Suicide by fire in Scotland: 1980-1990

Suicide by fire is relatively rare in the Western world, accounting for approximately 1% of completed suicides by all methods. This survey identified suicidal deaths among fatalities known to the Scottish Fire Brigades as having died in a fire incident during 1980 to 1990. It is accepted that this is just one possible definition of what constitutes a suicide by fire. Forty cases were identified as suicides from the circumstances of the death as narrated in the police and Fire Brigade reports of the incident. Autopsy and toxicological reports were examined for all cases and the characteristics of the victim and the incident are described. Most cases occurred in the home of the victim and three-quarters of the victims were pronounced dead at the scene or when first seen by a doctor. Smoke inhalation was the most frequently certified cause of death. Alcohol was present in less than half the cases and toxicological analysis for drugs was performed in the minority of cases. One-quarter of victims were reported to have made at least one suicide attempt previously. A range of apparently precipitating factors was observed: the number of cases which appeared to be impulsive responses to life events suggests that prevention is difficult.     

The potential role of bacterial toxins in Sudden Infant Death Syndrome (SIDS)

Summary Toxigenic bacteria have been implicated in some cases of Sudden Infant Death Syndrome (SIDS). Although there is not much evidence thatClostridia spp. are associated with SIDS in Britain, strains ofStaphylococcus aureus producing pyrogenic toxins have been isolated from significant numbers of these infants at autopsy. The pyrogenic toxins, produced by some strains of group AStreptococcus pyogenes as well as staphylococci, are powerful superantigens that have significant physiological effects including induction of fever > 38°C. In this article, interactions between genetic and environmental factors that might enhance colonization of epithelial surfaces by toxigenic staphylococci are analyzed: infant's expression of Lewis^a antigen which acts as a receptor for some microorganisms; viral infections; the effect of mother's smoking on susceptibility to respiratory infection. Based on epidemiological findings and laboratory investigations, a hypothesis is proposed to explain how bacteria producing pyrogenic toxins might contribute to some cot deaths.     

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.     

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.      

Advances in pediatric liver and intestinal transplantation

BACKGROUND: Significant progress has been made with liver and intestinal transplantation in pediatric patients. Shortage of whole-organ cadaveric grafts has resulted in a high mortality rate for children awaiting transplantation. New surgical procedures such as split-liver transplantation and living-related liver transplantation have evolved over the last decade to maximize donor utilization in pediatric patients. METHODS: In this article we review the current indications and contraindications for liver and intestinal transplantation in children, the surgical innovations to expand an exceedingly small cadaveric liver pool, postoperative management, and the impact on patient and graft survival. RESULTS: Reduced-size liver transplantation provides children with much needed small grafts; however, split-liver transplantation may eliminate the need for reduced-size and living-related liver transplantation except in urgent situations. CONCLUSION: Liver transplantation is a durable procedure that provides excellent long-term survival. The use of living-related and split-liver transplantation has dramatically reduced the waiting periods for children and improved survival. In the past decade significant progress has been made with intestinal transplantation owing to improvements in surgical technique, immunosuppressive agents, and early identification and treatment of postoperative complications.     

Aortic saddle embolus. A twenty-year experience.

Clinical experience with aortic saddle embolus (ASE) is not extensive due to the relative infrequent lodging of emboli at the aortic bifurcation. During the period 1962-1982, 26 patients (mean age, 56 years) were treated at the UCLA Medical Center for ASE and followed from 2 to 158 months (mean, 45 months). These cases were reviewed in order to identify features of diagnosis, anticoagulation, and operation which impact on results. All 26 patients presented with bilateral lower extremity ischemia with or without extension of clot to the iliac bifurcation. Ninety-six per cent of emboli were of cardiac origin and one-third occurred in patients who had previous symptoms of chronic lower extremity ischemia. Rest pain and motor/sensory deficits were main complaints in 92% of the patients, but did not become manifest until more than 6 hours, unlike more distal emboli which have an earlier presentation. Preoperative angiography, even in the patient with a history of claudication, has a small role in planning the surgical approach to patients with ASE and, although performed in 11 patients, it influenced operation in only two. Operation within the "golden period" of 6 hours after embolization did not significantly influence outcome after ASE, since 20 patients were operated on more than 6 hours after embolization, with results similar to six patients who were operated on less than 6 hours after embolization. Early high-dose heparinization, used in all patients and maintained for a mean of 12 days, may have contributed to this effect. In 22 patients (85%) Forgarty catheter extraction via bilateral groin approaches was used with a mortality of 14%; only one death was directly attributed to the catheter embolectomy. In 15% of patients, a direct approach on the aorta was selected with a zero mortality rate. Postoperative functional result was excellent with an amputation rate of only 2% (one limb). Re-embolization occurred in seven patients (27%) after discharge, five of whom had not been maintained on Coumadin and two who were not anticoagulated adequately. The authors conclude that the keys to successful treatment of ASE include high dose heparin which is maintained through the perioperative period, embolectomy without preoperative angiography, and maintenance of long-term oral anticoagulation.     

Ischemia and reperfusion injury in liver transplantation

Ischemia/reperfusion (I/R) injury is a multifactorial process detrimental to liver graft function. An understanding of the mechanisms involved in I/R injury is essential for the design of therapeutic strategies to improve the outcome of liver transplantation. The generation of reactive oxygen species subsequent to reoxygenation inflicts tissue damage and initiates a cellular cascade leading to inflammation, cell death, and ultimate organ failure. The accruing evidence suggests that Kupffer cells and T cells mediate the activation of neutrophil inflammatory responses. Activated neutrophils infiltrate the injured liver in parallel with increased expression of adhesion molecules on endothelial cells. The heme oxygenase (HO) system is among the most critical of the cytoprotective mechanisms activated during the cellular stress, exerting anti-oxidant and anti-inflammatory functions, modulating the cell cycle, and maintaining the microcirculation. The activation of toll-like receptors (TLR) on Kupffer cells may provide the triggering signal for pro-inflammatory responses in the I/R injury sequence. Indeed, dissecting TLR downstream signaling pathways plays a fundamental role in exploring novel therapeutic strategies based on the concept that hepatic I/R injury represents a case for host "innate" immunity.     

Factors influencing the acceleration of human factor XIa inactivation by antithrombin III

Controversy exists in the literature concerning the potentiating effect of heparin on the inactivation rate of factor XIa by antithrombin III (AT III) in both purified systems and in plasma. We have analyzed the factors that could influence this reaction and found that ionic strength of the medium, as well as the type and concentration of the heparin preparations accounted for the major discrepancies in the literature. At I = 0.43 N, a preparation of bovine lung heparin at 1 U/mL did not augment the inactivation rate of factor XIa by inhibitors in plasma or by purified AT III. However, when ionic strength was decreased, a progressive increase in the potentiating effect was observed, reaching 6.5-fold at I = 0.15 N. At saturating concentrations of heparin, which results in the formation of 100% AT III-heparin complex, (greater than ten-fold molar excess over AT III) in purified systems, all heparin preparations (porcine, bovine, low molecular weight [LMW], and high affinity) yielded an approximately 30-fold augmentation of the factor XIa inactivation rate. However, when heparin was less than saturating, we observed that various heparin preparations affected the AT III-induced inactivation of factor XIa to different degrees even though they exhibited the same inhibitory activity (1 U/mL) against thrombin. This variation resulted from differences in the number of AT III binding sites in each heparin preparation, despite a similar Kd for each. Addition of high molecular weight kininogen (HK) to AT III-heparin complexes did not enhance their ability to inhibit factor XIa, and high concentrations of HK decreased the inactivation rate. A high therapeutic dose of heparin only permits the formation of 2.5% to 16.5% of the AT III-heparin complexes that can be achieved at saturation. We observed that 1 U/mL heparin (bovine lung heparin) (high therapeutic concentration) in virtually undiluted plasma only accelerated the inactivation rate of factor XIa (in the absence of other active enzymes) less than two-fold. These new observations further support our previous conclusion that therapeutic levels of heparin have little to no influence on the inactivation rate of factor XIa in plasma.