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Purpose. To present a model-dependent approach for the assessment of the in vivo drug dissolution profile based on in vitrodata for the multiple unit dosage form, as an alternative to the numerical method proposed in the study by Hayashi et al, Pharm. Res. 12:1333–1337 (1995).
Methods. The data for aspirin granules administered to healthy subjects obtained in the above mentioned study were re-evaluated. The subject dissolution system was considered to consist of two subsystems connected in series, i.e. the subsystem describing the gastric-emptying process and the subsystem describing the intestinal dissolution process. The frequency response method was used to model the subject dissolution system.
Results. The model in vivodissolution profile of aspirin, assessed as the integral of the model weighting function of the subject dissolution system, was in agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method.
Conclusions. Comparison of dynamic properties of the subject dissolution system with the subsystem describing the gastric-emptying process yielded quantitative confirmation of the decisive role of the gastric-emptying process in the in vivodrug dissolution after administration in the multi unit dosage form. 相似文献
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A group of 54 patients with the original diagnosis of polycythemia vera were subjected to cytogenetic examination. Six (17.6%) of the 34 cases examined in the period of the advanced phase of the polycythemia vera had a chromosomal change. Thirteen (65%) of the 20 patients undergoing the cytogenetic examination in the period when the polycythemia vera turned into another myeloproliferative disease showed chromosomal aberration. This suggests a relationship between the number of chromosomal changes and the transformation of the disease. No connection between the cytogenetic changes and myelosuppressive cures could be confirmed in our material. The chromosomal change 20q- considered to be the most frequent kind in the polycythemia vera was not discovered until in patients with the polycythemia vera transformed into a different myeloproliferative disease. 相似文献
5.
Boudová L Fakan F Michal M Dusek J Curík R Husek K Voska L Kolník P Mukensnabl P Hes O Jindra P 《Ceskoslovenská patologie》2002,38(1):24-32
Herein we describe 7 cases of posttransplantation lymphoproliferative disease (PTLD), 5 in men and 2 in women (aged from 25 to 62 years), occurring from 4 months to 12 years (mean, 7 years) after transplantation. Our patients were recipients of kidney, kidney and pancreas, heart, and autologous peripheral haematopoetic stem cells. Four cases were diagnosed as monomorphic and three as polymorphic type of PTLD according to the WHO classification. Monoclonal immunoglobuline heavy chain gene rearrangement was detected in two monomorphic lesions and one polymorphic lesion by polymerase chain reaction (PCR). In the two cases of polymorphic and the one case of monomorphic PTLD, the presence of EBV was visualised by immunohistochemical staining of some transformed lymphoid cells for latent membrane protein (LMP) of EBV. The presence of type A EBV was demonstrated by PCR. The patients were treated by reduction or discontinuation of immunosuppression and by chemotherapy. In 2 cases, a part of the organ affected by lymphoma (sigmoid colon and pancreas) was surgically resected. Four patients died of causes related to PTLD (2 to 15 months after the diagnosis), mainly of infectious complications. Two other patients who achieved remission died of unrelated causes. Only the youngest man is alive and in the complete remission 10 months after the diagnosis of PTLD. 相似文献
6.
tefan Sre Frantiek Cisrik Ladislav Psztor Ladislav Harme
ko John M. Opitz 《American journal of medical genetics. Part A》1978,2(2):159-166
For several years the Clinical Genetics Research Laboratory at Martin, Czechoslovakia, has been studying alkaptonuria (AU) in the northern part of the District of Tren?ín in Slovakia. These affected individuals are part of a group of 103 alkaptonurics originated mostly in the mountainous parts of Slovakia. We report results of pedigree analyses; population and affected-family biochemical urine screening; estimation of inbreeding coefficient, of exogamy rate and of average marital distance and of calculation of the frequency of the AU allele, and of homozygotes and jeterozygotes in this portion of the Tren?ín District. Twelve homozygotes were found, but seven originated from a single hamlet in which a founder effect – genetic drift and inbreeding – are thought to account for the high prevalance of AU. 相似文献
7.
Induction of biologically active antineutrophil cytoplasmic antibodies by immunization with human apoptotic polymorphonuclear leukocytes 总被引:4,自引:0,他引:4
Rauova L Gilburd B Zurgil N Blank M Guegas LL Brickman CM Cebecauer L Deutsch M Wiik A Shoenfeld Y 《Clinical immunology (Orlando, Fla.)》2002,103(1):69-78
Translocation of intracellular components to the cell surface during the priming or apoptosis of polymorphonuclear leukocytes (PMN) is an important mechanism for interaction of antineutrophil cytoplasmic antibodies (ANCA) with these antigens. To test the capacity of apoptotic PMN to trigger production of ANCA, six groups of mice were immunized with either live or apoptotic lymphocytes, or with live, apoptotic, formalin-fixed, or lysed PMN. Mice immunized with both live and apoptotic neutrophils developed high titers of antibodies which gave a granular cytoplasmic immunofluorescent pattern. These antibodies were specific for lactoferrin and myeloperoxidase. Following a second intravenous infusion of apoptotic PMNs, mice developed anti-PR3 antibodies. Vasculitis lesions were not found in mice which developed ANCA. The ANCA-containing IgG fraction induced superoxide production by human PMNs. These results support the hypothesis that neutrophil-specific antigens presented on the cell membranes of apoptotic PMN may induce ANCA in the proper conditions. 相似文献
8.
Dolezal L Hálek J 《Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové》2004,47(4):293-295
In medical sonography, sonograph image quality is an essential aspect for the safety of both patient and doctor. Its evaluation therefore requires an accurate and objective method for measurement. In this regard, a number of methods are in current use. Most of these are based on tissue mimicking phantom imaging. In contrast, we have used another principle based on Point Spread Function (PSF) analysis which is a product of the measuring system we have developed. In this case, the measured sonograph scans a small metallic ball target that moves in a water bath on a specified trajectory. The Region Of Interest (ROI) of the sonogram containing the ball target picture is digitised and the amplitude of the pixels analysed. The result is the PSF from which we calculate the lateral resolution (LR). For this purpose, we use our own original software. Using this method, we have to date been able to plot LR characteristics over the scanning plane. The method allows us to differentiate separate scanning lines and even multiple focal areas for dynamic focussing systems. It can detect malfunctions in dynamic focussing, size of aperture, time gain compensation function and/or transducer element failure. The procedure itself is not as easy or as fast to use as tissue mimicking phantoms or 3D signal to noise ratio evaluation, but it provides accurate and objective numeric parameters corresponding to the quality of image at any specified point over the whole scanning area. It is also a very powerful tool when used in combination with the other methods mentioned above. 相似文献
9.
Maximal oxygen consumption,pulmonary function,body composition,and anthropometry of adolescent female athletes 总被引:2,自引:0,他引:2
Ladislav P. Novak M. Bierbaum H. Mellerowicz 《European journal of applied physiology》1973,31(2):103-119
Three groups of girl athletes — 10 gymnasts and 8 middle-distance swimmers averaging 14 years of age, and 8 middle-distance runners averaging almost 19 — were the subjects of this study. The maximal oxygen intake was determined by graded work load on a bicycle ergometer, certain pulmonary functions by spirometry, and total body potassium by wholebody counting of naturally radioactive40K. The total body water was obtained from measurements of deuterium oxide and application of the dilution principle, and creatinine excretion was determined from urine collections. Fat-free mass was calculated from total body water, and the amount of body fat was obtained by subtracting fat-free mass from body weight. Cell mass was calculated from total body potassium. Supporting evidence of leanness or fatness was provided by anthropometric measurements.The runners and swimmers achieved significantly higher maximal oxygen consumption per kg of body weight, fat-free mass, and cell mass; and the runners excelled the gymnasts in certain other pulmonary functions. Total body potassium in milliequivalents per kg of body weight, total body water expressed in percentage of body weight, and creatinine coefficients were similar in all three groups of subjects. These results indicated no differences in body composition. Calculations of body fat, fat-free mass, and cellular mass verified that conclusion; and supporting evidence was obtained from subcutaneous fat folds and from appraisal of leanness by corrected limb diameters or volumes, which also were similar in all three groups. 相似文献
10.
Ladislav Novotný Hassan Farghali Miloš Ryba Ivo Janků Jiří Beránek 《Cancer chemotherapy and pharmacology》1984,13(3):195-199
Summary Both transport and biotransformation processes for a series of pyrimidine nucleobases, ribonucleosides, 2-deoxyribonucleosides, and acetyl and 5-substituted derivatives of the cancerostatic agent araC were studied in the isolated everted rat jejunum with a continuous perfusion technique. Metabolic alterations during penetration were assessed by HPLC. 5-Halogeno and 5-deoxy derivatives of cytosine nucleosides exhibited higher transport rates and higher stability towards the deamination reaction than did unsubstituted derivatives. Octanol-buffer partition coefficients were estimated for the study compounds, and fragmental constants for the sugar moieties of nucleosides were assessed. With the present study compounds there was no correlation between lipophilicity and transport rate, as previously reported, but there was a correlation between lipophilicity and metabolic alteration of araC derivatives (r=0.99, n=5). 相似文献