Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at ...risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5.75 d (range 0-14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections.
Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)‐based assay enabled the identification of patients at ...risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high‐dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5·75 d (range 0–14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections.
We conducted comprehensive field investigations to characterise the trophic status and food web structure of Großer Vätersee (GV) and Kleiner Vätersee (KV), two stratified lakes in the Baltic lake ...region of northeastern Germany. The lakes will be used as manipulation (GV) and reference (KV) ecosystems in food web studies. Both lakes are mesotrophic to slightly eutrophic with mean epilimnetic total phosphorus (P) concentrations of 24 and 21 μg L–1 in GV and KV, respectively. Mean phytoplankton biomass was 0.9 and 0.5 cm3 m–3 in GV and KV. During summer, the algal community of both lakes was dominated by cyanobacterial picoplankton and Ceratium spp. Filamentous cyanobacteria (mostly Planktothrix sp.) prevailed in a deep chlorophyll maximum found within the chemocline of both lakes. Bacterial biomass in the epilimnion of GV usually ranged between 1 and 3 cm3 m–3. Mean ciliate abundance was 13 ind. mL –1 in GV and 14 ind. mL–1 in KV. While Oligotricha dominated in GV, Scuticociliata were found most frequently in KV. Mean annual crustacean biomass was high in both lakes (GV 2.5 cm3 m–3, KV 1.2 cm3 m–3); Eudiaptomus gracilis, E. graciloides and Daphnia spp. were the most prominent species. Total fish biomass of both lakes was dominated by roach (GV 52%; KV 57%) and perch (GV 24%; KV 34%) Vaucheria dichotoma and Chara spp. dominated the macrophyte community in GV; Chara spp. dominated in KV. The slightly more eutrophic character of GV was most likely a result of greater P accumulation in the sediments due to external loading, which resulted in greater hypolimnetic P concentrations throughout the summer in GV. However, on an annual basis these differences were only occasionally reflected at higher trophic levels. The differences in fish biomass, however, might have been a consequence of higher structural diversity in GV provided by submersed macrophytes rather than its more eutrophic character. We conclude that the trophic characteristics and food web structure of Großer Vätersee and Kleiner Vätersee are similar enough to be suitable as manipulation and reference lakes in food web experiments.
Amphiphilic carboxylates acting as peroxisome proliferators and hypolipidemic drugs induce enzymes of peroxisomal lipid beta-oxidation, certain drug-metabolizing enzymes in the liver, and a number of ...additional proteins. The peroxisome proliferators represent a well-established class of non-genotoxic hepatocarcinogens. In this study we characterized the hepatic elimination of the peroxisome proliferator nafenopin. In the rat in vivo, 1 hr after intravenous administration of 3Hnafenopin, approx. 40% of injected radioactivity was recovered in bile. HPLC analysis of bile samples revealed that only about 10% of the radioactivity recovered in bile was associated with non-metabolized nafenopin and approx. 90% with more polar metabolites. One of the main metabolites formed in the liver and excreted into bile was identified as nafenopin glucuronide by beta-glucuronidase-catalysed reconversion to nafenopin. In mutant rats deficient in the canalicular transport of leukotriene C4 and related amphiphilic anion conjugates, recovery of 3Hnafenopin-derived radioactivity in bile was reduced to 4% of the injected dose. Although nafenopin glucuronide could not be detected in bile, it was a major metabolite in the liver from these mutant rats. Using membrane vesicles enriched in bile canalicular membranes from normal rats, transport of nafenopin glucuronide was shown to be a primary-active ATP-dependent process which was inhibited by leukotriene C4 and S-dinitrophenyl glutathione with IC50 values of 0.2 and 12 microM, respectively. ATP-dependent transport was not detectable for non-conjugated nafenopin. In canalicular membrane vesicles prepared from the mutant rats, the rate of ATP-dependent transport of nafenopin glucuronide was less than 10% of the transport observed in vesicles from normal rats. These data indicate that conjugation and subsequent transport by the ATP-dependent export carrier for leukotriene C4 and related conjugates is a major pathway for the elimination of nafenopin and structurally-related peroxisome proliferators.
Background: Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age ...35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods: Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results: The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97-0.97), sex (OR 1.18, 95% CI 1.11-1.25), date of diagnosis (OR 1.05, 95% CI 1.04-1.06), 'diagnosis during screening' (OR 3.24, 95% CI 2.50-4.19) and place of residence (OR 1.23, 95% CI 1.16-1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8-83.9%). Conclusions: No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.
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