Biomedical subjects
Publications and source records attributed to J Lawson.
The theoretically determined molecular structures of N-protonated 1,3,4,6 methyl-substituted 4-(m-OH phenyl) piperidines are correlated to their experimentally derived analgesic activities. It is concluded that the orientation of the 3-methyl group plays a crucial role in determining agonism and antagonism.
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Two adult male chimpanzees reached through a hole in the wall of their home cage and, by tracking the images of their hands and of an otherwise hidden target object in a mirror or closed-circuit television picture, moved their hands in whichever direction was necessary to make contact with the target object. They discriminated between live video images and tapes and performed effectively when the target objects were presented in novel locations and when the video picture was presented at random in different orientations. There was thus no consistent relation between the location of images on the monitor and the location of their real-world counterparts. Comparable performances in monkeys and nonprimates seem unlikely.
Pyrazolo[1,5-a]pyrimidines (PZP) have been reported to be specific anxiolytic agents which do not potentiate ethanol or barbiturates. To further investigate these compounds, three of the most promising analogs were synthesized and a tritium-labeled analog of one of them prepared by a new synthetic procedure. These analogs did not compete with [3H]flunitrazepam or [3H]beta-carboline ethyl ester binding nor did they potentiate the [3H]flunitrazepam binding. Receptor binding studies with the [3H]PZP revealed a low affinity receptor site, distinct from that of the benzodiazepines, but with only a small fraction (20%) of specific binding. Behavioral tests using three different animal models for anxiety: muricide, approach/avoidance conflict and two-chamber exploration tests gave conflicting results, positive in the first and negative in the latter two. Furthermore, these compounds were found not to be antagonists of diazepam's anticonvulsant activity. Taken together, these results, while provocative, do not support evidence that these analogs are promising specific anxiolytic agents.
Stereoselective metabolism of mephenytoin has been investigated in four normal subjects by comparing urinary recoveries of hydroxylated metabolites after administration of racemic RS-mephenytoin (1.4 mmol/day) and R-mephenytoin (0.7 mmol/day) on separate occasions. Gas chromatography-mass spectrometry was employed to measure the urinary recovery of 3-methyl-5-(4-hydroxyphenyl)-5-ethylhydantoin (4-OH-M) and mephenytoin catechol, methylcatechol, and dihydrodiol metabolites. Following a single oral dose of racemic mephenytoin, 4-OH-M, mephenytoin catechol, and methylcatechol metabolites were identified in urine mainly as conjugates, whereas the dihydrodiol metabolite was recovered mainly in its unconjugated form. Urinary elimination of each metabolite was similar on days 1 and 10 of chronic racemic mephenytoin administration. Following R-mephenytoin administration, urinary recoveries of hydroxylated metabolites were five to 10 times smaller than after administration of the racemic drug. This implies substrate-stereoselective hydroxylation of the S-enantiomer of mephenytoin. In one subject with a genetic deficiency of aromatic mephenytoin hydroxylation deficiency, the excretion of each hydroxylated mephenytoin metabolite after RS-mephenytoin administration was decreased to 5-15% of the values found in the four extensively hydroxylating study volunteers. The impaired formation of hydroxylated mephenytoin metabolites in genetic hydroxylation deficiency, in conjunction with stereoselective hydroxylation of S-mephenytoin via an extensive NIH shift in normal man, is consistent with the hypothesis that the formation of the S-mephenytoin arene oxide is under genetic control and represents the initial enzymatic reaction of stereoselective aromatic mephenytoin hydroxylation. The formation of this potentially reactive metabolite of S-mephenytoin may have implications in mephenytoin-induced toxicity.
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Three chimpanzees learned to label three edibles as "foods" and three inedibles as "tools". Two chimpanzees could then similarly categorize numerous objects during blind trial 1 tests when shown only objects' names. The language-like skills of the chimpanzee who failed (Lana) illustrates that apes can use symbols in ways that emulate human usage without comprehending their representational function.
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The clinical, pathological and physiological features of two patients suffering from tracheobronchopathia osteochondroplastica (TO) are described. Unequivocal evidence of extrapulmonary airways obstruction was not able to be obtained by lung function testing, despite extensive central airway involvement in both patients. TO is a rare condition of which there is only one other clinical report from this country. As the bronchoscopic appearance may closely resemble that of endobronchial neoplasms, TO should be remembered in the differential diagnosis of patients with haemoptysis.
A coagulopathy associated with severe hemolysis was a limiting factor in obtaining long-term survivors among calves with total artificial hearts in 1969. Conversion of design from sac-type hearts to flexible diaphragm hearts, and from Silastic Dacron-fibril intimas to smooth polyurethane intimas, resulted in an abatement of the coagulopathy. In the most recent series of animals studied at this laboratory, platelet counts are normal and platelet survivals are half of normal. Plasma hemoglobins are normal. The coagulation system is still activated at specific loci within the total artificial heart, but is best compensated for in calves treated with antiplatelet drugs, having polyurethane hearts.
A randomized multiregimen clinical study was undertaken using Monistat Cream for the treatment of vulvovaginal candidiasis. The objective of the study was to find if there is a shorter regimen comparable in effectiveness to the currently marketed 14-day regimen. The results indicate that there is no significant difference between the cure rate obtained for 7 days of therapy and for 14 days of therapy.
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This report summarizes the surface changes seen in artificial hearts implanted in calves for periods up to four months. Fabrication defects as well as degradation resulting from wear are identified. SEM evaluation of the blood contacting surface as well as the surface of the diaphragm associated with the drive mechanisms has revealed potential problems with current heart designs and methods of fabrication. Materials evaluation of implanted hearts is crucial for a clinically useful system to evolve.