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  • 1
    ISSN: 1433-2981
    Schlagwort(e): Animals ; Blood chemistry ; Haematology ; Quality control ; Statistical analysis ; Survey
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The Clinical Pathology Testing Working group (CPTWG) of the Japanese Pharmaceutical Manufacturers Association (JPMA) reviewed published literature on abnormal values in clinical pathology parameters in repeat-dose toxicity studies, and conducted a survey on the use of a quality control (QC) concept and statistical analysis methods. Among the journals published between 1985 and 1992, ten were selected that listed many clinical pathology values from repeat-dose toxicity studies of pharmaceuticals. The frequency of ‘abnormal’ values which were statistically significant in clinical pathology examinations was checked. In all 787 papers, with a total of 15 030 sets of data, were examined to identify those abnormal values that were toxicologically meaningful and those that were not. Abnormal values that were toxicologically meaningful represented 30% and those that were not, 70%. The main criteria in judging abnormal values as ‘toxicologically meaningful’ included, but were not limited to, the following: pharmacological effects, histopathological changes, obvious changes in related pathology parameters, and dose dependency. Parameters with frequent ‘abnormal’ values were: haemoglobin (Hb); haematocrit (Ht); red blood cell count (RBC); white blood cell count (WBC); reticulocyte count; platelet count, for haematology; cholesterol; protein; alkaline phosphatase (ALP); urea nitrogen; phospholipid; triglyceride; GPT; potassium; GOT; sodium, for blood chemistry; and urine volume; urinary sodium; urinary potassium; specific gravity (sp. gr.), for urinalysis. These parameters, for each clinical pathology area, are regarded as ‘core’ parameters to be tested in all repeat-dose toxicity studies. CPTWG also reviewed the toxicity studies (total 930) published in the main Japanese journals between 1985 and 1992. The percentage of ‘correlation’ of changes in clinical pathology and histopathological examinations was 49% for clinical chemistry tests, 45% for haematology, and 33% of urinalysis. In order to increase the correlation of histopathological and clinical chemistry findings, it would be necessary to have high organ, tissue and species specificities. CPTWG surveyed the current maintenance status and quality control (QC) of equipment that is used for clinical pathology measurements. Maintenance of equipment used for haematology, clinical chemistry and urinalysis was provided in all the facilities surveyed. The scheduled maintenance of haematology equipment was provided by the manufacturers, at least twice a year, at most facilities. The scheduled maintenance by the inhouse technologist was conducted monthly to annually in more than half the facilities. A preoperational check was conducted by more than 90% of those facilities. The maintenance frequency of clinical chemistry equipment was similar. Methods of QC included the confirmation and verification of theoretical values to the actual values of control samples using the X-R control plot method (40% of the facilities) or the sample survey method (40% of the facilities). Most facilities used ‘± (2SD)’ or ‘within the minimum and the maximum ranges’ an acceptable criteria. The last survey CPTWG conducted concerned statistical analysis methods used to evaluate clinical pathology values. When the measured clinical pathology parameters were expressed as mean values and variances, ‘Rank Test’ or ‘Welch Test’ was most frequently used in the case of unequal variance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Comparative clinical pathology 5 (1995), S. 251-255 
    ISSN: 1433-2981
    Schlagwort(e): Cold storage ; Cold transport ; Dog ; Haematology ; Parameters ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A sample surveillance programme is scheduled to be conducted on measurement methods of haematology parameters which will include the participation of over 70 facilities. In preparation for that programme, a preliminary study was conducted, at five of the facilities, on the effects of cold storage and transport on rat and dog blood samples. The blood samples used in this study were taken from healthy, untreated rats and dogs from stocks held at each facility, and were anticoagulated with EDTA-2K. The blood samples were stored undisturbed at 4–10°C. The effects of transporting samples were also investigated by placing aliquots of the same samples in a cooler (4–13°C) containing a cold insulator. Red blood cell counts (RBC), total white blood cell counts (WBC), haematocrit (HCT), haemoglobin (HGB) and platelets (PLT) were measured twice for each sample, i. e., fresh and 24 hours later, and these results were compared. Although blood sampling conditions were similar for all facilities, each facility employed its own method with respect to the analysis. Automated haematology analysers used included the Toa Sysmex E4000/CS, Toa Sysmex E5000, Coulter S-Plus STRK, Technicon H*1 and Nihon Kohden MEK-4500. In the case of rat blood samples, measured values after undisturbed cold storage, fluctuating by −2 to +1% in comparison with values before storage. Measured values after cold transport fluctuated by −2 to +7% in comparison with those before transport. It was concluded, for rat blood samples, that neither storage condition had a significant effect on the results. In the case of dog blood samples, RBC, HCT and HGB values fluctuated by +1 to +2% and 0 to +2% in comparison with prestorage and pretransport values, respectively. They were not, therefore, significantly affected by undisturbed cold storage or cold transport. However, WBC values increased by +18% after undisturbed cold storage and by +18% after cold transport. Conversely, PLT values decreased by −20% both after undisturbed cold storage and cold transport. It is known that dog blood samples are affected by cold storage, and a similar trend was observed in this study. On the basis of these results, it was concluded that the distribution of rat blood samples for the conduct of a sample survey of analytical methods under cold storage is suitable, and that it will be necessary to have the samples prepared at a single facility.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1433-2981
    Schlagwort(e): Control survey ; Haematology ; Inter laboratory variation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A survey was conducted to determine the accuracy and quality control of automated haematology analysers used in non-clinical toxicity studies. Pooled blood samples from male Sprague-Dawley rats were distributed to 98 laboratory facilities throughout Japan, the samples being delivered under refrigeration to each facility within 18 h of sample preparation. At each facility, the samples were analysed within 4 h of receipt. Commercially available normal human blood samples from a single lot were also analysed at the same time. Most haematological results were within the mean ±3SD (standard deviation), but some facilities gave either high or low values consistently for both human and rat samples. No facility gave high or low values to certain parameters sporadically, which suggests no problem with the accuracy of the equipment. However, it was suspected that there would be some problem in comparing analytical values determined in a unique way by specific equipment design. The use of certain equipment resulted, in rat haematocrit values in particular, being either too high or too low. In these cases, it was deemed necessary to make some adjustments or calibration changes. There were also platelet values with a ‘plus drift’ which was apparently due to contamination with, or failure to identify small red blood cells (RBC). There was no deviation in values which could be attributed solely to the mechanical operation of any of the analytical equipment. Non-standard, initial setting up of the equipment (originally intended for human use, but now used for a variety of animal species) has been recognised as the main cause for a wider range of the analytical values seen. The results of this survey suggest that it may be necessary to review equipment calibration at each facility, and to re-establish the historical background data.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1433-2981
    Schlagwort(e): Key words:1,5-Anhydroglucitol – Blood glucose – Fructosamine – Glycaemic marker – Haemoglobin A1c– Mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract: We compared the usefulness of blood measurements of 1,5-anhydroglucitol (1,5-AG), fructosamine and blood haemoglobin A1c (HbA1c) levels in C57BL/KsJ mice with abnormal glucose metabolism and in controls. Both streptozotocin (STZ)-induced diabetic mice (db/m genotype) and genetically diabetic mice (db/db genotype) displaying a hyperglycaemia, plasma 1,5-AG level fell rapidly and dramatically. In contrast, both fructosamine and HbA1c increased so gradually that they provided an approximation of glycaemic conditions over a few weeks. Food-restricted mice displayed a slight hypoglycaemia, with fructosamine and HbA1c level reducing slightly but significantly at 4 and 12 weeks, respectively after commencement of treatment. These three glycaemic parameters were significantly correlated with blood glucose, suggesting that these three glycaemic parameters are specifically related to the abnormal glucose metabolism, and that their routine examination in mice may help delineate the metabolic derangement in the disease or provide analytical information in preclinical studies.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Comparative clinical pathology 5 (1995), S. 140-144 
    ISSN: 1433-2981
    Schlagwort(e): APTT ; Dog ; Human ; Monkey ; Mouse ; PT ; Rabbit ; Rat ; Stability ; Storage
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Changes in plasma activated partial thromboplastin times (APTT) and prothrombin times (PT) in mice, rats, rabbits, dogs, monkeys and human were examined for up to 96 h at storage temperatures of 4 and 25°C. Prolongation of APTT in rats was rapid and marked, with times doubling within 24 h post-sampling. Plasma APTT of human and monkey were also affected, but to a lesser extent. No effect was observed in mice, rabbits and dogs. On the other hand, the magnitude of PT changes was much smaller than that observed with APTT in all species. No significant differences were noted between the results from samples stored at 4°C or 25°C for either test. The false prolongation of APTT is clearly undesirable in a toxicity study, especially in rats. It is important therefore to minimise these changes by performing this test under strict time-controlled conditions.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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