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Biomedical subjects

A R Taylor

Publications and source records attributed to A R Taylor.

At least 19 recordsLinked to original sources

Comparative biodisposition and metabolism of 14C-(+/-)-fenfluramine in mouse, rat, dog and man.

1. The comparative metabolism of fenfluramine was investigated in mouse, rat, dog and man following a single oral dose of 14C-(+/-)-fenfluramine hydrochloride (1 mg/kg), and also in rat after eight consecutive 12-h subcutaneous doses (24 mg/kg). 2. Main route of excretion of radioactivity in all species and at all doses was into urine (> 80%), with only minor amounts of radioactivity found in faeces. 3. From all species examined a total of 11 metabolites were observed in urine and plasma by t.l.c. and h.p.l.c. analysis and no metabolite was present in the plasma which was not present in urine. 4. All species dealkylate fenfluramine to the active metabolite norfenfluramine, to a relative greater or lesser extent, with plasma metabolic ratios (norfenfluramine/fenfluramine) showing inter-animal variation (rat >> dog >> mouse = man). 5. These differences are due to the efficient deamination of both compounds to polar inactive metabolites in man, with less dealkylation and lower plasma levels of norfenfluramine compared with the other species studied. 6. In conclusion, major species differences in the metabolism of (+/-)-fenfluramine, both qualitative and quantitative were observed, and no one species had a similar metabolic profile to that found in man.

Animals

An immunohistochemical study of papillary tumors in the central nervous system.

An immunohistochemical study was performed on the paraffin sections of 25 tumors in the central nervous system (CNS) with prominent papillary configurations. These tumors included seven metastatic papillary carcinomas, six choroid plexus tumors, four papillary ependymomas, two myxopapillary ependymomas, two papillary pituitary adenomas, two astroblastomas, one papillary meningioma, and one anaplastic astrocytoma with significant papillary changes. The panel of antibodies applied included anti-glial fibrillary acidic protein (GFAP), anti-carcinoembryonic antigen (CEA), anti-vimentin (VM), anti-S-100 protein (S-100 P), anti-cytokeratin, and anti-prealbumin antisera. All ependymomas and astroblastomas examined expressed both VM and GFAP, which were either absent or focally expressed in choroid plexus tumors. In contrast, all choroid plexus tumors showed anti-cytokeratin immunoreactivity that was absent in the ependymomas and astroblastomas. Five choroid plexus tumors also expressed S-100 P, thus differentiating them from metastatic carcinoma that showed negative immunostaining. Anti-CEA antisera immunoreactivity was seen in six metastatic tumors, whereas none of the primary CNS tumors expressed CEA. Prealbumin was expressed in four choroid plexus tumors and two metastatic tumors. Immunohistochemical typing using a panel of antibodies has allowed the differentiation of most of the papillary tumors in the CNS examined in this study.

Astrocytoma

Arabinosylcytosine-induced accumulation of DNA nicks in myotube nuclei detected by in situ nick translation.

This laboratory has recently reported the occurrence of DNA nicking at the onset of terminal skeletal myogenesis by using the technique of in situ nick translation (Dawson and Lough: Dev. Biol., 127:362-367, 1988). Because 1-beta-D-arabinofuranosylcytosine (araC), a cytocidal agent that is routinely used to removed dividing fibroblasts from myogenic cultures, inhibits DNA repair, it was of interest to determine whether araC treatment resulted in an accumulation of the endogenously created nicks. Thus, we have assessed the accumulation of DNA nicks in myotube cells during a 20 hour araC treatment period at the onset of terminal myogenesis (44-64 hours in vitro) by using three techniques: alkaline sucrose gradient density centrifugation, kinetic in situ nick translation, and cellular in situ nick translation. Although alkaline sucrose gradient centrifugation revealed no detectable nicking after 20 hours, kinetic in situ nick translation analysis revealed subtle but significant increases in DNA nicks caused by araC within 7 hours of drug application, and a 1.5-fold increase in DNA repair sites after 20 hours of drug treatment. That these observations reflected nicking specifically in myotube nuclei was determined by immunocytochemical localization of nicked sites after repair with a biotinylated nucleotide analog (biotin-11-dUTP). The effects of araC were only incompletely reversible, whether or not the drug was removed from the cultures, within 2 days of the treatment period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Disposition, pharmacokinetics, and metabolism of 14C-fotemustine in cancer patients.

The pharmacokinetics and metabolism of intravenously infused 14C-fotemustine (about 100 mg/m2) were examined in 2 cancer patients. Plasma levels of radioactivity increased to a maximum of 4.1 and 5.5 micrograms equivalents per g when the infusion stopped then declined triexponentially with mean half-lives of about 1/2, 10 and 80 h for the initial, mid and terminal phases, respectively. Plasma levels of intact drug were lower, with maximum levels of 1.1 and 2.8 micrograms/ml, and declined monophasically with a half-life of about 24 min. Plasma clearance was high (1426 and 764 ml/min) with the volume of distribution based on areas of 47.7 and 26.4 l. Most of the radioactivity was eliminated in urine (50.1 and 61.3%) over 7 days with smaller amounts in the feces (6.8 and 0.3%) and only minimal quantities (under 0.1%) as expired carbon dioxide. Metabolites of fotemustine were identified as chloroethanol and N-nitroso-1-imidazolone-ethyl-diethylphosphonate in plasma and as 1-hydantoin-ethyl-diethyl-phosphonate and acetic acid in urine.

Aged

Elbow synovectomy and excision of the radial head in rheumatoid arthritis: a short term palliative procedure.

We present the results of synovectomy and excision of the radial head in 65 elbows affected by rheumatoid arthritis. Eighty-four percent of elbows had good pain relief 6 months after operation but after an average of 5 years only 54% remained relatively pain-free. Range of motion remained the same or improved in the majority of patients. Synovitis occurred in 39% of elbows during the followup period and intraarticular steroid injections were frequently given. This undoubtedly modified results of pain relief that might have been attributed to the operation. Destructive changes in the humeroulnar joint were considered the main cause of elbow pain at the time of review.

Arthritis, Rheumatoid

The social adaptation of mainstreamed mildly retarded children.

The purpose of the present study was to assess the social adaptation of mainstreamed mildly retarded children, comparing them to a matched sample of regular education students. Results indicated that mildly retarded children were quite rejected by their peers, and, compared to nonretarded classmates, they reported significantly more dissatisfaction and anxiety about their peer relations. With respect to behavioral style, there were no group differences in peer- or teacher-reported aggressiveness or disruptiveness. However, retarded children were perceived as more shy and avoidant, as less cooperative, and as less likely to exhibit leadership skills. Further analysis of the behavioral assessment data, via cluster analysis, revealed 2 subtypes of rejected retarded children: an internalizing group perceived as displaying high levels of shy/avoidant behavior and an externalizing group perceived as high in aggressive and/or disruptive behavior. In addition, the internalizing group reported higher social anxiety than did the externalizing group. Implications for school-based intervention research with mildly retarded children are discussed.

Achievement

Interaction of the recA protein of Escherichia coli with single-stranded DNA.

The interaction of recA protein with single-stranded (ss) phi X174 DNA has been examined by means of a nuclease protection assay. The stoichiometry of protection was found to be 1 recA monomer/approximately 4 nucleotides of ssDNA both in the absence of a nucleotide cofactor and in the presence of ATP. In contrast, in the presence of adenosine 5'-O-(thiotriphosphate) (ATP gamma S) the stoichiometry was 1 recA monomer/approximately 8 nucleotides. No protection was seen with ADP. In the absence of a nucleotide cofactor, the binding of recA protein to ssDNA was quite stable as judged by equilibration with a challenge DNA (t1/2 approximately 30 min). Addition of ATP stimulated this transfer (t1/2 approximately 3 min) as did ADP (t1/2 approximately 0.2 min). ATP gamma S greatly reduced the rate of equilibration (t1/2 greater than 12 h). Direct visualization of recA X ssDNA complexes at subsaturating recA protein concentrations using electron microscopy revealed individual ssDNA molecules partially covered with recA protein which were converted to highly condensed networks upon addition of ATP gamma S. These results have led to a general model for the interaction of recA protein with ssDNA.

Adenosine Diphosphate

Simple external fixation of open and complicated fractures.

Thirty patients were managed with the use of a simple means of external fixation. Ten of these patients had multiple injuries. In 18 the fractures were open. Five cases had loss of bone length and infected wounds when first seen and were treated with the aid of microvascular surgical procedures. Eight cases required skin grafting. One case required a vein graft to the popliteal artery. The method described is simple to use. It requires little previous experience and is cost effective. We recommend its use in the initial treatment of grade 2 and 3 open fractures. It may also be used on closed unstable fractures, and will maintain limb length in severe injuries with loss of bone substance while further treatment is considered or performed.

Bone Screws

Photolytic decomposition of indapamide.

Photolytic decomposition of indapamide (I) in nitrogen-flushed methanol yields 3-sulfamoyl-4-chlorobenzamide (II), 2-methylindoline (III), semicarbazide (IV), and 1-(N-formamido)-2-methylindoline (V); in oxygen-flushed methanol, II--V, 1-aminocarboxymethyl-2-methylindoline (VI), 3-sulfamoyl-4-chlorobenzoic acid (VII), methyl-3-sulfamoyl-4-chlorobenzoate (VIII), and 2-(N-acetamido)-benzoic acid (IX) are formed. A comparison is made with thermal decomposition of I.

Chemical Phenomena

Potential hazard of methylene blue.

The administration of methylene blue to assist the identification of insulin secreting pancreatic adenomata, during surgery in a patient with normal haemoglobin and red cells, was associated with an increase in the methaemoglobin concentration from 0.6% to 7.1%. In patients with unstable haemoglobins or abnormalities of the hexose monophosphate pathway the administration of large amounts of methylene blue is potentially dangerous.

Adenoma

Arthroplasty of the hip in ankylosing spondylitis.

In fifty-six patients with ankylosing spondylitis three types of arthroplasty had been performed in ninety-nine hips. Forty-one of the patients were men and fifteen were women, their average age at operation being forty-two years. Primary pseudarthrosis produced well-satisfied patients, but only a fair result in five hips, whereas cup arthroplasty resulted in a poor outcome for eight hips, all of which needed revision. Total replacement of eighty-six hips, however, led to 73 per cent being graded as good or excellent up to ten years later. The main complications were deep infection of five hips, para-articular ossification around nine hips (six leading to bony ankylosis), and fibrous ankylosis of six hips.

Adult

Excision of the head of the radius in rheumatoid arthritis.

The results of excision of the head of the radius in forty-four elbows affected by rheumatoid arthritis are presented. Relief of pain was obtained in 90 per cent and an increase in the range of flexion and extension was seen in 70 per cent. Involvement of the humero-ulnar joint seen radiologically is no contra-indication to the operation; simple excision of the radial head often gives gratifying results; In our experience the relief of pain and increased range of movement have greatly reduced the need for total replacement arthroplasty.

Adult

Obituary notices.

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History, 20th Century

Effects of structural variation in beta-monoglycerides and other lipids on ordering in synthetic membranes.

Studies of beta-monoglyceride multilayers were carried out using a variety of spin probes. Effects of variables such as chain length, unsaturation, and branching on organization of acyl chains in lipids of model membranes were assessed. In addition, effects of added cholesterol on membrane order were determined. Results indicated that pure beta-monolaurin yields highly ordered films, whereas, unsaturated glycerides such as beta-monoolein, beta-monolinolein, and analogous lecithins yield fluid films. Branched monoglycerides behaved similarly to beta-monoolein, suggesting that branching in acyl chains is an effective substitute for unsaturation in maintaining membrane integrity. Multilayers of beta-monoglycerides exhibited similar properties to those of more complex lipids such as phospholipids. beta-Monoglycerides, by virtue of the presence of a single acyl chain, provided a relatively simple and effective alternative to the use of phospholipids in studies of membrane architecture.

Binding Sites