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991.
Nordenström A Marcus C Axelson M Wedell A Ritzén EM 《The Journal of clinical endocrinology and metabolism》1999,84(4):1210-1213
Congenital adrenal hyperplasia in children is often treated with cortisone acetate and fludrocortisone. It is known that certain patients with congenital adrenal hyperplasia require very high substitution doses of cortisone acetate, and a few patients do not respond to this treatment at all. A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2 x day), was examined. The activation of cortisone to cortisol was assessed by measuring urinary metabolites of cortisone and cortisol. The patient's inability to respond to treatment with cortisone acetate was found to be caused by a low conversion of cortisone to cortisol, assumed to be secondary to low 11beta-hydroxysteroid dehydrogenase activity (11-oxoreductase deficiency). All exons and exon/intron junctions of the 11beta-hydroxysteroid dehydrogenase type1 gene (HSD11L) were sequenced without finding any mutations, but a genetic lesion in the promoter or other regulatory regions cannot be ruled out. The deficient 11-oxoreductase activity seems to have been congenital, in this case, but can possibly be attributable to a down-regulation of the enzyme activity. The results support the use of hydrocortisone, rather than cortisone acetate, for substitution therapy in adrenal insufficiency. 相似文献
992.
J W Sweetenham A M Carella G Taghipour D Cunningham R Marcus A Della Volpe D C Linch N Schmitz A H Goldstone 《Journal of clinical oncology》1999,17(10):3101-3109
PURPOSE: To investigate the results of high-dose therapy and autologous stem-cell transplantation (ASCT) in adults with Hodgkin's disease who do not enter remission after induction therapy, to determine overall survival (OS) and progression free survival (PFS), and to identify prognostic factors. PATIENTS AND METHODS: A retrospective analysis of 175 patients reported to the European Group for Blood and Marrow Transplantation between November 1979 and October 1995. One hundred were male and 75 were female, with a median age of 26.5 years. Responses to first-line therapy were defined as progressive disease (PD) in 88 and stable/minimally responsive disease (SD/MR) in 87. Seventy-five patients received ASCT after failure of one induction regimen. Second-line therapy was given to the remaining 100 patients. Response to second-line therapy was PD in 34 and SD/MR in 66. OS and PFS rates were determined, and prognostic factors were investigated using univariate and multivariate analyses. RESULTS: Responses to high-dose therapy and ASCT were complete response (30%), partial response (28%), no response (14%), PD (14%), and toxic death (14%). Actuarial 5-year OS and PFS rates were 36% and 32%, respectively. In univariate analysis for PFS and OS, adverse factors were use of a second-line chemotherapy regimen and interval of more than 18 months between diagnosis and ASCT. In multivariate analysis, the interval between diagnosis and ASCT maintained prognostic significance for OS. Response to the chemotherapy regimen given immediately before ASCT had no predictive value. CONCLUSION: High-dose therapy and ASCT is an effective treatment strategy for patients with Hodgkin's disease for whom induction chemotherapy fails. Outcome was equivalent for those with obvious PD or SD/MR in response to the regimen given immediately before high-dose therapy. Prospective randomized studies are required to compare this approach with conventional-dose salvage therapy. 相似文献
993.
Marcus EA Weber TK Rodriguez-Bigas MA Driscoll D Meropol NJ Petrelli NJ 《Cancer investigation》1999,17(4):249-252
This study evaluates prognostic factors that may influence survival in patients who present with carcinomatosis from colorectal cancer. Patients may present with carcinomatosis as the pattern of metastases at the initial diagnosis of colorectal cancer. Little is known about the natural history of carcinomatosis and the prognostic factors affecting outcome. All patients treated at Roswell Park Cancer Institute from 1988 to 1994 who presented with carcinomatosis at the initial diagnosis of colorectal cancer were identified. A retrospective review of the medical records for patient and tumor demographics was performed. Estimated survival distributions were calculated by the method of Kaplan and Meier. Tests of significance with respect to survival distribution were based on the log-rank test. Cox proportional hazards model was used for the multivariate analysis. There were 31 males and 38 females. The median age was 61 years (range, 26-80). The primary cancers were in the sigmoid with 24 patients (35%), cecum with 14 patients (20%), and transverse colon with 11 patients (16%). The remainder were distributed throughout the colon and rectum. The most common presentation was large bowel obstruction in 29 patients (42%). T3 and T4 cancers were present in 39 (57%) and 13 patients (19%), respectively. Lymph nodes were positive in 39 patients (57%), and mucin-producing tumors were also present in 39 patients (57%). Twelve patients (17%) had one site of disease, 17 patients (25%) had two sites of disease, and 37 (54%) patients had three or more sites of disease. Ascites was present in 29 patients (42%). Residual disease was present at the completion of surgery in 45 patients, absent in 13 patients, and status unknown in 11. The presence of residual disease (p = 0.0001), presence of ascites (p = 0.02), stage greater than T3 (p = 0.02), and increasing number of carcinomatosis sites (p = 0.006) were found to have a negative impact on survival on univariate analysis. On multivariate analysis, only the presence of residual disease at the completion of surgery was found to be an independent predictor of survival (p = 0.04). Overall median survival was 14 months with a 26% estimated 2-year survival. The presence of gross residual disease at the completion of surgery was shown to be the only independent factor negatively affecting survival. This has potential implications for the operative management of patients presenting with colorectal carcinomatosis. 相似文献
994.
Pinto BM Borrelli B King TK Bock BC Clark MM Roberts M Marcus BH 《Addictive behaviors》1999,24(1):75-86
This study examined characteristics associated with weight control smoking among 281 sedentary women enrolled in a smoking cessation trial. A series of regression models were developed to identify predictors of weight control smoking as measured by the Smoking Situations Questionnaire. Predictor variables included demographic variables, dietary intake, weight gain following previous quit attempts, dietary restraint, self-efficacy for weight management, smoking behavior, exercise behavior, negative affect and psychological constructs relevant to smoking cessation, and exercise adoption. In the final predictor model, anticipation of weight gain in the current quit attempt, higher dietary restraint, younger age, greater Fagerstrom scores, greater number of pounds gained in previous quit attempts, and lower levels of self-efficacy to manage weight in negative affect situations were associated with smoking for weight control. Treatment implications for women who smoke for weight control reasons are discussed. 相似文献
995.
Marcus Dill-Macky Christopher Frazer W Bastiaan de Boer 《Journal of Medical Imaging and Radiation Oncology》1999,43(3):315-320
The magnetic resonance imaging (MRI) features of 11 biopsy-proven lesions of focal nodular hyperplasia (FNH) of the liver were reviewed retrospectively. Only three lesions showed atypical features. It is believed MRI can reliably differentiate FNH from other liver tumours when strict criteria are fulfilled. 相似文献
996.
997.
Efficiency of Protection of Guinea Pigs against Infection with Bacillus anthracis Spores by Passive Immunization 总被引:7,自引:0,他引:7
David Kobiler Yehoshua Gozes Hagai Rosenberg Dino Marcus Shaul Reuveny Zeev Altboum 《Infection and immunity》2002,70(2):544-550
The efficacy of passive immunization as a postexposure prophylactic measure for treatment of guinea pigs intranasally infected with Bacillus anthracis spores was evaluated. Antisera directed either against the lethal toxin components (PA or LF) or against a toxinogenic strain (Sterne) were used for this evaluation. All antisera exhibited high enzyme-linked immunosorbent assay titers against the corresponding antigens, high titers of neutralization of cytotoxicity activity in an in vitro mouse macrophages cell line (J774A.1), as well as in vivo neutralization of toxicity when administered either directly to Fisher rats prior to challenge with the lethal toxin or after incubation with the lethal toxin. In these tests, anti-LF antiserum exhibited the highest neutralization efficiency, followed by anti-Sterne and anti-PA. The time dependence and antibody dose necessary for conferring postexposure protection by the various antibodies of guinea pigs infected with 25 50% lethal doses of Vollum spores was examined. Rabbit anti-PA serum was found to be the most effective. Intraperitoneal injections of anti-PA serum given 24 h postinfection protected 90% of the infected animals, whereas anti-Sterne and anti-LF were less effective. These results further emphasizes the importance of anti-PA antibodies in conferring protection against B. anthracis infection and demonstrated the ability of such antibodies to be effectively applied as an efficient postexposure treatment against anthrax disease. 相似文献
998.
Jarboe MD Juno RJ Stehr W Bernal NP Profitt S Erwin CR Warner BW 《Journal of pediatric surgery》2005,40(1):92-97
Background/Purpose
Intestinal adaptation is a compensatory response to massive small bowel loss in which there are increased numbers of absorptive enterocytes. However, the generation of secretory epithelial cell subtypes in this process has not been investigated. The purpose of this study was to examine the adaptive changes of several small intestinal cell lineage changes in response to massive small bowel resection (SBR).Methods
A 75% SBR or sham operation was performed on male Sprague-Dawley rats. On postoperative day 7, the remnant ileum was harvested and immunohistochemical staining for goblet, Paneth, and enteroendocrine cells was performed. Cell subtypes were evaluated as cells per micrometer of villus/crypt length and compared among operations.Results
A significant increase in goblet cell density occurred after SBR. Intestinal resection did not alter the number of Paneth and enteroendocrine cells. In additional experiments, inhibition of epidermal growth factor receptor signaling was associated with a diminished goblet cell density.Conclusions
The adaptive response of the intestine to massive bowel loss results in an expansion of the goblet cell population in addition to greater numbers of absorptive enterocytes. Although the mechanism and purpose for selective expansion of these stem cell-derived lineages are not presently known, epidermal growth factor receptor signaling appears to be a common pathway. 相似文献999.
A detailed musculoskeletal model of the distal equine forelimb was developed to study the influence of musculoskeletal geometry (i.e. muscle paths) and muscle physiology (i.e. force-length properties) on the force- and moment-generating capacities of muscles crossing the carpal and metacarpophalangeal joints. The distal forelimb skeleton was represented as a five degree-of-freedom kinematic linkage comprised of eight bones (humerus, radius and ulna combined, proximal carpus, distal carpus, metacarpus, proximal phalanx, intermediate phalanx and distal phalanx) and seven joints (elbow, radiocarpal, intercarpal, carpometacarpal, metacarpophalangeal (MCP), proximal interphalangeal (pastern) and distal interphalangeal (coffin)). Bone surfaces were reconstructed from computed tomography scans obtained from the left forelimb of a Thoroughbred horse. The model was actuated by nine muscle-tendon units. Each unit was represented as a three-element Hill-type muscle in series with an elastic tendon. Architectural parameters specifying the force-producing properties of each muscle-tendon unit were found by dissecting seven forelimbs from five Thoroughbred horses. Maximum isometric moments were calculated for a wide range of joint angles by fully activating the extensor and flexor muscles crossing the carpus and MCP joint. Peak isometric moments generated by the flexor muscles were an order of magnitude greater than those generated by the extensor muscles at both the carpus and the MCP joint. For each flexor muscle in the model, the shape of the maximum isometric joint moment-angle curve was dominated by the variation in muscle force. By contrast, the moment-angle curves for the muscles that extend the MCP joint were determined mainly by the variation in muscle moment arms. The suspensory and check ligaments contributed more than half of the total support moment developed about the MCP joint in the model. When combined with appropriate in vivo measurements of joint kinematics and ground-reaction forces, the model may be used to determine muscle-tendon and joint-reaction forces generated during gait. 相似文献
1000.
Isabelle Sermet-Gaudelus John P. Clancy David P. Nichols Jerry A. Nick Kris De Boeck George M. Solomon Marcus A. Mall James Bolognese Florilene Bouisset Wilhelmina den Hollander Nicolas Paquette-Lamontagne Nigel Tomkinson Noreen Henig J. Stuart Elborn Steven M. Rowe 《Journal of cystic fibrosis》2019,18(4):536-542
BackgroundCystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR.MethodsThis multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4 weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport.ResultsIn the homozygous cohort (n = 7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was ?3.0 mV (?6.6; 0.6) at day 15, ?4.1 mV (?7.8; ?0.4, p = .04) at day 26 (end of treatment) and ? 3.7 mV (?8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4 mV (1.1; 17.7, p = .04). The compound heterozygous cohort (n = 7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile.ConclusionsIn F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity. 相似文献