One core positive prostate biopsy is a poor predictor of cancer volume in the radical prostatectomy specimen

PURPOSE: In view of the recent increase in patients presenting with only 1 core positive for prostate carcinoma, we examined the correlation in tumor volume between the biopsy and the subsequent radical prostatectomy specimen. MATERIALS AND METHODS: We studied a total of 169 consecutive prostate biopsies with matched radical prostatectomy specimens and selected 48 patients with only 1 positive core. RESULTS: Cancers found in the biopsy regardless of their size were associated with a wide range of cancer volume in the radical prostatectomy specimens, and the amount of cancer in the biopsy was a poor predictor of the volume of cancer in the prostatectomy specimen. Even with a cancer of 3 mm. or less in the biopsy, 57% of patients had cancer of clinically significant volume (greater than 0.5 ml.). Other modalities for the evaluation of prostate cancer such as Gleason score and clinical stage were not helpful in segregating patients with clinically significant from those with insignificant volume of cancer. However, when combined with a preoperative serum prostate-specific antigen higher than 10 ng./ml., 1 core positive biopsy could reliably predict the presence of cancer of significant volume. CONCLUSIONS: One core only positive prostate biopsy, when accompanied by an elevated serum prostate specific antigen value (greater than 10 ng./ml.), strongly suggests the presence of clinically significant cancer.     

Teaching ethics in the engineering design process: a legal scholar's view

Engineering ethics are a critical "gap filler" in the regulation of technology. Engineers, as "professionals," are given professional autonomy in promoting risky activities, based on a promise that they will act in the public interest. The legal system, both in regulation and liability, puts constraints on the design process, but often leaves gaps that must be filled by ethical precepts. The conflict between the public interest and the private interest of the engineer is often most acute in the acceptance or rejection of relatively rare risks in the design of products. Rare risks normally involve the greatest uncertainty of injury. These rare risks of catastrophic injury can fall "under the radar" of regulatory systems, or technological advances may make regulatory systems obsolete. The other major risk category are "system risks," in which individual engineers assume that some other party will take care of the risk. Teaching engineers to recognize and deal with these risks is critical. In particular, reliance on regulatory approval may be inadequate. Designing products that hold paramount the public safety must be the benchmark for engineering ethics.     

Crystal structure of a DExx box DNA helicase

There are a wide variety of helicases that unwind helical DNA and RNA substrates. The twelve helicases that have been identified in Escherichia coli play a role in almost all cellular processes involving nucleic acids. We have solved the crystal structure of a monomeric form of a DNA helicase from Bacillus stearothermophilus, alone and in a complex with ADP, at 2.5 and 2.9 A resolution, respectively. The enzyme comprises two domains with a deep cleft running between them. The ATP-binding site, which is situated at the bottom of this cleft, is formed by motifs that are conserved across the superfamily of related helicases. Unexpected structural homology with the DNA recombination protein, RecA, suggests how ATP binding and hydrolysis may drive conformational changes of the enzyme during catalysis, and implies that there is a common mechanism for all helicases.     

Judicial Intervention and Its Key Battleground: Natural Justice

This paper explores what has been the most successful attempt to date to introduce an “escape hatch” into the adjudication process for those on the wrong end of decisions: the area of natural justice. The decisions of the Technology and Construction Court relating to this area reflect the complexity of the key policy consideration underlying them: the extent to which judges should second guess adjudicators when it comes to matters of procedure. The paper argues that the Technology and Construction Court has in recent years reached a high water mark of intervention before being reigned in by the then senior judge of that court and by the Court of Appeal. It suggests that a more stable and predictable position now prevails. That certainty, common approach, and balance have been welcomed by the construction industry. This paper suggests that welcome is a better benchmark of whether the intervention/nonintervention debate has been correctly resolved than any academic or theoretical approach.     

Regulatory and other public policy issues

Regulatory and other public policy issues in the future of biomedical engineering, as they relate to the development and use of medical devices, are discussed. At the federal level, agencies that directly influence the application of medical technology include the Food and Drug Administration (FDA), with its clinical trials and premarket and regulatory authority, and the Health Care Financing Administration (HCFA), with its reimbursement policy. The Occupational Safety and Health Administration (OSHA), the Environmental Protection Agency (EPA), and the Department of Commerce can have a considerable impact on corporate profitability, which is a driving force for most new technology and new product introductions. Another area of public policy that has been cited as significantly influencing health care and medical device development, namely, civil litigation, is also considered. To illustrate the issues, the impact of the regulatory environment on the application of computer software to a wide variety of medical products is examined. The humanistic and ethical problems brought about by technological advances are discussed. Ten key technologies that are likely to have the greatest importance in the next few years and ten external influences on the future of the medical device technology industry that have been identified by the Health Industry Manufacturers Association are described.     

Graphomotor perseveration and wandering in Alzheimer's disease

Perseveration, spatial orientation, and attention/concentration were assessed in 15 patients with a probable diagnosis of senile dementia of the Alzheimer's type. Subjects were divided into two groups, wanderers and nonwanderers, based on caregiver ratings using a modified version of the Caregiver Checklist. Graphic productions of wanderers on the Bender Visual Motor Gestalt Test and Clock Drawing Test displayed greater total perseveration and more recurrent and continuous perseverations than those of nonwanderers. Spatial orientation and attention/concentration were similar between groups. These preliminary results suggest that graphomotor perseverations exhibited during the mild to moderate stages may serve as a marker for wandering in Alzheimer's disease.     

Design, synthesis, and evaluation of 5'-diphenyl nucleoside analogues as inhibitors of the Plasmodium falciparum dUTPase

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent. Herein we report the synthesis and evaluation of some diphenyl analogues that have lower lipophilicity and molecular weight than the trityl lead compound. Co-crystal structures show that the diphenyl inhibitors bind in a similar manner to the corresponding trityl derivatives, with the two phenyl moieties occupying the predicted buried phenyl binding sites. The diphenyl compounds prepared show similar or slightly lower inhibition of PfdUTPase, and similar or weaker inhibition of parasite growth than the trityl compounds.     

The regulation of medical computer software as a 'device' under the Food, Drug, and Cosmetic Act

Recent developments in computer software have raised the possibility that federal regulators may claim to control medical computer software as a 'device' under the Food, Drug and Cosmetic Act (FDCA). The purpose of this paper is to analyze the FDCA to determine whether computer software is included in the statutory scheme, examine constitutional arguments relating to computer software, and discuss regulatory principles that should be taken into account when deciding appropriate regulation. This paper is limited to computer program output used by humans in deciding appropriate medical therapy for a patient.