Introduction: There are numerous prehosital descriptive scoring systems, and it is uncertain whether they are efficient in assessing of the severity of illness and whether they have a prognostic role in the estimation of the illness outcome (in comparison with that of the prognostic scoring system Acute Physiology and Chronic Health Evaluation [APACHE] II). The purpose of the present study was to assess the value of the various scoring systems in predicting outcome in nontraumatic coma patients and to evaluate the importance of mental status measurement in relation to outcome.

Thrombotic thrombocytopenic purpura (TTP) either occurs in a congenital form caused by ADAMTS13 gene mutations or it is acquired and most often due to ADAMTS13 inhibitory autoantibodies. In congenital TTP siblings are often affected, while acquired TTP occurs sporadically and familial clustering has not been described so far. We report identical twin sisters suffering from acquired TTP due to immunoglobulin G (IgG) autoantibodies inactivating ADAMTS13, suggesting an important role of hitherto unidentified genetic determinants of ADAMTS13 inhibitor formation. These cases also demonstrate that familial clustering is not sufficient for unambiguously diagnosing hereditary ADAMTS13 deficiency and congenital TTP. IntroductionThe metalloprotease ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 domains-13) 1-5 specifically cleaves the von Willebrand factor (VWF) subunit at the peptide bond Tyr842-Met843. 6,7 A severely deficient ADAMTS13 activity (Ͻ 5% of that in normal plasma) was found to be a strong risk factor for thrombotic thrombocytopenic purpura (TTP). 8,9 There are 2 fundamental mechanisms known to cause severe ADAMTS13 deficiency. Homozygous or compound heterozygous mutations of the ADAMTS13 gene lead to hereditary ADAMTS13 deficiency in congenital TTP, 3,10-14 often affecting siblings. In contrast, most cases of acquired TTP are caused by autoantibodies inactivating ADAMTS13. 8,9,15 Acquired TTP occurs sporadically, and familial clustering has not been described so far. Distinction between both forms is important as their management may differ. While regular infusion of limited amounts of fresh frozen plasma (FFP) usually reverts or prevents disease manifestations in congenital TTP, plasma exchange with FFP replacement, often combined with corticosteroids or other immunosuppressants, is the current therapy of choice in acute acquired TTP. 16 We report identical twin sisters suffering from acquired TTP due to severe ADAMTS13 deficiency caused by circulating inhibitory immunoglobulin G (IgG) autoantibodies. Study design PatientsPreviously healthy identical twin sisters suffered from a first episode of acute TTP at 23 (sister 1) and 24 (sister 2) years of age. Sister 1 presented with fever, neurologic symptoms, thrombocytopenia, and microangiopathic hemolytic anemia. Since therapy was initiated promptly, symptoms were less pronounced in sister 2. These episodes resolved under plasma exchange with FFP replacement and corticosteroids; sister 1 received vincristine, in addition. Follow-up for now 37 (sister 1) and 25 (sister 2) months was uneventful except for a short relapse in sister 1, which occurred 13 months after the initial episode and was treated by plasma exchange. Since then, no plasma has been administered to either of the sisters.Both sisters are otherwise healthy without indication of another autoimmune disease, especially systemic lupus erythematosus (SLE), and have the same living and working conditions. No pregnancy has so far occurred in either sister. No drugs, including ora...

In the light of clustered deaths in late 2001 associated with hemodialysis (HD), this article analyzes the pathochemical toxicity of the perfluorocarbon-5070 (PF-5070), a liquid used as test performance fluid for detecting capillary leaks during dialyzer manufacturing. Residual PF-5070 in some Athane dialyzers of the involved brands was infused in the injured patients during hemodialysis. The clinical presentation was in contrast with other previously described severe reactions to HD. Foam material was discovered in the right ventricle and caval vein of the patients who underwent postmortem examination. Deaths were attributed to gas embolism without the external causes identified. To explore the pathochemical toxicity of the inert liquid PF-5070, an animal model was developed. In a rabbit model, single slug intravenous injections as bolus of increasing doses of PF-5070 were performed. In a first set of experiments, three groups of three rabbits were administered increasing doses of PF-5070 at 4, 40, or 160 l/kg. After intravenous injection, the animals were observed for clinical signs of adverse effects and underwent autopsy after death. Doses were normalized to animal body weight to allow comparison with supposed patient exposure. Five of nine rabbits died soon after PF-5070 dosing: One rabbit died within 4 h in the 4 l/kg group, one rabbit died within 30 min in the 40 l/kg group, and three rabbits died within 30 min in the 160 l/kg group. In a second set of experiments, six rabbits were injected with a lethal dose of PF-5070 to analyze clinical symptoms and pathophysiology. All rabbits died on the day of dosing and displayed neurologic disorders (paralysis, nystagmus, rigidity, convulsions), then breathing abnormalities (rapid breathing, salivation, dark mucous membrane), and fatal collapse. Autopsy of rabbits showed evidence of gas retention in the lung tissue and gas bubbles in the right cardiac cavities. Histologic findings included alveolar hemorrhage with pulmonary edema, cerebellum, and cortex patchy areas of infarction. Single-dose intravenous administration of PF-5070 reproduced in a rabbit model the pathophysiologic effects observed in the hemodialysis patients. Severity of the symptoms observed in the animals was dose-dependent. Clinical and pathologic findings can be explained by the capacity of perfluorocarbon to emulsify blood at body temperature, to increase partial pressure in the pulmonary capillary bed, and to form bubbles in the pulmonary capillary circulation, thus blocking lung and visceral perfusion. Such experimental findings indicate the toxicity of PF-5070 administered intravenously and make the pathochemical toxicity link with the hemodialysisrelated deaths caused by the presence of residues of PF-5070 in the Althane dialyzers. We conclude, in light of this outbreak and the subsequent investigations, that liquid PF-5070 is a highly toxic compound when administered intravenously because of its emulsifying properties. The use of PF-5070 or any liquid fluorocarbon compounds in medical dev...

Aggressive natural killer-cell leukaemia (ANKL) is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV) and P-glycoprotein (P-gp) expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56+ NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

The use of cyclosporin has been associated with the development of cholelithiasis in transplant recipients. Cholelithiasis in turn enhances the effects of cyclosporin on increased platelet aggregation. In this report, a patient who had undergone a renal transplantation as a result of malignant hypertension, and who was on immunosuppressive therapy consisting of cyclosporin, prednisone and azathioprine, developed thrombosis of the central retinal vein 5 years following the transplantation. Seven years after the transplantation, cholelithiasis, cholecystitis, cholangitis and subsequently secondary chronic biliary sclerosis were detected. Latero-lateral anastomosis between the common bile duct and duodenum was performed during explorative laparotomy and ursodeoxycholic acid treatment was introduced. The possible inter-relationship of the cholestatis, central retinal vein thrombosis and immunosuppression are discussed.