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DNA flow cytometry in stage IB and II cervical carcinoma

In a retrospective study the prognostic significance of nuclear DNA content was investigated, as measured by flow cytometry, of the tumor specimens from 212 women with nonpretreated FIGO stage IB and II cervical cancer. One-hundred and thirty cases (62%) were found to be diploid, whereas 82 (38%) were aneuploid. Univariate analysis of the follow-up data showed an increased relative risk (RR) for recurrence free survival (RFS) for stage II tumors (RR = 1.87, 95% CI: 1.13–3.10, P = 0.015) and for age (RR = 1.52, 95% CI: 0.66–3.52 and RR = 2.35, 95% CI: 1.19–4.65, P = 0.032). Ploidy showed a relative risk of 1.33 (95% CI: 0.83–2.13, NS). In addition, univariate analysis of overall survival (OS) revealed similar results. For the subgroup of patients with primary surgery ( n = 151), positive pelvic nodes (RR = 5.38, 95% CI: 2.70–10.71, P = 0.0001) and parametrial extension (RR = 2.53, 95% CI: 1.24–5.17, P = 0.011) were significant factors for OS after univariate analysis, the estimated effects on RFS were slightly smaller. Multivariate analysis of RFS for the whole study population showed age, histologic grade and stage with a slightly increased risk, but no effect was significant. Ploidy with an RR of 0.97 (95% CI: 0.58–1.62) seems to have no influence on prognosis. For the subgroup with primary surgery, ploidy again failed statistical significance with an RR of 1.20 (95% CI: 0.58–2.49). Our results suggest that abnormalities of the nuclear DNA content in this homogeneous group of patients are associated with clinical and morphological prognosticators, however, ploidy is not an independent prognostic factor for RFS, or for the whole study population or for the subgroup with primary surgery.     

Population toxicokinetics of tetrachloroethylene

 In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of tetrachloroethylene (PERC) in humans. We derive statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979). The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between PERC exposure and fraction metabolized is obtained. Our median population estimate for the fraction of inhaled tetrachloroethylene that is metabolized, at exposure levels exceeding current occupational standards, is 1.5% [95% confidence interval (0.52%, 4.1%)]. At levels approaching ambient inhalation exposure (0.001 ppm), the median estimate of the fraction metabolized is much higher, at 36% [95% confidence interval (15%, 58%)]. This disproportionality should be taken into account when deriving safe exposure limits for tetrachloroethylene and deserves to be verified by further experiments. Received: 20 April 1995/Accepted: 24 August 1995     

Should every patient undergo cardiac catheterization after myocardial infarction?

During the past few decades, management of patients with myocardial infarction has dramatically evolved. High-risk patients are now identified by a variety of noninvasive tests, and aggressive use of reperfusion strategies has improved clinical outcomes. Despite the benefits of reperfusion, only a few patients are eligible to receive thrombolytic therapy. Mortality rates among patients excluded from thrombolytic trials (15% to 20%) have been far greater than those eligible for treatment (3% to 10%). Because most deaths occur within the first few days of infarction, interventions designed to reduce mortality should be performed acutely. Immediate catheterization allows identification of high-risk anatomy that may benefit from surgery and allows coronary angioplasty to be performed as a reperfusion strategy (when appropriate). Furthermore, catheterization allows documentation of ejection fraction, vessel patency, number of diseased vessels, and residual stenosis, all of which have been predictive of prognosis. Conversely, frequently repeated noninvasive diagnostic tests are associated with increased cost, are generally performed in low-risk patients, and 60% to 80% of patients with myocardial infarction ultimately require catheterization anyway. It is possible that early catheterization and percutaneous transluminal coronary angioplasty when indicated may effectively risk stratify patients (eliminating the need for noninvasive testing), may reduce morbidity and mortality, and shorten the length of hospital stay.     

Role of nuclear cardiology for determining management of patients with stable coronary artery disease

Both radionuclide angiography and myocardial perfusion imaging provide important insights that determine the management of patients with stable coronary artery disease. Both nuclear cardiology procedures have clearly demonstrated use in the noninvasvie identification of severe (left main or three-vessel) coronary artery disease and the noninvasive assessment of prognosis and thereby determine which patients should be sent to coronary angiography. Both radionuclide angiography and myocardial perfusion imaging provide prognostic information that is independent of resting left ventricular function and coronary anatomy and thereby influence the decision regarding which patients should be sent to coronary revascularization. This review considers the evidence supporting the uses of these nuclear cardiology procedures and provides suggestions regarding their cost-effective application.