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Biomedical subjects

R Dixon

Publications and source records attributed to R Dixon.

At least 163 records · Page 9Linked to original sources
PubMed1982

Midazolam: radioimmunoassay for pharmacokinetic studies in man.

A specific radioimmunoassay (RIA) for the determination of the new short-acting water soluble imidazo-1,4-benzodiazepine, midazolam, directly in plasma has been developed. Employing 3H-midazolam as the radioligand and a rabbit antiserum to a diazo conjugate of 5'-aminomidazolam and albumin, the method has a limit of sensitivity of 2 ng/ml of midazolam using a 20 microliters sample of plasma. The intra- and inter-assay coefficients of variation ranged from 4 to 7% and 13 to 15%, respectively. The specificity of the RIA was established by demonstrating good agreement with both EC-GC and GC-MS procedures in the analysis of multiple clinical plasma samples. The utility of the RIA for the pharmacokinetic evaluation of midazolam is illustrated with plasma concentration profiles of the drug obtained in subjects who had received midazolam intravenously, intramuscularly and orally.

Animals↗
PubMed1981

Contrasts between the response of the mouse haemopoietic system to 5-fluorouracil and irradiation.

We have studied the response of the mouse haemopoietic system to 5-fluorouracil, to shielded-limb irradiation and to total-body irradiation plus bone marrow injection. We have also studied the response to a dose of 5-FU given 10 weeks subsequent to each of these treatments. After 5-FU, the CFUs number rises rapidly reaching levels well above normal 11 days after treatment but the GM-CFC numbers increase more slowly and remain subnormal. By contrast, the GM-CFC number reaches normal 3-4 weeks after partial-body irradiation or irradiation/reconstitution although the CFUs number rises slowly and does not reach pre-treatment levels. Two possible explanations of the difference are discussed; one is that irradiation damages the haemopoietic environment in a way which prohibits fast proliferation of CFUs, the other that 5-FU inhibits the differentiation of CFUs into committed precursors. No difference which could be attributed to the exposure of stem cells to artificial media was seen between the responses to partial-body irradiation and to transplantation. The response to a subsequent dose of 5-FU was the same in all groups indicating that radiation damage to the stroma is either non-existent after 850R, or is repaired within 10 weeks, or is irrelevant to the recovery from 5-FU.

Animals↗
PubMed1981

Levorphanol: a simplified radioimmunoassay for clinical use.

A recently reported radioimmunoassay (RIA) procedure (Res. Comm. Chem. Pathol. Pharmacol 29, 535, 1980) developed for the quantitation of the narcotic analgesic, levorphanol, in dog plasma has been simplified for clinical use using the original antiserum to an albumin conjugate of (-)-3-hydroxy-N-carboxymethylmorphinan. Due to the absence of and/or insignificant concentrations of the cross-reactive metabolite, nor-levorphanol, in human plasma, the new simplified procedure allows for the specific quantitation of levorphanol directly in clinical plasma samples, thereby circumventing the extraction and chromatographic steps of the original procedure. The direct procedure has a limit of sensitivity of 1 ng/ml of levorphanol using a 20 microliter sample of plasma and is ideally suited for the routine determination of steady state plasma concentrations of levorphanol in patients receiving various therapeutic doses of the drug. In two subjects studied the apparent half-lives of elimination of levorphanol from plasma were 10 and 16 hr. The characteristics and use of another antiserum to levorphanol, obtained by immunization of rabbits with an albumin conjugate of (-)-3-O-carboxymethyl-N-methylmorphinan, is discussed.

Animals↗
PubMed1981

Tricyclic antidepressants: a simplified approach for the routine clinical monitoring of parent drug and metabolites in plasma using HPLC.

A simplified procedure for the routine clinical monitoring of amitriptyline, nortriptyline, imipramine and their metabolites in plasma using high performance liquid-chromatography (HPLC) has been developed. Commonly encountered problems in the analyses of tricyclic antidepressants such as low recovery, adsorption to glass and extensive "clean-up" procedures have been avoided by judicious choice of solvents, extraction procedures and chromatographic technique. The method involves a single extraction of 1 ml of plasma at pH 10.5 with iso-octane:methyl t-butyl ether (9:1) in a disposable polypropylene tube, solvent transfer to and evaporation in a similar tube followed by direct HPLC of the extract on a 10 micrometer silica gel column using methanol containing 0.1% concentrated ammonium hydroxide as the mobile phase and detection at 254 nm. Good chromatographic separation of amitriptyline (AT), 10-hydroxy-amitriptyline (10-OH-AT), nortriptyline of amitriptyline (NT), 10-hydroxy-nortriptyline (10-OH-NT), imipramine (IM) and desmethyl-imipramine (DMI) is achieved. IM is used as an internal standard for the analysis of plasma samples from patients receiving AT and NT, while NT is used as the internal standard for analysis of IM and its metabolite DMI. Overall recoveries exceed 80% and the limits of sensitivity are about 25 ng/ml for each compound quantitated. Although the utility of the method is illustrated in the analysis of a selection of plasma samples from patients receiving various therapeutic doses of AT, NT and IM, it would appear that the procedure offers a simplified approach for the analysis of other tricyclic antidepressants in a clinical setting.

Amitriptyline↗
PubMed1981

The effect of anterior orbital decompression on motility in thyroid exophthalmos.

Nineteen orbits from 13 patients with endocrine exophthalmos were effectively decompressed into the maxillary and ethmoid antra through an anterior orbitotomy. Six patients with preoperative diplopia had improved ocular ductions and return of binocular single vision in functional positions. Diplopia was not induced in five patients with normal pre-op motility. In one patient with active orbitopathy, a large postoperative esotropia was caused by worsening of medial rectus inflammation. This approach appears to lessen the incidence of postoperative diplopia and may make subsequent extraocular muscle procedures unnecessary.

Adult↗
PubMed1981

Haemopoietic stem cells: possibility of toxic effects of 5-fluorouracil on spleen colony formation.

Spleen colony formation (Till and McCulloch, 1961) by cells collected from mice treated with the cytotoxic drug 5-fluorouracil (5-FUBM) differs from spleen colony formation by normal bone marrow cells (NBM). The number of spleen colonies formed after the graft of 5-FUBM rises with the passage of time since the graft (extra spleen colonies). It does not after the graft of NBM. Hodgson and Bradley (1979) proposed that extra spleen colonies might form in this way: a progenitor of CFUs ('the pre-CFUs') seeded preferentially to the marrow of recipient mice. It formed CFUs there which migrated to the spleen and formed extra colonies. This hypothesis, if it were true, would support another hypothesis, the generation-age hypothesis (Rosendaal et al., 1976, 1979), which proposes that the number of divisions there have been in the history of a stem cell is one determinant of the order in which they start cycling to form other stem cells and differentiated cells. We investigated four possible sources of extra colonies. They might arise by reseeding of CFUs formed in the marrow or the spleen; they might arise from CFUs which settle in spleen but require a variable time until they can start to cycle, or they might arise after a variable time as CFUs repair the damage done them by 5-FU. We have established that the CFUs which eventually form spleen colonies are in the spleens of recipients 24 hours after the graft. Extra colonies too, do not arise by reseeding of CFUs formed in the spleens of recipients. It is possible that extra colonies arise as CFUs repair the damage done by 5-FU.

Animals↗
PubMed1980

Analysis of regulation of Klebsiella pneumoniae nitrogen fixation (nif) gene cluster with gene fusions.

Gene fusions in which the lac genes are under the control of each promoter in the Klebsiella pneumoniae, nitrogen fixation (nif) gene cluster have been constructed. These fusions have been used to examine positive control of the cluster and the response of individual genes to repression by ammonia and oxygen. De-repression of nif transcriptional units is coordinate and molybdate is required for maximal expression of the structural gene operon, which is autogenously regulated.

Ammonia↗
PubMed1980

Determination of estramustine and its 17-keto metabolite in plasma by high-performance liquid chromatography.

A rapid, sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed for the determination of estramustine and its 17-keto metabolite in plasma. The assay involves extraction of the compounds into hexane from plasma buffered to pH 9.0, the residue obtained by evaporation of the hexane extract is dissolved in the mobile phase hexane-ethanol (92.5:7.5) with HPLC analysis performed on a 5-micrograms silica gel column using a fluorescence detector with excitation at 195 nm and emission at wavelengths greater than 250 nm. The overall recoveries and limits of sensitivity for estramustine and the 17-keto metabolite are 74.7% and 40 ng/ml of plasma and 85.1% and 50 ng/ml of plasma, respectively. The method was used to obtain plasma concentration-time profiles in three subjects with prostatic cancer following oral administration of a single 7 mg/kg dose of estramustine phosphate.

Chromatography, High Pressure Liquid↗
PubMed1980

Radioimmunoassay of flurazepam in human plasma.

A radioimmunoassay for the determination of the hypnotic flurazepam in plasma was developed. Plasma levels of intact flurazepam were measured following oral administration of therapeutic doses to humans. The procedure employs an antiserum obtained from a rabbit immunized with 3-hemisuccinyloxyfluorazepam covalently coupled to bovine serum albumin and tritium-labeled flurazepam as the radioligand. Assay specificity was achieved by chromatographic isolation of flurazepam from plasma extracts on Sephadex LH-20 prior to analysis. The method has a sensitivity limit of 0.1 ng of flurazepam/ml using a 1-ml plasma sample, and the intra- and interassay coefficients of variation did not exceed 9% over a range of 0.1-5 ng/ml. In eight subjects who received a single 30-mg dose of flurazepam, peak plasma concentrations of 0.5-3.0 ng of intact drug/ml were reached after 0.5-1 hr, except in one subject where the peak occurred at 4 hr. The plasma concentrations of flurazepam declined with a harmonic mean apparent half-life of 2.3 hr.

Chromatography, Ion Exchange↗
PubMed1980

The use of translocatable genetic elements to construct a fine-structure map of the Klebsiella pneumoniae nitrogen fixation (nif) gene cluster.

The transposons Tn5, Tn7 and Tn10 and bacteriophage Mu have been used to derive insertion mutations in the Klebsiella pneumoniae nif gene cluster. A large number of deletion mutants have been derived by imprecise excision of insertion mutations and these deletions have been used to construct a fine-structure map of the nif cluster. Comparison of this genetic map with a physical map of the nif cluster derived by Reidel et al. (1979) showed a very good correlation between genetic and physical mapping methods. A new complementation group, designated nifU, has been identified and mapped between nifN and nifS. Polarity studies on the 14 nif cistrons now identified suggests that they are organized in at least seven transcriptional units and that all the multicistronic units are transcribed in the same direction.

Chromosome Deletion↗
PubMed1980

Estramustine phosphate: plasma concentrations of its metabolites following oral administration to man, rat and dog.

Estramustine phosphate, a nitrogen mustard derivative of estradiol used for the treatment of advanced prostatic cancer, was administered orally to man, rat and dog and the plasma concentrations of its unconjugated metabolites were determined by high performance liquid chromatography. In all species the drug was rapidly and completely dephosphorylated prior to reaching the peripheral circulation. In man and the rat, the 17-keto analogue of estramustine (estromustine) was the mamor metabolite found in plasma with considerably lesser amounts of estramustine itself. In the dog, significant concentrations of both estramustine and estromustine were present. Highly elevated levels of both estrone and estradiol, as a result of cleavage of the nitrogen mustard from the steroid, were observed in all species. Chronic administration of therapeutic doses of estramustine phosphate to man did not result in any apparent accumulation of circulating metabolites. The study suggests that the metabolite, estromustine, in addition to estramustine, may play an important role in the therapeutic efficacy of estramustine phosphate.

Administration, Oral↗
PubMed1980

Chlordiazepoxide concentrations in saliva and plasma measured by radioimmunoassay.

A new, sensitive and specific radioimmunoassay (RIA) for chlordiazepoxide was used to determine concentrations of the drug in microsamples of saliva and plasma obtained from subjects following intravenous and oral administration of the drug. Saliva and plasma concentrations of the drug were highly correlated (r = 0.95) and the saliva/plasma ratio had a mean value of about 0.03. Saliva levels of chlordiazepoxide were found to be equal to the concentration of unbound drug in the plasma. Drug half-lives determined from both plasma and saliva concentration-time curves were found to be equivalent.

Chlordiazepoxide↗
PubMed1980

Levorphanol:radioimmunoassay and plasma concentration profiles in dog and man.

A specific radioimmunoassay (RIA) procedure has been developed for the determination of the narcotic analgesic, levorphanol, in plasma using a rabbit antiserum to an albumin conjugate of (-)-3-hydroxy-N-carboxymethylmorphinan. Assay specificity was achieved by chromatogrphic isolation of levorphanol from plasma extracts on Sephadex LH-20 prior to analysis. The method has a limit of sensitivity of about 0.5 ng/ml of levorphanol using a 0.1 ml sample of plasma. Steady-state plasma concentrations of levorphanol have been determined for the first time in two cancer patients receiving chronic therapeutic doses of the drug. The plasma concentration-time profile for levorphanol following i.v. administration of 2 mg/kg to a dog declined biexponentially and the terminal elimination phase had a half-life of 2.4 hr. When another dog received orally 7 mg/kg of the drug in aqueous solution, the normalized area under the plasma concentration-time curve of intact levorphanol was less than 2% of the are observed after i.v. administration and suggests extensive "first-pass" metabolism of the drug in the dog.

Administration, Oral↗
PubMed1980

Radioimmunoassay and plasma concentrations of the anti-allergenic agent, 2-methoxy-11-oxo-11-H-pyrido[2,1-b]quinazoline-8-carboxylic acid in man.

A specific radioimmunoassay (RIA) for the determination of the antiallergenic agent, 2-methoxy-11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acid (I), directly in plasma has been developed employing a rabbit antiserum to an albumin conjugate of I. The RIA has a limit of sensitivity of 0.4 ng/ml of I using a 0.1 ml sample of plasma. The intra- and interassay coefficients of variation did not exceed 6 and 9%, respectively. The specificity of the RIA was established by comparison with a less sensitive high-performance liquid chromatographic procedure and excellent agreement (r = 0.98) was observed when plasma samples were assayed by both methods. The RIA was used to determine plasma concentrations of I in man, for the first time, following oral administration of single 2, 10 and 50 mg doses of the drug.

Adult↗
PubMed1979

Medial ectropion. A new technique.

Medial ectropion of the lower lid responds poorly to standard ectropion procedures. This region contains the initial parts of the nasolacrimal excretory system, which must be functionally reestablished. A new surgical approach to medial ectropion consists of a Z-plasty transposition skin flap from the upper to the lower lid, a plication of the lower crus of the medial canthal tendon, and a punctoplasty. The posterior and superior contraction forces in the transposition flap enhance and maintain the result. Seven lids have been successfully operated on with this technique from the functional and cosmetic point of view.

Aged↗