A Descriptive Analysis of the Epidemiology and Motivations for Laser Tattoo Removal in an Underserved Population

Journal of Community Health - Tattoos of formerly gang-involved and incarcerated individuals can negatively impact their ability to reintegrate into society. Laser tattoo removal is essential to...     

Isolation of the ERG2 gene,encoding sterol Δ8Δ→7 isomerase,from the rice blast fungus Magnaporthe grisea and its expression in the maize smut pathogen Ustilago maydis

The Magnaporthe grisea ERG2 gene, encoding ⁸⁷ sterol isomerase, was isolated from a genomic library by heterologous hybridization to a fragment of the Ustilago maydis ERG2 gene. The isolated gene contained a reading frame of 745 bp which encoded a protein of 221 amino acids. The coding region was interrupted by a single putative 79-bp-long intron. The deduced amino-acid sequence exhibited similarity to the ERG2 gene products of U. maydis and of Saccharomyces cerevisiae, particularly in the central region of the proteins. The NH₂-terminal of all three proteins contained a long stretch of amino acids that were strongly hydrophobic, suggesting that they may function by anchoring the protein to a membrane surface. The M. grisea ERG2 gene complemented a U. maydis deletion mutant in which the ERG2 gene had been removed using a one-step gene replacement procedure. The ⁸⁷ sterol isomerase produced by the M. grisea ERG2 gene exhibited a level of sensitivity to the sterol biosynthesis inhibitor, tridemorph, similar to that of the enzyme derived from the U. maydis ERG2 gene.     

Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer

Purpose: To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy.

Materials and Methods: Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value ≥ 1 ng/ml; or 2. a PSA value that rose ≥ 0.5 ng/ml in ≤ 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as (iPSA) + 10(GS-6), and high risk was defined as %rLN+ ≥ 15%. Univariate and multivariate analyses were performed.

Results: A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome.

Conclusion: Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.     

Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV.

UK-427,857 (4, 4-difluoro-N-[(1S)-3-[exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl]cyclohexanecarboxamide) is a novel CCR5 antagonist undergoing investigation for use in the treatment of human immunodeficiency virus (HIV) infection. Pharmacokinetic and metabolism studies have been performed in mouse, rat, dog, and human after single and multiple administration by oral and intravenous routes. The compound has physicochemical properties that are borderline for good pharmacokinetics, being moderately lipophilic (log D(7.4) 2.1) and basic (pK(a) 7.3), possessing a number of H-bonding functionalities, and with a molecular weight of 514. The compound was incompletely absorbed in rat (approximately 20-30%) but well absorbed in dog (>70%). Based on in vitro studies in Caco-2 cells, UK-427,857 has relatively poor membrane permeability, and transcellular flux is enhanced in the presence of inhibitors of P-glycoprotein. Further evidence for the involvement of P-glycoprotein in restricting the oral absorption of UK-427,857 was obtained in P-glycoprotein null mice (mdr1a/mdr1b knockout). In these animals, AUC after oral administration was 3-fold higher than in control animals. In oral dose escalation studies in humans, the compound demonstrated nonlinear pharmacokinetics, with increased dose-normalized exposure with increased dose size, consistent with saturation of P-glycoprotein. The oral dose-exposure relationship of UK-427,857 in humans was not reflected in either rat or dog. In animal species and humans, UK-427,857 undergoes some metabolism, with parent compound the major component present in the systemic circulation and excreta. Elimination of radioactive dose was primarily via the feces. In rat, parent compound was secreted via bile and directly into the gastrointestinal tract. Metabolites were products of oxidative metabolism and showed a high degree of structural consistency across species.     

“Flipped classrooms” in training in maxillofacial surgery: preparation before the traditional didactic lecture?

While virtual learning environments (VLE) can be used in medical education as stand-alone educational interventions, they can also be used in preparation for traditional “face-to-face” training sessions as part of a “flipped classroom” model. We sought to evaluate the introduction of this model in a single module on maxillofacial radiology from a course on trauma skills. Course delegates were randomised into two groups: one was given access to an e-learning resource (test group) and the other attended a traditional didactic lecture (control group). Knowledge and confidence were assessed before and after the course with a 20-question single-best-answer paper and a 10-situation 100 mm visual analogue scale (VAS) paper, respectively. All participants were then given free access to the VLE for 30 days and were invited to take part in an e-survey. Neither group showed improvements in the single-best-answer scores, but both groups showed comparable improvements in VAS (control: median (range) values improved from 40.8 (17.7–82.5) mm to 62.8 (35.3–88.7) mm, p = 0.001; test group: from 47.7 (10.9–58.1) mm to 60.5 (32.4–75.6) mm, p = 0.005). Half of the respondents stated that they preferred the “flipped classroom” approach, and 22/22 stated that they would be “likely” or “very likely” to use an e-learning resource with expanded content. The “flipped classroom” approach was well received and there were comparable improvements in confidence. As maxillofacial radiology lends itself to online instruction with its reliance on the recognition of patterns, and problem-based approach to learning, a piloted e-learning resource could be developed in this area.