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Biomedical subjects

R Dixon

Publications and source records attributed to R Dixon.

At least 181 records · Page 10Linked to original sources
PubMed1979

Phase II trial of cyclophosphamide, hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II) combination chemotherapy in advanced ovarian carcinoma.

A monthly four-drug regimen of cyclophosphamide, adriamycin, and cis-dichlorodiammineplatinum(II), each given iv of Day 1, and hexamethylmelamine, given orally on Days 1--14 (CHAP), was administered to 39 women with advanced epithelial ovarian carcinoma who had previously failed alkylating agent therapy. Of 35 evaluable patients with a measurable disease parameter, seven (20%) achieved a clinical complete response and ten (29%) achieved a clinical partial response. The median duration of complete response is greater than 9 months and the median duration of partial response is 4 months. Ninety percent of the patients required dose adjustments because of profound leukopenia, thrombocytopenia, or gastrointestinal intolerance. CHAP is an active but toxic regimen in the management of advanced ovarian cancer. The toxicity encountered reflected the intensity of the drug schedule as well as the combined influences of advanced stage of disease, poor nutritional and performance status, and prior therapy. The efficacy of this CHAP regimen warrants a controlled trial compared to other active drug programs.

Alkylating Agents↗
PubMed1978

Polarity of mutations induced by insertion of transposons Tn5, Tn7 and Tn10 into the nif gene cluster of Klebsiella pneumoniae.

Three new genes nifM, nifI and nifN have been mapped in the nif gene cluster of Klebsiella pneumoniae and a fourth gene nifJ has been confirmed as being a separate cistron. Polar nif mutations were obtained by transposition of Tn7 to plasmid pRD1, and of Tn5 and Tn10 to plasmid pMF100, a derivative of pRD1. Complementation analysis of the nif::Tn mutants led to the identification of at least six transcriptional units: nifB; nifA; nifJ; nifH, nifD and nifK; nifE and nifI; nifN, nifM and nifF. Biochemical and genetic evidence suggest that the three genes nifH, nifD and nifK, which are probably the structural genes for nitrogenase, belong to the same operon and are transcribed from nifH to nifK. A polypeptide with a molecular weight of approximately 120,000 is presumed to be the nifJ product.

Chromosome Mapping↗
PubMed1978

(-)-2-Hydroxy-n-cyclopropylmethylmorphinan: radioimmunoassay and phamacokinetic profile.

The pharmacokinetic profile of (-)-2-hydroxy-N-cyclopropylmethylmorphinan (HCMM), a narcotic antagonist and analgesic, has been evaluated in man following administration of 25 to 50 mg of the drug orally and 10 to 15 mg intramuscularly. A specific radioimmunoassay procedure was developed for the determination of HCMM in plasma and urine. The drug had a mean "apparent" elimination half-life in plasma of about 11 hr following both routes of administration. A mean of 47% of the oral dose was excreted in the urine as unconjugated and conjugated HCMM and only 5% of the dose was excreted as intact HCMM. In one subject studied, the plasma levels of conjugated HCMM were as much as 5-fold higher than the levels of unconjugated drug. Although there was considerable intersubject variability following both routes of administration, the overall pharmacokinetic parameters suggest that oral and intramuscular doses are bioequivalent.

Administration, Oral↗
PubMed1978

Dextromethorphan: radioimmunoassay and pharmacokinetics in the dog.

A specific radioimmunoassay (RIA) for the determination of the widely used non-narcotic antitussive agent, dextromethorphan (DM) in plasma and urine has been developed using an antiserum to DM which was obtained from rabbits following immunization with an albumin conjugate of (+)-3-methoxymorphinan-17-succinyloxyethyl. Specificity of the RIA was achieved by selective extraction of DM from its known metabolites into hexane at pH 6.5 with 86% recovery. Employing tritium labelled-DM as the radioligand the RIA had a limit of sensitivity of about 4 ng/ml of plasma using a 0.5 ml sample. Following I.V. administration of 2 mg/kg of DM to two dogs, the plasma levels of intact DM declined biexponentially; the terminal exponential phase having a half-life of 2.5-3.9 hr. The volume of distribution of the central compartment ranged from 5-6.4 l/kg while the metabolic clearance rate ranged from 2.5-2.6 1/hr/kg. Oral administration of 10 mg/kg of DM in gelatin capsule resulted in peak plasma levels of 50 and 92 ng/ml at 2 hr post-drug. Following both routes of administration, less than 3.5% of the dose was excreted in the urine as intact DM indicating almost complete biotransformation and/or alternate routes of excretion. In one human subject who received 0.5 mg/kg of DM P.O. in a syrup, the plasma levels were less than 1 ng/ml.

Animals↗
PubMed1977

Complementation analysis of Klebsiella pneumoniae mutants defective in nitrogen fixation.

A series of mutants defective in nitrogen fixation (nif) were isolated in Klebsiella pneumoniae strain M5a1. The nif mutations were either located on plasmid pRD1 or on the K. pneumoniae chromosome. A total of 37 plasmid mutants and 28 chromosomal mutants were employed in complementation tests using the acetylene reduction technique. Most mutants could be assigned to one of seven nif cistrons: nifA, nifB, nifD, nifE, nifF, nifH, and nifK. Complementation analysis of two nif deletion mutants confirmed transductional evidence that these strains carry nifB-A-F deletions. One deletion mutant had, in contrast to previous transductional analysis, a functional nifK cistron and presumably is deleted for nifB-A-F-E. Examination of the biochemical phenotype of several mutants suggests that the nifA product has a regulatory function, and nifK, nifD and nifH are most probably the structural genes for nitrogenase.

Chromosomes, Bacterial↗
PubMed1977

Pseudomonas species bacteremia caused by contaminated normal human serum albumin.

In May and June 1973, 11 patients on the surgical service at the University of Maryland Hospital had bacteremia caused by Pseudomonas species. Seven of the isolates recovered from blood cultures had the same antibiogram (sensitive only to chloramphenicol and tetracycline). Ten of the 11 patients were given 25% normal serum albumin (human) shortly before the onset of symptoms. In contrast, only two of seven patients with bacteremia due to Psuedomonas aeruginosa in May and June (P =0.013) and only nine of 20 patients located in surgical special care units during these months (P =0.014) were given this product. When cultured, the albumin in one of 54 previously unopened vials from the implicated lot yielded Pseudomonas cepacia sensitive only to chloramphenicol, tetracycline, and nalidixic acid. Subsequent investigation showed that five more patients in four other hospitals had symptoms of bacteremia shortly after the infusion of different lots of albumin from the same manufacturer, and in four cases P. cepacia was cultured from the suspect albumin. Since sterility testing by manufacturers may not detect low-frequency contamination, surveillance of nosocomial infections, investigation of unusual disease clusters, and prompt reporting of suspect reactions are essential in the control of such outbreaks.

Chloramphenicol↗
PubMed1977

Radioimmunoassay of the anti-hypertensive agent debrisoquin.

Antisera to debrisoquin, a widely used anti-hypertensive agent, have been obtained from rabbits following immunization with a conjugate of 4-[1,2,3,4-tetrahydroisoquinolin-2-yl)(imino)-methylamino] butanoic acid and bovine serum albumin. Employing tritium labelled debrisoquin as the radioligand for the antisera, a radioimmunoassay (RIA) was developed which allows for the specific determination of the drug directly in plasma. After logit transformation, a linear calibration line was obtained between 0.1 to 10 ng of unlabelled debrisoquin. The 4, 5, 6, 7 and 8-hydroxy derivatives of debrisoquion, known metabolites in man, showed less than 1.5% cross-reaction with the antisera. The specificity of the RIA was established when good agreement was obtained for the levels of debrisoquin in patients' plasma using the RIA and a specific GC/MS method. The simplicity of the RIA makes this method attractive for the routine clinical monitoring of the plasma levels and/or experimental protocols in which high sample throughput is required.

Animals↗
PubMed1977

Specific radioimmunoassay for amitriptyline and nortriptyline in plasma.

A specific radioimmunoassay (RIA) for the determination in plasma of the widely used tricyclic antidepressant amitriptyline (AT) and its major metabolite nortriptyline (NT) has been developed employing 3H-AT as the radioligand and a rabbit antiserum to a bovine serum albumin conjugate of N-succinyl-nortriptyline. Although the antiserum cross-reacts almost equally well with AT and NT, specificity is achieved by selective extraction of each compound from plasma at a different pH. A unique aspect of the assay is that at no time during the entire extraction procedure is the AT or NT taken out of solution. Both compounds are back extracted from the organic phase into 0.1 N HC1 and the acid fraction subjected to RIA directly. The method has a limit of sensitivity of about 2 ng/ml using a 0.5 ml sample of plasma. Satisfactory agreement was obtained for plasma levels of AT and NT when determined by the RIA and a specific GC/MS procedure. The correlation coefficients were 0.89 and 0.98 for AT and NT, respectively. THE RIA has been used to measure steady-state levels of AT and NT in man after chronic administration of AT and following a single oral 75 mg dose. The method also lends itself for the specific determination of NT alone in subjects receiving therapeutic doses of NT.

Amitriptyline↗
PubMed1977

An 125I-radioimmunoassay for the determination of the anticonvulsant agent clonazepam directly in plasma.

A simple and specific 125I-radioimmunoassay (RIA) for the determination of the anticonvulsant agent clonazepam directly in plasma has been developed using a previously reported antiserum to the drug. The 125I-radioligand was prepared by reaction of 3-aminoclonazepam with a commercially available acylating reagent, 125I-N-succinimidyl 3(4-hydroxyphenyl) propionate, of high specific activity (approximately 1500 Ci/mM). The method has a workable range between 5 and 100 ng/ml of clonazepam using a 10 mu1 sample of plasma for analysis, which is satisfactory for routine clinical monitoring. The intra and inter-assay coefficients of variation did not exceed 3 and 9% respectively. Recovery of clonazepam was quantitative when the drug was added to a pool of plasma obtained from subjects who had received a wide variety of other anticonvulsants. Clinical plasma samples from subjects receiving clonazepam chronically were assayed for clonazepam by the new 125I-RIA and a previously reported 3H-RIA. The data was subjected to linear regression analysis which gave a slope, intercept and correlation coefficient of 1,-0.33 ng/ml and 0.994 respectively and demonstrated that the two methods are equivalent. However, the 125I-RIA is more rapid and less costly for routine monitoring than the 3H-RIA.

Benzodiazepinones↗
PubMed1976

N-desmethyldiazepam: a new metabolite of chlordiazepoxide in man.

Following administration of chlordiazepoxide HCl to man, N-desmethyldiazepam, a known metabolite of diazepam (Valium), was identified in plasma. The metabolite was identified on the basis of its thin-layer chromatographic (TLC) mobility, electron-capture gas-chromatographic (EC-GC) retention time, and mass spectrum relative to authentic N-desmethyldiazepam. Plasma levels of N-desmethyldiazepam in subjects receiving both single and chronic doses of chlordiazepoxide were determined by an EC-GC method with a limit of sensitivity of 10 ng/ml using 2-ml samples and by a radioimmunoassay procedure which had a limit of sensitivity of 20 ng/ml using a 0.1-ml sample. Both assay methods gave good agreement for the levels of N-desmethyldiazepam. In subjects receiving a single 30-mg oral or intravenous dose of chlordiazepoxide, measurable levels of N-desmethyldiazepam in plasma (10 to 60 ng/ml) were obtained 24 to 72 hr after administration. In 5 subjects receiving 10 mg of chlordiazepoxide three times a day, steady-state levels of N-desmethyldiazepam in plasma were reached after about 1 wk of administration. The mean maximum and minimum steady-state levels of N-desmethyldiazepam were 260 and 220 ng/ml of plasma, respectively. Similar steady-state levels were observed on treatment with 30 mg of chlordiazepoxide over 24 hr.

Animals↗
PubMed1976

Simple modification of a liquid scintillation counter to decrease cost of and time for radioimmunoassay.

A simple, inexpensive modification in the elevator mechanism of a liquid scintillation counter allows for radioimmunoassay tubes (12 X 75 mm) containing the antibody-bound radioligand to be counted directly, thereby obviating the need for counting vials and considerably decreasing the amount of fluor used. Furthermore, because assay and counting are all done in the same tube, the modification shortens assay time and increases precision by avoiding what is often the most time consuming and inaccurate step, the transfer of antibody-bound radioligand to a counting vial. We find that use of this modification results in about a 75% decrease in the overall cost for materials and a substantial decrease in assay time.

Costs and Cost Analysis↗
PubMed1975

Quantitative determination of antibody in idiopathic thrombocytopenic purpura. Correlation of serum and platelet-bound antibody with clinical response.

We studied the clinical applicability of a recently developed technic that determines antiplatelet antibody directly on the platelet surface or in serum. The technic is a quantitative complement lysis-inhibition assay. Normal platelets have less than 0.4 pg of surface IgG. All patients with idiopathic thrombocytopenic purpura who were studied had greater than that value. Surface IgG was increased in inverse proportion to the platelet count. Surface levels of greater than 1.1 pg correlated with failure to respond to prednisone therapy. Incubation of normal serums with normal platelets did not increase surface IgG of such platelets, but the incubation with thrombocytopenic serums increased their surface IgG 0.5 to 100 times. The degree of increase did not predict response to treatment. However, quantitation of surface IgG of thrombocytopenic platelets was useful in predicting response to treatment.

Absorption↗