Beitrag zum Mechanismus der Bilirubinreaktion im Blut

Ohne Zusammenfassung     

Ein Beitrag zur Frage: Polyneuritis mercurialis oder syphilitica?

Ohne ZusammenfassungVortrag, gehalten in der Dermatologen-Vereinigung des rheinischwestphälischen Industriebezirks in Düsseldorf am 28. April 1901.     

Validation of Adult Relative Radiation Levels Using the ACR Dose Index Registry: Report of the ACR Appropriateness Criteria Radiation Exposure Subcommittee

The ACR Dose Index Registry (DIR) provides a new source of clinical radiation exposure data that has not been used previously to establish or update the relative radiation level (RRL) values in the ACR Appropriateness Criteria (AC). The results of a recent review of DIR data for 10 common CT examinations were compared with current ACR AC RRL values for the same procedures. The AC RRL values were previously determined by consensus of members of the AC Radiation Exposure Subcommittee based on reference radiation dose values from the literature (when available) and anecdotal information from individual members’ clinical practices and experiences. For 7 of the 10 examination types reviewed, DIR data agreed with existing RRL values. For 3 of 10 examination types, DIR data reflected lower dose values than currently rated in the AC. The Radiation Exposure Subcommittee will revise these RRL assignments in a forthcoming update to the AC (in October 2018) and will continue to monitor the DIR and associated reviews and analyses to refine RRL assignments for additional examination types. Given recent attention and efforts to reduce radiation exposure in CT and other imaging modalities, it is likely that other examination types will require revision of RRL assignments once information from the DIR database is considered.     

EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma

The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7–9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90–110 mg/m²) and dasatinib (100–200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9%) and thrombocytopenia in 11 patients (42.3%). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2–1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.     

Evaluation of Respiratory Function During Reeves Stretcher Use

Objective. We were aware of a small number of cases in our EMS system where patients in respiratory distress had a worsening of their condition after being removed from the home on a Reeves® stretcher (RS). We sought to determine if this prehospital lifting device causes additional respiratory effort used in normal subjects by describing changes in heart rate, pulse oximetry, tidal volume, minute ventilation, andrespiratory rate. Methods. Forty-nine subjects were entered into this study. Data were collected while the subject was supine on the floor in the RS andonce while suspended over the floor in the device. A randomized crossover design was used. Ten subjects were excluded because of inadvertent omission of a nose plug during spirometry. Data points were recorded in the final minute of a 3-minute exposure. Three minutes was chosen to simulate a prehospital transport time from the scene to the ambulance. Minute ventilation, tidal volume, heart rate, pulse oximetry, andrespiratory rate were recorded for each subject during each phase. Subjects were also asked to rate the difficulty of breathing using the modified Borg scale. Results. Data were obtained for 39 subjects. The mean respiratory rate while suspended was 9.9 ± 3.0 breaths per minute compared to 9.1 ± 2.5 breaths per minutes supine on the floor (p = 0.007). The mean minute ventilation while suspended in a RS was 8.17 ± 3.25 L/min versus 7.37 ± 2.37 while lying flat (p = 0.03). There was no difference in tidal volume, heart rate, pulse oximetry, or subjective modified Borg scale ratings. Conclusions. Subjects suspended in a RS for 3 minutes had statistically higher respiratory rates andminute ventilation than the same subjects lying flat. Although these modest changes are clinically insignificant in normal subjects, they could present a significant challenge to subjects in respiratory distress.     

Stimulation of progesterone synthesis in luteinized human granulosa cells by human chorionic gonadotropin and 8-bromo-adenosine 3',5'-monophosphate: the effect of low density lipoprotein

Primary cultures of luteinized human granulosa cells reduced progestin secretion when taken from serum- and gonadotropin-containing medium into serum- and hormone-free medium. When added individually hCG, 8-bromo-cAMP and low density lipoprotein (LDL) stimulated progestin secretion by the cells after they spent 48 h in serum- and hormone-free medium. However, combinations of hCG or 8-bromo-cAMP and LDL were most effective in increasing steroidogenesis. The effects of hCG in enhancing steroidogenesis in the presence of LDL were first detectable after 3 h, but were most marked after 20 h of culture. hCG and 8-bromo-cAMP increased the conversion of [3H]cholesteryl linoleate, which had been incorporated into the core of LDL, into [3H]progesterone. hCG also stimulated cellular accumulation of LDL cholesterol, as assessed by incorporation of [1-14C]oleic acid into sterol esters or by measurement of total cellular cholesterol in the presence of amino-glutethimide to block steroidogenesis. In contrast to progesterone secretion, estradiol secretion was not affected by the addition of LDL in the absence or presence of 8-bromo-cAMP. We conclude that LDL cholesterol is required for maximal rates of progestin synthesis by human luteinized granulosa cells. When granulosa cells are stimulated by hCG, uptake of LDL cholesterol is promoted, and there is increased utilization of LDL cholesterol for steroid synthesis.     

Effect of treatment with the Molecular Adsorbents Recirculating System on arterial amino acid levels and cerebral amino acid metabolism in patients with hepatic encephalopathy

BACKGROUND: Liver failure is associated with low concentrations of branched-chain amino acids and high concentrations of most other amino acids. In this study the effect of treatment with the Molecular Adsorbents Recirculating System (MARS) on arterial amino acid levels and cerebral amino acid metabolism was examined in patients with severe hepatic encephalopathy. METHODS: The study included seven patients with hepatic encephalopathy from fulminant hepatic failure (FHF) and five patients with hepatic encephalopathy from acute-on-chronic liver failure (AoCLF). Cerebral blood flow and cerebral arteriovenous differences in amino acids were measured before and after 6 h of treatment with MARS. RESULTS: During MARS treatment, the total arterial amino acid concentration decreased by 20% from 8.92 +/- 7.79 mmol/L to 7.16 +/- 5.64 mmol/L (P < 0.05). The concentration decreased in all amino acids with the exception of the branched-chain amino acids. Fischer's ratio of branched-chain to aromatic amino acids increased from 0.73 +/- 0.47 to 0.91 +/- 0.54 (P < 0.05). A net cerebral efflux of amino acids in patients with FHF (8.94 +/- 8.34 micromol/100 g/min) as well as AoCLF (7.35 +/- 24.97 micromol/100 g/min) was not affected by the MARS treatment. MARS had no effect on the cerebral metabolic rate of any single amino acid in either group. CONCLUSIONS: MARS treatment tends to normalize the arterial amino acid concentrations in patients with hepatic encephalopathy. Even though the overall reduction in plasma amino acids and improvement in amino acid dysbalance may well be beneficial, it was not accompanied by any immediate improvement in cerebral amino acid metabolism in patients with FHF or AoCLF.