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31.
Many single-gene disorders (especially dominant traits) are known to exhibit "incomplete penetrance," a term often criticized as reflecting our ignorance of genetic and environmental factors that may interact with the genotype to determine the ultimate phenotype of the individual. We explore the effects of an environmental factor on penetrance for a simple model of single gene-mediated susceptibility to environmental factors. We show that penetrance of the susceptible genotype increases with increasing frequency of exposure to the factor and the strength of interaction between the factor and the genotype (relative risk). For disorders with disease frequency of 0.001 or less (as seen with many congenital malformations), penetrance is generally low (less than 10%) if the exposure frequency is low (less than 10%) even in the face of strong gene-environment interaction. Such low penetrance can lead to low recurrence risks. Single-gene effects could easily be overlooked in genetic analysis unless specific environmental factors are considered. 相似文献
32.
33.
Abrahams NA MacLennan GT Khoury JD Ormsby AH Tamboli P Doglioni C Schumacher B Tickoo SK 《Histopathology》2004,45(6):593-602
AIMS: In some cases distinction between chromophobe renal cell carcinoma (CRCC), oncocytoma and clear cell (conventional) renal cell carcinoma (eosinophilic variant) using routine light microscopy remains problematic. The present study investigates the level of agreement in the diagnosis of CRCC, as well as the histological features most frequently used for this diagnosis by two pathologists with a special interest in renal neoplasia. The sensitivity and specificity of immunohistochemical markers in cases with overlapping histological features in the diagnosis of CRCC were also studied. Electron microscopy was performed, as a diagnostic gold standard, on all of the cases. METHODS AND RESULTS: Thirty-two renal tumours with predominantly eosinophilic cytoplasm were reviewed in a blinded fashion by two pathologists. The diagnosis and morphological features used to render each diagnosis were tabulated. Validation of the utility of keratin 7 and 20, epithelial membrane antigen (EMA), vimentin, CD10, parvalbumin, RCC antigen, antimitochondrial antibody and Hale's colloidal iron was performed by the construction of a tissue microarray (TMA) master block. Based on histological criteria alone, overall agreement on the diagnosis of these tumours was reached in 69% of the cases, while there was total disagreement in 12%. In 59% of the cases, total agreement was reached in classifying the case as a CRCC based on histology alone. Kappa statistics for interobserver variability were calculated as only slight agreement (kappa = 0.3). The histological features most frequently associated with a diagnosis of CRCC were accentuated cell borders (87%) and a combination of hyperchromatic wrinkled nuclei (79%) and perinuclear halos (74%). The most sensitive and specific marker for CRCC was parvalbumin (sensitivity 0.91; specificity 1.0). The immunohistochemical profile of EMA+/ vimentin- was useful but had low specificity (sensitivity 0.75; specificity 0.4). CD10 had the highest sensitivity (1.0) but worst specificity (0.25) for CRCC. Keratin 7 had high sensitivity (0.83) but fairly low specificity (0.37) for CRCC. Hale's colloidal iron and the RCC antigen marker were not contributory. Finally, the antimitochondrial antibody was found to be fairly sensitive (0.83) for excluding CRCC. CONCLUSIONS: A small but significant proportion of renal tumours with cells having eosinophilic cytoplasm cannot be classified, even by experienced pathologists, based on histology alone. In these cases it is imperative to use markers with known sensitivity and specificity for the diagnosis of CRCC. 相似文献
34.
Case series of infants with certain birth defect patterns and putative teratogenic exposures should be interpreted with caution since the presence of birth defects and the exposure among the same infants could be entirely due to chance. In the absence of other epidemiologic data, the plausibility for a causal association is strengthened by 1) rarity of the defect pattern, 2) rarity of the exposure in the population, 3) small source population, 4) short time period for the study, and 5) biologic plausibility for the association. These concepts are illustrated using case reports of putative teratogenicity of cocaine and etretinate. In the presence of epidemiologic data, the concept of attributable fraction in exposed (AFE) can be used to evaluate the likelihood that the defect pattern among infants with a particular exposure is attributable to the exposure. This quantity is related to the strength of the epidemiologic association between the defect pattern and the exposure, as measured in terms of relative risk R (or odds ratio), and is equal to (R-1)/R. Even for strong teratogens such as maternal diabetes and isotretinoin, where R is about 7, in more than 14% (1-AFE) of exposed infants with birth defects, the pattern of defects is not attributable to the exposure. Furthermore, AFE can be used to "correct" crude measures of sensitivity (the proportion of exposed malformed infants with a defect pattern attributable to the exposure) and positive predictive value (the proportion of malformed infants who have the exposure and have the defect pattern attributable to the exposure).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
35.
E L Khoury P M Cossio A Szarfman J C Marcos O García Morteo R M Arana 《American journal of clinical pathology》1978,69(1):62-65
One hundred fifty-six of 1,250 sera from patients with presumed connective tissue and related diseases showed vascular staining on mouse liver cryostat sections when they were routinely checked for antinuclear factor by the indirect immunofluorescence test. In a third of the cases, the vascular immunofluorescent pattern was given by the EVI antibody reacting with the plasma membrane of striated muscle fibers and endothelial cells, as has been recently described to occur in Chagas' disease. This led to the detection of previously unsuspected Trypanosoma cruzi infection in 67.8% of the serum samples in which the EVI antibody was detected after observation of a positive vascular pattern with mouse liver cryostat sections. On the other hand, no significant relationship between Chagas infection and sera with other anti-striated-muscle immunofluorescent patterns that also showed a vascular staining on mouse liver cryostat sections was established. Consideration of the vascular pattern observed with the EVI antibody on mouse liver cryostat sections can be helpful in detection of previously ignored T. cruzi infection in patients who have connective-tissue diseases and related conditions. This is of interest in view of the fact that anergic immunodepressive therapy, often used in these patients, significantly alters the host-parasite relationship and may lead to severe dissemination of the parasite. 相似文献
36.
John A. Morrison Philip R. Khoury Barbara N. Campaigne W. M. Cameron Chumlea Bonny Specker Barbara N. Campaign Shumei S. Guo 《American journal of human biology》1994,6(4):481-490
The purpose of this study was to compare estimates of body composition in two ethnic groups, 31 black and 38 white girls 10 through 16 years of age, to establish accurate and precise laboratory standards for field measures of body composition in the NHLBI Growth and Health Study HC 55025. The dual energy X-ray absorptiometry (DXA) measures of fat free mass (FFM) and % body fat (%BF) were made using Hologic QDR-1000/W. Corresponding values of FFM and %BF from underwater weighing (UWW) were determined using the two-component model of Siri, and these were corrected using the model of Lohman for white girls only. In the comparison of the different models and methods, the two-component model overestimated FFM compared to estimates from DXA for black girls, as did the corrected Lohman model for white girls. The two-component model significantly overestimated %BF in both white and black girls compared to corresponding estimates from DXA. The ratio of bone mineral content (BMC)/FFM affected the degree of %BF differences in black girls but not in white girls. Also, as the density of FFM increased or approached adult status in black girls (BMC/FFM increased), differences between the two-component model and estimates from DXA decreased. In both groups of girls, the relationship of %BF from UWW and DXA are a function of the level of body fatness. DXA values of %BF are greater than those from UWW under about 24% body fat, but the converse occurs above 25% body fat. The inability of UWW using the two-component model to account for the body composition in these girls can be corrected in part by measuring the variables for a multicomponent model or more easily by using DXA estimates of body composition. © 1994 Wiley-Liss, Inc. 相似文献
37.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
38.
Dalia Khoury Alexander Preiss Paul Geiger Mohd Anwar Kevin Paul Conway 《JMIR Public Health and Surveillance》2021,7(5)
BackgroundThe opioid crisis in the United States may be exacerbated by the COVID-19 pandemic. Increases in opioid use, emergency medical services (EMS) runs for opioid-related overdoses, and opioid overdose deaths have been reported. No study has examined changes in multiple naloxone administrations, an indicator of overdose severity, during the COVID-19 pandemic.ObjectiveThis study examines changes in the occurrence of naloxone administrations and multiple naloxone administrations during EMS runs for opioid-related overdoses during the COVID-19 pandemic in Guilford County, North Carolina (NC).MethodsUsing a period-over-period approach, we compared the occurrence of opioid-related EMS runs, naloxone administrations, and multiple naloxone administrations during the 29-week period before (September 1, 2019, to March 9, 2020) and after NC’s COVID-19 state of emergency declaration (ie, the COVID-19 period of March 10 to September 30, 2020). Furthermore, historical data were used to generate a quasi-control distribution of period-over-period changes to compare the occurrence of each outcome during the COVID-19 period to each 29-week period back to January 1, 2014.ResultsAll outcomes increased during the COVID-19 period. Compared to the previous 29 weeks, the COVID-19 period experienced increases in the weekly mean number of opioid-related EMS runs (25.6, SD 5.6 vs 18.6, SD 6.6; P<.001), naloxone administrations (22.3, SD 6.2 vs 14.1, SD 6.0; P<.001), and multiple naloxone administrations (5.0, SD 1.9 vs 2.7, SD 1.9; P<.001), corresponding to proportional increases of 37.4%, 57.8%, and 84.8%, respectively. Additionally, the increases during the COVID-19 period were greater than 91% of all historical 29-week periods analyzed.ConclusionsThe occurrence of EMS runs for opioid-related overdoses, naloxone administrations, and multiple naloxone administrations during EMS runs increased during the COVID-19 pandemic in Guilford County, NC. For a host of reasons that need to be explored, the COVID-19 pandemic appears to have exacerbated the opioid crisis. 相似文献
39.
B M Churchill G A McLorie A E Khoury P A Merguerian A M Houle 《The Urologic clinics of North America》1990,17(2):343-360
Posterior urethral valves have a broad spectrum of clinical severity determined by the degree and reversibility of the long stepwise sequence of secondary pathology. Neonatal azotemia and severe bilateral reflux are particularly important negative prognostic factors. In the mild cases, valve ablation with or without delayed reconstruction is good therapy. In the very severe cases, our interpretation of all the clinical and experimental information now available suggests that the time interval and the level of decompression are extremely important. Achievement of consistent low caliceal pressure without stasis and infections should be achieved as soon as possible. We do not agree with the philosophy of "valve ablation and wait and see" for secondary reconstruction as applied to the severe cases. An analogous philosophy would be treating all respiratory infections as upper respiratory infections and applying aggressive appropriate therapy for pneumonia only if the patient does not respond clinically. However, all controversy aside, the management of neonatal infants with posterior urethral valves remains a difficult and challenging problem for us all. The real challenge will be to improve published management results to the point that the family faced with decisions regarding an in utero diagnosis of posterior urethral valves will have enough hope to continue the pregnancy. 相似文献
40.
止泻散敷脐治疗婴幼儿腹泻100例 总被引:1,自引:1,他引:0
0 引言 腹泻乃小儿最常见病 ,尤以 2岁以下婴幼儿最为常见 .年龄越小 ,发病率越高 ,且多在夏、秋季发病 .小儿患病后惧怕打针 ,服药以及输液 ,给治疗带来一些困难 . 12 a来 ,我们用自拟的止泻散敷脐治疗婴幼儿泄泻 ,效果良好 .1 对象和方法1.1 对象 1998- 0 6 / 1999- 10婴幼儿腹泻发病高峰期门诊病例 10 0 (男 6 6 ,女 34 )例 ,年龄 2月龄~ 5岁 .肠炎 5 8例 ,单纯消化不良 42例 . 6 7例曾多次治疗 ,33例初诊 .凡接受治疗之患儿 ,一律停止用其他药物 .1.2 方法 药物组成 :川椒 12 g,干姜 12 g,小茴香 12 g,白芷 2 0 g,吴茱萸 5 g,… 相似文献