Different views on treatment decisions by first-year interprofessional healthcare students.

This study explored ethical treatment decisions of healthcare professional students beginning their education. As part of a first-semester modern medicine and bioethics course, 311 students watched and discussed, in interprofessional groups, a video titled Dax's Case: Who Should Decide? regarding the treatment of a life-threatening infectious disease against Dax's wish. The students then discussed and made their decision regarding treating or not. Their decisions, recorded on a worksheet, were classified as "will treat" or "won't treat." Professional groups' decision patterns were compared using the chi-square test. Overall, 151 (71%) opinions from students were classified as "will treat," and 61 (29%) as "won't treat." Nursing students were more likely to decide "won't treat" (in line with Dax's preference); however, the majority of other professions' students favoured treatment (against Dax's wish). Given the students' limited exposure to profession-specific education, our preliminary study supports the notion that healthcare profession students hold different values that align with their chosen profession at the start of their studies.

The role of BCL-2 and bax protein in monocyte-mediated apoptosis in human leukemic cell lines.

Monocytes or monocyte-derived supernatants are able to kill leukemic cells via apoptosis, thereby preferentially effecting more mature leukemic cells. In the present study, the relationship between apoptosis and the apoptosis related proteins, bcl-2 and bax, was investigated in a number of human leukemic cell lines. Monocyte-derived supernatant induces extensive apoptosis in U937 myeloid leukemia cells and minor apoptosis in HL60 cells. No apoptosis was seen in four other cell lines (THP1, HL60-D3, KG1, and K562). The expression of bcl-2 and bax protein was determined in both groups of leukemic cell lines by flow cytometry (bcl-2 and bax) and Western blotting (bcl-2) at baseline level and after incubation with monocyte supernatant after different time periods. No clear relation was found between baseline bcl-2 or bax protein expression and the occurrence of apoptosis after incubation with monocyte supernatant. After different incubation time periods, no change was found in bcl-2 protein expression in U937 and K562 cells, whereas in KG1, HL60, and especially in THP1 cells, a significant decrease could be noticed. On the other hand, there was an increase in bcl-2 expression in HL60-D3 cells. Bax protein expression, measured at the same time points, remained essentially unchanged in HL60-D3 cells, decreased significantly in U937, HL60, and THP1 cells and slightly in K562 cells, and increased significantly in KG1 cells. Also, the ratio bax/bcl-2 decreased in HL60D3, but especially in U937 and HL60 cells, increased slightly in THP1 and KG1 cells, and remained essentially unchanged in K562 cells. Rh-tumor necrosis factor-alpha (TNF-alpha), the main mediator of monocyte mediated cytotoxicity, induced apoptosis in U937, HL60, and THP1 cells, thereby showing changes in bcl-2 expression similar to those found for monocyte derived supernatants. We concluded that in human leukemic cell lines, there is no relation between either bcl-2 or bax protein expression or the ratio of both, and apoptosis mediated by monocyte derived supernatant or TNF-alpha.

Development of an orthotopic SCID mouse-human tumor xenograft model displaying the multidrug-resistant phenotype.

Multiple myeloma is a plasma cell malignancy which is generally incurable in spite of a high initial response to chemotherapy. While animal models of myeloma are known, the recent developments of human xenografts in nude and SCID mice suggests a promising experimental model. The SCID model, in particular, holds promise because these animals readily accept hematopoietic and lymphoid transplantation and do not generally develop graft versus host reaction. We have developed two drug-resistant variants of the human multiple myeloma cell line ARH-77 by in vitro exposure to gradually increasing concentrations of doxorubicin (ARH-D60) or mitoxantrone (ARM-80). When injected into irradiated SCID mice, the ARH-D60 cell line grew in an orthotopic pattern with the development of osteolytic lesions. This is in contrast to the 8226/C1N human myeloma cell line which grows in a disseminated but nonorthotopic manner in the SCID mouse. Both the ARH-D60 and ARM-80 cell lines are resistant to doxorubicin and cross-resistant to mitoxantrone, vinca alkaloids, taxol and m-AMSA while maintaining sensitivity to antimetabolites and alkylating agents. Growth characteristics and cell cycle kinetics, including S-phase, were not altered in the resistant sublines. The ARH-D60 and ARM-80 cell lines both displayed a classic multidrug-resistance (MDR) phenotype which was partially reversed by the addition of verapamil. These two cell lines represent the first MDR human myeloma cell lines which have demonstrated an orthotopic growth pattern in the SCID mouse and thus may be of value in studying the pathophysiology of this disease.

Follitropin-beta administered by pen device has superior local tolerance compared with follitropin-alpha administered by conventional syringe.

A receiver- and assessor-blind, randomized, single-centre, crossover study was performed in 60 healthy women volunteers, to compare the local tolerance of two recombinant FSH preparations administered by a pen device (delivering 150 IU follitropin-beta) or by conventional syringe (delivering 150 IU follitropin-alpha). Volunteers were randomized to one of two treatment sequences: pen device followed by conventional syringe, or the reverse. Each preparation was injected once, subcutaneously in the umbilical region and local tolerance reactions were assessed within 5 min, at 1 and 24 h after each administration. In addition, subjects were asked to rate the pain experienced during a period of 24 h after each injection by means of a visual analogue scale (VAS). At administration (within 5 min), severe to moderate pain was experienced in 70.0% of subjects injected by the conventional syringe, whereas only 21.7% of subjects treated with the pen device experienced pain. This difference was highly significant (P