Biomedical subjects
S Paterson
Publications and source records attributed to S Paterson.
Political power and the health care manager.
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Air cushion mower foot injuries.
AIMS: This study was undertaken to identify significant physical, social and psychological problems resulting from injuries caused to the feet by air cushion mowers. METHODS: Thirty-four patients seen with air cushion mower injuries were reviewed, either by personal assessment, or by questionnaire. RESULTS: A large number of patients had significant symptoms relating to their soft tissue or bone injuries, the majority experiencing some pain, and those who had amputations difficulty in some aspects of walking. CONCLUSIONS: Better education of the dangers of the misuse of these mowers may reduce the incidence of significant forefoot injuries.
Pharmacokinetics of dipipanone after a single oral dose.
A single oral dose of Diconal (dipipanone HCl 10 mg, cyclizine HCl 30 mg) was given to six volunteers. The mean peak plasma dipipanone concentration was 29 ng ml-1, the time to peak plasma concentration was 1-2 h, the mean elimination half-life was 3.5 h and the mean AUC was 156 ng ml-1 min. Less than 1% of the dose was excreted in urine unchanged over 24 h.
Correlation of tissue, blood, and air partition coefficients of volatile organic chemicals.
The physical chemical factors controlling partition coefficients between air, water, blood, and various tissues are discussed. It is suggested that improved insights into the relations between partition coefficients, which are frequently expressed as correlations, may be obtained by viewing the partition coefficients as ratios of solubilities or pseudosolubilities. A simple, novel correlation approach is developed and applied to 24 volatile organic chemicals, which enables tissue/blood, tissue/air, and blood/air partition coefficients to be estimated from water solubility and vapour pressure. An illustration is presented in which these solubilities are used to calculate the equilibrium distribution of dichloromethane between air, blood, and various tissues.
Measurement of dipipanone using capillary gas chromatography.
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A pharmacokinetic model of styrene inhalation with the fugacity approach.
The physiologically based pharmacokinetic model of J. C. Ramsey and M. E. Andersen (1984, Toxicol. Appl. Pharmacol. 73, 159-175) of styrene inhalation in rats, with extrapolation to humans, was reformulated with the chemical equilibrium criterion of fugacity instead of concentration to describe compartment partitioning. Fugacity models have been used successfully to describe environmental partitioning processes which are similar in principle to pharmacokinetic processes. The fugacity and concentration models are mathematically equivalent and produce identical results. The use of fugacity provides direct insights into the relative chemical equilibrium partitioning status of compartments, thus facilitating interpretation of experimental and model data. It can help to elucidate dominant processes of transfer, reaction and accumulation, and the direction of diffusion. Certain model simplifications become apparent in which compartments which remain close to equilibrium may be grouped. Maximum steady-state tissue concentrations for a known exposure may be calculated readily. It is suggested that pharmacokinetic fugacity models can complement conventional concentration models and may facilitate linkage to fugacity models describing environmental sources, pathways, and exposure routes.
A model for p-aminobenzoic acid ester narcosis in goldfish.
A three-parameter equation which successfully quantifies the turnover time in goldfish exposed to variable concentrations of eight alkyl esters of p-aminobenzoic acid is described. One parameter characterizes the target concentration necessary to induce narcosis, and the other two parameters represent the resistances encountered by the drug when it migrates through aqueous and lipid phases from source to target. The octanol-water partition coefficients, or aqueous solubilities, and melting points of the esters are included to account for variation in drug hydrophobicity, the relationship between these properties being quantified. The inactivity of high-melting-point esters is explained by the constraint imposed by melting point on the maximum aqueous concentration which can be achieved by solid solutes.
The acetylator phenotypes of Saudi Arabian diabetics.
There is a significant association between the rapid acetylator phenotype and diabetes in European populations. Diabetes is a common problem in Saudi Arabians with some clinical features differentiating it from the disorder in Europeans. A series of 100 Saudi diabetics and 100 Saudi controls has been acetylator phenotyped. The controls showed 33 rapid acetylators (R) and 67 slow acetylators (S), a result closely similar to that previously published for the Saudi population. Overall the diabetics showed 27 R and 73 S which is not significantly different from the controls. The type I diabetics, however, showed two R and 22 S which is not only significantly different from the controls and the type II diabetics, but also the reverse of the association found in European populations.
Intravesicular pH and iron uptake by immature erythroid cells.
The intravesicular pH of intact rabbit reticulocytes was measured by two methods; one based on the intracellular:extracellular distribution of DMO (5, 5, dimethyl + oxazolidin-2,4-dione), methylamine, and chloroquine and the other by quantitative fluorescence microscopy of cell-bound transferrin. The latter method was also applied to nucleated erythroid cells from the fetal rat liver. A pH value of approximately 5.4 was obtained with both methods and in both types of cells. Treatment of the cells with lysosomotrophic agents, metabolic inhibitors, and ionophores elevated the intravesicular pH and inhibited iron uptake from transferrin. When varying concentrations of NH4Cl were used, a close correlation was observed between the inhibition of iron uptake and elevation of the intravesicular pH. At pH 5.4 iron release from rabbit iron-bicarbonate transferrin in vitro was much more rapid than from iron-oxalate transferrin. The bicarbonate complex donates its iron to rabbit reticulocytes approximately twice as quickly as the oxalate complex. It is concluded that the acidic conditions within the vesicles provide the mechanism for iron release from the transferrin molecule after its endocytosis and that the low vesicular pH is dependent on cellular metabolism.
Lysine substitution increases mu-selectivity of potent di- and tri-peptide enkephalin analogs.
A general trend toward increased mu-selectivity has been reported in two classes of minimal structure enkephalin analogs which contain the essential structural and functional information for potent enkephalin-like biological activity. A single Lys residue added to the amino terminal of several tripeptide amides, and to the potent dipeptide amide Tyr-DAla-phenylpropylamide, causes a further increase in mu-selectivity as determined in the stimulated guinea pig ileum (GPI) and mouse vas deferens (MVD) assays, and in receptor binding studies in homogenates of guinea pig brain. The effect of Lys substitution was a significant decrease in the delta-related MVD potencies.
Metorphamide: isolation, structure, and biologic activity of an amidated opioid octapeptide from bovine brain.
Acid acetone extracts of caudate nucleus from bovine brain were found to contain an amidated opioid octapeptide with the following structure: Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2. The peptide has been named metorphamide. Bovine metorphamide appears to be derived by proteolytic cleavage from proenkephalin, the common precursor to [Met5]enkephalin and [Leu5]enkephalin. The cleavage within the precursor giving rise to the carboxyl terminus of metorphamide occurs at a single arginine residue and is followed by transformation of a carboxyl-terminal glycine into an amide group. Metorphamide was detected in bovine caudate nucleus extracts by radioimmunoassay, and it was purified to homogeneity by gel filtration and reversed-phase high performance liquid chromatography. Amino acid composition analysis and automated Edman degradation in the gas-phase sequencer confirmed the postulated amino acid sequence. Carboxyl-terminal amidation of bovine metorphamide was shown by stability to carboxypeptidase A digestion and full crossreactivity in a radioimmunoassay that required the carboxyl-terminal amide as part of the recognition site. A synthetic replicate of metorphamide as well as several synthetic analogs were tested for opioid activity in several bioassays and binding assays, and metorphamide was found to have a high mu-binding activity. Metorphamide is the only known naturally occurring opioid peptide that has a high mu-binding activity. The kappa-binding activity is approximately equal to 50% that of the mu-binding activity, but delta-binding activity is negligible.
Effect of changes in the ionic environment of reticulocytes on the uptake of transferrin-bound iron.
Rabbit reticulocytes were incubated with rabbit transferrin labelled with 59Fe and 125I in media in which the NaCl was replaced by other electrolytes or sucrose. Iron and transferrin uptake by the cells was affected by changes in the pH, ionic strength, ionic composition, and the osmolarity of the medium. Uptake was maximal at pH 7.4. A reduction in ionic strength produced by replacing NaCl with sucrose inhibited the uptake in a concentration-dependant manner, greatest inhibition occurring at lowest salt concentration. Similar results were obtained when KCl, LiCl, RbCl, Na2SO4, or K2SO4 were used instead of NaCl. Low ionic strength was found to inhibit the endocytotic uptake of transferrin labelled with colloidal gold, but had only a small effect on transferrin binding to cell membrane receptors. It was concluded that low ionic strength inhibits iron uptake primarily by blocking the endocytosis of transferrin. Three salts, NH4Cl, CaCl2, and MgCl2, produced different results from the above. NH4Cl inhibited iron uptake at all concentrations used. This action was due to an effect on the release of iron from transferrin, which appeared to be taken up by the cells in a normal manner. When the ionic strength of the sucrose medium was increased by adding low concentrations of CaCl2, iron uptake was greater than with equivalent concentrations of NaCl. However, with CaCl2 concentrations above 10 mM, iron uptake was inhibited, due to inhibition of transferrin uptake, possibly by blocking endocytosis. By contrast, MgCl2 stimulated iron uptake at all concentrations used. The results are discussed in terms of the possible effects of ionic strength, pH, and ionic composition of the extracellular fluid on the three main steps involved in iron uptake by immature erythroid cells: transferrin-receptor interaction, endocytosis, and iron release from transferrin.
Patients' expectations of health care: fulfilled and unfulfilled.
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Adjuvant therapy for carcinoma of the breast.
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Continued use of non-steroidal anti-inflammatory drugs: an index of clinical efficacy.
1 A double-blind entry to a trial of an active non-steroidal anti-inflammatory drug, flurbiprofen against placebo was undertaken until 100 patients with classical rheumatoid arthritis had been allocated to each treatment. 2 Each patient was given a long-term supply of drug and was asked to vary their own dosage within simple limits, according to the severity of their symptoms. They were instructed to return immediately they felt dissatisfied with their medication either on account of side-effect or of lack of effect. 3 The length of time that patients remained satisfied with their drug was used as the sole measure of efficacy of the drug. At 2 weeks there were only 30% remaining on placebo and by 4 months no patients remained satisfied with the inactive drug. Forty-three per cent were satisfied with flurbiprofen at the end of 1 year. 4 Clearly compliance with anti-rheumatic drugs is better if the drugs are effective and there is no long-term placebo response in rheumatoid arthritis.
Effect of alpha-blocking drugs in asthma.
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The status of Michigan's Medicaid program.
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