Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 degrees C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules.

Due to advanced disease at the time of diagnosis the prognosis of oesophageal cancer is generally poor. As mass screening for oesophageal cancer is neither feasible nor reasonable, high-risk groups should be identified and surveilled. The aim of this study was to define the risk of oesophageal cancer in patients with (previous) head and neck cancer. A total of 148 patients with (previous) head and neck cancer were prospectively screened for oesophageal cancer by video-oesophagoscopy and random oesophageal biopsies. Even in a macroscopically normal looking oesophagus, four biopsy specimens were taken every 3 cm throughout the entire length of the squamous oesophagus. Low-or high-grade squamous cell dysplasia was detected histologically in 10 of the 148 patients (6.8%). All but one dysplasias were diagnosed synchronously with the head and neck cancers. In addition, oesophageal squamous cell carcinoma was diagnosed in 11 of the 148 patients (7.4%). Most invasive cancers (63.6%) occurred metachronously. The risk of squamous cell neoplasia of the oesophagus is high in patients with (previous) head and neck cancer. Surveillance is recommended in this high-risk group.

REFLECT-HF demonstrates that there are some differences in evidence-based treatment decisions between the three main health services (HBC, OBC and GP) providing care for patients with HF in Germany. Advocating adherence to guideline recommendations and earlier adoption of these evidence-based treatments across all levels of care might further improve patient care.

Background: Optimal medical therapy (OMT) for patients with chronic heart failure and a reduced ejection fraction (HF-REF) includes angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists, plus a diuretic. Hypothesis: We hypothesized that OMT is less often prescribed in HF-REF patients (≤35%) with New York Heart Association (NYHA) class II symptoms compared with those with NYHA class III/IV symptoms. Methods: This was a cross-sectional, observational, multicenter survey of hospital-based cardiologists, office-based cardiologists, and general practitioners in Germany. For angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and β-blockers, prescription rates were high and comparable between groups. However, prescription rates for mineralocorticoid receptor antagonists were lower compared with other guideline-recommended treatments. Multivariate analyses indicated that OMT prescription was reduced for older patients and increased for patients cared for by an office-based cardiologist. Conclusions: Given the high proportion of patients with reduced left ventricular systolic function but only minor symptoms, HF-REF appears to be underdiagnosed, and a higher proportion of patients than are currently recognized could potentially be candidates for OMT.