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941.
Newcombe PA Sheffield JK Juniper EF Marchant JM Halsted RA Masters IB Chang AB 《Chest》2008,133(2):386-395
BACKGROUND: Chronic cough affects at least 7% of children, and the impact of this on families is significant. Although adult cough-specific quality-of-life (QOL) instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QOL for parents of children with chronic cough exists. This article compares two methods of item reduction (clinical impact and psychometric) and reports on the statistical properties of both QOL instruments. METHOD: One hundred seventy children (97 boys and 73 girls; median age, 4 years; interquartile range, 3 to 7.25 years) and one of their parents participated. A preliminary 50-item parent cough-specific QOL (PC-QOL) questionnaire was developed from conversations with parents of children with chronic cough (ie, cough for > 3 weeks). Parents also completed generic QOL questionnaires (eg, Pediatric Quality of Life Inventory, version 4.0 [PedsQL4.0] and the 12-item Short Form Health Survey, version 2 [SF-12v2]). RESULTS: The clinical impact and psychometric method of item reduction resulted in 27-item and 26-item PC-QOL questionnaires, respectively, with approximately 50% of items overlapping. Internal consistency among the final items from both methods was excellent. Some evidence for concurrent and criterion validity of both methods was established as significant correlations were found between subscales of the PC-QOL questionnaire and the scales of the SF-12v2 and PedsQL4.0 scores. The PC-QOL questionnaire derived from both methods was sensitive to change following an intervention. CONCLUSION: Chronic cough significantly impacts on the QOL of both parents and children. Although the PC-QOL questionnaires derived from a clinical impact method and from a psychometric method contained different items, both versions were shown to be internally consistent and valid. Further testing is required to compare both final versions to objective and subjective cough measures. 相似文献
942.
CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications 总被引:6,自引:3,他引:6
Janin A Deschaumes C Daneshpouy M Estaquier J Micic-Polianski J Rajagopalan-Levasseur P Akarid K Mounier N Gluckman E Socié G Ameisen JC 《Blood》2002,99(8):2940-2947
Fas (CD95) is a death receptor involved in apoptosis induction on engagement by Fas ligand (CD95L). Although CD95L-mediated apoptosis has been proposed as a pathogenic mechanism in a wide range of diseases, including graft-versus-host disease, systemic CD95 engagement in mice by agonistic CD95-specific antibodies or by soluble multimeric CD95L (smCD95L), though lethal, has been reported to cause apoptosis only in a limited range of cell types, that is, hepatocytes, hepatic sinusoidal endothelial cells, and lymphocytes. Another member of the tumor necrosis factor (TNF)/CD95L family, TNF-alpha, induces disseminated vascular endothelial cell apoptosis, which precedes apoptosis of other cell types and lethal multiorgan failure. Here we show that systemic CD95 engagement in vivo by agonistic CD95-specific antibody or smCD95L causes rapid, extensive, and disseminated endothelial cell apoptosis throughout the body, by a mechanism that does not depend on TNF-alpha. Disseminated endothelial cell apoptosis was also the first detectable lesion in a murine model of acute tissue damage induced by systemic transfer of allogeneic lymphocytes and did not occur when allogeneic lymphocytes were from CD95L-defective mice. Both vascular and additional tissue lesions induced by agonistic CD95-specific antibody, smCD95L, or allogeneic lymphocytes were prevented by treatment with an inhibitor of caspase-8, the upstream caspase coupled to CD95 death signaling. Vascular lesions are likely to play an important role in the pathogenesis of allogeneic immune responses and of other diseases involving circulating CD95L-expressing cells or smCD95L, and the prevention of CD95-mediated death signaling in endothelial cells may have therapeutic implications in these diseases. 相似文献
943.
944.
The insulin-like growth factor I receptor (IGF-IR) is expressed in many cell types and is critical for normal growth and development.
In the healthy mammary gland, the role of IGF-IR is not fully elucidated. However, IGF-IR, which is primarily expressed in
the mammary epithelial cells, is known to play an obligatory role in cellular transformation, facilitating the progression
to breast cancer. We have utilized the tetracycline regulatory (tet-on) system to generate an in vitro model system to allow
us to further investigate IGF-I/IGF-IR function in mammary epithelial cells. A plasmid construct containing a mutant IGF-I
receptor (IGF-IR-DN) fused to the tetracycline operator (tetOPhCMV-IGF-IR-DN) was stably transfected into MCF-7 human breast cancer cells. The conditional regulation of the IGF-IR-DN gene
expression was studied in four independent clonal lines. The translated IGF-IR-DN protein was detected only in the stably
transfected doxycycline-induced cells, and its expression was up-regulated (three- to sixfold) following induction. IGF-I
stimulated cell proliferation diminished (twofold) in doxycycline-induced cells compared to uninduced cells, demonstrating
that the transgene construct was functional and ruling out any pleiotropic effect that may be attributed to doxycycline. Interestingly,
autophosphorylation of the IGF-IR and phosphorylation of the downstream substrate, insulin receptor substrate-1 (IRS-1), was
not inhibited in doxycycline/IGF-I treated cells, suggesting the possibility that activation of downstream substrates other
than the IRS-1 may be critical for optimal cell proliferation. This novel in vitro model should allow us to more directly
examine the role of IGF-I/IGF-IR signaling and function in mammary epithelial cells. 相似文献
945.
An approach to fertility preservation in prepubertal and postpubertal females: A critical review of current literature
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946.
947.
Bougault V Lonsdorfer-Wolf E Charloux A Richard R Geny B Oswald-Mammosser M 《Chest》2005,127(4):1122-1131
STUDY OBJECTIVES: The monitoring of cardiac output (CO) during exercise rehabilitation in patients with COPD, often including strenuous exercise, is advisable. Invasive methods (thermodilution, Fick method) are accurate, but for clinical routine use noninvasive CO estimation is required. We have shown that impedance cardiography (Physio Flow; Manatec Biomedical; Macheren, France) is reliable in COPD patients at rest and during a recumbent, light-intensity exercise. The aim of our study was to evaluate the validity of this noninvasive device in COPD patients during a maximal incremental exercise test (IET) and also during a strenuous intermittent work exercise test (IWET). DESIGN: Prospective comparative study of the impedance cardiograph vs the direct Fick method applied to oxygen. PATIENTS: Eight patients with moderate-to-severe COPD (59 +/- 6 years old; FEV(1), 38 +/- 15% predicted; residual volume, 194 +/- 64% predicted) [mean +/- SD].Measurements and main results: Forty-nine simultaneous measurements of CO by means of the direct Fick method (COfick) and CO measured by the impedance cardiograph (COpf) were obtained during the IET, and 108 measurements were made during the IWET. The correlation coefficients between the two measurements were r = 0.85 and r = 0.71 for the IET and the IWET, respectively. COpf was higher than COfick. The difference between the two methods was 3.2 +/- 2.9 L/min during the IET and 2.5 +/- 2.1 L/min during the IWET. Expressed as a percentage of the mean of the two measurements, this corresponded to 31 +/- 21% and 25 +/- 20%, respectively. CONCLUSIONS: The relatively high number of values differing by > 20% precludes the use of impedance cardiography in clinical routine in such a difficult setting (hyperinflated patients and intense exercise). 相似文献
948.
Chondrocalcinosis can be associated with hyperparathyroidism, hemochromatosis, hypophosphatasia, and hypomagnesemia. Gitelman syndrome (GS), an inherited disorder due to loss of function mutations of the gene encoding the distal convoluted tubule Na-Cl cotransporter (NCCT), is characterized by hypokalemia metabolic alkalosis, hypomagnesemia, and hypocalciuria. A 53-year-old man, with history of recurrent joint effusions and pains affecting knees and wrists, had transient episodes of muscle pain, weakness, cramping, and fatigue over a one-year period. Laboratory tests showed hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia related to genetically proven GS. Radiographs of affected joints revealed calcium pyrophosphate dihydrate deposition. This observation points out the necessity to look for Mg depletion (and especially GS) in the biological investigation of chondrocalcinosis. Additionally, the association between GS (NCCT inactivation) and high bone mineral density provides a new insight into the possible role of thiazides in osteoporosis management. 相似文献
949.
Misra M Katzman DK Cord J Manning SJ Mendes N Herzog DB Miller KK Klibanski A 《The Journal of clinical endocrinology and metabolism》2008,93(8):3029-3036
BACKGROUND: Anorexia nervosa (AN) is a condition of severe undernutrition associated with low bone mineral density (BMD) in adolescent females with this disorder. Although primarily a disease in females, AN is increasingly being recognized in males. However, there are few or no data regarding BMD, bone turnover markers or their predictors in adolescent AN boys. HYPOTHESES: We hypothesized that BMD would be low in adolescent boys with AN compared with controls associated with a decrease in bone turnover markers, and that the gonadal steroids, testosterone and estradiol, and levels of IGF-I and the appetite regulatory hormones leptin, ghrelin, and peptide YY would predict BMD and bone turnover markers. METHODS: We assessed BMD using dual-energy x-ray absorptiometry and measured fasting testosterone, estradiol, IGF-I, leptin, ghrelin, and peptide YY and a bone formation (aminoterminal propeptide of type 1 procollagen) and bone resorption (N-telopeptide of type 1 collagen) marker in 17 AN boys and 17 controls 12-19 yr old. RESULTS: Boys with AN had lower BMD and corresponding Z-scores at the spine, hip, femoral neck, trochanter, intertrochanteric region, and whole body, compared with controls. Height-adjusted measures (lumbar bone mineral apparent density and whole body bone mineral content/height) were also lower. Bone formation and resorption markers were reduced in AN, indicating decreased bone turnover. Testosterone and lean mass predicted BMD. IGF-I was an important predictor of bone turnover markers. CONCLUSION: AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass. 相似文献
950.
Havranek EP Esler A Estacio RO Mehler PS Schrier RW;Appropriate Blood Pressure Control in Diabetes Trial 《American heart journal》2003,145(6):993-998