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101.
Loci exhibiting Hardy-Weinberg disequilibrium (HWD) are often excluded from association studies, because HWD may indicate genotyping error, population stratification or selection bias. For case-control studies, HWD can result from a genetic effect at the locus. We extend the modelling to accommodate both stratification and genetic effects. Theoretical genotype frequencies and HWD coefficients are derived under a general genetic model for a population with two strata. Maximum likelihood is used to estimate model parameters and a test for lack of fit identifies the models most consistent with the data. Simulations were used to assess the method.
The technique was applied to a group of ethnically and clinically heterogeneous kidney stone formers and controls, both exhibiting HWD for the R990G SNP of the CASR gene. Results indicate the best fitting model incorporates both stratification and genetic association. The ability of our method to apportion HWD to stratification and genetic effects may well be a significant advance in dealing with heterogeneity in case-control genetic association studies. 相似文献
The technique was applied to a group of ethnically and clinically heterogeneous kidney stone formers and controls, both exhibiting HWD for the R990G SNP of the CASR gene. Results indicate the best fitting model incorporates both stratification and genetic association. The ability of our method to apportion HWD to stratification and genetic effects may well be a significant advance in dealing with heterogeneity in case-control genetic association studies. 相似文献
102.
103.
Emmanuel N. Nsah G. William Moore Grover M. Hutchins 《Fetal and pediatric pathology》1991,11(2):261-269
The basis for persistence of the left superior vena cava (LSVC), usually associated with cardiac malformations, is poorly understood. We examined 351 staged, serially sectioned human embryos in the Carnegie Embryological Collection and 1208 specimens with congenital cardiovascular malformations in the Pathology Collection of the Johns Hopkins Hospital. A standardized questionnaire was answered for each embryo and autopsy case and a computer program was employed to tabulate concurrent anatomic features. In the normal embryos a symmetric venous system appeared with the heart tube at Carnegie stage 9; the sinoatrial junction translocated to the right and the relationship of the coronary sinus to the LSVC was established by stage 12. The LSVC was patent through stage 20 and subsequently underwent luminal obliteration by compression between the left atrium and the hilum of the left lung. Among the 1208 hearts with a congenital abnormality, 104 (9%) had a persistent LSVC with a coronary sinus connection. Statistically, significantly more frequent associations were found between persistent LSVC and atrioventricular canal defects, cor triatriatum, and mitral atresia and a significantly less frequent association was observed between persistent LSVC and atrial septal defect or patent foramen ovale as a primary defect. The normally late embryonic obliteration of the LSVC suggests that its persistence would be secondary to reduce cardiac compression or to blood flow redistribution at an early stage, and the malformations associated with persistent LSVC support that view. Identification of a persistent left superior vena cava with coronary sinus connection should suggest an associated malformation, especially atrioventricular canal, cor trialriatum, or mitral atresia. 相似文献
104.
Sushil Mittal Vimal Grover Kamala Dhall G. I. Dhall A. N. Gupta 《The Australian & New Zealand journal of obstetrics & gynaecology》1985,25(1):54-55
Summary: Culdocentesis was carried out in 92 suspected cases of ectopic pregnancy and was positive in 90%. Laparotomy confirmed the accuracy of culdocentesis in 97.5% of the cases of acute tubal rupture, 87.5% of tubal abortions and 80% of 'intact' tubal pregnancies. 相似文献
105.
106.
OBJECTIVE: This study was carried out to evaluate the progression of visual function impairment in carriers of X-linked recessive retinitis pigmentosa. We also assessed the relationship between the retinal findings at presentation and the extent of deterioration. DESIGN: Observational, retrospective, case series. PARTICIPANTS: Twenty-seven carriers of X-linked recessive retinitis pigmentosa. METHODS: Each carrier was clinically categorized into one of four grades (grades 0 through 3) depending on the presence or absence of a tapetal-like retinal reflex and the extent of peripheral pigmentary degeneration. A complete ophthalmologic examination was performed and data for visual acuity, visual field area, and electroretinographic measurements were collected on the most recent visit in both eyes. These were then compared with similar data obtained on their initial visits. MAIN OUTCOME MEASURES: A comparison of visual function was carried out between the initial visit and the most recent visit on each carrier. The visual acuity was measured with Snellen's acuity charts. The visual fields to targets V-4-e and II-4-e were planimeterized and used for the analysis. The electroretinographic (ERG) measures used were light-adapted single-flash b-wave amplitudes and 30-Hz red flicker for cone function, dark-adapted maximal b-wave amplitudes, and response to a low intensity blue-flash for rod function. RESULTS: None of the 11 carriers with a tapetal-like reflex only (grade 1) showed any significant change in visual acuity or fields as compared with 3 of 7 (43%) carriers with diffuse peripheral pigmentary findings (grade 3) who showed significant deterioration in visual acuity in at least one eye, and 6 of 7 (86%) who showed a significant decrease in visual field area with at least one target size in at least one eye. By comparison, only 1 of 10 carriers with a grade 1 fundus finding demonstrated a significant decrease in maximal dark-adapted ERG function as compared with 5 of 6 (83%) carriers with grade 3 in response to a single-flash stimulus and with 4 of 5 (80%) carriers in response to a single-flash blue stimulus. For the single-flash photopic response, none of the 10 carriers with grade 1 showed any significant deterioration, whereas 2 of 4 (50%) with grade 3 did show such deterioration. The ERG responses for carriers with grade 2 were in between the extent of decrease in ERG amplitudes of those in carriers with grades 1 and 3. CONCLUSIONS: In our cohort of X-linked retinitis pigmentosa carriers, those with only a tapetal-like retinal reflex at presentation had a better prognosis to retain visual function than those with peripheral retinal pigmentation. These data are useful in counseling such carriers as to their visual prognosis. 相似文献
107.
Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects 总被引:2,自引:0,他引:2
D R Rubinow M C Hoban G N Grover D S Galloway P Roy-Byrne R Andersen G R Merriam 《American journal of obstetrics and gynecology》1988,158(1):5-11
A variety of hypotheses have been proposed to explain the premenstrual syndromes. These hypotheses serve as rationales for an equally diverse range of proposed treatments. To investigate these hypotheses, we obtained multiple blood samples across the menstrual cycle in women with well-characterized menstrually related mood disorder and in control subjects. No diagnosis-related differences were observed in the levels or patterns of secretion of progesterone, estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone-estradiol-binding globulin, dehydroepiandrosterone sulfate, dihydrotestosterone, prolactin, or cortisol. Our data suggest that premenstrual syndrome does not represent a simple hormonal deficiency and that the cited rationales for several of the proposed treatments are of questionable merit. 相似文献
108.
Splenic dysfunction measured by pitted red cells (pit) was studied in hemoglobinopathies (SS-, SC-, and S beta-type thalassemias and CC-type hemoglobinopathy) in relation to age, in steady state, and during certain significant events. Our experience revealed that the pit count rose with age during steady state in most children with SS disease. A marked increase in pit count was noted in patients with CC disease. The pit count in four patients with S beta+ thalassemia remained normal (i.e., less than 3.5%) at all ages. In children with homozygous SS disease tested at the time of pneumococcal sepsis, the pit count was universally elevated. The pit count was in the normal range in one child with SS disease and osteomyelitis but was elevated in all others. All children had normal pit counts (less than 3.5%) at the onset of acute splenic sequestration crisis, and the counts remained normal during transfusion therapy. No correlation was detected between the pit count and the size of the spleen in patients under 1 year of age. 相似文献
109.
Free floating ball thrombus in left atrium 总被引:1,自引:0,他引:1
110.
The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy 总被引:1,自引:0,他引:1
McAlister FA Zarnke KB Campbell NR Feldman RD Levine M Mahon J Grover SA Lewanczuk R Leenen F Tobe S Lebel M Stone J Schiffrin EL Rabkin SW Ogilvie RI Larochelle P Jones C Honos G Fodor G Burgess E Hamet P Herman R Irvine J Culleton B Wright JM;Canadian Hypertension Recommendations Working Group 《The Canadian journal of cardiology》2002,18(6):625-641
OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually. 相似文献