activity, what do the results mean, and why is there still disagreement about some of the conclusions; (b) what do we understand about nucleosides and lymphocyte death; and (c) to what extent do we really understand nucleoside and nucleotide metabolism in lymphocytes? Experimental studies show that treatment of mice with deoxycoformycin, to produce accumulation of deoxyadenosine, leads to rapid thymus involution, elevated dATP concentrations in thymus and liver, and inhibition of adenosylhomocysteine hydrolase in these tissues. Deoxyguanosine inhibits the growth of mouse lymphoma L5178Y cells, and this toxicity is prevented by deoxycytidine plus adenine. In cells treated with deoxyguanosine, concentrations of both GTP and dGTP are elevated, and this is not affected by deoxycytidine. Adenine, however, reduces GTP concentrations to normal, and prevents most of the elevation in dGTP concentrations. Contrary to previous belief, it has been demonstrated that lymphocytes and nucleated bone marrow cells will synthesize purine nucleotides de novo if incubated in an appropriate medium; carbon dioxide is particularly important for this process.

Adenine↗

Prolonged hyporesponsiveness of vascular smooth muscle contraction after halothane anesthesia in rabbits.

Halothane diminishes smooth muscle contractility in vascular tissue. In order to further characterize this phenomenon we undertook a series of in vivo and ex vivo experiments. Pressor dose-response curves to the selective alpha 1-adrenergic agonist, phenylephrine, were constructed in groups of rabbits before, during and 2 hr after halothane anesthesia and the dose of phenylephrine that induced a 25 torr increase in mean arterial pressure (ED25) was derived by polynomial regression analysis. ED25 torr increased significantly during halothane anesthesia, and rabbits remained in this insensitive state when the ED25 was assessed 2 hr after anesthesia. The halothane-induced loss of responsiveness was corroborated by ex vivo experiments utilizing aortic rings from halothane-anesthetized rabbits. The maximal contraction to norepinephrine (NE) was significantly lower in halothane-treated aortic rings and only slowly returned to normal by 4 hr. The EC50 (the dose causing a 50% maximal contraction) for NE was significantly greater in aortic rings from halothane-anesthetized rabbits. This loss of sensitivity, reflected by the higher EC50 was not restored by 4 hr of ex vivo incubation in a halothane-free medium. We conclude that halothane induces loss of sensitivity to adrenergic agonists that persists for several hours after termination of the halothane anesthetic.

Anesthesia↗

Magnesium transport in the proximal straight tubule of the rabbit.

Magnesium transport was evaluated in proximal straight tubules of rabbits by in vitro perfusion. Magnesium transport from lumen to bath was less than the fractional absorption rates of sodium and calcium. Accordingly, the tubule fluid magnesium concentration increased with water absorption. Magnesium transport in proximal straight tubules obtained from rabbits maintained on high dietary magnesium intake was not different from normal animals, which suggests little, if any, change in tubular function. There were no discernible differences in magnesium fluxes between superficial and juxta-medullary proximal straight tubules. To assess bath-to-lumen magnesium flux, tubules were perfused with solutions containing zero magnesium concentration. Magnesium movement from the bath to lumen was small and dependent on the transepithelial magnesium concentration gradient. This magnesium influx may be sufficient to account for net magnesium entry provided the appropriate concentration gradients from interstitium to lumen are available in the intact kidney.

Absorption↗

Sequential versus simultaneous graphesthesia tasks in 6- and 10-year-old children.

Reported in the statistics of the Southern California Graphesthesia Test are significant sex differences for certain young age groups, with females scoring higher than males. In contrast, another study has reported that adult males scored higher than females on the same test. The purpose of this study was to examine the interaction between sex and age and to investigate a possible explanation for this interaction. Sixty-four normal children between the ages of 6.0 and 7.0 years, and 10.0 and 11.0 years were administered two graphesthesia tasks. One task was an adaptation of the Graphesthesia Test of the Southern California Sensory Integration Test (SCSIT). In this task, shapes were drawn sequentially on the palmar surface of the child's hand. A second task was devised whereby each of the same shapes was presented in a simultaneous manner, that is, the entire outline of each shape was pressed onto the palmar surface of the child's hand. Results indicated that for both tasks, younger boys performed relatively less ably than girls, but older boys equalled or surpassed the girls. At a level approaching significance, females scored relatively higher than males on the sequential task, and males scored relatively higher than females on the simultaneous task. However, this tendency toward an interaction between sex and the type of task does not fully explain the interaction between sex and age on graphesthesia tasks.

Age Factors↗

Alpha-adrenergic responsiveness correlates with epinephrine dose for arrhythmias during halothane anesthesia in dogs.

The dose of epinephrine required to elicit ventricular arrhythmias during halothane anesthesia may depend on end-organ sensitivity. We determined whether the arrhythmogenic dose for epinephrine (ADE) could be correlated with either alpha- or beta-adrenergic responsiveness. After ADE was determined in 26 dogs anesthetized with 1.2 MAC halothane, an in vivo assessment of adrenergic responsiveness was made. The alpha-adrenergic responsiveness was defined as the dose of phenylephrine required to increase mean arterial pressure by 75% (alpha 75), while the dose of isoproterenol causing a 75% increase in heart rate was a measure of beta-adrenergic responsiveness (beta 75). The correlation coefficients for alpha 75 and beta 75 vs ADE then were determined by multiple linear regression analysis. There was a highly significant correlation with the alpha 75 (F = 9.06; P less than 0.01), while no relationship existed with beta 75 (F = 0.52; P greater than 0.05). Thus the alpha-adrenergic responsiveness in individual patients may be used to predict the threshold for epinephrine-induced arrhythmias during halothane anesthesia.

Anesthesia, General↗

Halothane-epinephrine arrhythmias and adrenergic responsiveness after chronic imipramine administration in dogs.

The incidence of halothane-epinephrine arrhythmias increases after the short-term administration of imipramine, probably because of enhanced noradrenergic transmission. To determine whether this effect persists after long-term imipramine treatment, we have studied the arrhythmogenicity and adrenergic responsiveness in halothane anesthetized dogs after six weeks of imipramine administration, 150 mg X day-1, orally. The mean (+/- SD) arrhythmogenic dose of epinephrine (ADE) in nine dogs anesthetized with 1.2 MAC halothane was 2.57 (+/- 1.04) micrograms X kg-1 X min-1. The alpha-adrenergic responsiveness, assessed as the dose of phenylephrine that caused a 75% increase in mean arterial pressure (alpha 75), was 5.78 +/- 2.39 micrograms X kg-1 X min-1. The dose of isoproterenol that increased heart rate by 75% (beta 75) was 309 +/- 180 ng X kg-1 X min-1. After imipramine treatment, the ADE (2.63 +/- 1.26), alpha 75 (5.16 +/- 2.05), and beta 75 (386 +/- 266) were not statistically different from the pre-imipramine values (P greater than 0.05), despite a fivefold increase in circulating norepinephrine. We conclude that chronic imipramine does not alter arrhythmogenicity and adrenergic responsiveness, since compensatory mechanisms, at the sympathetic nerve terminal, may revert the initial hyper-responsiveness to normal.

Anesthesia↗

Comparison of hemoglobin Köln erythrocyte membranes with malondialdehyde-reacted normal erythrocyte membranes.

Splenectomized patients with hemoglobin (Hb) Köln have rigid RBCs with membrane polypeptide aggregates that are not dissociable with disulfide-reducing agents. Malondialdehyde (MDA) action on normal RBCs produced rigid RBCs with similar nondissociable aggregates. To test the hypothesis that Hb Köln RBC aggregates contained unsaturated MDA-type bonds, we reduced normal control RBC membranes, Hb Köln RBC membranes, and MDA-reacted membranes with [3H]NaBH4. Hb Köln RBC membranes and MDA-reacted membranes both had significantly more 3H incorporation than control membranes. Furthermore, 3H incorporation in both Hb Köln and MDA-treated membranes was located in the membrane polypeptide aggregates, presumably saturating the crosslinking bonds. After reaction of RBCs with [14C]MDA, the MDA label was similarly concentrated in the membrane polypeptide aggregates. Normal RBC membranes incubated with MDA were analyzed with and without reduction by NaBH4 prior to amino acid determination by high-performance liquid chromatography (HPLC). Reduction with NaBH4 after MDA treatment decreased the lysyl residues by 33% and the serine by 7% and increased by 10% the methionyl residues, but did not affect 12 other amino acids. Similar changes could be detected in NaBH4-reduced Hb Köln aggregates in methionine and serine content. MDA may also alter protein configuration, as evidenced by an increase in the protease susceptibility of membrane proteins from MDA-treated and Hb Köln RBCs. We conclude that Hb Köln RBC membranes, like MDA-treated membranes, have similar high molecular weight aggregates conferring decreased membrane deformability, [3H]NaBH4-reducible unsaturated bonds, changes in amino acid composition upon reduction, and protease-sensitive configurational changes.

Electrophoresis, Polyacrylamide Gel↗

Variation in erythrocyte purine metabolism among mouse strains.

Erythrocytes of five strains of mice had ATP concentrations of ca 2.7 mumol/ml packed cells, while those of CBA mice were 23% lower, and those of BALB/C mice were 40% lower. The ratio of the concentrations of ATP and GTP were ca 3.3 in four strains but greater than 27 in three other strains. When erythrocytes from different mouse strains were incubated with radioactive precursors, appreciable strain differences were found in the apparent activities of adenine and hypoxanthine-guanine phosphoribosyltransferase, adenosine kinase, adenosine deaminase, guanine deaminase and xanthine oxidase. The activities of adenosine deaminase and guanine deaminase in sera of mice of different strains also varied.

Adenine Phosphoribosyltransferase↗

Signs and symptoms of hangover: prevalence and relationship to alcohol use in a general adult population.

The post-intoxication state, commonly called hangover, has been known since antiquity; yet there has been little systematic research examining the signs and symptoms of hangover among the general population. The frequency and the various symptoms of hangovers, as well as the relationships between hangovers and alcohol consumption, were analyzed using a sample of 1041 adults 18 years and older living in Western New York State. Hangovers were experienced in the previous year by only about 50% of the population of heavier drinkers; the frequency was even less among those with lower alcohol consumption. Factor analysis of the various symptoms revealed significant clusters. The findings suggest that the aversive aspects of alcohol consumption, including the hangover syndrome, may deter excessive consumption; certain individuals in whom aversive reactions as hangover do not occur may be at high risk for excessive alcohol use.

Adult↗

Alcohol withdrawal syndromes - prediction from detailed medical and drinking histories.

The predictability of the withdrawal syndrome on the basis of the drinking history immediately prior to detoxification was investigated in 43 patients admitted to an inpatient Alcoholism Service; a pilot study consisted of 17 patients and a subsequent definitive study of 26. After obtaining informed consent, blood alcohol concentrations were measured. Each subject was extensively interviewed to obtain a medical and dietary history and to determine alcohol and drug intake in the past week and months. The levels of intoxication and withdrawal signs/symptoms were assessed on admission and daily for at least 3 days. Urine and blood toxicology screens were also performed for 19 subjects. Contrary to widespread impressions, most of the patients were able to give a detailed account of their drinking and drinking-related behavior in the 3 days prior to admission and 73% could do this for the previous 7 days. Subjects were consistent in their reporting; 85% gave drinking histories consistent among interviews conducted independently by the medical, research and counseling staff. A significant correlation (r = 0.55; P less than 0.01) was found between the severity of withdrawal and the total alcohol intake in the days immediately prior to admission. No significant correlation was evident between withdrawal severity and the number of years of heavy drinking. Amounts of benzodiazepines (diazepam and flurazepam) administered by the medical staff during the first 3 days of withdrawal and for the total hospital stay were also found to be significantly correlated with withdrawal severity (r = 0.58; P less than 0.01 for both). Regression analyses of these data also confirmed the statistically significant relationships between alcohol intake and withdrawal severity and between withdrawal severity and amounts of benzodiazepines used for detoxication. Of special interest was the finding that 50% of the subjects reported no hangovers within he past year or more and 23% reported that they had never experienced a hangover, despite very heavy drinking. In addition, only 50% of the patients had regularly consumed coffee or any caffeine-containing substance; this low incidence of caffeine intake was statistically significantly less than that found in extensive surveys of the general population in which only 3-10% eschew caffeine-containing beverages. It is concluded that the severity of alcohol withdrawal can be related to a cluster of variables among which is recent alcohol intake. The present results are, at the same time, consistent with previous observations of the appreciable differences among individuals in the consequences of abrupt cessation of chronic alcohol consumption.

Adult↗