Confirmation of death.

A working party set up to study the problems surrounding the confirmation of death investigated current practice by means of a questionnaire sent to a random sample of accident and emergency departments in district general hospitals. Of the 38 replying, 24 said that bodies were examined in the ambulance, four in the accident and emergency department, and 10 in both. Answers to the other questions also suggest that the present procedures are in general unsatisfactory, and some dissatisfaction was expressed by departments. The individuals and organisations consulted were unanimous that confirmation of death should not be carried out in the ambulance. A change of practice would, however, create practical problems. The working party recommends therefore that the standard practice should be for all bodies to be properly examined by a doctor in the accident and emergency department, and that funds should be made available for any building alterations and increase in staff made necessary by such changes.     

Madeleine's death.

Despite visits to two physicians and two hospitals within 4 days in September 1994, 7-week-old Madeleine Hunter died of flu-related dehydration. The coroner at an inquest into the baby''s death said he had never seen a case in which so many things went wrong. The coroner''s jury, which made 46 recommendations, determined that physicians and others involved in the care of very small infants should give "due respect to the instinct of the mother." Madeleine''s mother, Georgina Hunter, recounts the story of her baby''s death.     

Excitotoxic cell death.

Excitotoxicity refers to the ability of glutamate or related excitatory amino acids to mediate the death of central neurons under certain conditions, for example, after intense exposure. Such excitotoxic neuronal death may contribute to the pathogenesis of brain or spinal cord injury associated with several human disease states. Excitotoxicity has substantial cellular specificity and, in most cases, is mediated by glutamate receptors. On average, NMDA receptors activation may be able to trigger lethal injury more rapidly than AMPA or kainate receptor activation, perhaps reflecting a greater ability to induce calcium influx and subsequent cellular calcium overload. It is possible that excitotoxic death may share some mechanisms with other forms of neuronal death.     

Mechanisms of suicidal erythrocyte death.

Erythrocyte injury such as osmotic shock, oxidative stress or energy depletion stimulates the formation of prostaglandin E2 through activation of cyclooxygenase which in turn activates a Ca2+ permeable cation channel. Increasing cytosolic Ca2+ concentrations activate Ca2+ sensitive K+ channels leading to hyperpolarization, subsequent loss of KCl and (further) cell shrinkage. Ca2+ further stimulates a scramblase shifting phosphatidylserine from the inner to the outer cell membrane. The scramblase is sensitized for the effects of Ca2+ by ceramide which is formed by a sphingomyelinase following several stressors including osmotic shock. The sphingomyelinase is activated by platelet activating factor PAF which is released by activation of phospholipase A2. Phosphatidylserine at the erythrocyte surface is recognised by macrophages which engulf and degrade the affected cells. Moreover, phosphatidylserine exposing erythrocytes may adhere to the vascular wall and thus interfere with microcirculation. Erythrocyte shrinkage and phosphatidylserine exposure ('eryptosis') mimic features of apoptosis in nucleated cells which however, involves several mechanisms lacking in erythrocytes. In kidney medulla, exposure time is usually too short to induce eryptosis despite high osmolarity. Beyond that high Cl- concentrations inhibit the cation channel and high urea concentrations the sphingomyelinase. Eryptosis is inhibited by erythropoietin which thus extends the life span of circulating erythrocytes. Several conditions trigger premature eryptosis thus favouring the development of anemia. On the other hand, eryptosis may be a mechanism of defective erythrocytes to escape hemolysis. Beyond their significance for erythrocyte survival and death the mechanisms involved in 'eryptosis' may similarly contribute to apoptosis of nucleated cells.