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Biomedical subjects

I D Watson

Publications and source records attributed to I D Watson.

At least 19 recordsLinked to original sources
PubMed1991

Assessment of theophylline compliance in general practice using a 'compliance index' based on apparent drug clearance.

The monitoring of compliance in outpatients using serum drug levels suffers from the difficulty of relating concentrations to changes in dosage. Clearance is independent of dose for most drugs, and may be predicted using a Bayesian based forecasting program. This paper describes how the apparent clearance obtained following a single drug analysis can be compared with the Bayesian population value to derive a Compliance Index. In compliant individuals with stable hepatic and renal function this index should remain constant. We evaluated the usefulness of the Compliance Index in general practice with patients prescribed theophylline. Of 54 patients examined on up to five occasions, only 12% were deemed to be fully compliant at all times. Compliance improved during the study, but worsened again once regular consultation ceased. The results indicate that such a Compliance Index is a viable method of assessing compliance with the aid of concentration measurements.

Adolescent↗
PubMed1990

The effect of doxorubicin on the glutathione content and viability of cultured human lung cancer cell lines A549 and GLC4 210.

Glutathione was measured in doxorubicin-sensitive cells from small cell carcinoma of lung (GLC4 210), and the levels compared with those of cells with acquired resistance and a line of resistant non-small-cell adenocarcinoma A549 (Alveolar type 2). The effect of different doxorubicin concentrations on glutathione were measured by HPLC. The effect of doxorubicin on the viability of the cell lines was studied using thiazole blue dye reduction. An increase in A549 sensitivity to doxorubicin was produced using buthionine-S,R-sulfoximine at a non-toxic dose.

Adenocarcinoma↗
PubMed1990

An NMR compatible model for solid tumour.

An NMR model for the study of drug interactions with solid tumour is described. It is based on the use of packed cells in a simple medium. The system is capable of dealing with cellular biochemistry at a molecular level through experiments conducted in a homogeneous field by 1H spin-echo NMR spectroscopy. However, through a simple imaging technique, it is also possible to introduce a spatial element into the chemistry of the packed cells. The use of these complementary NMR methods are illustrated by the action of the cytotoxic agent doxorubicin on cellular glycolysis. A pattern of signals observed in a homogeneous field experiment following oxidative stress are duplicated in the imaging experiment to illustrate the toxins' ability to penetrate the model tumour.

Antineoplastic Agents↗
PubMed1990

Wilson's disease presenting as acute fulminant hepatic failure.

A fatal case of fulminant hepatic failure in an adolescent is described. Post-mortem examination revealed the cause to be Wilson's Disease. This rare presentation is characterised by apparently atypical changes in copper metabolism. Wilson's Disease should be a differential diagnosis of any adolescent presenting in liver failure.

Adolescent↗
PubMed1989

Comparison of microscale ultracentrifugation and equilibrium dialysis for the determination of the unbound fraction of theophylline in human serum.

A microscale ultracentrifugation procedure for the measurement of free theophylline in serum is described and evaluated by comparison with an equilibrium dialysis method. Provided an ultracentrifuge is available, micro-ultracentrifugation is a simple, cost-effective technique for the routine determination of free drug fractions.

Costs and Cost Analysis↗
PubMed1988

Doxorubicin-induced altered glycolytic patterns in the leukemic cell studied by proton spin echo NMR.

1H spin echo NMR of the leukemic cell line J-lll is reported. Phosphorylcholine, phosphorylcreatine, lactate and mobile triglyceride are identified as constituents of the cytosolic pool in the intact and viable cells. The concentration of cells in the NMR tube is high (approx. 10(9) in 0.4 ml) and as a result the available oxygen is restricted, making the NMR experiment a plausible in vitro tumour model in which kinetics in the living cell can be probed in a non-invasive manner. Treatment with pharmacological concentrations of the drug doxorubicin produced immediate enhanced anaerobic glycolysis and eventual cell death.

Doxorubicin↗
PubMed1988

Clinical pharmacokinetics of enzyme inhibitors in antimicrobial chemotherapy.

The effectiveness of some antimicrobial agents can be enhanced by using them in combination; such combinations are termed synergistic. Where one compound potentiates the effect of a second drug they may be coformulated. Inhibition of the bacterial degradation of an active antimicrobial is the basis of clavulanate and sulbactam-potentiated penicillin combinations, and inhibition of degradative pathways in the host is the rationale behind imipenem/cilastatin therapy. Trimethoprim/sulphonamide combinations depend on the maintenance of an effective ratio for synergistic action. In order to achieve potentiation the coformulated drugs should have similar pharmacokinetics. Trimethoprim was originally matched with sulphamethoxazole, since these two drugs have similar elimination half-lives, but the significantly poorer penetration of sulphonamides, their greater non-renal clearance, the emergence of resistance, and the adverse reactions attributable to them argue against the rationale that underlies their coformulation. Time-dependent inhibition of bacterial beta-lactamases by clavulanic acid and sulbactam has extended the use of penicillins which are highly susceptible to beta-lactamase inactivation. The beta-lactamase inhibitors must penetrate to the same extent as the penicillin used with them, and be present long enough to effect inhibition; thus, rapid penetration, similar or slower elimination and equivalent volume of distribution are necessary. These requirements are met for amoxycillin/clavulanic acid, ticarcillin/clavulanic acid and ampicillin/sulbactam combinations. Clavulanic acid is absorbed orally and is given with amoxycillin. However, since sulbactam is labile by this route, the combination of sulbactam with ampicillin to form the prodrug sultamicillin has been necessary to enable an oral form to be developed. Imipenem is metabolised by renal brush-border dehydropeptidases, and may cause proximal tubular necrosis. Cilastatin was designed to inhibit this metabolism, which it effectively does, thereby both potentiating the effect of imipenem and avoiding toxicity. Appropriate matching of the kinetics of coformulated drugs is intended to maximise potentiation and minimise the risk of emergent resistance. The kinetics of the above combinations are discussed in the light of these requirements and the effects of age and disease.

Anti-Bacterial Agents↗
PubMed1988

Trimethoprim analysis.

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Chromatography, High Pressure Liquid↗
PubMed1979

Obesity indices.

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Adipose Tissue↗
PubMed1977

Calorimetric studies of the ADP binding to myosin subfragment 1, heavy meromyosin, and to myosin filaments.

A calorimetric titration method was used to study the ADP binding to the chymotryptic subfragments of myosin, heavy meromyosin (HMM) and myosin subfragment 1 (S-1), and to myosin aggregated into filaments at low ionic strength. The binding constant (K) and heat of reaction (deltaH, kiloJoules (moles of ADP bound)-1) were determined. For HMM in 0.5 M KCl, 0.01 M MgCl2, 0.02 M Tris (pH 7.8) at 12 degrees, log K = 5.92 +/- 0.13 and deltaH = -70.9 +/- 3.6 kJ mol-1. These results agree with our previous findings for myosin in 0.5 M KCl at 12 degrees. When the KCl concentration was reduced to 0.1 M, the binding constant did not change significantly (log K = 6.09 +/- 0.06) but the binding was more exothermic (deltaH = -90.1 +/- 3.3 kJ mol-1). Similar results were obtained for myosin filaments in 0.1 M KCl and also for both the isoenzymes of S-1(S-1(A1) and S-1(A2) in 0.1 M KCl. In 0.5 M KCl, the binding curves suggest that about one ADP is bound per active site, but as 0.1 M KCl, the apparent stoichiometry drops from 0.7 to 0.75. The most probable explanation is that there is some site heterogeneity which is more evident at lower ionic strength.

Adenosine Diphosphate↗