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Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 631 records · Page 35Linked to original sources

Gastric and biliary excretion of meperidine in man.

The role and importance of enterogastric secretion in the disposition and elimination of the weak base, meperidine (pKa 8.63), was studied after intravenous administration (50 mg) of the drug to 6 normal volunteers. Continuous collection of the gastric fluid over a 4-hr period demonstrated the establishment of high gastric fluid/plasma concentration ratios for meperidine (mean about 50, range, 10 to 200). However, the total amount of drug recovered, even after correction for incomplete collection, was only a small percentage of the administered dose. Under basal conditions a mean +/- SE of 1.9 +/- 0.3 mg, equivalent to 3.7% of the administered dose, was found in the total gastric aspirate. Stimulation of gastric secretion by subcutaneous injection of betazole (1.5 mg/kg) increased this recovery to 3.6 +/- 0.3 mg (7.2%) primarily due to the increase in gastric volumen output. Aspiration of the gastric fluid in either the basal or stimulated situation had no observable effect upon the plasma concentration/time profile of meperidine whether assessed by the terminal half-life, t 1/2 beta, or the plasma clearance; control values were 3.8 +/- hr and 1,190 +/- 130 ml/min, respectively. In 2 subjects "bile fluid" was also collected for 2.5 hr and found to contain less than 0.2% of the administered dose. Enterosystemic recycling is therefore of minor importance in the disposition and elimination of meperidine in man.

Adult↗

Changes in mouse blood pressure, tumor blood flow, and core and tumor temperatures following nembutal or urethane anesthesia.

Female CBA and WHT mice with tumors transplanted into the right leg were immobilized in insulated capsules. Tumor blood flow, blood pressure, and core and tumor temperatures were monitored prior to and during anesthesia with either Nembutal or urethane. Nembutal caused a 5 degree C drop in both core and tumor temperatures in 20 minutes. Urethane induced a small fall in temperatures. Urethane initially caused a small drop in blood pressure followed by recovery; Nembutal caused a steady fall in blood pressure to 50% of resting value.

Anesthesia, Intravenous↗

Normal disposition of oxazepam in acute viral hepatitis and cirrhosis.

Oxazepam (Serax) is a tranquilizer-sedative of the benzodiazepine group that is predominantly metabolized to a pharmacologically inactive glucuronide and subsequently excreted by way of the kidneys. We administered this drug as a single oral dose to seven patients with acute viral hepatitis, to six with cirrhosis, and to age-matched control subjects. Elimination half-life (T1/2) and the apparent oral plasma clearance for the drug in patients with hepatitis and cirrhosis were comparable to values obtained in age-matched controls (P greater than 0.05). In addition, the apparent volume of distribution of oxazepam, its plasma binding, blood/plasma ratio, and the rate of urinary excretion of oxazepam, predominantly as the glucuronide, were comparable (p greater than 0.05) in the two groups of patients with liver disease and their respective controls. Unlike many other sedatives, oxazepam is eliminated normally in patients with parenchymal liver disease an therefore, on pharmacokinetic grounds, seems to be an excellent sedative for use in such persons.

Acute Disease↗

Cardiac pacemakers. Does radiation therapy affect performance?

Representative deman cardiac pacemakers were tested with several common radiation therapy devices and ancillary equipment. The experimental set-up essentially duplicated the dosimetric and electroconductive environment of the radiation therapy patient bearing a pacemaker. Observations of pulse width and interval confirmed that pacemaker output was generally not appreciably affected by the simulated treatments. Occasionally, changes were caused by ancillary equipment and start-up of treatment. We conclude that although interference hazards are sometimes seen, radiation therapy is not contraindicated in patients wearing pacemakers.

Humans↗

Differences in occipital cortical synapses from environmentally enriched, impoverished, and standard colony rats.

Initial and replication experiments were studied with littermate, S1, male rats 25-55 days of age placed in enriched (EC), standard colony (SC), and impoverished (IC) environments. Measurements of the length of postsynaptic thickenings were taken from asymmetrical axodendritic synapses in layer IV of the dorsal medial occipital cortex. This experiment differed from others of this nature, for animals from both experimental conditions were compared with the standard colony animals. The 8% (p less than 0.01) difference in postsynaptic thickening length between 675 synapses from EC and 680 synapses from IC was primarily due to the IC, as can be seen by comparing both with the SC. The number of synapses per unit area of neuropil was 15% (p less than 0.01) more in the IC than in the EC and this difference was primarily due to impoverishment. Both the original and the replication experiment verified this direction of change. Thus, environmental experience does significantly affect synaptic length and number, although the large magnitude previously reported by Mphillgaard et al. (1971) was not confirmed in the present experiments. The 7% cortical depth difference between the enriched and impoverished animals was seen to be attributed to both conditions when each was compared with the standard colony rats. The plasticity of synaptic dimensions is discussed in relation to our previous work and to work of others.

Animals↗

Quantitative GLC determination of conjugated estrogens in raw materials and finished dosage forms.

A GLC method is described for the quantitative analysis of conjugated estrogens. The procedure was used for the analysis of various estrogen mixtures obtained from formulations containing estrogen sodium sulfate salts. The method involves slurrying or dissolving a portion of the formulation pH 5.2 buffer, hydrolysis with sulfatase enzyme, extraction with ethylene dichloride, anf finally, GLC separation and quantitation of the corresponding trimethylsilyl ethers on a 2.5% diethylene glycol succinate column.

Animals↗

Oxygen consumption by acrylamide polymerization: a method for rapid screening of anticancer agents.

We have developed a rapid and sensitive method to measure oxygen consumption of tumor cells by acrylamide polymerization. This method could be used as an in vitro screen for potential chemotherapeutic agents. Previous techniques have lacked either the sensitivity or the speed required for use as an effective clinical tool. This method was modified from a technique previously developed in our laboratory for measuring oxygen in blood. Standard anticancer agents were tested against Walker 256 ascites tumor. Ascites was harvested from 20 rats on each of 50 days, incubated briefly with drugs, and acrylamide polymerization time was measured hourly. Individual controls were established for each drug-treated group, and oxygen uptake measured after one hour of incubation. Actinomycin, cyclohexamide, and cytosine arabinoside inhibited tumor cell oxygen consumption by 80%, 40%, and 30%, respectively. These results correlated with the known in vivo effects of these drugs on Walker carcinosarcoma. Therefore, this sensitive method could potentially be used directly on tumor cells removed from biopsy material so that the testing of anticancer drugs could be completed on the day of biopsy.

Acrylamides↗