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221.
222.
EL Silveira RH Elnecave EP Dos Santos V Moura EM Pinto I Van Der Linden Nader BB Mendonca TASS Bachega 《Clinical genetics》2009,76(6):503-510
Neonatal screening for congenital adrenal hyperplasia (CAH) is useful in diagnosing salt wasting form (SW). However, there are difficulties in interpreting positive results in asymptomatic newborns. The main objective is to analyze genotyping as a confirmatory test in children with neonatal positive results. Patients comprised 23 CAH children and 19 asymptomatic infants with persistently elevated 17‐hydroxyprogesterone (17OHP) levels. CYP21A2 gene was sequenced and genotypes were grouped according to the enzymatic activity of the less severe allele: A1 null, A2 < 2%, B 3–7%, C > 20%. Twenty‐one children with neonatal symptoms and/or 17OHP levels > 80 ng/ml carried A genotypes, except two virilized girls (17OHP < 50 ng/ml) without CAH genotypes. Patients carrying SW genotypes (A1, A2) and low serum sodium levels presented with neonatal 17OHP > 200 ng/ml. Three asymptomatic boys carried simple virilizing genotypes (A2 and B): in two, the symptoms began at 18 months; another two asymptomatic boys had nonclassical genotypes (C). The remaining 14 patients did not present CAH genotypes, and their 17OHP levels were normalized by 14 months of age. Molecular analysis is useful as a confirmatory test of CAH, mainly in boys. It can predict clinical course, identify false‐positives and help distinguish between clinical forms of CAH. 相似文献
223.
Baidas SM Winer EP Fleming GF Harris L Pluda JM Crawford JG Yamauchi H Isaacs C Hanfelt J Tefft M Flockhart D Johnson MD Hawkins MJ Lippman ME Hayes DF. 《Journal of the peripheral nervous system : JPNS》2001,6(1):65-66
Purpose: To determine the efficacy, safety, pharmacokinetics, and effect on serum angiogenic growth factors of two dose levels of thalidomide in patients with metastatic breast cancer. Patients and Methods: Twenty-eight patients with progressive metastatic breast cancer were randomized to receive either daily 200 mg of thalidomide or 800 mg to be escalated to 1,200 mg. Fourteen heavily pretreated patients were assigned to each dose level. Each cycle consisted of 8 weeks of treatment. Pharmacokinetics and growth factor serum levels were evaluated. Results: No patient had a true partial or complete response. On the 800-mg arm, 13 patients had progressive disease at or before 8 weeks of treatment and one refused to continue treatment. The dose was reduced because of somnolence to 600 mg for five patients and to 400 mg for two and was increased for one to 1,000 mg and for four to 1,200 mg. On the 200-mg arm, 12 patients had progressive disease at or before 8 weeks and two had stable disease at 8 weeks, of whom one was removed from study at week 11 because of grade 3 neuropathy and the other had progressive disease at week 16. Dose-limiting toxicities included somnolence and neuropathy. Adverse events that did not require dose or schedule modifications included constipation, fatigue, dry mouth, dizziness, nausea, anorexia, arrhythmia, headaches, skin rash, hypotension, and neutropenia. Evaluation of circulating angiogenic factors and pharmacokinetic studies failed to provide insight into the reason for the lack of efficacy. Conclusion: Single-agent thalidomide has little or no activity in patients with heavily pretreated breast cancer. Further studies that include different patient populations and/or combinations with other agents might be performed at the lower dose levels. 相似文献
224.
Leeflang EP; Tavare S; Marjoram P; Neal CO; Srinidhi J; MacFarlane H; MacDonald ME; Gusella JF; de Young M; Wexler NS; Arnheim N 《Human molecular genetics》1999,8(2):173-183
Trinucleotide repeat disease alleles can undergo 'dynamic' mutations in
which repeat number may change when a gene is transmitted from parent to
offspring. By typing >3500 sperm, we determined the size distribution of
Huntington's disease (HD) germline mutations produced by 26 individuals
from the Venezuelan cohort with CAG/CTG repeat numbers ranging from 37 to
62. Both the mutation frequency and mean change in allele size increased
with increasing somatic repeat number. The mutation frequencies averaged
82% and, for individuals with at least 50 repeats, 98%. The extraordinarily
high mutation frequency levels are most consistent with a mutation process
that occurs throughout germline mitotic divisions, rather than resulting
from a single meiotic event. In several cases, the mean change in repeat
number differed significantly among individuals with similar somatic allele
sizes. This individual variation could not be attributed to age in a simple
way or to ' cis ' sequences, suggesting the influence of genetic background
or other factors. A familial effect is suggested in one family where both
the father and son gave highly unusual spectra compared with other
individuals matched for age and repeat number. A statistical model based on
incomplete processing of Okazaki fragments during DNA replication was found
to provide an excellent fit to the data but variation in parameter values
among individuals suggests that the molecular mechanism might be more
complex.
相似文献
225.
BRCA1 Gene Mutation Screening for the Hereditary Breast and/or Ovarian Cancer Syndrome in Breast Cancer Cases: a First High Resolution DNA Melting Analysis in Indonesia 下载免费PDF全文
Farmaditya EP MundhofirCatharina Endah WulandariYan Wisnu PrajokoTri Indah Winarni 《Asian Pacific journal of cancer prevention》2016,17(3):1539-1546
Specific patterns of the hereditary breast and ovarian cancer (HBOC) syndrome are related to mutations in the BRCA1 gene. One hundred unrelated breast cancer patients were interviewed to obtain clinical symptoms and signs, pedigree and familial history of HBOC syndrome related cancer. Subsequently, data were calculated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk prediction model. Patients with high score of BOADICEA were offered genetic testing. Eleven patients with high score of BOADICEA, 2 patients with low score of BOADICEA, 2 patient's family members and 15 controls underwent BRCA1 genetic testing. Mutation screening using PCR-HRM was carried out in 22 exons (41 amplicons) of BRCA1 gene. Sanger sequencing was subjected in all samples with aberrant graph. This study identified 10 variants in the BRCA1 gene, consisting of 6 missense mutations (c.1480C>A, c.2612C>T, c.2566T>C, c.3113A>G, c.3548 A>G, c.4837 A>G), 3 synonymous mutations (c.2082 C> T, c.2311 T> C and c.4308T>C) and one intronic mutation (c.13435 G>T). All variants tend to be polymorphisms and unclassified variants. However, no known pathogenic mutations were found. 相似文献
226.
Background
To determine monthly cost and cost effectiveness of bilateral prostaglandin/prostamide therapy for lowering intraocular pressure (IOP) in patients taking bimatoprost 0.03% (Lumigan®, Allergan, Inc.), latanoprost 0.005% (Xalatan®, Pfizer, Inc.), or travoprost 0.004% (Travatan®, Alcon Laboratories, Inc.).Methods
Drops in five new 2.5-mL bottles were counted and then averaged for each drug. Average retail price was determined by surveys of pharmacies. Drop count, average retail price, average wholesale price, and IOP reduction data were used to compute annual cost, and cost effectiveness (annual cost-per-mm Hg of IOP reduction) of the three drugs.Results
Drops per 2.5-mL bottle averaged 113 for bimatoprost 0.03%, 84 for latanoprost 0.005%, and 83 for travoprost 0.004%. Average retail cost (2005) per bottle was $69.99 for bimatoprost 0.03%, $61.69 for latanoprost 0.005%, and $66.37 for travoprost 0.004%. The monthly retail cost of bilateral therapy was $37.92 for bimatoprost 0.03%, $44.75 for latanoprost 0.005%, and $49.25 for travoprost 0.004%. Cost effectiveness ranges were $57 to $65 per mm Hg reduction in IOP per year for bimatoprost, 0.03%, $67 to $90 per mm Hg for latanoprost 0.005%, and $74 to $84 per mm Hg for travoprost 0.004%.Conclusion
Bimatoprost 0.03% had the lowest monthly and annual costs and the greatest cost effectiveness for lowering IOP compared with latanoprost 0.005% and travoprost 0.004%.227.
228.
Barblu L Machmach K Gras C Delfraissy JF Boufassa F Leal M Ruiz-Mateos E Lambotte O Herbeuval JP;for the ANRS EP HIV Controllers Study Group 《The Journal of infectious diseases》2012,206(5):790-801
Background.Human immunodeficiency virus (HIV) controllers spontaneously control viremia and CD4 T-cell depletion in contrast to viremic patients. After HIV exposure, plasmacytoid dendritic cells (pDCs) produce high levels of interferon alpha (IFN-α) and express the apoptotic ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand). Simian models have shown that prolonged high levels of IFN-α production could be responsible for AIDS progression. Methods.We studied pDC activation in response to human immunodeficiency virus (HIV) using flow cytometry and 3D microscopy. Results.We show here that pDCs from controller patients produced higher levels of IFN-α in response to HIV than pDCs from viremic patients but similar levels to pDCs from healthy donors. Because binding of HIV to CD4 is essential for pDC activation, the low CD4 expression by pDCs from viremic patients may explain the weak IFN-α response to HIV. Three-dimensional microscopy revealed that pDCs from controllers and healthy donors expressed intracellular TRAIL that is relocalized to the membrane after HIV exposure. In contrast, pDCs from viremic patients expressed membrane TRAIL without any stimulation. Conclusions.We demonstrate that, in response to HIV, pDCs from controller patients produce IFN-α, express membrane TRAIL, and induce apoptosis of T-cell lines. 相似文献
229.
Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin 总被引:10,自引:0,他引:10
A B Hodsman J H Toogood B Jennings L J Fraher J C Baskerville 《The Journal of clinical endocrinology and metabolism》1991,72(3):530-540
Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function. 相似文献
230.
In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response. 相似文献