Myocardial imaging with technetium-99m-tetrofosmin: comparison of one-day and two-day protocols

There is no evidence of myocardial redistribution after tetrofosmin injection, therefore, two separate injections are needed to differentiate scar from ischemia with this tracer. The injections can be given on the same day (one-day protocol) or on separate days (two-day protocol). As part of a Phase II clinical study, a one-day protocol was compared with a two-day protocol. METHODS: Fifty-five patients with suspected coronary artery disease were studied according to the following protocol: on the first day at rest, anterior, left lateral, left anterior oblique 40 degrees and 70 degrees images were acquired 30 min after injection of 8 mCi of tetrofosmin for 5 min each. Two days later, exercise and rest images were acquired on the same day. At peak exercise, 8 mCi of tetrofosmin were injected and 30 min later the same four standard planar images were recorded as on Day one. Four hours after the exercise injection, 24 mCi of tetrofosmin were injected at rest and imaging was repeated 30 min later. Qualitative comparisons between the one- and two-day protocols were performed in 50 patients in whom all data were available following blinded evaluation of images by three readers. RESULTS: All three readers reported identical results for the 26 patients. A difference in extent or location between the observers was found in seven patients, differences between normal and abnormal in eight patients, while discrepancies between ischemia and necrosis were noted in four patients. In five patients, an ischemic area was found according to the one-day protocol, but according to the data of the two-day protocol, this area was judged to be necrotic. One observer reported the opposite in one patient. These discrepancies between the reversibility of defects were restricted to the inferior wall. Comparison with 201Tl data showed no systematic pattern of variation. CONCLUSION: Tetrofosmin can be used in a one-day protocol. However, in planar imaging, the inferior wall should be reported with caution.     

Composite finger metacarpophalangeal joint reconstruction in combined second and third free toe-to-hand transfers

Composite metacarpophalangeal joint reconstruction using the toe proximal phalanx and the metacarpal head, with a capsular repair, is an option during free toe transfer procedures for absent fingers. Eleven composite metacarpophalangeal finger joint reconstructions were performed in four patients concurrent with combined second and third toe-to-hand transfer. The average follow-up period was 5 years. Postoperative assessment included range of motion, stability, radiographic changes, and pain. The average range of motion was 52 degrees, average ulnar stress deviation was 14 degrees. No patients complained of pain. Composite metacarpophalangeal joint reconstruction should be considered in free toe-to-hand procedures when metacarpal head articular cartilage is preserved.     

Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.     

Contributions of empirical research to medical ethics

Empirical research pertaining to cardiopulmonary resuscitation (CPR), clinician behaviors related to do-not-resuscitate (DNR) orders and substituted judgment suggests potential contributions to medical ethics. Research quantifying the likelihood of surviving CPR points to the need for further philosophical analysis of the limitations of the patient autonomy in decision making, the nature and definition of medical futility, and the relationship between futility and professional standards. Research on DNR orders has identified barriers to the goal of patient involvement in these life and death discussions. The initial data on surrogate decision making also points to the need for a reexamination of the moral basis for substituted judgment, the moral authority of proxy decision making and the second-order status of the best interests standard. These examples of empirical research suggest that an interplay between empirical research, ethical analysis and policy development may represent a new form of interdisciplinary scholarship to improve clinical medicine.