A comparative examination of the in vitro metabolism of five cyclopenta[a]phenanthrenes of varying carcinogenic potential

Metabolites of 15,16-dihydrocyclopenta[a]phenanthren-17-oneand its 1- and 12-methyl homologues (all non-carcinogens) alongwith those from the 11-methyl and 11, 12-dimethyl-17-ketones(carcinogens), produced in vitro by hepatic microsomes frommethylcholanthrene induced rats, were separated by reverse phaseh.p.l.c. Identifications of individual metabolites were basedupon elution times, u.v. spectra, and in some cases by massspectrometry, circular dichroism, and identity with syntheticderivatives. All five compounds were biologically oxidised attheir terminal A and D rings to yield 1,2-dihydrodiols and 15-and 16- ols; with the exception of the 1-methyl compound, allalso gave similar amounts of 3, 4-dihydrodiols. The 1-methylcompound by contrast failed to produce this metabolite, furnishinginstead the 4-phenol and five other, probably related phenolicderivatives. Previous work has established that for the 11-methyl-17-ketone,the 3, 4-dihydrodiol is the proximate carcinogen. Thus, whereaslack of biological activity with the 1-methyl compound can beascribed to its failure to produce a 3,4-dihydrodiol, in thecase of the unsubstituted parent ketone and its 12-methyl derivativeother determining factors must come into play.     

Selecting patients with mitral regurgitation and left ventricular dysfunction for isolated mitral valve surgery

Background

American College of Cardiology/American Heart Association (ACC/AHA) Guidelines state that patients with an ejection fraction (EF) of 30% or less should not undergo mitral valve replacement for mitral regurgitation (MR). We sought to establish, using a national cardiac surgery database, whether patients with left ventricular dysfunction may safely undergo mitral valve surgery for MR, and if so, which ones.

Methods

We queried the Society of Thoracic Surgeons (STS) National Database to identify patients who had isolated mitral valve replacement or repair for MR between 1998 and 2001. Mortality and morbidity outcomes were compared by EF category (≤ 30% vs > 30%), and observed mortality compared by EF group, stratified by predicted risk for mortality. A classification and regression tree (CART) model was then used to determine which patient characteristics contributed most to designate the high-risk patient.

Results

Of the 14,582 patients who had mitral valve surgery, 727 had an EF of 30% or less and 13,855 had an EF of more than 30%. Observed mortality rates were higher for patients with an EF of 30% or less (5.4% vs 3.1%). However, for low-risk to medium-risk patients, mortality rates remained fairly constant across levels of EF. Mortality is notably increased in the high-risk patients (predicted risk > 10%). A classification tree identifies three key characteristics for high risk: age more than 75 years, renal failure, and emergent or salvage procedure.

Conclusions

When the predicted mortality risk is less than 10%, EF has minimal impact on operative mortality for mitral regurgitation. In contrast to the ACC/AHA Guidelines, our data show that operative risk for mitral valve surgery is not prohibitive for most patients with ventricular dysfunction.     

Self-reported nutrition proficiency is positively correlated with the perceived quality of nutrition training of family physicians in Washington State

BACKGROUND: Despite concerted scientific, educational, and congressional calls to increase nutrition coverage in medicine for more than half a century, most graduating medical students report an inadequate quality and quantity of nutrition training. Furthermore, practicing physicians report a lack of confidence and related proficiency in nutrition counseling skills because of inadequate training. Assessment of nutrition proficiency and related training of practicing physicians may support the prioritization of nutrition topics to be included in medical education. OBJECTIVE: We tested the hypothesis that the perceived adequacy of nutrition training (quality and quantity) of family physicians in Washington State is positively correlated with self-reported nutrition proficiency in 5 nutrition factors determined after confirmatory factor analysis. DESIGN: A randomized mail survey method (n = 778 possible respondents), which involved one mass-mailing follow-up, was used. RESULTS: A 39.3% response rate was achieved (n = 306 respondents). The 31-item questionnaire was reduced to 5 factors, explaining 48.5% of the total variance (alpha = 0.916). Perceived quality (poor to excellent) of nutrition training was positively correlated with self-reported nutrition proficiency scores for all 5 factors (P < 0.01). No significant differences were noted between zip code or sex and mean nutrition proficiency scores for all 5 factors. CONCLUSION: The examination of correlations between perceived quality of education and self-reported proficiency may be a useful gauge of effectiveness of nutrition training in medicine. Prioritization of nutrition information based on proficiency levels, including information on complementary and alternative medicines and nutritional management of disease, merits further investigation.     

A comparative analysis of freon substitutes in the purification of reovirus and calicivirus

Freon 113 (Freon) is an essential component used in some viral purification methods to separate virus from infected cell debris. With its environmental and toxic hazards, Freon's availability is limited and more tightly regulated. Several organic solvent substitutes were selected to identify a suitable Freon replacement for the purification of both cultivable reovirus and fastidious calicivirus. Reovirus was extracted from tissue cultured cells with each solvent tested and purified in cesium chloride gradients by standard techniques. Purified virions were analyzed for conservation of physical and biological properties by morphological examination and infectivity studies. The purification of calicivirus nucleic acid from stool samples using selected solvents was also examined. Solvent-extracted calicivirus RNA was reverse transcribed and quantified by polymerase chain reaction amplification of a standard diagnostic 117 bp amplicon. These studies indicated that Vertrel XF (a newly developed environmentally friendly Freon substitute) and a 7:3 mixture of isopentane/1-chlorobutane are suitable replacements. Considerations of flammability and ease of use suggest that Vertrel XF is the preferred choice as a Freon substitute for the purification of these non-enveloped viruses.     

Respiratory function after repair of congenital diaphragmatic hernia

Respiratory function studies were carried out in 22 infants who had successful repair of diaphragmatic herniae of the Bochdalek type. Thoracic gas volume was initially reduced in only 3 of these, but subsequent studies showed that improvement occurred. There were no consistent abnormalities in either dynamic compliance or mean pulmonary conductance. This is evidence that there is rapid adaptation which compensates for any alteration in the parenchymatous tissue in the lungs or abnormalities in the bronchial tree in infants soon after the repair of congenital diaphragmetic herniae. Further studies are necessary to determine the changes in these lungs with growth.