Automated reasoning system in histopathologic diagnosis and prognosis of prostate cancer and its precursors

OBJECTIVE: This article presents the rationale and options offered to diagnostic and prognostic decision support systems for prostate pathology by automated reasoning capabilities. METHODS: The symbolic information used in diagnostic decision-making is systematically ordered, compared, numerically assessed in its probability, and combined such that a conclusion can be drawn. The framework for the processing of such symbolic information may be an expert system, an inference network or a case-based reasoning system. Automated reasoning is implemented by the use of a rule base and information flow control modules. RESULTS: Automated reasoning allows decision support systems to follow highly adaptive decision sequences, capable of handling contradictory evidence, exceptions in diagnostic clue expression, and nonmonotonic decision-making. CONCLUSIONS: Automated reasoning capability in diagnostic and prognostic decision support systems allows highly flexible decision development, very close to human decision procedures.     

Partial purification of box jellyfish (Chironex fleckeri) nematocyst venom isolated at the beachside

Chironex fleckeri, the northern Australian box jellyfish produces one of, if not, the most potent animal venoms. Study of the venom has been hampered by the limits of the animals' range and the venom's thermolability. Using retained lethality and native polyacrylamide gel electrophoresis (NPAGE), we show that lyophilization of autolysis isolated nematocysts is an effective method of transporting the venom. In addition, Sephadex G-200 chromatography, spin concentration, and NPAGE fail to demonstrate the presence of a 600 kDa protein to which the bulk of the lethal activity has been ascribed. Sodium dodecyl sulfate capillary electrophoresis of crude venom yields several protein bands with a molecular weight range of 30-200 kDa. Freeze-thaw studies show a loss of activity and NPAGE bands after two freeze thaw cycles.     

Pharmacokinetics of a single dose of teicoplanin in burn patients

Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients. This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns. Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%). Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h). Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h). The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration. A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.     

Improved biochemical variables, nutrient intake, and hormonal factors in slow nocturnal hemodialysis: a pilot study

OBJECTIVE: To determine whether slow nocturnal hemodialysis (SNHD) can be safely performed in patients with end-stage renal disease to improve the biochemical and clinical outcome. MATERIAL AND METHODS: We conducted an 8-week pilot study in nondiabetic adult patients, who underwent dialysis 6 nights per week for 8 hours each night. A dialysate flow rate of 300 mL/min and a blood flow rate of 250 mL/min, through an internal jugular dual-lumen venous catheter, were used. The equipment used was a COBE Centry System 3 dialysis machine and Fresenius F-80 (1.8 m2) or Baxter CT 190 (1.9 m2) dialyzers. Five patients were enrolled in the study. RESULTS: Two patients did not complete the study because of catheter-related infections--one at day 7 and one after 4 weeks of SNHD. All patients had improved blood pressure control, and no intradialytic adverse events occurred. Dietary intake improved, urea and creatinine levels significantly decreased, and weekly delivery of dialysate increased on SNHD. Potassium, chloride, beta 2-microglobulin, phosphorus, calcium, and high-density lipoprotein cholesterol all improved on SNHD. Serum testosterone increased in the three men on SNHD, but parathyroid hormone, luteinizing hormone, and follicle-stimulating hormone remained unchanged. Erythropoietin levels increased on SNHD, despite no change in exogenous erythropoietin doses in three patients and discontinuation of administration of erythropoietin in one. The following biochemical factors did not change significantly: serum sodium, bicarbonate, vitamin B12, folate, alkaline phosphatase, total cholesterol, triglycerides, and albumin. CONCLUSION: Higher doses of hemodialysis benefit nutrition, improve biochemical variables, and may improve many hormonal systems.     

Elevated temperature tensile behavior of Ti-25AI-10Nb-3V-1Mo

The effects of microstructure and temperature on tensile and fracture behavior were explored for the titanium aluminide alloy Ti-25Al-10Nb-3V-lMo (atomic percent). Three microstructures were selected for study in an attempt to determine the role of the individual microstructural constituents in this α₂ + B2 alloy. Tensile testing of both round and flat specimens in vacuum indicated a change in deformation behavior from 25 °C to 450 °C. Observations suggested that this change in deformation behavior occurred within the α₂ phase. Failure initiation at 450 °C and above was by a ductile process and was associated with the B2 phase. Above 600 °C and at high strains, plastic deformation occurred predominantly in the B2 phase. Strain localization was observed above 600 °C and found to be due to the lower work-hardening rate of the B2 phase. Strain localization at slip band intersections with prior β grain boundaries resulted in rapid strain accumulation in the B2 phase. Alignment of secondary α₂ laths with the tensile axis at high deformation levels appeared to inhibit shear band localization between voids due to a lack of participation of the α₂ phase in deformation. Formerly Materials Scientist, Materials Directorate, Wright Laboratory, Wright-Patterson AFB, Dayton, OH 45433, is Program Manager, Air Force Office of Scientific Research, Boiling AFB, Washington, DC 20332. Formerly Professor, Carnegie Mellon University, Department of Materials Science and Engineering, Pittsburgh, PA 15213, is Scientist, Lawrence Berkeley Laboratory, Berkeley, CA 94720.     

CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients

Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1 SEF2-1 or 17q21.3 ERDA1 locus. Polymorphic expansions at SEF2-1 and ERDA1 appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of the SEF2-1 and ERDA1 loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by the SEF2-1 and ERDA1 loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported.     

The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases

A series of succinyl based mercaptoketones and diastereomeric mercaptoalcohols were prepared and evaluated in vitro as inhibitors of the matrix metalloproteinases collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).     

Requirement of vascular integrin alpha v beta 3 for angiogenesis

Angiogenesis depends on the adhesive interactions of vascular cells. The adhesion receptor integrin alpha v beta 3 was identified as a marker of angiogenic vascular tissue. Integrin alpha v beta 3 was expressed on blood vessels in human wound granulation tissue but not in normal skin, and it showed a fourfold increase in expression during angiogenesis on the chick chorioallantoic membrane. In the latter assay, a monoclonal antibody to alpha v beta 3 blocked angiogenesis induced by basic fibroblast growth factor, tumor necrosis factor-alpha, and human melanoma fragments but had no effect on preexisting vessels. These findings suggest that alpha v beta 3 may be a useful therapeutic target for diseases characterized by neovascularization.