Formal retrospective case review and sudden infant death

A review of 24 consecutive sudden infant deaths was undertaken to evaluate the importance of the various stages in the postmortem assessment of such cases. Death in three cases was caused by obvious trauma. Of the remainder, 16 were attributed to sudden infant death syndrome (SIDS), 4 to accidental asphyxia (identified by death scene examination and/or formal case review) and 1 to a lingual thyroglossal duct cyst. Three (14%) of 21 deaths thought to be SIDS after postmortem examination were attributed to asphyxia following subsequent formal case review.     

Specified principlism: what is it, and does it really resolve cases better than casuistry?

Principlism has been advocated as an approach to resolving concrete cases and issues in bioethics, but critics have pointed out that a main problem for principlism is its lack of a method for assigning priorities to conflicting ethical principles. A version of principlism referred to as 'specified principlism' has been put forward in an attempt to overcome this problem. However, none of the advocates of specified principlism have attempted to demonstrate that the method actually works in resolving detailed clinical cases. This paper shows that when one tries to use it, specified principlism fails to provide practical assistance in deciding how to resolve concrete cases. Proponents of specified principlism have attempted to defend it by arguing that it is superior to casuistry, but it can be shown that their arguments are faulty. Because of these reasons, specified principlism should not be considered a leading contender in the search for methods of making justifiable decisions in clinical cases.     

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Increased cerebrospinal fluid corticotropin-releasing factor concentrations during tryptophan depletion in healthy adults.

BACKGROUND: Brain serotonin neurotransmission and hypothalamic-pituitary-adrenal axis function are implicated in the pathophysiology of depression, and these systems interact in a reciprocal modulatory fashion. This study examined the effect of tryptophan depletion, which acutely reduces brain serotonin concentrations, on serial cerebrospinal fluid concentrations of corticotropin-releasing factor in healthy humans. METHODS: Five subjects completed a standard tryptophan depletion protocol, and four subjects participated in a comparison condition. Subjects underwent continuous sampling of cerebrospinal fluid via lumbar peristaltic pump. Concentrations of cerebrospinal fluid corticotropin-releasing factor were measured by radioimmunoassay. RESULTS: No mood changes were observed in either group. Tryptophan-depleted subjects exhibited significantly greater increases in corticotropin-releasing factor concentrations over time than subjects in the comparison condition. CONCLUSIONS: These findings highlight the potential importance of corticotropin-releasing factor and serotonin interactions and suggest that activation of corticotropin-releasing-factor-containing neurons could play a role in the emergence of mood symptoms following tryptophan depletion in vulnerable individuals.