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991.
The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CI-generated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward. 相似文献
992.
Discrimination of pathogenic clinical isolates and laboratory strains of Bacillus cereus by NMR-based metabolomic profiling 总被引:5,自引:0,他引:5
Six different Bacillus cereus strains were selected from two different ecotypes: (1) three commonly used laboratory strains that are considered avirulent, and (2) three clinical isolates from meningitis patients. Screening of genomic DNA for the presence of genes encoding known toxins gave no candidate genes that were unambiguously able to distinguish between the two groups. However, the application of multivariate pattern-recognition methods to metabolite profiles derived from the different strains using 1H nuclear magnetic resonance spectroscopy (metabolomics) was able to classify the different profiles. The two different ecotypes were clearly separated on the basis of their metabolite profiles, showing that it is possible to use metabolomic methods to classify pathogens on the basis of their expressed physiology, even when it is not possible to infer a direct mechanistic link to specific virulence factors. This metabolomic approach could also have a wide range of possible applications in both general microbiology and microbial ecology for distinguishing and identifying different functional/physiological ecotypes of bacterial strains or species. 相似文献
993.
In early-detection clinical trials, quantities such as the sensitivity of the screening modality and the preclinical duration of the disease are important to describe the natural history of the disease and its interaction with a screening program. Assume that the schedule of a screening program is periodic and that the sojourn time in the preclinical state has a piecewise density function. Modeling the preclinical sojourn time distribution as a piecewise density function results in robust estimation of the distribution function. Our aim is to estimate the piecewise density function and the examination sensitivity using both generalized least squares and maximum likelihood methods. We carried out extensive simulations to evaluate the performance of the methods of estimation. The different estimation methods provide complimentary tools to obtain the unknown parameters. The methods are applied to three breast cancer early-detection trials. 相似文献
994.
Sugiyama LS 《American journal of physical anthropology》2004,123(4):371-389
Human life history is distinguished by long lifespan, delayed reproduction, intergenerational asymmetric benefit transfers from adults to juveniles and between adults, and a large brain able to engage in unprecedented levels of learning, reasoning, and insight. The evolution of these traits depends on relatively low human mortality. Understanding why humans have low mortality is therefore critical for understanding the evolution of key human traits. One explanation is that the evolution of food provisioning during periods of health crisis reduced mortality. This hypothesis turns on health risk having posed a significant adaptive problem that could be effectively buffered by healthcare provisioning. Unfortunately, the frequency, duration, and fitness effects of temporary disability are difficult to estimate based on osteological evidence alone, and systematic ethno-biological research on these issues among extant small-scale societies with little access to Western medical care is lacking. Here I present data on 678 injuries and illnesses suffered by 40 Shiwiar forager-horticulturalists, based on physical evidence and informant reports. A subsample of 17 individuals provided data on incidence and duration of disability for 215 pathological incidents. Results indicate that injury and illness occur frequently across the lifespan. Most living individuals have suffered temporarily disabling health crises likely to have been lethal without provisioning. The fitness effects of surviving these episodes are high, suggesting that the Shiwiar population structure and lifeway are dependent on infrequent extended provisioning to temporarily disabled individuals, and that provisioning of aid during healthcare crises effectively lowers mortality in this small-scale society. 相似文献
995.
An apparently normal, non-tuberculin-reacting, splenectomized owl monkey presented tuberculosis-like lesions of the lung at necropsy. Histological and bacteriological examination failed to demonstrate the presence of acid-fast organisms. Retrospective inquiry showed the animal had been inoculated using complete Freund's adjuvant during a malaria vaccine trial. Lesions observed were compatible with lipid embolism of the adjuvant in the lungs. 相似文献
996.
997.
Feeding of aflatoxin B1 @ 1 ppm to 2-week old Japanese quail for a period of 8 weeks produced gross and microscopic changes in the liver, skeletal muscles, heart and bursa of Fabricius. These included fatty changes, bile duct hyperplasia and lymphoid aggregation in liver; haemorrhages in thigh, breast muscles and myocardium; mild depletion of lymphocytes, cystic degeneration and fibrous tissue proliferation in bursa of Fabricius. More or less similar lesions were seen in quail chicks fed on aflatoxin with sodium selenite @ 5 ppm but these were of lesser intensity and appeared at later stages of the experiment thereby indicating that supplementation of selenium had some protective action against the toxic effect of aflatoxin B1 in Japanese quail. 相似文献
998.
Steinberg D 《Journal of lipid research》2005,46(2):179-190
The first in this series of historical reviews dealt with the pioneering animal model work of Anitschkow, implicating blood cholesterol in the pathogenesis of atherosclerosis, and the pivotally important work of Gofman, providing evidence that lipoprotein-bound cholesterol was a major factor in the human disease. This second installment reviews the early lines of evidence linking hypercholesterolemia in humans to the progression of atherosclerosis and the risk of coronary heart disease. The argument is made that by 1970, the evidence was already strong enough to justify intervention to lower blood cholesterol levels if all the available lines of evidence had been taken into account. Yet, it would be almost two decades before lowering blood cholesterol levels became a national public health goal. Some of the reasons the "cholesterol controversy" continued in the face of powerful evidence supporting intervention are discussed. 相似文献
999.
Sampson AR Sill MW 《Biometrical journal. Biometrische Zeitschrift》2005,47(3):257-68; discussion 269-81
Drop-the-losers designs are statistical designs which have two stages of a trial separated by a data based decision. In the first stage k experimental treatments and a control are administered. During a transition period, the empirically best experimental treatment is selected for continuation into the second phase, along with the control. At the study's end, inference focuses on the comparison of the selected treatment with the control using both stages' data. Traditional methods used to make inferences based on both stages' data can yield tests with higher than advertised levels of significance and confidence intervals with lower than advertised confidence. For normally distributed data, methods are provided to correct these deficiencies, providing confidence intervals with accurate levels of confidence. Drop-the-losers designs are particularly applicable to biopharmaceutical clinical trials where they can allow Phase II and Phase III clinical trials to be conducted under a single protocol with the use of all available data. 相似文献
1000.
Gy?rgy?KériEmail author Richard?Schwab Orsolya?Szokolóczi Tamás?Szüts János?Szolcsányi 《International journal of peptide research and therapeutics》2005,11(1):3-15
TT-232 is a structural derivative of the peptide hormone somatostatin with selective anti-proliferative and anti-inflammatory properties. It has a strong anti-tumour activity both in vitro and in vivo on a wide range of tumour models and induces apoptosis. Its anti-tumour activity is mediated through the SSTR1 receptor and by the tumour specific isoform of pyruvate kinase. TT-232 has been shown to be a potent neurogenic inflammation inhibitory, anti-inflammatory and analgesic agent with a broader spectrum than presently available anti-inflammatory/analgesic drugs. In animal models it is effective against neurogenic inflammation and blocks neuropathic hyperalgesia where COX-1 or COX-2 inhibitors (e.g. diclofenac or meloxicam) proved ineffective. TT-232 has passed phase I clinical trials without toxicity and significant side effects. Human phase II efficacy studies are ongoing in melanoma indication. Two more oncological indications and phase II clinical trials in inflammatory diseases, including rheumatoid arthritis and burn injuries are in preparation. This compound has the perspective to become the first drug in molecularly targeted therapy of inflammation where a combined effect of anti-inflammatory, analgesic and neurogenic inflammation inhibiting activity can be achieved. 相似文献