Metastable oxidation states of tetrathiafulvalenes on the surface of liposomes.

Redox-active liposomes are prepared by the incorporation of tetrathiafulvalene-cholesterol conjugate 1 in phospholipid vesicles. The oxidation of tetrathiafulvalene (TTF) on the surface of the liposomes in aqueous solution is monitored by UV-vis spectroscopy. It is shown that metastable (TTF+˙)2π-dimers of the mono-oxidized cation radical are formed due to the high local concentration of TTF groups in the lipid membrane. These dimers can be further stabilized by the addition of cucurbit[8]uril or by reduction of the lateral mobility in the membrane by variation of the lipid composition.

Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.

Formation and structure of copper(II) oxalate layers on carboxy-terminated self-assembled monolayers.

Copper(II) oxalate was grown on carboxy-terminated self-assembled monolayers using a step-by-step approach by dipping the surfaces alternately in ethanolic solutions of copper(II) acetate and oxalic acid with intermediate thorough rinsing steps. The deposition was monitored by reflection absorption infrared spectroscopy (RAIRS), a quartz microbalance with dissipation measurement (QCM-D), scanning electron microscopy (SEM), and helium ion microscopy (HIM). Amounts of material corresponding to a coverage of 75% of a monolayer are deposited in each dipping step in copper(II) acetate solution while deposition of oxalic acid produces a viscoelastic layer that is partially removed by rinsing. This points toward initial aggregation but acid not bound to Cu(2+) ions as oxalate ions is removed by the rinsing steps. RAIRS further indicates that the material grows as copper(II) oxalate ribbons similar to the crystal structure but with ribbons oriented roughly parallel to the surface. SEM and HIM give evidence of the formation of needle-shaped structures which are a possible explanation for the viscoelastic behavior of the layer.

Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44).

BACKGROUND: We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m(2); q3w) followed by four cycles docetaxel (100 mg/m(2); q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy. RESULTS: TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis. CONCLUSIONS: The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates.

Whole-brain perfusion CT using a toggling table technique to predict final infarct volume in acute ischemic stroke.

PURPOSE: To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. MATERIALS AND METHODS: Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. RESULTS: The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. CONCLUSION: Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. KEY POINTS: ▶ Using PCT and the "toggling table technique" allows accurate quantification of the infarct core and penumbra. ▶ It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. ▶ The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals.

Whole-brain perfusion CT using a toggling table-technique to predict final infarct volume in acute ischemic stroke.

PURPOSE: To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. MATERIALS AND METHODS: Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. RESULTS: The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. CONCLUSION: Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision.

First-line therapy with moderate dose capecitabine in metastatic breast cancer is safe and active: results of the MONICA trial.

BACKGROUND: To determine activity and safety of capecitabine at a moderate dose of 2000 mg/m(2) as first-line therapy for metastatic breast cancer. METHODS: In this prospective phase II trial, patients with HER2-negative metastatic breast cancer received first-line capecitabine 2000 mg/m(2) on days 1-14 every 3 weeks. The primary aim was to exclude a time to progression (TTP) <6 months. Secondary end-points were overall response rate, overall survival (OS), toxicity and quality of life. RESULTS: Median age of the 161 included patients was 65 years. Median TTP and OS were 7.3 months [95% (confidence interval) CI: 6.2-8.4] and 17.1 months (95% CI: 14.0-20.3), respectively. An overall response rate of 26.1%, including 13 complete remissions was observed. Patients developing grade I-III hand-foot syndrome had a significantly longer TTP and OS and patients >65 years also achieved a significantly longer TTP. Haematological grade I-IV toxicities were leucopenia (64.0%), anaemia (50.9%) and thrombocytopenia (28.0%). Relevant non-haematological toxicities were hand-food-syndrome (37.3%), fatigue (34.2%), nausea (29.8%) and diarrhoea (20.5%). Quality of life assessment revealed an improved emotional function, but worsening of nausea and vomiting from cycle 1-10. CONCLUSIONS: Capecitabine at a dose of 2000 mg/m(2) is active and safe as first-line treatment of patients with metastatic breast cancer.

Embolisation of intracranial meningiomas without subsequent surgery.

In an open, prospective study, we embolised intracranial meningiomas in seven patients, without subsequent surgery. Follow-up over a mean of 20 months included serial neurological examination, MRI and MR spectroscopy. Clinically, embolisation had no adverse effects. Symptomatic patients showed clinical improvement. On MRI marked tumour shrinkage occurred after embolisation in six patients, and was most pronounced during the first 6 months. In a young boy the tumour was unchanged despite complete angiographic devascularisation. Embolisation without subsequent surgery may cause substantial tumour shrinkage and thus be used in selected in patients. However, thorough follow-up is mandatory to ascertain the effects of embolisation.

MR imaging- and MR spectroscopy-revealed changes in meningiomas for which embolization was performed without subsequent surgery.

We describe our experience with follow-up MR imaging and MR spectroscopy in two patients after embolization of meningiomas without subsequent surgery. In both patients there was a marked reduction in tumor size and a decrease in contrast enhancement associated with spectroscopic signs of fatty degeneration. We did not observe regrowth; however, in one patient with incomplete angiographic devascularization, residual vital tumor tissue was seen at follow-up examinations.

[Changes in chemical composition of tomatoes during processing]. / Veränderungen von Inhaltsstoffen bei der Verarbeitung von Tomaten.

The influences of processing conditions and composition on chemical changes during thermal processing of tomatoes were investigated. During the Cold and Hot Break process pectin is degraded to different extents. Due to the thermal impact at first cyclization of glutamine to pyroglutamic acid takes place. At higher dry weight contents and during drying processes Amadori compounds and browning can be detected. The reaction products formed during thermal processing can be analysed by amino acid analysis and-after proper derivatization-by capillary gas chromatography.

[Absence of nocturnal decrease in blood pressure in 24-hour blood pressure monitoring: an indication of secondary hypertension]. / Fehlender nächtlicher Blutdruckabfall in der 24-Stunden Blutdruckmessung: Hinweis auf eine sekundäre Hypertonie.

Non invasive 24 hours ambulatory blood pressure monitoring was performed in 81 patients with secondary hypertension (renoparenchymatous nephropathy n = 15, diabetic nephropathy n = 10, Conn's disease n = 4, renal artery stenosis n = 15, pheochromocytoma n = 2, hemodialysis patients n = 15 and patients after kidney transplantation n = 20). The results were compared to 201 patients with essential hypertension. The results showed that 98.5% of patients with essential hypertension have a nightly decline in blood pressure of at least 15 mmHg (systolic + diastolic), whereas 69% of patients with secondary hypertension showed either an attenuated circadian rhythm or no circadian rhythm. Patients with pheochromocytoma who had a night time increase in blood pressure demonstrated the greatest difference to the essential hypertension collective followed by patients with diabetic nephropathy, Conn's disease and the group of patients after kidney transplantation. After successful treatment of the condition leading to hypertension circadian periodicity returned in some patients. In summary these results suggest that the absence of a night time decline in blood pressure during 24-hour-ambulatory monitoring is an indication of secondary hypertension.