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381.
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383.
Permissive hypercapnia and gas exchange in lungs with high Qs/Qt: a mathematical model 总被引:1,自引:1,他引:0
Low volume ventilation with permissive hypercapnia is becoming widely used
in the treatment of acute respiratory distress syndrome. A mathematical
model was developed to examine the effects of hypoventilation on pulmonary
gas exchange in lungs with a range of shunt fractions. Hypoventilation did
not worsen gas exchange, provided the inspired oxygen concentration was
high enough to maintain PAO2 at an adequate level. In lungs with a high
shunt fraction, some improvement in gas exchange may result, but these
effects are small. A rightwards shift of the oxygen-haemoglobin
dissociation curve induced by hypercapnia, is likely to be beneficial
rather than detrimental in patients with acute respiratory distress
syndrome. This analysis was limited to the direct effects of
hypoventilation in lungs with constant shunt fractions, and did not
encompass a number of possible secondary effects such as changes in cardiac
output with PaCO2, changes in shunt fraction associated with a reduction in
mean airway pressure and possible direct effects of hypercapnia on the
pulmonary vasculature or airways.
相似文献
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385.
Xiaoying Chen Timothy Hickling Eugenia Kraynov Bing Kuang Chuenlei Parng Paolo Vicini 《The AAPS journal》2013,15(4):1141-1154
A mathematical pharmacokinetic/anti-drug-antibody (PK/ADA) model was constructed for quantitatively assessing immunogenicity for therapeutic proteins. The model is inspired by traditional pharmacokinetic/pharmacodynamic (PK/PD) models, and is based on the observed impact of ADA on protein drug clearance. The hypothesis for this work is that altered drug PK contains information about the extent and timing of ADA generation. By fitting drug PK profiles while accounting for ADA-mediated drug clearance, the model provides an approach to characterize ADA generation during the study, including the maximum ADA response, sensitivity of ADA response to drug dose level, affinity maturation rate, time lag to observe an ADA response, and the elimination rate for ADA–drug complex. The model also provides a mean to estimate putative concentration–time profiles for ADA, ADA–drug complex, and ADA binding affinity-time profile. When simulating ADA responses to various drug dose levels, bell-shaped dose–response curves were generated. The model contains simultaneous quantitative modeling and provides estimation of the characteristics of therapeutic protein drug PK and ADA responses in vivo. With further experimental validation, the model may be applied to the simulation of ADA response to therapeutic protein drugs in silico, or be applied in subsequent PK/PD models. 相似文献
386.
目的:观察Ad-aMMP-2cDNA转染原代培养的增殖期血管瘤内皮细胞后,对体外培养的血管内皮细胞生物学特性的影响。方法:实验于2003-10/2004-06在四川大学华西临床医学院肿瘤实验室,四川大学基础与法医学院电镜室完成。选用1名出生52d女性患儿左胸壁的海绵状血管瘤(病理诊断为增殖期血管瘤)作组织块原代培养,分离、纯化并传代培养至4代后,经形态学观察、免疫组织化学染色和电镜观察鉴定确认为增殖期血管瘤内皮细胞。将血管瘤内皮细胞分3组:①M199组:继续用无血清M199培养24h。②Ad-GFP组:用10μLAd-GFP(MOI=100)转染每孔的细胞,1h后追加无血清M199培养24h。③Ad-aMMP-2组:用10μLAd-aMMP-2cDNA(MOI=100)转染每孔的细胞,1h后追加无血清M199培养24h。观察Ad-aMMP-2组血管内皮细胞转染后24,48,120h基质金属蛋白酶2mRNA的表达。逆转录-聚合酶链反应、免疫印迹技术和明胶酶谱试验的方法检测在核酸水平和蛋白水平基质金属蛋白酶2基因的表达。结果:①组织块法原代培养的增殖期血管瘤内皮细胞:获取的第1代血管瘤内皮细胞纯度达70%,椎虫蓝染色显示成活率在95%以上。②逆转录-聚合酶链反应定量检测mRNA:Ad-aMMP-2组血管瘤内皮细胞转染Ad-aMMP-2后24h,与同时段的Ad-GFP组比较,基质金属蛋白酶2mRNA表达水平均开始下降0.327±0.034,0.531±0.158;48h后下降的趋势更加明显0.189±0.028,0.505±0.083,(P<0.05);120h后基质金属蛋白酶2mRNA的表达显著下降0.106±0.014,0.510±0.106,(P<0.01)。③明胶酶谱试验和免疫印迹技术检测表明:Ad-GFP组血管瘤内皮细胞表达基质金属蛋白酶2与M199组无明显差异,而Ad-aMMP-2组血管瘤内皮细胞表达基质金属蛋白酶2明显低于Ad-GFP组和M199组。结论:①用组织块法原代培养增殖期血管瘤内皮细胞,能获得纯度较高的血管瘤内皮细胞。②在体外实验中,反义基质金属蛋白酶-2cDNA可以有效抑制血管瘤内皮细胞分泌基质金属蛋白酶2。 相似文献
387.
388.
Several mechanisms have been proposed to explain the pathogenesis of severe congenital neutropenia (SCN); however, the mechanism(s) still remains unknown. In particular, clinical observations suggest that abnormal responsiveness of myeloid progenitors to hematopoietic growth factors (HGFs) is a possible mechanism. Therefore, to better define the status of hematopoietic progenitors in the bone marrow (BM) of patients with SCN, the responsiveness of myeloid progenitors to HGFs from two SCN patients was compared with the responsiveness of progenitors from healthy individuals. BM cells (BMCs) from the first SCN patient required higher (10- to 100-fold) concentrations of granulocyte colony- stimulating factor (G-CSF) to achieve maximal and half-maximal colony growth in vitro compared with BMCs from controls. In contrast, the dose- response of interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM- CSF) in colony formation was normal. Interestingly, IL-3, GM-CSF, and G- CSF at optimal doses showed reduced ability to induce neutrophil differentiation of BMCs from a SCN patient compared with BMCs from controls. Despite an abnormal responsiveness of mature myeloid progenitors to G-CSF in this SCN patient, myeloid progenitors responsive to the combination of stem cell factor (SCF) and G-CSF showed normal dose-response. In contrast to G-CSF alone, the combination of G-CSF and SCF induced the formation of neutrophils almost to the same extent compared with cultures of normal BMCs. Furthermore, also on BM progenitor cells obtained from the second patient with SCN, SCF highly synergized with G-CSF to promote neutrophil progenitor cell growth and differentiation in vitro. Thus, these results indicate that one mechanism of the pathogenesis in SCN patients is reduced responsiveness of neutrophil progenitor cells to G- CSF and that SCF can enhance the responsiveness of these cells to G-CSF. 相似文献
389.
G. Hutchinson F.W. Hickling 《International review of psychiatry (Abingdon, England)》2013,25(2-3):162-167
Societal problems are fundamental in fostering a clearer understanding of psychiatric epidemiology.We illustrate this by juxtaposing the findings of high rates of psychosis in the population of Caribbean origin in Britain with their dissatisfaction with mental health services in general.The problem in psychiatry is therefore mirrored by a problem in society which have similar bases in terms of relationships with institutional structures in Britain. The origins of psychiatry and the concept of schizophrenia are discussed with a view to identifying the historical and cultural influences which informed their genesis.An exploration of the assumptions which have informed psychiatric diagnosis and treatment and the factors that contribute to social inequality must be considered together in mounting appropriate research and clinical responses to the problems of this population in Britain. These findings in Britain therefore have important implications for the understanding of psychiatry as a socio-cultural as well as scientific practice and consequently for the categorization of mental illness. 相似文献
390.
Ottmann OG; Hoelzer D; Gracien E; Ganser A; Kelly K; Reutzel R; Lipp T; Busch FW; Schwonzen M; Heil G 《Blood》1995,86(2):444-450
This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patients were randomly assigned to receive either G-CSF (n = 37) or no growth factor (n = 39) in conjunction with a uniform chemotherapy consisting of cyclophosphamide, cytarabine, mercaptopurine, intrathecal methotrexate, and cranial irradiation. The median duration of neutropenia (absolute neutrophil count < 1 x 10(9)/L) during chemotherapy was 8 days in patients receiving C-CSF, compared with 12.5 days in the control group (P < .002). A similar reduction from 11.5 to 7 days was observed in patients with T-ALL receiving additional mediastinal irradiation (P = .13). Infections occurred in 43% and 56% of patients in the G-CSF and control arm, respectively (P = .25); the incidence of nonviral infections was reduced by 50%, from 32 episodes in the control arm to 16 episodes in the G-CSF arm. Prolonged interruptions of chemotherapy administration were less frequent, with delays of 2 weeks or more occurring in only 24% of patients receiving G-CSF as opposed to 46% in the control arm (P = .01). Accordingly, chemotherapy was completed significantly earlier with the use of G-CSF (39 v 44 days, P = .008). With a median follow-up of 20 months, the probability of disease-free survival was 0.45 in the G-CSF group and 0.43 in the control group (P = .34). In conclusion, adult ALL patients appear to benefit by the simultaneous administration of G-CSF with induction chemotherapy because of a significant reduction in the duration of neutropenia, a trend to fewer infections, and a more rapid completion of chemotherapy. 相似文献