Determining the cost of a clinical intervention through the use of shadow pricing

This article reviews the scientific literature in several areas important to the delivery of palliative care: multicultural issues, education, comprehensive outcome measures and ethics. Most of the research can be classified as fundamental rather than intervention research according to the Cancer Control Framework of the National Cancer Institute of Canada. Desired outcomes of interventions are most often defined from the health care professional's perspective but need to be defined from the patient's perspective. In areas such as multicultural issues and the effect of the volunteer on the patient, there is almost no research. The complexity of studying the best way to deliver palliative care would benefit from the input of colleagues who have experience addressing these issues in other patient populations.     

Preimplantation hormonal differences between the conception and non-conception menstrual cycles of 32 normal women

We compared daily urinary concentrations of oestrogen and progesterone metabolites in paired menstrual cycles (conception and non-conception) from 32 women. Volunteers with no known fertility problems were enrolled in the study at the time they began trying to become pregnant. They collected first-morning urine specimens and kept daily records of menstrual bleeding and sexual intercourse for 6 months or until they became clinically pregnant. Intercourse in non-conception cycles was close to the time of ovulation so that failure to conceive was caused by factors other than poorly timed intercourse. Compared with non-conception cycles, conception cycles had a steeper early luteal rise in progesterone and higher mid-luteal oestrogen and progesterone concentrations. These hormonal characteristics may be markers of better quality cycles, but because all these differences were in the luteal phase, we cannot rule out the possibility that the preimplantation embryo had stimulated early increases in steroid production. We propose an analysis strategy that could help support or refute the importance of preimplantation embryonic signalling, but our small sample size limits our own conclusions about this mechanism.     

Hprt- mutation spectrum in a closely related pair of human bladder tumour cell lines after gamma-irradiation at different dose-rates

Inactivation of p53 gene and overexpression of MDR1 gene are both associated with drug resistance. Previous studies have suggested that p53 gene can modulate the expression activity of MDR1 gene promoter in a promoter-CAT system. In the present study, wild-type p53 gene cDNA was introduced into a multidrug-resistant cell line, KBv200, in which endogenous p53 gene is aberrant. In wt-p53 transfected cells, the expression of MDRI gene was significantly increased, accumulation of adriamycin (ADM) was decreased, and the sensitivity to vincristine (VCR), ADM and 5-fluorouracil (5-FU) was increased compared with the parent KBv200 cells. After treatment with ADM and VCR, the p53-transfectants were more susceptible to apoptosis. The results suggest that the increase in drug sensitivity of the cells may be, at least in part, due to p53-dependent apoptosis induced by anticancer agents.     

Pregnancy-related impairments and the Americans with Disabilities Act

Congress passed the Americans with Disabilities Act (ADA) in 1990. The ADA's overriding purpose is to provide a national mandate for the elimination of discrimination against individuals with disabilities. This article addresses the emerging relationship between pregnancy-related disabilities and the employment provisions of the ADA, set forth in title I of the Act. In view of the high percentage of women who will become pregnant and their potential need for workplace accommodations during and after pregnancy, it is crucial that health professionals understand the impact of the ADA's employment provisions.     

Protection against lethal murine coccidioidomycosis by a soluble vaccine from spherules

The formaldehyde-killed, whole-spherule vaccine, which is protective against lethal challenge of laboratory animals with Coccidioides immitis, was fractionated. It yielded a soluble, multicomponent, subcellular fraction termed the 27K vaccine. This vaccine, when it was accompanied by adjuvant, protected mice against lethal intranasal and intravenous challenge with C. immitis.     

Hepatic hemangioma. Analysis of 103 cases. Clinical considerations and imaging methods

Hemangiomas are the most common benign vascular tumor found in the liver. In this study, 103 cases of hepatic hemangiomas were analysed in a retrospective manner. Image aspects such as those seen in ultrassonography, computed tomography, nuclear magnetic resonance and arteriography are discussed. The incidence was higher amongst the female sex, between individuals from 40 to 60 years old, which presented predominantly without symptoms (66%) and localized mainly in the right hepatic lobe (74%). The meaning of those aspects, when adopted, permits the clinicians to differentiate benign from malignant nodular lesions in the liver.     

Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of beta-chemokines

Escherichia coli leader peptidase, an integral membrane protein, is responsible for the cleavage of the signal sequence of many exported proteins. Recent studies suggest that it is a novel serine protease that utilizes a serine-lysine catalytic dyad. In an effort to further understand the mechanism of this enzyme, an internally quenched fluorescent peptide substrate incorporating the leader peptidase cleavage site of maltose binding protein signal peptide, Y(NO2)-F-S-A-S-A-L-A-K-I-K(Abz) (anthraniloyl), was designed and synthesized. In the intact peptide, the fluorescence of the anthraniloyl group is quenched by the 3-nitrotyrosine. This quenched fluorescence is liberated upon cleavage of the peptide by the leader peptidase, resulting in increased fluorescence that could then be monitored fluorometrically. The designed substrate can be cleaved effectively by E. coli leader peptidase as detected by both HPLC and fluorescent spectroscopy. Mass spectra of cleavage products demonstrated that the cleavage occurs at the predicted site (A-K). The cleavage of the peptide substrate has a linear dependence on the enzyme concentration (0.1 to 1.9 microM) and the kcat/K(m) was calculated to be 71.1 M-1 s-1. These data are comparable with the unmodified peptide substrate. This report represents the first direct continuous assay based on fluorescence resonance energy transfer for E. coli leader peptidase.