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991.
Williamson Kathleen A.; Hever Ann M.; Rainger Joe; Rogers R. Curtis; Magee Alex; Fiedler Zdenek; Keng Wee Teik; Sharkey Freddie H.; McGill Niolette; Hill Clare J.; Schneider Adele; Messina Mario; Turnpenny Peter D.; Fantes Judy A.; van Heyningen Veronica; FitzPatrick David R. 《Human molecular genetics》2006,15(12):2030
Table 1 相似文献
992.
OBJECTIVE: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). DESIGN: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications. RESULTS: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin. A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor ('statin') doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin. CONCLUSION: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised. 相似文献
993.
994.
995.
C. Fischer W. Gross J. Krüger M. Cremer F. Vogel T. Grimm 《Annals of human genetics》2006,70(2):237-248
For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations. 相似文献
996.
Michael R Horsman 《International journal of hyperthermia》2006,22(3):197-203
The most important physiological parameter influencing tissue response to heat is blood flow. At mild hyperthermia temperatures blood perfusion increases in many tumours and this effect is heating time-, temperature- and tumour-dependent. These flow increases can improve tumour oxygenation. When heating is terminated, perfusion and oxygenation commonly recover, although how quickly this occurs appears to be tumour-specific. While these effects are unlikely to have any anti-tumour activity they can be exploited to improve the combination of heat with other therapies. However, since similar physiological effects should occur in normal tissues, such combination therapies must be carefully applied. Heating tumours to higher temperatures typically causes a transient increase in perfusion during heating, followed by vascular collapse which if sufficient will increase tumour necrosis. The speed and degree of vascular collapse is dependent on heating time, temperature and tumour model used. Such vascular collapse generally occurs at temperatures that cause a substantial blood flow increase in certain normal tissues, thus preferential anti-tumour effects can be achieved. The tumour vascular supply can also be exploited to improve the response to heat. Decreasing blood flow, using transient physiological modifiers or longer acting vascular disrupting agents prior to the initiation of heating, can both increase the accumulation of physical heat in the tumour, as well as increase heat sensitivity by changing the tumour micro-environmental parameters, primarily an increase in tumour acidity. Such changes are generally not seen in normal tissues, thus resulting in a therapeutic benefit. 相似文献
997.
H. S. Tilney R. E. Lovegrove S. Purkayastha A. G. Heriot A. W. Darzi P. P. Tekkis 《Colorectal disease》2006,8(5):441-450
AIM: The present meta-analysis aims to compare short-term and long-term outcomes in patients undergoing laparoscopic or open subtotal colectomy for benign and malignant disease. METHODS: A literature search of Medline, Ovid, Embase and Cochrane databases was performed to identify studies published between 1992 and 2005, comparing laparoscopic (LSC) and open (OSC) subtotal colectomy. A random effect meta-analytical technique was used and sensitivity analysis performed on studies published since the beginning of 2000, higher quality papers, those reporting on more than 40 patients, and those studies reporting on adult cases or acute colitis. RESULTS: A total of eight studies satisfied the criteria for inclusion. These included outcomes on 336 patients, 143 (42.6%) of whom had undergone laparoscopic resection, with an overall conversion rate to open surgery of 5% (range 0-11.8%). Operative time was significantly longer in the laparoscopic group by 86.2 min (P < 0.001) and throughout subgroup analysis, although it was only in patients with acute colitis that this finding was without significant heterogeneity. Operative blood loss was less in the laparoscopic group by 57.5 millilitres in high quality and studies published since 2000, and 65.3 millilitres in those reporting on more than 40 patients. There was no significant difference in early or long-term complications between the groups. A statistically significant reduction in length of postoperative stay was observed in the laparoscopic groups by 2.9 days (P < 0.001). CONCLUSION: Laparoscopic subtotal colectomy was associated with longer operating times but a reduced length of stay compared to open surgery. Although short-term outcomes were equivalent in both groups, the suggested benefits in terms of reduced long-term obstructive complications were not supported by this meta-analysis. 相似文献
998.
Comparison of 2-dimensional and 3-dimensional acquisition for 18F-FDG PET oncology studies performed on an LSO-based scanner. 总被引:1,自引:0,他引:1
Martin A Lodge Ramsey D Badawi Richard Gilbert Pablo E Dibos Bruce R Line 《Journal of nuclear medicine》2006,47(1):23-31
Three-dimensional (3D) PET acquisition has the potential to reduce image noise but the advantage of 3D PET for studies outside the brain has not been well established. To compare the performance of 2-dimensional (2D) and 3D acquisition for whole-body (18)F-FDG applications, a series of patient studies were performed using a lutetium oxyorthosilicate (LSO)-based tomograph. METHODS: Comparative 2D and 3D images were acquired for 27 oncology patients using an LSO-based tomograph. Data acquisition (350-650 keV, 6 ns) started 99 +/- 12 min (mean +/- SD) after injection of 624 +/- 76 MBq (18)F-FDG. Bias caused by tracer redistribution and decay was eliminated by acquiring dynamic data over a single-bed position using a protocol that alternated between septa-in and septa-out modes (2D, 3D, 2D, 3D, 2D, 3D). Frames were combined to form 8 statistically independent sinograms: four 2D replicates (105 s) and four 3D replicates (90 s). The different frame durations in 2D and 3D compensated for the different number of overlapping bed positions required for an 85-cm whole-body study. Images were reconstructed with either 2D or fully 3D ordered-subsets expectation maximization (2 iterations and 8 subsets; 2D 6-mm gaussian, 3D 5- and 6-mm gaussian). Image target-to-background ratio was assessed by dividing the lesion maximum by the mean within a neighboring background region. Image noise was assessed by applying background regions of interest to the replicate images and calculating the within-patient coefficient of variation. RESULTS: The difference in target-to-background ratio between the 2D and 3D images, when they were filtered with 6-mm and 5-mm gaussian filters, respectively, was not highly statistically significant (P = 0.16). The mean ratio of 3D to 2D image values was 0.94 with 95% limits of agreement of 0.63-1.41. The within-patient coefficients of variation for the 2D and 3D images were 13% +/- 15% and 9% +/- 10%, respectively (P = 0.0005). CONCLUSION: Under conditions of matched target to-to-background ratios, the 3D mode was found to produce images with significantly less variability than the 2D mode. These data provide support for the use of 3D acquisition with LSO detectors to reduce scan times in whole-body (18)F-FDG applications. 相似文献
999.
C. J. M. Antens M. Oldenwening A. Wolse U. Gehring H. A. Smit R. C. Aalberse M. Kerkhof J. Gerritsen J. C. de Jongste B. Brunekreef 《Clinical and experimental allergy》2006,36(12):1525-1531
BACKGROUND: Studies of the association between indoor allergen exposure and the development of allergic diseases have often measured allergen exposure at one point in time. OBJECTIVE: We investigated the variability of house dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years. METHODS: Data were obtained in the Dutch PIAMA birth cohort study. Dust from the child's mattress, the parents' mattress and the living room floor was collected at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno assay. RESULTS: Mite allergen concentrations for the child's mattress, the parents' mattress and the living room floor were moderately correlated between time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on the child's mattress, the within-home variance was close to or smaller than the between-home variance in most cases. For Fel d 1, the within-home variance was almost always smaller than the between-home variance. Results were similar for allergen levels expressed per gram of dust and allergen levels expressed per square metre of the sampled surface. Variance ratios were smaller when samples were taken at shorter time intervals than at longer time intervals. CONCLUSION: Over a period of 4 years, mite and cat allergens measured in house dust are sufficiently stable to use single measurements with confidence in epidemiological studies. The within-home variance was larger when samples were taken 8 years apart so that over such long periods, repetition of sampling is recommended. 相似文献
1000.
C. Olgart Höglund J. Axén C. Kemi S. Jernelöv J. Grunewald C. Müller-Suur Y. Smith R. Grönneberg A. Eklund P. Stierna M. Lekander 《Clinical and experimental allergy》2006,36(8):982-992
BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others. 相似文献