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Wu M.-T.,Chang Gung Memorial Hospital Kaohsiung Medical Center | Pei S.-N.,Chang Gung University
Annals of Pharmacotherapy | Year: 2010

OBJECTIVE: To report a case of cephalosporin-induced factor V inhibitor development, an uncommon but potentially fatal condition characterized by severe hemorrhage. CASE SUMMARY: A 71-year-old Chinese man presented with factor V inhibitors after a 7-day cephradine course for a urinary tract infection, characterized by abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT), gross hematuria, upper gastrointestinal bleeding, and left groin hematoma. Systemic corticosteroid administration restored his factor V activity levels, PT, and aPTT to within normal limits, and hemorrhagic symptoms resolved. Three weeks after successful treatment of bleeding diathesis, he received another 8-day cephradine course for cellulitis. After another 4 weeks, he suffered from recurrent factor V inhibitors presented with abnormal PT, aPTT, and upper gastrointestinal bleeding. The patient eventually died due to hemorrhagic shock despite a second course of corticosteroids. DISCUSSION: Cephalosporins are known to cause coagulopathy via hypoprothrombinemia. Another pathway seldom mentioned in the literature is factor V inhibitor induction, which may result in factor V deficiency. In our patient, factor V deficiency due to inhibitors developed each time that the patient received repeated cephradine treatment. According to the Naranjo probability scale, the relation between the formation of factor V inhibitors and cephradine treatment was probable. CONCLUSIONS: Because cephalosporins are commonly used for their wide therapeutic index and few adverse effects, iatrogenic complications associated with these drugs may be neglected or underdiagnosed. On the basis of our patient's report, careful review of medical records to avoid reexposure to the offending drug cannot be overemphasized.

Chou C.K.,Chang Gung Memorial Hospital Kaohsiung Medical Center
The Journal of clinical endocrinology and metabolism | Year: 2013

Recent studies suggest that miR-146b deregulation in papillary thyroid carcinoma (PTC) was associated with advanced tumor characteristics. However, the influence of miR-146b expression on the prognosis of PTC remains unknown. We sought to correlate tumor expression levels of miR-146b with the prognosis of a previously reported PTC cohort and reveal the underlying mechanisms via a PTC cell line model. Expression levels of miR-146b were assessed via quantitative real-time PCR in 71 cases of PTC with distinct clinico-pathogenetic characteristics. All patients were classified into the disease-free or active disease group, based on their medical records at the end of the follow-up period. In vitro gain-of-function experiments were performed in a BCPAP human papillary thyroid cancer cell line model, which harbored the homozygous mutation of BRAF. BCPAP cells were transfected with a mimic-miR-146b and nonspecific microRNA (miRNA) control to determine whether miR-146b overexpression promotes cell migration and invasion. Proliferation assay, colony formation assay, and chemotherapy-induced apoptosis were also determined. Multivariate logistic regression analysis demonstrated advanced tumor stage, presence of cervical lymph node metastasis, and miR-146b expression were independent risk factors for poor prognosis in PTC. Patients with higher miR-146b expression levels had significantly poorer overall survival compared with those with lower miR-146b levels. The associated hazard ratio was 3.92 (95% confidence interval, 1.73-8.86, log-rank P < .05). Overexpression of miR-146b significantly increased cell migration and invasiveness. Furthermore, miR-146b also increased resistance to chemotherapy-induced apoptosis. Our results suggest that miR-146b is a novel prognostic factor of PTC. Furthermore, in vitro functional studies provided the mechanistic explanation for miR-146b in tumor aggressiveness. These results enhance understanding of the molecular mechanisms involved in tumor aggressiveness in PTC, provide new prognostic biomarkers, and ultimately offer new leads for developing therapies for PTC.

Abdou S.M.,National Heart Institute | Wu C.-J.,Chang Gung Memorial Hospital Kaohsiung Medical Center
Catheterization and Cardiovascular Interventions | Year: 2011

The optimal technique for bifurcation stenting of distal Left main (LM) lesions remains unestablished and controversial. Some techniques with superior stent apposition, such as culotte technique were supposed to be associated with lower rate of stent thrombosis. However, with culotte technique, the double-stent layer at the carina and in the proximal part of the bifurcation, may lead to difficult or improper rewiring of the side branch before final kissing balloon postdilatation (KBP). We describe a case of distal LM disease associated with distal left circumflex (LCX) and posterior descending artery stenosis. During LM stenting using culotte technique, improper rewiring of LCX before final KBP caused malapposition of the inner sent layer at the mid part of LM. Despite the optimal angiographic result, intravascular ultrasound (IVUS) was able to detect stent malapposition and guided further management to achieve complete stent apposition. The present case indicates that IVUS is an essential tool for LM stenting particularly when applying double stent strategy requiring final rewiring before KBP. Moreover, we suggest that some tools, such as Crusade and Venture catheters, can be used to ensure proper rewiring and hence, prevent subsequent stent malapposition, which may lead to catastrophic complications such as early and late LM stent thrombosis. © 2011 Wiley-Liss, Inc.

Hung Y.-C.,Chang Gung University | Hung Y.-C.,Chang Gung Memorial Hospital Kaohsiung Medical Center | Wang P.-W.,Chang Gung University | Pan T.-L.,Chang Gung University
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2010

Salvia miltiorrhiza is a Chinese herb widely used for cardiovascular disorder regimens, yet little is known about the cellular mechanisms that contribute to attenuated growth of smooth muscle cells (SMCs) under oxidative stress such as homocysteine (Hcy) treatment. As anticipated, a low dose (0.015 mg/mL) of S. miltiorrhiza aqueous extract (SMAE) significantly inhibited (> 60%) the growth of a rat smooth muscle cell line (A10) under Hcy stimulation and the intracellular reactive oxygen species (ROS) concentration obviously decreased after SMAE treatment in terms of reducing p47phox translocation and increasing catalase activity. Signaling profile suggests that SMAE inhibited Hcy-induced A10 cell growth via the PKC/MAPK-dependent pathway. Two-dimensional electrophoresis (2-DE) coupled with mass spectrometry revealed statistically significant changes in the intensity of 14 proteins in response to Hcy and Hcy/SMAE. Meanwhile, SMAE attenuated carbonyl-modification of specific cytoskeleton and chaperone proteins leading to cell type transformation. Moreover, a network analysis using MetaCore™ shed more light on the molecular basis associated with SMAE efficacy. SMAE exerts its protective effect through the scavenging of ROS and subsequent modulation of protein carbonylation to inhibit cell proliferation. These signature networks and functional proteomics highlighted herein may facilitate the evaluation of potential therapeutic targets and elucidate novel mechanisms through which protein functions can be regulated by the redox status. © 2010 Elsevier B.V. All rights reserved.

Chen C.-E.,Golden Hospital | Juhn R.-J.,Golden Hospital | Ko J.-Y.,Chang Gung Memorial Hospital Kaohsiung Medical Center | Ko J.-Y.,Chang Gung University
Archives of Orthopaedic and Trauma Surgery | Year: 2010

Introduction Various techniques have been reported for the treatment of middle-third clavicle (collar bone) fractures. This prospective study was conducted to evaluate the results of anterior-inferior plating using a 3.5-mm reconstruction plate for the treatment of middle-third clavicle fractures. Patients and methods Twenty-six patients with middlethird clavicle fractures were treated with anterior-inferior plating. The indications for surgery included complete displacement, severe comminution, and marked shortening of the clavicle (>2 cm). Results The mean time to union was 14 weeks (range 8-20 weeks). At the time of latest follow-up, all of the patients had returned to their pre-injury activity level. The plates were removed in ten patients after the fractures healed. No patients required plate removal due to implantrelated problems. Conclusion Anterior-inferior plating is an eVective treatment modality for middle-third clavicle fractures, with few complications and early return of shoulder function. The procedure provides stable fixation, avoids risk to vital structures below the clavicle, and is associated with a low rate of implant-prominence problems© Springer-Verlag 2009.

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