Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles

We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase.     

Influence of cerium implantation on the nucleation and growth of corrosion products on alloy 800H in a mixed sulphidizing/oxidizing environment

The influence of implantation of cerium on the corrosion behavior of an 32Ni-20Cr austenitic steel, Alloy 800H, in a simulated coal-gasification atmosphere has been examined at 700°C. The composition and microstructure of the corrosion products formed after exposure periods between 1 min and 200 h were examined with a range of surface-analytical techniques. The corrosion mechanism of Alloy 800H was characterized as a mixture of oxidation and sulphidation, primarily of Cr and Fe. The oxides provided protection against catastrophic sulphidation. Cerium implantation reduced the corrosive attack, providing the dose was sufficient. The corrosion was more uniform and the products had a higher Cr/Fe ratio compared to those on the unimplanted alloy. It is proposed that these changes resulted from the formation of a more protective and more stable oxide layer, due to the rapid formation of ceria particles, specifically hindering the formation of the less-stable oxides and sulphides.     

Changes in epoxy-coated aluminium due to exposure to water

An investigation was performed of the changes that occur in a typical epoxy-coated aluminium system due to exposure to water. The adhesion of the epoxy coating upon exposure to water was evaluated for different exposure temperatures and periods. The adhesion test results showed an initial loss of adhesion of the coating but after this the adhesion improved again and even significantly exceeded adhesion prior to exposure. The amount of adhesion improvement and the speed with which adhesion improvement occurred was found to be larger for higher exposure temperatures. The changes that occur in the epoxy-coated aluminium system due to exposure to water were investigated using a number of different analytical techniques. Based on this, a model was proposed for the processes that take place during exposure and which can explain the adhesion test results. First, the adhesion of the epoxy coating is lost upon exposure due to the accumulation of a significant amount of water at the interface. The water at the interface causes formation and growth of a thin oxyhydroxide layer underneath the epoxy coating. After some time, this oxyhydroxide layer re-establishes contact with the epoxy coating and forms a new, water-stable bond, hence explaining the improvement of the adhesion after its initial loss.

The temperature-dependence observed in the adhesion test results is explained by the fact that at a higher exposure temperature, more water accumulates at the interface, the oxyhydroxide layer grows faster and also attains a larger limiting thickness.     

Error correction techniques for high-performance differential A/Dconverters

Error correction techniques that overcome several error mechanism that can affect the accuracy of charge-redistribution analog-to-digital converters (ADCs) are described. A correction circuit and a self-calibration algorithm are used to improve the common-mode rejection of the differential ADC. A modified technique is used to self-calibrate the capacitor ratio errors and obtain higher linearity. The residual error of the ADC due to capacitor voltage dependence is minimized using a quadratic voltage coefficient (QVC) self-calibration scheme. A dual-comparator topology with digital error correction circuitry is used to avoid errors due to comparator threshold hysteresis. A fully differential charge-redistribution ADC implemented with these techniques was fabricated in a 5-V 1-μm CMOS process using metal-to-polysilicide capacitors. The successive-approximation converter achieves 16-b accuracy with more than 90 dB of common-mode rejection while converting at a 200-kHz rate     

Hospital experience and hospital mortality following partial pancreaticoduodenectomy in The Netherlands

OBJECTIVE: To analyse the effect of hospital experience on mortality after subtotal pancreaticoduodenectomy in the Netherlands. DESIGN: Retrospective evaluation. METHOD: Information on hospital mortality and pancreatic resection in 1994 and 1995 in the Netherlands was obtained from the National Medical Register. Subanalysis was carried out of surgical mortality by age and hospital experience. RESULTS: Approximately 50% of the pancreaticoduodenectomies in the Netherlands were performed in hospitals with limited experience (< 5 procedures per year). Hospital mortality was higher in small-volume hospitals than in hospitals with experience (> 25 procedures per year): in 1994 17.2 and 0% and in 1995 14.6 and 2.9%, respectively (p < 0.05). Mortality was higher in patients older than 70 years compared with patients younger than 55 (p < 0.05). CONCLUSION: There was a correlation between mortality after pancreaticoduodenectomy and hospital experience. Therefore these procedures should be performed in centres with experience.     

Temperature dependence of spontaneous otoacoustic emissions in the edible frog (Rana esculenta)

The change in frequency of individual emissions in the European edible frog (Rana esculenta) when the temperature of the frog is modified, is part of a complex pattern of interaction between spontaneous otoacoustic emissions. At high temperatures (above 24 degrees C) two emissions are always detected (e.g., one near 800 Hz and one near 1200 Hz). The higher-frequency emission is lower in level and has a wider bandwidth than the lower-frequency emission. It is also often asymmetric and sometimes breaks into two emissions when an external suppressor tone is applied. When the temperature is decreased, these emissions are reduced in frequency at a rate of 0.04 octave/degree C. The higher-frequency emission becomes narrower and taller, and the lower-frequency emissions becomes broader and less intense. At approximately 18 degrees C the lowest of these emissions (now between 600 and 700 Hz) disappears and is replaced by a new emission approximately 100 Hz lower in frequency. When the temperature is carefully controlled the two emissions can exist simultaneously. The lowest-frequency emission changes 0.015 degree C/octave suggesting that the mechanisms controlling the frequency of this emission may be different than those determining the frequencies of the other emissions. All but the lowest-frequency emissions are maximal in level and have minimal bandwidth when the frequency is close to 700 Hz, which is interpreted as evidence that these emissions are filtered by a temperature-independent process.     

Laboratory evaluation of tissue heart valves. A comparative assessment

Tissue of commercially prepared tissue heart valves were evaluated and compared with aluminium treated, fixed porcine valve tissue in vitro (tensile strength, scanning and transmission electron microscopy) and in vivo (calcification potential after subcutaneous implantation in the rat model). Valve leaflets (n = 40) were divided into four groups according to the method of treatment: Group I (fixed in 0.652% glutaraldehyde, control), Group II (fixed and treated with aluminium), Group III (fixed and treated with Toluidine blue) and Group IV (fixed and treated with watersoluble alkyl sulphate). Tensile strength was not influenced in Group II and III (p > 0.05). Group IV indicated a significant (p < 0.05) reduction in tensile strength. Scanning electron microscopy revealed damage and loss of surface endothelium in Group III and IV respectively. Transmission electron microscopy indicated damage to underlying matricial cells in Group III and IV. Calcification potential was significantly (p < 0.001) reduced in Group II to IV. We conclude that damage ultrastructure could contribute to the reduced tensile strength in Group IV and that reduced tensile strength might have an influence on the long-term durability of tissue heart valves. Antimineralization treatment of tissue heart valves does retard calcification but is yet unable to inhibit the process completely.