Zimelidine - a serotonin uptake blocker in the treatment of phobic anxiety.
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Biomedical subjects
Publications and source records attributed to G Moore.
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Death rates from skin cancer appear to be rising in Virginia, according to mortality data, with a sharp increase indicated in the 50-64 age group. Geographic configuration of the data suggests environmental changes, and the author sees the need for a formal study of Virginia's skin cancer mortality.
Norepinephrine (NE) and serotonin (5-HT) concentrations were determined in three areas of the rat brain following 8 wk exposure to differing physical activity and dietary regimens. Animals were divided into sedentary and exercise groups, and one-half of each received either a normal or atherogenic diet. The exercise consisted of 30 min of treadmill running, 5 days/wk, for 8 wk. Brains were weighed and sectioned into cerebral cortex, cerebellum, and remainder (midbrain), and fluorometrically analyzed for NE and 5-HT content. In most brain areas, NE and 5-HT levels were significantly greater among exercise-normal diet and exercise-fat diet compared to both sedentary groups. In the cerebral cortex, exercise-normal diet rats possessed higher levels of NE and lower concentrations of 5-HT than sedentary animals. The atherogenic diet did not affect amine levels other than 5-HT in the cortex among exercise rats. The NE results are consistent with prior research indicating its control of sympathetic function. Increased levels of 5-HT in the midbrain may be the neurotransmittal adaptation responsible for decreased appetite and enhanced weight loss following chronic endurance exercise.
Individuals with a G-6-PD deficiency have long been known to be at increased risk to experience acute hemolysis following exposure to elevated levels of certain oxidant drugs and industrial chemicals. However, the recognition of enhanced susceptibility to environmental (or ambient) pollutants has generally not been considered. Recent theoretical studies have suggested that elevated levels of ambient ozone may be an etiologic factor in the onset of acute hemolysis in the G-6-PD deficient individual. Furthermore, the proposed usage of either chloramines or chlorine dioxide as replacements for chlorine for the disinfection of drinking water should be investigated with respect to their potential adverse effects of individuals at increased risk to oxidant stressors. In order to test these theoretical associations, two mouse strains, one with low and the other with high levels of G-6-PD activity in their red blood cells are being investigated to determine if they simulate human G-6-PD deficient and normal individuals, respectively. Preliminary results indicate that the mouse strain with low G-6-PD activity is markedly more susceptible to sodium chlorite than mice of the high G-6-PD strain. This differential susceptibility to sodium chlorite toxicity between the high and low G-6-PD mouse strains suggests that further research designed to validate the efficacy of this mouse model as a predictor of the human situation is warranted.
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(8-Arginine)vasopressin, (8-arginine)vasotocin, oxytocin and oxypressin, the 'ring' derivatives pressinamide and tocinamide, and the extended-chain analogues Pro-Arg-Val-(8-arginine)vasopressin and (8-arginine)vasopressinoyl-Ala-Met-Ala-NH(2), were synthesized by the solid-phase method and purified by sequential gel filtration on Sephadex G-15 in 50% acetic acid and 0.2M-acetic acid. Controlled oxidation of the thiol groups of the reduced peptides obtained after deprotection with sodium in liquid ammonia gave rise to products that depended on the length of the peptide chain: (i) nonapeptides gave monomer and dimer species, (ii) hexapeptides produced mixtures containing higher polymers, and (iii) dodecapeptides gave predominantly monomer with some dimerized material. The evidence suggests that the presence of the acyclic tail tripeptide in the nonapeptide hormones induces a conformation in the preceding hexapeptide that favours the formation of an intramolecular disulphide bond. For (8-arginine)vasopressin, intramolecular disulphide-bond formation is enhanced by extension of the peptide chain from either the N- or the C-terminus. The possible significance of these studies to neurohypophysial hormone-prohormone relationships is discussed.
Plasma concentration-time profiles of meperidine after intravenous administration to 7 pregnant women during labor were investigated. There was considerable interpatient variation in initial plasma concentrations of meperidine and its volume of distribution. When the data in the literature on the disposition of meperidine in nonpregnant subjects were used for comparison, it was found that the initial dilution volume (V1), the volume of distribution at steady-state (Vss), and the apparent volume of distribution during the terminal exponential phase of drug elimination (Vbeta) were less (p less than 0.05) in pregnant subjects than in healthy nonpregnant control subjects but were not significantly different in pregnant subjects and nonpregnant surgical patients. Mean total systemic blood clearance was also significantly less in the pregnant subjects (843 ml/min) than previously reported for healthy nonpregnant control subjects (1,465 ml/min). The blood/plasma concentration ratio of meperidine in pregnant women (0.940) was higher than that in control subjects (0.768; p less than 0.01). Placental transfer of meperidine was investigated in 4 of the patients; in 2 the concentration of the drug was greater in cord plasma than in maternal plasma. Further study is indicated.
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Thirty-four cases of duodenal trauma, 23 caused by gunshot wounds, are reviewed. All but three patients had associated major organ injuries, a total of 97 injuries. Postoperative mortality was 14% for injuries into the duodenal lumen. Techniques for operative repair included simple primary closure, use of omental or serosal patches, controlled fistula with a duodenostomy tube, decompressive and feeding ostomies, "diverticulization", segmental duodenal resection and anastomosis, and total duodenectomy and pancreatectomy. It is emphasized that the surgeon finding duodenal injury must be familiar with all of these techniques, each of which has its indications. Treatment of duodenal injuries perhaps more than any other bowel trauma must be individualized.
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Standard methods of determining toxic vapor exposures rely heavily on charcoal tube sampling. The validity of results depends critically on accurate determination of the total air volume and avoidance of saturation breakthrough. The difficulty of substantiating sampling validity has stimulated a search for more absolute methods. A novel pump will be described which fulfills the requirement of true total volume measurement and has a flowrate capability down to 1 cc/min. This low flow feature lends itself to a variety of new detection techniques which will be outlined together with a detailed description of the unit's function.
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The maternal venous and umbilical venous plasma concentrations of bupivacaine were determined at delivery following epidural administration of the drug to 31 women in labor. In each case the umbilical venous plasma concentration of bupivacaine was lower than the maternal venous plasma concentration. There was no significant difference between the concentration of unbound bupivacaine in umbilical venous and maternal venous plasma at delivery. The difference in umbilical and maternal plasma concentrations of bupivacaine appears to be a consequence of greater bupivacaine binding to maternal than to fetal total plasma protein. The intersubject variation of the ratio of bupivacaine concentration in fetal plasma/bupivacaine concentration in maternal plasma was found to be related to individual variation in the extent of protein binding of bupivacaine in maternal and umbilical plasma and correlated positively with the variation of the ratio of total protein concentration in umbilical and maternal plasma.