Clothier Report and the dispensing doctor.
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Biomedical subjects
Publications and source records attributed to A Rogers.
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The relative analgesic potency of single graded intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer. When both intensity and duration of analgesia are considered (total analgesic effect), oxycodone was 2/3 to 3/4 as potent as morphine, while in terms of peak analgesia, it was 8/10 to equipotent. In doses producing equivalent peak effect, oxycodone had a shorter duration of action than morphine. Intramuscular oxycodone was also compared to intramuscular codeine in a similar patient group. In terms of total analgesic effect, oxycodone was 10 times as potent as codeine, while in terms of peak analgesia it was 12 times as potent. These relative potency relationships of oxycodone, taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine, oxymorphone and codeine, demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine, oxymorphone, codeine and oxycodone. The results of these studies do not appear to support the hypothesis that, in man, the analgesic activity of codeine is due to its O-demethylation to morphine.
The relative analgesic potency of oral and intramuscular codeine was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral codeine was 6/10 as potent as the intramuscular form. This is a high oral/parenteral analgesic relative potency ratio compared with morphine, metopon and oxymorphone and correlates well with the results of recent studies which have determined the oral vs. intramuscular bioavailability of codeine in man. Oral and intramuscular oxycodone were also compared in a similar patient group. Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.
To test the hypothesis that all cases of vaginal candidiasis are associated with a "reservoir" of this organism in the bowel, paired specimens of feces and vaginal material were cultured for Candida albicans simultaneously. Ninety-eight young women who complained of recurrent vaginitis were selected in sequence. The results showed that if C albicans was cultured from the vagina, it was always found in the stool. Conversely, if it was not isolated from the stool, it was never found in the vagina. These data are presented as an explanation for the recurrent nature of Candida vaginitis, and thus a cure of vaginitis would not be possible without prior eradication of C albicans from the gut. The gut-reservoir concept may well apply to other forms of candidiasis.
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The relative analgesic potency of oral and intramuscular oxymorphone was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral oxymorphone was 1/6 as potent as the intramuscular form. In terms of peak effect, however, oral oxymorphone was only 1/14 as potent. These values are almost identical to those obtained in a previous study comparing oral with intramuscular morphine. The analgesic effect of oral oxymorphone rose to a peak later and had a longer duration than the effect of intramuscular oxymorphone. Intramuscular oxymorphone and morphine were also compared in a similar patient group. Intramuscular oxymorphone proved to be 8.7 times as potent as morphine in terms of total analgesic effect and 13 times as potent in terms of peak effect. In roughly equinalgesic doses, the occurrence of side effects was qualitatively and quantitatively similar for oral and intramuscular oxymorphone and for intramuscular oxymorphone and morphine.
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Incubation of the ubiquitous pollutants, polychlorinated biphenyls (PCB), DDT and DDE with rat liver lysosomes shows that these lipophillic substrates are highly active labilizers of lysosomal membranes. The release of acid phosphatase was used as a marker enzyme and at high PCB, DDT and DDE concentrations (2X10(-3)M) the lytic activity was similar to that of the detergent Triton X-100; at lower concentrations most of the commercial PCB samples, DDT and DDE still retain considerably lytic activity.
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1. Cell-free lysates of human peripheral blood lymphocytes contained two casein kinase activities and two histone kinase activities, which could be separated by chromatography on DEAE-Sephadex. 2. Neither of the casein kinase activities were stimulated by cyclic AMP. The major activity was eluted from DEAE-Sephadex between 0.4 and 0.45M-KCl, had a molecular weight of approx. 130,000 (sucrose density gradients) and was stimulated by KCl (maximum 150mM). It also formed higher-molecular-weight aggregates when centrifuged in sucrose gradients containing 150mM-KCl. The minor activity was not retained by DEAE-Sephadex, had a molecular weight of approx. 50,000 and was not stimulated by KCl. 3. The major histone kinase activity was stimulated by cyclic AMP and was eluted from the DEAE-Sephadex column between 0.05 and 0.2M-KCl. The other activity was not stimulated by cyclic AMP and was insensitive to the rabbit muscle protein kinase inhibitor. 4. Evidence was obtained suggesting that the lymphocyte casein kinases were located primarily in the nuclei.
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