Practice guideline for forensic pathology. Members of the Forensic Pathology Committee, College of American Pathologists

The guideline for forensic pathology was prepared by the Forensic Pathology Committee of the College of American Pathologists. The definitional criteria for forensic pathology included in this guideline have been approved both by the House of Delegates and the Board of Governors of the College of American Pathologists. The guideline presents an overview of forensic pathology and an approach to the forensic autopsy and medicolegal death investigation. Emphasis is placed on the role of forensic pathology in maintaining public health, welfare, and safety. The guideline is intended to serve as an educational tool, and its use should be determined by the individual circumstances and settings of specific cases.     

Remarkable preservation of biomolecules in ancient radish seeds

Desiccated seeds from a 6th century AD storage vessel recovered from Qasr Ibr?m, Egypt, were examined for the presence of lipids and nucleic acids. A remarkable degree of lipid preservation was discovered, the fatty acid and sterol profiles being very similar to those of modern radish seeds. The only significant differences were hydrolysis of triacylglycerols and depletion of the polyunsaturated fatty acids (C18:2 and C18:3). The delta 13 C values of the principal fatty acids were in the range -25.4 to -29.2/1000, which is congruent with modern radish (C3 seeds) taking account of isotopic shifts caused by recent changes in atmospheric CO2. Deoxyribonucleosides and nucleic acid bases were detected by direct chemical analysis, and polymerase chain reactions gave products with sequences comparable to those from modern radish. The degree of lipid preservation, which was much greater than that reported for other archaeological remains, suggests that the microenvironment within desiccated seeds retards biomolecular decay. The results illustrate the utility of combined lipid-nucleic acid analysis in chemotaxonomic and genotypic studies of archaeobotanical remains.     

A dose response study of hepatitis A vaccine in healthy adults who are > or = 30 years old and weigh > or = 77 kg

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels.     

Dental practice patterns. II: Treatment related to oral health status

We report and describe the clinical findings of three patients who developed atonic pupil after uncomplicated extracapsular cataract extraction with posterior chamber intraocular lens implantation. All patients had normally reactive pupils one day postoperatively, but after two weeks, the pupils were dilated and nonreactive to light, accommodation, and miotics. To estimate the incidence of atonic pupil after cataract surgery, we sent a survey on the frequency, clinical features, and possible etiologies of this syndrome to members of the American Society of Cataract and Refractive Surgery. Of the 567 respondents, 60% had seen at least one case of atonic pupil in the past five years; they reported a total of 1543 cases during that time. This is probably a conservative figure since many cases undoubtedly go unnoticed because of a lack of visual disturbance. We believe this condition occurs more frequently than previously reported. The atonic pupil should be recognized as a possible complication of cataract surgery that should be included in the preoperative consent form.     

Voltage- and temperature-dependent gate capacitance and current model: application to ZrO/sub 2/ n-channel MOS capacitor

Based on the energy-dispersion relation in each region of the gate-dielectric-silicon system, a tunneling model is developed to understand the gate current as a function of voltage and temperature. The gate capacitance is self-consistently calculated from Schrodinger and Poisson equations subject to the Fermi-Dirac statistics, using the same band structure in the silicon as used for tunneling injection. Franz two-band dispersion is assumed in the dielectric bandgap. Using a Wentzel-Kramer-Brillouin (WKB)-based approach, direct and Fowler-Nordheim (FN) tunneling and thermionic emission are considered simultaneously. The model is implemented for both the silicon conduction and valence bands and both gate- and substrate-injected currents. ZrO/sub 2/ NMOSFETs were studied through temperature-dependent C/sub g/-V/sub g/ and I/sub g/-V, simulations. The extracted band gaps and band offsets of the ZrO/sub 2/- and interfacial-Zr-silicate-layer are found to be comparable with the reported values. The gate currents in ZrO/sub 2/-NMOSCAPs are found to be primarily contributed from the silicon conduction band and tunneling appears to be the most probable primary mechanism through the dielectric. Oscillations of gate currents and kinks of gate capacitance were observed near the flat-band in the experiments. These phenomena might be caused by the interface states.     

Comparison of 5-fluorouracil pharmacokinetics in patients receiving continuous 5-fluorouracil infusion and oral uracil plus N1-(2''-tetrahydrofuryl)-5-fluorouracil

In order to examine the relationship between long-term potentiation (LTP) and phosphoinositide (PI) turnover, we evaluated these throughout anesthetized rat brain using carbon-11-labeled diacylglycerol (11C-DAG). High-frequency tetanic stimulation (400 pulses at 400 Hz) to the perforant pathway induced LTP in rat dentate gyrus. In autoradiograms of rat brains, LTP was associated with the occurrence of multiple highly radioactive spots in many regions distant from the stimulated site. Following i.v. administration of an NMDA receptor antagonist prior to stimulation, however, no high-density spots were found. These findings directly demonstrate that potentiation of phosphoinositide-derived signaling was induced during LTP, and the finding of multiple location suggests the occurrence of polysynaptic neurotransmission through neural networks pertaining to learning and memory.     

Heat shock provides delayed protection against oxidative injury in cultured human umbilical vein endothelial cells

During both mild and severe ischemia, vascular endothelial cells lining large and small vessels of the ischemic organ are exposed to oxygen-derived free radicals resulting in oxidative damage to the organ. Heat shock has been shown to induce thermotolerance and also protect against ischemic injury, possibly via increased synthesis of heat shock proteins (HSPs). We hypothesized that heat shock preconditioning may protect human endothelial cells against oxidative damage. Cultured human umbilical vein endothelial cells (HUVEC) were subjected to heat shock (42 degrees C, 1 h) and allowed to recover for 2 or 20 h, at which times the cells were oxidatively stressed for 1 h by exposing them to 100-200 mumol/l of hydrogen peroxide (H2O2). Cellular damage was assessed immediately and 18 h later by morphology and release of lactate dehydrogenase (LDH). No protection of HUVEC was seen using the 2-hour recovery interval, but a significant protection (P < 0.05) was observed after the 20-hour delay. Northern blot analysis at 1 and 2 h after heating showed induction of HSP-70 mRNA. Western blot analysis demonstrated a significant increase in HSP-72 protein after 2 as well as 20 h of recovery from heat shock, although the amounts of protein at the two times were not significantly different. Furthermore, no differences in the activity of the antioxidant enzyme catalase were observed between heated and unheated HUVEC at 2 and 20 h after heat preconditioning. Thus, heat shock preconditioning induces delayed protection against oxidative injury in HUVEC, and the mechanism of protection appears to involve more than the expression of HSP-72 or activity of catalase.     

Model-based reliability analysis

Testing has typically been a key means of detecting anomalous performance and of providing a foundation for estimating reliability for weapon systems. The objective of model-based reliability analysis (MBRA) is to identify ways to capitalize on the insights gained from physical-response modeling both to supplement the information obtained from testing and to better-understand test results. Five general MBRA processes are identified which can capitalize on physical response modeling results to make both quantitative and qualitative statements about product reliability. A case study that explores 1 of these 5 processes was completed and is described in detail. It had the benefits: MBRA can be used to determine a performance baseline against which current and future test results can be compared; during the design process, MBRA can provide tradeoff studies such that development time and required test assets can be reduced; MBRA can be used to evaluate the impact of production and part changes, as well as aging degradation, if they arise during the product life cycle; and MBRA lays the foundation to evaluate anomalies that are observed in a test program. Typically it has been challenging to determine how anomalous behavior can manifest itself under different-but still valid-conditions. One can use modeling to inject hypothesized behaviors under different conditions and observe the consequences     

WorkSpace and the study of Chagas' disease

Chagas' disease afflicts more than 18 million people throughout South and Central America. Some areas of North America have also seen an increased incidence in recent years. The Trypanosoma cruzi (T. cruzi) parasite, which causes the disease, is most often transmitted by Triatomid bugs living in close proximity to humans. The T. cruzi parasite depends heavily on a small molecule called trypanothione to protect itself against damage from free radicals produced during normal metabolism. The concentration of trypanothione in the cell is carefully maintained by an enzyme called trypanothione reductase (TR). Drugs that inhibit TR should cause the parasite to die. Human cells have a similar enzyme-substrate pair: glutathione and glutathione reductase (GR). Fortunately, the enzyme GR differs electrostatically from TR, so there is hope of developing a drug that will be safe for human cells. The molecular structures of both TR and GR are known from ongoing X-ray crystallography studies. Both enzymes are dimers, that is, they consist of two equivalent domains, each having its own active site (the place where glutathione or trypanothione binds). One surprising feature of this system is a long tunnel passing through the center of the dimer and connecting the active sites of the two domains. While this is a naturally interesting feature to explore in a VR environment, the goal of the research is to evaluate the binding ability of particular drugs. For purposes of early testing, we chose chlorpromazine, an antidepressant drug. Large doses of the drug are known to kill the parasite, but are also toxic to the human host. It is possible that minor structural changes to this molecule would improve the selectivity and potency of the drug. For purposes of testing our VR environment, we present only a token calculation on chlorpromazine