Programmed death of nonproliferating androgen-independent prostatic cancer cells

Androgen ablation induces an energy-dependent process of programmed death in nonproliferating androgen-dependent prostatic cancer cells which involves fragmentation of genomic DNA into nucleosomal oligomers catalyzed by nuclear Ca2+, Mg(2+)-dependent endonuclease enzymes activated following a sustained elevation in intracellular free Ca2+ (Cai). In contrast, androgen-independent prostatic cancer cells are not induced to undergo such programmed cell death by androgen ablation. One explanation for the inability of androgen ablation to induce programmed death of androgen-independent prostatic cancer cells is that such ablation does not result in a sustained elevation in Cai in these cells. This raises the issue of whether androgen-independent prostatic cancer cells can be induced to undergo programmed death if an elevation in the Cai is sufficiently sustained by nonhormonal means. To test this possibility, androgen-independent, highly metastatic Dunning R-3327 AT-3 rat prostatic cancer cells were chronically exposed in vitro to the calcium ionophore ionomycin to sustain an elevation in their Cai. These studies demonstrated that an elevation of Cai as small as only 3-6-fold above baseline can induce the death of these cells if sustained for greater than 12 h. Temporal analysis demonstrated that the death of these cells does not require cell proliferation and involves Ca(2+)-induced fragmentation of genomic DNA into nucleosome-sized pieces as the commitment step in this process. These results demonstrate that even nonproliferating androgen-independent prostatic cancer cells can be induced to undergo programmed cell death if a modest elevation in the Cai is sustained for a sufficient time. These observations identify Cai as a potential target for therapy for androgen-independent prostatic cancer cells.     

The human carotid atherosclerotic plaque stimulates angiogenesis on the chick chorioallantoic membrane.

The chick chorioallantoic membrane was used to determine whether the carotid atherosclerotic plaque stimulates angiogenesis. Carotid endarterectomy specimens (1 mm3) with fibromuscular plaque (n = 8) and complicated plaque (n = 11) were implanted on the membrane on day nine of incubation and the response evaluated on day 11. Following fixation in situ with 10% formalin the angiogenic response was evaluated by: (1) examining whole membrane mounts, (2) quantitatively from a vascular density index and (3) from a histological study. Unmanipulated chorioallantoic membrane (n = 11) and plaque boiled prior to implantation (n = 6) served as controls. The vascularity of whole mounts of both fibromuscular and complicated plaque was greater than the controls. Vessel density of the membrane was estimated by counting the number of vessels intersecting four concentric circles (144.5 mm total circumference) placed on the formalin fixed membrane. The vascular density index due to the fibromuscular plaque (390.6 +/- 8.3) and complicated plaque (391.0 +/- 14.9) were similar (P greater than 0.9) but were significantly greater (P less than 0.001) than the unmanipulated membrane (327.9 +/- 5.6) or after treatment with the boiled plaque (283.8 +/- 15.6). Transforming growth factor beta 1 confirmed the validity of the experimental model to study angiogenesis. The histology of the chorioallantoic membrane due to either type of plaque was similar. Numerous vessels surrounded the plaque, and intraplaque vessels containing nucleated chick erythrocytes were observed. Although scattered vessels surrounded the boiled plaque, intraplaque vessels were not observed. This study demonstrates that the atherosclerotic plaque has angiogenic properties that may account for the increase in vasa vasorum that is associated with the plaque.     

The emergency physician and patient confidentiality: A review

Confidentiality is a promise rooted in tradition, law andmedical ethics. Emergency physicians treat a variety of patients to whom confidentiality is of vital importance: employees, celebrities, victims of violence or disaster, minors, students, criminals, drug abusers, and patients with STDs. EDs should develop methods of ensuring confidentiality for all patients.³⁴Although confidentiality is an important principle thatshould be respected and guarded, it is not absolute. Various laws mandate disclosure of certain patient information; in addition, an overriding moral duty may occasionally require, a breach of confidentiality. As Beauchamp and Childress noted, “the therapeutic role may sometimes have to yield to ones role as citizen and as protector of the interests of others”.¹⁹ In general, however, circumstances requiring a breach of confidentiality are rare.