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排序方式: 共有494条查询结果,搜索用时 31 毫秒
31.
For most of the 20th century, most drugs labeled by the United States Food and Drug Administration (USFDA) have not been adequately studied in the pediatric population. This lack of data has necessitated the continued dependence of practitioners on sub-optimal prescribing data placing pediatric patients at great risk of serious therapeutic misadventures. Recently, the USFDA has enacted and begun to enforce the Final Rule of 1997 which became effective on 1 April 1999. This rule is the culmination of the persistent efforts of numerous professional organizations, clinicians, academicians, the USFDA and others, to ensure the ready availability of appropriate data for medications intended for or that will be used in children. Unlike the 1994 Rule which voluntarily required pharmaceutical manufacturers to submit pediatric data, the Final Rule mandates submission of such data and, most importantly, empowers the USFDA to afford incentives and penalties for non-compliance including possible removal of already marketed products. This overview addresses many of the important components which must be included in the performance of a comprehensive clinical pharmacologic evaluation serving as the foundation for optimal dosing across the broad age range encompassing pediatric practice. Furthermore, the possible risk and/or benefits of the study must be reasonably defined prior to undertaking the study and clearly shared with the patient's caregivers. Consent should always be obtained from the caregiver and, when appropriate, assent obtained from the underage child. To facilitate such clinical investigations and to foster collaborative efforts with innovators and clinical research programs, the National Institutes of Health through the National Institute of Child Health and Human Development of the NIH established a network of Pediatric Pharmacology Research Units. These units have worked closely together and with other pediatric research centers to facilitate USFDA labeling of a number of commonly used medications. All of these very positive efforts highlight the many challenges that remain for the pediatric investigator and practitioner while underscoring the very positive environment in support of these efforts. 相似文献
32.
Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA)
causes a near immediate and total decrease of transepithelial electrical
resistance (TER), continuation of exposure for 3 to 4 days results in a
tachyphylactic response as TER begins to return to control levels. Recovery
of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control
level. A reciprocal change in the transepithelial flux of D-mannitol
indicates that the TER decrease is indicative of an increase in tight
junction permeability. Exposure of cell sheets to TPA for several days also
results in the appearance of multilayered polyp- like foci (PLFs) across
the otherwise one cell layer thick cell sheets. The pattern of penetration
of the electron dense dye, ruthenium red, from the apical surface, across
the tight junction and into the lateral intercellular space indicates that
the tight junctions of the cell sheet become uniformly leaky after acute
exposure to TPA. However, when exposure is continued for several days, only
the junctions of cells in the PLFs manifest leakiness. The decrease in TER
following acute TPA exposure correlates with the translocation of protein
kinase C-alpha (PKC alpha) into a membrane-associated compartment. With
exposure of several days, only a trace of PKC alpha is visible by Western
immunoblot, and this is in the membrane-associated compartment.
Immunofluorescent microscopy indicates that the trace of PKC alpha seen in
the Western immunoblots is ascribable distinctly to cells of the PLFs.
Monolayer areas between PLFs show no discernible immunofluorescent signal.
The data therefore indicate that tight junction barrier function may be
restored in certain areas by the down regulation of PKC alpha from the
membrane-associated compartment. Failure to down regulate may result in the
paracellular leakiness and abnormal cell architecture of the PLFs. Possible
implications of this model for in vivo epithelial tumor promotion are
discussed.
相似文献
33.
P Greally MJ Hussein AJ Cook AP Sampson PJ Piper JF Price 《Archives of disease in childhood》1993,68(3):389-392
It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo. 相似文献
34.
NRM Buist AP Prince KL Huntington JM Tuerck DD Waggoner 《Acta paediatrica (Oslo, Norway : 1992)》1994,83(S407):75-77
A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance. 相似文献
35.
36.
Natarajan MV Sivaseelam A Ayyappan S Bose JC Sampath Kumar M 《International orthopaedics》2005,29(5):309-313
We have analysed the results of 246 cases of distal femoral tumours treated by resection and prosthetic replacement between 1988 and 2002. Patient ages ranged from 6–67 years averaging 24 years; 133 were males. The most common tumour was osteosarcoma (67% of patients). The follow-up ranged from 2 to 14 years. Stage II tumours were seen in 72% of patients. The technique of sleeve resection of the quadriceps musculature was followed to achieve local clearance of the tumour. The prosthesis used was a rotating hinge custom mega-prosthesis manufactured locally. The functional result achieved was excellent or good in 87%; 86% of the patients had no evidence of disease, and 13% had died. The 10-year patient survival was 76.9%. Periprosthetic fracture and infection were the most common complications.
Résumé Nous avons analysé les résultats de 246 cas de tumeurs fémorales distales traitées par résection et remplacement prothétique entre 1988 et 2002. Lâges des malades sétendait de 6 à 67 ans avec une moyenne de 24 ans. Cent trente trois étaient des hommes. La tumeur la plus fréquente était lostéosarcome (67% des malades). Le suivi était de 2 à 14 années. Des tumeurs de stade II étaient présentes chez 72% des malades. La technique de résection a été conduite pour faire une ablation complète de la tumeur. La prothèse qui a été utilisée était une méga prothèse à charnière rotatoire fabriqué localement. Le résultat fonctionnel obtenu était excellent ou bon dans 87%. Quatre-vingt-six pourcent des malades navait pas dévidence de maladie et 13% étaient morts. La survie à dix ans était de 76,9%. Les fractures périprothétiques et linfection étaient les complications les plus fréquentes.相似文献
37.
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39.
Vijayaraghavan KS Ayyappan MK Ganesh S Bhattacharya K 《The international journal of lower extremity wounds》2004,3(1):47-48
Chronic wounds in which arterial and venous pathology coexist are relatively uncommon. The authors report a case of a diabetic lady who presented with claudication pain and a chronic nonhealing lower extremity wound of more than 6 months. In these patients, it is mandatory to treat the arterial insufficiency first, and it is also important to avoid compression bandaging, which is advised for venous ulcers. 相似文献
40.
Analysis of the Na,K-ATPase alpha- and beta-subunit expression profiles of bladder cancer using tissue microarrays 总被引:4,自引:0,他引:4
Espineda C Seligson DB James Ball W Rao J Palotie A Horvath S Huang Y Shi T Rajasekaran AK 《Cancer》2003,97(8):1859-1868
BACKGROUND: The purpose of this study was to determine the clinical significance of Na,K-ATPase alpha- and beta-subunit expression in a histopathologically well-characterized group of patients representing a wide spectrum of tumor grades and disease stages with transitional cell carcinomas (TCC). METHODS: Na,K-ATPase alpha- and beta-subunit protein expression patterns were analyzed using immunohistochemistry on urothelial cancer tissue microarrays (TMA) of 146 patients diagnosed with urothelial carcinoma. For each subunit, the maximum staining intensity and the percentage of positive cells staining at the maximal intensity were analyzed. RESULTS: Compared with the benign fields, the mean protein expression for both Na,K-ATPase alpha- and beta-subunits were found to be decreased overall in in situ and invasive tumors, as well as in tumor-adjacent dysplastic fields. When Na,K-ATPase alpha- and beta-subunit expression levels were dichotomized into distinct groups, they were both found to be significant predictors of recurrence risk in multivariate logistic regression analysis (P = 0.0062, odds ratio [OR] = 2.6 and P = 0.013, OR = 0.43, for Na,K-ATPase alpha- and beta-subunits, respectively). The authors also found that patients with high alpha- and low beta-subunit expression had a high risk for early recurrence, whereas patients with a low alpha- and high beta-subunit expression had a significantly longer median recurrence-free time (17 months and 125 months, respectively, log rank statistics P = 0.0005). CONCLUSIONS: The results suggested that Na,K-ATPase alpha- and beta-subunit expression levels may be useful predictors of clinical outcomes such as recurrence-free time of bladder cancer patients. 相似文献