2,4,5,2',4',5'-Hexachlorobiphenyl: distribution, metabolism, and excretion in the dog and the monkey.
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Biomedical subjects
Publications and source records attributed to D E Carter.
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The concentrations of lidocaine and mepivacaine were measured in stored cord blood samples from 200 deliveries. Newborn and obstetrical charts were reviewed for 100 deliveries for study of the association between cord blood concentrations, drug and route of recorded administration, Apgar scores at birth, and symptoms of possible toxicity. Detectable concentrations were commonly found (117/200), but toxic (3 micrograms/ml) levels were uncommon (4/200). However, recovery studies indicate these levels underestimate maximal exposure because both lidocaine and mepivacaine levels were shown to decrease in refrigerated stored blood. Although toxicity was seldom suspected, diagnostic accuracy was poor. The diagnosis was missed in the two patients with very high levels (5.0 and 9.0 micrograms/ml) of mepivacaine and levels measured in two suspected cases of toxicity were both low (0.4 microgram/ml). Associations between Apgar scores, cord levels, and route of administration (especially for lidocaine) were examined for 65 full-term uncomplicated deliveries. However, evaluation of these associations is problematic because dosages given, time or route of administration, and/or Apgar scores were often either not given or inconsistent with the clinical history. Detectable and potentially clinically significant local anesthetic drug concentrations were found in cord blood after all methods of administration, including local infiltration. These levels appear to underestimate the level of exposure because of instability of these anesthetics in stored cord blood samples. Local anesthetic toxicity appears to be difficult to detect clinically and may require cord blood level monitoring to detect.
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THREE MODELS OF CONDITIONAL DISCRIMINATION LEARNING BY PIGEONS ARE DESCRIBED: stimulus configuration learning, the multiple-rule model, and concept learning. A review of the literature reveals that true concept learning is not characteristic of the behavior of pigeons in matching-to-sample, oddity-from-sample, or symbolic matching studies. Instead, pigeons learn a set of sample-specific S(D) rules. Transfer of the discrimination to novel stimuli, at least along the hue dimension, is predicted by a "coding hypothesis", which holds that pigeons make a unique, but usually unobserved response, R(1), to each sample, and that the comparison stimulus chosen depends on which R(1) was emitted in the presence of the sample. Convincing evidence is found that pigeons do code sample hues, but there is little evidence that allows one to infer that the "coding event" must have behavioral properties. Parameters of the conditional discrimination paradigm are identified, and it is shown that by appropriate parametric manipulation, a variety of analogous tasks may be generated for both human and animal subjects. The tasks make possible the comparative study of complex learning, attention, memory, and information processing, with the added advantage that behavior processes may be compared systematically across tasks.
Bumetanide (3-N-butylamino-4-phenoxy-5-sulfamyl-benzoic acid) is a sulfonamide congener with potent diuretic activity in man. Oral administration of 14C-bumetanide (2 mg, 22 71Ci) to 4 adult male volunteers was rapidly and almost completely absorbed (greater than 95%). Its average apparent volume of distribution was 25 L. Bumetanide induced a ceiling diuresis at 1 hr, with loss of Na+ and water for 4 to 5 hr. Loss of K+ was minimal. Bumetanide was quickly eliminated by metabolism and urinary excretion with a plasma half-life of 1.5 hr. The administered radioactivity was almost completely recovered (96%), 81% appearing in the urine and the remainder in the feces. In one subject with bilary T tube, 14.4% of the dose was excreted in the bile which suggested that the radioactivity of the feces came from the bile. Thin-layer chromatography analysis of pooled urine, bile, and fecal samples showed the elimination of bumetanide could be explained by excretion of unchanged drug and side chain oxidative metabolism and conjugation.
Previous studies have shown the importance of phenytoin kinetics in the management of adult patients with seizure disorders. The long half-life in adults makes single daily dosing realistic in terms of blood levels and anticonvulsant effectiveness. This report shows a wide range in both half-lives and volumes of distribution of phenytoin in 11 children (ages 6 months to 6 years) with seizure disorders. Ten of these patients have very short phenytoin half-lives (1.2 to 6.7 hours). The data strongly suggest that current recommendations for phenytoin dosage regimens in adults cannot necessarily be used in children. Blood levels must be followed closely in this age group to determine the required dosage and dose interval.
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Pigeons had no greater difficulty learning a complex discrimination involving arbitrary among stimuli (symbolic matching) than one involving interrelations based on stimulus similarity (matching-to-sample). The relative rates of acquisitions of matching and symblic matching may be accounted for by the discriminability between sample stimuli and between comparison stimuli, with the former playing the more important role.
The effects of chronic steroid contraceptive therapy on drug clearance from plasma were studied by using plasma antipyrine, phenylbutazone, and cholecalciferol half-lives in women. After 3 mo of oral steroid therapy (Norinyl, 2 mg; norethindrone + mestranol), the antipyrine half-life was increased in 3 of 6 subjects, phenylbutazone half-life was not consistently altered, and vitamin D3 half-life was increased in 3 of 4 patients. After 1 to 7 yr of oral steroid theraphy, the antipyrine half-life was longer while taking the contraceptive than when the contraceptive treatment was discontinued in 4 of 6 subjects, whereas that of phenylbutazone was not consistently altered.
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