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Biomedical subjects

D S Smith

Publications and source records attributed to D S Smith.

At least 325 records · Page 18Linked to original sources

Repeatability and validity of a modified activities of daily living (ADL) index in studies of chronic disability.

In order to measure disability in a randomised controlled trial of different intensities of rehabilitation following stroke, a modification of existing methods has been developed; it makes use of 17 items of activities of daily living (ADL) which are rated on a three-point scale, and it has been subjected to tests of repeatability and validity. While some activities (e.g. use of taps, ascending or descending stairs) are either redundant or repetitive, others provide independent measures of disability. There was no significant inter-observer variability; the assessors disagreed on 78 (3.7%) out of a total of 2,125 paired observations. In a study of short-term within-patient variability, different scores were assigned on 49 (14.4%) out of a total of 340 observations made on two separate occasions. Minor differences (mainly in activities involving equipment e.g. cookers) emerged when scores obtained in hospital were compared with those obtained at home, but the two sets of scores were still highly correlated (r = 0.962. There was, however, considerable discrepancy between the hospital scores and those derived from the patients' own estimates of their activities at home, the latter falling below actual capabilities as indicated by the hospital scores. A clinical validation of the index showed a significant association between the hospital ADL scores and the extent of cerebral lesions determined by the number of neurological deficits. This modified ADL index is sufficiently repeatable and valid for the assessment of patients with moderate disability as a result of stroke and other chronic diseases; in most circumstances, it can probably be simplified to include only five or six items.

Activities of Daily Living↗

Point/counterpoint: declining public health organizations--will management make a difference?

Time is running out for public health organizations, says Charles Harper. Their traditional role in the health system is eroding rapidly. To reestablish the place they deserve in the health system will require an aggressive and united effort on the part of all public health professionals. As a counterpoint to Harper's article, Donald Smith asserts that the decline is a result more of a negative image and changing standards than of managerial problems.

Community Health Services↗

The role of plasmapheresis in renal transplantation.

Plasmapheresis has been studied in ten patients who received cadaveric renal allografts. In six patients (group A), plasma was carried out on the first post-operative day and then on alternate days until six treatments had been completed. No beneficial effect was observed but treatment was well tolerated and there were no complications. One patient retains a functioning graft. Plasma exchange was carried out on six consecutive days in five patients (group B) who were actively rejecting their grafts and in whom conventional methods of treatment had failed. All five patients showed improvement in graft function. Rejection was reversed in four patients and was contained in one patient. Subsequently rapid recrudescence of graft rejection occurred in one patient, extended graft survival was seen in two patients, and the other two patients have retained life supporting grafts. Plasmapheresis may have a part to play in the treatment of renal allograft rejection and further evaluation of this treatment is indicated.

Antibodies↗

Novel 125I-labeled nortriptyline derivatives and their use in liquid-phase or magnetizable solid-phase second-antibody radioimmunoassays.

Nortriptyline derivatives prepared by reaction with fluorescein isothiocyanate or conjugation to N-acetyl-L-histidine were radioiodinated and the products purified with Sephadex LH-20 columns to obtain two novel nortriptyline radioligands. Antisera were raised in rabbits by immunization with nortriptyline conjugated to succinylated ovine albumin. By use of the iodinated fluorescein derivative we developed a liquid-phase second-antibody radioimmunoassay that gives results correlating closely (r = 0.98) with those by an established radioimmunoassay of similar specificity in the assay of apparent total amitriptyline and its metabolite nortriptyline in serum or plasma from patients being treated with these drugs. With the iodinated N-acetyl-L-histidine derivative we developed a magnetizable solid-phase second-antibody radioimmunoassay. The cross reactivities of amitriptyline and nortriptyline could be made equal by performing the assay at pH 9.0, which makes it possible to measure true total active drug concentrations in patients receiving amitriptyline.

Amitriptyline↗

Continuous-flow fluoroimmunoassay of serum gentamicin, with automatic sample blank correction.

We describe the continuous-flow automation of a quenching fluoroimmunoassay for determination of the antibiotic gentamicin in serum. In the flow system, sample is mixed with fluorescein-labeled gentamicin, followed by antiserum, and after a short incubation the fluorescence is measured. The intrinsic blank signal of each sample is corrected for during its single passage through the system by pumping antiserum discontinuously, so as to divide the final stream into sections corresponding to conventional separate assay and blank mixtures. Analyses time for each sample is 6 min, and 20 samples can be run per hour. Sensitivity, precision, and accuracy are adequate for clinical purposes, and assays of patients' samples correlate satisfactorily with the results of manual quenching and polarization fluoroimmunoassays, and plate diffusion bioassay.

Fluorescence↗

Solid-phase fluoroimmunoassay of human albumin in biological fluids.

A simple fluoroimmunoassay for the determination of albumin levels in serum, urine and cerebrospinal fluid is described. It employs magnetisable particles to which antibodies to human serum albumin are covalently linked, and albumin labelled with fluorescein. Equilibrium is reached within 30 min, when separation of the bound and free fractions of the labelled albumin is performed by precipitation of the particles either with a magnet or by centrifugation. Measurement of the fluorescence in the supernatant (the free fraction) reflects the albumin concentration of the standards or samples. Correlation studies with an automated immunoprecipitation technique show good agreement.

Acrolein↗

Non-separation fluoroimmunoassay of human albumin in biological fluids.

Determination of albumin levels in biological fluids by a simple, rapid, non-separation fluoroimmunoassay is described. The method ("indirect quenching" fluoroimmunoassay) employs albumin labelled with fluorescein and antibodies against both albumin and fluorescein. Anti-fluorescein serum is added to the conventional immunoassay mixture of sample (or standard), labelled albumin and anti-albumin serum. The fluorescein groups of the free fraction of the labelled albumin become bound by anti-fluorescein antibody and their fluorescence is quenched, whereas the bound fraction is sterically protected from similar quenching. The extent of quenching thus reflects the relative amounts of the free and bound fractions in the unseparated assay mixture. Correlation studies with an automated immunoprecipitation technique show good agreement.

Albumins↗

Separation fluoroimmunoassay methods for phenytoin in serum.

A separation fluoroimmunoassay system for phenytoin was established based on the use of a specific rabbit antiserum, a fluorescein-labelled ligand, and precipitation of the antibody-bound fraction of the labelled ligand with sodium sulphate. Simple measures were taken to obviate non-specific binding and matrix effects. Either the free fraction (in the supernatant) or thebound fraction of the labelled ligand was quantitated fluorimetrically. Assays of patient serum samples by either method correlated well with established gas-liquid chromatographic and radioimmunoassay techniques. Advantages of a separation based procedure as compared with previously described non-separation hapten fluoroimmunoassay techniques are that only simple instrumentation and assay reagents are required, and that the separation step may enable the removal of any interfering intrinsic fluorescence of serum samples.

Fluorometry↗

The treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets.

We devised a method to enhance delivery of vinblastine to macrophages, the cells believed to be responsible for platelet destruction in idiopathic thrombocytopenic purpura. Our strategy was based on the ability of platelets to bind vinca alkaloids such as vinblastine. Platelets were incubated with an excess of vinblastine, concentrated and then, after excess alkaloid had been removed, given to 11 patients with idiopathic thrombocytopenia refractory to other treatment (including intravenous injections of vinca alkaloids). Platelet antibodies in the patients' plasma led to ingestion of the vinca-laden platelets by macrophages. There were six complete remissions, three partial remissions and two failures. Side effects in a few patients, reversible but annoying, were minimized as technics were refined. We conclude that in patients with idiopathic thrombocytopenia refractory to all other measures, including the use of vinca alkaloids, platelet-vinca complex may be effective.

Adolescent↗

Polarisation fluoroimmunoassay of phenytoin.

A polarisation fluoroimmunoassay for the determination of phenytoin levels in serum is described. Fluoresceinthiocarbamyl alpha,alpha-diphenylglycine (FTC-DPG) is used as an easily prepared fluorescent-labelled analogue of phenytoin. Interference from the non-specific binding of FTC-DPG by serum proteins is eliminated by proteolytic degradation of samples prior to assay. The method employs stable, non-radioactive reagents, requires no separation procedure, and involves only 1.25 microliter of serum. Analyses of serum samples from patients receiving phenytoin correlate well (r = 0.96) with an established gas-liquid chromatographic method.

Chromatography, Gas↗

Septate junctions in insects: comparison between intercellular and intramembranous structures.

Septate junctions have been studied in the hind-gut of Periplaneta americana, Incisitermes schwartzi and Thermobia domestica. The topographical disposition of intercellular septa revealed by lanthanum impregnation corresponds well with that of particle rows seen in freeze fracture preparations. However, there is no precise correspondence between the undulations of septa and the disposition of particles within a single row. The spacing of particles is variable and generally less than that of the undulation periodicity of septa. On the other hand, the disposition of septa, and of the rows of particles that correspond to them, appears to be variable: sometimes rectilinear and in close parallel, these may curve or form series of 'finger-print' loops. Moreover, the septa are evidently not deployed as continuous ribbons around the cell since intrruptions are freuqently observed. In addition to their mechanical role in intercellular cohesion, septate junctions apparently ensure a more or less complete closure of the intercellular space (i.e. provide a permeability barrier) and thus play a role comparable with that of tight junctions in epithelia of vertebrates.

Animals↗