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Biomedical subjects

M S Roberts

Publications and source records attributed to M S Roberts.

At least 181 records · Page 10Linked to original sources
PubMed1991

Effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) and its metabolites.

The effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) 500 mg and its metabolites were studied in 8 healthy men. The mean residence times for paracetamol or its metabolites were significantly altered by change in posture or by sleep, whereas other pharmacokinetic parameters were unchanged. The change in mean residence time is consistent with a faster absorption of paracetamol during ambulation. The present data suggest that the proposed posture-related changes in volume of distribution do not exist, and that there is no pharmacokinetic basis for a headache being relieved by taking paracetamol and lying down.

Acetaminophen↗
PubMed1990

Residence time distributions of solutes in the perfused rat liver using a dispersion model of hepatic elimination: 1. Effect of changes in perfusate flow and albumin concentration on sucrose and taurocholate.

The residence time distributions of sucrose and taurocholate have been determined from the outflow concentration-time profiles after bolus input into an in situ perfused rat liver preparation. The normalized variance (and the dispersion number) appeared to be independent of perfusate flow rate (10 to 37 ml/min) and perfusate albumin concentration (0.5%). The apparent volume of distribution for sucrose appeared to increase with flow rate but was unaffected by the concentration of albumin (0-5%) present in the perfusate. The changes in taurocholate availability with flow rate were adequately accounted for by the dispersion model, whereas taurocholate availability-protein binding changes required an albumin-mediated transport model to be used in conjunction with the dispersion model.

Albumins↗
PubMed1990

Residence time distributions of solutes in the perfused rat liver using a dispersion model of hepatic elimination: 2. Effect of pharmacological agents, retrograde perfusions, and enzyme inhibition on evans blue, sucrose, water, and taurocholate.

The effect of altered physiological conditions on the residence time distributions of sucrose, water, and taurocholate in the rat liver were studied using a bolus injection and quantifying fraction of total outflow per ml-time profiles. Retrograde perfusions increased the residence times of sucrose and water markedly and were associated with very low hepatic availabilities for taurocholate. Resistance by the inlet sinusoids sphincters, which become outlet sphincters during retrograde perfusions, is suggested as the explanation for the observation. Infusions of noradrenaline, propranolol, and lidocaine resulted in relatively small changes in the mean residence times for sucrose and water with no apparent relationship existing between the efficiency number of taurocholate and volumes of either water or sucrose. Taurochenodeoxycholate resulted in an increase in the availability and mean residence time for taurocholate relative to no infusion.

Animals↗
PubMed1990

The echogenic ependymal wall in intraventricular hemorrhage: sonographic-pathologic correlation.

Fifty-one patients with ultrasound diagnosis of intraventricular hemorrhage (Grades III and IV) were studied retrospectively for the presence of ependymal echogenicity. The sonographic findings were then correlated with histologic findings in six autopsy cases. Forty-one out of fifty-one newborns with intraventricular hemorrhage developed ependymal echogenicity on serial ultrasound studies. This echogenicity appeared approximately seven days after the hemorrhagic event and usually disappeared in about six weeks. Histologic examination revealed disruptions in the ependyma with proliferation and extension of subependymal glial cells onto the ventricular surface in those cases in which ependymal echogenicity was present at the time of death. This layer of proliferating subependymal glial cells may account for the ependymal echogenicity.

Cerebral Hemorrhage↗
PubMed1990

Low-dose immunosuppression by cyclosporine operating via antigen-presenting dendritic cells.

The inhibitory effect of cyclosporine on the stimulation of lymphocytes was tested in 20 microliters hanging drop cultures. Cells were stimulated by concanavalin A, or by allogeneic dendritic cells in a mixed leukocyte culture (MLC). Significant inhibition of lymphocyte proliferation was obtained with low concentrations of CsA (10(-9)-10(-7) micrograms/ml) in addition to the well-documented, dose-dependent inhibition at concentrations greater than or equal to 10(-1) micrograms/ml. Intermediate doses (10(-6)-10(-2) micrograms/ml) caused little inhibition. To establish whether the CsA was acting on the antigen-presenting cells or on the responding T cells, each population was pulsed with CsA before adding to the MLC. Higher doses of CsA were required to cause inhibition using this short-term pretreatment rather than continuous presence of CsA; however, when DC were pulsed with CsA, biphasic effects of the drug were seen. The time of DC pretreatment with 1 microgram/ml CsA was varied, and inhibition was seen after 1-3 hr and 16-24 hr pretreatment but not at intermediate time points. Similarly, a biphasic dose-response developed when DC-pretreatment time was fixed (2 hr) and drug concentration was varied. By contrast, on pulsing responder lymphocytes with CsA there was a biphasic effect in some experiments, but more often a single dose-dependent inhibition occurred, particularly when DC were removed from the responder cells. Major dose-dependent inhibitory effects of CsA may therefore act on both antigen-presenting DC and on lymphocytes, but this work reveals an additional low-dose inhibition that can operate via DC.

Animals↗
PubMed1990

Selective inhibition of platelet cyclooxygenase with controlled release, low-dose aspirin.

The hypothesis that slow administration of low doses of aspirin may selectively inhibit platelet cyclooxygenase and thromboxane A2 formation was evaluated using controlled release aspirin formulations. In the first study, doses of either 50, 100, 325 and 1,300 mg of these formulations and 300 mg soluble aspirin were ingested daily by healthy volunteers for one week. In the second study, doses of 5, 10, 25 and 50 mg controlled release aspirin, 50 mg soluble aspirin and 100 mg aspirin and glycine formulation were ingested daily for ten days. Platelet function and urinary prostaglandin production were assessed immediately before and on the seventh day of dosing in both studies and in the second study, repeated on the tenth day of dosing. Platelet function and serum thromboxane B2 production were fully inhibited by all formulations of 50 mg aspirin and above, but not by doses of controlled release aspirin below 50 mg doses. The excretion of urinary 6-keto-PGF1 alpha (a major metabolite of prostacyclin) was significantly reduced at controlled release aspirin doses above 100 mg and at all doses of rapidly absorbed aspirin tested. As no significant reduction in the urinary 6-keto-PGF1 alpha production was observed at doses of controlled release aspirin of 50 and 100 mg and below, it appeared that these doses did not inhibit the systemic vascular cyclooxygenase. These data are consistent with a selective inhibition of platelet function by daily doses of 50 and 100 mg of the controlled release formulation of aspirin.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Autonomic function and human immunodeficiency virus infection.

We compared autonomic function in 26 patients infected by the human immunodeficiency virus (HIV) (18 AIDS and 8 ARC) to 22 controls. A significant decline in autonomic function was present across groups. Autonomic dysfunction correlated strongly with signs of HIV-associated nervous system disease. We observed significant differences across groups in tests of heart rate variation (expiratory-inspiratory ratio, maximum minus minimum heart rate difference, and mean square successive difference), the mean arterial blood pressure fall to tilting, and the blood pressure response to isometric exercise. A trend of declining autonomic function from controls to AIDS was present in the 30:15 ratio, the Valsalva ration, the systolic blood pressure fall to standing and tilt, and the cold pressor test. We did not observe any correlation between autonomic dysfunction and individual neurologic signs, prior therapeutic agents, and concurrent HIV-associated inflammatory or neoplastic processes. This study provides support for the presence of autonomic dysfunction in association with HIV infection. Autonomic dysfunction occurs more frequently and with greater severity in patients with AIDS; however, it may be present in the early stages of HIV infection and appears to progress during the illness.

AIDS-Related Complex↗
PubMed1989

Identification and characterization of parathyroid hormone receptors in rat renal cortical plasma membranes using radioligand binding.

Parathyroid hormone (PTH) receptors have been described in renal tissue from several species, but not in the rat. In this study, radioligand binding techniques were used to identify and characterize PTH receptors in rat kidney cortical membranes. The sulfur-free PTH analog [Nle8,18Tyr34]bovine PTH-(1-34)amide was iodinated using the iodogen method. This ligand was suitable for use in identifying PTH receptors in canine renal membranes, but not rat renal membranes. Synthetic, unsubstituted rat PTH-(1-34) was iodinated using the milder, lactoperoxidase technique and was purified by HPLC on a C8 column. [125I]rat PTH-(1-34) bound rapidly to both rat and dog renal membranes. At 22 degrees C reaction reached steady state within 20 minutes, and this level was maintained for at least 3 h. Specific binding was routinely greater than 90% for rat kidney and greater than 95% for dog kidney. Similar results were obtained at 4 degrees C with a longer time required to attain steady state (approximately 45 minutes). Binding was reversible as demonstrated by dissociation of bound ligand after either infinite dilution or displacement with excess nonradioactive PTH. Binding was saturable and of high affinity (rat kidney: Bmax = 2.3 pmol/mg protein, Kd = 3.1 nM, dog kidney: Bmax = 2.1 pmol/mg protein, Kd = 3.7 nM). Rat renal cortical adenylate cyclase activity was stimulated by rat PTH in a dose-dependent manner with an EC50 of 4 nM, a value in good agreement with the binding data. This study demonstrates the feasibility of identifying and characterizing parathyroid hormone receptors in rat renal cortical plasma membranes using radioligand binding techniques.

Adenylyl Cyclases↗
PubMed1989

Percutaneous absorption of steroids: relative contributions of epidermal penetration and dermal clearance.

The permeation of triamcinolone, hydrocortisone, prednisolone, corticosterone, triamcinolone acetonide, testosterone, and betamethasone-17-valerate through excised human stratum corneum was quantified. The time course of permeation could be adequately described by a simple diffusion model suggesting that shunt transport may not be important. The disappearance of these steroids from aqueous solutions applied to human and rat dermis was also monitored. The concentrations of unbound steroid in the viable epidermis appeared to be mainly related to the blood perfusion rate in the dermis and, more importantly, to the lipophilicity of the steroid. The most lipophilic steroids penetrated the human epidermis at the fastest rates but are cleared from the viable epidermis at rates comparable to those found for more polar steroids.

Diffusion↗
PubMed1989

Availability predictions by hepatic elimination models for Michaelis-Menten kinetics.

Numerical methods have been used to compare the availability predictions of a number of hepatic elimination models when Michaelis-Menten kinetics is operative. Propranolol and galactose were used as model compounds. Lower availabilities were predicted by the dispersion model than by a segregated distribution model for both compounds. The differences in the predictions were most pronounced for models corresponding to a large variation in solute residence times in the liver. The predictions of the tank-in-series, dispersion model with mixed boundary conditions and dispersion model with Dankwerts boundary conditions were similar over all concentrations studied. Changes in blood flow and protein binding provided little discrimination between the model predictions. It is concluded that micromixing of blood between sinusoids and the anatomical sites of mixing are important determinants of availability when liver eliminating enzymes are partially saturated.

Biological Availability↗
PubMed1989

A survey of self-restraint, self-injury, and other maladaptive behaviors in an institutionalized retarded population.

Psychologists of a state school for mentally retarded persons were surveyed to assess the prevalence of self-restraint, self-injurious behavior (SIB), and other maladaptive behaviors for clients in their facility. Results indicated that almost all clients reliably identified as engaging in self-restraint also engaged in self-injurious behavior while other maladaptive behaviors for self-restraining clients occurred much less frequently. The occurrence of SIB in the school's population was substantially lower than in the self-restraining population. Results are discussed in terms of future research investigating a functional relationship between self-restraint and SIB. Clinical implications for the use of self-restraint as an intervention for SIB also are discussed.

Adolescent↗
PubMed1989

Salicylate pharmacokinetics in patients with rheumatoid arthritis.

1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations.

Aged↗
PubMed1989

Iontophoretic transport of weak electrolytes through the excised human stratum corneum.

The effect of iontophoresis on the rate of permeation of a number of therapeutically active weak acids and bases through excised human stratum corneum has been examined, over a range of pH values. It has been shown that the amount of ionized drug species present in the drug solution is an important factor in the delivery of acids and bases by this route and that the molecular weight of the drug does not influence the rate of delivery by iontophoresis.

Chromatography, High Pressure Liquid↗
PubMed1989

Transdermal delivery of drugs by iontophoresis: a review.

The advantages and limitations, theory, and factors in the use of electric current to deliver drugs across the skin are discussed. Application of the technique in the delivery of local anaesthetics, antibiotics/antibacterials, mydriatics, vinca alkaloids, non-electrolytes, biogenic amines, peptides, and other agents is reviewed. It is concluded that the method alone, or in combination with phonophoresis (delivery via ultrasonic perturbation), offers considerable scope in the transdermal delivery of drugs.

Administration, Cutaneous↗