Prolonged anticoagulation in rat poisoning.
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Biomedical subjects
Publications and source records attributed to E C Jones.
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A new hematologic syndrome with phenotypic features of mild Hb H disease was identified in three children from two unrelated black American families. Erythrocytes from each of these children contained Hb H (beta 4) and Hb Barts (gamma 4), as well as a slowly migrating hemoglobin fraction that made up 7-10% of the total hemoglobin. The parents of the affected children all showed mild thalassemia-like changes, with one of the parents in each family also expressing the variant hemoglobin; in the latter individuals the mutant alpha-chains made up less than 2% of the total, and were present mainly or exclusively in combination with delta-chains in the form of a slowly migrating Hb A2. Purified Hb Evanston showed an increased oxygen affinity, but its Bohr effect, cooperativity, and 2,3-diphosphoglycerate effect were normal. The mutant hemoglobin appeared to have normal stability to heat and to isopropanol, and the stability of its alpha-chain in an extended time course synthesis study also appeared to be similar to that of alpha A. However, the results from short-term globin synthesis studies, and from mRNA translation in vitro, suggest that the two types of alpha-chains were synthesized at relatively equal rates, with a major fraction of the newly synthesized variant alpha-chains undergoing rapid catabolism. The hematologic data taken in combination with DNA hybridization and globin synthesis findings indicate that the proposita in each of these families has the genotype--, alpha A/--, alpha Ev. These observations suggest that two separate mechanisms are contributing to the alpha-thalassemia-like expression of Hb Evanston : the newly synthesized alpha EV-chains are unstable and are subject to early proteolytic destruction; and the mutant alpha-allele is linked to an alpha-globin gene deletion.
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The bioavailability of codeine and extent of its transformation to morphine were stated in 12 smoking and 11 nonsmoking subjects after single doses 60 mg IM codeine and 60 mg codeine sulfate orally, given 1 wk apart. Codeine and morphine plasma concentrations over the 12-hr period after drug were determined by radioimmunoassay (RIA). No differences were found between smokers and nonsmokers with respect to maximum plasma concentration (Cmax) of codeine, time to attain this concentration (tmax), codeine plasma half-life (t1/2), or areas under plasma concentration-time curves (AUC) for codeine or morphine. There was a faster, but clinically unimportant, mean apparent plasma clearance in smokers (52.8 +/- 2.3 (SEM) ml/min/70 kg) than in nonsmokers (45.0 +/- 2.1 ml/min/70 kg) after intramuscular injection only. Mean oral codeine bioavailability in smokers (54.8 +/- 4.9%) and in nonsmokers (50.2 +/- 2.1%) did not offer. Plasma morphine AUC values were higher after oral doses than after intramuscular injections, suggesting a first-pass O-demethylation of codeine. For six of these subjects plasma morphine AUC values were very low after both routes of administration, suggesting less O-demethylation of codeine in these than in the remaining 17 subjects. The observation of higher morphine AUC values after oral codeine, coupled with clinical reports of greater analgesic potency with intramuscular codeine, does not support the hypothesis that the analgesic properties of this drug are mediated entirely by biotransformation to morphine.
We report the production and comparative specificities of antisera raised to different immunogens containing codeine, morphine, and oxycodone. Antisera raised to bovine serum albumin (BSA) conjugates of codeine-6-hemisuccinate, ethylmorphine-6-hemisuccinate, or oxycodone-6-carboxymethyloxime had greatest recognition of structural changes around the piperidine ring nitrogen atom and th 14-position. N-carboxypropylnormorphine-BSA, N-carboxypropylnorcodeine-BSA, and norcodeine-BSA (directly coupled) conjugates elicited antisera that recognized structural changes at the 3- and 6-positions best, but also clearly discerned changes in the 14-substituent. Attachment of codeine to BSA via the 8-position gave a conjugate that elicited antisera with specificity characteristics similar to those of the antiserum to N-carboxypropylnorcodeine-BSA. Thus clear relationships existed between immunogen structure and antiserum specificity. The utility of these antisera was illustrated by the application of antiserum to codeine-6-hemisuccinate-BSA and solvent extraction to a study of codeine disposition in the dog. The specific antisera of N-carboxypropylnormorphine-BSA and to norcodeine-BSA were applied directly to an examination of the distribution of codeine and metabolically produced morphine in the milk and plasma of a nursing mother.
One hundred eight GUEPAR knee arthroplasties have been studied with a follow-up of one year on 41; 2 years on 22 and 3 years on 45 knees. Overall results were 17% excellent, 44% good, 10% fair and 29% poor. Excellent results were comparatively fewer in rheumatoid arthritis. There was a deterioration in the quality of results of arthroplasty with longer follow-up. The incidence of deep infection was 11%. There was a significant correlation between early wound drainage and deep infection. More than half of the infected knees have not required intervenition as yet. One knee was revised and 3 had attempted arthrodesis with one successful fusion. Two patients died with septicemia. Axle migration occurred in 8 knees and femoral stem breakage in 2 knees. Loosening was found in 27% of the knees with progressive reduction in quality of the arthroplasty. Incomplete cementing predisposed to loosening. Patellar symptoms were present in 28% of the knees. Patellar subluxation and dislocation occurred in 49% of the knees. More than half of these were symptomatic. With normal patellofemoral alignment, pain was more common in the osteoarthritic knee. Use of a patellar implant with GUEPAR knee prostesis should be restricted to severely disabled patients with major fixed deformities. Mechanical failure can be minimized by proper positioning of the implant, correct alignment of the extensor mechanism and adequate cement around the entire stem.
Plasma concentrations of codeine and morphine were determined by specific radioimmunoassays in healthy human subjects at various times following oral administration of analgesic preparations containing therapeutic doses of codeine phosphate. Following administration of codeine phosphate (60 mg) in combination with aspirin (650 mg) or acetaminophen (600 mg) to two separate groups, mean peak codeine plasma concentrations and beta-phase elimination half-lives were 159 ng/ml and 2.9 hr or 138 ng/ml and 2.4 hr, respectively. Mean maximum concentrations of metabolically produced morphine were 6.8 ng/ml (aspirin-codeine phosphate administration) and 7.4 ng/ml (acetaminophen-codeine phosphate). Following drug administration, the mean ratio of the areas under the respective plasma concentration-time curves for morphine and codeine was 0.095 for the aspirin-codeine phosphate study and 0.12 for the acetaminophen-codeine phosphate study. Thus, free morphine represented about 10% of the free codeine area in each case. These results support the hypothesis that metabolically produced morphine may influence or be responsible for the analgesic efficacy of codeine.
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Twelve patients were studied following proximal-row carpectomy. Four had a follow-up of twenty years or more. The lesions for which the operation was done included Kienböck's disease, perilunar dislocations, and fractures of the carpal scaphoid. The major complaint of pain was relieved following surgery, and a functional range of motion was obtained. Mild degenerative arthritis of the wrist was not a contraindication and progressive degenerative arthritis of the radial capitate articulation did not occur. The operation did not result in weakness and all of the patients resumed their preoperative occupations. After conservative measures fail, proximal-row carpectomy rather than arthrodesis should be considered for disorders of the proximal row of carpal bones.
Differential counts of follicles of different sizes in the ovaries of intact and hypophysectomized strain A mice of various ages have been analysed statistically. The influence of age on the number of follicles in each size group is described. The number of small follicles in the ovarian pool declined exponentially, whereas numbers of follicles in other groups displayed two peaks, one during immaturity and the other in adult life. These appeared sequentially in follicles in successive groups. The proportion of follicles growing and dying was estimated and age dependent fluctuations in the time spent by follicles in each group were demonstrated. Further calculations then determined the mean inflow and outflow of follicles to and from the various groups throughout the lifespan. Hypophysectomy during post-puberty decreased only slightly the utilization of small follicles from the pool and did not prevent their subsequent development to the two-layered stage. Many follicles then died at this stage of development, indicating that the initial main site of gonadotrophic action may be on medium sized follicles with two layers of granulosa cells.
Cathodoluminescence observations on biological compounds are compared with previously established data from ultra violet and visible light excitation studies. The comparison demonstrates that the same molecules are responsible for the luminescence properties of macromolecules independent of the type of exciting radiation. Natural cathodoluminescence was also observed from cells. Moreover, advantages gained by the absorption of strongly cathodoluminiscent dyes into cells are demonstrated.
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