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991.
992.
Felicity Payne Rita Colnaghi Nuno Rocha Asha Seth Julie Harris Gillian Carpenter William E. Bottomley Eleanor Wheeler Stephen Wong Vladimir Saudek David Savage Stephen O’Rahilly Jean-Claude Carel Inês Barroso Mark O’Driscoll Robert Semple 《The Journal of clinical investigation》2014,124(9):4028-4038
Structural maintenance of chromosomes (SMC) complexes are essential for maintaining chromatin structure and regulating gene expression. Two the three known SMC complexes, cohesin and condensin, are important for sister chromatid cohesion and condensation, respectively; however, the function of the third complex, SMC5–6, which includes the E3 SUMO-ligase NSMCE2 (also widely known as MMS21) is less clear. Here, we characterized 2 patients with primordial dwarfism, extreme insulin resistance, and gonadal failure and identified compound heterozygous frameshift mutations in NSMCE2. Both mutations reduced NSMCE2 expression in patient cells. Primary cells from one patient showed increased micronucleus and nucleoplasmic bridge formation, delayed recovery of DNA synthesis, and reduced formation of foci containing Bloom syndrome helicase (BLM) after hydroxyurea-induced replication fork stalling. These nuclear abnormalities in patient dermal fibroblast were restored by expression of WT NSMCE2, but not a mutant form lacking SUMO-ligase activity. Furthermore, in zebrafish, knockdown of the NSMCE2 ortholog produced dwarfism, which was ameliorated by reexpression of WT, but not SUMO-ligase–deficient NSMCE. Collectively, these findings support a role for NSMCE2 in recovery from DNA damage and raise the possibility that loss of its function produces dwarfism through reduced tolerance of replicative stress. 相似文献
993.
Hematogenous metastasis to skeletal muscle from urothelial carcinoma is extremely rare and metastatic disease to skeletal muscle tends to be found in people with advanced-stage neoplasm. We report in this paper a case of left sartorius muscle metastasis from urothelial cell carcinoma. A left nephroureterectomy with bladder cuff excision was performed and revealed a high-grade papillary transitional cell carcinoma (TCC) of the pelvis. And 6 month later, recurrent bladder cancer was found regular cystoscopy and then treated with transurethral resection of the bladder. After 6 times resection of bladder, an invasion into the bladder muscle layer was found. We recommended additional radical cystectomy to prevent the disease from advancing. However, the patient refused additional surgery. 6 month later, the patient complained of left thigh pain, so ultrasonography-guided biopsy of the nodular mass lesion in the left sartorius muscle was performed. The pathological analysis of the biopsy specimen revealed poorly differentiated metastatic urothelial carcinoma. 相似文献
994.
Jong-Chan Youn Sang-Hyun Ihm Jang-Ho Bae Seong-Mi Park Dong Woon Jeon Byung-Chun Jung Tae Ho Park Nae Hee Lee Jong-Min Song Young Won Yoon Eun Seok Shin Ki Chul Sung In Hyun Jung Wook Bum Pyun Seung-Jae Joo Woo Jung Park Jin Ho Shin Seok-Min Kang 《Clinical therapeutics》2014
Purpose
The standard 60-mg dose of fimasartan, a newly developed selective angiotensin II receptor blocker, is effective and safe for use in patients with mild to moderate hypertension. This study aimed to compare the efficacy and safety of low-dose (30 mg) fimasartan and placebo or valsartan (80 mg) for 8 weeks in patients with mild to moderate hypertension.Methods
In this randomized trial, 293 patients (219 men; mean age, 54.24 [9.77] years) with mild to moderate hypertension were enrolled. After randomization to receive 30-mg fimasartan (n = 115), placebo (n = 117), or 80-mg valsartan (n = 61), the treatment dose was kept constant without dose escalation for 8 weeks. The primary end point was improvement in sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks that was compared between treatments with low-dose fimasartan and placebo. The secondary end point was the overall efficacy and safety of low-dose fimasartan compared with that of placebo or valsartan.Findings
At week 8, SiDBP changed by –9.93 (8.86) mm Hg in the fimasartan group and by –2.08 (9.47) mm Hg in the placebo group, which indicated significant antihypertensive efficacy (P < 0.0001). Efficacy was shown at week 4 as measured by SiDBP (–9.96 [7.73] vs –2.27 [7.85] mm Hg; P < 0.0001) or sitting systolic blood pressure (SiSBP) (–16.18 [14.44] vs –1.95 [13.48] mmHg; P < 0.0001) and at week 8 as determined by SiSBP (–15.35 [16.63] vs –2.30 [14.91] mm Hg; P < 0.0001). The fimasartan group exhibited more potent antihypertensive efficacy than the valsartan group both at week 4 (SiDBP, –9.96 [7.73] vs –6.53 [9.58] mm Hg [P = 0.0123]; SiSBP, –16.18 [14.4] vs –7.65 [12.89] mm Hg [P = 0.0002]) and at week 8 (SiDBP, –9.93 [8.86] vs –5.47 [8.96] mm Hg [P = 0.0021]; SiSBP, –15.35 [16.63] vs –7.49 [13.68] mm Hg [P = 0.0021]). Most treatment-emergent adverse events (TEAEs) were mild (89 of 95), and there were no serious TEAEs. The incidence of TEAEs was 19.1% in the fimasartan group, 22.6% in the placebo group, and 13.6% in the valsartan group, with no significant differences.Implications
Low-dose fimasartan (30 mg) was well tolerated during the study period with no significant TEAEs. Low-dose fimasartan had an effective blood pressure–lowering effect that was greater than that of 80-mg valsartan in patients with mild to moderate hypertension. ClinicalTrials.gov identifier: NCT01672476. 相似文献995.
Mucositis care in acute leukemia and non-Hodgkin lymphoma patients undergoing high-dose chemotherapy
José Manuel Martinez Dulcineia Pereira Sérgio Chacim Edgar Mesquita Inês Sousa Ângelo Martins Teresa Azevedo José Mário Mariz 《Supportive care in cancer》2014,22(9):2563-2569
Purpose
This study intends to provide new insights into the incidence and care of mucositis by the epidemiological characterization of patients with hematological malignancy treated at our institution. It also aims to understand the effectiveness of several treatments used.Methods
This is a longitudinal observational single-center study—convenience sample—which includes malignant hematologic inpatients submitted to high-dose CT from February to August 2012. We registered epidemiological data, diagnosis, oral mucositis daily questionnaire (OMDQ), World Health Organization (WHO) oral toxicity scale, and supportive medications used for mucositis.Results
We evaluated 30 patients who had 73 episodes of hospitalization, having recorded the development of mucositis in 21.9 % (n?=?16) episodes (22 patients with acute leukemia (AL) and 8 patients with non-Hodgkin lymphoma (NHL)). Grades 3–4 mucositis was reported in 4.1 % of the total episodes. The results of OMDQ showed some limitations in the quality of life, of patients with mucositis, related with the ability to eat and drink due to mouth pain (p?<?0.001). In patients with NHL and AL, neutropenia entails an increased risk of mucositis (p?<?0.001). Patients who did not initiate early prophylaxis with conservative measures developed mucositis earlier (p?<?0.05).Conclusions
The incidence of mucositis is high, being reported mainly in AL patients, with limitations in quality of life. Grade 4 neutropenia increases mucositis risk. Early prophylaxis with basic oral care may delay mucositis. Further studies are crucial to characterize mucositis epidemiology, physiopathology, and its management. 相似文献996.
Su-Hyuk Yim In Sun Kwon Dongkyun Hong Kyung Eun Jung Young Lee Young-Joon Seo Chong Won Choi 《ANNALS OF DERMATOLOGY》2021,33(2):147
BackgroundLongitudinal melanonychia (LM) is a common clinical finding. Most cases of LM are benign, and a wait-and-see approach is preferred in the management of this condition. Nevertheless, it is important for clinicians to distinguish subungual melanoma (SUM) from other benign LMs.ObjectiveTo evaluate the demographic and clinicopathologic characteristics of LM in the Korean population and to identify the predictor of SUM against other benign conditions.MethodsThis was a single-center retrospective cohort study including patients who underwent nail biopsy for LM from January 2000 to May 2019. To identify the predictor of SUM, receiver operating characteristic (ROC) analyses was performed.ResultsA total of 68 cases of biopsy-proven LM were included in the analysis. Among the 68 cases, 8 were SUM. In univariable analysis, patients diagnosed with SUM were older (p=0.035) and had a longer disease duration (p=0.004). They also showed multicolor pigmentation of LM (p=0.022), a larger width of LM (p<0.001), and associated nail plate dystrophy (p=0.010) than patients diagnosed with benign conditions. In multivariable logistic regression, width of LM showed statistical significance (odds ratio, 1.083; 95% confidence interval, 1.018~1.153). ROC analysis suggested that an LM width >28% of the whole nail was the predictor of SUM (area under the curve=0.883; p<0.001).ConclusionSUM has distinct demographic and clinical features. The width of LM can predict SUM against other benign LMs. 相似文献
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998.
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1000.
Sérgio Barra Rui Providência Francisca Caetano Inês Almeida Luís Paiva Paulo Dinis António Leit?o Marques 《World journal of cardiology》2013,5(6):196-206
AIM: To derive and validate a score for the prediction of mid-term bleeding events following discharge for myocardial infarction (MI).METHODS: One thousand and fifty patients admitted for MI and followed for 19.9 ± 6.7 mo were assigned to a derivation cohort. A new risk model, called BLEED-MI, was developed for predicting clinically significant bleeding events during follow-up (primary endpoint) and a composite endpoint of significant hemorrhage plus all-cause mortality (secondary endpoint), incorporating the following variables: age, diabetes mellitus, arterial hypertension, smoking habits, blood urea nitrogen, glomerular filtration rate and hemoglobin at admission, history of stroke, bleeding during hospitalization or previous major bleeding, heart failure during hospitalization and anti-thrombotic therapies prescribed at discharge. The BLEED-MI model was tested for calibration, accuracy and discrimination in the derivation sample and in a new, independent, validation cohort comprising 852 patients admitted at a later date.RESULTS: The BLEED-MI score showed good calibration in both derivation and validation samples (Hosmer-Lemeshow test P value 0.371 and 0.444, respectively) and high accuracy within each individual patient (Brier score 0.061 and 0.067, respectively). Its discriminative performance in predicting the primary outcome was relatively high (c-statistic of 0.753 ± 0.032 in the derivation cohort and 0.718 ± 0.033 in the validation sample). Incidence of primary/secondary endpoints increased progressively with increasing BLEED-MI scores. In the validation sample, a BLEED-MI score below 2 had a negative predictive value of 98.7% (152/154) for the occurrence of a clinically significant hemorrhagic episode during follow-up and for the composite endpoint of post-discharge hemorrhage plus all-cause mortality. An accurate prediction of bleeding events was shown independently of mortality, as BLEED-MI predicted bleeding with similar efficacy in patients who did not die during follow-up: Area Under the Curve 0.703, Hosmer-Lemeshow test P value 0.547, Brier score 0.060; low-risk (BLEED-MI score 0-3) event rate: 1.2%; intermediate risk (score 4-6) event rate: 5.6%; high risk (score ≥ 7) event rate: 12.5%.CONCLUSION: A new bedside prediction-scoring model for post-discharge mid-term bleeding has been derived and preliminarily validated. This is the first score designed to predict mid- term hemorrhagic risk in patients discharged following admission for acute MI. This model should be externally validated in larger cohorts of patients before its potential implementation. 相似文献