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1.
Heather A McKay Harri Siev?nen Moira A Petit Kerry J MacKelvie Ken M Forkheim Ken P Whittall Bruce B Forster Heather Macdonald 《Journal of clinical densitometry》2004,7(2):161-168
Conventional density measures by dual-energy X-ray absorptiometry (DXA) are confounded by increases in bone size and do not assess bone geometry. We assessed precision of magnetic resonance imaging (MRI) and used MRI, DXA, and hip structure analysis (HSA) to assess 7-mo changes in bone structure at the femoral neck in 18 prepubertal girls. At baseline, girls were 10.4 (0.5) yr, 144.0 (8.2) cm, and 35.2 (7.0) kg, on average. Total bone and cortical cross-sectional area (ToA and CoA) were calculated from high-resolution T1-weighted MRI oblique axial images of the femoral neck. We used proximal femur DXA scans (Hologic QDR-4500) and the HSA program to estimate bone cross-sectional area (CSA), and calculate section modulus. MRI precision was determined by scanning 10 volunteers (13-46 yr old) three times with and without repositioning. Precision (CVrms) was 2% for ToA and 7% for CoA. Significant correlations were observed between FN area and MRI-derived ToA (r = 0.57, p = 0.013) and CoA (r = 0.47, p = 0.050). There were significant positive changes over 7 mo by both methods. In conclusion, MRI provides useful information on femoral neck bone area in children. The reproducibility of cortical dimensions at the femoral neck needs improvement through technical modifications and appropriate analysis software. 相似文献
2.
Riitta Mustonen Eivor Elovaara Antti Zitting Kaija Linnainmaa Harri Vainio 《Archives of toxicology》1989,63(3):203-208
The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100mg/kg/ day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05–5 g/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 g/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly. 相似文献
3.
Kari Reijula Marina Leino Helena Mussalo-Rauhamaa Marjo Nikulin Harri Alenius Jari Mikkola Peter Elg Osmo Kari Soili M?kinen-Kiljunen Tari Haahtela 《Annals of allergy, asthma & immunology》2003,91(3):280-287
BACKGROUND: Alternaria alternata and Cladosporium herbarum are common fungi in outdoor environments, but their clinical significance has not been elucidated in Finland. OBJECTIVE: To evaluate the prevalence of IgE-mediated allergy and clinical outcomes caused by sensitization to fungal allergens in patients with suspected allergy. METHODS: Skin prick tests (SPTs) were performed with C. herbarum in 6,376 patients and also with A. alternata in 1,504 of these patients. SPTs were repeated in 40 patients who showed a positive reaction to either allergen using commercial and in-house extracts. The association of SPT with allergen-specific IgE antibodies in serum was evaluated. Seven patients also underwent a conjunctival challenge test with these fungal allergens. RESULTS: The prevalence of positive SPT results to A. alternata and C. herbarum was low (2.8% and 2.7%, respectively). Among the 40 patients, atopic eczema/dermatitis syndrome was found in 58%, asthma in 44%, and rhinitis in 31%. Most of the patients displayed SPT reactions also to several other fungal allergens, and 75% to 80% showed a positive SPT reaction to allergens of pet animals or pollens. Four patients had a positive reaction to A. alternata and 6 to C. herbarum in the conjunctival challenge test. CONCLUSION: In the Finnish population with allergic symptoms, IgE-mediated sensitization to 2 common fungal allergens was rare and of minor clinical importance. SPT reactions to fungi are mostly observed in patients with multiple sensitivity to various allergens. 相似文献
4.
Genome of the European elk papillomavirus (EEPV) 总被引:1,自引:0,他引:1
The genome of the European elk papillomavirus (EEPV) was found to be 8,095 base pairs (bp) long and its genetic organization was similar to that of other papillomaviruses. Ten open reading frames (ORFs), designated E1-E7 and L1-L3, were identified in the genome, all located on one strand. The presence of the L3 ORF is rare among the papillomaviruses and to date has only been identified in the genomes of EEPV, the deer papillomavirus (DPV) and the Cottontail papillomavirus (CRPV). The ORF is well conserved beteeen DPV and EEPV with regard to both length and sequence. Potential promoter regions were identified at the 5-end of the E6 ORF, at the 3-end of the E1 ORF and downstream of the L1 ORF. Furthermore, two potential polyadenylation signals were found, one located in the long control region (LCR), downstream of the L1 ORF, and another preceding the L2 ORF. The EEVP genome is closely related to the genome of the DPV, the most highly conserved regions being ORFs E1 (70%), E5 (69%), and L1 (74%). 相似文献
5.
The opening of sarcolemmal K(ATP) channels is considered to be an important endogenous cardioprotective mechanism. On the other hand, age-dependent changes in the myocardial susceptibility to ischemia and hypoxia have been observed in different species, including humans. Here, we have hypothesized that aging might be associated with the changes in sarcolemmal K(ATP) channels. Therefore, the main objective of the present study was to establish whether aging changes expression of cardiac sarcolemmal ATP-sensitive K+ (K(ATP)) channels. RT-PCR using primers specific for K(ATP) channel subunits, Kir6.2, Kir6.1 and SUR2A subunits was performed using total RNA from guinea-pig ventricular tissue. Whole cell electrophysiology was done on isolated guinea-pig ventricular cardiomyocytes. Western blotting using anti-Kir6.2 and anti-SUR2A antibodies was performed on cardiac membrane fraction. Tissue and cells were harvested from young and old, male and female guinea-pigs. RT-PCR analysis did not reveal significant age-related changes in levels of Kir6.1 or Kir6.2 mRNAs. However, levels of SUR2A were significantly lower in old than in young females. Such age-differences were not observed with cardiac tissue from male animals. In both old and young males, pinacidil (100 microM) induced outward currents. The difference between current density of pinacidil-sensitive component in females, but not males, was statistically significant. Western blotting analysis revealed higher levels of Kir6.2 and SUR2A proteins in cardiac membrane fraction from young than old females. The present study demonstrates that in females, but not males, aging is associated with decrease in number of cardiac K(ATP) channels which is due to decrease in levels of the SUR2A subunit. 相似文献
6.
Summary The effects of ageing and life-long endurance training on the collagen metabolism of skeletal muscle were evaluated in a longitudinal study. Wistar rats performed treadmill running 5 days a week for 2 years. The activities of collagen biosynthesis enzymes, prolyl-4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, were highest in the muscles of the youngest animals, decreased up to the age of 2 months and from then on remained virtually unchanged. The enzyme activity in young animals was higher in the slow collagenous soleus muscle than in the rectus femoris muscle. The enzyme activity in the soleus muscle was higher for older trained rats than older untrained rats. The relative proportion of type I collagen increased and that of type III collagen decreased with age, suggesting a more marked contribution by type I collagen to the agerelated accumulation of total muscular collagen. The results show that collagen biosynthesis decreases with maturation and that life-long endurance training maintains a higher level of biosynthesis in slow muscles. 相似文献
7.
Economic evaluation of pharmaceuticals: a European perspective 总被引:1,自引:0,他引:1
Drummond M Rutten F Brenna A Pinto CG Horisberger B Jönsson B Le Pen C Rovira J von der Schulenburg MG Sintonen H 《PharmacoEconomics》1993,4(3):173-186
In recent years there has been a large increase in the number of economic evaluations of pharmaceuticals. Many of these studies have been commissioned by individual pharmaceutical companies, in support of new or existing products. In 2 countries, Australia and Canada (in the province of Ontario), draft guidelines issued by the government have outlined the requirements for economic evaluations to be submitted in support of requests for reimbursement (government subsidy) of particular products. One consequence of the guidelines is that they clarify what is required, and in specifying the procedure for submission of dossiers, identify a clear audience for the economic evaluation. In contrast, the situation in Europe is diverse. A wide range of healthcare systems exist, including national health services and more liberal systems, involving a wide range of insurers and providers. European countries also differ widely in their approach to the pricing and reimbursement of pharmaceuticals. Because of this diversity, the nature, conduct and impact of economic evaluation in Europe is not clear. It is therefore difficult for pharmaceutical companies to develop appropriate strategies for economic evaluation and for analysts to decide on appropriate study methodology. This article reviews the nature of any official guidance or requirements for economic evaluation, the potential for use of economic evaluation, the range of studies carried out and the identifiable impacts. There is currently no official guidance in any country, although some countries are considering issuing guidelines. In some countries there is official encouragement to pharmaceutical companies to undertake studies, and where economic data have been presented they have been considered by the relevant committees. The potential uses of economic evaluation vary widely from country to country. These can be classified in terms of a potential role in undertaking national price negotiations, deciding on reimbursement status or copayment level, deciding on inclusion in local formularies or in treatment guidelines, or in improving prescribing decisions. Approximately 80 economic evaluations of pharmaceutical products have been conducted to date in Europe, covering a wide range of clinical areas. There are relatively few examples of identifiable effects of such studies. In part this is because it is often difficult to assess the part played by various items of data. Nevertheless, the overriding conclusion is that economic evaluation of medicines is likely to be more relevant in Europe in the future. The problem for the pharmaceutical industry is in determining when and how. 相似文献
8.
While medical knowledge on genetic skeletal dysplasias has expanded, very little is known about the patients' health-related
quality of life (HRQOL). To test the validity and sensitivity of the fifteen and sixteen dimensional measures of HRQOL in
patients with chondrodysplasias, we examined 121 adults aged 16–54 and 19 adolescents aged 12–15 with achondroplasia, cartilage-hair
hypoplasia and diastrophic dysplasia. The age and sex standardized overall HRQOL score of the adult patients (0.885 on a scale
from 0 to 1) was significantly lower than that of normal controls (0.928) (P < 0.001). The difference in the HRQOL between the patients and the controls consisted mainly of the differences in dimensions
of mobility, usual activities, sexual activity and discomfort, for which the patients reported a significantly lower status
(more problems) than the controls (P < 0.001). Adolescent patients demonstrated HRQOL profiles similar to those of adults. However, age-specific problems occurred
on the dimensions of school and hobbies, friends and physical appearance (P < 0.05). In a detailed examination of different patient groups, some clinically unexpected findings were observed, suggesting
that denial is at least in part involved.
Conclusion Subjective assessment of HRQOL of patients with chondrodysplasias is valuable for provision of optimal care. In treatment
and management special attention should be paid to those dimensions on which the patients' perceived status is currently suboptimal,
especially during adolescence which probably is the most critical period in the lives of these individuals.
Received: 7 April 1997 / Accepted in revised form: 31 July 1997 相似文献
9.
Sándor Drabant Katalin Balogh Nemes Viola Horváth Antal Tolokán Gyula Grézal Markku Anttila Béla Gachályi Harri Kanerva Samar Al-Behaisi George Horvai Imre Klebovich 《European journal of pharmaceutics and biopharmaceutics》2004,58(3):689-695
The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg tablet was evaluated in 18 healthy male volunteers in a randomised, single dose, two-way crossover study. The drug was administered following an overnight fast or a standardised high-fat breakfast. The plasma concentrations of deramciclane and N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS method. An effect of food on the bioavailability was indicated if the 90% confidence interval (CI) for the ratio of geometric means of fed and fasted treatments was not contained in the equivalence limit of 0.8-1.25 for AUC and C(max). The ratios of the mean C(max) and AUC(0-infinity) values of deramciclane were 1.24 (90% CI 1.12-1.38) and 1.31 (90% CI 1.21-1.41) in fed versus fasted subjects, which overlapped but exceeded the equivalence limit. In contrast to the parent compound, the 90% CI of the mean ratios for AUC(0-infinity) and C(max) of N-desmethylderamciclane were within the predefined range. The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters. 相似文献
10.
A prospective study of body size in different periods of life and risk of premenopausal breast cancer. 总被引:5,自引:0,他引:5
Elisabete Weiderpass Tonje Braaten Cecilia Magnusson Merethe Kumle Harri Vainio Eiliv Lund Hans-Olov Adami 《Cancer epidemiology, biomarkers & prevention》2004,13(7):1121-1127
The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m(2)] at enrollment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrollment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer. 相似文献