Identification of PUMA as an estrogen target gene that mediates the apoptotic response to tamoxifen in human breast cancer cells and predicts patient outcome and tamoxifen responsiveness in breast cancer.

Recognition of the pivotal role of estrogen in the aetiology of breast cancer has led to the development of antiestrogens (AE), such as tamoxifen (TAM) as effective therapies for the treatment and prevention of this disease. However, despite their widespread clinical efficacy, response to AEs is often short-lived, and acquired or innate therapeutic resistance remains a major obstacle in the successful treatment of breast cancer. Thus, delineating the intracellular pathways that mediate the cellular response to estrogen could potentially lead to new, more effective approaches to the treatment of breast cancer, particularly endocrine-resistant disease. Here, we have identified the BCL-2 homology 3 (BH3)-only, pro-apoptotic regulator, PUMA (p53 upregulated modulator of apoptosis) as an estrogen target gene that is acutely downregulated in response to estrogen in breast cancer cell lines, independently of their p53 status. PUMA is transcriptionally upregulated following treatment with TAM, and knock down of PUMA expression in these cells attenuates the apoptotic response to TAM. Furthermore, low PUMA expression in breast carcinomas is significantly associated with breast cancer-specific death (P=0.0014 and P=0.0115, for mRNA and protein, respectively), and worse outcome in TAM-treated patients (mRNA, P=1.49e-05). These findings suggest that the dysregulation of apoptotic signaling pathways such as those executed through PUMA, can significantly impact on both the progression and therapeutic responsiveness of breast cancer. Moreover, they provide a convincing rationale for exploring new therapeutic approaches involving endocrine and non-endocrine therapies that target apoptotic pathways as an effective strategy for tackling endocrine refractory disease.

[Use of the laryngeal mask in oral and dental surgery]. / Die Anwendung der Larynxmaske in der Mund-, Kieferund Gesichtschirurgie.

OBJECTIVE: The suitability of the laryngeal mask (LM) for anesthesia in oral and dental surgery of the face was investigated considering in particular the risks of aspiration and dislocation. We also examined acceptability to the surgeon. METHODS: In a prospective study, a total of 105 patients (ASA I-III) was included. Provided with flexible LMs, patients were operated upon the third molars (n = 64), around the dentoalveolar area (n = 32) and extraorally (n = 9). The number of placing efforts, preoperative leakage pressure, cuff pressure and complications occurring during the course of anesthesia were recorded. After the operation, the procedure was compared to endotracheal anesthesia (ETA) by the surgeon. A retrospective study comparing LM with ETA was performed on 1395 patients examining the time in between two operations, the period from the end of operation to the beginning of control of vital signs in the recovery room, and the time spent in the recovery room. The number of patients necessitating a change of anesthesia from LM to ETA was recorded. RESULTS: In 33 patients (31%), intraoperative leakage due to dislocation was observed. 33 patients (31%) had obstruction of the airway. Only when leakage occurred together with obstruction of the airway, SaO2 fell below 94% (n = 11). This was seen in particular during exposure of the wisdom teeth. In 2 of these cases, SaO2 decreased below 70 or 34% respectively. Aspiration of blood, gastric juice or dental and bone fragments was not observed. In one case, ETA became necessary. 19 patients complained of local pains (cough, sore throat, dysphagia). Operative conditions for the surgeon were comparable to oral ETA in 79% of the cases. The time in between two operations decreased about 35%, the period from the end of operation until first control of vital signs in the recovery room was reduced of about 41%, and the time spent in the recovery room decreased by 37% when compared to ETA. Out of 1111 anesthesias performed with the LM, 17 had to be exchanged for ETA. CONCLUSION: Leakage due to dislocation of the LM and airway obstruction only leads to a relevant risk of SaO2 to drop if both components occur simultaneously. With increasing experience and close cooperation between surgeon and anesthesiologist, they may be almost completely avoided so that even exposure of the lower, wisdorri teeth will seldom iiecessiiate the LM to be replaced by ETA. In relation to the tongue depressor, cuff pressure should be kept at low levels in order to obtain better flexibility of the LM. The LM provides sufficient protection against aspiration of intraoperative fluid in the pharynx. Acceptability to the surgeon is high because of good operative conditions and shortened periods in between two operations when compared to ETA. Improved protective reflex responses after the operation and its advantages when used in patients with tightness of the jaw make the LM a suitable instrument for anesthesia in oral and dental surgery.

[Heparin-induced thrombocytopenia Type II (HIT II) A fatal complication of heparin use for thromboembolism prevention]. / Heparininduzierte Thrombozytopenie Typ II (HIT II). Eine fatale Komplikation der medikamentösen Thromboseprophylaxe mit Heparinen.

Heparin-induced thrombocytopenia type II (HIT II) is the most severe complication during prophylactic treatment with low doses of heparin. Five cases demonstrate the life-threatening consequences of this immune-mediated thromboembolic disease. In order to improve prognosis it is most important to start therapy just before diagnosis is assured by laboratory tests. First choice treatment is the low-molecular-weight heparinoid Orgaran. In patients with an episode of HIT II both low-molecular-weight heparin and unfractionated heparin will be contraindicated for a life time.