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Biomedical subjects

D S Robinson

Publications and source records attributed to D S Robinson.

At least 163 records · Page 9Linked to original sources
PubMed1985

Operative risks in patients with colorectal cancer.

This study emphasizes the risks in the operative treatment of patients with colorectal cancer. In dissecting our overall operative mortality of 7.4 per cent in consecutive patients over a 5-year period, three factors influencing the outcome were identified. These were the age of the patient, the stage of the disease, and the availability of preoperative bowel preparation by mechanical cleansing and antibiotic suppression of the colonic bacterial flora. Earlier diagnosis and elective resection of prepared bowel offers marked improvement in the operative risk for patients with colorectal cancer.

Adenocarcinoma↗
PubMed1985

Metabolism and pharmacokinetics of phenelzine: lack of evidence for acetylation pathway in humans.

Earlier studies have suggested that patients with slow acetylation phenotype were more likely to respond to phenelzine treatment and more likely to experience side effects. The metabolism of phenelzine has not been extensively investigated in humans because of limitations in analytical methodology. A labeled form of phenelzine is required for metabolite identification because these same compounds can arise from endogenous substances e.g., phenylacetic acid. The use of a stable isotope-labeled compound has the advantage that in vivo studies can be performed without radiation exposure. Site-specific, stable isotope-labeled phenelzine analogs were synthesized and used in metabolic and pharmacokinetic studies in humans. The authors were unable to detect N-acetylphenelzine in any urine or plasma samples. The major metabolites phenylacetic acid and parahydroxyphenylacetic acid constitute up to 79% of the administered dose excreted via the urine in the first 96 hours. These studies indicate that N-acetylation of phenelzine is not a significant metabolic pathway in humans, which helps explain recent clinical studies that failed to find an association between acetylation phenotype and clinical effects of phenelzine.

Acetylation↗
PubMed1984

The use of heparin-sepharose affinity chromatography to separate two distinct lipoproteins from the low density lipoprotein fraction of rat plasma.

Heparin-Sepharose affinity chromatography resolved rat lipoproteins isolated in the density range 1.019-1.063 g/ml into two distinct fractions. The first, which eluted with 150 mM NaCl, was shown by immunodiffusion and by polyacrylamide gel electrophoresis to contain predominantly apo E. On this basis the major lipoprotein present is identified as high density lipoprotein1 (HDL1). The second, eluted with 325 mM NaCl, contains predominantly apoprotein B by the same techniques. The main lipoprotein present is therefore identified as low density lipoprotein (LDL). The lipid composition of the two lipoproteins is similar. Both are rich in cholesterol ester, with a free to ester cholesterol ratio of about 1 to 2.5. From lipid and protein analyses on the two fractions, the plasma concentrations of HDL1 and LDL can be calculated to be about 14 and 12 mg/100 ml, respectively. Their mean diameters are 13 +/- 2 nm and 18 +/- 5 nm, respectively.

Animals↗
PubMed1984

Torsade de pointes: a mechanism for sudden death associated with neuroleptic drug therapy?

An elderly institutionalized woman developed the ventricular arrhythmia torsade de pointes while receiving lithium and thioridazine, 800 mg daily. On hospital admission following a single syncopal episode the electrocardiogram showed sinus bradycardia with first degree AV block, markedly prolonged QT interval, and prominent U waves. Following discontinuation of thioridazine and lithium, episodes of recurrent torsade de pointes gradually subsided. Seven days later the electrocardiogram showed normal sinus rhythm with PR interval of 0.20 seconds and minimal U waves, and the arrhythmia has not recurred.

Aged↗
PubMed1983

Pharmacokinetics and pharmacodynamics of drug delivery.

The complex pharmacokinetics that promote transit of a drug from ingestion to elimination are characterized by variability. The rate and degree to which a drug undergoes absorption, distribution, biotransformation and excretion are a result of both endogenous and exogenous factors, some of which can be predicted, many of which cannot. One of the greatest problems associated with conventional drug formulations has been the dose-related appearance of side-effects that often accompany the initial surge of drug release. Drugs with short half-lives or narrow therapeutic ratios may alternately produce over-medication and under-medication in a patient. Innovations in drug form design have resulted in a new precision-release formulation that permits zero-order steady state drug release. Sodium indomethacin trihydrate ('Osmosin') is the first drug to be contained within this new precision-release formulation which approaches the objective of delivering drugs at a therapeutically optimal rate.

Absorption↗
PubMed1983

Plasma levels of catecholamines and dihydroxyphenylglycol during antidepressant drug treatment.

Plasma norepinephrine, epinephrine, and 3,4-dihydroxyphenylglycol levels were measured in depressed outpatients treated in a double-blind controlled clinical trial with 150 mg/day of amitriptyline or 60 mg/day of phenelzine for 6 weeks. Both antidepressant drug treatments were associated with a significant decline in plasma dihydroxyphenylglycol concentrations, which was more pronounced with phenelzine. Plasma norepinephrine levels also declined during phenelzine but not amitriptyline treatment, and the posttreatment values correlated with clinical improvement with the monoamine oxidase inhibiting drug. Reductions in norepinephrine and dihydroxyphenylglycol correlated highly with the degree of platelet monoamine oxidase inhibition. Mechanisms of these antidepressant drug effects on amine metabolism and their implications are discussed.

Adult↗
PubMed1982

Purification and characterization of rat adipose tissue lipoprotein lipase.

Lipoprotein lipase (EC 3.1.1.34) extracted from adipose tissue of glucose-fed rats with 5 mM-sodium barbital, pH 7.5, containing 20% (v/v) glycerol and 0.1% (v/v) Triton X-100, was partially purified by affinity chromatography on heparin linked to Sepharose 4B. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the partially purified enzyme preparation revealed the presence of two major Coomassie-staining bands (mol.wts. 62 000 and 56 000) as well as a number of minor bands. Treatment of partially purified enzyme with [1,3-3H]di-isopropyl fluorophosphate resulted in the incorporation of radiolabel into the band of mol.wt. 56 000, but not into the band of mol.wt. 62 000. Both the amount of the 56 000-mol.wt. polypeptide and the incorporation of [1,3-3H]di-isopropyl fluorophosphate into this band were greatly reduced in the enzyme preparations isolated from adipose tissue of 48 h-starved rats. whereas the amount of the 62 000-mol.wt. polypeptide was unaffected by starvation. Purification of lipoprotein lipase from adipose tissue of glucose-fed rats was also carried out using affinity chromatography on Sepharose 4B linked to heparin with low affinity for antithrombin-III. This procedure resulted in the presence of a single band of mol.wt. 56 000 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. These results suggest that the polypeptide of mol.wt. 56 000 corresponds to the subunit of lipoprotein lipase, whereas the 62 000-mol.wt. polypeptide probably represents antithrombin-III.

Adipose Tissue↗
PubMed1982

The influence of antigen density and a comparison of IgG and IgM antibodies in the anti-complementary modulation of lymphocytic surface immunoglobulin.

Experiments were carried out to determine the influence of antigen density on anti-complementary modulation, defined here as the conferring by anti-immunoglobulin (Ig) of resistance to lysis of guinea pig L2C leukaemic cells varied widely in their quantitative expression of surface membrane Ig as judged by the binding to cells of 125I-labelled Fab' fragments from anti-Ig, and a good correlation between the bulk antigen density and the percentage of cells lysed by anti-Ig plus C was obtained (P=0.02). In the presence of 10 mM sodium azide, which has been shown to diminish the modulation occurring during simultaneous incubations with anti-Ig and C, this correlation was even stronger (P less than 0.001). No zone could be defined in which the level of surface Ig expression was sufficient to serve complement lysis but too low for modulation. Furthermore, both the degrees and rates of modulation occurring on incubation with antibody at 37 degrees C, either before C addition or in the presence of lytic C, were similar for populations of high, low, or intermediate antigen density. Separation of cells by their size or density failed to yield populations differing in either their susceptibility to humoral killing through anti-Ig or their modulating capacity. IgG and IgM antibodies to the L2C cell surface Ig evoked similar levels of killing with syngeneic C, and when compared for their ability to promote anti-complementary modulation, no difference was revealed in either the rate or degree of modulation occurring during incubations at 37 degrees C with the two isotopes. The findings are discussed with particular reference to observations on the modulation of mouse thymus leukaemia (TL) antigens.

Animals↗
PubMed1982

Cardiovascular effects of phenelzine and amitriptyline in depressed outpatients.

Blood pressure and ECG changes were monitored in depressed outpatients treated for 6 weeks with amitriptyline, 150 mg/day, or phenelzine, 60 mg/day, as part of an ongoing double-blind study. Phenelzine produced significant decreases in blood pressure and a significant increase in orthostatic fall in pressure. Amitriptyline produced little overall change in blood pressure. The degree of MAO inhibition in phenelzine-treated patients was significantly correlated with blood pressure. Tricyclic plasma concentrations were also related to some blood pressure measures. Reported dizziness/faintness did not correlate with blood pressure changes in either group. Amitriptyline significantly increased heart rate, while phenelzine produced slowing. Amitriptyline was associated with significant prolongation of QRS and QTc but not PR intervals. Phenelzine produced significant shortening of the QTc interval.

Adult↗
PubMed1981

The removal of partially metabolized very-low-density lipoproteins by the perfused rat liver.

1. Donor perfused rat livers were used to prepare VLD (very-low-density) lipoproteins, labelled in their triacylglycerol and protein components with [1-14C]oleic acid and L-[4,5-3H]leucine respectively. Partially metabolized VLD lipoproteins, similarly labelled, were obtained from supradiaphragmatic rats injected with the parent VLD lipoproteins. 2. The triacylglycerol and protein components of the partially metabolized VLD lipoproteins were removed by recipient perfused rat livers at rates much higher than those of the parent VLD lipoproteins. No degradation of the partially metabolized VLD lipoproteins to LD (low-density) lipoproteins occurred during the perfusions. 3. Removal of hepatic lipase from the livers did not significantly affect the rate of removal of the partially metabolized VLD lipoproteins.

Animals↗
PubMed1981

Phenytoin-salicylate interaction.

Ten healthy adult subjects took a single daily dose of phenytoin for 9 days to achieve a steady-state serum phenytoin concentration in the therapeutic range. While continuing on phenytoin, subjects took increasing doses of salicylate in a step-wise fashion, each dose (325, 650, and 975 mg) given every 4 hr for 48 hr. Serum (total) and salivary (free) phenytoin concentrations and serum salicylate concentrations were measured before and after each dose level of salicylate. Protein binding displacement of phenytoin by salicylate occurred only at the highest salicylate dose. Serum phenytoin control levels fell from 13.5 +/- 1.2 to 10.3 +/- 0.8 micrograms/ml (p less than 0.01), salivary phenytoin levels rose from 0.97 +/- 0.09 to 1.13 +/- 0.12 micrograms/ml (p less than 0.05), and phenytoin free fraction (salivary/serum ratio) increased from 7.14 +/- 0.34% to 10.66 +/- 0.57% (p less than 0.01) in the highest salicylate dose periods. There was no difference in these parameters during low-dose or intermediate-dose salicylate therapy. Linear-regression analysis failed to show a relationship between serum salicylate concentration and serum or salivary phenytoin concentration. Although high-dose salicylate induced protein binding displacement of phenytoin, it is unlikely that this is of clinical importance since the rise (16%) in the free (salivary) phenytoin concentration was small. Serum total phenytoin concentration may fall during salicylate therapy but the dose of phenytoin should not be altered unless there are overt signs of toxicity.

Adult↗
PubMed1981

Antigenic modulation of lymphocytic surface immunoglobulin yielding resistance to complement-mediated lysis. I. Characterization with syngeneic and xenogeneic complements.

Following previous authors, the term antigenic modulation is used to describe the induction, by antibody, of resistance to lysis by antibody plus complement. A report is given of the rapid antigenic modulation in vitro of surface immunoglobulin (Ig) on guinea-pig L2C leukaemic lymphocytes: incubation of the cells for 2 min or longer at 37 degrees with anti-Ig diminished or removed completely the lysis occurring during subsequent incubation with anti-Ig plus complement. The modulation was effective for both xenogeneic (rabbit) and syngeneic (guinea-pig strain 2) complements, but more rapid for the latter. It appeared simply to require the action of antibody on a metabolically active cell: no requirement could be demonstrated for any serum component other than antibody, and there was a need to raise the temperature to 37 degrees after attachment of the antibody. There was molecular specificity inasmuch as modulation with anti-Ig failed to confer any resistance to lysis by another antibody (anti-Ia) plus complement.

Animals↗