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排序方式: 共有2308条查询结果,搜索用时 767 毫秒
1.
Emmi Helle Aldo Córdova-Palomera Tiina Ojala Priyanka Saha Praneetha Potiny Stefan Gustafsson Erik Ingelsson Michael Bamshad Deborah Nickerson Jessica X. Chong University of Washington Center for Mendelian Genomics Euan Ashley James R. Priest 《Genetic epidemiology》2019,43(2):215-226
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献
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Acute angle closure glaucoma generally occurs in older hypermetropic individuals, precipitated by pupillary dilation. However it is often forgotten that it can occur in younger people and that it does not occur solely as a result of the use of mydriatics or normal pupillary dilation in response to darkness. It is recognised that it can occur during or shortly after a surgical procedure done under either spinal or general anaesthetic. We describe a case of acute angle closure occurring in a 37-year-old woman, precipitated by labour. To our knowledge no such case has been described in the literature. 相似文献
6.
Rectal diazepam in the treatment of absence status: a pharmacodynamic study 总被引:7,自引:1,他引:6
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Norman Milligan Soraya Dhillon Alan Richens Jolyon Oxley 《Journal of neurology, neurosurgery, and psychiatry》1981,44(10):914-917
Rectal administration of diazepam is highly effective in terminating absence status as judged by reduction of spike-wave activity in the EEG. Pharmacokinetic studies indicate that diazepam can have antiepileptic properties at serum levels well below those previously reported as being necessary to achieve a therapeutic effect. 相似文献
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Phagocyte function and cytokine production in community acquired pneumonia. 总被引:8,自引:3,他引:5
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![点击此处可从《Thorax》网站下载免费的PDF全文](/ch/ext_images/free.gif)
K Moussa H J Michie I A Cree A C McCafferty J H Winter D P Dhillon S Stephens R A Brown 《Thorax》1994,49(2):107-111
BACKGROUND--It is possible that many deaths from pneumonia may involve the generation of inflammatory mediators and tissue damage by activated phagocytes. To test this hypothesis phagocyte function, plasma levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha), and soluble interleukin 2 receptor (IL-2R), disease severity, and outcome have been examined in 46 patients with community acquired pneumonia. METHODS--Polymorphonuclear leucocyte (PMNL) and monocyte function were measured daily by chemiluminescence in these patients during the first week of admission, and cytokine levels were subsequently determined by ELISA. A series of 61 healthy individuals were used as a control group for the chemiluminescence results. RESULTS--There was evidence of phagocyte, particularly PMNL, activation on admission in 76% of the patients. Most patients (86%) also had raised IL-2R levels on admission. IL-6 and unbound TNF alpha were present in 23% and 41% of patients at varying times during the course of the disease. There was little correlation between measurements of cytokine or phagocyte levels and outcome or indicators of disease severity, although this may be because of the small number of patients included in this preliminary study. CONCLUSIONS--These results are consistent with the hypothesis that activated phagocyte function and raised levels of circulating cytokines may contribute to the pathogenesis of community acquired pneumonia. There are striking similarities in this respect between pneumonia, adult respiratory distress syndrome, and sepsis. 相似文献
9.
R S Dhillon 《Journal of the Royal Society of Medicine》1988,81(12):710-713
A multicentre prospective trial was commenced in July 1984 to establish the incidence of otitis media with effusion (OME) in children born with a cleft of the palate. Additionally, the data recorded would allow an assessment of the effect of palatal closure on middle ear function. Prior to palatal closure, 97% of ears in a group of 50 patients had otitis media with effusion (OME). The insertion of a long-term ventilation tube provided a means of aeration of one ear with the non-ventilated ear acting as a control. Eighty percent of control ears had persistent OME during a 24-month follow-up period post palatal repair. It would seem that OME is universally present in children with a cleft palate prior to 4 months of age and this incidence is only marginally diminished by palatal surgery. The liaison between plastic surgical and ENT units should be even closer than before in order to manage these patients satisfactorily. 相似文献
10.
Focal reduction of villous blood flow in early indomethacin
enteropathy: a dynamic vascular study in the rat 总被引:3,自引:0,他引:3
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Background—Oral indomethacin causes villousshortening, microvascular damage, and distortion, which might inducemucosal ischaemia and necrosis.
Aims—In order to determine the early events inindomethacin induced jejunal injury we examined the temporal relationsbetween morphological damage and changes in villous blood flowfollowing indomethacin.
Methods—In anaesthetised rats, mid jejunal villiwere exteriorised in a chamber and observed by fluorescence microscopy.Blood flow in surface capillaries was calculated from velocities and diameters. Indomethacin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed andthe villi were processed for histological examination. Control animalsreceived intravenous or luminal bicarbonate (1.25%).
Results—Blood flow slowed in individual villi at20 minutes, and progressed to complete stasis (in another group) by 45 minutes. Histological examination at 20 minutes revealed microvascular distortion, but no villous shortening: crypt depth:villous height ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi(p>0.5). At stasis, the villi under study showed epithelial clumpingand were shortened: crypt depth:villous height ratios were 0.92 (0.2)in test and 0.42 (0.06) in surrounding villi (p<0.02). Vehicle alonehad no effect on either blood flow or histology.
Conclusions—Focal slowing of villous blood flowand microvascular distortion precede villus shortening and epithelialdisruption, and indicate that damage to surface microvasculature is anearly event in indomethacin induced mucosal injury in this model.
Aims—In order to determine the early events inindomethacin induced jejunal injury we examined the temporal relationsbetween morphological damage and changes in villous blood flowfollowing indomethacin.
Methods—In anaesthetised rats, mid jejunal villiwere exteriorised in a chamber and observed by fluorescence microscopy.Blood flow in surface capillaries was calculated from velocities and diameters. Indomethacin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed andthe villi were processed for histological examination. Control animalsreceived intravenous or luminal bicarbonate (1.25%).
Results—Blood flow slowed in individual villi at20 minutes, and progressed to complete stasis (in another group) by 45 minutes. Histological examination at 20 minutes revealed microvascular distortion, but no villous shortening: crypt depth:villous height ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi(p>0.5). At stasis, the villi under study showed epithelial clumpingand were shortened: crypt depth:villous height ratios were 0.92 (0.2)in test and 0.42 (0.06) in surrounding villi (p<0.02). Vehicle alonehad no effect on either blood flow or histology.
Conclusions—Focal slowing of villous blood flowand microvascular distortion precede villus shortening and epithelialdisruption, and indicate that damage to surface microvasculature is anearly event in indomethacin induced mucosal injury in this model.
Keywords:indomethacin; jejunum; villi; microcirculation; endothelium; microthrombi
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