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Biomedical subjects

M S Roberts

Publications and source records attributed to M S Roberts.

At least 163 records · Page 9Linked to original sources
PubMed1993

A clinical trial of a slow-release formulation of acetylsalicylic acid in patients at risk for preeclampsia.

The formation of thromboxane A2 (TXA2) in maternal and foetal cord serum was measured at birth in eight control patients and in 13 patients taking 100 mg of a slow-release formulation of acetylsalicylic acid. The serum concentrations of TXB2 (a stable end product of TXA2 hydrolysis) in both maternal and cord serum from patients who ingested the acetylsalicylic acid formulation were significantly lower (P < 0.01) than those in control subjects. Acetylsalicylic acid was not detected (< 30 ng ml-1) in maternal plasma from six mothers and in cord plasma from seven foetuses in the acetylsalicylic acid-treated group. The mean cord to maternal plasma concentration ratios for detectable acetylsalicylic acid and salicylate were 0.62 +/- 0.19 (s.d.) (n = 6) and 0.84 +/- 0.16 (n = 13), respectively. We conclude that low doses of acetylsalicylic acid given in a slow-release form to mothers during pregnancy cause depression of TXA2 formation in the foetal blood.

Adult↗
PubMed1993

Subcutaneous absorption kinetics and local tissue distribution of interferon and other solutes.

The subcutaneous absorption and consequent tissue distribution of interferon g was studied in an anaesthetized rat model. Interferon g showed a biphasic disappearance profile from a solution in a subcutaneous absorption cell. Both the initial rapid distribution phase and slower removal phase followed first order kinetics. The steady-state clearance of interferon g from the cell was 1.41 +/- 0.38 x 10(-3) mL min-1, and the absorption half-life (t1/2) was 3.8 +/- 1.1 h (n = 4). Noradrenaline did not significantly alter either the clearance or absorption of interferon g (1.18 +/- 0.44 x 10(-3) mL min-1, P > 0.05, absorption t1/2 4.96 +/- 1.9 h, P > 0.05). Given that the clearance of smaller solutes, such as tritiated water, is significantly reduced when noradrenaline is coadministered, it is suggested that interferon g is removed via the lymphatic system rather than by the local blood supply. The amount of interferon g recovered in the plasma, urine and muscle is minimal relative to other solutes where the recovery is almost complete.

Animals↗
PubMed1993

Kinetics of toxic doses of paraquat and the effects of hemoperfusion in the dog.

Knowledge of the kinetics of an intoxicant is required for designing potential therapies in poisoned patients. In the case of paraquat, elucidating the kinetics has been made difficult by the paraquat-induced renal failure and the consequent dose- and time-dependent elimination of the herbicide. In the current study, we have modelled the plasma and urinary concentrations of paraquat in dogs given a toxic dose, the elimination of which was nonlinear. This enabled us, in turn, to simulate the apparent concentrations of paraquat in the deep tissue compartment, part of which is constituted by the major target organ for paraquat toxicity, the lung. Finally, we defined conditions, if any, under which charcoal hemoperfusion could reduce exposure of the deep compartment to paraquat by > or = 25%. We found that the plasma concentrations of paraquat could be described by a two compartment model with non-linear elimination from the central compartment. Use of a three compartment model did not improve the fit over that for a two compartment. The volume of distribution of paraquat at steady state approximated that of total body water. Simulated hemoperfusion performed for eight or eighty hours did not reduce exposure of the deep compartment to paraquat by > or = 25%, unless begun at times < or = two hours of the infusion commencing. This is consistent with our experimental data in the dog. The lack of efficacy of hemoperfusion is due to the rapid renal elimination of most of the absorbed dose of paraquat over the first 12 hours after its administration, and the later limitation of the rate of removal of paraquat from the body by the slow efflux rate from the deep to central compartment.

Animals↗
PubMed1992

Inquiry about victimization experiences. A survey of patient preferences and physician practices.

BACKGROUND: It is unknown whether patients want primary care physicians to inquire about physical abuse (PA) or sexual abuse (SA) or how frequently physicians make such inquiries. METHODS: To determine patient preferences and physician practices, we surveyed 164 patients and 27 physicians at private and public primary care sites. Data were collected using confidential, anonymous, written, multiple-choice questionnaires and were evaluated using univariate analysis. RESULTS: Among patients, routine PA inquiry was favored by 78% and routine SA inquiry was favored by 68%. Only 7% were ever asked about PA and 6% about SA. A history of PA was reported by 16% and a history of SA by 17%. Ninety percent believed physicians could help with problems from PA and 89% felt physicians could help with problems from SA. Among physicians, one third believed that PA and SA questions should be asked routinely. However, SA inquiries were never made by 89% at initial visits or by 85% at annual visits. Physical abuse inquiries were never made by 67% at initial visits, or by 60% at annual visits. Eighty-one percent believed they could help with problems associated with PA and 74% with SA. CONCLUSIONS: Most patients favor inquiries about physical and sexual abuse and believe physicians can help with these problems. Physicians believe they can help with these problems though they frequently do not inquire.

Attitude to Health↗
PubMed1992

Axial tissue diffusion can account for the disparity between current models of hepatic elimination for lipophilic drugs.

An assumption of previous models of hepatic elimination is that there is negligible axial diffusion in the liver. We show, by construction of a stochastic model and analysis of published data, that compounds which are readily diffusible and partitioned into hepatocytes may undergo axial tissue diffusion. The compounds most likely to be affected by axial tissue diffusion are the lipophilic drugs for which the cell membranes provide little resistance and which are highly extracted, thereby creating steep concentration gradients along the sinusoid at steady state. This phenomenon greatly modifies the availability of the compound under conditions of altered hepatic blood flow and protein binding. For moderately diffusible compounds, these relationships are similar to those predicted by the simplistic venous-equilibrium model. Hence, the paradoxical ability of the venous-equilibrium model to describe the steady-state kinetics of lipophilic drugs such as lidocaine, meperidine, and propranolol may be finally resolved. The effects of axial tissue diffusion and vascular dispersion on hepatic availability of drugs are compared. Vascular dispersion is of major importance to the availability of poorly diffusible compounds, whereas axial tissue diffusion becomes increasingly dominant for highly diffusive and partitioned substances.

Computer Simulation↗
PubMed1991

Novel direct high-performance liquid chromatographic method for determination of salicylate glucuronide conjugates in human urine.

A novel direct high-performance liquid chromatographic (HPLC) assay for the simultaneous determination of three salicylate glucuronide conjugates and other salicylate metabolites in human urine has been developed. Salicylate glucuronide conjugates were purified by HPLC from the urine of a volunteer after oral administration of aspirin and identified by selective hydrolysis with beta-glucuronidase and with sodium hydroxide. This method gave high reproducibility with coefficients of variation less than 10%. The total urinary recovery of salicylic acid after a single 1.2-g dose of soluble aspirin was greater than 90%. This assay has been successfully used to re-evaluate the capacity-limited pharmacokinetics of salicylic acid in humans.

Administration, Oral↗
PubMed1991

Spectral analysis of heart rate in diabetic autonomic neuropathy. A comparison with standard tests of autonomic function.

Power spectral analysis of the heart rate was compared with standard tests of autonomic function performed on 15 insulin-dependent diabetic patients with symptoms of autonomic dysfunction. The high-frequency power, low-frequency power, and total power of the heart rate power spectrum measured in the supine position--possible measures of parasympathetic nervous system function--were significant predictors of the expiratory-inspiratory ratio, the beat-to-beat heart rate difference on deep respiration, the standard deviation of the resting heart rate, the 30:15 ratio, and the Valsalva ratio. The change in low-frequency power on moving from the supine to upright position, a possible measure of sympathetic nervous system function, was a modest predictor of the systolic and diastolic blood pressure fall in response to postural change, but a poor predictor of the blood pressure response to isometric exercise and a cold stimulus. This study supports the role of heart rate power spectral analysis as a clinical test of autonomic function in patients with known or suspected autonomic failure.

Adult↗
PubMed1991

Prediction of solute sorption by polyvinyl chloride plastic infusion bags.

The time course of the sorption of drugs by polyvinylchloride infusion bags has been approximated using a diffusion model in which the plastic is assumed to act as an infinite sink. This model appears to be suitable for estimation of storage times relevant to clinical usage and enables the magnitude of the uptake in a specific time to be described by a single parameter, referred to as the sorption number. This parameter is defined by the plastic-infusion solution partition coefficient, the diffusion coefficient in the plastic, the fraction un-ionized in solution, the volume of the infusion solution, and the surface area of the plastic. An approximation of the model allows a ready estimation of the sorption number from the fraction remaining in solution at a given time. The sorption number can be extrapolated to allow prediction of the effects of time, plastic surface area, solution volume, and solution pH on fractional solute loss. A reasonable correlation was established between the logarithm of this parameter and the logarithm of the octanol-water partition coefficients of various solutes. The model allows the fraction of a solute remaining in a plastic infusion bag at a given storage time to be estimated from the octanol-water partition coefficient of the solute and other readily available data.

Adsorption↗
PubMed1991

Model representation of salicylate pharmacokinetics using unbound plasma salicylate concentrations and metabolite urinary excretion rates following a single oral dose.

The pharmacokinetics of salicylic acid (SA) and its metabolites have been studied in 5 volunteers after administration of 3 g salicylic acid (as sodium salicylate) and collection of serial samples of blood and urine. SA and its metabolites were assayed with a HPLC method specific for each species. The urinary excretion rates of individual metabolites were analyzed using unbound plasma SA concentrations and Lineweaver-Burke plots. The analysis confirmed that the formation of SA urate (SU) and SA phenolic glucuronide (SPG) metabolites are saturable processes, and showed that the Michaelis-Menten values derived are consistent with earlier estimates derived solely from urinary data. The unbound salicylate plasma concentration-time profiles were then analyzed with various models assuming either saturable clearances for metabolite formation and/or saturable protein binding. The data were best described with a model that included both saturable protein binding and saturable metabolism. The model assumed first-order absorption kinetics and instantaneous distribution into extravascular and tissue compartments. The model was validated by comparing predicted relationships between the apparent volume of distribution, clearance, and plasma salicylate concentrations with previous relationships obtained using steady state data.

Administration, Oral↗
PubMed1991

Response to beta-blockers in maternal and fetal rat hearts in vitro.

The effects of beta-blockers on maternal and fetal heart rates have been assessed by comparing isoprenaline concentration-heart rate relationships of hearts isolated from pregnant rats. The normal and maximal heart rates obtained for the maternal and fetal hearts were similar to published data. A slightly but significantly higher concentration of isoprenaline was required to produce 50% of the maximal response of fetal hearts than maternal hearts, suggesting that fetal hearts were less sensitive to isoprenaline than the maternal hearts. The beta-blockers used (propranolol, labetalol, metoprolol and atenolol) all showed a lower affinity to the beta-receptors of fetal hearts than those of maternal hearts, as indicated by significant differences in the pA2 values. Given the similar effects of the beta-blockers in the maternal and fetal hearts it is concluded that pharmacokinetic considerations and beta-blocker selectivity should be used as the basis of choice when treating maternal hypertension during pregnancy.

Adrenergic beta-Antagonists↗
PubMed1991

Self-restraint: a review of etiology and applications in mentally retarded adults with self-injury.

Self-restraint has been noted in studies of self-injurious behavior (SIB) in mentally retarded individuals. These studies have investigated self-restraint in the context of SIB, and as a result it has been difficult to isolate the function of self-restraint within this complex clinical situation. This article summarizes and critically analyzes the literature on self-restraint, particularly its identification, etiology, modification, and relationship to SIB. At present there is some empirical evidence to suggest that self-restraint is negatively reinforced by the termination or avoidance of SIB. Other studies have demonstrated that self-restraint can develop stimulus control properties for the absence of SIB. Finally, it has been suggested that self-restraint may function independently of SIB and be maintained by escape from demands or by conditioned reinforcement. Clinical concerns include the need for a functional analysis of self-restraint, the undesirable effects on SIB of reducing self-restraint, and the necessity of replacing self-restraint topographies with ones which do not interfere with daily activities.

Adult↗
PubMed1991

Technology assessment in the Framingham Heart Study.

To assess the role of observational data bases in technology assessment, we examined 26 articles from the Framingham Heart Study that evaluated a technology, therapy, or predictive instrument. These assessments were grouped into four categories: (a) the study of a technology voluntarily in use by the cohort, (b) the application of an external technology to members of the cohort, (c) the use of the Framingham results to evaluate an unrelated assessment, and (d) the use of the results to validate predictive instruments from other studies. Factors that contribute to the ability of the study to assess voluntary and external technologies include long-term follow-up, a stable cohort, and storage of such nonnumeric data as cardiograms and blood samples. Framingham results have been used to determine outcome measures in later studies. Although the Framingham Study was not designed to assess a technology, we found that large-scale, observational data bases can and do contribute to technology assessment.

Cohort Studies↗
PubMed1991

Subcutaneous fluid administration in elderly subjects: validation of an under-used technique.

In a crossover study in six volunteers over the age of 65, absorption of 500 mL of normal saline given subcutaneously was compared with that given intravenously. Tritiated water and technetium pertechnetate were used as water tracers. Tritium radioisotope levels in the blood increased in a smooth curve during subcutaneous infusion, reaching equilibrium levels within 60 minutes. The area under the curve after subcutaneous infusion was almost identical to that after intravenous infusion in all subjects. Radioactivity could not be demonstrated at the subcutaneous site 1 hour after completion of the infusion. Subcutaneous infusion is an effective method of giving fluid to elderly people and deserves more widespread use.

Aged↗