Glyoxalase I activity in human prostate cancer: a potential marker and importance in chemotherapy

PURPOSE: To provide information on the activity of Gly-I in prostate cancer. MATERIALS AND METHODS: We performed qualitative Gly-I assay on prostate tissues. RESULTS: Gly-I activity between prostate cancer and noncancerous specimens differed substantially and significantly, although such activity also varied somewhat among cancer specimens. CONCLUSIONS: Gly-I activity is indeed higher in cancerous than in noncancerous specimens, suggesting that it may play a role in prostate cancer homeostasis and survival.     

Assessment of the Computing Component of Civil Engineering Education

This paper presents the results of two surveys conducted by the American Society of Civil Engineers’ Task Committee on Computing Education of the Technical Council on Computing and Information Technology to assess the current computing component of the curriculum in civil engineering. Previous surveys completed in 1989 and 1995 have addressed the question of what should be taught to civil engineering students regarding computing. The surveys reported in this paper are a follow-up study to the two earlier surveys. Key findings of the study include: (1) the relative importance of the top four skills (spreadsheets, word processors, computer aided-design, electronic communication) has remained unchanged; (2) programming competence is ranked very low by practitioners; (3) the importance and use of geographic information system and specialized engineering software have increased over the past decade; (4) the importance and use of expert systems have significantly decreased over the past decade; and (5) the importance and use of equation solvers and databases have declined over the past decade.     

Laparoscopic colorectal surgery and cancer

Review article of the actual level of knowledge about laparoscopic colorectal surgery and laparoscopic-assisted procedures. At present time laparoscopy for the cure of colorectal neoplasia should only be performed within prospective randomized trials. In the meantime it is perfectly appropriate to perform laparoscopy for palliation of metastatic disease. Patients with benign colorectal neoplasms can achieve better outcome if treated by laparoscopy rather than laparotomy. Other areas in which laparoscopy may be useful include enterolysis and possibly, treatment of rectal prolapse. Laparoscopy can be appropriately applied for the treatment of terminal ileal Crohn's disease, sigmoid diverticulitis, reversal of Hartmann's pouches and the construction of stomas.     

An adenosine deaminase (ADA) allele contains two newly identified deleterious mutations (Y97C and L106V) that interact to abolish enzyme activity

Genetic deficiency of the purine salvage enzyme adenosine deaminase (ADA) results in varying degrees of immunodeficiency, ranging from neonatal onset Severe Combined Immunodeficiency (SCID) to an adult onset immunodeficiency disorder. Multiple different mutations have now been identified in these immunodeficient patients. Additional mutations, initially identified in healthy individuals, abolish ADA in erythrocytes but retain 10-80% of activity in non-erythroid cells ('partial deficiency mutations'). In general, severity of disease correlates inversely with the amount of residual ADA expressed by the mutant enzymes and directly with the accumulation of the toxic metabolites deoxyATP and deoxyadenosine. We report two newly identified mutations (Y97C and L106V), both carried on the same allele of an immunodeficient patient who was diagnosed prenatally and successfully transplanted with haploidentical bone marrow. Based on the ability of mutant cDNAs to express ADA in vitro , the L106V mutation resulted in activity similar to 'partial' mutations (30% of normal) while the Y97C mutation resulted in detectable but markedly reduced activity (1.5% of normal). However, the presence of both mutations on the same allele virtually abolished detectable enzyme activity. Analysis of the crystallographic structure of ADA to understand the marked deleterious effect of the Y97C mutation suggested a previously unappreciated role of salt bridges in the catalytic mechanism of ADA. The patient was also heteroallelic for a previously described deletion of the promoter and exon 1. Testing of additional patients in whom we had not identified a mutation on the second allele revealed presence of this deletion in three of four patients tested. This deletion is therefore relatively common, accounting for 10% of almost 100 chromosomes studied by this and other laboratories, but is easily missed by currently used methods of mutation detection. Lastly, the finding of two mutations on the same allele that interact to reduce residual enzyme function emphasizes hazards in evaluating potential genotype-phenotype correlations in individuals analyzed only for the presence of single specific mutations.     

Patient treatment choice and compliance. Data from a substance abuse treatment program

Conservative surgery (CS) is widely accepted today as the treatment of choice for 60 to 80% of the primary breast cancer. Esthetic results of CS are not good in all the cases and improvement can be obtained thanks to the remodelling of the breast after tumorectomy. The scar should be selected according to the location of the tumor; the glandular tissue should be reshaped using local glandular flaps or following the principles of the reduction mammaplasties. Tumorectomy located in the upper part of the gland can be reshaped with an inferior pedicle type of mammoplasty. Defect located in the inferior part of the gland can be reconstructed with a superior pedicle mammoplasty. These sophisticated tumorectomies are providing good esthetic results on the reconstructed breast but require commonly a symmetry procedure on the contralateral breast. Such contralateral reduction allows a better exploration of the opposite breast and histological examination of the reduction specimen. In a series of 76 CS performed at the European Institute of Oncology (IEO), which were associated with some kind of plastic procedure to lower the risk of bad cosmetic results (representing 25% of the CS associated with plastic surgery), we confirmed the value of the mixed oncologic and plastic approach. The esthetic results observed in this series are better than those observed in another series previously published at the Gustave-Roussy Institute (IGR)--good results: 72% (IEO) vs 50% (IGR), and bad results: 6% (IEO) vs 20% (IGR). Statistically such comparison can be criticised, specially because of the short follow-up of the Milan series. However, the difference is rather important if we consider that the series of Milan was a selection of cases with poor esthetic expectation (25% of all the CS performed during the same period), while the series of Paris did not select the patients in what concerns the risk of poor esthetic result.     

Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease

Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.     

Cost-effectiveness of HIV-prevention skills training for men who have sex with men

OBJECTIVE: A previous study empirically compared the effects of two HIV-prevention interventions for men who have sex with men: (i) a safer sex lecture, and (ii) the same lecture coupled with a 1.5 h skills-training group session. The skills-training intervention led to a significant increase in condom use at 12-month follow-up, compared with the lecture-only condition. The current study retrospectively assesses the incremental cost-effectiveness of skills training to determine whether it is worth the extra cost to add this component to an HIV-prevention intervention that would otherwise consist of a safer sex lecture only. DESIGN: Standard techniques of incremental cost-utility analysis were employed. METHODS: A societal perspective and a 5% discount rate were used. Cost categories assessed included: staff salary, fringe benefits, quality assurance, session materials, client transportation, client time valuation, and costs shared with other programs. A Bernoulli-process model of HIV transmission was used to estimate the number of HIV infections averted by the skills-training intervention component. For each infection averted, the discounted medical costs and quality-adjusted life years (QALY) saved were estimated. One- and multi-way sensitivity analyses were performed to assess the robustness of base-case results to changes in modeling assumptions. RESULTS: Under base-case assumptions, the incremental cost of the skills training was less than $13,000 (or about $40 per person). The discounted medical costs averted by incrementally preventing HIV infections were over $170,000; more than 21 discounted QALY were saved. The cost per QALY saved was negative, indicating cost-savings. These results are robust to changes in most modeling assumptions. However, the model is moderately sensitive to changes in the per-contact risk of HIV transmission. CONCLUSIONS: Under most reasonable assumptions, the incremental costs of the skills training were outweighed by the medical costs saved. Thus, not only is skills training effective in reducing risky behavior, it is also cost-saving.