bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Expression of Aquaporin-2 Tagged with Photoconvertible Fluorescent Protein in mpkCCD Cells
Authors: Yip Kay-Pong , Cha Byeong J. , Tse Chung-Ming , Amin Mateus E. , Amin Jahanshah
Published: June 2015

Background: Vasopressin induced trafficking of aquaporin-2 (AQP2) containing vesicles has been studied in kidney cell lines using conventional fluorescent proteins as tags. However, trafficking of fluorescent tagged AQP2, which resembles the vectorial translocation of native AQP2 from cytoplasm to apical membrane has not been demonstrated at real time. Using a photoconvertible fluorescent protein tag on AQP2 might allow the simultaneous tracking of two separate populations of AQP2 vesicle after subcellular local photoconversion. Methods: A spacer was used to link a photoconvertible fluorescent protein (mEos2) to the amino-terminus of AQP2. The DNA constructs were expressed in mpkCCD cells. The trafficking of chimeric protein was visualized with high speed confocal microscopy in 4 dimensions. Results: Chimeric AQP2 expressed in mpkCCD cell conferred osmotic water permeability to the cells. Subcellular photoconversion with a 405 nm laser pulse converted green chimeras to red chimeras locally. Forskolin stimulation triggered chimeric AQP2 to translocate from acidic organelles to apical plasma membrane. By serendipity, the rate of apical accumulation was found to increase when mEos2 was tagged to the carboxyl-terminus in at least one of the AQP2 molecules within the tetramer. Conclusion: Functional photoconvertible chimeric AQP2 was successfully expressed in mpkCCD cells, in which forskolin induced apical trafficking and accumulation of chimeric AQP2. The proof-of-concept to monitor two populations of AQP2 vesicle simultaneously was demonstrated.
Identification and Characterization of Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma Cell Lines
Authors: Pozzi Valentina , Sartini Davide , Rocchetti Romina , Santarelli Andrea , Rubini Corrado , Morganti Stefano , Giuliante Rachela , Calabrese Stefania , Di Ruscio Giulia , Orlando Fiorenza , Provinciali Mauro , Saccucci Franca , Muzio Lorenzo Lo , Emanuelli Monica
Published: June 2015

Background/Aims: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. Methods: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. Results: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Conclusion: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy.
Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms
Authors: Sommerfeld Annika , Reinehr Roland , Häussinger Dieter
Published: June 2015

Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC) can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC)-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP) signal with induction of the dual specificity mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1), which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4) and c-jun-NH2-terminal kinase (JNK) activation. Furthermore, TUDC induced a protein kinase A (PKA)-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp)-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.
NBM-T-BMX-OS01, an Osthole Derivative, Sensitizes Human Lung Cancer A549 Cells to Cisplatin through AMPK-Dependent Inhibition of ERK and Akt Pathway
Authors: Chen Tian-Jun , Zhou Yue-Fei , Ning Jie-Juan , Yang Tian , Ren Hui , Li Yang , Zhang Shuo , Chen Ming-Wei
Published: June 2015

Background: Drug combination therapies using cisplatin and natural products are common practice in the treatment of human lung cancer. Osthole is a natural compound extracted from a number of medicinal plants and has been shown to exert strong anticancer activities with low toxicity. Methods: In the present study, NBM-T-BMX-OS01 (BMX), derived from the semi-synthesis of osthole, was evaluated in cisplatin treated A549 cells to investigate its effect on cisplatin resistance in human lung cancer. The anticancer effect of BMX were measured by cell viablity‚ colony formation‚ TUNEL staining‚ flow cytometry and cell cycle assay. The fluorescence staining was performed to detect intracellular and mitochondrial reactive oxygen species (ROS) generation. Western blot analysis, antagonists pretreatment and small interfering RNA (siRNA) transfection were used to determine the potential mechanism. Results: It was found that, in comparison with single cisplatin treatment, the combination of BMX and cisplatin resulted in greater efficacy in inhibition of proliferation and colony formation, apoptosis induction and cell cycle arrest. The results of fluorescence staining showed that the combination effect of BMX and cisplatin was due to oxidative stress induced by mitochondrial ROS generation. In addition, BMX significantly attenuated the phosphorylation of ERK and Akt, two important pro-survival kinases. In contrast, BMX inhibited the activation of AMPK, and knockdown of AMPK using specific siRNA partially reversed BMX-induced inhibition of ERK and Akt, as well as its synthetic effects on cisplatin induced anticancer activity in A549 cells. Conclusion: Taken together, this study provides that BMX might modulate cisplatin resistance through AMPK-ERK and AMPK-Akt pathways. These results also support the role of BMX as a potential drug candidate for use in combination with cisplatin in the treatment of human lung cancer.
Tubercular Meningitis and Lymphadenitis Mimicking a Relapse of Burkitt's Lymphoma on 18F-FDG-PET/CT: A Case Report
Authors: El Omri Halima , Hascsi Zsolt , Taha Ruba , Szabados Lajos , El Sabah Hesham , Gamiel Amna , Al Hijji Ibrahim
Published: June 2015

Tuberculosis (TB) can present with various forms and can occasionally be mistaken for malignancy. Hereby, we report a 53-year-old man diagnosed and treated for Burkitt's lymphoma in 2009 who achieved a complete remission confirmed by a computed tomography (CT) scan. During the follow-up 2 years later, he complained of left hip pain that warranted investigation with magnetic resonance imaging and whole-body 18F-fludeoxyglucose-positron emission tomography (FDG-PET)/CT which showed a benign lesion in the left hip associated with multiple lymph nodes in the chest and abdomen not amenable for biopsy. A follow-up PET/CT scan a few months later showed intense tracer uptake in the lymph nodes with size progression and appearance of new lymph nodes suspicious of lymphoma relapse. The patient was asymptomatic, and all investigations including viral and connective tissue disease studies were negative. Also the tuberculin skin test and QuantiFERON were negative. Lymph node biopsy was planned; however, the patient presented a few days earlier with fever, headache and photophobia. Cerebrospinal fluid (CSF) examination confirmed meningitis with lymphocytic pleocytosis and elevated protein. The CSF Gram stain, culture, viral and acid-fast bacilli were negative. CSF flow cytometry and cytopathology confirmed polyclonal lymphocytosis and suggested reactive causes. CSF TB culture grew Mycobacterium tuberculosis. Mediastinal lymph node biopsy also confirmed TB lymphadenitis. Four antituberculosis drugs were started. One year later, a PET/CT scan showed regression of all the involved lymph nodes. This case highlights the importance of excluding TB in patients with suspected malignancy, especially if they belong to endemic regions, and the increasing role of 18F-FDG-PET/CT in the early detection of extrapulmonary TB.
Blaschko Linear Enamel Defects - A Marker for Focal Dermal Hypoplasia: Case Report of Focal Dermal Hypoplasia
Authors: Gysin Stefan , Itin Peter
Published: June 2015

Focal dermal hypoplasia (FDH) is a rare genetic skin disorder. The inheritance of FDH or Goltz-Gorlin syndrome is X-linked dominant and the disease is associated with a PORCN gene mutation. This gene plays a key role in the Wnt pathway, which has an impact on embryonic development. Every tissue derived from meso- and ectoderm can be affected. Patients suffer from cutaneous, ocular, osseous, oral and dental defects. The skin and dental alterations manifest along the Blaschko lines. We present a woman (born in 1962) suffering from FDH with congenital skin changes and Blaschko linear enamel defects. Typical symptoms (e.g. fat herniations, scoliosis, syndactyly, microphthalmia, caries and alopecia) plus vertical grooving of all teeth gave a first indication. Molecular genetic testing confirmed the definitive diagnosis of FDH. We hypothesize that, in the context of typical skin changes, visible Blaschko lines on the teeth in the form of vertical grooves are almost pathognomonic for FDH.
Predictors of Clinical Progression of Subjective Memory Impairment in Elderly Subjects: Data from the Clinical Research Centers for Dementia of South Korea (CREDOS)
Authors: Hong Yun Jeong , Yoon Bora , Shim Yong S. , Kim Seon-Ok , Kim Hwa Jung , Choi Seong Hye , Jeong Jee Hyang , Yoon Soo Jin , Yang Dong Won , Lee Jae-Hong
Published: June 2015

Background/Aims: The aims of this study were to determine baseline factors related to the progression of subjective memory impairment (SMI) in elderly subjects and to develop a new modeling scale to predict progression. Methods: Elderly subjects with SMI were recruited from the nationwide Clinical Research Centers for Dementia of South Korea (CREDOS) multicenter cohort and divided into two groups: (1) progressed to mild cognitive impairment or Alzheimer's disease or (2) stable without progression. Baseline clinical characteristics were compared between the groups, and the most relevant predictors of progression were assessed. A new modeling scale combining the predictors was developed. Results: In total, 129 subjects with SMI were analyzed. The follow-up duration was 0.5-4.7 years, and the median time to event was 3.64 years. The progressing group (n = 29) differed from the stable group (n = 100) in terms of baseline age, apolipoprotein E4 (APOE4) status, and some cognitive domains. Older age, a lower Mini-Mental State Examination recall score, APOE4 carrier, and a lower verbal delayed recall score were the most relevant predictors of progression, and a new modeling scale with these 4 predictors provided a better explanation of progression. Conclusion: SMI subjects with a higher risk of progression can be identified using a new modeling scale and might need further evaluations and more frequent follow-up.
Hypermetabolism in the Initial Phase of Intensive Care Is Related to a Poor Outcome in Severe Sepsis Patients
Authors: Wu Chao , Wang Xinying , Yu Wenkui , Tian Feng , Liu Sitong , Li Pei , Li Jieshou , Li Ning
Published: June 2015

Objective: To assess the incidence of hypermetabolism, defined as high resting energy expenditure, in severe sepsis ICU patients, and evaluate the suitability of excessive resting energy expenditure (REE) as a risk factor of their clinical outcome. Methods: In a single-center, prospective, six-month observational study in China, the measured REE (MREE) was estimated daily using indirect calorimetry (IC) for the first 5 days of ICU admission. The predicted REE (PREE) was determined using the Harris-Benedict equation. ICU severity criteria (APACHE II and SOFA scores), baseline and health characteristics, and laboratory test results, were compared between the hyper-metabolic (MREE/PREE ratio ≥1.3) and the normometabolic (MREE/PREE ratio <1.3) groups, and between the survivor and non-survivor groups, classified according to 28-day mortality. Results: Of the 62 included ICU patients (age, 57.1 ± 19.5 years), 34 patients (55%) were hypermetabolic. The 28-day mortality rate in the hypermetabolic and normometabolic groups was 35 and 18%, respectively (p < 0.001). The MREE/PREE ratio and C-reactive protein (CRP) plasma concentration were significantly higher in non-survivors than survivors (p = 0.017), and were significantly (p < 0.05) associated with 28-day mortality (ORMREE/ PREE = 1.018, 95% CI, 1.010-2.544, p = 0.031 and ORCRP = 1.010, 95% CI, 1.005-2.173, p = 0.025, respectively). Conclusion: In critical sepsis patients admitted to ICU, the MREE/PREE ratio may be a valuable evaluation index of the clinical outcome.
Heterogeneous Bovine Acellular Dermal Matrix for Mucosal Repair in Reconstructive Surgery for Laryngeal and Hypopharyngeal Carcinoma
Authors: He Jian , Tian Yongquan , Wu Ping , Liao Lingfeng , Quan Huatao , Kang Jing , Tang Yaoyun
Published: June 2015

Background: We performed this study to explore the clinical effects of a heterogeneous bovine acellular dermal matrix (ADM) used for repairing mucosal defects in reconstructive surgery following resection for laryngeal and hypopharyngeal carcinoma. Patients and Methods: A summary analysis was carried out on the surgical data of 93 patients who underwent reconstructive surgery using a heterogeneous bovine ADM following resection of laryngeal and hypopharyngeal carcinoma. The patients underwent an electronic laryngoscope review. Results: After 3-6 months, the repaired mucosa had replaced the mucosal defects in 88 patients who had undergone stage I reconstruction, recovering local function. Due to infection, 3 patients had a laryngeal fistula and 2 patients had a pharyngeal fistula; the fistula incidence rate was 5.4%. 86 patients underwent successful tracheal extubation (extubation rate, 92.5%). The duration from tracheotomy to extubation was 8-31 days; the average duration was 10.4 days. Conclusion: The heterogeneous bovine ADM is a new, safe, and effective material for reconstructive surgery. In patients with large mucosal defects, it avoids the trauma caused by flap repair.
Intestinal Endometriosis: Mimicker of Inflammatory Bowel Disease?
Authors: Guadagno Antonio , Grillo Federica , Vellone Valerio Gaetano , Ferrero Simone , Fasoli Alberto , Fiocca Roberto , Mastracci Luca
Published: June 2015

Background/Aims: Endometriosis of the intestinal tract (IE) is thought to mimic inflammatory bowel disease (IBD) both clinically and pathologically but robust data on a large unselected series are missing. Diagnostic problems arise both at colonoscopy as well as on resection specimens for IE when IBD-like features are encountered. The aim was to establish the frequency of IBD-like histology in IE and which type of histological lesions are shared by these two entities. Methods: One hundred consecutive, unselected cases of surgically resected IE were collected and clinical features and histopathology reviewed and reevaluated. Results: Seventy-five surgical specimens showed no histological alterations except for endometriosis foci. Twenty-two cases showed focal architectural alterations in the absence of significant inflammation. Three cases showed marked inflammatory and architectural mucosal changes making a differential diagnosis with IBD particularly challenging. On follow-up, however, these patients remained symptom-free and with no need for anti-inflammatory therapy after surgical resection of IE. Conclusions: Diagnostic problems may arise in women who have IBD-like symptoms and histology at colonoscopy but who lack a known diagnosis of endometriosis. Clinicians must be aware that the diagnosis of IBD in patients with IE should be reevaluated over time.
Diffuse Dermal Angiomatosis: A Clue to the Diagnosis of Atherosclerotic Vascular Disease
Authors: Sriphojanart Tueboon , Vachiramon Vasanop
Published: June 2015

Diffuse dermal angiomatosis (DDA) is a benign, acquired, reactive vascular proliferation. DDA is clinically characterized by painful purpuric plaque with central ulceration. The histopathologic hallmark is diffuse proliferation of endothelial cells that are arranged interstitially between collagen bundles of the reticular dermis. DDA has been reported in association with peripheral atherosclerotic disease, arteriovenous fistula and heavy smoking. We report the case of a 49-year-old Asian male with DDA who presented with a painful stellate-shaped purpuric patch on the right thigh. Histopathologic examination showed proliferation of CD34-positive spindle cells in the dermis. Our patient underwent vascular bypass surgery along with tight control of cardiovascular risk factors, which yielded successful results.
Intracranial Cerebral Artery Dissection of Anterior Circulation as a Cause of Convexity Subarachnoid Hemorrhage
Authors: Fukuma Kazuki , Ihara Masafumi , Tanaka Tomotaka , Morita Yoshiaki , Toyoda Kazunori , Nagatsuka Kazuyuki
Published: June 2015

Background: Convexity subarachnoid hemorrhage (cSAH), defined as intrasulcal bleeding restricted to hemispheric convexities, has several etiologies: reversible cerebral vasoconstriction syndrome, cerebral amyloid angiopathy, and internal carotid artery (ICA) stenosis or occlusion. However, it remains unknown whether cerebral artery dissection causes cSAH. Methods: We retrospectively investigated patients admitted to our hospital between 2005 and 2013 with ischemic stroke or transient ischemic attack caused by cerebral artery dissection. Cerebral artery dissection was diagnosed by cervical or cerebral magnetic resonance imaging (MRI) or computed tomography (CT) showing a wall hematoma. CT angiography, ultrasonography, or intra-arterial digital-subtraction angiography detected cerebral artery dissection if a double lumen, string sign, intimal flap, or dissecting aneurysm was observed at a nonbifurcation site. We used CT or MRI to detect cSAH, which was defined as blood collection restricted to one or few cerebral sulci without extending to the basal cisterns, ventricles, or Sylvian and interhemispheric fissures. Demographic, neuroimaging, treatment, and prognostic data were collected. Results: In total, 82 patients were diagnosed with ischemic stroke caused by cerebral artery dissection. The following arteries were affected: the ICA (9 patients), anterior cerebral artery (ACA; 12 patients), middle cerebral artery (MCA; 12 patients), vertebral artery (37 patients), basilar artery (5 patients), posterior cerebral artery (2 patients), and posterior inferior cerebellar artery (4 patients). In addition, 1 patient presented with simultaneous dissection in both the vertebral and internal carotid arteries, and 6 patients (7%) presented with cSAH (3 men and 3 women, age 39-67 years). The MCA was dissected in four cases and the ACA in two cases, with cSAH frequencies of 33 (4 of 12) and 17% (2 of 12), respectively, in those vessels. Artery dissection in the vertebrobasilar artery system was not responsible for cSAH (0 of 48). In all the MCA dissection cases, cSAH occurred in the arterial border zone between the ACA and MCA territories. Although 2 patients showed early reperfusion with temporary cSAH enlargement, cSAH was self-limiting. Antithrombotic treatment did not complicate the clinical course when used in 4 patients during acute or subacute phases. All patients achieved a 3-month poststroke modified Rankin Scale of 0-2. Conclusion: Our data suggest that cSAH caused by intracranial cerebral artery dissection is not rare. Further investigations are needed to elucidate the precise mechanism underlying cSAH in cerebral artery dissection.
Utilization of Signal-to-Cutoff Ratio of Hepatitis C Virus Antibody Assay in Predicting HCV Viremia among Hemodialysis Patients
Authors: Kao Hao-Hsi , Chen Kuo-Su , Lin Chih-Lang , Chang Jia-Jang , Lee Chien-Hung
Published: June 2015

Background: Hepatitis C virus (HCV) infection is a common cause of acute and chronic hepatitis among the hemodialysis population. To prevent cross infection between hemodialysis patients during the hemodialysis procedure, routine screening of anti-HCV antibody is recommended. However, a reactive anti-HCV EIA test is not equal to active HCV infection. An expensive RT-PCR study is required to confirm HCV viremia. This will significantly increase the cost burden because payment for each hemodialysis treatment is very low in Taiwan. Thus, it is useful to identify parameters that could predict HCV viremia among anti-HCV-reactive patients. In this study, we examined the usefulness of signal-to-cut (S/CO) ratio of anti-HCV antibody in discriminating HCV viremia from non-viremia among the anti-HCV-reactive hemodialysis population. Materials and Methods: In a cross-sectional measurement of anti-HCV antibody among 369 chronic hemodialysis patients, 44 showed reactive and 9 grey zone reaction for anti-HCV. These 53 patients underwent further blood tests for the measurement of AST, ALT and HCV RNA (by RT-PCR). The results of RT-PCR were used as a dependent variable. Then, S/CO ratios of anti-HCV, serum AST, ALT levels, age and duration of hemodialysis were used as independent variables to undergo ROC curve and logistic regression analysis. Results: Thirty-six of the 53 reactive and grey zone patients were positive for HCV RNA in the RT-PCR study. Patients who were positive for HCV RNA had a higher S/CO ratio (p < 0.01), higher AST and ALT levels (p < 0.01), and longer duration on hemodialysis (p < 0.05) than those negative for HCV RNA. Logistic regression revealed that only S/CO ratio was a significant predictor for HCV viremia (p = 0.004). ROC curve analysis showed that S/CO ratio had a highest area under curve (0.967, p < 0.001), followed by ALT (0.826, p < 0.001), AST (0.778, p = 0.001), duration on hemodialysis (0.606, p = 0.215) and age (0.426, p = 0.386) in discriminating HCV viremia from non-viremia. Using a cutoff S/CO ratio of 65, we can confirm HCV viremia with a diagnostic specificity of 100%, sensitivity of 80.1% and positive predictive value of 100%. Conclusion: S/CO ratio is a useful indicator in predicting HCV viremia among anti-HCV-reactive hemodialysis patients. Patients with an S/CO ratio >65 can be regarded as those with active HCV infection. Alternatively, patients with reactive anti-HCV but with an S/CO ratio <65 should receive further RT-PCR test.
Septic Cerebral Embolisation in Fulminant Mitral Valve Infective Endocarditis
Authors: Doolub Gemina
Published: June 2015

A 37-year-old male with known intravenous drug use was admitted with an acute onset of worsening confusion and speech impairment. His vitals and biochemical profile demonstrated severe sepsis, with a brain CT showing several lesions suspicious for cerebral emboli. He then went on to have a bedside transthoracic echocardiogram that was positive for vegetation on the mitral valve, with associated severe mitral regurgitation. Unfortunately, before he was stable enough to be transferred for valve surgery, he suffered an episode of acute pulmonary oedema requiring intubation and ventilation on intensive care unit.
Hypokalemia Associated with Colonic Pseudo-Obstruction (Ogilvie's Syndrome)
Authors: Sunnoqrot Naseem , Reilly Robert F.
Published: June 2015

We report a case of hypokalemia resulting from colonic pseudo-obstruction or Ogilvie's syndrome. Colonic pseudo-obstruction is characterized by profuse watery diarrhea that has a low sodium and high potassium concentration. It is seen in a variety of medical and surgical conditions, but its exact cause remains unknown. It is thought to result from an imbalance of sympathetic and parasympathetic input in the distal colon. The diarrhea is secretory and driven by potassium secretion rather than the inhibition of sodium reabsorption or chloride secretion, which are the most common pathophysiologic mechanisms of secretory diarrhea. Affected patients often lose >100 mmol of potassium daily. Colonic pseudo-obstruction is associated with a dramatic upregulation of the maxiK or BK potassium channel. This channel plays a prominent role in flow-mediated potassium secretion in the connecting tubule and collecting duct and is also upregulated in the distal colon in patients with advanced chronic kidney disease and end-stage renal disease. In vitro studies show that the channel is regulated by catecholamine binding to the β receptor and cyclic AMP upregulation, somatostatin and aldosterone, insights that can be used to help guide pharmacologic therapy. Nephrologists should be aware of colonic pseudo-obstruction as a cause of extrarenal potassium loss.
Helicobacter suis-Infected Nodular Gastritis and a Review of Diagnostic Sensitivity for Helicobacter heilmannii-Like Organisms
Authors: Goji Shigeki , Tamura Yasuhiro , Sasaki Makoto , Nakamura Masahiko , Matsui Hidenori , Yamagata Murayama Somay , Ebi Masahide , Ogasawara Naotaka , Funaki Yasushi , Kasugai Kunio
Published: June 2015

Helicobacter heilmannii-like organisms (HHLOs) are associated with mucosa-associated lymphoid tissue lymphoma and peptic ulcer. However, the sensitivity of diagnostic tests for HHLOs, such as rapid urease test (RUT), urea breath test (UBT) and blood antibody, is not high. Tightly coiled spiral microorganisms were found in the gastric mucosal biopsy specimen of a 48-year-old asymptomatic woman. Her findings were positive for RUT and UBT, but negative for blood antibody and stool antigen against H. pylori. A 7-day course of esomeprazole, amoxicillin and clarithromycin was administered, resulting in the successful eradication of the HHLOs. Analysis of the 16S rRNA and urease genes suggested a diagnosis of the HHLO H. suis. The sensitivity results of RUT, UBT, culture, blood antibody, immunohistochemistry and stool antigen were 40.0, 14.8, 0, 23.1, 40.0 and 0%, respectively. We report asymptomatic nodular gastritis due to an HHLO. Histological techniques, most likely with smears, are expected to be the most effective method for diagnosing infections by HHLOs, and genetic diagnosis by polymerase chain reaction can be very useful to identify the species of HHLOs.
Case of Small Vessel Disease Associated with COL4A1 Mutations following Trauma
Authors: Plancher Joao McONeil , Hufnagel Robert B. , Vagal Achala , Peariso Katrina , Saal Howard M. , Broderick Joseph P.
Published: June 2015

With this case report, we would like to heighten the awareness of clinicians about COL4A1 as a single-gene disorder causing cerebral small vessel disease and describe a previously unreported pathogenic missense substitution in COL4A1 (p.Gly990Val) and a new clinical presentation. We identified a heterozygous putatively pathogenic mutation of COL4A1 in a 50-year-old female with a history of congenital cataracts and glaucoma who presented with multiple diffusion-positive infarcts and areas of contrast enhancement following mild head trauma. We believe that this presentation of multiple areas of acute brain and vascular injury in the setting of mild head trauma is a new manifestation of this genetic disorder. Imaging findings of multiple acute infarcts and regions of contrast enhancement with associated asymptomatic old deep microhemorrhages and leukomalacia in adults after head trauma should raise a high suspicion for a COL4A1 genetic disorder. Radiographic patterns of significant leukoaraiosis and deep microhemorrhages can also be seen in patients with long-standing vasculopathy associated with hypertension, which our patient lacked. Our findings demonstrate the utility of genetic screening for COL4A1 mutations in young patients who have small vessel vasculopathy on brain imaging but who do not have significant cardiovascular risk factors.
Renal Phospholipase A2 Receptor in Hepatitis B Virus-Associated Membranous Nephropathy
Authors: Xie Qionghong , Li Yan , Xue Jun , Xiong Zuquan , Wang Liang , Sun Zhuxing , Ren Yueheng , Zhu Xiaoye , Hao Chuan-Ming
Published: June 2015

Objective: This study examined the expression of renal phospholipase A2 receptor (PLA2R) in idiopathic and secondary membranous nephropathy (MN). Methods: Patients with biopsy-proven MN and non-MN were enrolled. Renal PLA2R was examined using an anti-PLA2R antibody (anti-PLA2R-Ab), and circulating PLA2R-Ab was detected by indirect immunofluorescence. Results: Renal PLA2R was detected along the capillary loop in 84% patients with idiopathic MN but not in those with any other primary glomerulonephritis. Only 1 of 38 patients with class V lupus nephritis showed renal PLA2R positive. In hepatitis B virus-associated MN (HBV-MN), 64% showed renal PLA2R positive, and PLA2R overlapped with HBsAg along the capillary loop. In addition, renal PLA2R positivity was closely associated with serum PLA2R-Ab. Renal PLA2R positive was present in all the patients with serum PLA2R-Ab positive and in 53% of patients with serum PLA2R-Ab negative. However, in patients with renal PLA2R negative, serum PLA2R-Ab was all negative. Conclusion: Renal biopsy PLA2R positivity was common in idiopathic MN and HBV-MN but rare in lupus-associated MN, and it was closely associated with serum PLA2R-Ab production. Further studies examining the association between PLA2R and HBV-MN may shed light on the mechanism of idiopathic MN or HBV-MN.
Short Door-to-Needle Times in Acute Ischemic Stroke and Prospective Identification of Its Delaying Factors
Authors: Van Schaik Sander M. , Scott Saskia , de Lau Lonneke M.L. , Van den Berg-Vos Renske M. , Kruyt Nyika D.
Published: June 2015

Background: The clinical benefit of intravenous thrombolysis (IVT) in acute ischemic stroke is time dependent. Several studies report a short median door-to-needle time (DNT; 20 min), mainly in large tertiary referral hospitals equipped with a level 1 emergency department, a dedicated stroke team available 24/7, and on-site neuroimaging facilities. Meanwhile, in daily practice, the majority of stroke patients are admitted to secondary care hospitals, and in practice, even the generous benchmark of the American Heart Association (a DNT of 60 min in >80% of the cases) is met for a minority of patients treated with IVT. The first objective of our study was to investigate if, in a secondary care teaching hospital rather than a tertiary referral hospital, similar short DNTs can be accomplished with an optimized IVT protocol. Our second objective was to prospectively identify factors that delay the DNT in this setting. Methods: A multicenter, consecutive cohort study of patients treated with IVT in one of two secondary care teaching hospitals. In both hospitals, data of consecutive stroke patients as well as median DNTs and factors delaying this were prospectively assessed for each patient. Multivariable logistic regression analysis was used to evaluate associations between patient-related and logistic factors with a delayed (i.e. exceeding 30 min) DNT. Results: In total, 1,756 patients were admitted for ischemic stroke during the study period. Out of these, 334 (19.0%) patients were treated with IVT. The median DNT was 25 min (interquartile range: 20-35). A total of 71% (n = 238) had a DNT below 30 min. In 63% of the patients treated with IVT the DNT was delayed by at least one factor. Patients without any delaying factor had a 10 min shorter median DNT compared to patients with at least one delaying factor (p < 0.001). The following factors were independently associated with a delayed DNT: uncertainty about symptom onset, uncontrolled blood pressure, fluctuating neurological deficit, other treatment before IVT, uncertainty about (anti-)coagulation status, other patient-related factors, and incorrect triage. Conclusions: Short median DNTs can also be accomplished in secondary care. Despite the short DNTs, several delaying factors were identified that could direct future improvement measures. This study supports the view that as a performance measure, the current DNT targets are no longer ambitious enough and it adds to the knowledge of factors delaying the DNT.
CYP3A4*1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients
Authors: Yuan Jing-Jing , Hou Jun-Kai , Zhang Wei , Chang Yan-Zi , Li Zhi-Song , Wang Zong-Yu , Du Ying-Ying , Ma Xiao-Jing , Zhang Li-Rong , Kan Quan-Cheng , Candiotti Keith A.
Published: June 2015

Purpose: This study aimed to investigate whether CYP3A4*1G genetic polymorphism influences the metabolism of fentanyl in human liver microsomes in Chinese patients. Methods: The human liver microsomes were obtained from 88 hepatobiliary surgery patients who accepted liver resection surgery in this study. A normal liver sample (confirmed by the Department of Pathology) was taken from the outer edge of the resected tissue. The metabolism of fentanyl in human liver microsomes was studied. The concentration of fentanyl was measured by high performance liquid chromatography. The CYP3A4*1G variant allele was genotyped using the PCR restriction fragment length polymorphism method. Results: The frequency of the CYP3A4*1G variant allele was 0.188 in the 88 Chinese patients who had received hepatobiliary surgery. The metabolic rate of fentanyl in patients homozygous for the *1G/*1G variant (0.85 ± 0.37) was significantly lower than that in patients bearing the wild-type allele *1/*1 (1.89 ± 0.58) or in patients heterozygous for the *1/*1G variant (1.82 ± 0.65; p < 0.05). There were no gender-related differences in the metabolic rate of fentanyl (p > 0.05) nor was there any correlation between age and metabolic rate of fentanyl (p > 0.05). Results from different hepatobiliary diseases showed no significant difference in the metabolic rate of fentanyl (p > 0.05). The difference of CYP3A4 mRNA among different CYP3A4*1G variant alleles was significant (p < 0.05). There was positive correlation between CYP3A4 mRNA and metabolic rate of fentanyl (p < 0.01). Conclusions:CYP3A4*1G genetic polymorphism decreases the metabolism of fentanyl. There is a positive correlation between CYP3A4 mRNA level and metabolism of fentanyl.
Hepatosplenomegaly Associated with Transient Abnormal Myelopoiesis in Down Syndrome: An Autopsy Case of a Stillborn Fetus
Authors: Yuki Michiko , Emoto Yuko , Kinoshita Yuichi , Yoshizawa Katsuhiko , Yuri Takashi , Tsubura Airo
Published: June 2015

A 38-year-old primiparous mother (gravida 1, para 0) at 27 weeks and 6 days' gestation reported that fetal movements had been absent for 6 days. All serological markers for infection were negative. Chorionic villus sampling at stillbirth delivery revealed trisomy 21 (47, XX, +21), indicative of Down syndrome. The macerated baby was female and weighed 1,290 g. There was no evidence of hydrops fetalis. Proliferating blast cells expressing megakaryoblastic/megakaryocytic antigen CD61 were mainly seen within the vessels, and some cells infiltrated outside of the vessels in almost all organs. Vessels of the umbilical cord and chorionic villi were filled with proliferating blast cells, but the blast cells were not apparent in the bone marrow. The diagnosis of transient abnormal myelopoiesis in Down syndrome was made. Hepatomegaly (64.5 g) was due to congestion and infiltration of CD61-positive blast cells within the vascular lumina and expanding outside the lumina accompanied by fibrotic change. The cause of death was attributed to liver insufficiency caused by liver fibrosis. An umbilical cord and chorionic villi examination may be helpful in the diagnosis of transient abnormal myelopoiesis when post-mortem examination is not permitted.
Bronchopulmonary Neuroendocrine Neoplasms and Their Precursor Lesions in Multiple Endocrine Neoplasia Type 1
Authors: Bartsch Detlef K. , Albers Max B. , Lopez Caroline L. , Apitzsch Jonas C. , Walthers Eduard M. , Fink Ludger , Fendrich Volker , Slater Emily P. , Waldmann Jens , Anlauf Martin
Published: June 2015

Objective: The prevalence and clinical behavior of bronchopulmonary neuroendocrine tumors (bNET) associated with multiple endocrine neoplasia type 1 (MEN1) are not well defined. This study aimed to determine the prevalence, potential precursor lesions and prognosis of bNET in patients with MEN1. Methods: A database of 75 prospectively collected MEN1 cases was retrospectively analyzed for bNET. Patient characteristics, imaging and treatment were evaluated. Resection specimens of operated patients were reassessed by two specialized pathologists. Available CT scans of the whole cohort were reviewed to determine the prevalence of bronchopulmonary nodules. Results: Five of the 75 MEN1 patients (6.6%; 2 male, 3 female) developed histologically confirmed bNET after a median follow-up of 134 months. The median age at diagnosis of bNET was 47 years (range 31-67), and all patients were asymptomatic. Four patients underwent anatomic lung resections with lymphadenectomy; the remaining patient with multiple lesions had only a wedge resection of the largest bNET. Tumor sizes ranged from 7 to 32 mm in diameter, and all bNET were well differentiated. Two patients had lymph node metastases. Two of 4 reevaluated resection specimens revealed multifocal bNET, and 3 specimens showed tumorlets (up to 3) associated with multifocal areas of a neuroendocrine cell hyperplasia within the subsegmental bronchi. One bNET-related death (1.3%) occurred during long-term follow-up. Review of the available CT scans of the patients without proven bNET revealed small bronchopulmonary lesions (≥3 mm) in 16 of 53 cases (30.2%). Conclusions: bNET in MEN1 might be more common than previously recognized. Their natural course seems to be rather benign. Multifocal tumorlets and multifocal neuroendocrine cell hyperplasia might represent their precursor lesions.
РОЗРОБКА СПЕКТРОФОТОМЕТРИЧНОЇ МЕТОДИКИ ВИЗНАЧЕННЯ ФЛАВОНОЇДІВ У КОМПЛЕКСНОМУ ЛІКАРСЬКОМУ ЗАСОБІ НА ОСНОВІ ЕКСТРАКТІВ ЦМИНУ ПІЩАНОГО, НАГІДОК, МОРКВИ ДИКОЇ ТА КУРКУМИ ДОВГОЇ
Authors: Смалюх О. Г.
Published: June 2015

розроблено спектрофотометричну методику кількісного визначення суми флавоноїдів у лікарському засобі на основі екстрактів цмину піщаного, нагідок, моркви дикої та куркуми довгої в перерахунку на ізосаліпурпузид. Проведено валідацію розробленної методики за такими характеристиками, як лінійність, правильність, прецизійність та робасність.
МОНІТОРИНГ ОСНОВНИХ ГРУП ПРЕПАРАТІВ ДЛЯ КОМПЛЕКСНОГО ЛІКУВАННЯ ГОСТРИХ РЕСПІРАТОРНИХ ВІРУСНИХ ЗАХВОРЮВАНЬ
Authors: Сятиня М. Л. , Глущенко О. М. , Каврайський Д. П.
Published: June 2015

проведено маркетингове дослідження асортименту лікарських засобів аптек КП «Фармація» міста Києва, які використовують для профілактики та лікування гострих респіраторних, в т.ч. вірусних, захворювань та гострих респіраторних вірусних інфекцій. Встановлено перелік основних препаратів, яким віддають перевагу споживачі та фармацевтичні фахівці.
ПІДХОДИ ЩОДО ФОРМУВАННЯ КОНКУРЕНТНОГО ПОТЕНЦІАЛУ ТОРГОВИХ МАРОК НА ПРИКЛАДІ ПРОТИВИРАЗКОВИХ ПРЕПАРАТІВ
Authors: Волкова А. В.
Published: June 2015

за результатами аналізу узагальнено основні підходи щодо визначення понять «конкурентоспроможність» та «конкурентний потенціал», а також систематизовано показники оцінки конкурентоспроможності товарів за соціальною, виробничою та маркетинговою складовими.Встановлено, що на формування конкурентного потенціалу торгових марок впливають раціональні та емоційні критерії, оцінка яких передбачає проведення комплексного маркетингового і фармакоекономічного аналізу лікарських препаратів. На прикладі торгових марок групи противиразкових препаратів обґрунтовано розроблену модель формування конкурентного потенціалу з урахуванням існуючого рівня розвитку та факторів впливу на формування перспективного потенціалу.
ДОСЛІДЖЕННЯ ГОСТРОЇ ТОКСИЧНОСТІ НОВОГО РОСЛИННОГО ЗАСОБУ КАПСУЛ «ФІТОВЕНОЛ»
Authors: Томашевська Ю. О.
Published: June 2015

адекватну фармакотерапію хронічної венозної хвороби можуть забезпечити препарати, які поряд з вираженим фармакологічним ефектом не виявляють негативного впливу при вживанні. Цим вимогам найбільш відповідають фітопрепарати. Саме тому метою даного дослідження стало вивчення гострої токсичності капсул «Фітовенол», до складу якого були введені плоди гіркокаштану лікарського, листя гамамелісу віргінського, плоди вівса посівного, плоди софори японської, трава золотушника звичайного, трава гадючника в’язолистого, трава буркуну лікарського.
ОПТИМІЗАЦІЯ ПРОВЕДЕННЯ ПРАКТИЧНИХ НАВИЧОК ІЗ МІКРОСКОПІЧНОГО АНАЛІЗУ ПРИ ВИВЧЕННІ ФАРМАКОГНОЗІЇ
Authors: Ковальська Н. П. , Михалюк О. Б.
Published: June 2015

у статті розглянуто спосіб оптимізації засвоєння студентами практичних навичок з мікроскопічного аналізу шляхом заохочення до проведення мікрохімічних реакцій на практичних заняттях з фармакогнозії, що сприяє формуванню високої професійної компетентності майбутніх спеціалістів.
ПОЕТАПНІСТЬ НАВЧАННЯ ЛІКАРІВ-ХІРУРГІВ НА КУРСАХ ЕНДОСКОПІЧНОЇ ХІРУРГІЇ В ТЕРНОПІЛЬСЬКОМУ ДЕРЖАВНОМУ МЕДИЧНОМУ УНІВЕРСИТЕТІ
Authors: Ковальчук О. Л. , Гнатюк М. С. , Шев'як П. І. , Сморщок Ю. С. , Кулянда І. С.
Published: June 2015

Стрімкий розвиток ендоскопічної хірургії зробив актуальним питання підготовки лікарів-хірургів. На циклі тематич-
ного вдосконалення в Тернопільському державномумедичному університеті використовується поетапне засвоєння прак-
тичних навичок і теоретичних знань. Хірурги оволодівають практичними навиками в тренажерному залі, під час навчальних операцій на тваринах і в клініці. Такий підхід дозволяє найбільш оптимально засвоїти навчальний матеріал.
МЕТОДОЛОГІЧНІ АСПЕКТИ ВИКЛАДАННЯ ЕЛЕКТИВНОГО КУРСУ “СУЧАСНІ ПРОБЛЕМИ МОЛЕКУЛЯРНОЇ БІОЛОГІЇ” У ВИЩІЙ МЕДИЧНІЙ ШКОЛІ
Authors: Шевчук Т. І. , Піскун Р. П. , Горбатюк С. М. , Ніколаєнко О. О.
Published: June 2015

У даній статті розглядаються особливості методології викладання елективного курсу “Сучасні проблеми молекулярної
біології” на кафедрі медичної біології. Досліджується процес отримання знань і умінь з молекулярної біології і вказуєть-
ся необхідність застосування сучасних методик викладання з метою удосконалення якості професійної підготовки май-
бутніх лікарів.
ДОСВІД ВИКЛАДАННЯ ІНОЗЕМНИМ СТУДЕНТАМ НА КАФЕДРІ ХІРУРГІЇ З АНЕСТЕЗІОЛОГІЄЮ № 2
Authors: Олійник О. В. , Вайда А. Р. , Господарський А. Я. , Костів С. Я. , Чепіль І. В. , Гнатів В. В. , Костів О. І.
Published: June 2015

Cтаття присвячена аналізу досвідунавчання іноземних студентів в ТДМУ. Описані основні методики, що застосовують-
ся в процесі навчання, роль самостійної підготовки.
ДЕЯКІ АСПЕКТИ КОНСУЛЬТАТИВНОЇ РОБОТИ, ЯКА ПРОВОДИТЬСЯ НА КАФЕДРІ НЕЙРОХІРУРГІЇ І НЕВРОЛОГІЇ ОДЕСЬКОГО ДЕРЖАВНОГО МЕДИЧНОГО УНІВЕРСИТЕТУ
Authors: Сон А. С. , Добровольський В. В. , Горанський Ю. І. , Стоянов О. М. , Добровольська Н. В.
Published: June 2015

У статті представлений аналіз методичних підходів проведення консультативної роботи співробітниками кафедри
нейрохірургії і неврології Одеського державного медичного університету та рекомендації щодо підвищення її якості.
ВЗАЄМОВІДНОСИНИ ЛІКАРЯ ТА ПАЦІЄНТА – ОСНОВА ЕФЕКТИВНОГО ЛІКУВАННЯ
Authors: Степанов Ю. М. , Кононов І. М. , Латфуліна А. В. , Шендрик Л. М.
Published: June 2015

В основі лікувального процесу лежить довіра між пацієнтом і медичним працівником. Цей процес включає доброзич-
ливість, конфіденційність, достатній час спілкування, доступність у викладі інформації, володіння навичками встанов-
лення контакту між лікарем і пацієнтом, вміння ведення бесіди з пацієнтом.
Impact of Freezing Time and Balloon Size on the Thermodynamics and Isolation Efficacy During Pulmonary Vein Isolation Using the Second Generation Cryoballoon
Authors: Takami Mitsuru , Lehmann H. Immo , Misiri Juna , Parker Kay D. , Sarmiento Ray I. , Johnson Susan B. , Packer Douglas L.
Published: June 2015

Background—

The differences in ablation characteristics of freezing time and balloon size using second generation cryoballoon are still unknown.

Methods and Results—

Twenty-six dogs underwent pulmonary vein (PV) isolation. Balloon and tissue temperatures (left atrial–PV junction, phrenic nerve, and internal esophagus) were monitored. The ablation duration was randomized to either 3 or 4 minutes, which did not show significant differences in temperature profiles, PV isolation success rate, complications, or histological changes. Twenty dogs underwent cryoablation using 28-mm cryoballoon, 6 dogs were done using the 23-mm cryoballoon. Positioning of the 23-mm cryoballoon was more distal in the PV, which resulted in better PV occlusion. Temperature profiles showed lower temperatures in the 23-mm cryoballoon than in the 28-mm cryoballoon (inner balloon, median [range]: −51.5 [−66.0 to −31.0] versus −43.0 [−64.0 to −26.0]°C,
P
<0.001; balloon surface: −43.0 [−60.0 to −15.8] versus −6.5 [−46.2 to 28.9]°C,
P
<0.001; left atrial–PV junction: −6.7 [−20.0 to 21.4] versus 15.8 [−14.4 to 35.1]°C,
P
<0.001), and trended toward a higher PV isolation success rate in the 23-mm cryoballoon. Histologically, deeper extensions of ablative lesions into the PV were seen with 23-mm cryoballoon, and larger ablative lesions were seen in the left atrial antrum using 28-mm cryoballoon.

Conclusions—

The efficacy of 3-minute ablation was not significantly different from 4-minute ablation in dogs. The 23-mm cryoballoon had a greater cooling effect than the 28-mm cryoballoon for small PVs, but showed narrower ablative lesions in the left atrial antrum.