Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.     

Serial prognostic capabilities of electrocardiographic indices of infarcted and hibernating myocardium in predicting short- and long-term outcome following coronary artery bypass surgery

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.     

Paget bone disease involving young adults in 3 generations of a Korean family

Pancreatic cancer is an aggressive disease with a dismal prognosis. It has long been regarded as one of the most difficult cancers to accurately diagnose and stage preoperatively. The purpose of this review is to provide an update of the state-of-the-art for early detection, diagnosis, and staging of pancreatic cancer. These methods include spiral CT scans, magnetic resonance imaging, positron emission tomography (PET) imaging, laparoscopy, endoscopic ultrasound, CA 19-9 serology, fine needle aspiration cytology, ERCP brush cytology, and screening for p53 and ras oncogenes. These advanced techniques should help us to detect pancreatic cancers in high-risk populations at a curative stage and to decrease pancreaticoduodenectomies for benign disease which could otherwise be treated with less morbid procedures. In addition, these tests will help reliably diagnose pancreatic cancer preoperatively.     

High-throughput screening: advances in assay technologies

The expression and up-regulation of cell adhesion molecules on a human colonic epithelial cell line HT-29, and the peripheral blood T lymphocyte proliferation responses to bacterial superantigens presented by this cell line were investigated, compared with peripheral blood monocytes. In HT-29 cells, there was constitutive expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) at a low level, but no constitutive expression of HLA-DR, LFA-1, B7-1 and B7-2 molecules. After stimulation with the supernatants of staphylococcal enterotoxin B (SEB)-stimulated peripheral blood mononuclear cells for 48 h, there was significant up-regulation of HLA-DR and ICAM-1 molecules (both > 90% positive). However, this stimulation had no effect on the expression of LFA-1, B7-1, B7-2 and LFA-3 molecules. In the presence of all tested superantigens SEB, toxic shock syndrome toxin-1, and streptococcal pyogenic exotoxin A, stimulated HT-29 cells caused significant T cell proliferation. When monocytes were used as antigen-presenting cells (APC), the MoAbs against HLA-DR, B7-2 and LFA-3 showed a significant inhibition of SEB-induced T cell proliferation. Anti-ICAM-1 MoAb had no effect on this response. On the other hand, when stimulated HT-29 cells were used as APC, the MoAbs against HLA-DR and ICAM-1 significantly inhibited SEB-induced T cell proliferation. In contrast to monocytes, anti-B7-2 and anti-LFA-3 had no effect on this response. SEB could not induce HT-29 cells to produce IL-8 directly; however, SEB significantly induced the stimulated HT-29 cells to produce IL-8 in the presence of T cells. Thus these data demonstrate that the products of superantigen-stimulated T cell activation can increase the expression of HLA-DR and ICAM-1 molecules on HT-29 cells significantly. Stimulated HT-29 cells can serve as APC to bacterial superantigens. This response is an HLA-DR- and ICAM-1-dependent, but B7-2- and LFA-3-independent process, which was different from professional APC monocytes.     

Laser Doppler flowmetry during open reduction for developmental dysplasia of the hip

Laser Doppler flowmetry was used intraoperatively to monitor femoral head perfusion during open reduction of 13 congenital hip dislocations in 11 patients. Laser Doppler determinations ranged from 12 to 400 mV before reduction and 30 to 300 mV after reduction. Three patients had magnitude changes in excess of 50%. One had increased perfusion, and two had decreased blood flow. Avascular necrosis of the hip occurred in one patient that was not predicted by laser Doppler flowmetry. Femoral head perfusion measured 175 mV for the dislocated hip and 180 mV after reduction of the femoral head and completion of the pelvic osteotomy. The authors conclude that laser Doppler flowmetry is not a reliable method for monitoring femoral head perfusion during open reduction of the hip for developmental hip dysplasia.     

Racial differences in lens opacities: the Salisbury Eye Evaluation (SEE) project

Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro. Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro. The human NSCs can also replace specific deficient neuronal populations. Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective. By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders.