Increased effective lung volume following lung volume reduction surgery in emphysema.

STUDY OBJECTIVES: Lung volume reduction surgery (LVRS) for emphysema has a variable effect on spirometry with improvement linked to increases in lung elastic recoil. The mechanism by which recoil increases following LVRS has not been described completely. This study examines preoperative and postoperative pulmonary function to describe a mechanism for changes in airflow obstruction. DESIGN: Change in pulmonary function following LVRS. Setting : Public teaching hospital in Australia. PATIENTS: Patients with severe emphysema and pulmonary function measurements made before and after LVRS. MEASUREMENTS: Routine pulmonary function testing performed with ventilated lung alveolar volume (VA) derived from the gas transfer measurement used as a proxy for the effective lung volume. RESULTS: Pulmonary function tests from 36 consecutive patients with measurements made at the same laboratory were analyzed. The mean FEV(1) was 29.1% predicted presurgery and increased following LVRS from 0.900 L (SD, 0.427 L) to 1.283 L (SD, 0.511 L; p < 0.0001) and TLC (143% predicted) decreased from 8.19 L (SD, 1.492 L) to 7.07 L (SD, 1.52 L; p < 0.0001; n = 35). The mean VA increased by 0.674 L (SD, 0.733 L) from 4.04 to 4.72 L (p < 0.0001; n = 34). The change in FEV(1) correlated well with the change in VA (r = 0.63). The change in FEV(1) in those patients whose VAs did not increase (n = 7) was not significant. CONCLUSIONS: The increase in VA reflects an increase of functional or ventilating lung volume and is associated with an improvement in spirometry following LVRS.

Reducing the cost of cyclosporin assays: modification of the EMIT 2000 method.

Cyclosporin is the leading immunosuppressant agent in organ transplantation, and therapeutic drug monitoring forms an integral part of patient management in most institutions. In the authors' laboratory, the cost of cyclosporin assays represents a major fraction of total consumable expenditure. At present, an average of 4,300 patient cyclosporin assays are performed annually using the EMIT 2000 method (Behring-Syva) on the Cobas Mira analyser (Roche), at a cost of AUD$50,000 in kits alone. As a means of reducing laboratory costs, the manufacturer's recommended method was modified by decreasing all of the reagent and sample volumes in the "Analytical" section of the Cobas Mira cyclosporin programme by 33%. Assay performance was monitored over a 10-month period and compared to that of the unmodified method. Calibration curves were stable, requiring a one-point correction on average of once every 12 days, and a full calibration once ever 1.7 months. Interassay variability was not different to that previously reported for the unchanged method, with mean (SD, CV) concentrations for trilevel quality control specimens of 86.5 micrograms/L (10.2, 11.9%), 185.9 micrograms/L (11.4, 6.2%) and 408.5 micrograms/l (28.9, 7.1%). From 24 specimens assayed in an international quality assurance programme, the results of 23 were within 1.2 SD of the group mean for the EMIT method, with an average bias of 0.8%. With the current modifications, we were able to perform an average of 105 patient assays per kit compared to the previous 71, equating to an annual saving the AUD$16,600.

Enzyme-multiplied immunoassay (EMIT 2000) digoxin assay compared with fluorescence polarization immunoassay and amerlex 125I-radioimmunoassay at two Australian centers.

Digoxin assays in plasma from patients treated with the drug have played an integral role in its therapeutic management. Commercial digoxin immunoassays have been criticized for poor performance owing to various interferences and limited sensitivity. The present study compared the performance of a new enzyme-multiplied immunoassay technique (EMIT 2000) to fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA) in two separate Australian centers. Comparisons were made using standard indices of precision and accuracy, samples taken from patients, quality-assurance samples, and cord blood samples from neonates, in which high concentrations of digoxin-like immunoreactive substances (DLIS) would be anticipated. The results confirmed satisfactory precision and accuracy for therapeutic drug monitoring purposes, a sensitivity of < 0.1 microgram/L, and very low DLIS interference, as assessed by assay of neonatal cord blood samples.

Dextromoramide pharmacokinetics following sublingual administration.

The extent of absorption and other pharmacokinetic parameters of dextromoramide following sublingual administration were assessed in five patients receiving chronic opioid analgesia. The use of the standard 5 mg tablet formulation was associated with negligible absorption in two patients, a prolonged time to peak concentration in the other three and substantial variability in clearance. The study concluded that the standard tablet formulation cannot be recommended for sublingual use where reliable, rapid onset analgesia is required.

Experiences with the enzyme-multiplied immunoassay cyclosporine specific assay in a therapeutic drug monitoring laboratory.

Cyclosporin-A (CsA) monitoring is well established in the management of most organ transplant patients. The present communication reviews the performance of the recently introduced specific enzyme-multiplied immunoassay (EMIT) CsA method during the first 7 months of its operation and compares costs of providing this service with those of the specific 125I radioimmunoassay (RIA) method previously employed in this clinical laboratory. Results suggest that the EMIT method performed well, giving long calibration curve stability (up to 12 weeks), and only 4.4% of the 31 kits through this period were consumed in assaying calibration standards compared with 20.8% with RIA. However, more quality control assays were performed, with the net result that only a slight improvement in the percentage of kit consumed in patient assays was noted (74.0% compared with 70.3%) with the EMIT method. This method appears to have been well accepted clinically as the CsA assay request rate over this period increased by 23% and, since it is both specific and rapid, is, therefore, recommended as the best CsA method currently available.

Specific enzyme-multiplied immunoassay and fluorescence polarization immunoassay for cyclosporin compared with Cyclotrac [125I]radioimmunoassay.

The analysis of cyclosporin-A (CsA) has proved a valuable adjunct to clinical care of patients who have received organ grafts. The measurement of CsA in whole blood by specific methods has recently taken a new direction with the introduction of a range of rapid methods, including a homogeneous enzyme immunoassay technique (EMIT) and a monoclonal fluorescence polarization immunoassay (FPIA). The present paper compares these two methods with the established Cyclotrac specific [125I]RIA (radioimmunoassay) using both commercial CsA-spiked control material as well as a group of 60 patient specimens (predominantly renal transplants). While each of the new methods showed acceptable precision and accuracy with the commercial quality control material, significant differences were demonstrated with patient specimens, such that FPIA was 12.5% greater than [125I]RIA (p less than 0.0001), which was in turn 5.9% greater than EMIT (p = 0.007). These data suggested that the FPIA may have residual CsA-metabolite interference and that the EMIT method was the most "specific" for parent CsA of the three tested, potentially therefore more comparable to high-performance liquid chromatography (HPLC).

Improved high-performance liquid chromatography assay for atenolol in plasma and urine using fluorescence detection.

An improved assay for racemic atenolol (AT) concentrations in human plasma and urine is described using a high-performance liquid chromatographic method with fluorescence detection. The method has a sensitivity limit of 0.5 micrograms/L in plasma with acceptable within- and between-run reproducibilities, and demonstrated linearity at concentrations up to 2,000 micrograms/L. A pilot clinical evaluation of the assay was undertaken on 56 trough plasma specimens from 36 outpatients on established AT therapy. Atenolol concentrations in these patients showed large variations at all prescribed doses, including undetectable levels in four patients (revealing unsuspected noncompliance). Because of its sensitivity and applicability to urinary analysis, the method can be used for pharmacokinetic studies and, under certain circumstances, may be valuable in clinical therapeutic drug monitoring.

Interference from digoxin-like immunoreactive substance(s) in commercial digoxin kit assay methods.

We have examined the current state of interference by digoxin-like immunoreactive substance(s) (DLIS) in 10 commercially available digoxin assay methods, ie 5 radioimmunoassays (RIA) and 5 non-radioactive immunoassays. Fifty-five specimens of maternal venous blood (30 from third trimester pregnancy and 25 at delivery) and 32 cord samples from their offspring were tested (none of the subjects being medicated with digoxin). The results demonstrated a wide range of DLIS interference with values up to 1.1 micrograms.l-1 being obtained in the cord blood specimens. Of the methods tested the "Coat-a Count" RIA (Diagnostic Products Corporation) and the EMIT column method (Syva) run on the Cobas MIRA (Roche) consistently showed the least interference with respect to all 3 sources of specimens. The Delfia Method (LKB/Wallac) consistently showed the greatest crossreactivity with DLIS. The present study thus demonstrates that DLIS interference persists in several commercial digoxin methods and suggests that the use of data obtained from such methods may compromise patient management.

Alteration in doxorubicin and doxorubicinol plasma concentrations with repeated courses to patients.

Fifteen cancer patients were studied following repeated courses of doxorubicin (12-44 mg/m2) (together with other anticancer agents) to consider the possibility of enhanced metabolism as a cause of the previously reported reduction in doxorubicin plasma concentrations with repeated courses. Plasma doxorubicin and doxorubicinol concentrations were measured by a modified high-performance liquid chromatography/fluorescence method. The results presented confirmed the significant decline in doxorubicin plasma concentration-dose ratios measured 3 h after the 1-h infusion. Although the degree of this reduction varied markedly between patients, it was shown not to be associated with a rise in the plasma concentration-dose ratio of the major metabolite doxorubicinol or with altered renal and/or hepatic function, which may have influenced disposition. Alternative mechanisms that might explain the reduction in doxorubicin concentrations, such as increased doxorubicin clearance or volume of distribution, were not considered in the present study.