Overcoming language barriers when teaching the Advanced Trauma Life Support course

OBJECTIVES: To determine whether blurred vision caused by exposure to triethylamine (TEA) can be detected by the measurement of contrast sensitivity. METHODS: 41 cold box core makers of three foundries and 82 control workers were examined. A detailed ocular and medical history was obtained from the subjects. The contrast sensitivity of the core makers was measured on Monday and Friday of the same week both before and immediately after work and also on a third day, when air samples of TEA were collected. Contrast sensitivity and visual acuity were measured by optotype figures at full contrast, 2.5% contrast, and 0.6% contrast. The changes in contrast sensitivity were used for the analysis. The results of binocular vision and the results of the dominant eye were analysed. Urine specimens for the analysis of TEA were collected on every occasion when contrast sensitivity was measured. RESULTS: 78% of the core makers had had symptoms of blurred vision, and 31% had had trouble driving or working. The breathing zone eight hour time weighted average TEA concentrations were 0.3-60 mg/m3. The mean urinary TEA concentration after the shift was 35 mmol/mol creatinine. Continuous monitoring showed high peaks of TEA leakage at a core making machine. Changes in binocular visual acuity did not differ between the exposed and unexposed workers. The contrast sensitivity decreased in 49% of the core makers and 21% of the controls (P = 0.002). CONCLUSIONS: The blurred vision caused by exposure to TEA can be documented by measuring contrast sensitivity. The mechanism by which TEA produces symptoms remains an issue of further study.     

The folding of centromeric DNA strands into intercalated structures: a physicochemical and computational study

We have carried out a physicochemical and computational analysis on the stability of the intercalated structures formed by cytosine-rich DNA strands. In the computational study, the electrostatic energy components have been calculated using a Poisson-Boltzmann model, and the non-polar energy components have been computed with a van der Waals function and/or a term dependent on the solvent-accessible surface area of the molecules. The results have been compared with those obtained for Watson-Crick duplexes and with thermodynamic data derived from UV experiments. We have found that intercalated DNA is mainly stabilized by very favorable electrostatic interactions between hydrogen-bonded protonated and neutral cytosines, and by non-polar forces including the hydrophobic effect and enhanced van der Waals contacts. Cytosine protonation electrostatically promotes the association of DNA strands into a tetrameric structure. The electrostatic interactions between stacked C.C+ pairs are strongly attenuated by the reaction field of the solvent, and are modulated by a complex interplay of geometric and protonation factors. The forces stabilizing intercalated DNA must offset an entropic penalty due to the uptake of protons for cytosine protonation, at neutral pH, and also the electrostatic contribution to the solvation free energy. The latter energy component is less favorable for protonated DNA due to the partial neutralization of the negative charge of the molecule, and probably affects other protonated DNA and RNA structures such as C+-containing triplexes.     

Determining the cost of a clinical intervention through the use of shadow pricing

This article reviews the scientific literature in several areas important to the delivery of palliative care: multicultural issues, education, comprehensive outcome measures and ethics. Most of the research can be classified as fundamental rather than intervention research according to the Cancer Control Framework of the National Cancer Institute of Canada. Desired outcomes of interventions are most often defined from the health care professional's perspective but need to be defined from the patient's perspective. In areas such as multicultural issues and the effect of the volunteer on the patient, there is almost no research. The complexity of studying the best way to deliver palliative care would benefit from the input of colleagues who have experience addressing these issues in other patient populations.     

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.     

Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer

BACKGROUND: In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake. METHODS: In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided. RESULTS: The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03). CONCLUSIONS: Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted.     

Clinical significance of echocontrast enchancement in neurovascular diagnosis. Review of experience following a year of use

AIM OF THE STUDY: To evaluate the potential and limitations of echocontrast enhancement using Levovist in a non selected consecutive cohort of neurological patients with insufficient native ultrasound investigations. METHODS: In 91 patients an indication for echocontrast application was seen after an insufficient extracranial (n = 17), transtemporal (n = 54), and transforaminal (n = 20) Doppler- und color-coded Duplex sonography. Levovist was injected at a concentration of 400 mg/ml and 200-400 mg/ml for the transcranial and extracranial approach, respectively. The effect of the echocontrast enhancement was assessed semiquantitatively with respect to signal enhancement, imaging quality, and diagnostic confidence. RESULTS: In a total of 83 patients (91%) the signal enhancement led to a moderate to high imaging quality allowing to reach 67 definite neurovascular diagnoses (74%). In subgroup analysis, the amount of sufficiently confident examinations was significantly higher for the transtemporal and transforaminal (both 80%) than for the extracranial approach (47%). The latter was mostly due to artificial signals derived from adjacent neck vessels. CONCLUSION: Levovist constitutes a safe and highly effective diagnostic tool especially for the transtemporal and transforaminal neurosonographical imaging. By means of a differentiated application of echocontrast agents, its cost-effectiveness can be increased and the need for other potential invasive and expansive neuroimaging methods can be further reduced.     

Electrophysiological basis of arrhythmogenicity of QT/T alternans in the long-QT syndrome: tridimensional analysis of the kinetics of cardiac repolarization

Tachycardia-dependent QT/T alternans occurs in patients with the congenital or idiopathic form of long-QT syndrome (LQTS) and may presage the onset of polymorphic ventricular tachyarrhythmias. To examine the electrophysiological basis of arrhythmogenicity of QT/T alternans in LQTS, the tridimensional repolarization pattern of QT/T alternans was studied in the anthopleurin-A model of LQTS, a surrogate for LQT3. In 11 anesthetized mongrel puppies, tridimensional repolarization and activation patterns were analyzed from 256 to 384 unipolar electrograms. Cardiac repolarization was evaluated as the activation-recovery interval (ARI) of local electrograms. To induce QT/T alternans, the pacing cycle length (CL) was abruptly shortened in steps of 50 ms from a basic drive of 1000 ms. ARIs were calculated at epicardial (Epi), midmyocardial (Mid), and endocardial (End) sites. ARI restitution at each site was assessed by using a single premature stimulation delivered after the basic drive. ARI alternans occurred at longer CLs at Mid sites compared with End and Epi sites, and the magnitude of alternans at Mid sites was greater. Two factors contributed to the modulation of ARI during QT/T alternans: (1) differences in restitution kinetics at Mid sites, characterized by larger DeltaARI and a slower time constant (tau), and (2) differences in diastolic intervals resulting in different input to restitution at the same constant CL. These 2 factors could explain not only the onset of alternans at Mid sites at longer CLs but also the critical observation that ARI dispersion between Epi and Mid sites during alternans was greater than during the slower basic CL. Marked ARI alternans could be present in local electrograms without manifest alternation of the QT/T segment in the surface ECG. The latter was seen at critically short CLs associated with reversal of the gradient of ARI between Epi and Mid sites, with a consequent reversal of polarity of the intramyocardial QT wave in alternate cycles. The arrhythmogenicity of QT/T alternans was primarily due to the greater degree of spatial dispersion of repolarization during alternans than during slower rates not associated with alternans. This could result in functional conduction block and reentrant ventricular tachyarrhythmias during the fixed drive associated with alternans.     

Noncanonical conformation of nucleic acids: structure with slipped-loops, occurring in DNA oligonucleotides

A HPLC method was developed and validated for the quantitation of 9-cis-retinoic acid (ALRT1057) and its major metabolite, 4-oxo-9-cis-retinoic acid (LG100182) in human plasma. Samples were buffered and extracted with methyl-tert-butyl-ether. The analytes and an I.S. were separated on a C18 HPLC column using a shallow gradient of 70-89% organic solvent. The analytes were quantitated by UV detection at 348 nm. Selectivity against endogenous compounds and potential metabolites (retinol, all trans-, 13-cis-, and 4-hydroxy-9-cis-retinoic acid) was demonstrated. The run time was 29 min. The standard curve was linear from 2.5 to 450 ng ml-1. Interassay precision for both analytes in quality control samples was less than 5.0% RSD. Accuracy was within 11.0% RE for both compounds. Analyte stability during sample storage, extraction processing, and chromatography was established. Method ruggedness was tested by two analysts and on two HPLC systems. This method has been applied to the quantitation of clinical samples.