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11.
Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia 总被引:3,自引:0,他引:3
C Quigley C Cowell M Jimenez H Burger J Kirk M Bergin M Stevens J Simpson M Silink 《The New England journal of medicine》1989,321(3):143-151
To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early. 相似文献
12.
Racial differences in the cause-specific prevalence of blindness in east Baltimore 总被引:14,自引:0,他引:14
A Sommer J M Tielsch J Katz H A Quigley J D Gottsch J C Javitt J F Martone R M Royall K A Witt S Ezrine 《The New England journal of medicine》1991,325(20):1412-1417
BACKGROUND. Bilateral blindness unrelated to simple refractive error is twice as prevalent among blacks as among whites, although the difference narrows among the elderly. The reasons for this race- and age-related pattern are uncertain. METHODS AND RESULTS. A randomly selected, stratified, multistage cluster sample of 2395 blacks and 2913 whites 40 years of age and older in East Baltimore underwent detailed ophthalmic examinations by a single team. We identified 64 subjects who were blind in both eyes. The leading causes of blindness were unoperated senile cataract (accounting for blindness in 27 of the total of 128 eyes), primary open-angle glaucoma (17 eyes), and age-related macular degeneration (16 eyes). Together, these three disorders accounted for 47 percent of all blindness in this sample. Unoperated cataract accounted for 27 percent of all blindness among blacks, among whom it was four times more common than among whites; whites were almost 50 percent more likely than blacks to have undergone cataract extraction before the age of 80 (P less than 0.002). Primary open-angle glaucoma accounted for 19 percent of all blindness among blacks; it was six times as frequent among blacks as among whites and began 10 years earlier, on average. By contrast, age-related macular degeneration resulting in blindness was limited to whites, among whom it was the leading cause of blindness (prevalence, 2.7 per 1000; 95 percent confidence interval, 1.2 to 5.4); it affected 3 percent of all white subjects 80 years of age or older. CONCLUSIONS. The pattern of blindness in urban Baltimore appears to be different among blacks and whites. Whites are far more likely to have age-related macular degeneration, and blacks to have primary open-angle glaucoma. The high rate of unoperated cataracts among younger blacks and among elderly subjects of both races suggests that health services are underused. Half of all blindness in this urban population is probably preventable or reversible. 相似文献
13.
Previous studies demonstrated distinct cardiovascular patterns associated with threat and challenge appraisals for groups of participants. We extend these results by assessing whether appraisals continue to be associated with these cardiovascular response patterns within an individual as appraisals change. Participants completed four verbal mental arithmetic tasks for which they made appraisals before and after each task. Cardiac reactivity and total peripheral resistance (TPR) were calculated for the first and last minutes of each task, and the number of responses and percent correct were measured for each task. In line with our prediction, pretask appraisals were related to some task-related cardiac responses across the four tasks. In addition, task-related cardiovascular reactivity and behaviors both influenced appraisals following the task. Our findings suggest that an idiographic analysis of appraisals, cardiovascular physiology, and task-related behaviors provides a richer understanding of the appraisal process and reveals sex differences deserving further assessment. 相似文献
14.
Summary The purposes of this investigation were to determine the validity of critical power (CP) as a measure of the work rate that can be maintained for a very long time without fatigue and to determine whether this corresponded with the maximal lactate steady-state (lass,max). Eight highly trained endurance cyclists (maximal oxygen uptake 74.1 ml · kg–1 · min–1, SD 5.3) completed four cycle ergometer tests to exhaustion at predetermined work rates (360, 425, 480 and 520 W). From these four co-ordinates of work and time to fatigue the regression of work limit on time limit was calculated for each individual (CP). The cyclists were then asked to exercise at their CP for 30 min. If CP could not be maintained, the resistance was reduced minimally to allow the subject to complete the test and maintain a blood lactate plateau. Capillary blood was sampled at 0, 5, 10, 20 and 30 min into exercise for the analysis of lactate. Six of the eight cyclists were unable to maintain CP for 30 min without fatigue. In these subjects, the mean power attained was 6.4% below that estimated by CP. Mean blood lactates (n = 8) reached a steady-state (8.9 mmol · l–1, SD 1.6) during the last 20 min of exercise indicating that CP slightly overestimated lass, max. Individual blood lactates during the last 20 min of exercise were more closely related to the y-intercept of the CP curve (r=0.78, P<0.05) than either CP (0.34, NS) or mean power output (r=0.42, NS). The present investigation has shown that highly trained endurance cyclists can tolerate previously unreported levels of blood lactate during 30 min of exercise at or near their CP. Blood lactates during continuous exercise are higher than at the same work rate during an incremental test. The CP provides a simple and inexpensive means of assessing the exercise intensity which can be maintained continuously, while avoiding the methodological difficulties associated with ventilatory and lactate thresholds. 相似文献
15.
Quigley CA Tan JA He B Zhou ZX Mebarki F Morel Y Forest MG Chatelain P Ritzén EM French FS Wilson EM 《Mechanisms of ageing and development》2004,125(10-11):683-695
Partial androgen insensitivity with sex phenotype variation in two unrelated families was associated with missense mutations in the androgen receptor (AR) gene that disrupted the AR NH(2)-terminal/carboxy terminal interaction. Each mutation caused a single amino acid change within the region of the ligand-binding domain that forms activation function 2 (AF2). In one family, the mutation I737T was in alpha helix 4 and in the other F725L was between helices 3 and 4. Neither mutation altered androgen binding as determined by assays of mutant AR in the patient's cultured genital skin fibroblasts or of recombinant mutant receptors transfected into COS cells. In transient cotransfection assays in CV1 cells, transactivation with the AR mutants at low concentrations of DHT was reduced several fold compared with wild-type AR but increased at higher concentrations. Defects in NH(2)-terminal/carboxy terminal interactions were identified in mammalian two hybrid assays. In similar assays, there was reduced binding of the p160 coactivators TIF2/SRC2 and SRC1 to the mutant AR ligand binding domains (LBD). In the family with AR I737T, sex phenotype varied from severely defective masculinization in the proband to a maternal great uncle whose only manifestation of AIS was severe gynecomastia. He was fertile and passed the mutation to two daughters. The proband of the F725L family was also incompletely masculinized but was raised as a male while his half-sibling by a different father was affected more severely and reared as a female. These studies indicate that the function of an AR AF2 mutant in male development can vary greatly depending on the genetic background. 相似文献
16.
Reassessment of faecal alpha-1-antitrypsin excretion for use as screening test for intestinal protein loss. 总被引:1,自引:0,他引:1 下载免费PDF全文
E M Quigley I N Ross M R Haeney I B Holbrook M N Marsh 《Journal of clinical pathology》1987,40(1):61-66
Faecal alpha-1-antitrypsin and 51Cr-albumin losses in 42 patients with either gastrointestinal or hepatic disease were compared. The reference range was derived from measurements in 20 controls without gastrointestinal disease. Alpha-1-antitrypsin excretion was increased in patients with excessive 51Cr-albumin loss, and correlations were found between alpha-1-antitrypsin clearance and 51Cr-albumin excretion. Because of the considerable overlap of faecal alpha-1-antitrypsin excretion between controls and patients, sensitivity and specificity of the test were only 58% and 80%, respectively. This poor reliability could not be explained by sampling error or temporal variations in alpha-1-antitrypsin excretion. These results show that although faecal alpha-1-antitrypsin excretion correlates with 51Cr-albumin excretion when whole groups of patients are studied, its poor sensitivity makes it an unreliable measure of enteric protein loss. 相似文献
17.
18.
Ryan Schutt Jamie Case Sunil M. Kurian Samantha R. Spierling Bagsic Bethany L. Barrick Alice E. Toll Qiuheng Zhang Elaine F. Reed Michael M. Quigley Randolph Schaffer Jonathan S. Fisher James C. Rice Christopher L. Marsh 《Transplantation proceedings》2021,53(3):950-961
Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection. 相似文献
19.
20.
Berger RA Quigley LR Jacobs JJ Sheinkop MB Rosenberg AG Galante JO 《The Journal of bone and joint surgery. American volume》1999,81(12):1682-1691
BACKGROUND: The decision as to whether to revise or retain a well fixed cemented acetabular component during revision of a femoral component is especially difficult; the rate of loosening of cemented acetabular components is high, whereas that of porous-coated acetabular components inserted during revision is low. However, removal of a well fixed cemented acetabular component can result in increased operative morbidity and cost and in loss of acetabular bone. Data that can be used to predict the long-term survival of retained well fixed cemented acetabular components are therefore needed. METHODS: We studied the five to thirteen-year clinical and radiographic results in a group of twenty-six consecutive patients in whom a well fixed cemented acetabular component had been retained during revision of a femoral component. Typical demographic data on the patients and information about the components were recorded, and the cemented acetabular components were graded as A through F, according to the system of Ranawat et al., at the time of the femoral revision. The average duration of follow-up was 8.4 years (range, 5.0 to 12.7 years). No patient was lost to follow-up. RESULTS: Four acetabular components (15 percent) had progressive radiolucency (at forty-eight, forty-eight, fifty-nine, and seventy-five months after the femoral revision) and were considered radiographically loose despite not being associated with symptoms. All four components were graded as either E or F at the time that they were retained during the femoral revision; radiographic loosening was significantly related to these two grades (p < 0.01). No acetabular component with a grade of A, B, C, or D loosened. The components that loosened had been in vivo for a relatively shorter, as opposed to longer, duration before the femoral revision compared with the components that did not loosen (p < 0.05). CONCLUSIONS: Retention of the well fixed cemented acetabular components was associated with good clinical results but with a 15 percent rate of loosening. Revision of a cemented acetabular component solely on the basis of the duration that it was in vivo or whether a previous revision had been done does not appear to be warranted. Our findings suggest that acetabular components with a grade of A, B, C, or D at the time of a femoral revision may be retained, as these components continued to function at the time of the five to thirteen-year follow-up in the current study. 相似文献