Modified Thrombolysis in Myocardial Infarction (TIMI) risk score to risk stratify patients in the emergency department with possible acute coronary syndrome

Objective To assess the prognostic utility of the Thrombolysis in Myocardial Infarction (TIMI) risk score in patients in the emergency department (ED) evaluated for possible acute coronary syndrome (ACS). Background The ability of the TIMI risk score to risk stratify patients at initial presentation in the ED with chest pain of unclear etiology is uncertain. Methods We investigated the prognostic utility of the TIMI risk score in 947 consecutive patients evaluated in the ED for possible ACS. A multivariate analysis was done to evaluate the independent predictive power of the individual components of the TIMI risk score to predict an adverse event at 30 days (all-cause death, myocardial infarction, and coronary revascularization). Results There were 151 (16%) patients diagnosed with ACS. At 30 days there were 48 (5%) deaths, 84 (9%) myocardial infarctions, and 49 (5%) coronary revascularization procedures. The mean TIMI risk score was significantly higher in patients with an adverse event compared with those without (2.6 ± 1.3 vs. 1.7 ± 1.2, P < 0.0001). Four of the 7 TIMI risk factors (age ≥65 years, ST segment deviation ≥0.5 mm elevated troponin I, and coronary stenosis ≥50%) were independently associated with adverse events. A simplified TIMI risk score was computed and was found to have similar prognostic ability as the 7 variable TIMI risk score. Conclusion A modified TIMI risk score may simplify risk stratification of ED patients with undifferentiated chest pain.     

Lungenembolie

In the population the annual incidence of pulmonary embolism amounts to 1.3-2.8 per 1000 at the age of 65-89 years. Mortality reaches about 17% within the first 3 months. Acute pulmonary embolism is characterized by an increase in pulmonary arterial pressure and an impairment of the pulmonary gas exchange. Elevation of the right cardiac pressure up to right heart decompensation may follow. In addition, hypoxemia, hyperventilation, dead space ventilation, right to left shunting, bronchoconstriction, and vasoconstriction may occur. Clinical examination, ECG, laboratory findings such as elevated D-dimer, blood gas analysis, ultrasound examination of the veins of the lower extremities, and transthoracic echocardiography are acutely available diagnostic methods of an emergency department. In addition, extensive diagnostic procedures like pulmonary scintigraphy and pulmonary angiography may be required. The aim is to get a definite diagnosis as quickly as possible to direct therapy. In acute pulmonary embolism with cardiac shock, monitoring and stabilization of the circulatory function as well as an appropriate anticoagulant therapy are essential. In some cases surgery or a local fibrinolytic intervention is indicated.     

Leukocytapheresis (LCAP) in the Management of Chronic Active Ulcerative Colitis—Results of a Randomized Pilot Trial

Recent studies suggest that leukocytapheresis with Cellsorba is a valuable therapy for ulcerative colitis after failure of conventional treatment. In this study the potential of leukocytapheresis to induce remission in refractory chronic colitis under the conditions of European treatment guidelines was investigated. The therapeutic benefit of leukocytapheresis in the maintenance of remission was additionally elucidated. Twenty patients were treated weekly for 5 weeks. A significant decrease in the activity index was observed. Fourteen patients achieved clinical remission, and mucosal healing was observed endoscopically in six patients. After randomization these 14 patients in remission entered a second period of either monthly leukocytapheresis or no further treatment. In both groups steroids were tapered down. After 6 months, only one patient in the control group remained in remission, in contrast to five of eight patients in the leukocytapheresis group. In conclusion, leukocytapheresis may offer a therapeutic option in the induction and the maintenance of remission in chronic active ulcerative colitis.     

Lipoma of the aortic valve in a patient with acute myocardial infarction

We hereby report the first--to the best of our knowledge--case of primary lipoma of the aortic valve. The tumor has been diagnosed by echocardiography supported by magnetic resonance imaging in a 63-year-old man with acute inferior ST-elevation myocardial infarction (STEMI) and one-vessel coronary artery disease. Five weeks from the onset of STEMI, direct implantation of a bare metal stent into the right coronary artery was successfully undertaken and 6 weeks later aortic valve with an encapsulated mass was excised with subsequent artificial valve implantation. Histological examination revealed typical features of lipoma. Three months after the operation the patient was asymptomatic and exhibited a good function of the artificial valve.     

Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development

Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that TP53INP1 expression is dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and this decrease occurs early during pancreatic cancer development. TP53INP1 reexpression in the pancreatic cancer-derived cell line MiaPaCa2 strongly reduced its capacity to form s.c., i.p., and intrapancreatic tumors in nude mice. This anti-tumoral capacity is, at least in part, due to the induction of caspase 3-mediated apoptosis. In addition, TP53INP1(-/-) mouse embryonic fibroblasts (MEFs) transformed with a retrovirus expressing E1A/ras(V12) oncoproteins developed bigger tumors than TP53INP1(+/+) transformed MEFs or TP53INP1(-/-) transformed MEFs with restored TP53INP1 expression. Finally, TP53INP1 expression is repressed by the oncogenic micro RNA miR-155, which is overexpressed in PDAC cells. TP53INP1 is a previously unknown miR-155 target presenting anti-tumoral activity.     

High blood lead levels in recreational indoor-shooters

Introduction  Recreational shooting in indoor firing ranges is very popular in Germany. Lead-containing ammunition is still in use. Therefore we checked the blood lead levels (BLL) from 129 subjects doing several types of shooting disciplines. Methods  In total, BLLs of 129 shooters (nine female) from 11 different shooting ranges with a mean age of 49 years were measured. The blood samples were taken after the volunteers had given written informed consent. Determination of lead was carried out by graphite furnace atomic absorption (GF-AAS) under strict internal and external quality control schemes. Results  While individuals shooting only with airguns (n = 20) showed a median BLL of 33 μg/l (range 18–127 μg/l), those who were also users of .22 lr weapons (n = 15) turned out to have a median of 87 μg/l (range 14–172 μg/l). Shooters of .22 lr and large calibre handguns (9 mm or larger) (n = 51) had median 107 μg/l (range 27–375 μg/l) and those only using large calibre handguns (n = 32) had median 100 μg/l (range 28–326 μg/l). The IPSC-group (n = 11) had the highest median with 192 μg/l (range 32–521 μg/l). Conclusion  Our results show clearly that many shooters have high blood levels; some of them are still exceeding threshold limit values (TLVs) for lead exposed workers. Especially for younger women there is a high potential risk if they become pregnant. So there is a clear need for improving the situation whether by use of lead-free ammunition or by better ventilation systems.     

The tyrosine kinase inhibitor AMN107 (Nilotinib) exhibits off-target effects in lymphoblastic cell lines

The aminopyrimidine inhibitor AMN107 (Nilotinib) was rationally designed to antagonize the aberrant tyrosine kinase activity of Bcr-Abl-positive cells. We here evaluated, whether AMN107 is also able to induce apoptosis in Bcr-Abl-negative cells of lymphatic origin. The B-cell lines DOHH-2 and WSU-NHL and the T-cell lines Jurkat and HUT78 were incubated with increasing amounts of AMN107 corresponding to clinically achievable dosages. Subsequently, induced molecular changes were assessed by FACS analysis, Western blot, and enzyme activity assays. Although AMN107 exhibited only a minor apoptosis-inducing effect in the T-cell lines, it exerted a considerable, dose-dependent cytotoxicity in the B-cell lines. Using selective caspase-inhibitors, we show that apoptosis in responder cell lines critically relies on activation of caspase-6 and caspase-9. Cell lines sensitive and resistant towards AMN107 can be discriminated by their differential expression of Src-kinases. Although the AMN107-sensitive cell lines DOHH-2 and WSU-NHL exhibited low or no expression of the Src-kinases Lck, phosphorylated Lck, and Yes with a concomitant high expression of Hck, Lyn, and phosphorylated Lyn, the expression pattern of these kinases was inverse in the AMN107-resistant T-cell lines. In conclusion, this is the first report providing evidence that activity of AMN107 is not restricted to Bcr-Abl, c-Kit, or PDGFR-positive cells, but also extends to lymphatic cell lines of B-cell origin.     

Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR–ABL-positive acute lymphoblastic leukemia—retrospective analysis of Polish Adult Leukemia Group (PALG)

Patients with Philadelphia chromosome-positive (Ph+) and/or BCR–ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR–ABL+ ALL registered in Poland in 1997–2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR–ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.