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Biomedical subjects

L Nye

Publications and source records attributed to L Nye.

12 recordsLinked to original sources

Kt/V, nutritional parameters, serum cortisol, and insulin growth factor-1 levels and patient outcome in hemodialysis.

Despite many technical advances in dialysis care, morbidity and mortality in chronic hemodialysis patients in the United States remains high. In this study, we analyzed the effects of Kt/V, nutritional parameters (serum albumin level, triceps skin-fold thickness, mid-arm muscle circumference, and normalized protein catabolic rate), and predialysis serum cortisol and insulin growth factor-1 levels on predicting morbidity and mortality. The cohort studied consisted of 52 patients recruited from a single outpatient dialysis facility. Cox proportional hazards modeling indicated that only Kt/V predicted subsequent mortality (P = 0.02), while both predialysis cortisol levels (P = 0.03) and Kt/V (P = 0.03) predicted hospitalization. Kaplan-Meier analysis demonstrated that the ability of cortisol levels to predict hospitalization was largely confined to the group with values greater than 22 micrograms/dL predialysis. High serum cortisol levels were correlated with low serum albumin levels and a trend toward low triceps skin-fold thickness and higher normalized protein catabolic rate, suggesting a catabolic state. Both predialysis serum cortisol and insulin growth factor-1 levels were higher than those in age- and sex-matched normal human controls. These results demonstrate the importance role of Kt/V in predicting subsequent hospitalization rates and mortality, and that high predialysis serum cortisol levels correlate with a high hospitalization rate.

Adult↗

Multiple-dose pharmacokinetics of piperacillin and azlocillin in 12 healthy volunteers.

The pharmacokinetic profile of piperacillin and azlocillin after multiple-dose administration to healthy volunteers was studied. Twelve healthy volunteers received either piperacillin 4 g (as the sodium salt) or azlocillin 4 g (as the sodium salt) as a 20-minute infusion every six hours for five doses. After a one-week washout period, subjects received identical treatment with the alternate drug. Serum and urine concentrations of piperacillin and azlocillin were measured using a reversed-phase high-performance liquid chromatographic assay, and the pharmacokinetic analysis of serum concentration-versus-time data was performed using a computerized program. A standard open-model equation for i.v. infusions was used. Mean serum concentrations of piperacillin and azlocillin after dose 5 were 344 +/- 66 micrograms/mL and 414 +/- 86 micrograms/mL, respectively. The terminal elimination half-life of azlocillin (1.1 +/- 0.2 hr) was significantly longer than that of piperacillin (0.75 +/- 0.13 hr) (p less than 0.05). Total body clearance of azlocillin (125 +/- 25 mL/min) was significantly less than that of piperacillin (226 +/- 43 mL/min) after dose 5. Azlocillin showed accumulation between the first and fifth doses. Twelve hours after administration of dose 5, 75% of azlocillin and 57% of piperacillin were excreted unchanged into the urine. In healthy volunteers, azlocillin produced higher and more prolonged serum concentrations than piperacillin after administration of equivalent i.v. doses. Further studies are needed to determine the clinical importance of these observations.

Adult↗

An investigation of the clonality of human autoimmune thyroglobulin antibodies and their light chains.

Thyroglobulin antibodies in the sera from 31 patients with a variety of disorders were studied by isoelectric focusing. Only one gave a spectrotype indicative of a monoclonal response, the other 30 giving spectrotypes characteristic of polyclonal responses. There was evidence of clonal dominance in some of the sera and each gave a different spectrotype. Light chains were prepared from five thyroglobulin antibodies purified by affinity chromatography. There was no restriction in the spectrotypes when compared with light chains prepared from normal immunoglobulin.

Antibodies, Monoclonal↗

Isoelectric focusing of human antibodies directed against a high molecular weight antigen.

A simple technique has been developed to assess the spectrotypes of antigen-specific human autoantibodies. Following isoelectric focusing in 3 M urea at 1200 V for 2 h, immunoglobulins were fixed in polyacrylamide gels by precipitation with sheep anti-human immunoglobulin in the presence of sodium sulphate. Specific anti-thyroglobulin antibody bands were labelled by reaction with [125I]thyroglobulin, an antigen with a molecular weight of 660,000 daltons which is too large to enter the gel. The advantages of this method include increased sensitivity and reproducibility, and the ability to produce sharper bands and less non-specific binding than other methods.

Antibody Specificity↗

Restrictions in the response to autologous thyroglobulin in the human.

Fragments of thyroglobulin containing the autoreactive epitopes were prepared by an existing procedure, plus an ion-exchange chromatography step which increased their purity. Before purification, 39% of the fragmental material was bound by rabbit anti-human thyroglobulin whereas only 8% was bound by autoantibody, thus confirming earlier reports of more limited epitopes for human autoantibodies than heterologous antibody. Thyroglobulin autoantibodies in the globulin fractions from six human sera showed between 70 and 100% cross-reaction with one another, indicating that the majority of antibodies are directed against the same epitopes. The data are consistent with an estimated of two distinct major epitopic specificities with occasional sera having antibodies directed against a third site. Chemical modification of tyrosine residues by iodination did not inhibit the binding of thyroglobulin to either human autoantibodies or rabbit anti-human thyroglobulin; thus tyrosine residues do not contribute significantly to the epitopes for either auto- or heteroantibodies.

Animals↗

Automated tests for the assessment of thyroid function.

Fully automated methods have been developed for the determination of thyroxine and triiodothyronine levels, antibodies to thyroglobulin and the assessment of thyroid hormone binding proteins in serum, using a continuous flow radioimmunoassay system. In addition the feasibility of a partially automated assay for thyrotrophin levels has been demonstrated. These employ Auto Analyzer modules and antibodies covalently linked to a magnetisable solid phase support. Separation of bound and free antigen is achieved by applying an external magnetic field. The system currently operates at a rate of 30 samples/h and requires only 10 minutes incubation since it is not necessary to reach equilibrium. The results are similar to those obtained by conventional manual techniques, however the precision is improved and operator error eliminated.

Female↗

Solid-phase, magnetic particle radioimmunoassay.

A solid-phase radioimmunoassay system has been developed based on the use of antibodies covalently linked to polymer-coated iron oxide (EnzacrylR). An electro-magnet is employed both to mix the particles during incubation (by switching the field on and off) and to separate the antibody-bound and free fractions. This obviates the need for vertical rotation and for the time-consuming, multiple centrifugations required with conventional solid phase procedures. The system is universally applicable and methods have been established for the assay of thyroxine, human placental lactogen and digoxin. The thyroxine assay was employed as a model and it was shown that the results obtained for serum samples correlated closely with those using a routine liquid-phase radioimmunoassay. The applicability of employing a second antibody linked to the iron oxide particles was also studied.

Binding Sites, Antibody↗

Introduction of a rapid, simple radioimmunoassay and quality control scheme for thyroxine.

A simple radioimmunoassay has been developed for service purposes to determine serum total thyroxine levels. Only three additions are required, of standard or sample, labelled thyroxine and antibody in polyethylene glycol. After 2 hours' incubation at room temperature the antibody-bound and free fractions are separated by centrifugation. Serum total thyroxine levels were measured in 195 euthyroid subjects and it was established that normal values lay within the range 57 to 155 nmol/1. Serial blood samples taken over a 24-hour period, from 11 subjects, indicated that there was no circadian rhythm so that samples for total thyroxine assay can be taken at any time of the day. Similar results were obtained using serum or plasma. Satisfactory results were obtained for three quality control sera when measured by seven different laboratories using this method.

Adolescent↗

A detailed investigation of circulating IgE levels in a normal population.

Total circulating IgE levels were measured in a carefully selected normal population, using a highly sensitive double antibody assay. The mean level of 36.3 u/ml found in this group is much lower than that reported in all previous studies. No circadian rhythm was evident, but IgE levels varied slightly from day-to-day. IgE levels in 100 serum samples were compared using the double antibody assay and the Phadebas test kit, based on a solid phase technique. A poor correlation was obtained with values below 100 u/ml, however, there was an excellent correlation for samples with IgE levels above this figure.

Adolescent↗

Stability of thyroxine and triiodothyronine in biological fluids.

The stability of thyroxine and triiodothyronine in serum has been investigated. Apparent levels of total thryroxine, as determined by two different protein-binding assays employing thyroxine-binding globulin as the binding protein, increased significantly in serum and plasma samples stored at room temperature and were signficantly lower in haemolysed samples. Values did not change significantly in samples stored at 4 degrees C, nor in samples stored at room temperature when determined by radioimmunoassay. Total triiodothyronine levels, as determined by radioimmunoassay, fell slightly on storage. Failure to appreciate the effect of storing samples at room temperature on apparent levels of total thyroxine, as determined by some protein-binding assays, could lead to an incorrect assessment of thyroid status.

Drug Stability↗

The effect of portacaval anastomosis on oral carbohydrate tolerance and on plasma insulin levels.

In patients with portal hypertension, plasma insulin levels were raised both fasting and after oral glucose or intravenous tolbutamide. This supports previous suggestions that resistance to endogenous insulin plays a major role in producing the impaired glucose tolerance found in chronic hepatic dysfunction. The operation of portacaval anastomosis was followed by impaired oral fructose tolerance, but did not significantly change oral glucose tolerance. Plasma insulin levels were unchanged by the operation, either fasting or following the stimulus of an oral glucose load or intravenous tolbutamide. The insulin response after operation was only higher after intensive pancreatic beta cell stimulation by a combination of glucose, tolbutamide, and glucagon. These results indicate that, in patients with hepatic dysfunction, little insulin is being removed by the liver from the portal blood except when the insulin secretory rate is unusually high.

Fasting↗