[Septic shock with purpura fulminans after a dog bite]. / Sepsis mit Purpura Fulminans nach Hundebiss.

HISTORY AND CLINICAL FINDINGS: A 61-year-old man presented with a four-day history of back pain and nonspecific abdominal pain. His condition had significantly worsened since the day before admission with generalized weakness and dyspnea. His temperature was 39.1 C, he had tachycardia and was tachypneic. Peripheral cyanosis was noted. The abdomen was soft with mild epigastric tenderness. A diffuse skin rash developed with increasing petechial bleeding and central necrosis. It was revealed that he had been bitten by a dog several weeks before admission. INVESTIGATIONS: Laboratory data indicated an acute inflammatory process with a marked increase in white blood cells and C-reactive protein. An elevated procalcitonin level suggested a systemic bacterial infection. Chest X-ray and abdominal CT scan were unremarkable. Echocardiography revealed a globally hypokinetic heart with no evidence of valvular vegetations. One set of blood cultures grew micro-aerophilic, Gram-negative rods. Gene sequencing identified the slow growing, fastidious bacillus as CAPNOCYTOPHAGA CANIMORSUS. TREATMENT AND COURSE: The patient was admitted to the intensive care unit and initially treated with intravenous piperacillin/tazobactam and hydrocortisone for septic shock. Transfusions of platelets and blood products were given because of disseminated intravascular coagulation. The patient developed multi-organ failure requiring ventilation and hemodialysis; he died four days after admission. CONCLUSIONS: As a rare cause of septicemia, especially in immunocompromised patients, Capnocytophaga canimorsus infection should be considered after an animal bite. Given the slow growth of this bacterium in culture, Gram-staining of a peripheral blood smear may provide an early diagnosis and avoid delay before appropriate antibiotic therapy, which may favorably influence the potentially fatal course, is started.

Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis.

The canonical Wnt signalling pathway plays a key role during embryogenesis and defects in this pathway have been implicated in the pathogenesis of various types of tumours, including breast cancer. The gene for secreted frizzled-related protein 1 (SFRP1) encodes a soluble Wnt antagonist and is located in a chromosomal region (8p22-p12) that is often deleted in breast cancer. In colon, lung, bladder and ovarian cancer SFRP1 expression is frequently inactivated by promoter methylation. We have previously shown that loss of SFRP1 protein expression is a common event in breast tumours that is associated with poor overall survival in patients with early breast cancer. To investigate the cause of SFRP1 loss in breast cancer, we performed mutation, methylation and expression analysis in human primary breast tumours and breast cell lines. No SFRP1 gene mutations were detected. However, promoter methylation of SFRP1 was frequently observed in both primary breast cancer (61%, n=130) and cell lines analysed by methylation-specific polymerase chain reaction (MSP). We found a tight correlation (P<0.001) between methylation and loss of SFRP1 expression in primary breast cancer tissue. SFRP1 expression was restored after treatment of tumour cell lines with the demethylating agent 5-aza-2'-deoxycytidine. Most interestingly, SFRP1 promoter methylation was an independent factor for adverse patient survival in Kaplan-Meier analysis. Our results indicate that promoter hypermethylation is the predominant mechanism of SFRP1 gene silencing in human breast cancer and that SFRP1 gene inactivation in breast cancer is associated with unfavourable prognosis.

[Effective data collection in cancer research: an all-in-one database solution]. / Effektive Datenerfassung in der Krebsforschung: eine "all-in-one" Lösung.

Tissue banks containing human malignant and benign tissue have become highly important for modem cancer research. They provide an excellent source of information with respect to pathological states and processes. Nowadays tissue samples can be examined using a broad variety of molecular biology methods, at the levels of DNA, RNA and protein. However, these new possibilities impose great expectations from the user side towards tissue banks and their associated databases. Nowadays a database that only manages tissue samples is not timely anymore. In fact a modern database should be capable of registering arbitraty amounts of tissue relevant information in an easily searchable way. In order to simplify the often complicated and time consuming process of data collection, we have developed a software solution that centralizes various aspects of tumor tissue banking. The main task of this software is not only to administer tissue samples but also to provide a centralized data platform for scientists which support their research. To achieve our goals we have constructed a tissue database which is supported by an Oracle System. The access to this database has been made possible with a light-weight, self-developed Java Client Program. The system possesses high levels of security and the access to information in the database is strictly controlled by preset permissions. A flexible search mechanism is also readily available for speedy data extraction according to various criteria. This solution provides us with an "All-in-one" tool for the purpose of flexible and efficient data collection and management in cancer research.