The COBAS AMPLICOR CT/NG test for Neisseria gonorrhoeae cross-reacts with certain strains of nonpathogenic Neisseria species. In some strains, the target sequence is identical to that of N. gonorrhoeae, whereas other strains have a small number of mismatches within the regions recognized by the primers or probe used in the COBAS AMPLICOR NG test. These cross-reactive strains are occasionally present in urogenital specimens, causing false-positive results in the COBAS AMPLICOR NG test. Analysis of the data generated in a large multicenter clinical trial showed that 2.9% of the specimens gave signals between A 660 s of 0.2 and 3.5 but that one-half of these equivocal specimens did not contain N. gonorrhoeae. Most of these equivocal specimens were correctly classified as true positive or true negative by retesting in duplicate and defining a PCR-positive result as two of three results with an A 660 of >2.0. If specimens had been classified as positive or negative based on a single test result using a cutoff of an A 660 of 0.2, specificity would have ranged from 96.2 to 98.9% depending on specimen type, sex, and presence of symptoms. By employing the equivocal zoneretesting algorithm, specificity increased to 98.6 to 99.9% with little effect (0.1 to 4.9% decrease) on sensitivity in most specimen types, enabling the test to achieve a positive predictive value of at least 90% in populations with a prevalence of 4% or higher. In lower-prevalence populations, the test could be used to screen for presumptive infections that would have to be confirmed by an independent test.The COBAS AMPLICOR CT/NG test provides a powerful diagnostic tool for screening for both chlamydial and gonococcal infections. We and others have observed that the NG portion of the test (COBAS AMPLICOR NG) cross-reacts with some isolates of certain nonpathogenic Neisseria species (4). When the original, recommended cutoff (A 660 of 0.2) is used, the COBAS AMPLICOR NG test can produce false-positive results for Neisseria gonorrhoeae, presumably due to the presence of cross-reactive Neisseria species in some urogenital specimens. In one population, approximately 26% of COBAS AMPLICOR NG-positive results were false positives, which corresponded to approximately 3% of the total population (4). In contrast, the same laboratory observed fewer than 1% falsepositive results among urogenital specimens from a second population (4).In this paper, we confirm that the test does cross-react with some isolates of Neisseria subflava (4) and Neisseria cinerea and compare the target sequences in these cross-reactive species with that of N. gonorrhoeae. Using data from a multicenter trial (n ϭ 4,173 patients; prevalence ϭ 13.1%) conducted at six sites in the United States (8), we show how test sensitivity and specificity vary with the cutoff value used. We then assess whether both sensitivity and specificity can be optimized by establishing a large equivocal zone and using an algorithm that involves additional testing of specimens yielding equivocal results. Implementat...
1Mexiletine was given to 156 patients by intravenous or oral routes of administration. 2 There was great interpatient variation in kinetics and plasma concentrations with both routes of administration. 3 The mean volume of distribution was 6.63 1/kg. The mean plasma elimination half-life after chronic oral therapy was 11.31 h.4 Plasma concentrations between 0.75 and 2.00 gg/ml were usually effective. Within this therapeutic range severe side effects were uncommon. 5Plasma concentrations within this range were achieved in 72% of patients when doses of 10-14 mg-' kg-l day were given orally.
1 The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. 2 Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function.3 In patients with severe renal impairment (GFR values below 30 ml min7l 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.
1 Single dose studies of theophylline kinetics were compared in groups of young and elderly smokers and non-smokers to assess the effect of age on theophylline absorption and the effect of smoking on drug metabolising enzyme activity in old age. 2 The rate and extent of absorption was not affected by age. Distribution and elimination kinetics were similar in young and elderly non-smokers. 3 In young subjects the elimination half-life of theophylline was shorter and clearance was significantly greater in smokers than in non-smokers. 4 In the elderly mean elimination half-life was significantly shorter in smokers and their plasma clearance was 40% higher than in non-smokers. The statistical difference for clearance was at the 7% level of significance. 5 These data indicate that ageing per se does not affect theophylline elimination and also that induction of theophylline metabolism due to smoking occurs in old age. Smoking is a variable that should be taken account of when assessing drug metabolism in elderly patients.
Chronic liver disease is known to alter the absorption and disposition of many drugs. To assess the influence of chronic alcoholic liver disease on the disposition of naproxen, we administered the drug both as a single dose and to steady state to 10 individuals with alcoholic cirrhosis and to 10 healthy controls. Plasma and serum samples collected after naproxen dosing were assayed for both total and (following equilibrium dialysis) unbound drug concentration. Clearance calculated based on both total and unbound naproxen concentration revealed no change in total plasma clearance of the drug at steady state but a marked reduction of approximately 60% in clearance based on unbound drug. Naproxen volume of distribution changed only minimally. Because clearance based on unbound drug concentration at a given dosing rate determines the plasma or blood free drug concentration, this concentration may increase significantly in patients with alcoholic liver disease given usual doses of naproxen. Unbound drug concentration is thought to determine the pharmacologic effect of a drug. We therefore recommend that naproxen dosing be reduced by at least half in patients with chronic alcoholic liver disease. In the absence of data to the contrary, this recommendation can be extended to individuals with other forms of hepatic disease.
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