Comment on: withdrawal of growth-promoting antibiotics in Europe and its effects in relation to human health

In response to a review titled 'Withdrawal of growth-promoting antibiotics in Europe and its effects in relation to human health', published in this Journal by Ian Phillips, we hereby comment on the review. Phillips makes use of data from the Danish Integrated Antimicrobial Resistance Monitoring and Research Programme (DANMAP) reports and studies on Campylobacter and enterococci. Unfortunately, we find these data frequently misinterpreted by Phillips, leading to false conclusions such as inferences that the ban of antibiotic growth promoters should cause an increased prevalence of resistant enterococci and Campylobacter.     

Hexyl-aminolevulinate-mediated photodynamic therapy: how to spare normal urothelium. An in vitro approach

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) of superficial bladder cancer may cause damages to the normal surrounding bladder wall. Prevention of these is important for bladder healing. We studied the influence of photosensitizer concentration, irradiation parameters, and production of reactive oxygen species (ROS) on the photodynamically induced damage in the porcine urothelium invitro. The aim was to determine the threshold conditions for the cell survival. METHODS: Living porcine bladder mucosae were incubated with solution of hexylester of 5-aminolevulinic acid (HAL). The mucosae were irradiated with increasing doses and cell alterations were evaluated by scanning electron microscopy and by Sytox green fluorescence. The urothelial survival score was correlated with Protoporphyrin IX (PpIX) photobleaching and intracellular fluorescence of Rhodamine 123 reflecting the ROS production. RESULTS: The mortality ratio was dependent on PpIX concentration. After 3 hours of incubation, the threshold radiant exposures for blue light were 0.15 and 0.75 J/cm(2) (irradiance 30 and 75 mW/cm(2), respectively) and for white light 0.55 J/cm(2) (irradiance 30 mW/cm(2)). Photobleaching rate increased with decreasing irradiance. Interestingly, the DHR123/R123 reporter system correlated well with the threshold exposures under all conditions used. CONCLUSIONS: We have determined radiant exposures sparing half of normal urothelial cells. We propose that the use of low irradiance combined with systems reporting the ROS production in the irradiated tissue could improve the in vivo dosimetry and optimize the PDT.     

Predicting retroperitoneal histology in postchemotherapy testicular germ cell cancer: a model update and multicentre validation with more than 1000 patients

OBJECTIVES: Surgical resection of postchemotherapy retroperitoneal lymph nodes is often performed in patients with advanced nonseminomatous testicular germ cell cancer. We previously developed a model to predict the probability that the lymph nodes contain only necrotic or fibrotic (benign) tissue versus mature teratoma and viable cancer (tumour) to identify patients who actually need resection. The present study used an updated model with new patient data and studied the validity of the updated model across various settings. METHODS: We combined data of 544 patients from the original model with data of 550 new patients and performed a new logistic regression analysis, which included the same six predictors: histology of the primary tumour, prechemotherapy serum levels of alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, residual mass size measured on computed tomography, and change in mass size. The validity of the updated model was studied in individual centres. Calibration of the predicted probabilities was assessed graphically and with the Hosmer-Lemeshow test. Discrimination was studied with the concordance (c)-statistic. RESULTS: The updated model had slightly different, although more precise, regression coefficients. Statistically nonsignificant Hosmer-Lemeshow tests confirmed good calibration in most centres. The c-statistic for all centres except one exceeded 0.80. The updated model was valid over the complete range of predicted probabilities across a broad spectrum of centres. CONCLUSIONS: This finding gives confidence in the applicability of the model to select patients for resection, particularly patients with small residual masses and low predicted probabilities of benign tissue (i.e., substantial predicted risks of residual tumour).     

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