EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

Angiotensin I conversion and coronary constriction by angiotensin II in ischemic and hypoxic isolated rat hearts.

Dose-response curves of angiotensin I (AI, 1.0-1000.0 pmol) and angiotensin II (AII, 1.25-1250.00 pmol) were obtained in isolated rat hearts subjected to control conditions, mild hypoxia (PO2 = 145 mm Hg), reoxygenation, ischemic (perfusion pressure = 35 mm Hg) and reperfusion. Both AI and AII caused dose-dependent coronary flow (CF) of 26 +/- 3 and 27 +/- 2%, respectively. The effects of both AI and AII were substantially attenuated during hypoxia, but were fully restored upon reoxygenation. During ischemia, the effect of AII was unaltered while the effect of AI was enhanced compared to the control (P less than 0.05). This enhancement was reversible on reperfusion. Cardiac conversion of AI, calculated from ED50 values for AI and AII, was significantly increased during ischemia (P less than 0.05). Infusion of saralasin (0.5-5.0 micrograms/min) did not increase CF in any of the groups. We conclude that (1) the coronary vasoconstrictive effect of AII is preserved in ischemia but attenuated in hypoxia and (2) cardiac conversion of AI to AII is enhanced in hearts injured by ischemia.     

Toxic epidermal necrolysis; 15 years'' experience in a Dutch burns centre

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe and potentially fatal drug reaction characterized by an extensive skin rash with blisters and exfoliation, frequently accompanied by mucositis. The wounds caused by TEN are similar to second-degree burns and severe cases may involve large areas of skin loss. OBJECTIVES: Analysis of our results in patients with TEN and evaluation of the variety of therapeutic interventions that has been studied and suggested in TEN. PATIENTS/METHODS: Retrospective analysis of 19 consecutive patients with TEN treated in our burns centre between 1989 and 2004. RESULTS: Immediate withdrawal of any potentially fatal drug, maximum supportive care, and a restricted and tailored antibiotic, medical and surgical treatment regimen confined mortality to 21%, whereas prognosis scores like APACHE II and SCORTEN predicted mortality of 22 and 30%, respectively. A positive contribution of selective digestive decontamination is suggested but has yet to be established. CONCLUSIONS: Because of a potentially fatal outcome, fast referral of a patient suspected of TEN to a specialized centre (mostly a burns unit or specialized dermatology centre) for expert wound management and tailored comprehensive care is strongly advised and contributes to survival.     

Heparininduzierte Thrombozytopenie

Heparin-induced thrombocytopenia (HIT) represents a serious side effect caused by an atypical immune response to platelet factor 4 leading to platelet activation and thrombin formation. These patients are at high risk of thromboembolism, with a rapid drop in platelet count between days 5 and 14 after the initiation of heparin treatment. In single cases, especially after major surgery, platelet count reduction might be absent or hidden by preceding thrombocytosis. Different clinical manifestations of HIT include unspecific skin reactions with potential necrosis at the site of heparin injection, mostly after the application of unfractionated heparin but also with low molecular weight heparin. In heparin-induced skin necrosis, administration of unfractionated or low molecular weight heparin is contraindicated and heparin therapy should be stopped immediately. Instead, an alternative anticoagulant in the form of a direct thrombin inhibitor such as argatroban, and respectively lepirudin, or danaparoid sodium must be administered. Due to frequent misinterpretations of heparin-induced unspecific skin reactions, especially in the absence of thrombocytopenia, we present two case reports which should increase the awareness of HIT’s various clinical pictures.     

女性慢性下腹痛的干预性治疗

1背景 育龄妇女常见慢性下腹痛，可造成身体损害、情绪忧伤及导致巨大的健康服务费用。美国在这方面的花费超过8亿8千万美元（Mathias 1996）。英国全国数据库的一般性诊治资料显示，慢性下腹痛发病率及流行率与偏头痛、背部痛、哮喘发病率相似（Zondervan 1999）。     

Hemolytic properties and riboflavin synthesis of Helicobacter pylori: cloning and functional characterization of the ribA gene encoding GTP-cyclohydrolase II that confers hemolytic activity to Escherichia coli

Various strains of Helicobacter pylori were able to lyse erythrocytes from sheep, horse, and human when grown on blood agar. The hemolysis did not depend on the production of the vacuolating cytotoxin VacA as demonstrated by the hemolytic behavior of an isogenic vacA-negative mutant strain. The hemolytic activity could be detected in cell-free supernatants and was not regulated by iron. To isolate genes coding for proteins involved in the destruction of erythrocytes, a plasmid-based DNA library was screened for expression of lytic activity on blood agar. This approach revealed that the H. pylori ribA gene confers hemolytic properties to Escherichia coli. The ribA gene encodes the enzyme GTP-cyclohydrolase II [EC 3.5.4.25] that catalyzes the initial step in the synthesis of riboflavin. The predicted amino acid sequence of the H. pylori RibA protein showed a high degree of similarity to equivalent enzymes from microorganisms and from plants. The single gene on a plasmid restored riboflavin synthesis in a ribA mutant of E. coli and induced hemolytic activity. Furthermore, ribA overexpression was associated with the production of a fluorescent yellow molecule that was not identical with riboflavin. Hemolysis was also seen for the ribA gene from E. coli, indicating that this feature was not specific for the H. pylori gene. The presence of ribA in various H. pylori strains was confirmed by Southern blot hybridization and by polymerase chain reaction with specific primers. This analysis revealed that microdiversity exists within the DNA region upstream from ribA, which was further confirmed by nucleotide sequence analysis. Received: 25 July 1997