Imaging of the transplant liver.

PubMed

Babyn, Paul Sheppard

2010-04-01

As the number of patients with liver transplants continues to increase, radiologists need to be aware of the normal post-operative appearance of the different liver transplants currently performed along with the wide variety of complications encountered. The complications commonly affect the biliar and vascular systems and can include anastomotic bile leakage and biliary stenosis along with stenosis or obstruction of the hepatic artery, portal or hepatic veins and IVC. Other complications include parenchymal abnormalities such as hepatic infarction, organ rejection, localized collections and post transplant lymphoproliferative disorder. This article reviews and illustrates the role of imaging for pediatric transplantation including the role of interventional radiology.

[Pulmonary arteriovenous fistula with Rendu-Osler-Weber disease].

PubMed

Segawa, Masataka; Touge, Masayoshi; Seki, Kouji; Kusajima, Yoshinori; Saito, Katsuhiko

2012-09-01

A 36-year-old man was admitted to our hospital for examination of a nodular shadow in the left lung. Chest 3-dimensional computed tomography (3D-CT) revealed a pulmonary arteriovenous fistula (PAVF) of 21 mm in diameter composed of the feeding artery (A4) and the draining vein (V4) in the left S4. Abdominal enhanced CT revealed multiple hepatic arteriovenous fistula. Brain CT revealed a cavernous hemangioma in right occipital cerebrum. He had a family history, habitual epistaxis, and oral telangiectasia and was diagnosed as Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia:HHT). According to his family history, PAVF was likely to be a risk factor of brain infarction and abscess, and the wedge resection of the lingual lobe was performed to remove PAVF.

21 CFR 862.1440 - Lactate dehydrogenase test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Systems § 862.1440 Lactate dehydrogenase test system. (a) Identification. A lactate dehydrogenase test system is a device intended to measure the activity of the enzyme lactate dehydrogenase in serum. Lactate... hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction...

MRI-based in vivo assessment of early cerebral infarction in a mouse filament perforation model of subarachnoid hemorrhage.

PubMed

Sasaki, Kazumasu; Mutoh, Tatsushi; Nakamura, Kazuhiro; Kojima, Ikuho; Taki, Yasuyuki; Suarez, Jose Ignacio; Ishikawa, Tatsuya

2017-07-13

Experimental subarachnoid hemorrhage (SAH) by endovascular filament perforation method is used widely in mice, but it sometimes present acute cerebral infarctions with varied magnitude and anatomical location. This study aimed to determine the prevalence and location of the acute ischemic injury in this experimental model. Male C57BL/6 mice were subjected to SAH by endovascular perforation. Distribution of SAH was defined by T2*-weighted images within 1h after SAH. Prevalence and location of acute infarction were assessed by diffusion-weighted MR images on day 1 after the induction. Among 72 mice successfully acquired post-SAH MR images, 29 (40%) developed acute infarction. Location of the infarcts was classified into either single infarct (ipsilateral cortex, n=12; caudate putamen, n=3; hippocampus, n=1) or multiple lesions (cortex and caudate putamen, n=6; cortex and hippocampus, n=2; cortex, hippocampus and thalamus/hypothalamus, n=3; bilateral cortex, n=2). The mortality rate within 24h was significantly higher in mice with multiple infarcts than those with single lesion (30% versus 0%; P=0.03). Distribution of the ischemic lesion positively correlated with MRI-evidenced SAH grading (r 2 =0.31, P=0.0002). Experimental SAH immediately after the vessel perforation can induce acute cerebral infarction in varying vascular territories, resulting in increased mortality. The present model may in part, help researchers to interpret the mechanism of clinically-evidenced early multiple combined infarction. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of multiple infarctions and ICAS with outcomes of minor stroke and TIA.

PubMed

Pan, Yuesong; Meng, Xia; Jing, Jing; Li, Hao; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2017-03-14

To estimate the association of different patterns of infarction and intracranial arterial stenosis (ICAS) with the prognosis of acute minor ischemic stroke and TIA. We derived data from the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A total of 1,089 patients from 45 of 114 participating sites of the trial undergoing baseline MRI/angiography were included in this subgroup analysis. Patterns of infarction and ICAS were recorded for each individual. The primary efficacy outcome was an ischemic stroke at the 90-day follow-up. We assessed the associations between imaging patterns and prognosis of patients using multivariable Cox regression models. Among the 1,089 patients included in this subgroup analysis, 93 (8.5%) patients had a recurrent ischemic stroke at 90 days. Compared with those without infarction or ICAS, patients with single infarction with ICAS (11.9% vs 1.3%, hazard ratio [HR] 6.25, 95% confidence intervals [CIs] 1.40-27.86, p = 0.02) and single infarction without ICAS (6.8% vs 1.3%, HR 4.65, 95% CI 1.05-20.64, p = 0.04) were all associated with an increased risk of ischemic stroke at 90 days. Patients with both multiple infarctions and ICAS were associated with approximately 13-fold risk of ischemic stroke at 90 days (18.0% vs 1.3%, HR 13.14, 95% CI 2.96-58.36, p < 0.001). The presence of multiple infarctions and ICAS were both associated with an increased risk of 90-day ischemic stroke in patients with minor stroke or TIA, while the presence of both imaging features had a combined effect. NCT00979589. © 2017 American Academy of Neurology.

Trends in myocardial infarction rates and case fatality by anatomical location in four United States communities, 1987 to 2008 (from the Atherosclerosis Risk in Communities Study).

PubMed

Newman, Jonathan D; Shimbo, Daichi; Baggett, Chris; Liu, Xiaoxi; Crow, Richard; Abraham, Joellyn M; Loehr, Laura R; Wruck, Lisa M; Folsom, Aaron R; Rosamond, Wayne D

2013-12-01

Although the incidence of and mortality after ST-segment elevation myocardial infarction (STEMI) is decreasing, time trends in anatomical location of STEMI and associated short-term prognosis have not been examined in a population-based community study. We determined 22-year trends in age- and race-adjusted gender-specific incidences and 28-day case fatality of hospitalized STEMI by anatomic infarct location among a stratified random sample of 35- to 74-year-old residents of 4 communities in the Atherosclerosis Risk in Communities study. STEMI infarct location was assessed by 12-lead electrocardiograms from the hospital record and was coded as anterior, inferior, lateral, and multilocation STEMIs using the Minnesota code. From 1987 to 2008, a total of 4,845 patients had an incident STEMI; 37.2% were inferior STEMI, 32.8% were anterior, 16.8% occurred in multiple infarct locations, and 13.2% were lateral STEMI. For inferior, anterior, and lateral STEMIs in both men and women, significant decreases were observed in the age-adjusted annual incidence and the associated 28-day case fatality. In contrast, for STEMI in multiple infarct locations, neither the annual incidence nor the 28-day case fatality changed over time. The age- and race-adjusted annual incidence and associated 28-day case fatality of STEMI in anterior, inferior, and lateral infarct locations decreased during 22 years of surveillance; however, no decrease was observed for STEMI in multiple infarct locations. In conclusion, our findings suggest that there is room for improvement in the care of patients with multilocation STEMI. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores

PubMed Central

Ryzhov, Sergey; Tikhomirov, Oleg; Duarte, Christine W.; Congdon, Clare Bates; Lessard, Craig R.; McFarland, Samuel; Rochette-Egly, Cecile; Tran, Truc-Linh; Galindo, Cristi L.; Favreau-Lessard, Amanda J.; Sawyer, Douglas B.

2016-01-01

To determine whether hepatic depletion of vitamin A (VA) stores has an effect on the postnatal heart, studies were carried out with mice lacking liver retinyl ester stores fed either a VA-sufficient (LRVAS) or VA-deficient (LRVAD) diet (to deplete circulating retinol and extrahepatic stores of retinyl esters). There were no observable differences in the weights or gross morphology of hearts from LRVAS or LRVAD mice relative to sex-matched, age-matched, and genetically matched wild-type (WT) controls fed the VAS diet (WTVAS), but changes in the transcription of functionally relevant genes were consistent with a state of VAD in LRVAS and LRVAD ventricles. In silico analysis revealed that 58/67 differentially expressed transcripts identified in a microarray screen are products of genes that have DNA retinoic acid response elements. Flow cytometric analysis revealed a significant and cell-specific increase in the number of proliferating Sca-1 cardiac progenitor cells in LRVAS animals relative to WTVAS controls. Before myocardial infarction, LRVAS and WTVAS mice had similar cardiac systolic function and structure, as measured by echocardiography, but, unexpectedly, repeat echocardiography demonstrated that LRVAS mice had less adverse remodeling by 1 wk after myocardial infarction. Overall, the results demonstrate that the adult heart is responsive to retinoids, and, most notably, reducing hepatic VA stores (while maintaining circulating levels of VA) impacts ventricular gene expression profiles, progenitor cell numbers, and response to injury. PMID:27084391

Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.

PubMed

Asson-Batres, Mary Ann; Ryzhov, Sergey; Tikhomirov, Oleg; Duarte, Christine W; Congdon, Clare Bates; Lessard, Craig R; McFarland, Samuel; Rochette-Egly, Cecile; Tran, Truc-Linh; Galindo, Cristi L; Favreau-Lessard, Amanda J; Sawyer, Douglas B

2016-06-01

To determine whether hepatic depletion of vitamin A (VA) stores has an effect on the postnatal heart, studies were carried out with mice lacking liver retinyl ester stores fed either a VA-sufficient (LRVAS) or VA-deficient (LRVAD) diet (to deplete circulating retinol and extrahepatic stores of retinyl esters). There were no observable differences in the weights or gross morphology of hearts from LRVAS or LRVAD mice relative to sex-matched, age-matched, and genetically matched wild-type (WT) controls fed the VAS diet (WTVAS), but changes in the transcription of functionally relevant genes were consistent with a state of VAD in LRVAS and LRVAD ventricles. In silico analysis revealed that 58/67 differentially expressed transcripts identified in a microarray screen are products of genes that have DNA retinoic acid response elements. Flow cytometric analysis revealed a significant and cell-specific increase in the number of proliferating Sca-1 cardiac progenitor cells in LRVAS animals relative to WTVAS controls. Before myocardial infarction, LRVAS and WTVAS mice had similar cardiac systolic function and structure, as measured by echocardiography, but, unexpectedly, repeat echocardiography demonstrated that LRVAS mice had less adverse remodeling by 1 wk after myocardial infarction. Overall, the results demonstrate that the adult heart is responsive to retinoids, and, most notably, reducing hepatic VA stores (while maintaining circulating levels of VA) impacts ventricular gene expression profiles, progenitor cell numbers, and response to injury. Copyright © 2016 the American Physiological Society.

[Association of estrogen receptor gene polymorphism with cerebral infarction, a case-control study].

PubMed

Zhang, Yan; Xie, Ruping; Wang, Yinhua; Chen, Dafang; Wang, Guoying; Xu, Xiping

2002-11-10

To explore the association between estrogen receptor (ER) gene PvuII and XbaI polymorphisms and cerebral infarction among Chinese Han people. Samples of peripheral blood white cell were extracted among 234 patients with cerebral infarction, aged 63.9 +/- 10.3, and 259 controls without cerebrovascular disease, aged 59.2 +/- 9.2, all of Chinese Han nationality. PCR-RFLP and genotyping of ER PvuII and XbaI polymorphisms were performed. Multiple Logistic regression analysis was made to explore the risk factors for cerebral infarction. After adjustment for major confounders including age, gender, smoking, alcohol drinking, education, history of hypertension, diabetes mellitus, coronary artery disease and hyperlipoidemia, multiple Logistic regression analysis showed that: (1) The Pp genotype of ER PvuII polymorphism increased the risk of cerebral infarction significantly (OR = 1.97, 95% CI: 1.21 - 3.21); (2) The ER XbaI polymorphism was not in association with cerebral infarction significantly; (3) The PPXx/Ppxx genotypes increased the risk of cerebral infarction significantly (OR = 1.67, 2.52 and 2.18 respectively, P < 0.05) before or after all subjects were stratified by the history of hypertension or hyperlipoidemia; and (4) The positive interaction between the ER PvuII polymorphism and the presence of hypertension or diabetes or hyperlipoidemia could increase the risk of cerebral infarction significantly. ER gene may be one of the genetic candidate genes for cerebral infarction among Chinese Han population.

Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) liver imaging: Potential application in liver transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodle, E.S.; Vera, D.R.; Ward, R.E.

1984-01-01

Tc-NGA is a hepatocyte receptor-specific imaging agent whose uptake by the liver has been shown to be dependent upon blood flow and receptor concentration. The combination of anatomic and physiologic information obtained with Tc-NGA may provide a new tool for studying hepatic function in liver transplant recipients. To evaluate the potential role of Tc-NGA in liver transplant recipients, studies were performed in four groups of pigs: controls (n=18); common bile duct (CBD) ligation (n=8); orthotopic liver transplant (n=9); and acute hepatic artery ligation (n=1). Serial studies performed in two animals with CBD ligation demonstrated normal imaging anatomy with minor changesmore » in the hepatic time-activity curves when compared to control studies. Studies in liver-transplanted animals showed significant changes in the hepatic time-activity curves during acute rejection and in preservation-related ischemic injury. Tc-NGA also demonstrated focal areas of hepatic infarction in a hepatic allograft within 24 hours of transplantation. The hepatic artery ligation study showed massive changes in the hepatic time-activity curve within two hours after ligation, with a diffuse decrease in hepatic activity. These results indicate that: (1) extrahepatic biliary tract obstruction causes only minor changes in Tc-NGA uptake; (2) Tc-NGA uptake by the liver is very sensitive to acute hepatic ischemia; (3) Tc-NGA may indicate the presence of preservation damage in the early postoperative period; and (4) Tc-NGA hepatic time-activity curves demonstrate significant changes during acute rejection.« less

HDACi Valproic Acid (VPA) and Suberoylanilide Hydroxamic Acid (SAHA) Delay but Fail to Protect against Warm Hepatic Ischemia-Reperfusion Injury.

PubMed

Ruess, Dietrich A; Probst, Moriz; Marjanovic, Goran; Wittel, Uwe A; Hopt, Ulrich T; Keck, Tobias; Bausch, Dirk

2016-01-01

Histone deacetylases (HDAC) catalyze N-terminal deacetylation of lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In various animal models, such as trauma/hemorrhagic shock, ischemic stroke or myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and organoprotective and promotes survival. HDACi reduce stress signaling, cell death and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver resection or transplantation increases morbidity and mortality. Assuming protective properties, the aim of this study was to investigate the effect of the HDACi VPA and SAHA on warm hepatic I/R. Male Wistar-Kyoto rats (age: 6-8 weeks) were randomized to VPA, SAHA, vehicle control (pre-) treatment or sham-groups and underwent partial no-flow liver ischemia for 90 minutes with subsequent reperfusion for 6, 12, 24 and 60 hours. Injury and regeneration was quantified by serum AST and ALT levels, by macroscopic aspect and (immuno-) histology. HDACi treatment efficiency, impact on MAPK/SAPK-activation and Hippo-YAP signaling was determined by Western blot. Treatment with HDACi significantly enhanced hyperacetylation of Histone H3-K9 during I/R, indicative of adequate treatment efficiency. Liver injury, as measured by macroscopic aspect, serum transaminases and histology, was delayed, but not alleviated in VPA and SAHA treated animals. Importantly, tissue destruction was significantly more pronounced with VPA. SAPK-activation (p38 and JNK) was reduced by VPA and SAHA in the early (6h) reperfusion phase, but augmented later on (JNK, 24h). Regeneration appeared enhanced in SAHA and VPA treated animals and was dependent on Hippo-YAP signaling. VPA and SAHA delay warm hepatic I/R injury at least in part through modulation of SAPK-activation. However, these HDACi fail to exert organoprotective effects, in this setting. For VPA, belated damage is even aggravated.

"Spice" (Synthetic Marijuana) Induced Acute Myocardial Infarction: A Case Series.

PubMed

Ul Haq, E; Shafiq, A; Khan, A A; Awan, A A; Ezad, S; Minteer, W J; Omar, B

2017-01-01

Marijuana is the most widely abused "recreational" substance in the United States, with highest prevalence in young adults. It is reported to cause ischemic strokes, hepatitis, anxiety, and psychosis. Although it is associated with dose dependent tachycardia and can lead to coronary vasospasm, it has not been directly related to acute myocardial infarction (AMI). Marijuana induced coronary vasospasm can result in endothelial denudation at the site of a vulnerable atherosclerotic plaque in response to hemodynamic stressors, potentially causing an AMI. Spice refers to herbal mixture with composition and effects similar to that of marijuana and therefore is referred to as "synthetic marijuana." Herein, we report 3 cases of spice induced ST-segment elevation myocardial infarction. All patients were relatively young and had few or absolutely no risk factors for cardiovascular disease. All patients underwent emergent coronary angiography, with two needing stent placement and the third requiring only aspiration thrombectomy. Our case series emphasizes the importance of suspecting and investigating synthetic marijuana use in low risk young adults presenting with AMI.

Novel Resuscitation from Lethal Hemorrhage Suspended Animation for Delayed Resuscitation

DTIC Science & Technology

2005-10-01

hypothermia on rat hippocampal proteomic profiles after 30 minutes of complete cerebral ischemia. American Stroke Association; Fellows’ Research Day, Hilton...well as traumatic brain injury , stroke , hemorrhagic shock, myocardial infarction, hepatic failure, and even pulmonary failure with sepsis. Additional...specific secondary injury 64 Chapter 5 mechanisms, such as local cerebral inflammation, were shown. State-of-the- art reviews by central nervous system

Hepatic arterial embolization in the management of blunt hepatic trauma: indications and complications.

PubMed

Letoublon, Christian; Morra, Irene; Chen, Yao; Monnin, Valerie; Voirin, David; Arvieux, Catherine

2011-05-01

The objective was to clarify the role of hepatic arterial embolization (AE) in the management of blunt hepatic trauma. Retrospective observational study of 183 patients with blunt hepatic trauma admitted to a trauma referral center over a 9-year period. The charts of 29 patients (16%) who underwent hepatic angiography were reviewed for demographics, injury specific data, management strategy, angiographic indication, efficacy and complications of embolization, and outcome. AE was performed in 23 (79%) of the patients requiring angiography. Thirteen patients managed conservatively underwent emergency embolization after preliminary computed tomography scan. Six had postoperative embolization after damage control laparotomy and four had delayed embolization. Arterial bleeding was controlled in all the cases. Sixteen patients (70%) had one or more liver-related complications; temporary biliary leak (n=11), intra-abdominal hypertension (n=14), inflammatory peritonitis (n=3), hepatic necrosis (n=3), gallbladder infarction (n=2), and compressive subcapsular hematoma (n=1). Unrecognized hepatic necrosis could have contributed to the late posttraumatic death of one patient. AE is a key element in modern management of high-grade liver injuries. Two principal indications exist in the acute postinjury phase: primary hemostatic control in hemodynamically stable or stabilized patients with radiologic computed tomography evidence of active arterial bleeding and adjunctive hemostatic control in patients with uncontrolled suspected arterial bleeding despite emergency laparotomy. Successful management of injuries of grade III upward often entails a combined angiographic and surgical approach. Awareness of the ischemic complications due to angioembolization is important.

Relationship Between Visceral Infarction and Ischemic Stroke Subtype.

PubMed

Finn, Caitlin; Hung, Peter; Patel, Praneil; Gupta, Ajay; Kamel, Hooman

2018-03-01

Most cryptogenic strokes are thought to have an embolic source. We sought to determine whether cryptogenic strokes are associated with visceral infarcts, which are usually embolic. Among patients prospectively enrolled in CAESAR (Cornell Acute Stroke Academic Registry), we selected those with a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. Our exposure variable was adjudicated stroke subtype per the Trial of ORG 10172 in Acute Stroke Treatment classification. Our outcome was renal or splenic infarction as assessed by a single radiologist blinded to stroke subtype. We used Fisher exact test and multiple logistic regression to compare the prevalence of visceral infarcts among cardioembolic strokes, strokes of undetermined etiology, and noncardioembolic strokes (large- or small-vessel strokes). Among 227 patients with ischemic stroke and a contrast-enhanced abdominal computed tomographic scan, 59 had a visceral infarct (35 renal and 27 splenic). The prevalence of visceral infarction was significantly different among cardioembolic strokes (34.2%; 95% confidence interval [CI], 23.7%-44.6%), strokes of undetermined etiology (23.9%; 95% CI, 15.0%-32.8%), and strokes from large-artery atherosclerosis or small-vessel occlusion (12.5%; 95% CI, 1.8%-23.2%; P =0.03). In multiple logistic regression models adjusted for demographics and vascular comorbidities, we found significant associations with visceral infarction for both cardioembolic stroke (odds ratio, 3.5; 95% CI, 1.2-9.9) and stroke of undetermined source (odds ratio, 3.3; 95% CI, 1.1-10.5) as compared with noncardioembolic stroke. The prevalence of visceral infarction differed significantly across ischemic stroke subtypes. Cardioembolic and cryptogenic strokes were associated with a higher prevalence of visceral infarcts than noncardioembolic strokes. © 2018 American Heart Association, Inc.

The Effects of Physical Conditioning on Heat Tolerance in Chemical Defense Gear.

DTIC Science & Technology

1986-06-01

symptoms and electrocardiographic signs of impending or acute myocardial infarction and myocar- ditis and aortic stenosis 6. Acute infectious diseases...systolic blood pressure over 200 mm Hg 12. Electrolyte abnormalities 13. Any serious systemic disorder ( mononucleosis , hepatitis, etc.) 14...34Mechanisms of Acclimitization to Heat in Man.- M, 34: 323-380, 1955. Baxter, C.R. "Prevention, Recognition and Treatment of Heat Disorder." Texas State

Stroke in Primary Hyperoxaluria Type I

PubMed Central

Rao, Neal M.; Yallapragada, Anil; Winden, Kellen D.; Saver, Jeffrey; Liebeskind, David S.

2014-01-01

We report the case of a 27-year-old man with a history of previously undiagnosed renal disease that presented with multiple cerebrovascular infarctions. Workup for traditional causes of cerebrovascular infarction including cardiac telemetry, multiple echocardiograms, and hypercoagulative workup was negative. However, a transcranial Doppler detected circulating microemboli at the rate of 14 per hour. A serum oxalate level greater than the supersaturation point of calcium oxalate was detected, providing a potential source of the microemboli. Furthermore, serial imaging recorded rapid mineralization of the infarcted territories. In the absence of any proximal vessel irregularities, atherosclerosis, valvular abnormalities, arrhythmias, or systemic shunt as potential stroke etiology in this patient, we propose that circulating oxalate precipitate may be a potential mechanism for stroke in patients with primary oxalosis. PMID:23551880

Hemichorea after multiple bee stings.

PubMed

An, Jin Young; Kim, Ji Seon; Min, Jin Hong; Han, Kyu Hong; Kang, Jun Ho; Lee, Suk Woo; Kim, Hoon; Park, Jung Soo

2014-02-01

Bee sting is one of the most commonly encountered insect bites in the world. Despite the common occurrence of local and systemic allergic reactions, there are few reports of ischemic stroke after bee stings. To the best our knowledge, there have been no reports on involuntary hyperkinetic movement disorders after multiple bee stings. We report the case of a 50-year-old man who developed involuntary movements of the left leg 24 hours after multiple bee stings, and the cause was confirmed to be a right temporal infarction on a diffusion magnetic resonance imaging scan. Thus, we concluded that the involuntary movement disorder was caused by right temporal infarction that occurred after multiple bee stings.

Evolution of multiple sclerosis in France since the beginning of hepatitis B vaccination.

PubMed

Le Houézec, Dominique

2014-12-01

Since the implementation of the mass vaccination campaign against hepatitis B in France, the appearance of multiple sclerosis, sometimes occurring in the aftermath of vaccinations, led to the publication of epidemiological international studies. This was also justified by the sharp increase in the annual incidence of multiple sclerosis reported to the French health insurance in the mid-1990s. Almost 20 years later, a retrospective reflection can be sketched from these official data and also from the national pharmacovigilance agency. Statistical data from these latter sources seem to show a significant correlation between the number of hepatitis B vaccinations performed and the declaration to the pharmacovigilance of multiple sclerosis occurring between 1 and 2 years later. The application of the Hill's criteria to these data indicates that the correlation between hepatitis B vaccine and multiple sclerosis may be causal.

Multiple Thromboembolic Cerebral Infarctions from the Aorta in a Patient with Churg-Strauss Syndrome.

PubMed

Okada, Hideo

2017-02-01

Ischemic stroke is a rare complication of Churg-Strauss syndrome (CSS) and its pathogenesis has not been well clarified yet. We report a case of cerebral infarction in a patient with CSS due to embolism from a thrombus on the wall of the aorta. A 39-year-old man had multiple cerebral infarctions with symptoms of mild left hemiparesis and reduced vision. He was clinically diagnosed to have CSS based on remarkable eosinophilia, history of asthma, sinusitis, pulmonary infiltrates, and histologically proven extravascular eosinophilic infiltrates in the specimen of gastric mucosa. Cerebral angiography did not show any stenotic lesions in cerebral arteries. A thrombus was detected on the wall of the aorta by transesophageal echocardiography, which was considered as the source of embolism. The thrombus resolved on follow-up examination 3 months after the onset of the stroke. This is the first case report on cerebral infarction caused by aortogenic thromboembolism in a CSS patient. Other than cerebral vasculitis, embolism from cardiovascular system, including the wall of the aorta, is a possible cause of cerebral infarctions in a CSS patient. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Impact of Multiple Complex Plaques on Short-and Long-Term Clinical in Patients Presenting with ST-Segment Elevation Myocardial Infarction (From the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Trial)

PubMed Central

Keeley, Ellen C.; Mehran, Roxana; Brener, Sorin J.; Witzenbichler, Bernhard; Guagliumi, Giulio; Dudek, Dariusz; Kornowski, Ran; Dressler, Ovidiu; Fahy, Martin; Xu, Ke; Grines, Cindy L.; Stone, Gregg W.

2014-01-01

It is not known whether the extent and severity of non-culprit coronary lesions correlate with outcomes in patients with STEMI referred for primary PCI. We sought to quantify complex plaques in ST-segment elevation myocardial infarction (STEMI) patients referred for primary percutaneous coronary intervention (PCI) and to determine their effect on short- and long-term clinical outcomes by examining the core laboratory database for plaque analysis from the HORIZONS-AMI study. Baseline demographic, angiographic, and procedural details were compared between patients with single vs. multiple complex plaques undergoing single vessel PCI. Multivariable analysis was performed for predictors of long-term major adverse cardiac events (MACE), a combined end point of death, reinfarction, ischemic target vessel revascularization, or stroke, and for death alone. Single vessel PCI was performed in 3,137 patients (87%): 2,174 (69%) had multiple complex plaques and 963 (31%) had a single complex plaque. Compared to those with a single complex plaque, patients with multiple complex plaques were older (p<0.0001) and had more comorbidities. The presence of multiple complex plaques was an independent predictor of 3-year MACE (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.26–1.98, p<0.0001), and death alone (HR: 1.68; 95% CI: 1.05–2.70, p=0.03). In conclusion, multiple complex plaques are present in the majority of STEMI patients undergoing primary PCI and their presence is an independent predictor of short- and long-term MACE, including death. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) PMID:24703369

Immunogenomics reveal molecular circuits of diclofenac induced liver injury in mice

PubMed Central

Lee, Eun-Hee; Oh, Jung-Hwa; Selvaraj, Saravanakumar; Park, Se-Myo; Choi, Mi-Sun; Spanel, Reinhard

2016-01-01

Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue of immune-mediated DILI mechanisms an immunogenomic study was carried out. Diclofenac treatment of mice at 30 mg/kg for 3 days caused significant serum ALT and AST elevations, hepatomegaly and degenerative changes including hepatic glycogen depletion, hydropic swelling, cholesterolosis and eosinophilic hepatocytes with one animal presenting subsegmental infarction due to portal vein thrombosis. Furthermore, portal/periportal induction of the rate limiting enzyme in ammonia detoxification, i.e. carbamoyl phosphate synthetase 1 was observed. The performed microarray studies informed on > 600 differential expressed genes of which 35, 37 and 50 coded for inflammation, 51, 44 and 61 for immune and 116, 129 and 169 for stress response, respectively after single and repeated dosing for 3 and 14 days. Bioinformatic analysis defined molecular circuits of hepatic inflammation with the growth hormone (Ghr)− and leptin receptor, the protein-tyrosine-phosphatase, selectin and the suppressor-of-cytokine-signaling (Socs) to function as key nodes in gene regulatory networks. Western blotting confirmed induction of fibronectin and M-CSF to hallmark tissue repair and differentiation of monocytes and macrophages. Transcript expression of the macrophage receptor with collagenous structure increased > 7-fold and immunohistochemistry of CD68 evidenced activation of tissue-resident macrophages. Importantly, diclofenac treatment prompted strong expression of phosphorylated Stat3 amongst individual animals and the associated 8- and 4-fold Soc3 and Il-6 induction reinforced Ghr degradation as evidenced by immunoblotting. Moreover, immunohistochemistry confirmed regulation of master regulatory proteins of diclofenac treated mice to suggest complex pro-and anti-inflammatory reactions in immune-mediated hepatic injury. The findings encourage translational research. PMID:26934552

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors

PubMed Central

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-01-01

Objective(s): Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. Materials and Methods: The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Results: Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Conclusion: Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production. PMID:29299201

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors.

PubMed

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-11-01

Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production.

Portal, superior mesenteric and splenic vein thrombosis secondary to hyperhomocysteinemia with pernicious anemia: a case report.

PubMed

Venkatesh, Prashanth; Shaikh, Nissar; Malmstrom, Mohammad F; Kumar, Vajjala R; Nour, Bakr

2014-08-25

Acute portomesenteric vein thrombosis is an uncommon but serious condition with potential sequelae, such as small-bowel gangrene and end-stage hepatic failure. It is known to be caused by various pro-thrombotic states, including hyperhomocysteinemia. We describe what is, to the best of our knowledge, the first reported case of concomitant thrombosis of portal, superior mesenteric and splenic veins due to hyperhomocysteinemia secondary to pernicious anemia and no other risk factors. A 60-year-old Indian man presented with epigastric pain, diarrhea and vomiting. An abdominal imaging scan showed that he had concomitant pernicious anemia and concomitant portal, superior mesenteric and splenic vein thrombosis. A work-up for the patient's hypercoagulable state revealed hyperhomocysteinemia, an undetectable vitamin B12 level and pernicious anemia with no other thrombophilic state. He developed infarction with perforation of the small bowel and subsequent septic shock with multi-organ dysfunction syndrome, and he ultimately died due to progressive hepatic failure. This report demonstrates that pernicious anemia, on its own, can lead to hyperhomocysteinemia significant enough to lead to lethal multiple splanchnic vein thrombosis. Our case also underscores the need to (1) consider portomesenteric thrombosis in the differential diagnosis of epigastric abdominal pain, (2) perform a complete thrombotic work-up to elucidate metabolic abnormalities that could be contributing to a pro-thrombotic state and (3) initiate aggressive measures, including early consideration of multi-visceral transplantation, in order to avoid decompensation and a significant adverse outcome.

Splenic infarction associated with sickle cell trait at low altitude.

PubMed

Seegars, Mary Beth; Brett, Allan S

2015-12-01

Sickle cell trait is widely known to be associated with splenic infarction at high altitudes. Although textbooks and reviews imply that this complication does not occur at low altitudes, we encountered such a case and identified several previous cases in the literature. An 18-year-old woman with sickle cell trait who resided near sea level presented with left upper quadrant abdominal pain and was found to have multiple splenic infarcts. She was otherwise well, with no comorbidities that would predispose to hypoxemia or vascular injury. A review of the literature revealed 12 previously published cases of low-altitude splenic infarction in patients with sickle trait; 7 of those patients had comorbidities that likely predisposed to splenic infarction. None. Spontaneous splenic infarction can occur in patients with sickle trait who live at low altitudes. It is unclear whether this complication is rare, or whether it is relatively common but under-recognized.

Unusual causes of abdominal pain: sickle cell anemia.

PubMed

Ahmed, Shahid; Shahid, Rabia K; Russo, Linda A

2005-04-01

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crises. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestation of the disease. Abdominal pain is an important component of vaso-occlusive painful crises. It often represents a substantial diagnostic challenge in this population of patients. These episodes are often attributed to micro-vessel occlusion and infarcts of mesentery and abdominal viscera. Abdominal pain due to sickle cell vaso-occlusive crisis is often indistinguishable from an acute intra-abdominal disease process such as acute cholecystitis, acute pancreatitis, hepatic infarction, ischemic colitis and acute appendicitis. In the majority of cases, however, no specific cause is identified and spontaneous resolution occurs. This chapter will focus on etiologies, pathophysiology and management of abdominal pain in patients with sickle cell disease.

[Cerebellar infarction in vascular teritorry of arteria cerebelli superior].

PubMed

Savić, Dejan; Savić, Ljiljana

2010-01-01

Cerebellar vascular diseases are focal cerebrovascular diseases in posterior circulation--vertebrobasilar system. The cerebellum is supplied by three main arteries arising from the vertebrobasilar system: arteria cerebelli inferior posterior, arteria cerebelli inferior anterior and arteria cerebelli superior. Cerebelar infarctions are rare but unpredictable disorders. The aim of this study was determination of main risk factors, clinical presentation and prognosis of the cerebellar infarctions in distal vascular teritorry of the arteria cerebelli superior. We evaluated 60 patients hospitalized after acute cerebellar infarction among other hospitalized patients in five year period. In 18 patients computerized tomography demonstrated infarction in distal vascular teritorry of the arteria cerebelli superior. All patients underwent clinical and other diagnostic investigations (computerized tomography, electrocardyography and standard blood tests) and were questioned by phone after finishing hospital treatment. Cerebellar infarcts in distal vascular teritorry of arteria cerebell superior was 30% of all cerebellar infarcts. The most frequent risk factor was hypertension (66.7%). Symptomatology and clinical signs were heterogenous but the most frequent were instability (77.8%), vertigo (72.2%) and vomiting (55.6%) followed by ataxia of the limbs (77.8%) and the body (61.1%), nystagmus (55.6%) and disarthria (33.3%) in clinical presentation. All patients had good recovery in hospital and one year afterwards. Infarctions in distribution of arteria cerebelli superior are rare and have multiple risk factors and various clinical features in majority of other studies as in this one. Mass effects are present in several studies but none in this one which reflects contraversions present in other published investigations. Cerebellar infarctions in vascular teritorry of arteria cerebelli superior have multiple risk factors, mostly heterogenous clinical presentations with predominance of instability, vertigo and vomiting with ataxia of the limbs and the body as well as nystagmus and disarthria in clinical presentation. The outcome and prognosis of disease is good despite the large amount of arteria cerebelli superior vascular teritorry.

Vascular occlusion and infarction in sickle cell crisis and the sickle chest syndrome.

PubMed Central

Athanasou, N A; Hatton, C; McGee, J O; Weatherall, D J

1985-01-01

A young adult with homozygous sickle cell anaemia (Hb SS) suffered a fatal sickle cell crisis complicated by the sickle chest syndrome. At necropsy multiple large infarcts of the lung, bone marrow, and pituitary gland were found. The large majority of pulmonary infarcts were not associated with either gross or microscopic vaso-occlusion. These findings are discussed and correlated with past and current opinions of sickle cell crisis and the sickle chest syndrome. Images PMID:4008666

[Management of hepatic injuries with multiple trauma in the emergency unit. Report of three cases].

PubMed

Qamouss, Y; Belyamani, L; Azendour, H; Balkhi, H; Haimeur, C; Atmani, M

2006-01-01

The problems put by the blunt hepatic injuries at the multiple traumas are discussed after the exposition of three observations. 60% of the blunt hepatic injuries are due to the accidents of the public way. The strategy diagnosis and therapeutic facing a hepatic lesion remains guided by the patient's state haemodynamic. The exam essential to the arrival in the sieve of the emergencies is the abdominal scan that searches for one extrusion intra and possibly retroperitoneal and analyze the hepatic parenchyrma. However, it depends extensively on the experience of the echographist. The city scan stood to the first plan of the medical imagery: it permits a precise diagnosis of the parenchymateuses hepatic lesions, specify the abundance of the hemoperitoine, facilitate the therapeutic conduct in presence of associated lesions and the surveillance of the blunt hepatic injuries.

Multiple small hemorrhagic infarcts in cerebral air embolism: a case report.

PubMed

Togo, Masaya; Hoshi, Taku; Matsuoka, Ryosuke; Imai, Yukihiro; Kohara, Nobuo

2017-11-16

Cerebral air embolism is a rare cause of cerebral infarction. In cerebral air embolism, T2 star-weighted imaging shows numerous spotty hypointense signals. Previous reports have suggested that these signals represent air in the brain and are gradually diminished and absorbed. We experienced two cases of cerebral air embolism, and in one of them, we conducted an autopsy. Case 1 was a 76-year-old Japanese man with lung cancer and emphysema. A spasmodic cough induced massive cerebral and cardiac air embolisms and the patient died because of cerebral herniation. T2 star-weighted imaging of brain magnetic resonance imaging showed multiple spotty low signals. Brain autopsy showed numerous spotty hemorrhagic infarcts in the area of T2 star-weighted imaging signals. Case 2 was an 85-year-old Japanese man with emphysema who suffered from acute stroke. Similar spotty T2 star-weighted imaging signals were observed and remained unchanged 2 months after the onset. These findings indicate that T2 star-weighted imaging in cerebral air embolism partially represents micro-hemorrhagic infarction caused by air bubbles that have migrated into the brain.

Right upper-quadrant pain in a patient with drug abuse, secondary syphilis and occult hepatitis B virus.

PubMed

Fielding, Cory M; Angulo, Paul

2014-01-01

To describe the etiology of hepatitis and identify occult hepatitis B virus (HBV) infection. A 40-year-old man presented with severe abdominal pain and jaundice, a history of acute HBV infection that had cleared as well as the use of acetaminophen, methamphetamine, buprenorphine and marijuana. He admitted to having had unprotected sex with multiple partners of both genders. A thorough skin examination revealed papulosquamous lesions on his penis, scrotum, upper and lower extremities and feet. Transaminases and bilirubin were elevated. His rapid plasma reagin was reactive, and hepatitis serologies showed occult HBV. Liver biopsy showed severe hepatitis, but the stains for hepatitis B surface antigen and hepatitis B core antigen were negative. The pathological findings were highly indicative of drug-induced hepatitis without evidence of chronic hepatitis, reactivation of HBV or syphilitic hepatitis. With supportive management and abstinence from drugs, his condition improved. This case describes a patient with multiple potential causes for hepatitis and highlights the importance of obtaining a detailed social history. Further, one should consider the presence of occult HBV and recognize the serologic pattern. © 2014 S. Karger AG, Basel.

Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C.

PubMed

Takata, Kazuhide; Shakado, Satoshi; Sakamoto, Keiko; Fukuda, Hiromi; Yamauchi, Ryo; Fukuda, Sho; Kunimoto, Hideo; Umeda, Kaoru; Tanaka, Takashi; Yokoyama, Keiji; Morihara, Daisuke; Takeyama, Yasuaki; Irie, Makoto; Sakisaka, Shotaro

2017-10-01

Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.

Asian American Health - Multiple Languages

MedlinePlus

... Are You At Risk? Information for Asian Americans - English PDF Hepatitis B - Are You At Risk? Information ... Family Has Hepatitis B: Information for Asian Americans - English PDF Hepatitis B and Your Family - When Someone ...

Multiple hepatic lesions in a case of isolated hepatic tuberculosis simulating metastases on 18F-FDG PET/CT imaging.

PubMed

Karunanithi, Sellam; Sharma, Punit; Jain, Tarun Kumar; Vijay, Maneesh Kumar; Kumar, Rakesh

2014-01-01

Hepatic tuberculosis is an unusual form of extrapulmonary tuberculosis and constitutes less than 1% of all cases of tuberculosis. Imaging studies for hepatic tuberculosis are nonspecific and mimic primary or metastatic carcinoma. Here we present ¹⁸F-FDG PET/CT images of a 25-year-old male patient with isolated hepatic tuberculosis.

Angiostrongylus vasorum Causing Severe Granulomatous Hepatitis with Concurrent Multiple Acquired PSS.

PubMed

Cook, Simon; Priestnall, Simon L; Blake, Damer; Meeson, Richard L

2015-01-01

A 14 mo old female Jack Russell terrier presented with a 12 hr history of vomiting and inappetence. She was subsequently diagnosed with multiple acquired portosystemic shunts during an exploratory celiotomy. Gross and histopathological hepatic abnormalities were consistent with chronic disease, including features suggestive of portal hypertension that was potentially caused by migrating and resident Angiostrongylus vasorum larvae. Fecal analysis and polymerase chain reaction of hepatic tissue confirmed the presence of Angiostrongylus vasorum . The dog recovered clinically following empirical treatment and supportive care. A lack of parasite burden was confirmed 9 wk postdiagnosis; however, serum biochemical analysis at that time was suggestive of ongoing hepatic dysfunction.

MTHFR and ACE Gene Polymorphisms and Risk of Vascular and Degenerative Dementias in the Elderly

ERIC Educational Resources Information Center

Pandey, Pratima; Pradhan, Sunil; Modi, Dinesh Raj; Mittal, Balraj

2009-01-01

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as…

What is the best ST-segment recovery parameter to predict clinical outcome and myocardial infarct size? Amplitude, speed, and completeness of ST-segment recovery after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

PubMed

Kuijt, Wichert J; Green, Cindy L; Verouden, Niels J W; Haeck, Joost D E; Tzivoni, Dan; Koch, Karel T; Stone, Gregg W; Lansky, Alexandra J; Broderick, Samuel; Tijssen, Jan G P; de Winter, Robbert J; Roe, Matthew T; Krucoff, Mitchell W

ST-segment recovery (STR) is a strong mechanistic correlate of infarct size (IS) and outcome in ST-segment elevation myocardial infarction (STEMI). Characterizing measures of speed, amplitude, and completeness of STR may extend the use of this noninvasive biomarker. Core laboratory continuous 24-h 12-lead Holter ECG monitoring, IS by single-photon emission computed tomography (SPECT), and 30-day mortality of 2 clinical trials of primary percutaneous coronary intervention in STEMI were combined. Multiple ST measures (STR at last contrast injection (LC) measured from peak value; 30, 60, 90, 120, and 240min, residual deviation; time to steady ST recovery; and the 3-h area under the time trend curve [ST-AUC] from LC) were univariably correlated with IS and predictive of mortality. After multivariable adjustment for ST-parameters and GRACE risk factors, STR at 240min remained an additive predictor of mortality. Early STR, residual deviation, and ST-AUC remained associated with IS. Multiple parameters that quantify the speed, amplitude, and completeness of STR predict mortality and correlate with IS. Copyright © 2017. Published by Elsevier Inc.

Dental calculus is associated with death from heart infarction.

PubMed

Söder, Birgitta; Meurman, Jukka H; Söder, Per-Östen

2014-01-01

We studied whether the amount of dental calculus is associated with death from heart infarction in the dental infection-atherosclerosis paradigm. Participants were 1676 healthy young Swedes followed up from 1985 to 2011. At the beginning of the study all subjects underwent oral clinical examination including dental calculus registration scored with calculus index (CI). Outcome measure was cause of death classified according to WHO International Classification of Diseases. Unpaired t-test, Chi-square tests, and multiple logistic regressions were used. Of the 1676 participants, 2.8% had died during follow-up. Women died at a mean age of 61.5 years and men at 61.7 years. The difference in the CI index score between the survivors versus deceased patients was significant by the year 2009 (P < 0.01). In multiple regression analysis of the relationship between death from heart infarction as a dependent variable and CI as independent variable with controlling for age, gender, dental visits, dental plaque, periodontal pockets, education, income, socioeconomic status, and pack-years of smoking, CI score appeared to be associated with 2.3 times the odds ratio for cardiac death. The results confirmed our study hypothesis by showing that dental calculus indeed associated statistically with cardiac death due to infarction.

Cerebral infarction due to smoker’s polycythemia

PubMed Central

Thakur, Kiran Teresa; Westover, M Brandon

2011-01-01

A 65-year-old man presented with fluctuating focal neurological deficits and neuroimaging findings of multiple small cerebral infarctions. His medical investigation revealed a >100 pack/year smoking history, and a haematocrit >60. Subsequent investigations led to a diagnosis of cerebral infarction due to smoker’s polycythemia, the third such case reported in the medical literature. The patient’s neurological deficits resolved completely with subsequent haematocrit reduction. This brief report reviews the differential diagnosis of polycythemia, current knowledge of the mechanisms by which smoker’s polycythemia may lead to ischemic stroke, and recommendations for management. PMID:22675101

Pancreatic Cancer in Pregnancy Presenting with Thromboembolic Events: Case Report and Review of the Literature.

PubMed

Wakefield, Brian W; Masterson, Crystal M C; Borges, Manuel T; Hurt, K Joseph

2018-06-08

Stroke and hepatic vein thrombosis are highly associated with neoplasia but are extremely rare events in young, pregnant women. Rare and recurrent thrombotic events in pregnancy increase the suspicion for occult malignancy. We describe the case of a healthy 31-year-old G2P1 who presented with visual changes and dysarthria during pregnancy. Imaging showed cerebral infarcts. Her thrombophilia evaluation was negative. During delivery, she was diagnosed with fulminant Budd-Chiari Syndrome. Hepatic ultrasound suggested malignancy or metastasis, and postpartum CT scan and biopsy confirmed the diagnosis of Stage IV pancreatic cancer. Although rare in pregnancy, a new diagnosis of malignancy should be considered in patients with recurrent unexplained hypercoagulable complications. We propose an evidence-based algorithm for evaluation of occult malignancy in pregnancy based upon this case and review of the literature. © 2018 S. Karger AG, Basel.

[Ischemic cholangiopathy induced by extended burns].

PubMed

Cohen, Laurence; Angot, Emilie; Goria, Odile; Koning, Edith; François, Arnaud; Sabourin, Jean-Christophe

2013-04-01

Ischemic cholangiopathy is a recently described entity occurring mainly after hepatic grafts. Very few cases after intensive care unit (ICU) for extended burn injury were reported. We report the case of a 73-year-old woman consulting in an hepatology unit, for a jaundice appearing during a hospitalisation in an intensive care unit and increasing from her leaving from ICU, where she was treated for an extended burn injury. She had no pre-existing biological features of biliary disease. Biological tests were normal. Magnetic resonance imaging acquisitions of biliary tracts pointed out severe stenosing lesions of diffuse cholangiopathy concerning intrahepatic biliary tract, mainly peri-hilar. Biopsie from the liver confirmed the diagnosis, showing a biliary cirrhosis with bile infarcts. This case is the fourth case of ischemic cholangiopathy after extended burn injury, concerning a patient without a prior history of hepatic or biliary illness and appearing after hospitalisation in intensive care unit. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chromium supplementation improved post-stroke brain infarction and hyperglycemia.

PubMed

Chen, Wen-Ying; Mao, Frank Chiahung; Liu, Chia-Hsin; Kuan, Yu-Hsiang; Lai, Nai-Wei; Wu, Chih-Cheng; Chen, Chun-Jung

2016-04-01

Hyperglycemia is common after acute stroke and is associated with a worse outcome of stroke. Thus, a better understanding of stress hyperglycemia is helpful to the prevention and therapeutic treatment of stroke. Chromium is an essential nutrient required for optimal insulin activity and normal carbohydrate and lipid metabolism. Beyond its nutritional effects, dietary supplement of chromium causes beneficial outcomes against several diseases, in particular diabetes-associated complications. In this study, we investigated whether post-stroke hyperglycemia involved chromium dynamic mobilization in a rat model of permanent focal cerebral ischemia and whether dietary supplement of chromium improved post-stroke injury and alterations. Stroke rats developed brain infarction, hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Post-stroke hyperglycemia was accompanied by elevated secretion of counter-regulatory hormones including glucagon, corticosterone, and norepinephrine, decreased insulin signaling in skeletal muscles, and increased hepatic gluconeogenesis. Correlation studies revealed that counter-regulatory hormone secretion showed a positive correlation with chromium loss and blood glucose increased together with chromium loss. Daily chromium supplementation increased tissue chromium levels, attenuated brain infarction, improved hyperglycemia, and decreased plasma levels of glucagon and corticosterone in stroke rats. Our findings suggest that stroke rats show disturbance of tissue chromium homeostasis with a net loss through urinary excretion and chromium mobilization and loss might be an alternative mechanism responsible for post-stroke hyperglycemia.

Integrated multimodal-catheter imaging unveils principal relationships among ventricular electrical activity, anatomy, and function.

PubMed

Rao, Liyun; Ling, Yuesheng; He, Renjie; Gilbert, April L; Frangogiannis, Nikolaos G; Wang, Jianwen; Nagueh, Sherif F; Khoury, Dirar S

2008-02-01

Multiple imaging modalities are employed independent of one another while managing complex cardiac arrhythmias. To combine electrical, anatomical, and functional imaging in a single catheter system, we developed a balloon catheter that carried 64 electrodes on its surface and an intracardiac echocardiography (ICE) catheter through a central lumen. The catheter system was inserted, and the balloon was inflated inside the left ventricle (LV) of eight dogs with 6-wk-old infarction, created by occlusion in the left anterior descending coronary artery. Anatomy was constructed by ICE imaging (9 MHz) through the balloon. Single-beat noncontact mapping (NCM) was performed via the multielectrode array to reconstruct unipolar endocardial electrograms during sinus rhythm. Standard contact mapping (CM) of the endocardium was also carried out for reference. Myocardial infarction in anterior LV extending from the middle to apical regions was localized both by ICE and NCM and validated by CM and pathology. The overall difference in the activation times between NCM and CM was 3 +/- 1 ms. Unipolar voltage in infarcted middle anterior LV was smaller than the voltage in normal middle inferior LV both by NCM (11 +/- 4 vs. 16 +/- 3 mV; P = 0.002) and CM (11 +/- 3 vs. 20 +/- 4 mV; P < 0.001). Unipolar voltage was also inversely related to infarct transmurality, both by NCM (r = -0.87; P = 0.005) and CM (r = -0.94; P < 0.001). The infarct area by ICE (7.7 +/- 2.9 cm(2)) was in agreement with CM (bipolar voltage, <1 mV; and area, 7.6 +/- 3.3 cm(2); r = 0.80; P = 0.016). Meanwhile, the voltage threshold that depicted the infarct area by NCM was directly related to the smallest unipolar voltage reconstructed within the infarct (r = 0.96; P < 0.001). In conclusion, combining NCM and ICE imaging in a single catheter system is feasible. The preclinical development of such an integrated system and its evaluation in experimental myocardial infarction demonstrate capabilities for single-beat mapping at multiple sites as well as the online assessment of anatomy and myocardial function.

Impact of Right-Sided Aneurysm, Rupture Status, and Size of Aneurysm on Perforator Infarction Following Microsurgical Clipping of Posterior Communicating Artery Aneurysms with a Distal Transsylvian Approach.

PubMed

Tanabe, Jun; Ishikawa, Tatsuya; Moroi, Junta; Sakata, Yoshinori; Hadeishi, Hiromu

2018-03-01

Posterior communicating artery (PCoA) aneurysms are among the most common aneurysms. Because blockage of the PCoA and perforators can cause adverse outcomes, occlusion of these arteries by surgical clipping should be avoided. The impact of factors on PCoA perforator infarction when using a distal transsylvian approach for PCoA aneurysms was examined. A total of 183 patients underwent PCoA aneurysm clipping, excluding application of fenestrated clips. Patients were divided into 2 groups: patients with PCoA perforator infarction (infarction group) and patients without infarction (noninfarction group). Multiple factors were analyzed in the 2 groups. Twenty-two of the 183 patients (12.0%) showed perforator infarction, mainly on magnetic resonance imaging evaluation, resulting in permanent deficits in 2 patients (1.1%). The proportion of right-sided operations (86.4% vs. 53.4%; P = 0.005) and surgery for rupture (90.9% vs. 55.9%; P = 0.002) were significantly higher in the infarction group than in the noninfarction group. Aneurysms were significantly larger in the infarction group (8.4 ± 3.8 mm) than in the noninfarction group (6.3 ± 3.0 mm; P = 0.02). Ruptured status (odds ratio [OR], 7.35; P = 0.01), right side (OR, 5.19; P = 0.01), and aneurysm size (OR, 1.18; P = 0.02) remained independent predictors of perforator infarction on multivariate logistic regression analysis. Ruptured status, right side, and large PCoA aneurysm were independent predictors of PCoA perforator infarction. Symptoms due to PCoA perforating infarction were mostly transient and rarely affected outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Spectral analysis of epicardial 60-lead electrograms in dogs with 4-week-old myocardial infarction.

PubMed

Hosoya, Y; Ikeda, K; Komatsu, T; Yamaki, M; Kubota, I

2001-01-01

There were few studies on the spectral analysis of multiple-lead epicardial electrograms in chronic myocardial infarction. Spectral analysis of multi-lead epicardial electrograms was performed in 6 sham-operated dogs (N group) and 8 dogs with 4-week-old myocardial infarction (MI group). Four weeks after the ligation of left anterior descending coronary artery, fast Fourier transform was performed on 60-lead epicardial electrograms, and then inverse transform was performed on 5 frequency ranges from 0 to 250 Hz. From the QRS onset to QRS offset, the time integration of unsigned value of reconstructed waveform was calculated and displayed as AQRS maps. On 0-25 Hz AQRS map, there was no significant difference between the 2 groups. In the frequency ranges of 25-250 Hz, MI group had significantly smaller AQRS values than N group solely in the infarct zone. It was shown that high frequency potentials (25-250 Hz) within QRS complex were reduced in the infarct zone.

Surgical lung biopsy to diagnose Behcet's vasculitis with adult respiratory distress syndrome.

PubMed

Vydyula, Ravikanth; Allred, Charles; Huartado, Mariana; Mina, Bushra

2014-10-01

A 34-year-old female presented with fever and abdominal pain. Past medical history includes Crohn's and Behcet's disease. Examination revealed multiple skin ulcerations, oral aphthae, and bilateral coarse rales. She developed respiratory distress with diffuse bilateral alveolar infiltrates on chest radiograph requiring intubation. PaO2/FiO2 ratio was 132. The chest computed tomography revealed extensive nodular and patchy ground-glass opacities. Bronchoalveolar lavage demonstrated a predominance of neutrophils. Methylprednisolone 60 mg every 6 h and broad-spectrum antimicrobials were initiated. No infectious etiologies were identified. Surgical lung biopsy demonstrated diffuse alveolar damage (DAD) mixed with lymphocytic and necrotizing vasculitis with multiple small infarcts and thrombi consistent with Behcet's vasculitis. As she improved, steroids were tapered and discharged home on oral cyclophosphamide. Pulmonary involvement in Behcet's is unusual and commonly manifests as pulmonary artery aneurysms, thrombosis, infarction, and hemorrhage. Lung biopsy findings demonstrating DAD are consistent with the clinical diagnosis of adult respiratory distress syndrome. The additional findings of necrotizing vasculitis and infarcts may have led to DAD.

Relation of cardiac troponin I measurements at 24 and 48 hours to magnetic resonance-determined infarct size in patients with ST-elevation myocardial infarction.

PubMed

Hallén, Jonas; Buser, Peter; Schwitter, Jürg; Petzelbauer, Peter; Geudelin, Bernard; Fagerland, Morten W; Jaffe, Allan S; Atar, Dan

2009-12-01

Levels of circulating cardiac troponin I (cTnI) or T are correlated to extent of myocardial destruction after an acute myocardial infarction. Few studies analyzing this relation have employed a second-generation cTnI assay or cardiac magnetic resonance (CMR) as the imaging end point. In this post hoc study of the Efficacy of FX06 in the Prevention of Mycoardial Reperfusion Injury (F.I.R.E.) trial, we aimed at determining the correlation between single-point cTnI measurements and CMR-estimated infarct size at 5 to 7 days and 4 months after a first-time ST-elevation myocardial infarction (STEMI) and investigating whether cTnI might provide independent prognostic information regarding infarct size at 4 months even taking into account early infarct size. Two hundred twenty-seven patients with a first-time STEMI were included in F.I.R.E. All patients received primary percutaneous coronary intervention within 6 hours from onset of symptoms. cTnI was measured at 24 and 48 hours after admission. CMR was conducted within 1 week of the index event (5 to 7 days) and at 4 months. Pearson correlations (r) for infarct size and cTnI at 24 hours were r = 0.66 (5 days) and r = 0.63 (4 months) and those for cTnI at 48 hours were r = 0.67 (5 days) and r = 0.65 (4 months). In a multiple regression analysis for predicting infarct size at 4 months (n = 141), cTnI and infarct location retained an independent prognostic role even taking into account early infarct size. In conclusion, a single-point cTnI measurement taken early after a first-time STEMI is a useful marker for infarct size and might also supplement early CMR evaluation in prediction of infarct size at 4 months.

Variations in the use of emergency PCI for the treatment of re-infarction following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.

PubMed

Edmond, J J; French, J K; Aylward, P E G; Wong, C K; Stewart, R A H; Williams, B F; De Pasquale, C G; O'connell, R L; Van den Berg, K; Van de Werf, F J; Simes, R J; White, H D

2007-06-01

Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival. To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02] in analyses which excluded deaths within 12 h. Treatment of re-infarction with reperfusion therapies was markedly under-utilized, especially in non-western countries. PCI for re-infarction, in particular, was associated with a lower 30-day mortality, which may reflect both patient selection and effects of treatment.

Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

PubMed

Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

Long-Term Health Effects of Repeated Exposure to Multiple Vaccines

DTIC Science & Technology

2004-01-01

0.945 Hepatits B surface antigen 0.0% 0.0% NT Anti-hepatitis C antibody 0.0% 2.0% 1.000 HLA - B27 9.8% 10.6% 0.868 NT, not tested. a Tests are two-tailed...536 The distribution of markers for hepatitis A, hepatitis B, hepatitis C, and HLA B27 was similar between groups (Table 1), supporting comparability

Scrub typhus: radiological and clinical findings in abdominopelvic involvement.

PubMed

Kim, Kun Yung; Song, Ji Soo; Park, Eun Hae; Jin, Gong Yong

2017-03-01

To describe the clinical and radiological findings of abdominopelvic involvement in scrub typhus. Abdominopelvic computed tomography (CT) of 78 patients with scrub typhus were evaluated by two readers. The presence of gallbladder wall thickening, arterial inhomogeneous enhancement of the liver, periportal edema, splenic infarction, hepatomegaly, splenomegaly, ascites, pleural effusion, and sites of lymphadenopathy were evaluated. Patients were divided into four clinical subgroups according to laboratory findings. Association between imaging findings and subgroups was analyzed by Chi squared test or Fisher's exact test. The most common CT finding was hepatomegaly (74.4%), followed by splenomegaly (66.7%). The majority of patients had at least three areas of abdominopelvic lymphadenopathy (71.8%). Pelvic lymphadenopathy was most commonly seen when eschar was found in the ipsilateral lower extremity (left, n = 5/7; right, n = 8/13). Significant association between hepatic dysfunction and perigastric lymphadenopathy was documented (p = 0.03). Scrub typhus has a spectrum of variable clinical and radiological findings mimicking those of acute hepatitis. Diffuse abdominopelvic lymphadenopathy involving the retroperitoneum and pelvic area may aid in early diagnosis of scrub typhus. Perigastric lymphadenopathy could be a sign of severe scrub typhus combined with hepatic dysfunction.

Spontaneous Retro-Orbital Subperiosteal Hemorrhage with Complete Resolution Following Percutaneous Coronary Intervention for Acute Myocardial Infarction.

PubMed

Wu, Hsu-Ping; Tsai, Chia-Jung; Tsai, Jui-Peng; Hung, Chung-Lieh; Kuo, Jen-Yuan; Hou, Charles Jia-Yin

2013-03-01

Among the several treatment strategies available for acute myocardial infarction, primary percutaneous coronary intervention concomitant with antithrombotic agents is the primary treatment used to facilitate coronary reperfusion. However, bleeding can create major complications. Here we have presented a case of acute myocardial infarction treated with reperfusion therapy, after which developed a sudden onset of proptosis, with high intraocular pressure, blurred vision, and ecchymosis of the left eye. Spontaneous retro-orbital subperiosteal hemorrhage, a rare complication, was diagnosed based on those symptoms as noted above, as well as other orbital signs and imaging evaluation. Multiple antithrombotic agents, including antiplatelets, low molecular weight heparin, and glycoprotein IIb/IIIa receptor inhibitor were thought to be the main precipitating factors of this complication. Thereafter, conservative medical treatment was applied. In the following 2 weeks, all the patient's orbital signs resolved gradually without visual impairment. In conclusion, our experience with a rare case of complications arising from reperfusion therapy used to treat myocardial infarction suggests that clinicians should remain vigilant for any hemorrhagic events during acute myocardial infarction treatment. Acute myocardial infarction; Percutaneous coronary intervention; Retro-orbital subperiosteal hemorrhage.

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs.

PubMed

Andreka, Gyorgy; Vertesaljai, Marton; Szantho, Gergely; Font, Gusztav; Piroth, Zsolt; Fontos, Geza; Juhasz, Eszter D; Szekely, Laszlo; Szelid, Zsolt; Turner, Mark S; Ashrafian, Houman; Frenneaux, Michael P; Andreka, Peter

2007-06-01

Ischaemic preconditioning results in a reduction in ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non-vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential.

Recurrent Fat Embolic Strokes in a Patient With Duchenne Muscular Dystrophy With Long Bone Fractures and a Patent Foramen Ovale.

PubMed

Bugnitz, Christopher J; Cripe, Linda H; Lo, Warren D; Flanigan, Kevin M

2016-10-01

Individuals with Duchenne muscular dystrophy have an increased risk of long bone fractures. Such fractures are sometimes associated with brain dysfunction due to fat embolism syndrome, although this syndrome has seldom been documented in muscular dystrophy patients. We describe a child with Duchenne muscular dystrophy who developed fat embolism syndrome with neurological dysfunction following multiple long bone fractures. He experienced recurrent cerebral infarctions that probably resulted from embolization through a patent foramen ovale. The patent foramen ovale was closed by an occluder device in the cardiac catheterization laboratory, and he did not experience further infarctions. Fat embolism with ischemic cerebral infarction can occur in individuals with Duchenne muscular dystrophy following long bone fractures. In this setting it is important to identify and close atrial level shunts in order to prevent additional infarctions. Copyright © 2016 Elsevier Inc. All rights reserved.

Fluctuating drowsiness following cardiac catheterisation: artery of Percheron ischaemic stroke causing bilateral thalamic infarcts.

PubMed

Hammersley, Daniel; Arora, Ankur; Dissanayake, Madhava; Sengupta, Nabarun

2017-01-02

An 81-year-old man underwent cardiac catheterisation to investigate breathlessness and left ventricular impairment of unknown cause. He had unobstructed coronary arteries. Immediately following the procedure, he became suddenly unresponsive with vertical gaze palsy, anisocoria and bilateral upgoing plantar responses. He made a rapid recovery to his premorbid state 25 min later with no residual focal neurological signs. He then had multiple unresponsive episodes, interspaced with complete resolution of symptoms and neurological signs. MRI of the brain identified bilateral medial thalamic infarcts and midbrain infarcts, consistent with an artery of Percheron territory infarction. By the time the diagnosis was reached, the thrombolysis window had elapsed. The unresponsive episodes diminished with time and the patient was discharged to inpatient rehabilitation. At 6-month review after the episode, the patient has a degree of progressive cognitive impairment. 2017 BMJ Publishing Group Ltd.

Job characteristics in relation to the prevalence of myocardial infarction in the US Health Examination Survey (HES) and the Health and Nutrition Examination Survey (HANES).

PubMed

Karasek, R A; Theorell, T; Schwartz, J E; Schnall, P L; Pieper, C F; Michela, J L

1988-08-01

Associations between psychosocial job characteristics and past myocardial infarction (MI) prevalence for employed males were tested with the Health Examination Survey (HES) 1960-61, N = 2,409, and the Health and Nutrition Examination Survey (HANES) 1971-75, N = 2,424. A new estimation method is used which imputes to census occupation codes, job characteristic information from national surveys of job characteristics (US Department of Labor, Quality of Employment Surveys). Controlling for age, we find that employed males with jobs which are simultaneously low in decision latitude and high in psychological work load (a multiplicative product term isolating 20 per cent of the population) have a higher prevalence of myocardial infarction in both data bases. In a logistic regression analysis, using job measures adjusted for demographic factors and controlling for age, race, education, systolic blood pressure, serum cholesterol, smoking (HANES only), and physical exertion, we find a low decision latitude/high psychological demand multiplicative product term associated with MI in both data bases. Additional multiple logistic regressions show that low decision latitude is associated with increased prevalence of MI in both the HES and the HANES. Psychological workload and physical exertion are significant only in the HANES.

Job characteristics in relation to the prevalence of myocardial infarction in the US Health Examination Survey (HES) and the Health and Nutrition Examination Survey (HANES).

PubMed Central

Karasek, R A; Theorell, T; Schwartz, J E; Schnall, P L; Pieper, C F; Michela, J L

1988-01-01

Associations between psychosocial job characteristics and past myocardial infarction (MI) prevalence for employed males were tested with the Health Examination Survey (HES) 1960-61, N = 2,409, and the Health and Nutrition Examination Survey (HANES) 1971-75, N = 2,424. A new estimation method is used which imputes to census occupation codes, job characteristic information from national surveys of job characteristics (US Department of Labor, Quality of Employment Surveys). Controlling for age, we find that employed males with jobs which are simultaneously low in decision latitude and high in psychological work load (a multiplicative product term isolating 20 per cent of the population) have a higher prevalence of myocardial infarction in both data bases. In a logistic regression analysis, using job measures adjusted for demographic factors and controlling for age, race, education, systolic blood pressure, serum cholesterol, smoking (HANES only), and physical exertion, we find a low decision latitude/high psychological demand multiplicative product term associated with MI in both data bases. Additional multiple logistic regressions show that low decision latitude is associated with increased prevalence of MI in both the HES and the HANES. Psychological workload and physical exertion are significant only in the HANES. PMID:3389427

A retrospective analysis of negative diffusion-weighted image results in patients with acute cerebral infarction

PubMed Central

Zuo, Lian; Zhang, Yue; Xu, Xiahong; Li, Ying; Bao, Huan; Hao, Junjie; Wang, Xin; Li, Gang

2015-01-01

We aimed to investigate the clinicoradiologic determinants of negative diffusion-weighted image (DWI) results in patients with acute cerebral infarction (ACI). The medical records were reviewed of ACI patients. Patients were divided to the DWI positive and negative group. Positive DWI was used as independent variable and patients' clinicoradiologic factors were used as co-variables for multivariate logistic regression analysis. 349 patients received initial cerebral MRI within 72 hours of admission. Lacunar infarction was most common (42.1%) followed by posterior circulation infarction (30.1%) and partial anterior circulation infarction (18.1%). The majority of the patients (72.2%) had an NIHSS score of less than 5 at admission. 316 patients (90.54%) were positive on initial DWI. Patients with smoking, initial SBP ≥ 140 or DBP ≥ 90 mmHg, initial fasting plasma glucose (FPG) ≥7.0 mmol/L, initial MRI from onset of disease >1 d and anterior circulation infarction were liable to show positive DWI. Furthermore, DWI negative patients had significantly lower NIHSS scores (IQR 0,1,2) than DWI positive patients (IQR 1,2,4) (P = 0.000) at two weeks post onset of acute cerebral infarction. In conclusion, multiple clinicoradiologic factors are associated with negative and positive DWI and further delineation of these factors is required in future prospective studies. PMID:25777182

[Post Traumatic Pseudoaneurysm of the Hepatic Artery - Clinical report].

PubMed

Rolim, Dalila; Sampaio, Sérgio; Almeida Pinto, João; Oliveira, Manuel

2014-01-01

Hepatic artery aneurysms are a rare condition that can be fatal if rupture happens. Often, they are incidentally identified in routine imaging. Intervention is indicated when symptomatic, if they reach 2cm or more of size, in patients presenting with multiple hepatic artery aneurysms and in all pseudoaneurysms. We describe the case of a 57 year-old female, to whom a post-traumatic hepatic artery aneurysm was diagnosed. Open surgical repair was successfully accomplished.

Redefining Myocardial Infarction: What Is New In The ESC/ACCF/AHA/WHF Third Universal Definition Of Myocardial Infarction?

PubMed Central

Alam, Mahboob; Virani, Salim S.; Bozkurt, Biykem

2013-01-01

Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Each year, an estimated 785,000 persons will have a new MI in the United States alone, and approximately every minute an American will succumb to one.1 In addition, MI has major psychological and legal implications for patients and the society and is an important outcome measure in research studies. The prevalence of MI provides useful data regarding the burden of coronary artery disease and offers insight into health care planning, policy, and resource allocation. The importance of accurately and reproducibly defining MI is therefore self-evident. The Third Universal Definition of Myocardial Infarction (MI) expert consensus document was published in October 2012 by the global Myocardial Infarction Task Force.2 This landmark document was cosponsored by multiple cardiovascular societies and included both updated definitions and a modified classification of MI that have important clinical, epidemiological, and research implications. We hereby present a critical overview of this important document and summarize its key recommendations. PMID:24066201

Redefining myocardial infarction: what is new in the ESC/ACCF/AHA/WHF Third Universal Definition of myocardial infarction?

PubMed

Jneid, Hani; Alam, Mahboob; Virani, Salim S; Bozkurt, Biykem

2013-01-01

Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Each year, an estimated 785,000 persons will have a new MI in the United States alone, and approximately every minute an American will succumb to one.1 In addition, MI has major psychological and legal implications for patients and the society and is an important outcome measure in research studies. The prevalence of MI provides useful data regarding the burden of coronary artery disease and offers insight into health care planning, policy, and resource allocation. The importance of accurately and reproducibly defining MI is therefore self-evident. The Third Universal Definition of Myocardial Infarction (MI) expert consensus document was published in October 2012 by the global Myocardial Infarction Task Force.2 This landmark document was cosponsored by multiple cardiovascular societies and included both updated definitions and a modified classification of MI that have important clinical, epidemiological, and research implications. We hereby present a critical overview of this important document and summarize its key recommendations.

Measuring the Consistency in Change in Hepatitis B Knowledge among Three Different Types of Tests: True/False, Multiple Choice, and Fill in the Blanks Tests.

ERIC Educational Resources Information Center

Sahai, Vic; Demeyere, Petra; Poirier, Sheila; Piro, Felice

1998-01-01

The recall of information about Hepatitis B demonstrated by 180 seventh graders was tested with three test types: (1) short-answer; (2) true/false; and (3) multiple-choice. Short answer testing was the most reliable. Suggestions are made for the use of short-answer tests in evaluating student knowledge. (SLD)

Diffusion-weighted MRI determined cerebral embolic infarction following transcatheter aortic valve implantation: assessment of predictive risk factors and the relationship to subsequent health status.

PubMed

Fairbairn, Timothy A; Mather, Adam N; Bijsterveld, Petra; Worthy, Gillian; Currie, Stuart; Goddard, Anthony J P; Blackman, Daniel J; Plein, Sven; Greenwood, John P

2012-01-01

'Silent' cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma (arch and descending aorta; r=0.91, p<0.001, r=0.69, p=0.001, respectively) and catheterisation time (r=0.45, p=0.02) were predictors of the number of new cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary increased significantly (32.4±6.2 vs 36.5±7.2; p=0.03) with no significant change in mental component summary (43.5±11.7 vs. 43.1±14.3; p=0.85). The EQ5D score and Visual Analogue Scale showed no significant change (0.56±0.26 vs. 0.59±0.31; p=0.70, and 54.2±19 vs. 58.2±24; p=0.43). Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were 'silent' with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

[The clinico-epidemiological premises for antioxidant prevention and treatment in chronic myocardial infarct].

PubMed

Azoicăi, D; Mitu, F; Iacobovici, A; Pavel, M; Jerca, L; Ungureanu, D; Popovici, I; Cojocaru, M; Ivan, A; Gheorghiţă, N

1996-01-01

The improvement of therapeutic and recoverable proceeding to chronic myocardial infarction (IMC) imposes a complex epidemiological estimation of the global cardiovascular risk, of their clinical and biological status. The retrospective evaluation of the risk factors (RF) by epidemiological methods, in 38 hospitalized prevalence of both constitutional and behavioral factors, and the quantification of the risk state, according to graph Euro 194, has pointed on the fact that 50% of IMC cases have presented a global risk of 10-20%. That justified the application of a preventive conduct in order to continually neutralize the associates FR. The biochemical determinations have allowed to frame the dyslipidemic patients, according to the ARCOL classification in the classes D (29.2%), E (25.0%) and B (20.8%) with direct implication in the adopted therapy. The colorimetric dozing with thyo-barbituric acid of the malonly dialdehyde (MAD) each is a product of the lipidic peroxidation, as well as the interpreting or correlation of the registered values with an evolutive clinic stage, and with the existence of some existing diseases (diabetes, chronic hepatitis etc.) along with signification of other dismethabolical parameters (cholesterol, triglycerides, LDLc, apoB) have confirmed the necessity of a complex therapy, including an antioxidative treatment, having the role to directly inhibit or exclude the free radicals resulted after the oxidative stress of the infarct.

'Postconditioning' the human heart: multiple balloon inflations during primary angioplasty may confer cardioprotection.

PubMed

Darling, Chad E; Solari, Patrick B; Smith, Craig S; Furman, Mark I; Przyklenk, Karin

2007-05-01

Growing evidence from experimental models suggests that relief of myocardial ischemia in a stuttering manner (i.e., 'postconditioning' [PostC] with brief cycles of reperfusion-reocclusion) limits infarct size. However, the potential clinical efficacy of PostC has, to date,been largely unexplored. Using a retrospective study design, our aim was to test the hypothesis that creatine kinase release (CK: clinical surrogate of infarct size) would be attenuated in ST-segment elevation myocardial infarction (STEMI) patients requiring multiple balloon inflations-deflations during primary angioplasty versus STEMI patients who received minimal balloon inflations and/or direct stenting. To investigate this concept, we reviewed the records of all STEMI patients with single vessel occlusion who presented to our institution from November 2004 - April 2006 for primary angioplasty. Exclusion criteria were: previous MI, cardiogenic shock, patients resuscitated from cardiac arrest, or pre-infarct angina. Patients were prospectively divided into two subsets: those receiving 1-3 balloon inflations (considered the minimum range to achieve patency and stent placement) versus those in whom 4 or more inflations were applied. Peak CK release was significantly lower in patients requiring > or =4 versus 1-3 inflations (1655 versus 2272 IU/L; p<0.05), an outcome consistent with the concept that relief of sustained ischemia in a stuttered manner (analogous to postconditioning) may evoke cardioprotection in the clinical setting.

Curing the historically incurable: treatment success with ledipasvir/sofosbuvir for chronic hepatitis C virus in a heavily treatment-experienced individual.

PubMed

Johnson, S W; Davis, M M; Stever, L M; Priest, D H

2016-12-01

Significant progression in the treatment of chronic hepatitis C virus has been made with the introduction of direct-acting antivirals (DAAs). However, limited data are available for the retreatment of individuals who have failed multiple prior DAAs. We report a single case of an individual who was unsuccessfully treated with five prior hepatitis C virus treatment regimens including simeprevir plus sofosbuvir who was successfully cured after treatment with ledipasvir/sofosbuvir. Ledipasvir/sofosbuvir may be an option for treating patients who have failed multiple prior DAA regimens; however, further research is warranted. © 2016 John Wiley & Sons Ltd.

Optimized energy of spectral CT for infarct imaging: Experimental validation with human validation.

PubMed

Sandfort, Veit; Palanisamy, Srikanth; Symons, Rolf; Pourmorteza, Amir; Ahlman, Mark A; Rice, Kelly; Thomas, Tom; Davies-Venn, Cynthia; Krauss, Bernhard; Kwan, Alan; Pandey, Ankur; Zimmerman, Stefan L; Bluemke, David A

Late contrast enhancement visualizes myocardial infarction, but the contrast to noise ratio (CNR) is low using conventional CT. The aim of this study was to determine if spectral CT can improve imaging of myocardial infarction. A canine model of myocardial infarction was produced in 8 animals (90-min occlusion, reperfusion). Later, imaging was performed after contrast injection using CT at 90 kVp/150 kVpSn. The following reconstructions were evaluated: Single energy 90 kVp, mixed, iodine map, multiple monoenergetic conventional and monoenergetic noise optimized reconstructions. Regions of interest were measured in infarct and remote regions to calculate contrast to noise ratio (CNR) and Bhattacharya distance (a metric of the differentiation between regions). Blinded assessment of image quality was performed. The same reconstruction methods were applied to CT scans of four patients with known infarcts. For animal studies, the highest CNR for infarct vs. myocardium was achieved in the lowest keV (40 keV) VMo images (CNR 4.42, IQR 3.64-5.53), which was superior to 90 kVp, mixed and iodine map (p = 0.008, p = 0.002, p < 0.001, respectively). Compared to 90 kVp and iodine map, the 40 keV VMo reconstructions showed significantly higher histogram separation (p = 0.042 and p < 0.0001, respectively). The VMo reconstructions showed the highest rate of excellent quality scores. A similar pattern was seen in human studies, with CNRs for infarct maximized at the lowest keV optimized reconstruction (CNR 4.44, IQR 2.86-5.94). Dual energy in conjunction with noise-optimized monoenergetic post-processing improves CNR of myocardial infarct delineation by approximately 20-25%. Published by Elsevier Inc.

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2016-12-01

Lisinopril oral solution (Qbrelis) for the treatment of hypertension, heart failure, and acute myocardial infarction; etanercept-szzs (Erelzi) for multiple autoimmune disorders; and lumacaftor/ivacaftor (Orkambi) for cystic fibrosis.

Prospective study of the frequency of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas.

PubMed

Horii, Kimberly A; Drolet, Beth A; Frieden, Ilona J; Baselga, Eulalia; Chamlin, Sarah L; Haggstrom, Anita N; Holland, Kristen E; Mancini, Anthony J; McCuaig, Catherine C; Metry, Denise W; Morel, Kimberly D; Newell, Brandon D; Nopper, Amy J; Powell, Julie; Garzon, Maria C

2011-01-01

Multiple cutaneous infantile hemangiomas have been associated with hepatic hemangiomas. Screening of infants with five or more cutaneous infantile hemangiomas with abdominal ultrasound is often recommended. The aim of this study was to determine the frequency with which hepatic hemangiomas occur in infants with five or more cutaneous infantile hemangiomas compared to those with one to four cutaneous infantile hemangiomas and to characterize the clinical features of these hepatic hemangiomas. A multicenter prospective study of children with cutaneous infantile hemangiomas was conducted at pediatric dermatology clinics at Hemangioma Investigator Groups sites in the United States, Canada, and Spain between October 2005 and December 2008. Data were collected, and abdominal ultrasonography was performed on infants younger than 6 months old with five or more cutaneous infantile hemangiomas and those with one to four cutaneous infantile hemangiomas. Twenty-four (16%) of the 151 infants with five or more cutaneous infantile hemangiomas had hepatic hemangiomas identified on abdominal ultrasound, versus none of the infants with fewer than five (p = 0.003). Two of the 24 infants with hepatic hemangiomas received treatment specifically for their hepatic hemangiomas. Infants with five or more cutaneous infantile hemangiomas have a statistically significantly greater frequency of hepatic hemangiomas than those with fewer than 5. These findings support the recommendation of five or more cutaneous infantile hemangiomas as a threshold for screening infants younger than 6 months old for hepatic hemangiomas but also demonstrate that the large majority of these infants with hepatic hemangiomas do not require treatment. © 2011 Wiley Periodicals, Inc.

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs

PubMed Central

Andreka, Gyorgy; Vertesaljai, Marton; Szantho, Gergely; Font, Gusztav; Piroth, Zsolt; Fontos, Geza; Juhasz, Eszter D; Szekely, Laszlo; Szelid, Zsolt; Turner, Mark S; Ashrafian, Houman; Frenneaux, Michael P

2007-01-01

Background Ischaemic preconditioning results in a reduction in ischaemic‐reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non‐vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. Objective To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Methods Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Results Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. Conclusion Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential. PMID:17449499

[Multiple cerebral infarctions in a patient with hypereosinophilic syndrome with Löffler endocarditis: a case report].

PubMed

Ishii, Junko; Yamamoto, Shiro; Yoshimura, Hajime; Todo, Kenichi; Kawamoto, Michi; Kohara, Nobuo

2015-01-01

An 82-year-old woman with a history of asthma was admitted to our hospital because of dyspnea. On admission, laboratory testing showed a white blood cell count of 17,700/μl with hypereosinophilia of 9,204/μl (52% of all white blood cells). Various examinations, including a bone marrow biopsy for the cause of eosinophilia, were unremarkable. The patient was diagnosed with hypereosinophilic syndrome (HES). Treatment with intravenous methylprednisolone was initiated. The patient's eosinophil count normalized within 1 day. On the 6th day, she developed left-sided hemiparesis. Magnetic resonance imaging (MRI) of the brain showed acute multiple infarcts in arterial border zones of bilateral cerebral and cerebellar hemispheres, and in bilateral basal ganglia and the thalamus. Magnetic resonance angiography was normal. Coagulation factors were normal, except for an elevated D-dimer level (12.9 μg/ml). A transthoracic echocardiogram showed thickening of the left ventricular endocardium with immobile thrombus, compatible with Löffler endocarditis. Treatment with oral prednisolone was started at 30 mg/day and then tapered to a maintenance dose of 5 mg/day. Anticoagulation was concurrently started for prevention of stroke. Ten months later, an echocardiogram showed that the thrombus had decreased in size, and MRI revealed no new cerebral infarctions. The cause of cerebral infarction in patients with hypereosinophilia is thought to be thromboembolism or cerebrovascular endothelial toxicity of eosinophils. In this patient, the cerebral infarcts may have been the result of embolism from the left ventricular thrombus. Because HES with Löffler endocarditis is frequently associated with a poor prognosis, cardiovascular problems should be evaluated and treatment started as soon as possible.

[Two cases of cerebral infarction caused by fat embolism during orthopedic bone surgeries].

PubMed

Takinami, Yoshikazu

2009-08-01

I report on two cases of cerebral infarction caused by fat embolism during the orthopedic surgeries. The first patient was a 77-year-old woman with a femur neck fracture, who developed coma after orthopedic operation. The other was a 70-year-old woman with open fractures in the femur and the fibula, who developed hemiplegia after operation. By echogram, no embolus was demonstrated in the heart, in the carotid arteries or in deep veins, also paradoxical cerebral infarction was denied in the both cases. Diffusion-weighted MR image and FLAIR MR image showing multiple hyperintense signals in the hemispheres were very useful as a diagnosing modality in acute stage. The patients gradually recovered with the intensive treatment.

Posttraumatic venous gas in the liver - a case report and review of the current literature.

PubMed

Fahrner, René; Rauchfuss, Falk; Scheuerlein, Hubert; Settmacher, Utz

2018-03-02

There are numerous causes of hepatic gas formation that range from serious pathologies to incidental findings, including mesenteric infarction, liver abscess, inflammatory bowel disease or minimally invasive hepatic interventions. We report a case of a 50-year-old man who was admitted to the emergency room after a car accident. The clinical examination and further diagnostics revealed a craniocerebral injury with a fracture of the skull, concomitant soft tissue lesions and subarachnoidal bleeding. Furthermore, a blunt thoracic trauma with hemopneumothorax due to rib fractures was treated with a chest tube. No obvious abdominal pathology was seen. While in the operating theatre for the surgical revision of the cranial soft tissue lesions, a femoral venous catheter was inserted without any complications. A routine ultrasound of the abdomen six hours after the trauma revealed unclear hepatic gas formation. A contrast-enhanced computer tomography (CT) scan of the abdomen was performed, and the gas formation was found to be localized within the left hepatic vein. Afterwards, there was no specific treatment of the hepatic venous gas formation, as no alterations of liver function or liver enzymes were seen. The further course of the patient was uneventful regarding the gas formation in the liver, and another ultrasound two days later revealed no further gas in the liver. The placement of a femoral venous catheter is a risk factor for gas formation in liver veins. No further treatment is needed in cases with stable liver function. To rule out serious pathologies, diagnostic findings (e.g., ultrasound, CT), clinical history and underlying diseases need to be analyzed carefully after the detection of intrahepatic gas formation. With contrast-enhanced CT, the localization of the gas and its potential causes might be detectable.

Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study.

PubMed

Brown, Jennifer; Plummer, Ruth; Bauer, Todd M; Anthony, Stephen; Sarantopoulos, John; De Vos, Filip; White, Mike; Schupp, Marco; Ou, Ying; Vaishampayan, Ulka

2017-01-01

Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles. The primary objective was to assess the influence of hepatic impairment on carfilzomib PK following 27 and 56 mg/m 2 doses. The majority of patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since patients with multiple myeloma do not tend to have severe hepatic impairment in the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14 moderate, and 4 severe hepatic impairment patients were enrolled. Compared with patients with normal hepatic function, patients with mild and moderate hepatic impairment had 44 and 26% higher carfilzomib AUC 0-last , respectively (27 mg/m 2 dose); increases at the 56 mg/m 2 dose were 45 and 21%, respectively. Considerable PK variability (% coefficient of variation in AUC ≤100%) was discerned and no consistent trend of increasing exposure resulting from increasing hepatic impairment severity (moderate vs. mild) was seen. The observed adverse event (AE) profile in patients of mostly solid tumors was consistent with the known safety profile of carfilzomib, with the exception of an increased frequency of AEs consistent with hepatic function abnormalities. In this population of primarily advanced solid tumor patients, patients with mild and moderate hepatic impairment had approximately 20-50% higher carfilzomib AUC vs. normal hepatic function patients. These increases are unlikely to be clinically significant, in light of the intrinsic PK variability and exposure-response relationship of carfilzomib. Trial registration http://clinicaltrials.gov NCT01949545; date of registration: September 6, 2013.

Laparoscopic liver resection: when to use the laparoscopic stapler device

PubMed Central

Gumbs, Andrew A.; Gayet, Brice

2008-01-01

Minimally invasive hepatic resection was first described by Gagner et al. in the early 1990s and since then has become increasingly adopted by hepatobiliary and liver transplant surgeons. Several techniques exist to transect the hepatic parenchyma laparoscopically and include transection with stapler and/or energy devices, such as ultrasonic shears, radiofrequency ablation and bipolar devices. We believe that coagulative techniques allow for superior anatomic resections and ultimately permit for the performance of more complex hepatic resections. In the stapling technique, Glisson's capsule is usually incised with an energy device until the parenchyma is thinned out and multiple firings of the staplers are then used to transect the remaining parenchyma and larger bridging segmental vessels and ducts. Besides the economic constraints of using multiple stapler firings, the remaining staples have the disadvantage of hindering and even preventing additional hemostasis of the raw liver surface with monopolar and bipolar electrocautery. The laparoscopic stapler device is, however, useful for transection of the main portal branches and hepatic veins during minimally invasive major hepatic resections. Techniques to safely perform major hepatic resection with the above techniques will be described with an emphasis on when and how laparoscopic vascular staplers should be used. PMID:18773113

Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment-Elevation Myocardial Infarction: Results of a Large Prospective Registry.

PubMed

Bodi, Vicente; Monmeneu, Jose V; Ortiz-Perez, Jose T; Lopez-Lereu, Maria P; Bonanad, Clara; Husser, Oliver; Minana, Gemma; Gomez, Cristina; Nunez, Julio; Forteza, Maria J; Hervas, Arantxa; de Dios, Elena; Moratal, David; Bosch, Xavier; Chorro, Francisco J

2016-01-01

To assess predictors of reverse remodeling by using cardiac magnetic resonance (MR) imaging soon after ST-segment-elevation myocardial infarction (STEMI). Written informed consent was obtained from all patients, and the study protocol was approved by the institutional committee on human research, ensuring that it conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Five hundred seven patients (mean age, 58 years; age range, 24-89 years) with a first STEMI were prospectively studied. Infarct size and microvascular obstruction (MVO) were quantified at late gadolinium-enhanced imaging. Reverse remodeling was defined as a decrease in left ventricular (LV) end-systolic volume index (LVESVI) of more than 10% from 1 week to 6 months after STEMI. For statistical analysis, a simple (from a clinical perspective) multiple regression model preanalyzing infarct size and MVO were applied via univariate receiver operating characteristic techniques. Patients with reverse remodeling (n = 211, 42%) had a lesser extent (percentage of LV mass) of 1-week infarct size (mean ± standard deviation: 18% ± 13 vs 23% ± 14) and MVO (median, 0% vs 0%; interquartile range, 0%-1% vs 0%-4%) than those without reverse remodeling (n = 296, 58%) (P < .001 in pairwise comparisons). The independent predictors of reverse remodeling were infarct size (odds ratio, 0.98; 95% confidence interval [CI]: 0.97, 0.99; P = .04) and MVO (odds ratio, 0.92; 95% CI: 0.86, 0.99; P = .03). Once infarct size and MVO were dichotomized by using univariate receiver operating characteristic techniques, the only independent predictor of reverse remodeling was the presence of simultaneous nonextensive infarct-size MVO (infarct size < 30% of LV mass and MVO < 2.5% of LV mass) (odds ratio, 3.2; 95% CI: 1.8, 5.7; P < .001). Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling. © RSNA, 2015

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

PubMed

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Cardiomyopathy in captive African hedgehogs (Atelerix albiventris).

PubMed

Raymond, J T; Garner, M M

2000-09-01

From 1994 to 1999, 16 captive African hedgehogs (Atelerix albiventris), from among 42 necropsy cases, were diagnosed with cardiomyopathy. The incidence of cardiomyopathy in this study population was 38%. Fourteen of 16 hedgehogs with cardiomyopathy were males and all hedgehogs were adult (>1 year old). Nine hedgehogs exhibited 1 or more of the following clinical signs before death: heart murmur, lethargy, icterus, moist rales, anorexia, dyspnea, dehydration, and weight loss. The remaining 7 hedgehogs died without premonitory clinical signs. Gross findings were cardiomegaly (6 cases), hepatomegaly (5 cases), pulmonary edema (5 cases), pulmonary congestion (4 cases), hydrothorax (3 cases), pulmonary infarct (1 case), renal infarcts (1 case), ascites (1 case), and 5 cases showed no changes. Histologic lesions were found mainly within the left ventricular myocardium and consisted primarily of myodegeneration, myonecrosis, atrophy, hypertrophy, and disarray of myofibers. All hedgehogs with cardiomyopathy had myocardial fibrosis, myocardial edema, or both. Other common histopathologic findings were acute and chronic passive congestion of the lungs, acute passive congestion of the liver, renal tubular necrosis, vascular thrombosis, splenic extramedullary hematopoiesis, and hepatic lipidosis. This is the first report of cardiomyopathy in African hedgehogs.

L-NAME reduces infarction, neurological deficit and blood-brain barrier disruption following cerebral ischemia in mice.

PubMed

Ding-Zhou, Li; Marchand-Verrecchia, Catherine; Croci, Nicole; Plotkine, Michel; Margaill, Isabelle

2002-12-20

The role of nitric oxide (NO) in the development of post-ischemic cerebral infarction has been extensively examined, but fewer studies have investigated its role in other outcomes. In the present study, we first determined the temporal evolution of infarct volume, NO production, neurological deficit and blood-brain barrier disruption in a model of transient focal cerebral ischemia in mice. We then examined the effect of the nonselective NO-synthase inhibitor N(omega)-nitro-L-arginine-methylester (L-NAME). L-NAME given at 3 mg/kg 3 h after ischemia reduced by 20% the infarct volume and abolished the increase in brain NO production evaluated by its metabolites (nitrites/nitrates) 48 h after ischemia. L-NAME with this protocol also reduced the neurological deficit evaluated by the grip test and decreased by 65% the extravasation of Evans blue, an index of blood-brain barrier breakdown. These protective activities of L-NAME suggest that NO has multiple deleterious effects in cerebral ischemia.

Spinal cord infarction as a rare complication of fat embolism syndrome following bilateral intramedullary nailing of femur fractures.

PubMed

Kearsley, RoseMarie; Galbraith, John; Dalton, David; Motherway, Catherine

2016-09-13

Fat embolism syndrome (FES) is a rare and potentially fatal complication occurring most often after long bone or pelvic fractures and orthopaedic procedures. It can consist of pulmonary, central nervous system and cutaneous manifestations. The exact pathophysiology of emboli reaching the arterial circulation is poorly understood.1 It is suggested that this may occur by either 'paradoxical' embolism or microembolism.2 3 Its true incidence is unknown but increases in the presence of multiple closed fractures. It can be a diagnostic dilemma for clinicians and if suspected diffusion-weighted MRI is the modality of choice for the investigation of the central nervous system.4 We present the case of a 22-year-old man who developed multifocal cerebral infarcts, a right-sided cerebellar infarct and an infarct in the anterior cord bilaterally at the level of C5-C6 as a result of FES. 2016 BMJ Publishing Group Ltd.

Association of Lifestyle-Related Comorbidities With Periodontitis

PubMed Central

Lee, Jae-Hong; Lee, Jung-Seok; Park, Jin-Young; Choi, Jung-Kyu; Kim, Dong-Wook; Kim, Young-Taek; Choi, Seong-Ho

2015-01-01

Abstract The aim of this study was to determine the association of periodontitis with lifestyle-related comorbidities (LCs) using data in the Korean National Health Insurance Cohort Database from 2002 to 2013. This was a retrospective study involving a large national cohort with patient samples (representing 2% of the total Korean population) stratified on the basis of sociodemographic information. Using this precisely extracted database, the correlations between LCs (cerebral infarction, angina pectoris, myocardial infarction, hypertension, diabetes mellitus, rheumatoid arthritis, erectile dysfunction, osteoporosis, and obesity) and periodontitis were investigated while adjusting for confounding bias. Univariate and multiple logistic regression analyses were used to evaluate differences in variable factors. Among a total of 1,025,340 samples, 321,103 (31.3%) cases were diagnosed with periodontitis. Statistically significant associations were found between all LCs except myocardial infarction and periodontitis (P < 0.005). Periodontitis is significantly and positively correlated with LCs (except for myocardial infarction) after adjusting for confounding bias. In particular, lifestyle-related diseases, erectile dysfunction, and osteoporosis seem to be intimately related to periodontitis. PMID:26376407

Towards Comprehensive Cardiac Repair and Regeneration after Myocardial Infarction: Aspects to Consider and Proteins to Deliver

PubMed Central

Awada, Hassan K.; Hwang, Mintai P.; Wang, Yadong

2016-01-01

Ischemic heart disease is a leading cause of death worldwide. After the onset of myocardial infarction, many pathological changes take place and progress the disease towards heart failure. Pathologies such as ischemia, inflammation, cardiomyocyte death, ventricular remodeling and dilation, and interstitial fibrosis, develop and involve the signaling of many proteins. Proteins can play important roles in limiting or countering pathological changes after infarction. However, they typically have short half-lives in vivo in their free form and can benefit from the advantages offered by controlled release systems to overcome their challenges. The controlled delivery of an optimal combination of proteins per their physiologic spatiotemporal cues to the infarcted myocardium holds great potential to repair and regenerate the heart. The effectiveness of therapeutic interventions depends on the elucidation of the molecular mechanisms of the cargo proteins and the spatiotemporal control of their release. It is likely that multiple proteins will provide a more comprehensive and functional recovery of the heart in a controlled release strategy. PMID:26757257

Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.

PubMed

Li, Jibiao; Woolbright, Benjamin L; Zhao, Wen; Wang, Yifeng; Matye, David; Hagenbuch, Bruno; Jaeschke, Hartmut; Li, Tiangang

2018-01-01

Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study further investigated the role of Sort1 in modulating BA detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger BA pool size than sham-operated wildtype (WT) mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic BA accumulation and smaller BA pool size. After 14 days BDL, Sort1 KO mice showed significantly lower hepatic BA concentration and reduced expression of inflammatory and fibrotic marker genes, but similar degree of liver fibrosis compared with WT mice. Unbiased quantitative proteomics revealed that Sort1 KO mice had increased hepatic BA sulfotransferase 2A1, but unaltered phase-I BA metabolizing cytochrome P450s or phase-III BA efflux transporters. Consistently, Sort1 KO mice showed elevated plasma sulfated taurocholate after BDL. Finally, we found that liver Sort1 was repressed after BDL, which may be due to BA activation of farnesoid x receptor. In conclusion, we report a role of Sort1 in the regulation of hepatic BA detoxification and cholestatic liver injury in mice. The mechanisms underlying increased hepatic BA elimination in Sort1 KO mice after BDL require further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antifungal Activity and Pharmacokinetics of Posaconazole (SCH 56592) in Treatment and Prevention of Experimental Invasive Pulmonary Aspergillosis: Correlation with Galactomannan Antigenemia

PubMed Central

Petraitiene, Ruta; Petraitis, Vidmantas; Groll, Andreas H.; Sein, Tin; Piscitelli, Stephen; Candelario, Myrna; Field-Ridley, Aida; Avila, Nilo; Bacher, John; Walsh, Thomas J.

2001-01-01

The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg/kg per os; or amphotericin B (AMB) at 1 mg/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (P < 0.01). There was dosage-dependent microbiological clearance of A. fumigatus from lung tissue in response to POC. Serum creatinine levels were greater (P < 0.01) in AMB-treated animals than in UC and POC- or ITC-treated rabbits. There was no elevation of serum hepatic transaminase levels in POC- or ITC-treated rabbits. The pharmacokinetics of POC and ITC in plasma demonstrated dose dependency after multiple dosing. The 2-, 6-, and 20-mg/kg dosages of POC maintained plasma drug levels above the MICs for the entire 24-h dosing interval. In summary, POC at ≥6 mg/kg/day per os generated sustained concentrations in plasma of ≥1 μg/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg/kg/day and more effective than cyclodextrin ITC at ≥6 mg/kg/day per os in persistently neutropenic rabbits. PMID:11181372

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.

PubMed

Cichoż-Lach, Halina; Michalak, Agata

2013-01-07

Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses.

Synchronous occurrence of multiple focal nodular hyperplasia and huge hepatic perivascular epithelioid cells tumor (PEComa) in young woman after oral contraceptive use--is there a common pathogenesis?

PubMed

Durczyński, Adam; Hogendorf, Piotr; Szymański, Dariusz; Sporny, Stanisław; Strzelczyk, Janusz

2012-09-01

The association of focal nodular hyperplasia (FNH) and various neoplasms was described, but coincidence of multiple FNH and hepatic perivascular epithelioid cells tumor (PEComa) has not been reported. The clinical debate of oral contraceptive (OC) influence on FNH growth is ongoing, but no evidence exists about association of hepatic PEComa with OC use. Herein, we report a case of two FNH lesions and huge (150x100x80 mm) left hepatic lobe PEComa that occurred simultaneously in 18-year-old female with previous two year history of OC use, who underwent left hemihepatectomy and right hepatic FNH enucleation. Up to date, the patient has been followed-up for 65 months and remained disease-free. FNH and PEComa have a common vascular cytogenetic denominator. Our case raising a question of a causal relationship of FNH and PEComa with OC use that might be attributed to vascular changes. Future researches of larger sample sizes should further address this issue.

Reperfusion therapy of myocardial infarction in Mexico: A challenge for modern cardiology.

PubMed

Martínez-Sánchez, Carlos; Arias-Mendoza, Alexandra; González-Pacheco, Héctor; Araiza-Garaygordobil, Diego; Marroquín-Donday, Luis Alfonso; Padilla-Ibarra, Jorge; Sierra-Fernández, Carlos; Altamirano-Castillo, Alfredo; Álvarez-Sangabriel, Amada; Azar-Manzur, Francisco Javier; Briseño-de la Cruz, José Luis; Mendoza-García, Salvador; Piña-Reyna, Yigal; Martínez-Ríos, Marco Antonio

Mexico has been positioned as the country with the highest mortality attributed to myocardial infarction among the members of the Organization for Economic Cooperation and Development. This rate responds to multiple factors, including a low rate of reperfusion therapy and the absence of a coordinated system of care. Primary angioplasty is the reperfusion method recommended by the guidelines, but requires multiple conditions that are not reached at all times. Early pharmacological reperfusion of the culprit coronary artery and early coronary angiography (pharmacoinvasive strategy) can be the solution to the logistical problem that primary angioplasty rises. Several studies have demonstrated pharmacoinvasive strategy as effective and safe as primary angioplasty ST-elevation myocardial infarction, which is postulated as the choice to follow in communities where access to PPCI is limited. The Mexico City Government together with the National Institute of Cardiology have developed a pharmaco-invasive reperfusion treatment program to ensure effective and timely reperfusion in STEMI. The model comprises a network of care at all three levels of health, including a system for early pharmacological reperfusion in primary care centers, a digital telemedicine system, an inter-hospital transport network to ensure primary angioplasty or early percutaneous coronary intervention after fibrinolysis and a training program with certification of the health care personal. This program intends to reduce morbidity and mortality associated with myocardial infarction. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Histological quantification of brain tissue inflammatory cell infiltration after focal cerebral infarction: a systematic review.

PubMed

Russek, Natanya S; Jensen, Matthew B

2014-03-01

Ischemic stroke is a leading cause of death and disability, and current treatments to limit tissue injury and improve recovery are limited. Cerebral infarction is accompanied by intense brain tissue inflammation involving many inflammatory cell types that may cause both negative and positive effects on outcomes. Many potential neuroprotective and neurorestorative treatments may affect, and be affected by, this inflammatory cell infiltration, so that accurate quantification of this tissue response is needed. We performed a systematic review of histological methods to quantify brain tissue inflammatory cell infiltration after cerebral infarction. We found reports of multiple techniques to quantify different inflammatory cell types. We found no direct comparison studies and conclude that more research is needed to optimize the assessment of this important stroke outcome.

Bacillus cereus causing fulminant sepsis and hemolysis in two patients with acute leukemia.

PubMed

Arnaout, M K; Tamburro, R F; Bodner, S M; Sandlund, J T; Rivera, G K; Pui, C H; Ribeiro, R C

1999-01-01

Hemolysis is so rarely associated with Bacillus cereus sepsis that only two very well documented cases have been reported. This article reports two unusual cases of Bacillus cereus sepsis with massive intravascular hemolysis in patients who had acute lymphoblastic leukemia (ALL). A 20-year-old woman who was 9 weeks pregnant experienced a relapse of ALL. A therapeutic abortion was performed. During week 4 of reinduction the patient had abdominal pain, nausea, and vomiting, with severe neutropenia but no fever. Her condition deteriorated rapidly with cardiovascular collapse, acute massive intravascular hemolysis, and death within hours of the onset of symptoms. Blood cultures were positive for Bacillus cereus. Postmortem histologic examination and cultures revealed Bacillus cereus and Candida albicans in multiple organs. The second patient, a 10-year-old girl, presented with relapsed T-cell ALL. In the second week of reinduction, she had abdominal pain followed by hypotension. Again, no fever was noted. Laboratory studies showed intravascular hemolysis 12 hours after admission. Aggressive support was promptly initiated. Despite disseminated intravascular coagulation; cardiovascular, hepatic, and renal failure; and multiple intracerebral hypodense lesions believed to be infarcts, the patient recovered fully and resumed reinduction therapy. Bacillus cereus infection can have a fulminant clinical course that may be complicated by massive intravascular hemolysis. This pathogen should be suspected in immunosuppressed patients who experience gastrointestinal symptoms and should not be precluded by the absence of fever, especially if steroids such as dexamethasone are being given. Exchange transfusion may be lifesaving in Bacillus cereus septicemia associated with massive hemolysis.

Vertebral Artery Dissection Causing Stroke After Trampoline Use.

PubMed

Casserly, Courtney S; Lim, Rodrick K; Prasad, Asuri Narayan

2015-11-01

The aim of this study was to report a case of a 4-year-old boy who had been playing on the trampoline and presented to the emergency department (ED) with vomiting and ataxia, and had a vertebral artery dissection with subsequent posterior circulation infarcts. This study is a chart review. The patient presented to the emergency department with a 4-day history of vomiting and gait unsteadiness. A computed tomography scan of his head revealed multiple left cerebellar infarcts. Subsequent magnetic resonance imaging/magnetic resonance angiogram of his head and neck demonstrated multiple infarcts involving the left cerebellum, bilateral thalami, and left occipital lobe. A computed tomography angiogram confirmed the presence of a left vertebral artery dissection. Vertebral artery dissection is a relatively common cause of stroke in the pediatric age group. Trampoline use has been associated with significant risk of injury to the head and neck. Patients who are small and/or young are most at risk. In this case, minor trauma secondary to trampoline use could be a possible mechanism for vertebral artery dissection and subsequent strokes. The association in this case warrants careful consideration because trampoline use could pose a significant risk to pediatric users.

Hepatitis - Multiple Languages

MedlinePlus

... Viral Hepatitis - العربية (Arabic) Bilingual PDF Health Information Translations Chinese, Simplified (Mandarin dialect) (简体中文) Expand Section Viral ... Chinese, Simplified (Mandarin dialect)) Bilingual PDF Health Information Translations Chinese, Traditional (Cantonese dialect) (繁體中文) Expand Section Viral ...

Hepatitis A - Multiple Languages

MedlinePlus

... gaw Karen) Khmer (ភាសាខ្មែរ) Kinyarwanda (Rwanda) Korean (한국어) Marshallese (Ebon) Nepali (नेपाली) Oromo ( ... PDF Centers for Disease Control and Prevention Kinyarwanda (Rwanda) Expand Section Vaccine Information Statement (VIS) -- Hepatitis A ...

[Prediction of mortality in patients with acute hepatic failure].

PubMed

Eremeeva, L F; Berdnikov, A P; Musaeva, T S; Zabolotskikh, I B

2013-01-01

The article deals with a study of 243 patients (from 18 to 65 years old) with acute hepatic failure. Purpose of the study was to evaluate the predictive capability of severity scales APACHE III, SOFA, MODS, Child-Pugh and to identify mortality predictors in patients with acute hepatic failure. Results; The best predictive ability in patients with acute hepatic failure and multiple organ failure had APACHE III and SOFA scales. The strongest mortality predictors were: serum creatinine > 132 mmol/L, fibrinogen < 1.4 g/L, Na < 129 mmol/L.

Surgery of intracranial aneurysms at Yonsei University: 780 cases.

PubMed

Lee, K C

1991-03-01

Seven hundred and eighty patients with intracranial aneurysm, which were surgically treated by the author since 1976, were analyzed. Strategies important for intracranial aneurysm surgery were the timing of surgery, preoperative preparation and intraoperative management. The best management outcome could be achieved by early operation, removal of subarachnoid blood clot, maintenance of circulating blood volume, administration of nimodipine, and meticulous surgical tactics to avoid pitfalls. Indications for aneurysm surgery in the acute phase were determined by intracerebral hematoma, angiographic findings, clinical grade, general physical status and readiness of the surgical team. Important goals to be considered during the operation were obtaining a slack brain, preparation of proximal control, protection of the brain, awareness of microsurgical anatomy, and complete dissection of the sac. The morbidity and mortality were 2.7% and 4.0%, respectively. The mortality was attributed to intracranial causes in 20 cases (poor grade, delayed ischemic deficits, rebleeding, postoperative infarction, and postoperative epidural hematoma), extracranial causes in 7 cases (pulmonary embolism, heparin induced intracerebral hemorrhage, hepatic failure, myocardial infarction, and gastrointestinal bleeding), and unknown problems in 5 cases. The postoperative intracerebral hemorrhage occurred in 16 cases and seemed to be caused by one or more of the following events: cerebral infarction developed during the preoperative period, occlusion of the cerebral veins during the Sylvian dissection, cerebral retraction and/or sudden change of intracranial hemodynamics. Hydrocephalus, almost always a communicating type as confirmed by isotope cisternography, was managed by lumboperitoneal shunt.(ABSTRACT TRUNCATED AT 250 WORDS)

Stress, social support, and stopping smoking after myocardial infarction in England.

PubMed Central

Greenwood, D C; Muir, K R; Packham, C J; Madeley, R J

1995-01-01

STUDY OBJECTIVE--To examine the effect on mortality of stopping smoking after myocardial infarction and the psychosocial factors that influence the decision to stop. DESIGN--Analysis of smokers in a large prospective study. Self completed questionnaires provided information on psychosocial factors. SETTING--Coronary care units at six English hospitals participating in a multicentre clinical trial. SUBJECTS--These comprised consenting myocardial infarction survivors who had been identified as smokers and who completed questionnaires within seven days of infarct at six hospitals participating in the Anglo-Scandinavian study of early thrombolysis. The 532 patients identified have been followed for over five and a half years. The main outcome measure was five year all cause mortality. MAIN RESULTS--Smokers who stopped within one month showed significantly reduced mortality compared with those who persisted, adjusting for other prognostic indicators (odds ratio 0.56, 95% confidence interval 0.33, 0.98). Overall, 74% stopped smoking. Being married, low life stress levels before infarct, and higher social class were associated with stopping smoking but the differentials were small. Of the clinical variables, a final diagnosis of definite myocardial infarction was associated with stopping smoking. All associations remained after multiple logistic regression. CONCLUSION--Smoking cessation can halve the smokers' odds of dying after myocardial infarction and psychosocial factors play a small but important role in the important decision to stop smoking. Health professionals should continue to stress the importance of stopping smoking to all patients as there is little evidence to support specific directing of advice to relatively "stress or "socially isolated" groups. PMID:8596092

Triple therapy greatly increases myocardial salvage during ischemia/reperfusion in the in situ rat heart.

PubMed

Yang, Xi-Ming; Cui, Lin; Alhammouri, Ahmad; Downey, James M; Cohen, Michael V

2013-10-01

Cangrelor, a P2Y12 receptor blocker, administered just prior to reperfusion reduced but did not eliminate myocardial infarction in rabbits. Combining cangrelor with ischemic postconditioning offered no additional protection suggesting they protected by a similar mechanism. To determine if cangrelor's protection might be additive to other cardioprotective interventions we tested cangrelor in combination with ischemic preconditioning, cariporide, a sodium-hydrogen exchange blocker, and mild hypothermia. Open-chest rats underwent 30-min coronary occlusion/2-h reperfusion. Cangrelor, administered as a bolus (60 μg/kg) 10 min before reperfusion and continued as an infusion (6 μg/kg/min) for the duration of the experiment, decreased infarction from 45.3 % of risk zone in control hearts to 25.0 %. Combining cangrelor and ischemic preconditioning offered no additional protection. Mild hypothermia (32-33 °C) instituted by peritoneal lavage with cold saline just prior to coronary occlusion resulted in 25.2 % infarction, and combining cangrelor and hypothermia nearly halved infarction to 14.1 % of risk zone. Cariporide (0.5 mg/kg) just prior to occlusion resulted in 27.2 % infarction and 15.8 % when combined with cangrelor. Combining cangrelor, hypothermia and cariporide further halved infarction to only 6.3 %. We also tested another P2Y12 inhibitor ticagrelor which is chemically similar to cangrelor. Ticagrelor (20 mg/kg) fed 1 h prior to surgery reduced infarct size by an amount similar to that obtained with cangrelor (25.6 % infarction), and this protective effect was abolished by chelerythrine and wortmannin, thus implicating participation of PKC and PI3-kinase, resp., in signaling. Cardioprotection from a P2Y12 receptor antagonist can be combined with at least 2 other strategies to magnify the protection. Combining multiple interventions that use different cardioprotective mechanisms could provide powerful protection against infarction in patients with acute coronary thrombosis.

Biliary leakage due to a rapidly growing post-traumatic hepatic artery pseudoaneurysm: a case report.

PubMed

Hasegawa, Satoshi; Moriwaki, Yoshihiro; Uchida, Keiji; Kosuge, Takayuki; Yamamoto, Toshiro; Sugiyama, Mitsugi

2004-01-01

Post-traumatic hepatic pseudoaneurysms are rare. We report a very unusual case of bile duct injury complicated with an asymptomatic post-traumatic hepatic pseudoaneurysm. A previously healthy 17-year-old man sustained multiple traumas after a motorcycle accident. Post-traumatic hepatic pseudoaneurysms were detected after blunt liver injury. The rapid growth of the pseudoaneurysms in the hepatic hilus compressed the common hepatic bile duct and caused extrahepatic bile leakage at the lateral lobe. At first, the hepatic arterial pseudoaneurysms were embolized and bile leakage at the left lobe was treated conservatively. Finally, however, segment 2 and 3 partial liver resection should have been performed to stop the bile leakage. Post-traumatic pseudoaneurysm should be ruled out, in addition to the presence of biliary tract injury, if the intraperitoneal bile leakage appears after liver injury.

Novel Index (Hepatic Receptor: IHR) to Evaluate Hepatic Functional Reserve Using (99m)Tc-GSA Scintigraphy.

PubMed

Hasegawa, Daisuke; Onishi, Hideo; Matsutomo, Norikazu

2016-02-01

This study aimed to evaluate the novel index of hepatic receptor (IHR) on the regression analysis derived from time activity curve of the liver for hepatic functional reserve. Sixty patients had undergone (99m)Tc-galactosyl serum albumin ((99m)Tc-GSA) scintigraphy in the retrospective clinical study. Time activity curves for liver were obtained by region of interest (ROI) on the whole liver. A novel hepatic functional predictor was calculated with multiple regression analysis of time activity curves. In the multiple regression function, the objective variables were the indocyanine green (ICG) retention rate at 15 min, and the explanatory variables were the liver counts in 3-min intervals until end from beginning. Then, this result was defined by IHR, and we analyzed the correlation between IHR and ICG, uptake ratio of the heart at 15 minutes to that at 3 minutes (HH15), uptake ratio of the liver to the liver plus heart at 15 minutes (LHL15), and index of convexity (IOC). Regression function of IHR was derived as follows: IHR=0.025×L(6)-0.052×L(12)+0.027×L(27). The multiple regression analysis indicated that liver counts at 6 min, 12 min, and 27 min were significantly related to objective variables. The correlation coefficient between IHR and ICG was 0.774, and the correlation coefficient between ICG and conventional indices (HH15, LHL15, and IOC) were 0.837, 0.773, and 0.793, respectively. IHR had good correlation with HH15, LHL15, and IOC. The finding results suggested that IHR would provide clinical benefit for hepatic functional assessment in the (99m)Tc-GSA scintigraphy.

Paroxysmal dyskinesia as an unusual and only presentation of subcortical white matter ischaemia: a report of two cases.

PubMed

Norlinah, M I; Shahizon, A M M

2008-12-01

Secondary paroxysmal dyskinesias (PxD) have been previously reported in patients with multiple sclerosis, lacunar infarcts, head trauma, metabolic disorders such as hyperglycaemia, hypocalcaemia, migraine and central nervous system (CNS) infections. The causative lesions typically involve the basal ganglia structures, medulla and rarely the spinal cord. We report two patients who presented with paroxysmal dyskinesias as the only manifestation of subcortical white-matter ischaemia. Patient 1 presented with 3-year history of paroxysmal kinesigenic dyskinesia (PKD) and patient 2 with 6-month history of paroxysmal nonkinesigenic dyskinesia (PNKD). All investigations, including CSF oligoclonal bands were negative, except for a brain MRI which showed multiple, non-enhancing subcortical white matter lacunar infarcts. Therefore, subcortical white matter ischaemia should also be included in the differential diagnosis of PxD.

Establishment of a Novel Murine Model of Ischemic Cardiomyopathy with Multiple Diffuse Coronary Lesions

PubMed Central

Nakaoka, Hajime; Nakagawa-Toyama, Yumiko; Nishida, Makoto; Okada, Takeshi; Kawase, Ryota; Yamashita, Taiji; Yuasa-Kawase, Miyako; Nakatani, Kazuhiro; Masuda, Daisaku; Ohama, Tohru; Sonobe, Takashi; Shirai, Mikiyasu; Komuro, Issei; Yamashita, Shizuya

2013-01-01

Objectives Atherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques. Recently, a new murine model, HypoE mouse was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis and myocardial infarction; however, the HypoE mice died too early to make possible investigation of cardiac remodeling. Therefore, we aimed to modify the HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused by atherosclerotic lesions, which the ligation model does not exhibit. Methods and Results In our study, the sustained Paigen diet for the HypoE mice was shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen diet intervention starting when the mice were 8 weeks old was adequate to permit the mice to survive myocardial infarction. Our murine model, called the “modified HypoE mouse”, was maintained until 8 weeks, with a median survival period of 36 days, after the dietary intervention (male, n = 222). Echocardiography demonstrated that the fractional shortening 2 weeks after the Paigen diet (n = 14) significantly decreased compared with that just before the Paigen diet (n = 6) (31.4±11.9% vs. 54.4±2.6%, respectively, P<0.01). Coronary angiography revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were identified by serial analyses of cardiac morphological features and mRNA expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and TGF-β. Conclusion Modified HypoE mice are a suitable model for ischemic cardiomyopathy with multiple diffuse lesions and may be considered as a novel and convenient model for investigations of cardiac remodeling on a highly atherogenic background. PMID:23950999

Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.

PubMed

Teren, A; Kirsten, H; Beutner, F; Scholz, M; Holdt, L M; Teupser, D; Gutberlet, M; Thiery, J; Schuler, G; Eitel, I

2017-02-03

Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10 -5 ), and regulation of inflammatory response (p = 1.86 × 10 -3 ). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction.

Oxygen in the Setting of Acute Myocardial Infarction: Is It Really a Breath of Fresh Air?

PubMed

Loomba, Rohit S; Nijhawan, Karan; Aggarwal, Saurabh; Arora, Rohit R

2016-03-01

Supplemental oxygen has been used in the setting of acute myocardial infarction (AMI). Once an official recommendation in the guidelines for the management of acute ST-segment elevation myocardial infarction, it is now mentioned as an intervention to be considered. Data for the use of supplemental oxygen or AMI are limited, and some data have suggested associated harm. We performed a systematic review of the literature and a subsequent meta-analysis of the data to determine the effect of high concentration oxygen versus titrated oxygen or room air in the setting of AMI. The following end points were studied: in-hospital mortality, opiate use, percentage of infarcted myocardium by magnetic resonance imaging (MRI), and mass of infarcted myocardium by MRI. No significant difference was noted with end points when comparing those randomized to high-concentration oxygen versus those randomized to titrated oxygen or room air in the setting of AMI. No significant publication bias was identified although this could not be assessed for all end points. High-concentration oxygen may not offer any benefit when compared to titrated oxygen or room air. A large, randomized trial is warranted to further delineate these differences with respect to multiple end points. © The Author(s) 2015.

Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage.

PubMed

Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T

2008-07-28

Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.

Reversal of liver cirrhosis: current evidence and expectations.

PubMed

Jung, Young Kul; Yim, Hyung Joon

2017-03-01

In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis.

Reversal of liver cirrhosis: current evidence and expectations

PubMed Central

Jung, Young Kul; Yim, Hyung Joon

2017-01-01

In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis. PMID:28171717

Genetic Architecture of Lacunar Stroke.

PubMed

Traylor, Matthew; Bevan, Steve; Baron, Jean-Claude; Hassan, Ahamad; Lewis, Cathryn M; Markus, Hugh S

2015-09-01

Lacunar strokes comprise ≈20% of all strokes. Despite this frequency, their pathogenesis is poorly understood. Previous genome-wide association studies in lacunar stroke have been disappointing, which may be because of phenotypic heterogeneity. Pathological and radiological studies suggest that there may be different pathologies underlying lacunar strokes. This has led to the suggestion of 2 subtypes: isolated lacunar infarcts and multiple lacunar infarcts and leukoaraiosis. We performed genome-wide analyses in a magnetic resonance imaging-verified cohort of 1012 younger onset lacunar stroke cases and 964 controls. Using these data, we first estimated the heritability of lacunar stroke and its 2 hypothesized subtypes, and secondly, we determined whether this is enriched for regulatory regions in the genome, as defined by data from Encyclopedia of DNA Elements (ENCODE) and other sources. Finally, we determine the evidence for a polygenic contribution from rare variation to lacunar stroke and its subtypes. Our results indicate a substantial heritable component to magnetic resonance imaging-verified lacunar stroke (20%-25%) and its 2 subtypes (isolated lacunar infarct, 15%-18%; multiple lacunar infarcts/leukoaraiosis, 23%-28%). This heritable component is significantly enriched for sites affecting expression of genes. In addition, we show that the risk of the 2 subtypes of lacunar stroke in isolation, but not in combination, is associated with rare variation in the genome. Lacunar stroke, when defined on magnetic resonance imaging, is a highly heritable complex disease. Much of this heritability arises from regions of the genome affecting gene regulation. Rare variation affects 2 subtypes of lacunar in isolation, suggesting that they may have distinct genetic susceptibility factors. © 2015 The Authors.

A pharmacokinetic and pharmacodynamic comparison of immediate-release metoprolol and extended-release metoprolol CR/XL in patients with suspected acute myocardial infarction: a randomized, open-label study.

PubMed

Karlson, Björn W; Dellborg, Mikael; Gullestad, Lars; Aberg, Jan; Sugg, Jennifer; Herlitz, Johan

2014-01-01

Previous metoprolol studies in myocardial infarction patients were performed with immediate-release (IR) metoprolol. This study aims to evaluate if extended-release metoprolol CR/XL once daily gives a similar β-blockade over 24 h compared to multiple dosing of metoprolol IR. After 2 days of routine metoprolol treatment, 27 patients with suspected acute myocardial infarction were randomized to open-label treatment with metoprolol IR (50 mg four times daily or 100 mg twice daily) or metoprolol CR/XL 200 mg once daily for 3 days. Metoprolol CR/XL 200 mg once daily gave more pronounced suppression of peak heart rate, with lower peak and less variation in peak to trough plasma levels. There were no differences in AUC between the CR/XL and IR formulations, although the trough plasma metoprolol levels were comparable for metoprolol CR/XL 200 mg once daily and metoprolol IR 50 mg four times daily, but lower for metoprolol IR 100 mg twice daily. Both treatments were well tolerated. Metoprolol CR/XL 200 mg once daily showed lower peak and less variation in peak to trough plasma levels compared to multiple dosing of metoprolol IR with the same AUC. This was accompanied by a more uniform β-blockade over time, which was reflected by heart rate, and a more pronounced suppression of peak heart rate with similar tolerability. This suggests metoprolol CR/XL may be used as an alternative to metoprolol IR in patients with myocardial infarction. © 2013 S. Karger AG, Basel.

[Acute myocardial infarction in Morocco: FES-AMI registry data].

PubMed

Akoudad, H; El Khorb, N; Sekkali, N; Mechrafi, A; Zakari, N; Ouaha, L; Lahlou, I

2015-12-01

Acute myocardial infarction is the most dangerous complication of coronary atherothrombosis. There are several disparities in regard to its management around the world. The aim of this study is to analyze the specificities of management of acute myocardial infarction in Morocco. FES-AMI (Fès Acute Myocardial Infarction) is a prospective monocentric registry conducted in cardiology department of Hassan II university hospital in Fès. In this registry, we enrolled patients with acute myocardial infarction who presented within 5 days after symptom onset. From January 2005 to August 2015, we enrolled 1835 patients. Seventy-five percent of patients were males and mean age was 60 years old. Fifty-one percent of patients were smokers, 27% were hypertensives and 14% were diabetics. Sixty-six percent of patients had more than 2 risk factors. Time from symptom onset to hospital admission was less than six hours for 40% of the patients. Thirty-six percent of patients were admitted more than twelve hours after the onset of chest pain. Only 37% of patients received reperfusion therapy, 31% with in-hospital thrombolysis and 6% with primary angioplasty. In-hospital mortality was 7.6%. The patients enrolled in our registry have late presentation of acute myocardial infarction and less rate of reperfusion therapy. Furthermore, the majority of our patients have multiple risk factors and this result underlines the failure of preventive interventions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Intestinal microbiota determine severity of myocardial infarction in rats

PubMed Central

Lam, Vy; Su, Jidong; Koprowski, Stacy; Hsu, Anna; Tweddell, James S.; Rafiee, Parvaneh; Gross, Garrett J.; Salzman, Nita H.; Baker, John E.

2012-01-01

Signals from the intestinal microbiota are important for normal host physiology; alteration of the microbiota (dysbiosis) is associated with multiple disease states. We determined the effect of antibiotic-induced intestinal dysbiosis on circulating cytokine levels and severity of ischemia/reperfusion injury in the heart. Treatment of Dahl S rats with a minimally absorbed antibiotic vancomycin, in the drinking water, decreased circulating leptin levels by 38%, resulted in smaller myocardial infarcts (27% reduction), and improved recovery of postischemic mechanical function (35%) as compared with untreated controls. Vancomycin altered the abundance of intestinal bacteria and fungi, measured by 16S and 18S ribosomal DNA quantity. Pretreatment with leptin (0.12 μg/kg i.v.) 24 h before ischemia/reperfusion abolished cardioprotection produced by vancomycin treatment. Dahl S rats fed the commercially available probiotic product Goodbelly, which contains the leptin-suppressing bacteria Lactobacillus plantarum 299v, also resulted in decreased circulating leptin levels by 41%, smaller myocardial infarcts (29% reduction), and greater recovery of postischemic mechanical function (23%). Pretreatment with leptin (0.12 μg/kg i.v.) abolished cardioprotection produced by Goodbelly. This proof-of-concept study is the first to identify a mechanistic link between changes in intestinal microbiota and myocardial infarction and demonstrates that a probiotic supplement can reduce myocardial infarct size.—Lam, V., Su, J., Koprowski, S., Hsu, A., Tweddell, J. S., Rafiee, P., Gross, G. J., Salzman, N. H., Baker, J. E. Intestinal microbiota determine severity of myocardial infarction in rats. PMID:22247331

Flow dynamics and energy efficiency of flow in the left ventricle during myocardial infarction.

PubMed

Vasudevan, Vivek; Low, Adriel Jia Jun; Annamalai, Sarayu Parimal; Sampath, Smita; Poh, Kian Keong; Totman, Teresa; Mazlan, Muhammad; Croft, Grace; Richards, A Mark; de Kleijn, Dominique P V; Chin, Chih-Liang; Yap, Choon Hwai

2017-10-01

Cardiovascular disease is a leading cause of death worldwide, where myocardial infarction (MI) is a major category. After infarction, the heart has difficulty providing sufficient energy for circulation, and thus, understanding the heart's energy efficiency is important. We induced MI in a porcine animal model via circumflex ligation and acquired multiple-slice cine magnetic resonance (MR) images in a longitudinal manner-before infarction, and 1 week (acute) and 4 weeks (chronic) after infarction. Computational fluid dynamic simulations were performed based on MR images to obtain detailed fluid dynamics and energy dynamics of the left ventricles. Results showed that energy efficiency flow through the heart decreased at the acute time point. Since the heart was observed to experience changes in heart rate, stroke volume and chamber size over the two post-infarction time points, simulations were performed to test the effect of each of the three parameters. Increasing heart rate and stroke volume were found to significantly decrease flow energy efficiency, but the effect of chamber size was inconsistent. Strong complex interplay was observed between the three parameters, necessitating the use of non-dimensional parameterization to characterize flow energy efficiency. The ratio of Reynolds to Strouhal number, which is a form of Womersley number, was found to be the most effective non-dimensional parameter to represent energy efficiency of flow in the heart. We believe that this non-dimensional number can be computed for clinical cases via ultrasound and hypothesize that it can serve as a biomarker for clinical evaluations.

Artery of Percheron: an unusual stroke presentation.

PubMed

Pitts-Tucker, Toby; Small, Jeremy

2018-03-28

An 86-year-old woman was admitted with multiple episodes of transient loss of consciousness. She was initially treated for seizures, and stroke was not considered likely. MRI on the same day of admission showed acute bilateral medial thalamic infarcts in keeping with the Artery of Percheron (AOP) territory infarcts. Investigation for polycythaemia and thrombocytosis showed JAK2 positive myeloproliferative neoplasm.A diagnosis of AOP infarction is often missed or delayed because it is rare and presents with variable neurological symptoms. Initial imaging in the form of CT is often negative, and some report that initial MRI findings may also be normal.An awareness of a wide range of differential diagnoses alongside a multi-modality imaging approach is required to reach a diagnosis.Although there are several other case reports of AOP infarction in the literature, this is the first to present with transient symptoms initially mistaken for seizure activity. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction

PubMed Central

Ma, Yonggang; Mouton, Alan J.; Lindsey, Merry L.

2018-01-01

Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging. Following myocardial infarction (MI), macrophages recruited to the infarct produce both proinflammatory and anti-inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation. These diverse properties are attributed to distinct macrophage subtypes and polarization status. Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post- MI. Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation. PMID:29106912

Quantitative assessment of the hepatic metabolic volume product in patients with diffuse hepatic steatosis and normal controls through use of FDG-PET and MR imaging: a novel concept.

PubMed

Bural, Gonca G; Torigian, Drew A; Burke, Anne; Houseni, Mohamed; Alkhawaldeh, Khaled; Cucchiara, Andrew; Basu, Sandip; Alavi, Abass

2010-06-01

The aim of this study was to compare hepatic standardized uptake values (SUVs) and hepatic metabolic volumetric products (HMVP) between patients of diffuse hepatic steatosis and control subjects with normal livers. Twenty-seven subjects were included in the study (13 men and 14 women; age range, 34-72 years). All had 18F-2-fluoro-2-D-deoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) scans with an interscan interval of 0-5 months. Twelve of 27 subjects had diffuse hepatic steatosis on MRI. The remaining 15 were selected as age-matched controls based on normal liver parenchyma on MRI. Mean and maximum hepatic SUVs were calculated for both patient groups on FDG-PET images. Hepatic volumes were measured from MRI. HMVP in each subject was subsequently calculated by multiplication of hepatic volume by mean hepatic SUV. HMVPs as well as mean and maximum hepatic SUVs were compared between the two study groups. HMVPs, mean hepatic SUVs, and maximum hepatic SUVs were greater (statistically significant, p < 0.05) in subjects with diffuse hepatic steatosis compared to those in the control group. The increase in HMVP is the result of increased hepatic metabolic activity likely related to the diffuse hepatic steatosis. The active inflammatory process related to the diffuse hepatic steatosis is the probable explanation for the increase in hepatic metabolic activity on FDG-PET study.

Cumulative exposure to air pollution and long term outcomes after first acute myocardial infarction: A population-based cohort study. Objectives and methodology

PubMed Central

2010-01-01

Background Cardiovascular disease is a leading cause of morbidity and mortality worldwide and epidemiological studies have consistently shown an increased risk for cardiovascular events in relation to exposure to air pollution. The Israel Study of First Acute Myocardial Infarction was designed to longitudinally assess clinical outcomes, psychosocial adjustment and quality of life in patients hospitalized with myocardial infarction. The current study, by introducing retrospective air pollution data, will examine the association between exposure to air pollution and outcome in myocardial infarction survivors. This report will describe the methods implemented and measures employed. The study specifically aims to examine the relationship between residential exposure to air pollution and long-term risk of recurrent coronary event, heart failure, stroke, cardiac and all-cause death in a geographically defined cohort of patients with myocardial infarction. Methods/Design All 1521 patients aged ≤65 years, admitted with first myocardial infarction between February 1992 and February 1993 to the 8 hospitals serving the population of central Israel, were followed for a median of 13 years. Data were collected on sociodemographic, clinical and environmental factors. Data from air quality monitoring stations will be incorporated retrospectively. Daily measures of air pollution will be summarised, allowing detailed maps to be developed in order to reflect chronic exposure for each participant. Discussion This study addresses some of the gaps in understanding of the prognostic importance of air pollution exposure after myocardial infarction, by allowing a sufficient follow-up period, using a well-defined community cohort, adequately controlling for multiple and multilevel confounding factors and providing extensive data on various outcomes. PMID:20576121

Congenital intrahepatic portosystemic shunts: Imaging findings and endovascular management

PubMed Central

Chandrasekharan, Rajsekar; Pullara, Sreekumar K; Thomas, Tixon; Kader, Nazar Puthukudiyil; Moorthy, Srikanth

2016-01-01

We present two cases of congenital intrahepatic portosystemic shunts in which the right portal vein directly communicated with the inferior venacava (IVC) in one patient and with the hepatic vein in the other. Multiple hepatic nodules consistent with focal nodular hyperplasia (FNH) were seen in the first patient. The second patient presented with recurrent history of hepatic encephalopathy. Percutaneous transhepatic embolization was performed using coils and Amplatz device following which she completely recovered. PMID:27081230

[Occupational exposure to blood in multiple trauma care].

PubMed

Wicker, S; Wutzler, S; Schachtrupp, A; Zacharowski, K; Scheller, B

2015-01-01

Trauma care personnel are at risk of occupational exposure to blood-borne pathogens. Little is known regarding compliance with standard precautions or occupational exposure to blood and body fluids among multiple trauma care personnel in Germany. Compliance rates of multiple trauma care personnel in applying standard precautions, knowledge about transmission risks of blood-borne pathogens, perceived risks of acquiring hepatitis B, hepatitis C and human immunodeficiency virus (HIV) and the personal attitude towards testing of the index patient for blood-borne pathogens after a needlestick injury were evaluated. In the context of an advanced multiple trauma training an anonymous questionnaire was administered to the participants. Almost half of the interviewees had sustained a needlestick injury within the last 12 months. Approximately three quarters of the participants were concerned about the risk of HIV and hepatitis. Trauma care personnel had insufficient knowledge of the risk of blood-borne pathogens, overestimated the risk of hepatitis C infection and underused standard precautionary measures. Although there was excellent compliance for using gloves, there was poor compliance in using double gloves (26.4 %), eye protectors (19.7 %) and face masks (15.8 %). The overwhelming majority of multiple trauma care personnel believed it is appropriate to test an index patient for blood-borne pathogens following a needlestick injury. The process of treatment in prehospital settings is less predictable than in other settings in which invasive procedures are performed. Periodic training and awareness programs for trauma care personnel are required to increase the knowledge of occupational infections and the compliance with standard precautions. The legal and ethical aspects of testing an index patient for blood-borne pathogens after a needlestick injury of a healthcare worker have to be clarified in Germany.

The Main Anatomic Variations of the Hepatic Artery and Their Importance in Surgical Practice: Review of the Literature.

PubMed

Noussios, George; Dimitriou, Ioannis; Chatzis, Iosif; Katsourakis, Anastasios

2017-04-01

Anatomical variations of the hepatic artery are important in the planning and performance of abdominal surgical procedures. Normal hepatic anatomy occurs in approximately 80% of cases, for the remaining 20% multiple variations have been described. The purpose of this study was to review the existing literature on the hepatic anatomy and to stress out its importance in surgical practice. Two main databases were searched for eligible articles during the period 2000 - 2015, and results concerning more than 19,000 patients were included in the study. The most common variation was the replaced right hepatic artery (type III according to Michels classification) which is the chief source of blood supply to the bile duct.

Dementia in a retired world boxing champion: case report and literature review.

PubMed

Nowak, L A; Smith, G G; Reyes, P F

2009-01-01

Dementia in retired boxers, also referred to as "dementia pugilistica" (DP), is usually attributed to repeated concussive and subconcussive blows to the head. We report the case of a former world boxing champion whose progressive cognitive decline could be ascribed to DP, cerebral infarcts and Wernicke-Korsakoff syndrome. This case demonstrates that dementia in retired boxers may be caused and/or exacerbated by etiologic factors other than DP. We correlated the clinical features with the histochemical and immunohistochemical changes observed on autopsy brain material from a retired boxer, reviewed the literature on boxing-related dementia, and compared our findings with previous reports on DP. Neuropathologic examination revealed numerous neurofibrillary tangles (NFTs), rare neuritic plaques (NPs), multiple cerebral infarcts, fenestrated septum pellucidum, atrophic and gliotic mamillary bodies, and pale substantia nigra and locus ceruleus. Our neuropathologic data confirmed the notion that dementia in retired boxers could be due to several factors such as DP, multiple cerebral infarcts and Wernicke-Korsakoff syndrome. Our findings illustrate the need to comprehensively examine former boxers with dementia as well as carefully evaluate the neuropathologic changes that may cause or contribute to the patient's cognitive and behavioral symptoms. Such an approach is crucial in order to provide prompt and more definitive therapies.

Giant right coronary artery aneurysm in an adult male patient with non-ST myocardial infarction.

PubMed

Halapas, Antonios; Lausberg, Henning; Gehrig, Thomas; Friedrich, Ivar; Hauptmann, Karl E

2013-01-01

The combination of a giant coronary aneurysm with multiple coronary aneurysms in adults is an extremely rare entity--especially in atherosclerotic patients, since it is most commonly associated with Kawasaki disease in children. We report an interesting case of a 59-year-old male patient with multiple atherosclerotic aneurysms of the left coronary system and a giant aneurysm of the right coronary artery. The patient was admitted to our hospital because of a non-ST myocardial infarction. Diagnosis was established by echocardiography, computed tomography angiogram, and coronary angiography. In view of the clinical symptoms and the extent of the giant right coronary aneurysm, with the associated risk of rupture, the patient was successfully treated with urgent surgical intervention. We also present a review of the current literature on this anomaly and a statistical analysis of all atherosclerotic giant coronary artery aneurysms previously reported.

Multiple cerebral and cerebellar infarcts as the first clinical manifestation in a patient with Churg-Strauss syndrome: case report and literature review.

PubMed

Cheng, Meng-Ju; Huang, Pai-Hao; Liao, Pin-Wen; Chen, Jen-Tse; Chiang, Tsuey-Ru

2012-12-01

Churg-Strauss syndrome (CSS) is a rare autoimmune disease with small-vessel vasculitis. Neurological manifestation of CSS is common. Central nervous system is less frequently involved than that of peripheral nervous system. We report a case of 60-year-old man who presented with acute onset of right hemiparesis and impaired cognition. The presence of hypereosinophilia, asthma, sinusitis and extravascular eosinophil accumulation led to the diagnosis of Churg-Strauss syndrome. Brain magnetic resonance imaging (MRI) revealed multiple infarcts in bilateral cerebral and cerebellar hemispheres. The neurophysiology study did not reveal peripheral neuropathy. The patient was effectively treated with methylprednisolone, cyclophosphamide and warfarin. Symptoms and signs of central nervous system can be the initial neurological manifestation of CSS patients. CSS should be considered while patients have stroke and hypereosinophilia. In our patient, there is a good response to timely steroid, immunosuppressant and anticoagulant therapies.

ANCA-Negative Churg-Strauss Syndrome Presenting as Acute Multiple Cerebral Infarcts: A Case Report.

PubMed

Psychogios, Klearchos; Evmorfiadis, Ilias; Dragomanovits, Spyros; Stavridis, Athanasios; Takis, Konstantinos; Kaklamanis, Loukas; Stathis, Pantelis

2017-03-01

Eosinophilic granulomatosis with polyangiitis (EGPA, previously named Churg-Strauss syndrome) is a form of necrotizing vasculitis occurring in patients with asthma and eosinophilia. Ischemic stroke is a relatively rare complication of the disease. We report a case of a 63-year-old woman with multiple embolic infarcts, hypereosinophilia (for >7 years), and skin rash. Elevated cardiac enzymes and cardiac magnetic resonance imaging were consistent with endomyocarditis. The simultaneous presence of history of asthma, sinusitis, hypereosinophilia, and vasculitis led to the diagnosis of EGPA. This case contributes to the recent debate of the 2 possible presentations of the disease according to the ANCA (antineutrophil cytoplasmic antibodies) status. We furthermore underscore the need for careful differential diagnosis of the "ANCA negative" cases with persistent hypereosinophilia from the idiopathic hypereosinophilic syndrome. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

[The 455th case: swollen leg, jaundice and mental disturbance].

PubMed

Dong, R; Weng, L; Guo, T; Zhu, T N; Zhao, J L; Wu, Q J; Zeng, X F

2017-04-01

A 17-year-old young man with a history of swollen leg and intermittent jaundice was presented to Peking Union Medical College Hospital with acute fever and mental disturbance. He developed deep venous thrombosis, acute myocardial infarction and plantar skin necrosis during the past four years, and was presented with an acute episode of fever, thrombocytopenia, acute kidney injury, acute myocardial infarction, mental disturbance, and obstructive jaundice. Laboratory tests showed schistocytes on peripheral blood smear.High titer of antiphospholipid antibodies was detected.Strikingly, the activity of a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)was significantly decreased without the production of inhibitors. Images indicated stenosis of the common bile duct, common hepatic duct, and cystic duct, which caused dilation of bile ducts and the gall bladder. Corticosteroids and anticoagulation therapy were effective at first, but the disease relapsedonce the corticosteroids tapered down. Plasma exchange was administrated for 17 times, which was effective temporarily during this episode. Methylprednisolone pulse therapy, intravenous immunoglobulin, rituximab, anticoagulation therapy, and bile drainage, were all tried but still could not control the disease. The patient's family agreed to withdraw treatment after he developed septic shock.

Homozygous factor V Leiden mutation in type IV Ehlers-Danlos patient

PubMed Central

Refaat, Marwan; Hotait, Mostafa; Winston, Brion

2014-01-01

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. Several hemostatic abnormalities have been described in EDS patients that increase the bleeding tendencies of these patients. This case report illustrates a patient with an unusual presentation of a patient with type IV EDS, platelet δ-storage pool disease and factor V Leiden mutation. Young woman having previous bilateral deep vein thrombosis and pulmonary emboli coexisting with ruptured splenic aneurysm and multiple other aneurysms now presented with myocardial infarction. Presence of factor V Leiden mutation raises the possibility that the infarct was due to acute coronary thrombosis, although coronary artery aneurysm and dissection with myocardial infarction is known to occur in vascular type EDS. This is the first report in the medical literature of factor V Leiden mutation in an EDS patient which made the management of our patient challenging with propensity to both bleeding and clotting. PMID:24653990

Stress-induced cardiomyopathy caused by heat stroke.

PubMed

Chen, Wei-Ta; Lin, Cheng-Hsin; Hsieh, Ming-Hsiung; Huang, Chun-Yao; Yeh, Jong-Shiuan

2012-07-01

Heat stroke is defined by central nervous system abnormalities and failure of proper maintenance of thermoregulation as a result of high core body temperature ensuing from exposure to high environmental temperatures or strenuous exercise. Common complications include acute respiratory distress syndrome, disseminated intravascular coagulation, acute renal injury, hepatic injury, and rhabdomyolysis. Myocardial injury may also occur during heat stroke, resulting in cardiac enzyme increase and ST-segment changes on the ECG. Such findings might behave as diagnostic pitfalls by mimicking the presentation of coronary artery occlusive myocardial infarction. A previous case report described a patient with heat stroke and ST-segment elevation, in which the definite cause of the ST-segment elevation was unclear; however, acute myocardial infarction caused by coronary artery disease was ruled out according to the clinical signs, serial ECG changes, and serum level of cardiac biomarkers. Stress-induced cardiomyopathy (Takotsubo cardiomyopathy) was suspected, but it could not be confirmed because of the lack of coronary angiography. We herein report a case of heat stroke presenting with ST-segment elevation and cardiogenic shock. Coronary angiography was performed and coronary artery occlusive myocardial infarction was ruled out because of the presence of patent coronary arteries. Left ventriculography showed midventricular and apical hypokinesis, and stress-induced cardiomyopathy was then determined to be the appropriate diagnosis. Heat stroke causes increase of serum catecholamine levels, in which oversecretion and abnormal responses to catecholamines are a possible cause of stress-induced cardiomyopathy. Catecholamines may therefore be the key in linking heat stroke and stress-induced cardiomyopathy. Copyright © 2011. Published by Mosby, Inc.

Urban environmental health applications of remote sensing, summary report

NASA Technical Reports Server (NTRS)

Rush, M.; Goldstein, J.; Hsi, B. P.; Olsen, C. B.

1975-01-01

Health and its association with the physical environment was studied based on the hypothesis that there is a relationship between the man-made physical environment and health status of a population. The statistical technique of regression analysis was employed to show the degree of association and aspects of physical environment which accounted for the greater variation in health status. Mortality, venereal disease, tuberculosis, hepatitis, meningitis, shigella/salmonella, hypertension and cardiac arrest/myocardial infarction were examined. The statistical techniques were used to measure association and variation, not necessarily cause and effect. Conclusions drawn show that the association still exists in the decade of the 1970's and that it can be successfully monitored with the methodology of remote sensing.

Genetic Analysis of Hepatitis A Virus Strains That Induced Epidemics in Korea during 2007–2009

PubMed Central

Lee, Hyeokjin; Jeong, Hyesook; Yun, Heasun; Kim, Kisang; Kim, Jong-Hyun; Yang, Jai Myung

2012-01-01

Hepatitis A virus is one of the most prominent causes of fecally transmitted acute hepatitis worldwide. In order to characterize the viral agents causing an outbreak in Korea (comprising North and South Korea) from June 2007 to May 2009, we collected specimens and performed genotyping of the VP1/P2A and VP3/VP1 regions of hepatitis A virus. We then used a multiple-alignment algorithm to compare the nucleotide sequences of the 2 regions with those of reference strains. Hepatitis A virus antibodies were detected in 64 patients from 5 reported outbreaks (North Korea, June 2007 [n = 11]; Jeonnam, April 2008 [n = 15]; Daegu, May 2008 [n = 13]; Seoul, May 2009 [n = 22]; and Incheon, May 2009 [n = 3]). We found 100% homology between strains isolated from the Kaesong Industrial Region and Jeonnam. While those strains were classified as genotype IA strains, strains from Seoul and Incheon were identified as genotype IIIA strains and showed 98.9 to 100% homology. Genotype IIIA was also dominant in Daegu, where strains were 95.7 to 100% homologous. All hepatitis A virus strains isolated from the Kaesong Industrial Region, Jeonnam, Seoul, and Incheon belonged to a single cluster. However, strains from Daegu could be classified into 2 clusters, suggesting that the outbreak had multiple sources. This study indicates that hepatitis A virus strains of 2 different genotypes are currently cocirculating in Korea. Moreover, it documents an increasing prevalence of genotype IIIA strains in the country. PMID:22238447

New Approaches to Attenuated Hepatitis a Vaccine Development: Cloning and Sequencing of Cell-Culture Adapted Viral cDNA.

DTIC Science & Technology

1987-10-13

after multiple passages in vivo and in vitro. J. Gen. Virol. 67, 1741- 1744. Sabin , A.B. (1985). Oral poliovirus vaccine : history of its development...IN (N NEW APPROACHES TO ATTENUATED HEPATITIS A VACCINE DEVELOPMENT: Q) CLONING AND SEQUENCING OF CELL-CULTURE ADAPTED VIRAL cDNA I ANNUAL REPORT...6ll02Bsl0 A 055 11. TITLE (Include Security Classification) New Approaches to Attenuated Hepatitis A Vaccine Development: Cloning and Sequencing of Cell

"Know More Hepatitis:" CDC's National Education Campaign to Increase Hepatitis C Testing Among People Born Between 1945 and 1965.

PubMed

Jorgensen, Cynthia; Carnes, C Amanda; Downs, Alycia

2016-01-01

In 2012, CDC issued recommendations calling for those born between 1945 and 1965, or baby boomers, to get tested for the hepatitis C virus. To help implement this recommendation, CDC developed "Know More Hepatitis," a multimedia national education campaign. Guided by behavioral science theories and formative research, the campaign used multiple strategies to reach baby boomers and health-care providers with messages encouraging baby boomers to get tested for hepatitis C. With a limited campaign budget, the "Know More Hepatitis" campaign relied mostly on donated time and space from broadcast and print outlets. Donated placements totaled approximately $14.7 million, which reflected a more than 12-to-1 return on the campaign investment. This effort was supplemented with a small, paid digital advertising campaign. Combining audience impressions from both paid and donated campaign efforts resulted in more than 1.2 billion audience impressions.

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

PubMed Central

Henao-Mejia, Jorge; Elinav, Eran; Jin, Cheng-Cheng; Hao, Liming; Mehal, Wajahat Z.; Strowig, Till; Thaiss, Christoph A.; Kau, Andrew L.; Eisenbarth, Stephanie C.; Jurczak, Michael J.; Camporez, Joao-Paulo; Shulman, Gerald I.; Gordon, Jeffrey I.; Hoffman, Hal M.; Flavell, Richard A.

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty percent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different animal models reveal that inflammasome deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic TNF-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient animals to wild type mice results in exacerbation of hepatic steatosis, glucose intolerance, and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders. PMID:22297845

Selective transcatheter embolization for treatment of post-traumatic hepatic artery and portal vein pseudoaneurysms.

PubMed

Laopaiboon, Vallop; Aphinives, Chalida; Pugkem, Ake; Thummaroj, Jureerat; Puttharak, Warinthorn; Soommart, Yamuna

2006-02-01

The authors report a case of post-traumatic hepatic artery and portal vein pseudoaneurysms caused by blunt abdominal trauma, with multiple organ injuries including liver laceration. Abdominal spiral CT, CDS and DSA were performed to confirm the diagnosis. Both pseudoaneurysms were treated successfully with selective transcatheter embolization.

Modulation of transcription factors by curcumin.

PubMed

Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

2007-01-01

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

[Fascioliasis case in the patient with hepatitis A].

PubMed

Kvitashvili, M A; Dvali, Sh A; Kokaia, I Zh

2005-03-01

There is some portion of patients with clinically manifested acute viral hepatitis, which are seronegative to hepatitis A markers. They have to be differentiated with other patients with B, C, D hepatitis, mechanical jaundice, etc. Such clinical cases make physician to recall the parasitic diseases, such as fascioliasis, which affects hepatobiliary system, causes prolongation of cholestasis and dystrophic changes in the biliary tract and likely to cause liver cirrhosis. In the presented case the initial diagnosis was severe acute Hepatitis A (anti-HAV IgM+), though the peripheral blood examination showed moderate eosinophilia, ultrasound investigation revealed multiple sites of damage in the liver, which made us to consider fascioliasis, the latter was confirmed by the serological analysis. Appropriate medical treatment was effective and the state of the patient has improved.

Malignant insulinoma with hepatic and pulmonary metastases associated with primary hyperparathyroidism. Case report and review of the literature

PubMed Central

A., Albu; A., Zirnea; O., Georgescu; D., Terzea; D., Jinga; S., Fica

2008-01-01

Malignant insulinomas are rare tumors (10% of insulinomas) that often present as multicentric macro nodules with multiple liver metastases before diagnosis. We report the case of a 55 year old female with a medical history of severe hypoglycemic attacks for two months. Blood tests showed a decreased value of glycemia (30mg/dl) associated with increased insulin level (16μU/ml) and an increased glycemia/insulinemia ratio of 1.87 supporting the diagnosis of insulinoma. Abdominal CT showed a 1.5 cm mass localized in the head of the pancreas with disseminated hepatic tumors, confirmed as neuroendocrine metastases by biopsy (which proved the presence of a malignant insulinoma). Primary hyperparathyroidism was diagnosed based on mild elevation of calcium (10.4 mg/dl) associated with a high level of PTH (71,2 pg/ml). The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN 1). Because of multiple hepatic masses and liver function impairment, surgery and hepatic artery embolization were not performed. Somatostatin analog therapy was started with symptomatic control in the beginning, but rapid loss of beneficial effect. Finally, systemic chemotherapy with doxorubicin was administered, but the disease was progressive and after three months we decided to stop it. The patient died at home after one month, probably in hypoglycemic coma. PMID:20108468

Complete remission of a case of hepatocellular carcinoma with tumor invasion in inferior vena cava and with pulmonary metastasis successfully treated with repeated arterial infusion chemotherapy.

PubMed

Kogure, Takayuki; Iwasaki, Takao; Ueno, Yoshiyuki; Kanno, Noriatsu; Fukushima, Koji; Yamagiwa, Yoko; Nagasaki, Futoshi; Kakazu, Eiji; Matsuda, Yasunori; Kido, Osamu; Nakagome, Yu; Ninomiya, Masashi; Shimosegawa, Tooru

2007-01-01

We report the case of a patient having hepatocellular carcinoma with tumor invasion to the inferior vena cava and with multiple pulmonary metastases who was treated with repeated one-shot administration of epirubicin, cisplatin, and mitomycin C by hepatic artery and bronchial artery, which led to complete remission. A 72-year-old woman was diagnosed with infiltrative hepatocellular carcinoma with Vv3, multiple intrahepatic metastases, and multiple pulmonary metastases associated with compensated liver cirrhosis. One-shot infusion of epirubicin, cisplatin, and mitomycin C was performed through proper hepatic artery and bronchial artery for twice at eight weeks of intervals. Pulmonary metastases disappeared and intrahepatic lesions indicated marked shrinkage leaving a scar-like lesion with decreases in tumor markers. After six months and 20 months, tumor markers indicated increasing tendency but no evident recurrence was found by computed tomography or hepatic arteriography. One-shot infusion of the same regimens through proper hepatic artery was performed and tumor markers decreased to normal levels. After 14 months of the last therapy, no evidence of recurrence has been found on image analysis or in tumor markers. This arterial infusion therapy is well tolerated for the patients with compensated liver cirrhosis and might be promising for the effective treatment of advanced hepatocellular carcinoma with pulmonary metastases.

More than a virus: a qualitative study of the social implications of hepatitis B infection in China.

PubMed

Wallace, J; Pitts, M; Liu, C; Lin, V; Hajarizadeh, B; Richmond, J; Locarnini, S

2017-08-01

China has the largest absolute number of people living with hepatitis B with up to 300,000 people estimated to die each year from hepatitis B related diseases. Despite advances in immunisation, clinical management, and health policy, there is still a lack of accessible and affordable health care for people with hepatitis B. Through in-depth interviews, this study identifies the personal, social and economic impact of living with hepatitis B and considers the role of stigma and discrimination as barriers to effective clinical management of the disease. Semi-structured qualitative interviews were held with 41 people living with hepatitis B in five Chinese cities. Participants were recruited through clinical and non-government organisations providing services to people with hepatitis B, with most (n = 32) being under the age of 35 years. People living with hepatitis B experience the disease as a transformative intergenerational chronic infection with multiple personal and social impacts. These include education and employment choices, economic opportunities, and the development of intimate relationships. While regulations reducing access to employment and education for people with hepatitis B have been repealed, stigma and discrimination continue to marginalise people with hepatitis B. Effective public policy to reduce morbidity and mortality associated with hepatitis B needs to address the lived impact of hepatitis B on families, employment and educational choices, finances, and social marginalisation.

Surgical treatment of celiomesenteric trunk aneurysm-7 case report.

PubMed

Wang, Chunxi; Cai, Xiangjun; Liang, Faqi; Chu, Futao; Chen, Gang; Duan, Zhiquan

2014-01-01

The celiomesenteric trunk is a rare anomaly characterized by a common origin of the celiac axis and superior mesenteric artery from the aorta, which accounts for less than 1% of all celiac artery anomalies, so the aneurysm occurred in such trunk is even rarer. There have been few reports on how to diagnose and deal with such malformed celiomesenteric trunk aneurysms till now. This paper tries to summarize the experience of how to expose and excise such kind of aneurysm according to the seven cases' data. The clinic data were collected retrospectively. There were seven cases with celiomesenteric trunk aneurysm from February 2000 to February 2013, including 5 males and 2 females aged 35~62. The operations were done including aneurysm resection and vascular reconstruction under general anesthesia. The operated patients were followed-up at the sixth month and each year post operation. The vascular stomas were detected or examined by Color Doppler Sonography, spiral Computed Tomography angiography (SCTA). The seven operated patients were cured and discharged from hospital, and they were followed up for 3~10 years (mean time 5 years), with four patients being followed up longer than 5 years. No sign of intestinal ischemia or hepatic ischemia or splenic ischemia was found, and no image of anastomosis stricture or stenosis was found during the follow-up. Five patients are alive now while two patients were dead, with one dying of large area myocardial infarction unexpectedly at 6 years post operation and the other dying of cerebral infarction abruptly at 4 years post operation. It is an effective and safe method to treat the celiomesenteric trunk aneurysm by using by-pass operation with artificial blood vessels, originating from inferior kidney aorta to visceral arteries including hepatic artery, splenic artery and superior mesenteric artery. Its short-term and middle-term effects are relatively better.

Timing of Acute Palliative Care Consultation in Critically Ill Patients

ClinicalTrials.gov

2016-08-03

Multiple Organ Failure; End Stage Cardiac Failure; End Stage Chronic Obstructive Airways Disease; Chronic Kidney Disease Stage 5; Hepatic Encephalopathy; Sepsis; Dementia; Multiple Sclerosis; Parkinson's Disease; In-Hospital Cardiac Arrest; Solid Organ Cancer

Interspecies scaling and prediction of human clearance: comparison of small- and macro-molecule drugs

PubMed Central

Huh, Yeamin; Smith, David E.; Feng, Meihau Rose

2014-01-01

Human clearance prediction for small- and macro-molecule drugs was evaluated and compared using various scaling methods and statistical analysis.Human clearance is generally well predicted using single or multiple species simple allometry for macro- and small-molecule drugs excreted renally.The prediction error is higher for hepatically eliminated small-molecules using single or multiple species simple allometry scaling, and it appears that the prediction error is mainly associated with drugs with low hepatic extraction ratio (Eh). The error in human clearance prediction for hepatically eliminated small-molecules was reduced using scaling methods with a correction of maximum life span (MLP) or brain weight (BRW).Human clearance of both small- and macro-molecule drugs is well predicted using the monkey liver blood flow method. Predictions using liver blood flow from other species did not work as well, especially for the small-molecule drugs. PMID:21892879

Fatal hepatic hemorrhage by peliosis hepatis in X-linked myotubular myopathy: a case report.

PubMed

Motoki, T; Fukuda, M; Nakano, T; Matsukage, S; Fukui, A; Akiyoshi, S; Hayashi, Y K; Ishii, E; Nishino, I

2013-11-01

We report a 5-year-old boy with X-linked myotubular myopathy complicated by peliosis hepatis. At birth, he was affected with marked generalized muscle hypotonia and weakness, which required permanent ventilatory support, and was bedridden for life. He died of acute fatal hepatic hemorrhage after using a mechanical in-exsufflator. Peliosis hepatis, defined as multiple, variable-sized, cystic blood-filled spaces through the liver parenchyma, was confirmed by autopsy. To avoid fatal hepatic hemorrhage by peliosis hepatis, routine hepatic function tests and abdominal imaging tests should be performed for patients with X-linked myotubular myopathy, especially at the time of using artificial respiration. Copyright © 2013 Elsevier B.V. All rights reserved.

Liver transplantation for severe hepatic trauma: Experience from a single center

PubMed Central

Delis, Spiros G; Bakoyiannis, Andreas; Selvaggi, Gennaro; Weppler, Debbie; Levi, David; Tzakis, Andreas G

2009-01-01

Liver transplantation has been reported in the literature as an extreme intervention in cases of severe and complicated hepatic trauma. The main indications for liver transplant in such cases were uncontrollable bleeding and postoperative hepatic insufficiency. We here describe four cases of orthotopic liver transplantation after penetrating or blunt liver trauma. The indications were liver failure, extended liver necrosis, liver gangrene and multiple episodes of gastrointestinal bleeding related to portal hypertension, respectively. One patient died due to postoperative cerebral edema. The other three patients recovered well and remain on immunosuppression. Liver transplantation should be considered as a saving procedure in severe hepatic trauma, when all other treatment modalities fail. PMID:19340909

Is Technological Change in Medicine Always Worth It? The Case of Acute Myocardial Infarction

PubMed Central

Staiger, Douglas; Fisher, Elliott

2007-01-01

We examine Medicare costs and survival gains for Acute Myocardial Infarction (AMI) during 1986–2002. Like Cutler and McClellan, we find overall gains in post-AMI survival more than justified the increases in costs during this period. Since 1996, however, survival gains have stagnated, while expenditures have continued to increase. We also consider changes in expenditures and outcomes at the regional level. Regions experiencing the largest expenditure gains were not those realizing the greatest improvements in survival. Factors yielding the greatest benefits to health (aspirin, beta blockers, and reperfusion) were not the factors that drove up costs (multiple physicians), and conversely. PMID:16464904

[Medial longitudinal fasciculus (MLF) syndrome in a patient with giant cell arteritis].

PubMed

Uenaka, Takeshi; Hamaguchi, Hirotoshi; Sekiguchi, Kenji; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

2015-01-01

A 76-year-old female was referred to our department because of diplopia for two months and intermittent claudication for five months. She showed medial longitudinal fasciculus (MLF) syndrome. Brain MRI (T2WI) showed multiple infarctions in the right pontine tegmentum and left paramedian midbrain. A biopsy of superficial temporal artery showed the characteristic findings of glanulomatous inflammation indicative of giant cell arteritis. We thought the mechanism of this cerebral infarction as artery to artery embolization or intracranial arteritis. Treatment with oral prednisolone (1 mg/kg/day) improved her limb claudication and normalized serum C-reactive protein level.

False-positive liver scan in a patient with hepatic amyloidosis: case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, K.; Okuda, K.; Yoshida, T.

1976-01-01

A case of secondary hepatic amyloidosis exhibiting a large liver and multiple defects on the $sup 198$Au-radiocolloid scintigraph is presented. Biopsy and angiographic studies indicated that the areas of reduced colloid uptake represented heavy amyloid deposition, and the area of the left lobe with contrasting high activity most probably represented compensatory hypertrophy. (auth)

Sensitive detection of multiple hepatitis A virus genotypes with a single polony-based assay

USDA-ARS?s Scientific Manuscript database

Hepatitis A virus (HAV) is one of the major causes of non-bacterial gastroenteritis in humans worldwide. HAV is mostly transmitted via direct person-to-person contact, or by consumption of contaminated foods and water. Since only a few viral particles may cause disease, detection of low levels of HA...

[Peculiarities of laparoscopic diagnosis of the closed hepatic traumatic damage].

PubMed

Kapshitar', A A; Kapshitar', A V; Syrbu, I F

2008-01-01

Diagnostic possibilities of laparoscopy were studied in 24 injured persons, suffering closed hepatic damage in noninformity of results of clinical, laboratory-biochemical, roentgenologic, ultrasound investigations and diagnostic peritoneal lavage as well, were studied. Isolated trauma was revealed in 8 injured persons, the multiple one in 7 and the combined--in 9. Open operation was performed in 21 patients, relaparotomy--in 3, laparoscopic intervention with curative intent--in 3 hepatic wound tamponade, using hemostatic sponge with ambene, lubricated by dicinon. Three patients died due to severe combined trauma.

Hepatitis-associated aplastic anaemia: a poor prognosis.

PubMed

Gonçalves, Vivian; Calado, Rita; Palaré, Maria João; Ferrão, Anabela; Morais, Anabela

2013-02-13

A 13-year-old boy presented with spontaneous skin and mucosal bleeds 3 weeks after acute hepatitis of unknown aetiology. Laboratory analyses revealed pancytopenia and bone marrow biopsy that confirmed the diagnosis of aplastic anaemia. Other causes of congenital and acquired aplastic anaemia were excluded. He was diagnosed with hepatitis-associated aplastic anaemia. He developed a critical clinical condition, becoming totally dependent on erythrocyte and platelet transfusions, and severe neutropenia, which led to invasive bacterial infection. He died due to sepsis with multiple organ failure 3 months after admission.

Rehabilitation-triggered cortical plasticity after stroke: in vivo imaging at multiple scales (Conference Presentation)

NASA Astrophysics Data System (ADS)

Allegra Mascaro, Anna Letizia; Conti, Emilia; Lai, Stefano; Spalletti, Cristina; Di Giovanna, Antonino Paolo; Alia, Claudia; Panarese, Alessandro; Sacconi, Leonardo; Micera, Silvestro; Caleo, Matteo; Pavone, Francesco S.

2017-02-01

Neurorehabilitation protocols based on the use of robotic devices provide a highly repeatable therapy and have recently shown promising clinical results. Little is known about how rehabilitation molds the brain to promote motor recovery of the affected limb. We used a custom-made robotic platform that provides quantitative assessment of forelimb function in a retraction test. Complementary imaging techniques allowed us to access to the multiple facets of robotic rehabilitation-induced cortical plasticity after unilateral photothrombotic stroke in mice Primary Motor Cortex (Caudal Forelimb Area - CFA). First, we analyzed structural features of vasculature and dendritic reshaping in the peri-infarct area with two-photon fluorescence microscopy. Longitudinal analysis of dendritic branches and spines of pyramidal neurons suggests that robotic rehabilitation promotes the stabilization of peri-infarct cortical excitatory circuits, which is not accompanied by consistent vascular reorganization towards pre-stroke conditions. To investigate if this structural stabilization was linked to functional remapping, we performed mesoscale wide-field imaging on GCaMP6 mice while performing the motor task on the robotic platform. We revealed temporal and spatial features of the motor-triggered cortical activation, shining new light on rehabilitation-induced functional remapping of the ipsilesional cortex. Finally, by using an all-optical approach that combines optogenetic activation of the contralesional hemisphere and wide-field functional imaging of peri-infarct area, we dissected the effect of robotic rehabilitation on inter-hemispheric cortico-cortical connectivity.

Concurrent Autoimmune Hepatitis and Grave's Disease in Hepatitis C during Pegylated Interferon α-2a and Ribavirin Therapy

PubMed Central

Trikudanathan, Guru V.; Ahmad, Imad; Israel, Jonathan L

2011-01-01

Classical interferon-α has been shown to be associated with the development of a variety of autoimmune disorders. A 34-year-old white woman with chronic hepatitis C virus infection who was treated with pegylated interferon α-2a and ribavirin, developed Grave's disease and autoimmune hepatitis (AIH) at 32 and 44 weeks, respectively, following initiation of the therapy. The diagnosis of AIH was made based on the new development of anti-smooth muscle antibodies, anti-mitochondrial antibodies, and liver biopsy findings. It was confirmed by positive response to steroid challenge and was assessed according to the international AIH scoring system. Based on the previous case reports, we review the existing literature. Clinicians should be aware of the possibility of multiple autoimmune disorders during interferon-based therapy for chronic hepatitis. PMID:21912063

Concurrent autoimmune hepatitis and grave's disease in hepatitis C during pegylated interferon α-2a and ribavirin therapy.

PubMed

Trikudanathan, Guru V; Ahmad, Imad; Israel, Jonathan L

2011-01-01

Classical interferon-α has been shown to be associated with the development of a variety of autoimmune disorders. A 34-year-old white woman with chronic hepatitis C virus infection who was treated with pegylated interferon α-2a and ribavirin, developed Grave's disease and autoimmune hepatitis (AIH) at 32 and 44 weeks, respectively, following initiation of the therapy. The diagnosis of AIH was made based on the new development of anti-smooth muscle antibodies, anti-mitochondrial antibodies, and liver biopsy findings. It was confirmed by positive response to steroid challenge and was assessed according to the international AIH scoring system. Based on the previous case reports, we review the existing literature. Clinicians should be aware of the possibility of multiple autoimmune disorders during interferon-based therapy for chronic hepatitis.

Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study.

PubMed

Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars; Rhodes, John F; Larsen, Coby C; Jacobson, Joth

2017-12-01

Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus patent foramen ovale closure (with GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder) or antiplatelet therapy alone. Subjects will be prospectively followed for up to five years. Neuroimaging is required for all subjects at baseline and at two years or study exit. Study outcomes The two co-primary endpoints for the study are freedom from recurrent clinical ischemic stroke through at least 24 months post-randomization and incidence of new brain infarct (defined as clinical ischemic stroke or silent brain infarct) through 24 months. The primary analyses are an unadjusted log-rank test and a binomial test of subject-based proportions, respectively, both on the intent-to-treat population, with adjustment for testing multiplicity. Discussion The REDUCE trial aims to target a patient population with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent clinical ischemic stroke or new silent brain infarct; the neuroimaging data will provide an opportunity to further support the proof of concept. The main results are anticipated in 2017. Registration Clinical trial registration-URL: http://clinicaltrials.gov/show/NCT00738894.

Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection.

PubMed

Ono, Hirohisa; Nishijima, Yoji; Ohta, Shigeo; Sakamoto, Masaki; Kinone, Kazunori; Horikosi, Tohru; Tamaki, Mituyuki; Takeshita, Hirosi; Futatuki, Tomoko; Ohishi, Wataru; Ishiguro, Taichi; Okamoto, Saori; Ishii, Shou; Takanami, Hiroko

2017-11-01

Molecular hydrogen (H 2 ) acts as a therapeutic antioxidant. Inhalation of H 2 gas (1-4%) was effective for the improvement of cerebral infarction in multiple animal experiments. Thus, for actual applications, a randomized controlled clinical study is desired to evaluate the effects of inhalation of H 2 gas. Here, we evaluate the H 2 treatment on acute cerebral infarction. Through this randomized controlled clinical study, we assessed the safety and effectiveness of H 2 treatment in patients with cerebral infarction in an acute stage with mild- to moderate-severity National Institute of Health Stroke Scale (NIHSS) scores (NIHSS = 2-6). We enrolled 50 patients (25 each in the H 2 group and the control group) with a therapeutic time window of 6 to 24 hours. The H 2 group inhaled 3% H 2 gas (1 hour twice a day), and the control group received conventional intravenous medications for the initial 7 days. The evaluations included daily vital signs, NIHSS scores, physical therapy indices, weekly blood chemistry, and brain magnetic resonance imaging (MRI) scans over the 2-week study period. The H 2 group showed no significant adverse effects with improvements in oxygen saturation. The following significant effects were found: the relative signal intensity of MRI, which indicated the severity of the infarction site, NIHSS scores for clinically quantifying stroke severity, and physical therapy evaluation, as judged by the Barthel Index. H 2 treatment was safe and effective in patients with acute cerebral infarction. These results suggested a potential for widespread and general application of H 2 gas. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical Significance of Reciprocal ST-Segment Changes in Patients With STEMI: A Cardiac Magnetic Resonance Imaging Study.

PubMed

Hwang, Ji-Won; Yang, Jeong Hoon; Song, Young Bin; Park, Taek Kyu; Lee, Joo Myung; Kim, Ji-Hwan; Jang, Woo Jin; Choi, Seung-Hyuk; Hahn, Joo-Yong; Choi, Jin-Ho; Ahn, Joonghyun; Carriere, Keumhee; Lee, Sang Hoon; Gwon, Hyeon-Cheol

2018-02-22

We sought to determine the association of reciprocal change in the ST-segment with myocardial injury assessed by cardiac magnetic resonance (CMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We performed CMR imaging in 244 patients who underwent primary PCI for their first STEMI; CMR was performed a median 3 days after primary PCI. The first electrocardiogram was analyzed, and patients were stratified according to the presence of reciprocal change. The primary outcome was infarct size measured by CMR. Secondary outcomes were area at risk and myocardial salvage index. Patients with reciprocal change (n=133, 54.5%) had a lower incidence of anterior infarction (27.8% vs 71.2%, P < .001) and shorter symptom onset to balloon time (221.5±169.8 vs 289.7±337.3min, P=.042). Using a multiple linear regression model, we found that patients with reciprocal change had a larger area at risk (P=.002) and a greater myocardial salvage index (P=.04) than patients without reciprocal change. Consequently, myocardial infarct size was not significantly different between the 2 groups (P=.14). The rate of major adverse cardiovascular events, including all-cause death, myocardial infarction, and repeat coronary revascularization, was similar between the 2 groups after 2 years of follow-up (P=.92). Reciprocal ST-segment change was associated with larger extent of ischemic myocardium at risk and more myocardial salvage but not with final infarct size or adverse clinical outcomes in STEMI patients undergoing primary PCI. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

PubMed Central

Juurlink, David N.; Gomes, Tara; Ko, Dennis T.; Szmitko, Paul E.; Austin, Peter C.; Tu, Jack V.; Henry, David A.; Kopp, Alex; Mamdani, Muhammad M.

2009-01-01

Background Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. Methods We conducted a population-based nested case–control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31–90 days) or remote (91–180 days). Results Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03–1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70–1.47). Interpretation Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction. PMID:19176635

Glatiramer Acetate administration does not reduce damage after cerebral ischemia in mice.

PubMed

Poittevin, Marine; Deroide, Nicolas; Azibani, Feriel; Delcayre, Claude; Giannesini, Claire; Levy, Bernard I; Pocard, Marc; Kubis, Nathalie

2013-01-15

Inflammation plays a key role in ischemic stroke pathophysiology: microglial/macrophage cells and type-1 helper cells (Th1) seem deleterious, while type-2 helper cells (Th2) and regulatory T cells (Treg) seem protective. CD4 Th0 differentiation is modulated by microglial cytokine secretion. Glatiramer Acetate (GA) is an immunomodulatory drug that has been approved for the treatment of human multiple sclerosis by means of a number of mechanisms: reduced microglial activation and pro-inflammatory cytokine production, Th0 differentiation shifting from Th2 to Th2 and Treg with anti-inflammatory cytokine production and increased neurogenesis. We induced permanent (pMCAo) or transient middle cerebral artery occlusion (tMCAo) and GA (2 mg) or vehicle was injected subcutaneously immediately after cerebral ischemia. Mice were sacrificed at D3 to measure neurological deficit, infarct volume, microglial cell density and qPCR of TNFα and IL-1β (pro-inflammatory microglial cytokines), IFNγ (Th2 cytokine), IL-4 (Th2 cytokine), TGFβ and IL-10 (Treg cytokines), and at D7 to evaluate neurological deficit, infarct volume and neurogenesis assessment. We showed that in GA-treated pMCAo mice, infarct volume, microglial cell density and cytokine secretion were not significantly modified at D3, while neurogenesis was enhanced at D7 without significant infarct volume reduction. In GA-treated tMCAo mice, microglial pro-inflammatory cytokines IL-1β and TNFα were significantly decreased without modification of microglial/macrophage cell density, cytokine secretion, neurological deficit or infarct volume at D3, or modification of neurological deficit, neurogenesis or infarct volume at D7. In conclusion, Glatiramer Acetate administered after cerebral ischemia does not reduce infarct volume or improve neurological deficit in mice despite a significant increase in neurogenesis in pMCAo and a microglial pro-inflammatory cytokine reduction in tMCAo. Copyright © 2012 Elsevier B.V. All rights reserved.

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction.

PubMed

Guo, Yiru; Wysoczynski, Marcin; Nong, Yibing; Tomlin, Alex; Zhu, Xiaoping; Gumpert, Anna M; Nasr, Marjan; Muthusamy, Senthikumar; Li, Hong; Book, Michael; Khan, Abdur; Hong, Kyung U; Li, Qianhong; Bolli, Roberto

2017-03-01

We have recently demonstrated that repeated administrations of c-kit POS cardiac progenitor cells (CPCs) have cumulative beneficial effects in rats with old myocardial infarction (MI), resulting in markedly greater improvement in left ventricular (LV) function compared with a single administration. To determine whether this paradigm applies to other species and cell types, mice with a 3-week-old MI received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that we have recently described. CMCs or vehicle were infused percutaneously into the LV cavity, 14 days apart. Compared with vehicle-treated mice, the single-dose group exhibited improved LV ejection fraction (EF) after the 1st infusion (consisting of CMCs) but not after the 2nd and 3rd (vehicle). In contrast, in the multiple-dose group, LV EF improved after each CMC infusion, so that at the end of the study, LV EF averaged 35.5 ± 0.7% vs. 32.7 ± 0.6% in the single-dose group (P < 0.05). The multiple-dose group also exhibited less collagen in the non-infarcted region vs. the single-dose group. Engraftment and differentiation of CMCs were negligible in both groups, indicating paracrine effects. These results demonstrate that, in mice with ischemic cardiomyopathy, the beneficial effects of three doses of CMCs are significantly greater than those of one dose, supporting the concept that multiple treatments are necessary to properly evaluate the full therapeutic potential of cell therapy. Thus, the repeated-treatment paradigm is not limited to c-kit POS CPCs or to rats, but applies to other cell types and species. The generalizability of this concept dramatically augments its significance.

Noninvasive Assessment of Advanced Fibrosis Based on Hepatic Volume in Patients with Nonalcoholic Fatty Liver Disease.

PubMed

Hayashi, Tatsuya; Saitoh, Satoshi; Fukuzawa, Kei; Tsuji, Yoshinori; Takahashi, Junji; Kawamura, Yusuke; Akuta, Norio; Kobayashi, Masahiro; Ikeda, Kenji; Fujii, Takeshi; Miyati, Tosiaki; Kumada, Hiromitsu

2017-09-15

Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the hepatic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD. A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diagnosing fibrosis ≥F3-4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify variables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio. The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confidence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associated with the L/R ratio (coefficient, 0.121; p<0.0001). The L/R ratio, which is not influenced by pathological parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD.

Urban environmental health applications of remote sensing

NASA Technical Reports Server (NTRS)

Rush, M.; Goldstein, J.; Hsi, B. P.; Olsen, C. B.

1974-01-01

An urban area was studied through the use of the inventory-by-surrogate method rather than by direct interpretation of photographic imagery. Prior uses of remote sensing in urban and public research are examined. The effects of crowding, poor housing conditions, air pollution, and street conditions on public health are considered. Color infrared photography was used to categorize land use features and the grid method was used in photo interpretation analysis. The incidence of shigella and salmonella, hepatitis, meningitis, tuberculosis, myocardial infarction and veneral disease were studied, together with mortality and morbidity rates. Sample census data were randomly collected and validated. The hypothesis that land use and residential quality are associated with and act as an influence upon health and physical well-being was studied and confirmed.

Perceived Neighborhood Social Cohesion and Myocardial Infarction

PubMed Central

Kim, Eric S.; Hawes, Armani M.; Smith, Jacqui

2015-01-01

Background The main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviors. Though important, emphasis on individuals has diverted focus and responsibility away from neighborhood characteristics, which also strongly influence people’s behaviors. Although a growing body of research has repeatedly demonstrated strong associations between neighborhood characteristics and cardiovascular health, it has typically focused on negative neighborhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighborhood characteristics, such as perceived neighborhood social cohesion. Methods Using multiple logistic regression models, we tested whether higher perceived neighborhood social cohesion was associated with lower incidence of myocardial infarction. Prospective data from the Health and Retirement Study—a nationally representative panel study of American adults over the age of 50—were used to analyze 5,276 participants with no history of heart disease. Respondents were tracked for four years and analyses adjusted for relevant sociodemographic, behavioral, biological, and psychosocial factors. Results In a model that adjusted for age, gender, race, marital status, education, and total wealth, each standard deviation increase in perceived neighborhood social cohesion was associated with a 22% reduced odds of myocardial infarction (OR = 0.78, 95% CI, 0.63–0.94. The association between perceived neighborhood social cohesion and myocardial infarction remained even after adjusting for behavioral, biological, and psychosocial covariates. Conclusions Higher perceived neighborhood social cohesion may have a protective effect against myocardial infarction. PMID:25135074

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samuelson, Shaun D.; Louie, John D.; Sze, Daniel Y., E-mail: dansze@stanford.edu

Purpose. Avoidance of nontarget microsphere deposition via hepatoenteric anastomoses is essential to the safety of yttrium-90 radioembolization (RE). The hepatic hilar arterial network may remain partially patent after coil embolization of major arteries, resulting in persistent risk. We retrospectively reviewed cases where n-butyl cyanoacrylate (n-BCA) glue embolization was used to facilitate endovascular hepatic arterial skeletonization before RE. Methods. A total of 543 RE procedures performed between June 2004 and March 2012 were reviewed, and 10 were identified where n-BCA was used to embolize hepatoenteric anastomoses. Arterial anatomy, prior coil embolization, and technical details were recorded. Outcomes were reviewed to identifymore » subsequent complications of n-BCA embolization or nontarget RE. Results. The rate of complete technical success was 80 % and partial success 20 %, with one nontarget embolization complication resulting in a minor change in treatment plan. No evidence of gastrointestinal or biliary ischemia or infarction was identified, and no microsphere-related gastroduodenal ulcerations or other evidence of nontarget RE were seen. Median volume of n-BCA used was <0.1 ml. Conclusion. n-BCA glue embolization is useful to eliminate hepatoenteric networks that may result in nontarget RE, especially in those that persist after coil embolization of major vessels such as the gastroduodenal and right gastric arteries.« less

Scrub typhus associated hepatic dysfunction and abdominal CT findings

PubMed Central

Park, Man Je; Lee, Hyoun Soo; Shim, Sang Goon; Kim, So Hee

2015-01-01

Objective: This retrospective study investigated abnormal hepatic dysfunction and abdominal computed tomography (CT) findings in scrub typhus. Methods: Three hundred forty nine adult patients were diagnosed with scrub typhus. Ninety four underwent abdominal CT. The CT images were reviewed by the attending radiologist. Patient data of history, symptoms, signs, and results of laboratory tests were collected from the electronic medical records. Results: In 349 patients with scrub typhus, elevation of aspartate aminotransferase (78.5%) and alanine aminotransferase (63.0%) were dominant compared to alkaline phosphatase (27.2%) and total bilirubin (16.1%). Abdominal CT findings of 94 patients were, in descending order of frequency, enlarged lymph node (53.2%), inhomogeneous enhancement of liver (47.9%), splenomegaly (46.8%), ascites (28.7%), low attenuation of periportal areas (27.7%), gallbladder wall thickening (17.0%), and splenic infarct (6.4%). Also, the level of aspartate aminotransferase tended to be elevated according to the number of CT findings (P= 0.028) Conclusions: We found that abdominal CT manifestations of scrub typhus with elevated aminotransferases were varied and not specific. However, knowledge of these findings may evoke the recognition of scrub typhus by clinicians in endemic areas. PMID:26101478

Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease.

PubMed

Guarner, Verónica; Rubio-Ruiz, Maria Esther

2015-01-01

Aging is associated with immunosenescence and accompanied by a chronic inflammatory state which contributes to metabolic syndrome, diabetes and their cardiovascular consequences. Risk factors for cardiovascular diseases (CVDs) and diabetes overlap, leading to the hypothesis that both share an inflammatory basis. Obesity is increased in the elderly population, and adipose tissue induces a state of systemic inflammation partially induced by adipokines. The liver plays a pivotal role in the metabolism of nutrients and exhibits alterations in the expression of genes associated with inflammation, cellular stress and fibrosis. Hepatic steatosis and its related inflammatory state (steatohepatitis) are the main hepatic complications of obesity and metabolic diseases. Aging-linked declines in expression and activity of endoplasmic reticulum molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the unfolded protein response. These changes predispose aged individuals to CVDs. CVDs and endothelial dysfunction are characterized by a chronic alteration of inflammatory function and markers of inflammation and the innate immune response, including C-reactive protein, interleukin-6, TNF-α, and several cell adhesion molecules are linked to the occurrence of myocardial infarction and stroke in healthy elderly populations and patients with metabolic diseases. 2015 S. Karger AG, Basel.

Renal transplantation from hepatitis B surface antigen (HBsAg)-positive donors to HBsAg-negative recipients: a case of post-transplant fulminant hepatitis associated with an extensively mutated hepatitis B virus strain and review of the current literature.

PubMed

Magiorkinis, E; Paraskevis, D; Pavlopoulou, I D; Kantzanou, M; Haida, C; Hatzakis, A; Boletis, I N

2013-08-01

The purpose of this study was to present a fatal case of fulminant hepatitis B (FHB) that developed in a renal transplant recipient, immunized against hepatitis B, 1 year post transplantation. Polymerase chain reaction amplification and full genome sequencing were performed to investigate whether specific mutations were associated with hepatitis B virus (HBV) transmission and FHB. Molecular analysis revealed multiple mutations in various open reading frames of HBV, the most important being the G145R escape mutation and a frameshift mutation-insertion (1838insA) within the pre-C/C reading frame. Our results highlight the possibility of developing FHB, despite previous immunization against HBV or administration of hyperimmune gammaglobulin, because of the selection of escape virus mutants. The current literature and guidelines regarding renal transplantation from hepatitis B surface antigen (HBsAg)-positive to HBsAg-negative patients were also reviewed. © 2013 John Wiley & Sons A/S.

Single-Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment.

PubMed

Dudkowski, Caroline; Karim, Aziz; Zhao, Zhen; Alonso, Alberto B; Garg, Dyal; Preston, Richard A

2018-01-01

Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M-II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single-center, open-label, phase 1 parallel-group study that examined the single-dose (day 1) and multiple-dose (days 4-8) - 40 mg - pharmacokinetics of AZL and M-II in 16 subjects with mild and moderate hepatic impairment by Child-Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M-II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M-II. Single and multiple doses of AZL-M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL-M is required for subjects with mild and moderate hepatic impairment. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI.

PubMed

Kim, Yong-Woo; Kim, Hak Jin; Choi, Seon Hee; Kim, Dong Chan

2014-10-01

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute infarction at 4 days. The prominent hypointense veins on SWI may have good agreement with the increased MTT ratio. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[Antiphospholipid syndrome with autoimmune hemolytic anemia which mimics thrombotic thrombocytopenic purpura].

PubMed

Karasawa, Naoki; Taniguchi, Yasuhiro; Hidaka, Tomonori; Katayose, Keiko; Kameda, Takuro; Side, Kotaro; Shimoda, Haruko; Nagata, Kenji; Kubuki, Yoko; Matsunaga, Takuya; Shimoda, Kazuya

2010-04-01

A 67-year-old woman was admitted to the hospital for lethargy, fever, hemolytic anemia, thrombocytopenia, and consciousness disturbance. Direct Coombs test was positive, and anti-cardiolipin beta2-glycoprotein I antibody was detected. She was diagnosed with antiphospholipid syndrome complicated with autoimmune hemolytic anemia (AIHA). She demonstrated variable consciousness disturbance, inability to distinguish right from left, dysgraphia and dyscalculia. Multiple cerebral infarctions, especially dominant cerebral hemisphere infarctions, were observed on magnetic resonance imaging. A ventilation-perfusion scan demonstrated the presence of a ventilation-perfusion mismatch in both lung fields, and multiple veinous embolisms in the right femoral, bilateral the great saphenous and popliteal veins. Therefore, pulmonary embolism and thrombophlebitis were diagnosed. Based on these findings, it was necessary to distinguish this diagnosis from thrombotic thrombocytopenic purpura (TTP). As ADAMTS-13 activity was within the normal range, TTP was denied. Thereafter, the patient was treated with 1 mg/kg of prednisolone for AIHA, 3 mg of warfarin, and 3500 units of low-molecular-weight heparin for thrombosis, and her condition improved.

Diagnosis of viral hepatitis

PubMed Central

Easterbrook, Philippa J.; Roberts, Teri; Sands, Anita; Peeling, Rosanna

2017-01-01

Purpose of review Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and HIV–HBV and HCV coinfection are major causes of chronic liver disease worldwide. Testing and diagnosis is the gateway for access to both treatment and prevention services, but there remains a large burden of undiagnosed infection globally. We review the global epidemiology, key challenges in the current hepatitis testing response, new tools to support the hepatitis global response (2016–2020 Global Hepatitis Health Sector strategy, and 2017 WHO guidelines on hepatitis testing) and future directions and innovations in hepatitis diagnostics. Recent findings Key challenges in the current hepatitis testing response include lack of quality-assured serological and low-cost virological in-vitro diagnostics, limited facilities for testing, inadequate data to guide country-specific hepatitis testing approaches, stigmatization of those with or at risk of viral hepatitis and lack of guidelines on hepatitis testing for resource-limited settings. The new Global Hepatitis Health Sector strategy sets out goals for elimination of viral hepatitis as a public health threat by 2030 and gives outcome targets for reductions in new infections and mortality, as well as service delivery targets that include testing, diagnosis and treatment. The 2017 WHO hepatitis testing guidelines for adults, adolescents and children in low-income and middle-income countries outline the public health approach to strengthen and expand current testing practices for viral hepatitis and addresses who to test (testing approaches), which serological and virological assays to use (testing strategies) as well as interventions to promote linkage to prevention and care. Summary Future directions and innovations in hepatitis testing include strategies to improve access such as through use of existing facility and community-based testing opportunities for hepatitis testing, near-patient or point-of-care assays for virological markers (nucleic acid testing and HCV core antigen), dried blood spot specimens used with different serological and nucleic acid test assays, multiplex and multi-disease platforms to enable testing for multiple analytes/pathogens and potential self-testing for viral hepatitis. PMID:28306597

[Case of CNS-limited ANCA-associated vasculitis presenting as recurrent ischemic stroke].

PubMed

Wakisaka, Kayo; Hagiwara, Noriko; Kanazawa, Yuka; Arakawa, Shuji; Ago, Tetsuro; Kitazono, Takanari

2014-01-01

A 73-year-old man was admitted to our hospital because of a decrease in spontaneity. His medical history included two stroke episodes, probably related to hypertension. Brain MRI on admission demonstrated acute infarction in the right caudate nucleus and left putamen. Intravenous infusion of a low molecular-weight heparin added to oral antiplatelets was started. Following admission, he developed a low grade fever and severe inflammatory reaction. The focus of infection was not evident, and none of the antibiotics tried were effective. Ten days after admission, he developed right hemiparesis, and an additional brain MRI showed new multiple infarctions. We also determined the presence of a high MPO-ANCA titer (57 EU), and we diagnosed the patient's condition to be ANCA-associated vasculitis (AAV). Steroid therapy improved his inflammatory reaction and stroke recurrence was not observed. We suggest that vasculitis should be considered as a potential risk factor for repeated small infarctions with fever of unknown origin, especially those of perforating artery territories.

Dynamic regulation of hepatic lipid droplet properties by diet.

PubMed

Crunk, Amanda E; Monks, Jenifer; Murakami, Aya; Jackman, Matthew; Maclean, Paul S; Ladinsky, Mark; Bales, Elise S; Cain, Shannon; Orlicky, David J; McManaman, James L

2013-01-01

Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands.

Dynamic Regulation of Hepatic Lipid Droplet Properties by Diet

PubMed Central

Crunk, Amanda E.; Monks, Jenifer; Murakami, Aya; Jackman, Matthew; MacLean, Paul S.; Ladinsky, Mark; Bales, Elise S.; Cain, Shannon; Orlicky, David J.; McManaman, James L.

2013-01-01

Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands. PMID:23874434

Factors relating to transmission of viral hepatitis in a United States military population stationed in Thailand.

PubMed

Scott, R M; Schneider, R J; Snitbhan, R; Karwacki, J J

1981-05-01

To determine the incidence of clinical and inapparent hepatitis in a US military population stationed in Thailand, the authors prospectively studied a cohort of 326 men during one year. Clinical hepatitis A occurred in one man (clinical attack rate = 3.1/1000 men/year), and clinical hepatitis B was found in four men (clinical attack rate = 12.3/1000 men/year). No non-A, non-B hepatitis was identified. There was no serologically identified inapparent hepatitis A but inapparent hepatitis B occurred in 17 men. The apparent/inapparent ratio for hepatitis B was 1:4.25. Serotype analysis suggested that hepatitis B virus largely originated from Thai contacts, although 23% of cases were derived from western sources. To determine the relative contribution of 16 statistically significant (out of 67 studied) behavioral variables to the transmission of HBV, a factor analysis and a multivariate correlation analysis were employed. Factor analysis indicated that social and sexual contact with the indigenous population, including prostitutes, residence within the Thai community and marijuana use were behavioral areas that were associated with the acquisition of hepatitis B. Residence in the Thai community during the first four-month period in Thailand, sexual contact with a prostitute during the third four-month period, and ever having maintained a Thai mistress were found to be significant and independent risk factors by multiple regression analysis.

Pediatric hepatic hemangiosarcoma in a rhesus macaque (Macaca mulatta)

PubMed Central

Mejía, A.F.; Gierbolini, L.; Jacob, B.; Westmoreland, S.V.

2009-01-01

Background Pediatric hepatic angiosarcoma is a rare condition in children with poor prognosis. Microscopically this neoplasm has a particular ‘Kaposi-form’ arrangement. Hemangiosarcoma in non-human primates is a rare finding. Methods Gross and microscopic examination of a 3-year-old rhesus were performed. Immunohistochemistry was used to characterize the hepatic hemangiosarcoma. Results The gross necropsy revealed hemoabdomen and a 4 × 3 × 3 cm mass in the liver with multiple smaller masses throughout the hepatic parenchyma. Histopathology confirmed a poorly differentiated hemangiosarcoma. Other organs submitted were free of metastases. Conclusions Hemangiosarcoma in non-human primates has been rarely reported. Diagnosis was confirmed by expression of endothelial-specific markers CD31 and vWF by immunohistochemistry. Due to the young age of this monkey and the particular solid pattern throughout the mass this neoplasm resembles pediatric hepatic angiosarcoma in humans. PMID:18671765

Sofosbuvir-based therapy cures hepatitis C virus infection after prior treatment failures in a patient with concurrent lymphoma.

PubMed

Romagnoli, Dante; Marrazzo, Alessandra; Ballestri, Stefano; Lonardo, Amedeo; Bertolotti, Marco

2015-08-01

We report on the first well-tolerated and successful use of sofosbuvir-based therapy in a patient in whom chronic infection with hepatitis C had preceded the development of B-cell non-Hodgkin's lymphoma. The patient had previously failed numerous attempts to clear the hepatitis C virus with traditional antiviral schedules. We demonstrate that sofosbuvir-based therapy resulted in cure of hepatitis C in a patient who had relapsed during combination therapy with an NS5A inhibitor, an NS3 protease inhibitor and ribavirin, as well as treatment failures to multiple courses of interferon-based therapy. This report also suggests that eradication of hepatitis C virus may result in the short-term prevention of B-cell non-Hodgkin's lymphoma relapse. The findings from our case require further validation in future cohorts of patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Cat-scratch disease presenting as multiple hepatic lesions: case report and literature review.

PubMed

Baptista, Mariana Andrade; Lo, Denise Swei; Hein, Noely; Hirose, Maki; Yoshioka, Cristina Ryoka Miyao; Ragazzi, Selma Lopes Betta; Gilio, Alfredo Elias; Ferronato, Angela Esposito

2014-01-01

Although infectious diseases are the most prevalent cause of fevers of unknown origin (FUO), this diagnosis remains challenging in some pediatric patients. Imaging exams, such as computed tomography (CT) are frequently required during the diagnostic processes. The presence of multiple hypoattenuating scattered images throughout the liver associated with the history of cohabitation with cats should raise the suspicion of the diagnosis of cat-scratch disease (CSD), although the main etiologic agent of liver abscesses in childhood is S taphylococcus aureus . Differential diagnosis by clinical and epidemiological data with Bartonella henselae is often advisable. The authors report the case of a boy aged 2 years and 9 months with 16-day history of daily fever accompanied by intermittent abdominal pain. Physical examination was unremarkable. Abdominal ultrasound performed in the initial work up was unrevealing, but an abdominal CT that was performed afterwards disclosed multiple hypoattenuating hepatic images compatible with the diagnosis of micro abscesses. Initial antibiotic regimen included cefotaxime, metronidazole, and oxacillin. Due to the epidemiology of close contact with kittens, diagnosis of CSD was considered and confirmed by serologic tests. Therefore, the initial antibiotics were replaced by clarithromycin orally for 14 days followed by fever defervescence and clinical improvement. The authors call attention to this uncommon diagnosis in a child presenting with FUO and multiple hepatic images suggestive of micro abscesses.

Quantitation of 87 Proteins by nLC-MRM/MS in Human Plasma: Workflow for Large-Scale Analysis of Biobank Samples.

PubMed

Rezeli, Melinda; Sjödin, Karin; Lindberg, Henrik; Gidlöf, Olof; Lindahl, Bertil; Jernberg, Tomas; Spaak, Jonas; Erlinge, David; Marko-Varga, György

2017-09-01

A multiple reaction monitoring (MRM) assay was developed for precise quantitation of 87 plasma proteins including the three isoforms of apolipoprotein E (APOE) associated with cardiovascular diseases using nanoscale liquid chromatography separation and stable isotope dilution strategy. The analytical performance of the assay was evaluated and we found an average technical variation of 4.7% in 4-5 orders of magnitude dynamic range (≈0.2 mg/L to 4.5 g/L) from whole plasma digest. Here, we report a complete workflow, including sample processing adapted to 96-well plate format and normalization strategy for large-scale studies. To further investigate the MS-based quantitation the amount of six selected proteins was measured by routinely used clinical chemistry assays as well and the two methods showed excellent correlation with high significance (p-value < 10e-5) for the six proteins, in addition for the cardiovascular predictor factor, APOB: APOA1 ratio (r = 0.969, p-value < 10e-5). Moreover, we utilized the developed assay for screening of biobank samples from patients with myocardial infarction and performed the comparative analysis of patient groups with STEMI (ST- segment elevation myocardial infarction), NSTEMI (non ST- segment elevation myocardial infarction) and type-2 AMI (type-2 myocardial infarction) patients.

Computer-Aided Diagnostic (CAD) Scheme by Use of Contralateral Subtraction Technique

NASA Astrophysics Data System (ADS)

Nagashima, Hiroyuki; Harakawa, Tetsumi

We developed a computer-aided diagnostic (CAD) scheme for detection of subtle image findings of acute cerebral infarction in brain computed tomography (CT) by using a contralateral subtraction technique. In our computerized scheme, the lateral inclination of image was first corrected automatically by rotating and shifting. The contralateral subtraction image was then derived by subtraction of reversed image from original image. Initial candidates for acute cerebral infarctions were identified using the multiple-thresholding and image filtering techniques. As the 1st step for removing false positive candidates, fourteen image features were extracted in each of the initial candidates. Halfway candidates were detected by applying the rule-based test with these image features. At the 2nd step, five image features were extracted using the overlapping scale with halfway candidates in interest slice and upper/lower slice image. Finally, acute cerebral infarction candidates were detected by applying the rule-based test with five image features. The sensitivity in the detection for 74 training cases was 97.4% with 3.7 false positives per image. The performance of CAD scheme for 44 testing cases had an approximate result to training cases. Our CAD scheme using the contralateral subtraction technique can reveal suspected image findings of acute cerebral infarctions in CT images.

American childhood football as a possible risk factor for cerebral infarction.

PubMed

Brosch, Jared R; Golomb, Meredith R

2011-12-01

Three adolescent football players who had ischemic stroke associated with football practice and play are described. The literature on stroke associated with childhood sports and football in particular is reviewed, and the multiple mechanisms by which football can contribute to ischemic stroke are discussed.

Hepatic arteriovenous fistulae and portal vein hypoplasia in a Labrador retriever.

PubMed

Schaeffer, I G; Kirpensteijn, J; Wolvekamp, W T; Van den Ingh, T S; Rothuizen, J

2001-03-01

An 18-month-old male Labrador retriever was referred for investigation of chronic intermittent diarrhoea and vomiting of two months duration. A diagnosis of hepatic arteriovenous fistulae was made. These are extremely rare hepatic vascular anomalies which confer arterial pressure to the portal vein. Liver atrophy, portal vein hypoplasia, portal hypertension and multiple acquired portosystemic collateral vessels are the main complications. Surgical excision is a challenge as resection of large lesions may be associated with significant blood loss. In this dog, persistence of portal vein hypoplasia and extensive collateral pathways following surgery led to a reserved prognosis.

On bioartificial liver assist system: theoretical exploration and strategies for further development.

PubMed

Shi, Q

2000-11-01

The major difficulty in establishing a clinical effective bioartificial liver assist device for treatment of fulminate hepatic failure is limitation of our knowledge and technologies about fresh cell behaviors in culture and a lack of knowledge about the etiology and pathogenesis of hepatic coma. Increasing data from clinical and laboratory investigation have accrued indicating that toxins from necrotic liver tissue, mainly as oxygen reactive substances, have a role in the pathogenesis of hepatic encephalopathy and even multiple system organs failure. This paper presents the data available and suggests a new pathway for artificial and bioartificial liver assist system.

Risk factors and seroprevalence of markers for hepatitis A, B and C in persons subject to homelessness in inner Sydney.

PubMed

Poulos, Roslyn; Ferson, Mark; Orr, Karen; Lucy, Adrienne; Botham, Susan; McCarthy, Michele; Stern, Jerome; Dixon, Julie; Murray, Carolyn; Polis, Suzanne

2007-06-01

To determine the seroprevalence of hepatitis A, B and C and the prevalence of risk factors for blood-borne infections in persons subject to homelessness attending a medical clinic in inner Sydney. During 2003-05, 201 clients were enrolled in a prospective study to determine the acceptance, completion rates and immunogenicity of the standard vaccination schedule for hepatitis A and B. On enrolment, clients completed a risk factor assessment questionnaire and undertook pre-vaccination serological screening for hepatitis A, B and C. Forty-five per cent (85/188) of clients were positive for anti-HCV antibodies; 32% (60/189) showed evidence of past infection with HBV (anti-HBc); and 48% (89/189) were positive for anti-HAV antibodies. It was not uncommon for clients to have multiple markers of hepatitis. A past history of injecting drug use was significantly associated with markers for hepatitis B and C; age predicted presence of anti-HAV. A verbal history of infection appeared more reliable for hepatitis C, but considerably less so for hepatitis A and B. Persons subject to homelessness are at risk of blood-borne infection. The seroprevalence of markers for hepatitis B and C are higher than in the general population. Despite the high proportion of clients with serological markers for hepatitis A and B, at least 69% of clients could potentially benefit from hepatitis A and/or B vaccination.

The A's and B's of vaccine-preventable hepatitis: improving prevention in high-risk adults.

PubMed

Oldfield, Edward C; Keeffe, Emmet B

2007-01-01

Acute hepatitis A and acute hepatitis B are associated with significant morbidity, time away from work or usual activities, substantial cost to the healthcare system, and some mortality. Despite the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, and a combined hepatitis A and B vaccine since 2001, immunization rates against these vaccine-preventable diseases are appallingly low. In particular, several groups of adults, such as men who have sex with men, heterosexuals with multiple partners, injection drug users, persons with human immunodeficiency virus infection, travelers to endemic areas, and persons with chronic liver disease, are at particularly high risk for acute hepatitis A and B or for a more severe illness or a higher rate of chronicity in the case of hepatitis B. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients in these populations, although patients with more advanced disease may respond less well. These observations have led to the recommendation that patients falling into the above risk groups undergo hepatitis A and B vaccination early in the natural history of their underlying risk behavior or diseases. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. The use of a combined vaccination, possibly using an accelerated administration schedule, provides convenience and may increase compliance.

Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy.

PubMed

Ding, Zhi-Ming; Xiao, Yue; Wu, Xikun; Zou, Haixia; Yang, Shurong; Shen, Yiyun; Xu, Juehua; Workman, Heather C; Usborne, Amy L; Hua, Haiqing

2018-01-01

Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods. Male C57BL/6 mice fed Western diet developed progressive hepatic steatosis/macrovesicular vacuolation, inflammation, and hepatocyte degeneration, as well as perisinusoidal fibrosis and occasionally portal fibrosis as early as 2 months after initiation of the Western diet. In the same period, the mice exhibited elevated ALT (alanine aminotransferase) and AST (aspartate aminotransferase) enzyme activities, CK18 (cytokeratin-18), PIIINP (N-terminal propeptide of type III collagen), and TIMP-1 (tissue inhibitor of metalloproteinase-1). Hepatic steatosis diminished rapidly when the Western diet was replaced by normal rodent chow diet and hepatic inflammation and hepatocyte degeneration were also reduced. Interestingly, perisinusoidal fibrosis and portal fibrosis regressed 8 months after chow diet replacement. To understand pharmacotherapy for NASH, mice with established NASH hepatic lesions were treated with either FXR agonist obeticholic acid (Ocaliva), or CCR2/5 antagonist Cenicriviroc. Similar to the diet replacement, metabolic modulator Ocaliva markedly reduced steatosis/macrovesicular vacuolation, hepatic inflammation, and hepatocyte degeneration effectively, but exhibited no significant effect on liver fibrosis. Anti-inflammation drug Cenicriviroc, on the other hand, markedly decreased inflammation and hepatocyte degeneration, and mildly decreased liver fibrosis, but exhibited no effect on hepatic steatosis/macrovesicular vacuolation. In conclusion, we found the progression of NASH hepatic steatosis/macrovesicular vacuolation, and inflammation eventually lead to hepatocyte death and fibrosis. Life style change and current pharmacotherapies in development may be effective in treating NASH, but their effects on NASH-induced fibrosis may be mild. Since fibrosis is known to be an independent risk for decompensated cirrhosis, cardiovascular events, and mortality, our study suggests that effective anti-fibrosis therapy should be an essential component of the combined pharmacotherapy for advanced NASH.

Chronic periodontitis with multiple risk factor syndrome: a case report.

PubMed

Shimoe, Masayuki; Yamamoto, Tadashi; Iwamoto, Yoshihiro; Shiomi, Nobuyuki; Maeda, Hiroshi; Nishimura, Fusanori; Takashiba, Shogo

2011-07-01

Multiple risk factor syndrome is a clustering of cardiovascular risk factors, such as diabetes, dyslipidemia, hypertension, and obesity associated epidemiologically with insulin resistance. This report describes the clinical course of a patient suffering from severe periodontitis with multiple risk factor syndrome, and discusses the association between periodontal infection and systemic health. The patient had a history of type 2 diabetes, dyslipidemia, and hypertension for over 10 years. At baseline, her hemoglobin A1 c was 8.1%. However, she had no diabetic complications except periodontitis. The IgG antibody titers against Porphyromonas gingivalis FDC 381 and SU63 were elevated above the mean of healthy subjects +2 standard deviations. Intensive periodontal treatment, including periodontal surgery, was performed to reduce periodontal infection and bacteremia. Her systemic and periodontal conditions were evaluated longitudinally for 10 years. Following periodontal treatment, antibody titers against Porphyromonas gingivalis and hemoglobin A1c values were significantly improved. The other clinical data and medication for her systemic condition also remained stable during supportive periodontal therapy. However, she developed myocardial infarction, and showed continuous deterioration of hemoglobin A1 c level and periodontitis. The long-term clustering of risk factors, such as diabetes, dyslipidemia, hypertension, and periodontitis, are associated with the development of myocardial infarction. Treatment of systemic conditions in combination with comprehensive periodontal treatment is important in management of patients with multiple risk factor syndrome.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levy, H.M.; Smith, R.

Two cases of thalassemia major are presented in which bone scintigraphy demonstrated diffuse hepatic uptake of Tc-99m diphosphonate. Although abnormal splenic and renal uptake of Tc-99m phosphates has been reported in patients with thalassemia major, hepatic uptake has not been reported previously. This scintigraphic finding is presumably due to increased iron deposition in the liver, resulting from increased iron turnover and retention in these patients and from multiple previous blood transfusions.

[The influence of fasting, of a hyperprotein diet and of nicotinamide on hepatic L-threonine deaminase].

PubMed

Aleo, M F; Casella, A; Marinello, E

1981-09-15

The induction of L-threonine deaminase, following nicotinamide injection has been studied: the effect of fasting and of hyperproteic diet have been also taken in consideration. Maximal induction is observed after 5 days hyperproteic diet, and is additional only with nicotinamide treatment. Results are interpreted assuming a different hepatic content and behavior of multiple forms of the enzyme.

CADASIL accelerated by acute hypotension: Arterial and venous contribution to leukoaraiosis.

PubMed

Pettersen, Jacqueline A; Keith, Julia; Gao, Fuqiang; Spence, J David; Black, Sandra E

2017-03-14

To underline the importance of blood pressure regulation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to describe changes that occur in the veins in this condition, specifically venous collagenosis associated with leukoaraiosis. Case report with neuroimaging and pathologic data. A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He died 5 weeks post trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy and multiple cavitations involving deep subcortical gray and white matter. Small arteries had thickened walls, disruption of the muscularis, and intimal periodic acid-Schiff (PAS)-positive material. Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis. There was no pathologic evidence of global hypoxia or diffuse axonal injury. The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. In addition, collagenosis of veins in the affected white matter regions suggests that the veins may play an important, though largely overlooked, role in maintaining white matter integrity. © 2017 American Academy of Neurology.

Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial.

PubMed

Kubica, Jacek; Adamski, Piotr; Ostrowska, Małgorzata; Sikora, Joanna; Kubica, Julia Maria; Sroka, Wiktor Dariusz; Stankowska, Katarzyna; Buszko, Katarzyna; Navarese, Eliano Pio; Jilma, Bernd; Siller-Matula, Jolanta Maria; Marszałł, Michał Piotr; Rość, Danuta; Koziński, Marek

2016-01-14

The currently available data indicate a drug-drug interaction between morphine and oral P2Y12 receptor inhibitors, when administered together. The aim of this trial was to assess the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with acute myocardial infarction. In a single-centre, randomized, double-blind trial, patients were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry and ticagrelor antiplatelet effects were measured with up to three different platelet function tests: vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow. The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0-12): 6307 vs. 9791 ng h/mL; P = 0.003), and 37% (AUC(0-12): 1503 vs. 2388 ng h/mL; P = 0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; P = 0.004). Multiple regression analysis showed that lower AUC(0-12) values for ticagrelor were independently associated with the administration of morphine (P = 0.004) and the presence of ST-segment elevation myocardial infarction (P = 0.014). All three methods of platelet reactivity assessment showed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in patients receiving morphine. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction. ClinicalTrials.gov Identifier: NCT02217878. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Multiple Risk Factors of Alcoholic and Non-Alcoholic Myocardial Infarction Patients.

PubMed

Harisharan; Singh, Awnish Kumar; Dangal, Nidhu Ram; Surapaneni, Krishna Mohan; Joshi, Ashish

2015-05-17

Myocardial infarction (MI) is one of the most critical medical emergency and contributor to morbidity and mortality worldwide. Myocardial infarction is the most common form of coronary heart disease and leading cause of premature death. Past century has seen substantial advancement in the field of medical sciences but still mortality trends due to myocardial infarction is increasing in developing countries including India. We have conducted this study to compare the Sociodemographic characteristics of alcoholic and non alcoholic MI patients admitted in coronary care unit of Saveetha Medical College, Chennai, India. An exploratory cross sectional study was performed by enrolling a convenient sample of 100 Myocardial Infarction patients. Information about Sociodemographic characteristics, past medical history, alcohol and tobacco intake, physical activity, psychological stress and biochemical measurements was gathered. The mean age of the respondents was 46 (SD=6) years and majority of them were male i.e. 82%. 100% married and 89% literate, there were 24% past and 22% present alcoholics. Consumption of alcohol on a monthly, weekly and daily basis was 8%, 11% and 5% respectively. Preference to brandy was 67%, rum was 21% and that the beer was 12%. Current smoker were 20% and former were 11%. 93% and 52% respondents were under medication of beta blocker and angiotensin-converting-enzyme (ACE) inhibitors respectively. Worldwide, MI is the most common cause of mortality and morbidity and hence early diagnosis and management is most essential. Results from our study revealed that, participants had sedentary lifestyles where risk factors of MI such as alcohol consumption, and smoking does existed.

Perceived neighbourhood social cohesion and myocardial infarction.

PubMed

Kim, Eric S; Hawes, Armani M; Smith, Jacqui

2014-11-01

The main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviours. Although important, emphasis on individuals has diverted focus and responsibility away from neighbourhood characteristics, which also strongly influence people's behaviours. Although a growing body of research has repeatedly demonstrated strong associations between neighbourhood characteristics and cardiovascular health, it has typically focused on negative neighbourhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighbourhood characteristics, such as perceived neighbourhood social cohesion. Using multiple logistic regression models, we tested whether higher perceived neighbourhood social cohesion was associated with lower incidence of myocardial infarction. Prospective data from the Health and Retirement Study--a nationally representative panel study of American adults over the age of 50--were used to analyse 5276 participants with no history of heart disease. Respondents were tracked for 4 years and analyses adjusted for relevant sociodemographic, behavioural, biological and psychosocial factors. In a model that adjusted for age, gender, race, marital status, education and total wealth, each SD increase in perceived neighbourhood social cohesion was associated with a 22% reduced odds of myocardial infarction (OR=0.78, 95% CI 0.63 to 0.94. The association between perceived neighbourhood social cohesion and myocardial infarction remained even after adjusting for behavioural, biological and psychosocial covariates. Higher perceived neighbourhood social cohesion may have a protective effect against myocardial infarction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Maternal hepatitis B infection and gestational diabetes mellitus.

PubMed

Lao, Terence T; Chan, Ben C P; Leung, Wing-Cheong; Ho, Lai-Fong; Tse, Ka-Yu

2007-07-01

This retrospective cohort study was performed to examine the relationship between maternal hepatitis B virus infection, as indicated by the surface antigen status, with the development of gestational diabetes mellitus in a normal-risk Chinese obstetric population. Maternal demographics, risk factors, and pregnancy outcome of 13,683 singleton pregnancies delivering in 1998-2001 were analysed according to maternal hepatitis B surface antigen status, which was routinely screened. Multiple logistic regression analysis was performed to examine the role of hepatitis B infection in the development of gestational diabetes mellitus. The 1138 women (8.3%) with hepatitis B infection had lower mean weight and body mass index, similar prevalence of chronic medical diseases and smokers, but increased prevalence of gestational diabetes mellitus, which remained significant (odds ratio 1.24, 95% confidence interval 1.01-1.51) after adjustment for confounding variables. However, there was no difference in pregnancy outcome. Our results confirmed the independent association between hepatitis B infection with gestational diabetes mellitus. The magnitude of chronic hepatitis B infection in the developing world and certain ethnic groups could have contributed to the high prevalence of gestational and possibly type 2 diabetes in these populations. Further studies on the long-term implications of our finding are warranted.

Gastrointestinal and hepatic complications of sickle cell disease.

PubMed

Ebert, Ellen C; Nagar, Michael; Hagspiel, Klaus D

2010-06-01

Sickle cell disease (SCD) is an autosomal recessive abnormality of the beta-globin chain of hemoglobin (Hb), resulting in poorly deformable sickled cells that cause microvascular occlusion and hemolytic anemia. The spleen is almost always affected by SCD, with microinfarcts within the first 36 months of life resulting in splenic atrophy. Acute liver disorders causing right-sided abdominal pain include acute vaso-occlusive crisis, liver infarction, and acute hepatic crisis. Chronic liver disease might be due to hemosiderosis and hepatitis and possibly to SCD itself if small, clinically silent microvascular occlusions occur chronically. Black pigment gallstones caused by elevated bilirubin excretion are common. Their small size permits them to travel into the common bile duct but cause only low-grade obstruction, so hyperbilirubinemia rather than bile duct dilatation is typical. Whether cholecystectomy should be done in asymptomatic individuals is controversial. The most common laboratory abnormality is an elevation of unconjugated bilirubin level. Bilirubin and lactate dehydrogenase levels correlate with one another, suggesting that chronic hemolysis and ineffective erythropoiesis, rather than liver disease, are the sources of hyperbilirubinemia. Abdominal pain is very common in SCD and is usually due to sickling, which resolves with supportive care. Computed tomography scans might be ordered for severe or unremitting pain. The liver typically shows sickled erythrocytes and Kupffer cell enlargement acutely and hemosiderosis chronically. The safety of liver biopsies has been questioned, particularly during acute sickling crisis. Treatments include blood transfusions, exchange transfusions, iron-chelating agents, hydroxyurea, and allogeneic stem-cell transplantation. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Systemic Embolic Complications of Pulmonary Vein Angioplasty in Children.

PubMed

Esch, Jesse J; Porras, Diego; Bergersen, Lisa; Jenkins, Kathy J; Marshall, Audrey C

2015-10-01

Pulmonary vein stenosis (PVS) carries significant morbidity and mortality for affected children, and its management often requires multiple angioplasty procedures. PVS angioplasty can be complicated by systemic embolic events such as stroke, but incidence and risk factors are poorly understood. We reviewed pediatric catheterizations involving PVS angioplasty and/or stent placement performed at Boston Children's Hospital between July 2005 and February 2014. A total of 406 cases were performed in 144 distinct patients. Patients underwent a median of two catheterizations, at median age 1 year and weight 6.9 kg. Eleven (2.7 %) catheterizations were complicated by clinically apparent systemic embolic events, comprising 10 strokes (one with associated hepatic embolism) and 1 renal infarct. Prevalence of clinically evident stroke among this cohort was 7.6 %. Using a prior (uncomplicated) catheterization to allow each patient to serve as their own control, we sought to identify potentially modifiable risk factors for systemic embolic events. Although this analysis was limited by low power, complicated and uncomplicated angioplasties did not appear to differ in case time, contrast dose, anticoagulation management, use of cutting balloons, number of catheter exchanges, or size of long sheath used. Significant non-embolic adverse events were common, occurring in 25 % of catheterizations. Systemic embolism appears to complicate PVS angioplasty at a rate much higher than that described for other congenital catheterizations. This risk may be inherent to the procedure rather than related to any modifiable or operator-dependent factors.

Hydrogen sulphide increases hepatic differentiation of human tooth pulp stem cells compared with human bone marrow stem cells.

PubMed

Okada, M; Ishkitiev, N; Yaegaki, K; Imai, T; Tanaka, T; Fukuda, M; Ono, S; Haapasalo, M

2014-12-01

To determine the differences in stem cell properties, in hepatic differentiation and in the effects of hydrogen sulphide (H2 S) on hepatic differentiation between human bone marrow stem cells (hBMC) and stem cells from human exfoliated primary tooth pulp (SHED). CD117(+) cells were magnetically separated and subjected to hepatic differentiation. CD117(+) cell lineages were characterized for transcription factors indicative of stem cells by qRT-PCR. For the last 9 days of the differentiation, the test cells were exposed to 0.1 ng mL(-1) H2 S. Immunocytochemistry and flow cytometry of albumin, alpha-fetoprotein and carbamoyl phosphate synthetase were carried out after differentiation. Urea concentration and glycogen synthesis were also determined. Genes expressed in SHED were also expressed in BMC. No difference in expression level of hepatic markers was shown by immunofluorescence. SHED showed more positive cells than hBMC (P < 0.01). H2 S increased the number of positive cells in both cultures (P < 0.01). Urea concentration and glycogen synthesis increased significantly after H2 S exposure (P < 0.001 and P < 0.05, respectively). Real-time PCR data were analysed by RT(2) profiler RT-PCR Array Data Analysis version 3.5 (Qiagen), and ELISA data were analysed by Bonferroni's multiple comparison using Windows spss version 16 (SPSS Inc, Chicago, IL, USA). Bonferroni's multiple comparison test was also carried out after angle transformation for the percentage data of flow cytometer using Windows spss(®) version 16 (SPSS Inc). Statistical significance was accepted at P < 0.05. Stem cells from human exfoliated primary tooth pulp and BMC have similar properties. The level of hepatic differentiation in SHED compared with BMC was the same or higher. H2 S increased the level of hepatic differentiation. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis.

PubMed

Haffar, Samir; Shalimar; Kaur, Ravinder J; Wang, Zhen; Prokop, Larry J; Murad, Mohammad H; Bazerbachi, Fateh

2018-04-19

Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4. Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors. We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA. Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Computerized tomographic findings of hepatic fascioliasis compared with melioidosis-caused liver abscesses.

PubMed

Chamadol, Nittaya; Laopaiboon, Vallop; Techasatian, Pennapa; Sukeepaisanjaroen, Wattana; Sripanuskul, Anan

2010-07-01

To compare the computerized tomographic (CT) findings of hepatic fascioliasis (HF) vs. melioidosis-caused liver (ML) abscesses. CT images of 15 patients with hepatic fascioliasis (HF) and 16 patients with melioidosis-caused liver (ML) abscesses were retrospectively reviewed. The authors evaluated and compared HF and ML abscesses (by chi2 and Fisher exact tests) vis-a-vis their location of liver involvement, size, shape, number margins, enhancement patterns, subcapsular lesions, internal architecture, dilatation of intrahepatic bile duct and combination with splenic abscesses. Fourteen HF patients had only liver abscesses and 1 had combined liver and splenic abscesses. Four ML patients had liver abscesses alone while 12 had combined liver and splenic abscesses (p = 0.000). Eight of the 15 HF (53.3%) and 2 of the 16 ML (12.5%) patients had subcapsular lesions (p = 0.019). The liver abscesses were round or oval with linear tracts in 8 of the 15 HF (53.3%) and none of the ML patients (p = 0.001). Between the respective HF and ML patients, there was a significant difference in those with round shaped in ML (p = 0.008), multiple and conglomerately distributed in HF (p = 0.050), multiple and discretely distributed in ML (p = 0.001) no (or minimal) peripheral contrast enhancement in HF (p = 0.011) and moderate or mark peripheral enhancement in ML (p = 0.011). The CT findings of liver abscesses that helped to differentiate hepatic fascioliasis from melioidosis liver abscesses were: their number shape, enhancement pattern, presence of subcapsular lesion (s) and co-occurrence with splenic abscesses. The diagnosis of hepatic fascioliasis by CT is suggested when the following characteristics were seen: (1) multiple, small round or oval (with linear tracts) conglomerates presenting as hypodense lesions; (2) no (or minimal) peripheral contrast enhancement; (3) subcapsular lesions; or (4) less frequent co-occurrence with splenic abscesses.

Utility of texture analysis for quantifying hepatic fibrosis on proton density MRI.

PubMed

Yu, HeiShun; Buch, Karen; Li, Baojun; O'Brien, Michael; Soto, Jorge; Jara, Hernan; Anderson, Stephan W

2015-11-01

To evaluate the potential utility of texture analysis of proton density maps for quantifying hepatic fibrosis in a murine model of hepatic fibrosis. Following Institutional Animal Care and Use Committee (IACUC) approval, a dietary model of hepatic fibrosis was used and 15 ex vivo murine liver tissues were examined. All images were acquired using a 30 mm bore 11.7T magnetic resonance imaging (MRI) scanner with a multiecho spin-echo sequence. A texture analysis was employed extracting multiple texture features including histogram-based, gray-level co-occurrence matrix-based (GLCM), gray-level run-length-based features (GLRL), gray level gradient matrix (GLGM), and Laws' features. Texture features were correlated with histopathologic and digital image analysis of hepatic fibrosis. Histogram features demonstrated very weak to moderate correlations (r = -0.29 to 0.51) with hepatic fibrosis. GLCM features correlation and contrast demonstrated moderate-to-strong correlations (r = -0.71 and 0.59, respectively) with hepatic fibrosis. Moderate correlations were seen between hepatic fibrosis and the GLRL feature short run low gray-level emphasis (SRLGE) (r = -0. 51). GLGM features demonstrate very weak to weak correlations with hepatic fibrosis (r = -0.27 to 0.09). Moderate correlations were seen between hepatic fibrosis and Laws' features L6 and L7 (r = 0.58). This study demonstrates the utility of texture analysis applied to proton density MRI in a murine liver fibrosis model and validates the potential utility of texture-based features for the noninvasive, quantitative assessment of hepatic fibrosis. © 2015 Wiley Periodicals, Inc.

Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake.

PubMed

Cedó, Lídia; Santos, David; Roglans, Núria; Julve, Josep; Pallarès, Victor; Rivas-Urbina, Andrea; Llorente-Cortes, Vicenta; Laguna, Joan Carles; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

2017-01-01

Human hepatic lipase (hHL) is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL) is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT). In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL)-mediated free fatty acid (FFA) lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL.

Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake

PubMed Central

Cedó, Lídia; Santos, David; Roglans, Núria; Julve, Josep; Pallarès, Victor; Rivas-Urbina, Andrea; Llorente-Cortes, Vicenta; Laguna, Joan Carles

2017-01-01

Human hepatic lipase (hHL) is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL) is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT). In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL)-mediated free fatty acid (FFA) lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL. PMID:29244870

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

PubMed

Youns, Mаhmoud; Abdel Halim Hegazy, Wael

2017-01-01

Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways

PubMed Central

Youns, Mаhmoud; Abdel Halim Hegazy, Wael

2017-01-01

Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes. PMID:28052097

Characterization of European-ancestry NAFLD-Associated Variants in Individuals of African and Hispanic Descent

PubMed Central

Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon LR; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

2013-01-01

Nonalcoholic Fatty Liver Disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European-ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African and/or Hispanic Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African-American (n=3124) and one Hispanic-American (n=849) cohorts. All analyses controlled for variation in age, age2, gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African-American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9kg/m2, respectively. Hepatic steatosis was 0.20–0.34 heritable in African-and Hispanic-American families (p<0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Conclusions We show for the first time that multiple genetic variants are associated with hepatic steatosis across ancestries and explain a substantial proportion of the genetic predisposition in African and Hispanic Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. PMID:23564467

Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and Hispanic descent.

PubMed

Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon L R; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

2013-09-01

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African- and/or Hispanic-Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African American (n = 3,124) and one Hispanic American (n = 849) cohorts. All analyses controlled for variation in age, age(2) , gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9 kg/m(2) , respectively. Hepatic steatosis was 0.20-0.34 heritable in African- and Hispanic-American families (P < 0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Multiple genetic variants are associated with hepatic steatosis across ancestries. This explains a substantial proportion of the genetic predisposition in African- and Hispanic-Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. © 2013 by the American Association for the Study of Liver Diseases.

Prospective Evaluation of 18F-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome.

PubMed

Rischpler, Christoph; Dirschinger, Ralf J; Nekolla, Stephan G; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

2016-04-01

The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI (18)F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of (18)F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed (18)F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, (99m)Tc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of (18)F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that (18)F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14(high)/CD16(+) monocytes correlated with the infarction size and (18)F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). (18)F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P<0.04, Δ end-diastolic volume: P<0.02, Δ end-systolic volume: P<0.005). In this study, the intensity of (18)F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, (18)F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. © 2016 American Heart Association, Inc.

Emerging options for treating hepatitis C infection.

PubMed

Fantasia, Heidi Collins

2015-01-01

Hepatitis C infection can cause chronic liver disease and liver carcinoma and can necessitate liver transplantation. Of the more than 3 million people infected with hepatitis C, more than two-thirds were born between 1945 and 1965. Many individuals are unaware that they're infected, which can delay treatment and lead to disease progression. Once infection is diagnosed, typical treatment regimens can involve multiple medications and side effects that can make it challenging for some people to complete therapy. In October 2014 the U.S. Food and Drug Administration (FDA) approved Harvoni®, a fixed dose combination pill of ledipasvir/sofosbuvir that provides a new option for treatment. © 2015 AWHONN.

Gene expression profile associated with superimposed non-alcoholic fatty liver disease and hepatic fibrosis in patients with chronic hepatitis C.

PubMed

Younossi, Zobair M; Afendy, Arian; Stepanova, Maria; Hossain, Noreen; Younossi, Issah; Ankrah, Kathy; Gramlich, Terry; Baranova, Ancha

2009-10-01

Hepatic steatosis occurs in 40-70% of patients chronically infected with hepatitis C virus [chronic hepatitis C (CH-C)]. Hepatic steatosis in CH-C is associated with progressive liver disease and a low response rate to antiviral therapy. Gene expression profiles were examined in CH-C patients with and without hepatic steatosis, non-alcoholic steatohepatitis (NASH) and fibrosis. This study included 65 CH-C patients who were not receiving antiviral treatment. Total RNA was extracted from peripheral blood mononuclear cells, quantified and used for one-step reverse transcriptase-polymerase chain reaction to profile 153 mRNAs that were normalized with six 'housekeeping' genes and a reference RNA. Multiple regression and stepwise selection assessed differences in gene expression and the models' performances were evaluated. Models predicting the grade of hepatic steatosis in patients with CH-C genotype 3 involved two genes: SOCS1 and IFITM1, which progressively changed their expression level with the increasing grade of steatosis. On the other hand, models predicting hepatic steatosis in non-genotype 3 patients highlighted MIP-1 cytokine encoding genes: CCL3 and CCL4 as well as IFNAR and PRKRIR. Expression levels of PRKRIR and SMAD3 differentiated patients with and without superimposed NASH only in the non-genotype 3 cohort (area under the receiver operating characteristic curve=0.822, P-value 0.006]. Gene expression signatures related to hepatic fibrosis were not genotype specific. Gene expression might predict moderate to severe hepatic steatosis, NASH and fibrosis in patients with CH-C, providing potential insights into the pathogenesis of hepatic steatosis and fibrosis in these patients.

Characteristics of an outpatient chronic hepatitis B virus infection cohort

PubMed Central

de Assis, Danyenne Rejane; Tenore, Simone de Barros; Pinho, João Renato Rebello; Lewi, David Salomão; Ferreira, Paulo Roberto Abrão

2015-01-01

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID:26154539

Multiple inflammatory and serum amyloid A positive telangiectatic hepatic adenomas with glycogenated nuclei arising in a background of nonalcoholic steatohepatitis.

PubMed

Lim, Kiat H; Ward, Stephen C; Roayaie, Sasan; Cohen, Emil; Schwartz, Myron; Fiel, M Isabel; Thung, Swan N

2008-11-01

The authors describe multiple telangiectatic or inflammatory adenomas in a 53-year-old woman with steatohepatitis who presented with acute right upper quadrant abdominal pain. Magnetic resonance imaging revealed 6 lesions consistent with multiple hepatic adenomas, 2 of which showed hemorrhage. She underwent right lobectomy and nonanatomical segment 2 liver resections and seven nodules ranging in size from 1.0 to 5.0 cm were identified. All nodules contained portal-like structures and ductular reaction, features seen in focal nodular hyperplasia, as well as significant inflammation, telangiectatic sinusoids and immunoreactivity for serum amyloid A, placing them according to a recently described classification systems as telangiectatic or inflammatory adenomas. The diffuse positivity of the serum amyloid A staining results in this case suggests an important diagnostic role of this stain in smaller tissue samples, such as in core biopsy specimens.

[A case of multiple hepatocellular carcinoma with rapidly progressing bilateral portal vein tumor thrombosis--a complete remission achieved with dual treatment of reductive surgery plus percutaneous isolated hepatic perfusion].

PubMed

Tsuchida, Shinobu; Fukumoto, Takumi; Tominaga, Masahiro; Iwasaki, Takeshi; Kusunoki, Nobuya; Sugimoto, Takemi; Kido, Masahiro; Takebe, Atsushi; Tanaka, Motofumi; Hisoka, Kinoshita; Ku, Yonson

2005-10-01

We herein report a case of multiple advanced hepatocellular carcinoma (HCC) with rapidly progressing portal vein tumor thrombosis (PVTT). All of the hepatic tumors have completely disappeared for more than two years by a dual treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP). A 55-year-old man was referred to our institution on June 30, 2003. The abdominal CT scan demonstrated multiple massive HCC in the entire liver with PVTT reaching the portal trunk (Vp4). Two weeks later, the PVTT rapidly progressed to the umbilical portion of the left portal vein, and to the confluence of the superior mesenteric vein and to the splenic vein. Thus, we semi electively performed an extended right hepatectomy together with thrombectomy of the PVTT. Subsequently, he underwent a repeated PIHP (1st; doxorubicin 90 mg/m2, 2nd doxorubicin 65 mg/m2). This treatment produced complete tumor clearance of all of the residual tumors in the left liver. In March 2005, he underwent partial pneumonectomy for a metastatic lung. This again resulted in normalization of serum AFP and PIVKA-II levels. Dual treatment is considered to be the strongest therapeutic modality for multiple advanced HCC with severe PVTT. In addition, a close follow-up is required because in such far advanced cases, metastatic lesions most likely recur in the liver but also in the distant organs.

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2016-10-01

Obeticholic acid (Ocaliva) for primary biliary cholangitis; sofosbuvir 400 mg/velpatasvir 100 mg (Epclusa) for chronic hepatitis C virus infection; and daclizumab (Zinbryta) for relapsing multiple sclerosis.

Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in Type 2 diabetes.

PubMed

Kong, C; Nimmo, L; Elatrozy, T; Anyaoku, V; Hughes, C; Robinson, S; Richmond, W; Elkeles, R S

2001-06-01

We have studied the relationships between hepatic lipase activity, smoking, dyslipidaemia insulin resistance, and early atherosclerosis in 67 Type 2 diabetic subjects, 47 non-smokers and 20 smokers. Insulin resistance was measured using an insulin modified frequently sampled intravenous glucose tolerance test. Early atherosclerosis was assessed using high-resolution ultrasound to measure carotid intima media thickness (IMT) and an arterial ultrasonic score (AUS). Smokers had higher serum cholesterol and triglyceride, lower HDL and HDL2 cholesterol as well as increased hepatic lipase activity. They were also more insulin resistant than non-smokers. Smokers also had higher patient AUS scores. On multiple regression analysis, hepatic lipase activity emerged as the most significant variable affecting patient AUS. We suggest that smoking accentuates the dyslipidaemia of Type 2 diabetic subjects and this is associated with increased hepatic lipase activity. This may be one mechanism whereby smoking further increases the risk of cardiovascular disease in Type 2 diabetes.

Discordances originated by multiple meta-analyses on interventions for myocardial infarction: a systematic review.

PubMed

Lucenteforte, Ersilia; Moja, Lorenzo; Pecoraro, Valentina; Conti, Andrea A; Conti, Antonio; Crudeli, Elena; Galli, Alessio; Gensini, Gian Franco; Minnelli, Martina; Mugelli, Alessandro; Proietti, Riccardo; Shtylla, Jonida; D'Amico, Roberto; Parmelli, Elena; Virgili, Gianni

2015-03-01

To clarify the impact of multiple (covering the same population, intervention, control, and outcomes) systematic reviews (SRs) on interventions for myocardial infarction (MI). Clinical Evidence (BMJ Group) sections and related search strategies regarding MI were used to identify multiple SRs published between 1997 and 2007. Multiple SRs were classified as discordant if they featured conflicting results or interpretation of them. Thirty-six SRs (23.5% of 153 on the treatment or prevention of MI) were classified as multiple and grouped in 16 clusters [ie, at least two SRs with the same PICO (population, condition/disease, intervention, control) and at least one common outcome] exploring angioplasty, angiotensin-converting enzyme inhibitors, anticoagulants, antiplatelets, β-blockers, and stents. Complete agreement on statistically significant differences between interventions was found in 7 of 10 clusters with a shared composite outcome. Agreement was reduced when single outcomes were considered. Despite substantial variation and limited agreement in reporting of major outcomes, SRs agreed in their conclusions on the superiority of either the intervention or control in 14 of 16 clusters. Sources of minor discrepancies were found in terms of study and outcome selection, subgroup analyses, and interpretation of findings. Multiple SRs agreed in their qualitative conclusions but not on reporting and on analyses of hard outcomes. Discordance on significance of treatment effects was due to a combination of variation in design with inclusion of different studies and lack of precision for single hard outcomes compared with a composite outcome. Such inconsistencies among SRs could potentially slow the translation of SRs' results to clinical and public health decision making and suggest the need for a broader methodological and clinical agreement on their design. Copyright © 2015 Elsevier Inc. All rights reserved.

Imaging predictors of poststroke depression: methodological factors in voxel-based analysis

PubMed Central

Gozzi, Sophia A; Wood, Amanda G; Chen, Jian; Vaddadi, Krishnarao; Phan, Thanh G

2014-01-01

Objective The purpose of this study was to explore the relationship between lesion location and poststroke depression using statistical parametric mapping. Methods First episode patients with stroke were assessed within 12 days and at 1-month poststroke. Patients with an a priori defined cut-off score of 11 on the Hospital Anxiety and Depression Scale (HADS) at follow-up were further assessed using the Mini-International Neuropsychiatric Interview (MINI) to confirm a clinical diagnosis of major or minor depression in accordance with Diagnostic and Statistical Manual-IV (DSM-IV) inclusion criteria. Participants were included if they were aged 18–85 years, proficient in English and eligible for MRI. Patients were excluded if they had a confounding diagnosis such as major depressive disorder at the time of admission, a neurodegenerative disease, epilepsy or an imminently life-threatening comorbid illness, subarachnoid or subdural stroke, a second episode of stroke before follow-up and/or a serious impairment of consciousness or language. Infarcts observed on MRI scans were manually segmented into binary images, linearly registered into a common stereotaxic coordinate space. Using statistical parametric mapping, we compared infarct patterns in patients with stroke with and without depression. Results 27% (15/55 patients) met criteria for depression at follow-up. Mean infarct volume was 19±53 mL and National Institute of Health Stroke Scale (NIHSS) at Time 1 (within 12 days of stroke) was 4±4, indicating a sample of mild strokes. No voxels or clusters were significant after a multiple comparison correction was applied (p>0.05). Examination of infarct maps showed that there was minimal overlap of infarct location between patients, thus invalidating the voxel comparison analysis. Conclusions This study provided inconclusive evidence for the association between infarcts in a specific region and poststroke depression. PMID:25001395

Prevalence and Prognosis of Hyperkalemia in Patients with Acute Myocardial Infarction

PubMed Central

Grodzinsky, Anna; Goyal, Abhinav; Gosch, Kensey; McCullough, Peter A.; Fonarow, Gregg C.; Mebazaa, Alexandre; Masoudi, Frederick A.; Spertus, John A.; Palmer, Biff F.; Kosiborod, Mikhail

2016-01-01

Background Hyperkalemia is common and potentially dangerous in hospitalized patients; its contemporary prevalence and prognostic importance following acute myocardial infarction are not well described. Methods In 38,689 consecutive acute myocardial infarction patients from the Cerner Health Facts database, we evaluated the association between maximum in-hospital potassium levels (max K) and in-hospital mortality. Patients were stratified by dialysis status, and grouped by max K as follows: <5 mEq/L, 5–<5.5 mEq/L, 5.5–<6.0 mEq/L, 6.0–<6.5 mEq/L, and ≥ 6.5 mEq/L. Multivariable logistic regression was used to adjust for multiple patient and site characteristics. The relationship between number of hyperkalemic values and in-hospital mortality was also evaluated. Results Of 38,689 acute myocardial infarction patients, 886 were on dialysis. The rate of hyperkalemia (max K ≥ 5.0 mEq/L) was 22.6% in non-dialysis and 66.8% in dialysis patients. Moderate-severe hyperkalemia (max K ≥ 5.5 mEq/L) occurred in 9.8% of patients. There was a steep increase in mortality with higher max K levels. In-hospital mortality exceeded 15% once max K ≥5.5 mEq/L regardless of dialysis status. The relationship between higher max K and increased mortality risk persisted after multivariable adjustment. In addition, patients with greater number of hyperkalemic values (vs. a single value) experienced higher in-hospital mortality. Conclusions Hyperkalemia is common in patients hospitalized with acute myocardial infarction. Higher max K levels and number of hyperkalemic events are associated with a steep mortality increase; with higher risks for adverse outcomes observed even at mild levels of hyperkalemia. Whether more intensive management of hyperkalemia may improve outcomes in acute myocardial infarction patients merits further study. PMID:27060233

Prevalence and Prognosis of Hyperkalemia in Patients with Acute Myocardial Infarction.

PubMed

Grodzinsky, Anna; Goyal, Abhinav; Gosch, Kensey; McCullough, Peter A; Fonarow, Gregg C; Mebazaa, Alexandre; Masoudi, Frederick A; Spertus, John A; Palmer, Biff F; Kosiborod, Mikhail

2016-08-01

Hyperkalemia is common and potentially dangerous in hospitalized patients; its contemporary prevalence and prognostic importance after acute myocardial infarction are not well described. In 38,689 consecutive patients with acute myocardial infarction from the Cerner Health Facts database, we evaluated the association between maximum in-hospital potassium levels and in-hospital mortality. Patients were stratified by dialysis status and grouped by maximum potassium as follows: <5 mEq/L, 5 to <5.5 mEq/L, 5.5 to <6.0 mEq/L, 6.0 to <6.5 mEq/L, and ≥6.5 mEq/L. Multivariable logistic regression was used to adjust for multiple patient and site characteristics. The relationship between the number of hyperkalemic values and the in-hospital mortality was evaluated. Of 38,689 patients with acute myocardial infarction, 886 were on dialysis. The rate of hyperkalemia (maximum potassium ≥5.0 mEq/L) was 22.6% in patients on dialysis and 66.8% in patients not on dialysis. Moderate to severe hyperkalemia (maximum potassium ≥5.5 mEq/L) occurred in 9.8% of patients. There was a steep increase in mortality with higher maximum potassium levels. In-hospital mortality exceeded 15% once maximum potassium was ≥5.5 mEq/L regardless of dialysis status. The relationship between higher maximum potassium and increased mortality risk persisted after multivariable adjustment. In addition, patients with a greater number of hyperkalemic values (vs a single value) experienced higher in-hospital mortality. Hyperkalemia is common in patients who are hospitalized with acute myocardial infarction. Higher maximum potassium levels and number of hyperkalemic events are associated with a steep mortality increase, with higher risks for adverse outcomes observed even at mild levels of hyperkalemia. Whether more intensive management of hyperkalemia may improve outcomes in patients with acute myocardial infarction merits further study. Copyright © 2016 Elsevier Inc. All rights reserved.

[Surgical outcome of external decompression associated with anterior and medial temporal lobectomy for massive hemispheric infarction due to internal carotid artery occlusion].

PubMed

Yamazaki, Takaaki; Kamiyama, Kenji; Osato, Toshiaki; Sasaki, Takehiko; Nakagawara, Jyoji; Nakamura, Hirohiko

2010-01-01

Acute occlusion of the internal carotid artery (ICA) can lead the massive cerebral hemispheric infarction and cause massive cerebral edema and may result in tentorial herniation and death. The mortality rate is estimated at 80% with maximum conservative medical treatment. We have performed external decompression associated with anterior and medial temporal lobectomy (AMTL) as internal decompression for lifesaving. This study evaluated our surgical results and gives an analysis of the prognostic factors. Twenty one consecutive patients with massive cerebral infarction caused by internal carotid artery occlusion who underwent external decompression associated with AMTL for lifesaving between June 2000 and December 2005 were included in this retrospective analysis. Survivors were divided into two functional groups at three months after surgery: good (Barthel index; BI> or =50) and poor (B1<50). The characteristics of the two groups were compared using statistical analysis. The patients consisted of 11 males and 10 females aged from 28 to 81 years with a mean age of 65.0+/-11.6 years. Eight patients had an infarction restricted to the middle cerebral artery (MCA) territory, others had additional anterior cerebral artery (ACA) or posterior cerebral artery (PCA) territory infarctions. The mean time between stroke onset and operation was 43.5+/-30 hours and ranged from 7 to 148 hours. Two patients died, so the mortality was 9.5%. Elderly patients (> or =60 years) (P=0.038), high preoperative Japan coma scale (> or =3 digit) (P=0.013), low preoperative Glasgow coma scale (GCS<8) (P=0.044), and multiple arterial territory (MCA+ACA or PCA) infarction (P=0.045) were significantly associated with poor functional outcome. External decompression associated with AMTL can immediately relieve peduncle compression and could be effective in preserving life as effectively as "early" external decompression.

Autologous Fat Used for Facial Filling Can Lead to Massive Cerebral Infarction Through Middle Cerebral Artery or Facial Intracranial Branches.

PubMed

Wang, Xian; Wu, Min; Zhou, Xing; Liu, Hengdeng; Zhang, Yongchao; Wang, Haiping

2018-05-31

Autologous fat injection is a procedure aimed at eliminating grave defects in the skin surface by subcutaneous injection of the patient's fatty tissue. Fat embolism is a rare but severe complication of this procedure, especially cerebral infarction. It is first reported by Thaunat in 2004. were presented to the hospital with sudden unconsciousness and left limb weakness in 24 hours after facial fat injection. Brain computed tomography and magnetic resonance imaging were performed immediately after admission. Frontal temporoparietal decompressive craniectomy plus multiple treatments scheduled for patients. Pictures and videos were taken during follow-up. Figures are edited with Adobe Photograph CS6. Patients were diagnosed with extensive cerebral infarction of the right hemisphere through the middle cerebral artery or facial-intracranial branches. Routine cosmetic procedures of facial fat injections could cause devastating and even fatal complications to patients. The small volume of fat grafts can be inserted through the internal carotid artery or go through the communicating branches between the facial artery and the intracranial artery into the brain.

Hepatic Encephalopathy: From the Pathogenesis to the New Treatments

PubMed Central

Cordoba, Juan

2014-01-01

Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis; the pathophysiology of this complication is not fully understood although great efforts have been made during the last years. There are few prospective studies on the epidemiology of this complication; however, it is known that it confers with high short-term mortality. Hepatic encephalopathy has been classified into different groups depending on the degree of hepatic dysfunction, the presence of portal-systemic shunts, and the number of episodes. Due to the large clinical spectra of overt EH and the complexity of cirrhotic patients, it is very difficult to perform quality clinical trials for assessing the efficacy of the treatments proposed. The physiopathology, clinical manifestation, and the treatment of HE is a challenge because of the multiple factors that converge and coexist in an episode of overt HE. PMID:27335836

Splenic Infarction in Acute Infectious Mononucleosis.

PubMed

Naviglio, Samuele; Abate, Maria Valentina; Chinello, Matteo; Ventura, Alessandro

2016-01-01

The evaluation of a febrile patient with acute abdominal pain represents a frequent yet possibly challenging situation in the emergency department (ED). Splenic infarction is an uncommon complication of infectious mononucleosis, and may have a wide range of clinical presentations, from dramatic to more subtle. Its pathogenesis is still incompletely understood, yet it may be associated with the occurrence of transient prothrombotic factors. We report the case of a 14-year-old boy who presented with fever, sore throat, left upper quadrant abdominal pain, and splenomegaly, with no history of recent trauma. Laboratory tests revealed a markedly prolonged activated partial thromboplastin time and positive lupus anticoagulant. Abdominal ultrasonography showed several hypoechoic areas in the spleen consistent with multiple infarctions. Magnetic resonance imaging eventually confirmed the diagnosis. He was admitted for observation and supportive treatment, and was discharged in good condition after 7 days. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Spontaneous splenic infarction should be considered in the differential list of patients presenting with left upper quadrant abdominal pain and features of infectious mononucleosis; the diagnosis, however, may not be straightforward, as clinical presentation may also be subtle, and abdominal ultrasonography, which is often used as a first-line imaging modality in pediatric EDs, has low sensitivity in this scenario and may easily miss it. Furthermore, although treatment is mainly supportive, close observation for possible complications is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnetic resonance imaging correlates of bee sting induced multiple organ dysfunction syndrome: A case report.

PubMed

Das, Sushant K; Zeng, Li-Chuan; Li, Bing; Niu, Xiang-Ke; Wang, Jing-Liang; Bhetuwal, Anup; Yang, Han-Feng

2014-09-28

Occasionally systemic complications with high risk of death, such as multiple organ dysfunction syndrome (MODS), can occur following multiple bee stings. This case study reports a patient who presented with MODS, i.e., acute kidney injury, hepatic and cardiac dysfunction, after multiple bee stings. The standard clinical findings were then correlated with magnetic resonance imaging (MRI) findings, which demonstrates that MRI may be utilized as a simpler tool to use than other multiple diagnostics.

Place of Arterial Embolization in Severe Blunt Hepatic Trauma: A Multidisciplinary Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monnin, Valerie, E-mail: val_monnin@yahoo.fr; Sengel, Christian; Thony, Frederic

2008-09-15

This study evaluates the efficacy of arterial embolization (AE) for blunt hepatic traumas (BHT) as part of a combined management strategy based on the hemodynamic status of patients and CT findings. From 2000 to 2005, 84 patients were admitted to our hospital for BHT. Of these, 14 patients who had high-grade injuries (grade III [n = 2], grade IV [n = 9], grade V [n = 3]) underwent AE because of arterial bleeding and were included in the study. They were classified into three groups according to their hemodynamic status: (1) unresponsive shock, (2) shock improved with resuscitation, and (3)more » hemodynamic stability. Four patients (group 1) underwent, first, laparotomy with packing and, then, AE for persistent bleeding. Ten patients who were hemodynamically stable (group 1) or even unstable (group 2) underwent AE first, based on CT findings. AE was successful in all cases. The mortality rate was 7% (1/14). Only two angiography-related complications (gallbladder infarction) were reported. Liver-related complications (abdominal compartment syndrome and biliary complications) were frequent and often required secondary interventions. Our multidisciplinary approach for the management of BHT gives a main role to embolization, even for hemodynamically unstable patients. In this strategy AE is very efficient and has a low complication rate.« less

Alpha-lipoic acid impairs body weight gain of young broiler chicks via modulating peripheral AMPK.

PubMed

Wang, Yufeng; Everaert, Nadia; Song, Zhigang; Decuypere, Eddy; Vermeulen, Daniel; Buyse, Johan

2017-09-01

In mammals, the AMP-activated protein kinase (AMPK) pathways in the central and peripheral tissues coordinately integrate inputs from multiple sources to regulate energy balance. The present study was aimed to explore the potential role of hepatic AMPK in the energy homeostasis of broiler chickens. Diets with 0, 0.05% or 0.1% alpha-lipoic acid (α-LA), a known AMPK inhibitor were provided to broiler chicks for 7days. As a result, α-LA supplementation decreased the relative growth rate of broiler chicks. Hepatic AMPKα2 mRNA levels were significantly upregulated by dietary α-LA, in concert with the increased phosphorylated AMPKα protein levels. In addition, hepatic FAS mRNA levels together with the malonyl-CoA to total CoA ester ratio were reduced by α-LA supplementation. Moreover, the hepatic phosphorylated glycogen synthase levels were increased resulting in a markedly decreased hepatic glycogen content. In conclusion, dietary α-LA supplementation decreased the in vivo hepatic glycogenesis and lipogenesis via stimulating hepatic AMPKα mRNA levels and the phosphorylated gene product. The stimulatory effect of α-LA on hepatic AMPK mRNA and pAMPKα protein levels together with our previous observations regarding its inhibitory effect on hypothalamic AMPK may have altered the energy balance and hence impaired body weight gain of broiler chicks. Copyright © 2017 Elsevier Inc. All rights reserved.

Epidemiological study of hepatitis A, B and C in the largest Afro-Brazilian isolated community.

PubMed

Matos, Márcia A D; Reis, Nádia Rúbia S; Kozlowski, Aline G; Teles, Sheila A; Motta-Castro, Ana Rita C; Mello, Francisco C A; Gomes, Selma A; Martins, Regina M B

2009-09-01

This study was conducted to estimate the prevalence and molecular epidemiological features of viral hepatitis A, B and C in the Kalunga population, which represents the largest Afro-Brazilian isolated community. Among 878 individuals studied, the overall prevalence of anti-hepatitis A virus antibodies was 80.9%, with a significant rise from 44.8% to near 100% between the first and fourth decade of life. Rates for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) of 1.8% and 35.4%, respectively, were found. Increasing age, male gender, illiteracy and history of multiple sexual partners were associated with hepatitis B virus (HBV) infection. An occult HBV infection rate of 1.7% (5/295) was found among anti-HBc-positive individuals. HBV genotype A (subtype Aa) was dominant in this community. Only 5/878 individuals (0.6%) were positive for anti-hepatitis C virus (HCV). HCV RNA was detected in three of them, who were infected with genotype 1 (subtype 1a). These findings point out high, intermediate and low endemicity for hepatitis A, B and C, respectively, in the Kalunga community in Brazil. Circulation of HBV genotype A (subtype Aa) in this Afro-Brazilian isolated community indicates the introduction of this virus during the slave trade from Africa to Brazil.

Methylprednisolone liver toxicity: A new case and a French regional pharmacovigilance survey.

PubMed

Dumortier, Jérôme; Cottin, Judith; Lavie, Caroline; Guillaud, Olivier; Hervieu, Valérie; Chambon-Augoyard, Christine; Scoazec, Jean-Yves; Vukusic, Sandra; Vial, Thierry

2017-09-01

Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug. In addition, 3 of these 5 patients underwent unintended single or multiple positive MP rechallenge. Our 5 patients scored a RUCAM score from 6 (probable) to 10 (highly probable). MP-induced liver injury is probably very rare, since only less than 30 cases have been reported in the literature. Nevertheless, our cases strongly illustrates that many cases could have been unrecognized; final diagnosis in 3 of 5 of our patients was made after the second or third episode of acute hepatitis. In conclusion, these cases we report here strongly illustrates that high-dose MP-induced liver injury can occur in patients treated for MS or auto-immune disorder. Unintended re-challenge can confirm the diagnosis and can help to distinguish it from autoimmune hepatitis. Performing liver function tests routinely both before and after MP administration would be beneficial, as the timely recognition of this complication and early drug withdrawal may prevent progression of severe necrosis hepatic injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hepatic Cyst Compressing The Right Atrial and Ventricular Inflow Tract: An Uncommon Cardiac Complication.

PubMed

Panchal, Maulik; Alansari, Ahmed; Wallack, Marc; Visco, Ferdinand; Williams, Susan; Sy, Alexander M

2018-01-01

Commonly reported complications of hepatic cysts are spontaneous hemorrhage, rupture into the peritoneal cavity, infection and compression of the biliary tree however cardiac complications are not commonly reported. We are presenting a case of a large liver cyst presenting with right atrial and ventricular inflow tract impingement resulting in cardiac symptoms. A 68 year-old Hispanic female presented with one month of fatigue and shortness of breath after household work and walking less than one block, right upper quadrant pain and weight loss. She had history of multiple hepatic cysts for more than 12 years, well-controlled diabetes and hypertension. Examination of the heart revealed tachycardia with regular heart sounds. There were no murmurs. She had tenderness in her right upper quadrant on palpation and an enlarged smooth liver. Rest of physical examination was unremarkable. CT scan of the abdomen showed multiple non-enhancing liver cysts in both lobes, with the largest measuring 12 x 15 x 17 cm which was significantly increased from her baseline of 7 x 8 x 10 cm in 2003. Echocardiogram showed normal left ventricular ejection fraction, grade 1 diastolic dysfunction and a hepatic cyst impinging RA and RV inflow tract. She had successful laparoscopic enucleation of liver cyst and subsequent relief from tachycardia, fatigue and shortness of breath. In conclusion, this case illustrates that hepatic cysts may become symptomatic after remaining quiescent for an extended period. They may present with unusual symptoms and clinicians should be mindful of rare complications, such as in this case.

Assessment of hepatitis B virus and hepatitis C virus infections and associated risk factors in HIV infected patients at Debretabor hospital, South Gondar, Northwest Ethiopia

PubMed Central

Balew, Melashu; Moges, Feleke; Yismaw, Gizachew; Unakal, Chandrashekhar

2014-01-01

Objective To assess hepatitis B and hepatitis C virus infections and associated risk factors among HIV infected patients at Debretabor hospital. Methods A cross-sectional study was conducted among HIV/AIDS patients attending Debretabor hospital from February to April, 2012. Venous blood samples were collected from study participants for HBsAg and anti HCV antibody tests. Bivariate and multivariate analyses were used to identify associated variables with HBsAg and anti HCV positivity. Variables having P<0.05 was taken as statistically significant association. Results From a total of 395 HIV infected patients included in this study, 234 (59.2%) were females and 161 (40.8%) males with mean (±SD) age of 36.31 (±9.91) years. The prevalence of HBsAg and anti HCV antibody was 6.1% and 1.3%, respectively. In multivariate analysis, multiple sexual partner (AOR=8.1, 95% CI=1.8-33.97) and history of opportunistic infections (AOR=3.17, 95% CI=1.3-7.7) were statistically associated with HBsAg positivity. History of blood transfusion (AOR=5.61, 95% CI= 1.03-36.59) was associated with presence of anti-HCV antibody. Conclusions The prevalence of HBsAg and anti HCV antibodies in HIV coinfected patients was intermediate. However, it is relevant for HIV infected patients since viral hepatitis co-infections in HIV patients can cause multiple complications. Therefore, routine HBV and HCV screening with reliable diagnostic markers need to be carried out for close monitoring and better management in HIV patients.

Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats

PubMed Central

Yang, Shuai; Abbott, Geoffrey W.; Gao, Wei Dong; Liu, Jin; Luo, Chaozhi

2017-01-01

Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway. NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury. However, it is unclear whether ischemic conditioning of visceral organs such as the liver, the largest metabolic organ in the body, can produce cardioprotection. This is the first study to show the cardioprotective effect of remote liver ischemic conditioning in a rat model of myocardial I/R injury. We also, for the first time, demonstrated these protective properties are associated with glycogen synthase kinase-3β-dependent cell-survival signaling pathway. PMID:28153944

Fatty liver disease, glucose tolerance and insulin resistance in obese adolescents.

PubMed

Slyper, A H; Rosenberg, H; Kabra, A; Huang, W-M; Blech, B; Matsumura, M M

2015-12-01

Adult studies suggest that intra-hepatic fat predicts 2-h blood glucose levels and type 2 diabetes, and may have a role in the development of insulin resistance. Our study objective was to explore relationships between intra-hepatic fat and (i) blood glucose levels and (ii) insulin resistance determined by homeostasis model assessment (HOMA) in a group of obese adolescents. Subjects were 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index >95th percentile for age and 2-h blood glucose <200 mg dL(-1) . Each subject underwent 2-h glucose tolerance testing and measurement of haemoglobin A1c, ultrasensitive C-reactive protein and fasting insulin. Visceral, subcutaneous abdominal and intra-hepatic fat were determined by magnetic resonance imaging. Intra-hepatic fat was measured by gradient echo chemical shift imaging. Alanine aminotransferase levels and hepatic phase difference were not significant correlates of fasting or 2-h glucose. In a multiple regression model including hepatic phase difference and visceral fat volume, visceral fat volume was the sole predictor of HOMA. This study provides no support to the notion that intra-hepatic fat has a role in the regulation of fasting blood glucose, 2-h postprandial blood glucose or systemic insulin resistance. © 2014 World Obesity.

Beyond Parasitism: Hepatic Lesions in Stranded Harbor Porpoises (Phocoena phocoena) Without Trematode (Campula oblonga) Infections.

PubMed

Hiemstra, S; Harkema, L; Wiersma, L C M; Keesler, R I

2015-11-01

The liver can be an indicator of the health of an individual or of a group, which can be especially important to identify agents that can cause disease in multiple species. To better characterize hepatic lesions in stranded harbor porpoises (Phocoena phocoena), we analyzed the livers from 39 porpoises that stranded along the Dutch coast between December 2008 and December 2012. The animals were selected because they had either gross or histologic liver lesions with minimal autolysis and no evidence of trematode (Campula oblonga) infection. The most common finding was a chronic hepatitis (22/39, 56.4%) that was often associated with significant disease reported in another organ system (18/22, 81.8%), of which 14 had chronic systemic disease. One case of chronic hepatitis was so severe as to mimic lymphoma, which could only be differentiated with immunohistochemistry. The other common lesions were lipidosis (11/39, 28.2%) and acute hepatitis (6/39, 15.4%), often in combination with mild chronic changes. Overall, although there were no consistent trends in etiology for the hepatic lesions, lipidosis was associated with starvation (8/11, 72.7%) and acute disease, and acute hepatitis was associated with bacterial infections and sepsis (6/6, 100%). © The Author(s) 2014.

Dietary proanthocyanidins boost hepatic NAD(+) metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats.

PubMed

Aragonès, Gerard; Suárez, Manuel; Ardid-Ruiz, Andrea; Vinaixa, Maria; Rodríguez, Miguel A; Correig, Xavier; Arola, Lluís; Bladé, Cinta

2016-04-22

Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD(+)) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD(+) precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD(+). Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD(+) availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD(+) levels.

Dietary proanthocyanidins boost hepatic NAD+ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats

PubMed Central

Aragonès, Gerard; Suárez, Manuel; Ardid-Ruiz, Andrea; Vinaixa, Maria; Rodríguez, Miguel A.; Correig, Xavier; Arola, Lluís; Bladé, Cinta

2016-01-01

Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD+) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD+ precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD+. Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD+ availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD+ levels. PMID:27102823

Usefulness of Single Photon Emission Computed Tomography/Computed Tomography Fusion-Hybrid Imaging to Evaluate Coronary Artery Disorders in Patients with a History of Kawasaki Disease.

PubMed

Abe, Masanori; Fukazawa, Ryuji; Ogawa, Shunichi; Watanabe, Makoto; Fukushima, Yoshimitsu; Kiriyama, Tomonari; Hayashi, Hiromitsu; Itoh, Yasuhiko

2016-01-01

The coronary arterial lesions of Kawasaki disease are mainly dilative lesions, aneurysms, and stenotic lesions formed before, after, and between aneurysms; these lesions develop in multiple branches resulting in complex coronary hemodynamics. Diagnosis of myocardial ischemia and infarction and evaluation of the culprit coronary arteries and regions is critical to evaluating the treatment and prognosis of patients. This study used hybrid imaging, in which multidetector computed tomographic (CT) images for coronary CT angiography (CCTA) and stress myocardial perfusion single-photon emission CT (SPECT) images were fused. We investigated the diagnosis of blood vessels and regions responsible for myocardial ischemia and infarction in patients with complex coronary arterial lesions; in addition, we evaluated myocardial lesions that developed directly under giant coronary artery aneurysms. The subjects were 17 patients with Kawasaki disease with multiple coronary arterial lesions (median age, 18.0 years; 16 male). Both CCTA using 64-row CT and adenosine-loading myocardial SPECT were performed. Three branches, the right coronary artery (RCA), left anterior descending branch (LAD), and left circumflex branch, were evaluated with the conventional side-by-side interpretation, in which the images were lined up for diagnosis, and hybrid imaging, in which the CCTA and SPECT images were fused with computer processing. In addition, the myocardial lesions directly under giant coronary artery aneurysms were investigated with fusion imaging. Images sufficient for evaluation were acquired in all 17 patients. In the RCA, coronary arterial lesions were detected with CCTA in 16 patients. The evaluations were consistent between the side-by-side and fusion interpretation in 14 patients, and the blood vessel responsible for the myocardial ischemic region was identified in 2 patients. In the left circumflex branch, coronary arterial lesions were confirmed with 3-dimensional CT in 5 patients, and the the culprit coronary arteries for myocardial ischemia/infarction were confirmed with the fusion interpretation but not with the side-by-side interpretation. In the LAD, coronary arterial lesions were present in all patients, and the diagnosis was made with the fusion interpretation in 10 patients. In the LAD, small-range infarct lesions were detected directly under the giant coronary artery aneurysm in 8 patients, but were not confirmed with the side-by-side interpretation. Fusion imaging was capable of accurately evaluating myocardial ischemia/infarction as cardiovascular sequelae of Kawasaki disease and confirming the culprit coronary arteries. In addition, analysis of fusion images confirmed that small-range infarct lesions were concomitantly present directly under giant coronary artery aneurysms in the anterior descending coronary artery.

Prospective Evaluation of Transcatheter Arterial Chemoembolization (TACE) with Multiple Anti-Cancer Drugs (Epirubicin, Cisplatin, Mitomycin C, 5-Fluorouracil) Compared with TACE with Epirubicin for Treatment of Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahara, Shinya; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@mail.wakayama-med.ac.jp

Purpose: To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC). Materials and Methods: The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis;more » Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group. Results: No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019). Conclusion: TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone.« less

Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

PubMed

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

2014-01-01

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.

A novel neuroimaging model to predict early neurological deterioration after acute ischemic stroke.

PubMed

Huang, Yen-Chu; Tsai, Yuan-Hsiung; Lee, Jiann-Der; Yang, Jen-Tsung; Pan, Yi-Ting

2018-05-16

In acute ischemic stroke, early neurological deterioration (END) may occur in up to one-third of patients. However, there is still no satisfying or comprehensive predictive model for all the stroke subtypes. We propose a practical model to predict END using magnetic resonance imaging (MRI). Patients with anterior circulation infarct were recruited and they underwent an MRI within 24 hours of stroke onset. END was defined as an elevation of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) within 72 hours of stroke onset. We examined the relationships of END to individual END models, including: A, infarct swelling; B, small subcortical infarct; C, mismatch; and D, recurrence. There were 163 patients recruited and 43 (26.4%) of them had END. The END models A, B and C significantly predicted END respectively after adjusting for confounding factors (p=0.022, p=0.007 and p<0.001 respectively). In END model D, we examined all imaging predictors of Recurrence Risk Estimator (RRE) individually and only the "multiple acute infarcts" pattern was significantly associated with END (p=0.032). When applying END models A, B, C and D, they successfully predicted END (p<0.001; odds ratio: 17.5[95% confidence interval: 5.1-60.8]), with 93.0% sensitivity, 60.0% specificity, 45.5% positive predictive value and 96.0% negative predictive value. The results demonstrate that the proposed model could predict END in all stroke subtypes of anterior circulation infarction. It provides a practical model for clinical physicians to select high-risk patients for more aggressive treatment to prevent END. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sex differences in perceived stress and early recovery in young and middle-aged patients with acute myocardial infarction.

PubMed

Xu, Xiao; Bao, Haikun; Strait, Kelly; Spertus, John A; Lichtman, Judith H; D'Onofrio, Gail; Spatz, Erica; Bucholz, Emily M; Geda, Mary; Lorenze, Nancy P; Bueno, Héctor; Beltrame, John F; Krumholz, Harlan M

2015-02-17

Younger age and female sex are both associated with greater mental stress in the general population, but limited data exist on the status of perceived stress in young and middle-aged patients presenting with acute myocardial infarction. We examined sex difference in stress, contributing factors to this difference, and whether this difference helps explain sex-based disparities in 1-month recovery using data from 3572 patients with acute myocardial infarction (2397 women and 1175 men) 18 to 55 years of age. The average score of the 14-item Perceived Stress Scale at baseline was 23.4 for men and 27.0 for women (P<0.001). Higher stress in women was explained largely by sex differences in comorbidities, physical and mental health status, intrafamily conflict, caregiving demands, and financial hardship. After adjustment for demographic and clinical characteristics, women had worse recovery than men at 1 month after acute myocardial infarction, with mean differences in improvement score between women and men ranging from -0.04 for EuroQol utility index to -3.96 for angina-related quality of life (P<0.05 for all). Further adjustment for baseline stress reduced these sex-based differences in recovery to -0.03 to -3.63, which, however, remained statistically significant (P<0.05 for all). High stress at baseline was associated with significantly worse recovery in angina-specific and overall quality of life, as well as mental health status. The effect of baseline stress on recovery did not vary between men and women. Among young and middle-aged patients, higher stress at baseline is associated with worse recovery in multiple health outcomes after acute myocardial infarction. Women perceive greater psychological stress than men at baseline, which partially explains women's worse recovery. © 2015 American Heart Association, Inc.

Effect of Common Neuropathologies on Progression of Late Life Cognitive Impairment

PubMed Central

Yu, Lei; Boyle, Patricia A.; Leurgans, Sue; Schneider, Julie A.; Kryscio, Richard J.; Wilson, Robert S.; Bennett, David A.

2015-01-01

Brain pathologies of Alzheimer’s, cerebrovascular and Lewy body diseases are common in old age, but the relationship of these pathologies with progression from normal cognitive function to the various stages of cognitive impairment is unknown. In this study, we fit latent Markov models from longitudinal cognitive data to empirically derive three latent stages corresponding to no impairment, mild impairment, and moderate impairment; then, we examined the associations of common neuropathologies with the rates of transition among these stages. Cognitive and neuropathological data were available from 653 autopsied participants in two ongoing cohort studies of aging who were cognitively healthy at baseline (mean baseline age 79.1 years) and had longitudinal cognitive data. On average, participants in these analyses developed mild impairment 5 years after enrollment, progressed to moderate impairment after an additional 3.4 years, and stayed impaired for 2.8 years until death. AD and chronic macroscopic infarcts were associated with a higher risk of progression to mild impairment and subsequently to moderate impairment. By contrast, Lewy bodies were associated only with progression from mild to moderate impairment. The 5-year probability of progression to mild or moderate impairment was 20% for persons without any of these three pathologies, 38% for AD only, 51% for AD and macroscopic infarcts, and 56% for AD, infarcts and Lewy bodies. Thus, the presence of AD pathology alone nearly doubles the risk of developing cognitive impairment in late life, and the presence of multiple pathologies further increases this risk over multiple years prior to death. PMID:25976345

Genetic heterogeneity of hepatitis E virus in Darfur, Sudan, and neighboring Chad.

PubMed

Nicand, Elisabeth; Armstrong, Gregory L; Enouf, Vincent; Guthmann, Jean Paul; Guerin, Jean-Philippe; Caron, Mélanie; Nizou, Jacques Yves; Andraghetti, Roberta

2005-12-01

The within-outbreak diversity of hepatitis E virus (HEV) was studied during the outbreak of hepatitis E that occurred in Sudan in 2004. Specimens were collected from internally displaced persons living in a Sudanese refugee camp and two camps implanted in Chad. A comparison of the sequences in the ORF2 region of 23 Sudanese isolates and five HEV samples from the two Chadian camps displayed a high similarity (>99.7%) to strains belonging to Genotype 1. But four isolates collected in one of the Chadian camps were close to Genotype 2. Circulation of divergent strains argues for possible multiple sources of infection. Copyright (c) 2005 Wiley-Liss, inc.

[Financial burden of hepatitis B-related diseases and factors influencing the costs in Shenzhen, China].

PubMed

Liang, Sen; Zhang, Shun-xiang; Ma, Qi-shan; Xiao, He-wei; Lü, Qiu-ying; Xie, Xu; Mei, Shu-jiang; Hu, Dong-sheng; Zhou, Bo-ping; Li, Bing; Chen, Jing-fang; Cui, Fu-qiang; Wang, Fu-zhen; Liang, Xiao-feng

2010-12-01

To investigate the direct, indirect and intangible costs due to hepatitis B-related diseases and to explore main factors associated with the costs in Shenzhen. Cluster sampling for cases collected consecutively during the study period was administrated. Subjects were selected from eligible hepatitis B-related patients. By pre-trained professional investigators, health economics-related information was collected, using a structured questionnaire. Hospitalization expenses were obtained through hospital records after the patients were discharged from hospital. Total economic burden of hepatitis B-related patients would involve direct, indirect and intangible costs. Direct costs were further divided into direct medical costs and direct nonmedical costs. Human Capital Approach was employed to measure the indirect costs both on patients and the caregivers in 1-year time span. Willing to pay method was used to estimate the intangible costs. Multiple linear stepwise regression models were conducted to determine the factors linked to the economic burden. On average, the total annual cost of per patient with hepatitis B-related diseases was 81 590.23 RMB Yuan. Among which, direct, indirect and intangible costs were 30 914.79 Yuan (account for 37.9%), 15 258.01 Yuan (18.7%), 35 417.43 Yuan (43.4%), respectively. The total annual costs per patient for hepatocellular carcinoma, severe hepatitis B, decompensated cirrhosis, compensated cirrhosis, chronic hepatitis B and acute hepatitis B were 194 858.40 Yuan, 144 549.20 Yuan, 120 333.60 Yuan, 79 528.81 Yuan, 66 282.46 Yuan and 39 286.81 Yuan, respectively. The ratio of direct to indirect costs based on the base-case estimation foot add to 2.0:1, increased from hepato-cellular carcinoma (0.7:1) to compensated cirrhosis (3.5:1), followed by acute hepatitis B (3.3:1), severe hepatitis B (2.8:1), decompensate cirrhosis (2.3:1) and chronic hepatitis B (2.2:1). Direct medical costs were more than direct nonmedical. Ratio between the sum total was 16:1. The proportions of total annual cost per patient with hepatitis B-related diseases accounted for annual patient income were 285.3%, and 75.4% for annual household income. Furthermore, proportions of direct costs accounted for annual patient income and annual household income were 108.1% and 28.6%. The total annual indirect cost per person was 8123.38 Yuan for patients of all hepatitis B-related diseases, while 7134.63 Yuan for caregivers. Corresponding work-loss days were 55.74 days for patients and 19.83 days for caregivers. Based on multiple linear stepwise regression analysis, age of patients was a common influencing factor to all kinds of costs. Other factors were as follows: complicated with other diseases, antiviral medication, monthly household income and self-medications. The economic burden of hepatitis B-related diseases was substantial for patients and their families. All costs tended to increase with the severity of disease. The direct costs were larger than the indirect costs. And the direct medical costs were more than the direct ones. Indirect costs based on patients were larger than the ones of caregivers.

Ophthalmological implications of the chronic infections with the hepatitis C Virus.

PubMed

Anisia-Iuliana, Alexa; Alina, Cantermir; Elena, Ciuntu Roxana; Dorin, Chiseliţă

2015-01-01

Objectives. Report of a clinical case reuniting the dry eye syndrome in a severe form, the Mooren's ulcer and necrotizing anterior scleritis with inflammation, with bilateral affectation in the context of chronic infection with the hepatitis C virus. Methods. A female patient aged 66 diagnosed with chronic hepatitis with HCV, with ophthalmological antecedents of Mooren's ulcer and severe form of dry eye syndrome in both eyes, comes to the emergency unit with hypopyon corneal ulcer in the right eye, shortly afterwards developing necrotizing anterior scleritis with inflammation. The patient is administered treatment for chronic hepatitis C, following which the ARN-HCV viremia decreases without ocular exacerbations. When the viremia level increases again, two lesions indicating necrotizing anterior scleritis are observed in the left eye. The evolution is favourable with topical and systemic treatment with corticosteroids. Complicated cataract is surgically treated in the right eye and vitreous humour is collected during surgery. Results. Visual acuity increases in the right eye after the surgery, while antibodies-HCV are identified in the vitreous humour. Conclusions. Chronic infection with hepatitis C virus displays multiple extra-hepatic manifestations and the ophthalmological ones require a multidisciplinary approach from both the chronic diseases practitioner and the ophthalmologist.

Ophthalmological implications of the chronic infections with the hepatitis C Virus

PubMed Central

Anisia-Iuliana, Alexa; Alina, Cantermir; Elena, Ciuntu Roxana; Dorin, Chiseliţă

2015-01-01

Objectives. Report of a clinical case reuniting the dry eye syndrome in a severe form, the Mooren’s ulcer and necrotizing anterior scleritis with inflammation, with bilateral affectation in the context of chronic infection with the hepatitis C virus. Methods. A female patient aged 66 diagnosed with chronic hepatitis with HCV, with ophthalmological antecedents of Mooren’s ulcer and severe form of dry eye syndrome in both eyes, comes to the emergency unit with hypopyon corneal ulcer in the right eye, shortly afterwards developing necrotizing anterior scleritis with inflammation. The patient is administered treatment for chronic hepatitis C, following which the ARN-HCV viremia decreases without ocular exacerbations. When the viremia level increases again, two lesions indicating necrotizing anterior scleritis are observed in the left eye. The evolution is favourable with topical and systemic treatment with corticosteroids. Complicated cataract is surgically treated in the right eye and vitreous humour is collected during surgery. Results. Visual acuity increases in the right eye after the surgery, while antibodies-HCV are identified in the vitreous humour. Conclusions. Chronic infection with hepatitis C virus displays multiple extra-hepatic manifestations and the ophthalmological ones require a multidisciplinary approach from both the chronic diseases practitioner and the ophthalmologist. PMID:29450318

Hepatitis A virus infection: new insights from seroepidemiologic studies.

PubMed

Dienstag, J L; Szmuness, W; Stevens, C E; Purcell, R H

1978-03-01

The prevalence of exposure to hepatitis A virus (HAV) increases with increasing age; decreases with increasing socioeconomic class; increases with increasing serologic evidence of prior hepatitis B virus (HBV) exposure but is much more common than HBV exposure; is independent of sex and race; varies in different parts of the world as a function of hygienic, developmental, and unrecognized geographic factors; and is not affected by immune deficiency or immaturity. Transmission of type A hepatitis is enhanced by poor personal hygiene such as that seen in institutions for the mentally retarded. On the other hand, there is no increased exposure to HAV among homosexuals, who have frequent and intimate contact with multiple sexual partners; among hemodialysis patients and staff; or among multiply transfused individuals, all of whom are at significantly increased risk of exposure to HBV. No epidemiologic evidence has confirmed the existence of viremic or intestinal carriers of HAV, and the virus is rarely, if ever, spread by parenteral mechanisms. Finally, HAV appears to play no role in chronic liver disease and a very minor role in fulminant hepatitis; however, HAV is responsible for a sizable proportion (approximately 20%--40%) of sporadic hepatitis among urban adults.

Collapsed Reticular Network and its Possible Mechanism during the Initiation and/or Progression of Hepatic Fibrosis

PubMed Central

Wen, Shi-Lei; Feng, Shi; Tang, Shi-Hang; Gao, Jin-Hang; Zhang, Lin-hao; Tong, Huan; Yan, Zhao-Ping; Fang, Ding Zhi

2016-01-01

Among the researches on hepatic fibrosis, great attention was paid to both hepatocytes and extracellular matrix (ECM). However, little focus was drawn on reticular fibrous network, which is important for demarcation and support of hepatocytes. The aim of this study was to investigate the change pattern of reticular fibers in hepatic fibrosis/cirrhosis and its underlying mechanism. In this study, thioacetamide (TAA) and bile duct ligation (BDL) were utilized to induce rat hepatic fibrosis respectively, and Human liver cirrhotic microassay was analyzed with IHC to confirm the results in animal experiment and to detect the metalloproteinases (MMPs) expressions. As a result, the reticular fibers decreased markedly after 1 week in TAA and 1 day in BDL treated rats. Multiple representative regulators of MMPs and MMPs increased significantly in their expressions and activities. Further more, in human liver cirrhotic microassay, MMPs expressions also showed similar patterns as that of animal experiment. In Conclusions: Degradation or collapse of reticular fibers in hepatic sinusoid can be considered as a pathological feature during the initiation and/or progression of hepatic fibrosis. Moreover, such degradation is associated with and probably caused by the over/dysregulated expression of MMPs. PMID:27739503

Hepatic abscess linked to oral actinomycetes: a case report.

PubMed

De Farias, Deborah G

2015-01-01

Organ abscesses are rare, life-threatening complications that can be caused by bacteremia from oral infections. Metastatic infection is a well-established concept. Dental and periapical infections can cause infections in distant organs and tissues. The frequency of these systemic infections and systemic diseases is open to debate, as some patients are more susceptible to infections than others. This article presents the case report of a 52-year-old woman who was hospitalized with a hepatic abscess after a routine periodontal maintenance procedure. The patient had poor oral health, involving several nonrestorable teeth, multiple failed endodontic treatments, and asymptomatic chronic periapical pathologies. Her dental history included previous diagnoses of moderate generalized chronic periodontitis and advanced localized periodontitis. It was possible that bacteremia developed during her most recent dental treatment, leading to the hepatic abscess. Systemic antibiotic therapy, drainage of the hepatic abscess, and oral rehabilitation resulted in complete recovery.

Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.

PubMed

Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

2014-04-14

Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

Silent killers: Transfusion Transmissible Infections-TTI, among asymptomatic population of Pakistan.

PubMed

Saeed, Muhammad; Hussain, Shahida; Rasheed, Farhan; Ahmad, Maqsood; Arif, Mizna; Hamid Rahmani, Muhammad Tariq

2017-03-01

To analyse transfusion transmissible infections in asymptomatic population. This study was conducted at the Allama Iqbal Medical College and Jinnah Hospital, Lahore, Pakistan, from December 2014 to November 2015, and comprised healthy asymptomatic blood donors.Every sample was screened for the presence of antibodies/antigens of hepatitis C virus, human immunodeficiency virus, treponemapallidum, hepatitis B virus and malaria parasite through rapid immunochromatographic technique. Of the 18,274 blood donors, 17,276(94.53%) were found healthy and 998(5.46%) were infected. Besides, 71(0.38%) had multiple infections. The overall frequency of anti-hepatitis C virus, treponemapallidum (syphilis), hepatitis B surface antigen, malaria parasite and anti-human immunodeficiency virus was 480(2.62%), 284(1.55%), 210(1.10%), 20(0.10%) and 4(0.02%), respectively. Blood transfusion was found to be a significant but preventable mode of spread of transfusion transmissible infections.

Conceptual framework for outcomes research studies of hepatitis C: an analytical review

PubMed Central

Sbarigia, Urbano; Denee, Tom R; Turner, Norris G; Wan, George J; Morrison, Alan; Kaufman, Anna S; Rice, Gary; Dusheiko, Geoffrey M

2016-01-01

Hepatitis C virus infection is one of the main causes of chronic liver disease worldwide. Until recently, the standard antiviral regimen for hepatitis C was a combination of an interferon derivative and ribavirin, but a plethora of new antiviral drugs is becoming available. While these new drugs have shown great efficacy in clinical trials, observational studies are needed to determine their effectiveness in clinical practice. Previous observational studies have shown that multiple factors, besides the drug regimen, affect patient outcomes in clinical practice. Here, we provide an analytical review of published outcomes studies of the management of hepatitis C virus infection. A conceptual framework defines the relationships between four categories of variables: health care system structure, patient characteristics, process-of-care, and patient outcomes. This framework can provide a starting point for outcomes studies addressing the use and effectiveness of new antiviral drug treatments. PMID:27313473

Artifact Suppression in Imaging of Myocardial Infarction Using B1-Weighted Phased-Array Combined Phase-Sensitive Inversion Recovery

PubMed Central

Kellman, Peter; Dyke, Christopher K.; Aletras, Anthony H.; McVeigh, Elliot R.; Arai, Andrew E.

2007-01-01

Regions of the body with long T1, such as cerebrospinal fluid (CSF), may create ghost artifacts on gadolinium-hyperenhanced images of myocardial infarction when inversion recovery (IR) sequences are used with a segmented acquisition. Oscillations in the transient approach to steady state for regions with long T1 may cause ghosts, with the number of ghosts being equal to the number of segments. B1-weighted phased-array combining provides an inherent degree of ghost artifact suppression because the ghost artifact is weighted less than the desired signal intensity by the coil sensitivity profiles. Example images are shown that illustrate the suppression of CSF ghost artifacts by the use of B1-weighted phased-array combining of multiple receiver coils. PMID:14755669

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

PubMed

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-09-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

Pacemaker limitation of tachycardia in hypovolemic shock.

PubMed

Sparacino, Nicholas; Geninatti, Marilyn; Moore, Gregory

2011-11-01

A 49-year-old white man was admitted to the emergency department with nausea and diarrhea of 11 hours duration. He had experienced crampy abdominal pain as well. He reported that his stools had been dark and malodorous. He had no prior history of gastrointestinal disorders, nor travel, unusual oral or liquid intake. There was a remote history of alcohol abuse, but no hepatitis or cirrhosis. Recent alcohol intake was denied by the patient. He had no medical allergies. His past medical history was pertinent for a history of hypertension, congestive heart failure, and a dual chamber pacemaker insertion. There was no history of diabetes mellitus, smoking, or myocardial infarction. Medications included lisinopril, a small dose of aspirin daily, and thyroid supplement. Family history was negative for cardiomyopathy, sudden cardiac death, gastric or duodenal ulcers, colon cancer, or any congenital abnormalities.

Hepatic findings in long-term clinical trials of ximelagatran.

PubMed

Lee, William M; Larrey, Dominique; Olsson, Rolf; Lewis, James H; Keisu, Marianne; Auclert, Laurent; Sheth, Sunita

2005-01-01

In clinical trials, the efficacy and safety of the oral direct thrombin inhibitor ximelagatran have been evaluated in the prevention or treatment of thromboembolic conditions known to have high morbidity and mortality. In these studies, raised aminotransferase levels were observed during long-term use (>35 days). The aim of this analysis is to review the data regarding these hepatic findings in the long-term trials of ximelagatran. The prospective analysis included 6948 patients randomised to ximelagatran and 6230 patients randomised to comparator (warfarin, low-molecular weight heparin followed by warfarin or placebo). Of these, 6931 patients received ximelagatran for a mean of 357 days and 6216 patients received comparator for a mean of 389 days. An algorithm was developed for frequent testing of hepatic enzyme levels. A panel of four hepatologists analysed all cases of potential concern with regard to causal relation to ximelagatran treatment using an established evaluation tool (Roussel Uclaf Causality Assessment Method [RUCAM]). An elevated alanine aminotransferase (ALT) level of >3 x the upper limit of normal (ULN) was found in 7.9% of patients in the ximelagatran group versus 1.2% in the comparator group. The increase in ALT level occurred 1-6 months after initiation of therapy and data were available to confirm recovery of the ALT level to <2 x ULN in 96% of patients, whether they continued to receive ximelagatran or not. There was some variability in the incidence of ALT level elevation between indications, those with simultaneous acute illnesses (acute myocardial infarction or venous thromboembolism) having higher incidences. Combined elevations of ALT level of >3 x ULN and total bilirubin level of >2 x ULN (within 1 month of the ALT elevation), regardless of aetiology, were infrequent, occurring in 37 patients (0.5%) treated with ximelagatran, of whom one sustained a severe hepatic illness that appeared to be resolving when the patient died from a gastrointestinal haemorrhage. No death was observed directly related to hepatic failure caused by ximelagatran. Treatment with ximelagatran has been associated with mainly asymptomatic elevation of ALT levels in a mean of 7.9% of patients in the long-term clinical trial programme and nearly all of the cases occurred within the first 6 months of therapy. Rare symptomatic cases have been observed. An algorithm has been developed for testing ALT to ensure appropriate management of patients with elevated ALT levels. Regular ALT testing should allow the clinical benefits of ximelagatran to reach the widest population of patients while minimising the risk of hepatic adverse effects.

Hepatic disposition of the acyl glucuronide 1-O-gemfibrozil-beta-D-glucuronide: effects of clofibric acid, acetaminophen, and acetaminophen glucuronide.

PubMed

Sabordo, L; Sallustio, B C; Evans, A M; Nation, R L

2000-10-01

Glucuronidation of carboxylic acid compounds results in the formation of electrophilic acyl glucuronides. Because of their polarity, carrier-mediated hepatic transport systems play an important role in determining both intra- and extrahepatic exposure to these reactive conjugates. We have previously shown that the hepatic membrane transport of 1-O-gemfibrozil-beta-D-glucuronide (GG) is carrier-mediated and inhibited by the organic anion dibromosulfophthalein. In this study, we examined the influence of 200 microM acetaminophen, acetaminophen glucuronide, and clofibric acid on the disposition of GG (3 microM) in the recirculating isolated perfused rat liver preparation. GG was taken up by the liver, excreted into bile, and hydrolyzed within the liver to gemfibrozil, which appeared in perfusate but not in bile. Mean +/- S. D. hepatic clearance, apparent intrinsic clearance, hepatic extraction ratio, and biliary excretion half-life of GG were 10.4 +/- 1.4 ml/min, 94.1 +/- 17.9 ml/min, 0.346 +/- 0.046, and 30.9 +/- 4.9 min, respectively, and approximately 73% of GG was excreted into bile. At the termination of the experiment (t = 90 min), the ratio of GG concentrations in perfusate, liver, and bile was 1:35:3136. Acetaminophen and acetaminophen glucuronide had no effect on the hepatic disposition of GG, suggesting relatively low affinities of acetaminophen conjugates for hepatic transport systems or the involvement of multiple transport systems for glucuronide conjugates. In contrast, clofibric acid increased the hepatic clearance, extraction ratio, and apparent intrinsic clearance of GG (P <.05) while decreasing its biliary excretion half-life (P <.05), suggesting an interaction between GG and hepatically generated clofibric acid glucuronide at the level of hepatic transport. However, the transporter protein(s) involved remains to be identified.

Induced hypothermia reduces the hepatic inflammatory response in a swine multiple trauma model.

PubMed

Fröhlich, Matthias; Hildebrand, Frank; Weuster, Matthias; Mommsen, Philipp; Mohr, Juliane; Witte, Ingo; Raeven, Pierre; Ruchholtz, Steffen; Flohé, Sascha; van Griensven, Martijn; Pape, Hans-Christoph; Pfeifer, Roman

2014-06-01

Mild therapeutic hypothermia following trauma has been introduced in several studies to reduce the posttraumatic inflammation and organ injury. In this study, we analyzed the effects of induced mild hypothermia (34°C) on the inflammation of the shock organs liver and kidney. In a porcine model of multiple trauma including blunt chest trauma, liver laceration, and hemorrhagic shock followed by fluid resuscitation, the influence of induced hypothermia on hepatic and renal damage and organ-specific inflammation were evaluated. A total of 40 pigs were randomly assigned to four groups, which were sham (anesthesia only) or trauma groups receiving either hypothermia or normothermia. The parameters analyzed were laboratory parameters (aspartate transaminase [AST], lactate dehydrogenase, urea, creatinine) as well as hepatic and renal cytokine expression determined by real-time polymerase chain reaction (interleukin 6 [IL-6], IL-8). Blinded analysis of histologic changes in the liver and kidney was performed. Fifteen and a half hours following combined trauma, hepatic cytokine expression and liver damage were significantly increased in animals with normothermia compared with the respective sham group. Hypothermia, however, resulted in a fivefold reduced hepatic expression of IL-8 (mean ± SE, 2.4 ± 1.3; p = 0.01) when compared with the normothermic trauma group (IL-8, 12.8 ± 4.7). Accordingly, granulocyte infiltration and a histologic, semiquantitative score for liver injury were significantly higher in the normothermic trauma group. Serum AST levels raised significantly after trauma and normothermia compared with the respective sham group, while AST levels showed no difference from the sham groups in the hypothermic trauma group. In contrast, neither trauma nor hypothermia influenced the expression of IL-6 and IL-8 and tissue injury in the kidney. Therapeutic hypothermia seems to attenuate the hepatic inflammatory response and the associated liver injury after severe trauma. Therefore, induced hypothermia might represent a potential therapeutic strategy to avoid posttraumatic organ dysfunction.

Lycopene attenuated hepatic tumorigenesis via differential mechanisms depending on carotenoid cleavage enzyme in mice

PubMed Central

Ip, Blanche C.; Liu, Chun; Ausman, Lynne M.; von Lintig, Johannes; Wang, Xiang-Dong

2014-01-01

Obesity is associated with increased liver cancer risks and mortality. We recently showed that apo-10’-lycopenoic acid, a lycopene metabolite generated by beta-carotene-9’,10’-oxygenase (BCO2), inhibited carcinogen-initiated, high-fat diet (HFD)-promoted liver inflammation and hepatic tumorigenesis development. The present investigation examined the outstanding question of whether the lycopene could suppress HFD-promoted hepatocellular carcinoma (HCC) progression, and if BCO2 is important in BCO2-knockout (BCO2-KO) and wild-type male mice. Results showed that lycopene supplementation (100 mg/kg diet) for 24 weeks resulted in comparable accumulation of hepatic lycopene (19.4 vs 18.2 nmol/g) and had similar effects on suppressing HFD-promoted HCC incidence (19% vs 20%) and multiplicity (58% vs 62%) in wild-type and BCO2-KO mice, respectively. Intriguingly, lycopene chemopreventive effects in wild-type mice were associated with reduced hepatic pro-inflammatory signaling (phosphorylation of nuclear factor-κB p65 and signal transducer and activator of transcription 3; interleukin-6 protein) and inflammatory foci. In contrast, the protective effects of lycopene in BCO2-KO but not in wild-type mice were associated with reduced hepatic endoplasmic reticulum stress-mediated unfolded protein response (ERUPR), through decreasing ERUPR-mediated protein kinase RNA-activated like kinase– eukaryotic initiation factor 2α activation, and inositol requiring 1α–X-box binding protein 1 signaling. Lycopene supplementation in BCO2-KO mice suppressed oncogenic signals including Met mRNA, β-catenin protein, and mammalian target of rapamycin (mTOR) complex 1 activation, which was associated with increased hepatic microRNA (miR)-199a/b and miR-214 levels. These results provided novel experimental evidence that dietary lycopene can prevent HFD-promoted HCC incidence and multiplicity in mice, and may elicit different mechanisms depending on BCO2 expression. PMID:25293877

The hepatocyte-specific HNF4α/miR-122 pathway contributes to iron overload-mediated hepatic inflammation.

PubMed

Li, Min; Tang, Yuxiao; Wu, Lusha; Mo, Fengfeng; Wang, Xin; Li, Hongxia; Qi, Ruirui; Zhang, Hongwei; Srivastava, Arun; Ling, Chen

2017-08-24

Hepatic iron overload (IO) is a major complication of transfusional therapy. It was generally thought that IO triggers substantial inflammatory responses by producing reactive oxygen species in hepatic macrophages. Recently, a decrease in microRNA-122 (miR-122) expression was observed in a genetic knockout (Hfe -/- ) mouse model of IO. Because hepatocyte-enriched miR-122 is a key regulator of multiple hepatic pathways, including inflammation, it is of interest whether hepatocyte directly contributes to IO-mediated hepatic inflammation. Here, we report that IO induced similar inflammatory responses in human primary hepatocytes and Thp-1-derived macrophages. In the mouse liver, IO resulted in altered expression of not only inflammatory genes but also >230 genes that are known targets of miR-122. In addition, both iron-dextran injection and a 3% carbonyl iron-containing diet led to upregulation of hepatic inflammation, which was associated with a significant reduction in HNF4α expression and its downstream target, miR-122. Interestingly, the same signaling pathway was changed in macrophage-deficient mice, suggesting that macrophages are not the only target of IO. Most importantly, hepatocyte-specific overexpression of miR-122 rescued IO-mediated hepatic inflammation. Our findings indicate the direct involvement of hepatocytes in IO-induced hepatic inflammation and are informative for developing new molecular targets and preventative therapies for patients with major hemoglobinopathy. © 2017 by The American Society of Hematology.

Elevated hepatic fatty acid elongase-5 activity corrects dietary fat-induced hyperglycemia in obese BL/6J mice[S

PubMed Central

Tripathy, Sasmita; Torres-Gonzalez, Moises; Jump, Donald B.

2010-01-01

Elevated hepatic fatty acid elongase-5 (Elovl5) activity lowers blood glucose in fasted chow-fed C57BL/6J mice. As high-fat diets induce hyperglycemia and suppress hepatic Elovl5 activity, we tested the hypothesis that elevated hepatic Elovl5 expression attenuates hyperglycemia in high-fat-diet-induced obese mice. Increasing hepatic Elovl5 activity by a recombinant adenoviral approach restored blood glucose and insulin, HOMA-IR, and glucose tolerance to normal values in obese mice. Elevated Elovl5 activity increased hepatic content of Elovl5 products (20:3,n-6, 22:4,n-6) and suppressed levels of enzymes (Pck1, G6Pc) and transcription factors (FoxO1 and PGC1α, but not CRTC2) involved in gluconeogenesis. Effects of Elovl5 on FoxO1 nuclear abundance correlated with increased phosphorylation of FoxO1, Akt, and the catalytic unit of PP2A, as well as a decline in cellular abundance of TRB3. Such changes are mechanistically linked to the regulation of FoxO1 nuclear abundance and gluconeogenesis. These results show that Elovl5 activity impacts the hepatic abundance and phosphorylation status of multiple proteins involved in gluconeogenesis. Our findings establish a link between fatty acid elongation and hepatic glucose metabolism and suggest a role for regulators of Elovl5 activity in the treatment of diet-induced hyperglycemia. PMID:20488798

In vitro hepatic differentiation of human endometrial stromal stem cells.

PubMed

Yang, Xin-yuan; Wang, Wei; Li, Xu

2014-02-01

Human endometrial stromal stem cells (hESSCs) can differentiate into mesodermal and ectodermal cellular lineages in the endometrium. However, whether hESSCs can differentiate into functional hepatic-like cells is unknown. In this study, we developed a multiple-step induction protocol to differentiate hESSCs into functional hepatic-like cells in vitro. Endometrial stromal cells were isolated by magnetic affinity sorting using anti-epithelial cell adhesion molecule-coated Dynabeads. The enriched hESSCs were analyzed by flow cytometry and were able to differentiate into osteoblasts or adipocytes under proper induction media. To differentiate into hepatic-like cells, hESSCs were cultured in a stepwise system containing hepatocyte growth factor, fibroblast growth factor-4, oncostatin M, and trichostatin A for a total of 24 d. The hepatic-like cell differentiation was analyzed by confocal microscopy and immunocytochemical staining. Glycogen storage, cellular urea synthesis, and ammonia concentrations were measured. Hepatic-like cells were successfully generated from hESSCs and were identified by their epithelial-like shape characteristics and expression of specific biomarkers albumin and cytokeratin 8 accompanied with a reduction of alpha-fetoprotein and alpha-smooth muscle actin expression. The hepatic-like cells generated were functional as evidenced by urea synthesis and glycogen storage. Our study demonstrated that hESSCs were able to differentiate into hepatic-like cells in vitro. Thus, endometrial stromal cells may be used as an easily accessible alternative source of stem cells for potential therapeutic applications in liver disease.

Pattern of Hepatitis A Incidence According to Area Characteristics Using National Health Insurance Data

PubMed Central

Seo, Joo Youn; Seo, Jae Hee; Kim, Myoung Hee; Ki, Moran; Park, Hee Suk

2012-01-01

Objectives Over the past several years, the incidence of hepatitis A infection has been increasing rapidly in the young-adult population in Korea. We examined the effects of area-level socioeconomic status and environmental hygiene on the incidence of hepatitis A. Methods This study is based on the registered national population of Korea and the national health insurance data from 2004 to 2008. A total of 73 459 individuals were confirmed to have had hepatitis A. The standardized incidences of hepatitis A in 232 districts adjusted for sex and age of people were calculated for each year, and the rate ratios of the incidence rates were estimated according to area-level socioeconomic status and environmental hygiene using multiple Poisson regression models. Results The incidence rates of hepatitis A infection were 15.6 (per 100 000) in 2004, 19.0 (per 100 000) in 2005, 27.2 (per 100 000) in 2006, 25.1 (per 100 000) in 2007, and 61.7 (per 100 000) in 2008. The analysis of the area-level effects showed that residential areas of the less deprived than other regions, areas with higher levels of education, and heavily populated areas were significantly associated with increased risk. Conclusions There is a very strong possibility that both area-level socioeconomic status and environmental hygiene play a role in increasing the risk of hepatitis A infection in Korea. Therefore, to reduce hepatitis A infection, we need a nationwide strategy that considers these area-level characteristics. PMID:22712043

Multiple yellow plaques assessed by angioscopy with quantitative colorimetry in patients with myocardial infarction.

PubMed

Inami, Shigenobu; Ishibashi, Fumiyuki; Waxman, Sergio; Okamatsu, Kentaro; Seimiya, Koji; Takano, Masamichi; Uemura, Ryota; Sano, Junko; Mizuno, Kyoichi

2008-03-01

Multiple angioscopic yellow plaques are associated with diffuse atherosclerotic plaque, and may be prevalent in patients with myocardial infarction (MI), so in the present study the yellow plaques in the coronary arteries of patients with MI was evaluated using quantitative colorimetry, and compared with those of patients with stable angina (SA). In the recorded angioscopic images of 3 coronary vessels in 29 patients (15 patients with MI, 14 with SA), yellow plaques were determined as visually yellow regions with b* value >0 (yellow color intensity) measured by the quantitative colorimetric method. A total of 90 yellow plaques were identified (b* =19.35+/-8.3, 3.05-45.35). Yellow plaques were significantly more prevalent in 14 (93%) of 15 culprit lesions of MI as compared with 8 (57%) of 14 of SA (p=0.03). In non-culprit segments, yellow plaques were similarly prevalent in 13 (87%) patients with MI and 11 (79%) with SA (p=0.65). Overall, multiple (> or =2) yellow plaques were prevalent in 13 (87%) patients with MI, similar to the 10 (71%) with SA (p=0.38). The number of yellow plaques was significantly higher in patients with MI (3.8+/-1.9) than in those with SA (2.4+/-1.6, p=0.03). The present study suggests that patients with MI tend to have diffuse atherosclerotic plaque in their coronary arteries.

Regulation of hepatic level of fatty-acid-binding protein by hormones and clofibric acid in the rat.

PubMed Central

Nakagawa, S; Kawashima, Y; Hirose, A; Kozuka, H

1994-01-01

Regulation of the hepatic level of fatty-acid-binding protein (FABP) by hormones and p-chlorophenoxyisobutyric acid (clofibric acid) was studied. The hepatic level of FABP, measured as the oleic acid-binding capacity of the cytosolic FABP fraction, was decreased in streptozotocin-diabetic rats. The level of FABP was markedly increased in adrenalectomized rats, and the elevation was prevented by the administration of dexamethasone. Hypothyroidism decreased the level of FABP and hyperthyroidism increased it. A high correlation between the incorporation of [14C]oleic acid in vivo into hepatic triacylglycerol and the level of FABP was found for normal, diabetic and adrenalectomized rats. The level of FABP was increased by administration of clofibric acid to rats in any altered hormonal states, as was microsomal 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, a peroxisome-proliferator-responsive parameter. These results suggest that the hepatic level of FABP is under regulation by multiple hormones and that clofibric acid induces FABP and 1-acyl-GPC acyltransferase by a mechanism which may be distinct from that by which hormones regulate the level of FABP. PMID:8110197

[The effect of a scenario-based simulation communication course on improving the communication skills of nurses].

PubMed

Huang, Ya-Hsuan; Hsieh, Suh-Ing; Hsu, Li-Ling

2014-04-01

Limited disease knowledge is frequently the cause of disease-related anxiety in myocardial infarction patients. The ability to communicate effectively serves multiple purposes in the professional nursing practice. By communicating effectively with myocardial infarction patients, nurses may help reduce their anxiety by keeping them well informed about their disease and teaching them self-care strategies. This research evaluates the communication skills of nurses following scenario-based simulation education in the context of communication with myocardial infarction patients. This study used an experimental design and an educational intervention. The target population comprised nurses of medicine (clinical qualified level N to N2 for nursing) working at a municipal hospital in Taipei City, Taiwan. A total 122 participants were enrolled. Stratified block randomization divided participants into an experimental group and a control group. The experimental group received clinical scenario-based simulation education for communication. The control group received traditional class-based education for communication. Both groups received a pre-test and a Communication Skills Checklist post-test assessment. Results were analyzed using SPSS 17.0 for Windows software. A t-test showed significant increases in communication skills (p < .001) in the experimental group and ANCOVA results identified significant between-group differences (p < .001) in communication skills following the education intervention. The results indicate that clinical scenario-based simulation education for communication is significantly more effective than traditional class-based education in enhancing the ability of nurses to communicate effectively with myocardial infarction patients.

GPU-Accelerated Voxelwise Hepatic Perfusion Quantification

PubMed Central

Wang, H; Cao, Y

2012-01-01

Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using CUDA-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, non-linear least squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626400 voxels in a patient’s liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10−6. The method will be useful for generating liver perfusion images in clinical settings. PMID:22892645

Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis

PubMed Central

Corbin, Karen D.; Abdelmalek, Manal F.; Spencer, Melanie D.; da Costa, Kerry-Ann; Galanko, Joseph A.; Sha, Wei; Suzuki, Ayako; Guy, Cynthia D.; Cardona, Diana M.; Torquati, Alfonso; Diehl, Anna Mae; Zeisel, Steven H.

2013-01-01

Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism. When SNPs were examined individually, using logistic regression, we only identified a single SNP (PNPLA3 rs738409) that was significantly associated with severity of hepatic steatosis after adjusting for confounders and multiple comparisons (P=0.02). However, when groupings of SNPs in similar metabolic pathways were defined using unsupervised hierarchical clustering, we identified groups of subjects with shared SNP signatures that were significantly correlated with steatosis burden (P=0.0002). The lowest and highest steatosis clusters could also be differentiated by ethnicity. However, unique SNP patterns defined steatosis burden irrespective of ethnicity. Our results suggest that analysis of SNP patterns in genes of choline/1-carbon metabolism may be useful for prediction of severity of steatosis in specific subsets of people, and the metabolic inefficiencies caused by these SNPs should be examined further.—Corbin, K. D., Abdelmalek, M. F., Spencer, M. D., da Costa, K.-A., Galanko, J. A., Sha, W., Suzuki, A., Guy, C. D., Cardona, D. M., Torquati, A., Diehl, A. M., Zeisel, S. H. Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis. PMID:23292069

Bronchobiliary fistula and cholangiocarcinoma: a case report and principles of management.

PubMed

Delande, S; Goffette, P; Verbaandert, C; Rahier, J; Graux, C; Mazzeo, F; Humblet, Y; Machiels, J P

2007-01-01

A 64-year-old woman was admitted with fever and cough. At admission, she had jaundice, hepatomegaly, and green-stained sputum. Computed tomography (CT) showed an intrahepatic abscess located near the dome, multiple hepatic metastases, biliary tract dilatation, and a right pleural effusion. Percutaneous transhepatic cholangiography demonstrated a communication between the intrahepatic biliary ducts and the bronchial tree. The patient was treated with antibiotic therapy, pleural and biliary drainages and a percutaneous drainage of the hepatic abscess.

Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction

PubMed Central

Sabatine, Marc S.; Morrow, David A.; Higgins, Luke J.; MacGillivray, Catherine; Guo, Wei; Bode, Christophe; Rifai, Nader; Cannon, Christopher P.; Gerszten, Robert E.; Lee, Richard T.

2014-01-01

Background ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide (NT-proBNP), has not been established. Methods and Results We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY–Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT-proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT-proBNP (r=0.14). After adjustment for baseline characteristics and NT-proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure (third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P<0.0001 for trend). When both ST2 and NT-proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 (95% confidence interval, 0.77 to 0.87) to 0.86 (95% confidence interval, 0.81 to 0.90) (P=0.017). Conclusions In ST-elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT-proBNP, and the combination of ST2 and NT-proBNP significantly improves risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers of biomechanical strain in ST-elevation myocardial infarction. PMID:18378613

Acute cardioembolic cerebral infarction: answers to clinical questions.

PubMed

Arboix, Adria; Alio, Josefina

2012-02-01

Cardioembolic cerebral infarction (CI) is the most severe subtype of ischaemic stroke but some clinical aspects of this condition are still unclear. This article provides the reader with an overview and up-date of relevant aspects related to clinical features, specific cardiac disorders and prognosis of CI. CI accounts for 14-30% of ischemic strokes; patients with CI are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of CI, including sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke's aphasia or global aphasia without hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacunar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely. The most common disorders associated with a high risk of cardioembolism include atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, dilated myocardiopathy and mitral rheumatic stenosis. Patent foramen ovale and complex atheromatosis of the aortic arch are potentially emerging sources of cardioembolic infarction. Mitral annular calcification can be a marker of complex aortic atheroma in stroke patients of unkown etiology. Transthoracic and transesophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhythmia can be detected by Holter monitoring. Magnetic resonance imaging, transcranial Doppler, and electrophysiological studies are useful to document the source of cardioembolism. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as compared with other subtypes of cerebral infarction. Secondary prevention with anticoagulants should be started immediately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent. Dabigatran has been shown to be non-inferior to warfarin in the prevention of stroke or systemic embolism. All significant structural defects, such as atrial septal defects, vegetations on valve or severe aortic disease should be treated. Aspirin is recommended in stroke patients with a patent foramen ovale and indications of closure should be individualized. CI is an important topic in the frontier between cardiology and vascular neurology, occurs frequently in daily practice, has a high impact for patients, and health care systems and merits an update review of current clinical issues, advances and controversies.

[A clinical study on the pathogenesis of lung cancer-related cerebral infarction].

PubMed

Xie, X R; Qin, C; Chen, L; Cheng, D B; Huang, J Y; Wei, X X; Yu, L X; Liang, Z J

2017-02-01

Objective: To explore the risk factors for lung cancer-related cerebral infarction. Methods: The hospitalized active lung cancer patients on anti-cancer therapy with no traditional stroke risk factors, who experienced an acute cerebral infarct in the First Affiliated Hospital of Guangxi Medical University from January 2005 to December 2015, were consecutively collected as the LCRS (lung cancer-related stroke) group. The active lung cancer patients without cerebral infarction hospitalized at the same peroid matched with the LCRS group for age and gender were collected as the LC (lung cancer) group. Clinical data from the two groups were analyzed. Results: A total of 139 LCRS patients and 139 LC patients were enrolled in the study, with 110 male and 29 female in each group, and there were no significant difference for the mean age between the LCRS group (52.1±10.4 years old ) and the LC group (52.1±10.1 years old). Two or more acute ischemic lesions of the brain were showed by MRI in most patients in the LCRS group (117 cases, 84.2%). Compared with the LC group, more patients in the LCRS group were found with adenocarcinoma, metastasis, elevated plasma D-dimer, CA125 and CA199 levels [88 cases (63.3%) vs 47 cases (33.8%); 98 cases (70.5%) vs 56 cases (40.3%); (468.38±291.37) μg/L vs (277.59±191.22) μg/L; (221.42±146.34) U/ml vs (106.84±69.97) U/ml; (254.68±185.84) U/ml vs (97.15±63.64) U/ml; with all P <0.001]. By logistic regression analysis of multiple factors, the elevated plasma D-dimer, CA125 and CA199 levels were showed to be independent risk factors for the cerebral infarction ( OR =1.003, 95% CI 1.001-1.004; OR =1.006, 95% CI 1.003-1.010; OR =1.011, 95% CI 1.007-1.015). Conclusions: The elevated plasma D-dimer, CA125 and CA199 levels are the risk factors for the lung cancer related cerebral infarction, which may lead to hypercoagulation and induce cerebral infarction eventually.

Color Doppler sonography and angioscintigraphy in hepatic Hodgkin’s lymphoma

PubMed Central

Stojković, Mirjana V; Artiko, Vera M; Radoman, Irena B; Knežević, Slavko J; Lukić, Snezana M; Kerkez, Mirko D; Lekić, Nebojsa S; Antić, Andrija A; Žuvela, Marinko M; Ranković, Vitomir I; Petrović, Milorad N; Šobić, Dragana P; Obradović, Vladimir B

2009-01-01

AIM: To estimate the characteristics of Color Doppler findings and the results of hepatic radionuclide angiography (HRA) in secondary Hodgkin’s hepatic lymphoma. METHODS: The research included patients with a diagnosis of Hodgkin’s lymphoma with metastatic focal lesions in the liver and controls. Morphologic characteristics of focal liver lesions and hemodynamic parameters were examined by pulsed and Color Doppler in the portal, hepatic and splenic veins were examined. Hepatic perfusion index (HPI) estimated by HRA was calculated. RESULTS: In the majority of patients, hepatomegaly was observed. Lesions were mostly hypoechoic and mixed, solitary or multiple. Some of the patients presented with dilated splenic veins and hepatofugal blood flow. A pulse wave was registered in the centre and at the margins of lymphoma. The average velocity of the pulse wave was higher at the margins (P > 0.05). A continuous venous wave was found only at the margins of lymphoma. There was no linear correlation between lymphoma size and velocity of pulse and continuous wave (r = 390, P < 0.01). HPI was significantly lower in patients with lymphomas than in controls (P < 0.05), pointing out increased arterial perfusion in comparison to portal perfusion. CONCLUSION: Color Doppler ultrasonography is a sensitive method for the detection of neovascularization in Hodgkin’s hepatic lymphoma and estimation of its intensity. Hepatic radionuclide angiography can additionally help in the assesment of vascularisation of liver lesions. PMID:19598303

Comparing the effects of nano-sized sugarcane fiber with cellulose and psyllium on hepatic cellular signaling in mice

PubMed Central

Wang, Zhong Q; Yu, Yongmei; Zhang, Xian H; Floyd, Z Elizabeth; Boudreau, Anik; Lian, Kun; Cefalu, William T

2012-01-01

Aim To compare the effects of dietary fibers on hepatic cellular signaling in mice. Methods Mice were randomly divided into four groups (n = 9/group): high-fat diet (HFD) control, cellulose, psyllium, and sugarcane fiber (SCF) groups. All mice were fed a HFD with or without 10% dietary fiber (w/w) for 12 weeks. Body weight, food intake, fasting glucose, and fasting insulin levels were measured. At the end of the study, hepatic fibroblast growth factor (FGF) 21, AMP-activated protein kinase (AMPK) and insulin signaling protein content were determined. Results Hepatic FGF21 content was significantly lowered, but βKlotho, fibroblast growth factor receptor 1, fibroblast growth factor receptor 3, and peroxisome proliferator-activated receptor alpha proteins were significantly increased in the SCF group compared with those in the HFD group (P < 0.01). SCF supplementation also significantly enhanced insulin and AMPK signaling, as well as decreased hepatic triglyceride and cholesterol in comparison with the HFD mice. The study has shown that dietary fiber, especially SCF, significantly attenuates lipid accumulation in the liver by enhancing hepatic FGF21, insulin, and AMPK signaling in mice fed a HFD. Conclusion This study suggests that the modulation of gastrointestinal factors by dietary fibers may play a key role in both enhancing hepatic multiple cellular signaling and reducing lipid accumulation. PMID:22787396

Detection of bat hepatitis E virus RNA in microbats in Japan.

PubMed

Kobayashi, Tomoya; Murakami, Shin; Yamamoto, Terumasa; Mineshita, Ko; Sakuyama, Muneki; Sasaki, Reiko; Maeda, Ken; Horimoto, Taisuke

2018-05-29

Several recent studies have reported that various bat species harbor bat hepatitis E viruses (BatHEV) belonging to the family Hepeviridae, which also contains human hepatitis E virus (HEV). The distribution and ecology of BatHEV are not well known. Here, we collected and screened 81 bat fecal samples from nine bat species in Japan to detect BatHEV RNA by RT-PCR using HEV-specific primers, and detected three positive samples. Sequence and phylogenetic analyses indicated that these three viruses were BatHEVs belonging to genus Orthohepevirus D like other BatHEV strains reported earlier in various countries. These data support the first detection of BatHEVs in Japanese microbats, indicating their wide geographical distribution among multiple bat species.

[Severe infections in children with sickle cell disease: clinical aspects and prevention].

PubMed

Bégué, P; Castello-Herbreteau, B

2001-09-01

Sickle-cell disease (SCD) is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumonococcal bacteremia and meningitis due to S. pneumoniae are often lethal and justify the penicillin prophylaxis, which has provided a dramatic decrease in early mortality bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia, because they are often intricated. Osteomyelitis is generally due to Salmonella, most often S. enteritidis. Multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Osteomyelitis is less frequent in developed countries and must been differentiated with bone infarction by use of bone scintigraphy. Parvovirus B19 infection causes acute erythroblastopenias. Malaria does not result in cerebral malaria, but can lead to severe anaemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (osteomyelitis, meningitis), and M. pneumoniae (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at three months of age and no closely-spaced immunizations, most notably against peumococci, hepatitis B virus, S. typhi and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. New conjugated pneumococcal vaccines are effective in protecting very young infants and should therefore be used in sickle cell patients.

Body mass index and myocardium at risk in patients with acute coronary syndrome.

PubMed

Arrebola-Moreno, A L; Marfil-Alvarez, R; Catena, A; García-Retamero, R; Arrebola, J P; Melgares-Moreno, R; Ramirez-Hernández, J A; Kaski, J C

2014-04-01

Whilst traditional studies have shown that obese individuals are at a higher risk of cardiovascular events compared to lean subjects, recent studies in patients with acute myocardial infarction (AMI) have suggested that obesity may exert protective effects (the "obesity paradox"). We sought to assess the relationship between body mass index (BMI) and the BARI score (BARIsc), a validated tool used to assess myocardium at risk, in patients with acute coronary syndrome. Participants were 116 consecutive patients (mean age, 60.6 years; 97 men) with AMI (68 ST elevated myocardial infarction, STEMI; 48 non-ST elevated myocardial infarction, NSTEMI). Demographics, BMI, risk factors, biochemistry data, left ventricular function, angiographic data and the BARIsc were assessed in every patient. Multiple linear regression analyses showed that BMI significantly correlated with BARIsc; β=.23, p<0.02. This was found only in the overweight/obese patients, β=.27, p<0.01, but not in patients with normal BMIs, β=0.08, p=0.71. An increased body weight is associated with an increased area of myocardium at risk in patients with ACS. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The effect of matrix stiffness of injectable hydrogels on the preservation of cardiac function after a heart attack.

PubMed

Plotkin, Marian; Vaibavi, Srirangam Ramanujam; Rufaihah, Abdul Jalil; Nithya, Venkateswaran; Wang, Jing; Shachaf, Yonatan; Kofidis, Theo; Seliktar, Dror

2014-02-01

This study compares the effect of four injectable hydrogels with different mechanical properties on the post-myocardial infarction left ventricle (LV) remodeling process. The bioactive hydrogels were synthesized from Tetronic-fibrinogen (TF) and PEG-fibrinogen (PF) conjugates; each hydrogel was supplemented with two levels of additional cross-linker to increase the matrix stiffness as measured by the shear storage modulus (G'). Infarcts created by ligating the left anterior descending coronary artery in a rodent model were treated with the hydrogels, and all four treatment groups showed an increase in wall thickness, arterial density, and viable cardiac tissue in the peri-infarct areas of the LV. Echocardiography and hemodynamics data of the PF/TF treated groups showed significant improvement of heart function associated with the attenuated effects of the remodeling process. Multi-factorial regression analysis indicated that the group with the highest modulus exhibited the best rescue of heart function and highest neovascularization. The results of this study demonstrate that multiple properties of an injectable bioactive biomaterial, and notably the matrix stiffness, provide the multifaceted stimulation necessary to preserve cardiac function and prevent adverse remodeling following a heart attack. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Prevalence of risk factors and mechanisms of transmission of acute viral hepatitis type B and C in Bucharest municipality: 2001-2008].

PubMed

Ion-Nedelcu, Niculae; Iordăchescu, Corina; Gherasim, Patricia; Mihailovici, Rodica; Dragomirescu, Cornelia; Dumitrache-Marian, Ruxanda; Moculescu, Cristina

2009-01-01

Analysis of risk factors for achieving clinically overt hepatitis B and hepatitis C in the population of Bucharest municipality. retrospective and descriptive study on hospital patients cohort. Cases - in the study have been enrolled all acute viral hepatitis B and C confirmed by the two infectious diseases university clinics of Bucharest municipality, during the time interval 2001-2008, among the residents of the municipality. Infection risk factors - for every case of hepatitis B and hepatitis C with the simptoms onset placed during the time interval 2001-2008, it was associated "the most plausible" risk factor, detected by case investigation. For contemplation of control strategies the risk factors were stratified by mechanisms of virus transmission and by age groups. The analysis consists mainly in statistical comparing of cases prevalence in each etiology by risk factors and mechanisms of visus transmission. Patients cohort included 1440 hepatitis B cases and 227 hepatitis C cases, respectively. The most prevalent individual risk factor in hepatitis B was the sexual contact with multiple partners (51,0%) while in hepatitis C the use of ilegal injectable drugs (46,3%). The prevalences of hepatitis B and hepatitis C cases by the four mechanisms of virus transmmission were similar (p = 0,52). For both etiologies the high risk behaviours represented the principal mechanism of virus transmission (64,1% in hepatitis B and 63,4% in hepatitis C, respectively); additionaly, for both etiologies the most prevalent mechanisms of virus transmission by age groups were indentically, namely: (a) consumption of medical services in the age group 55+ years, (b) high risk behaviours in the age group 13-54 years and (c) contact with case or virus carrier in the age group 0-12 years, respectively. in the time period 2001 - 2008 the structure by mechanisms of virus transmission in hepatitis B and hepatitis C cases reported in the population of Bucharest municipaly was statistically similar, for both etiologies the most prevalent mechanism (> 60%) was represented by high risk behaviours. This reality strongly suggests that additionaly to the current strategies for prevention of the infection with hepatitic visuses B and C, the decisive strategy to control of the two infection needs to be extended with an effective education satelite focused on high risk groups.

Simultaneous occurrence of diabetic ketoacidosis, thyroid storm, and multiple cerebral infarctions due to Moyamoya disease.

PubMed

Noh, Byoungho H; Cho, Sang-Won; Ahn, Sung Yeon

2016-02-01

Diabetic ketoacidosis (DKA) is one of the precipitating factors that can evoke a thyroid storm. Thyroid storm may cause cerebral ischemia in Moyamoya disease, which can coexist in patients with Graves' disease. A 16-year-old girl complaining of dizziness and palpitations visited the emergency department and was diagnosed with DKA combined with hyperthyroidism. A thyroid storm occurred 6 h after the start of DKA management. Her Burch and Wartofsky score was 65 points. Right hemiplegia developed during the thyroid storm, and brain magnetic resonance (MR) diffusion-weighted images revealed multiple acute infarcts in both hemispheres. MR angiography showed stenosis of both distal internal carotid arteries and both M1 portions of the middle cerebral arteries, consistent with Moyamoya disease. After acute management for the thyroid storm with methimazole, Lugol solution and hydrocortisone, the patient's neurological symptoms completely resolved within 1 month, and free T4 level normalized within 2 months. Thyroid storm may trigger cerebral ischemia in Moyamoya disease and lead to rapid progression of cerebrovascular occlusive disease. As a simultaneous occurrence of DKA, thyroid storm and cerebrovascular accident in Moyamoya disease highly elevates morbidity and mortality, prompt recognition and management are critical to save the patient's life.

Feasibility of Multiple Burr Hole With Erythropoietin in Acute Moyamoya Patients.

PubMed

Hong, Ji Man; Lee, Seong-Joon; Lee, Jin Soo; Choi, Mun Hee; Lee, Sung Eun; Choi, Jin Wook; Lim, Yong Cheol

2018-05-01

In patients with acute symptomatic moyamoya (<2 weeks), the feasibility of a combination therapy of multiple burr hole procedure under local anesthesia and intravenous erythropoietin pretreatment was assessed. We also identified the factors associated with transdural revascularization. In this prospective single-arm study, perfusion-impaired patients presenting with transient ischemic attack or acute cerebral infarction were assessed. Combination therapy was performed to patients lacking transdural collaterals. Primary outcomes were evaluated clinically with modified Rankin Scale scores and radiologically with revascularization success (transhemispheric, trans-burr hole, and sufficient revascularizations [filling ≥33% of ipsilateral supratentorium]) at 6 months. Treatment-related adverse events were analyzed in 3 phases: pre burr hole, post burr hole, and after-discharge as secondary outcome. Factors associated with sufficient revascularization were investigated. Fifty hemispheres from 37 patients were included. Compared with discharge, modified Rankin Scale score at 6 months significantly improved (2.0 [0.0-5.0] versus 1.0 [0.0-4.0]; P <0.001). Majority had successful revascularization: trans-burr hole arteriogenesis (89.5%), transhemispheric arteriogenesis (98.0%), and sufficient revascularization (52.0%). There was no significant pre burr hole or post burr hole complication. Two (5.4%) transient ischemic attack and 1 (2.7%) cerebral infarction occurred after discharge. Presentation with acute infarction (odds ratio, 4.8; 95% confidence interval, 1.1-21.4), ipsilateral basal moyamoya vessels (odds ratio, 13.9; 95% confidence interval, 1.3-144.2), and delayed mean transit time (odds ratio, 3.9; 95% confidence interval, 1.3-12.2) predicted sufficient revascularization. Combination therapy allows safe and effective revascularization in moyamoya patients with acute ischemic presentation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03162588. © 2018 American Heart Association, Inc.

Cardio-chemical exchange saturation transfer magnetic resonance imaging reveals molecular signatures of endogenous fibrosis and exogenous contrast media.

PubMed

Vandsburger, Moriel; Vandoorne, Katrien; Oren, Roni; Leftin, Avigdor; Mpofu, Senzeni; Delli Castelli, Daniela; Aime, Silvio; Neeman, Michal

2015-01-01

Application of emerging molecular MRI techniques, including chemical exchange saturation transfer (CEST)-MRI, to cardiac imaging is desirable; however, conventional methods are poorly suited for cardiac imaging, particularly in small animals with rapid heart rates. We developed a CEST-encoded steady state and retrospectively gated cardiac cine imaging sequence in which the presence of fibrosis or paraCEST contrast agents was directly encoded into the steady-state myocardial signal intensity (cardioCEST). Development of cardioCEST: A CEST-encoded cardiac cine MRI sequence was implemented on a 9.4T small animal scanner. CardioCEST of fibrosis was serially performed by acquisition of a series of CEST-encoded cine images at multiple offset frequencies in mice (n=7) after surgically induced myocardial infarction. Scar formation was quantified using a spectral modeling approach and confirmed with histological staining. Separately, circulatory redistribution kinetics of the paramagnetic CEST agent Eu-HPDO3A were probed in mice using cardioCEST imaging, revealing rapid myocardial redistribution, and washout within 30 minutes (n=6). Manipulation of vascular tone resulted in heightened peak CEST contrast in the heart, but did not alter redistribution kinetics (n=6). At 28 days after myocardial infarction (n=3), CEST contrast kinetics in infarct zone tissue were altered, demonstrating gradual accumulation of Eu-HPDO3A in the increased extracellular space. cardioCEST MRI enables in vivo imaging of myocardial fibrosis using endogenous contrast mechanisms, and of exogenously delivered paraCEST agents, and can enable multiplexed imaging of multiple molecular targets at high-resolution coupled with conventional cardiac MRI scans. © 2013 American Heart Association, Inc.

Symptom clusters and treatment time delay in Korean patients with ST-elevation myocardial infarction on admission.

PubMed

Kim, Hee-Sook; Eun, Sang Jun; Hwang, Jin Yong; Lee, Kun-Sei; Cho, Sung-Il

2018-05-01

Most patients with acute myocardial infarction (AMI) experience more than one symptom at onset. Although symptoms are an important early indicator, patients and physicians may have difficulty interpreting symptoms and detecting AMI at an early stage. This study aimed to identify symptom clusters among Korean patients with ST-elevation myocardial infarction (STEMI), to examine the relationship between symptom clusters and patient-related variables, and to investigate the influence of symptom clusters on treatment time delay (decision time [DT], onset-to-balloon time [OTB]). This was a prospective multicenter study with a descriptive design that used face-to-face interviews. A total of 342 patients with STEMI were included in this study. To identify symptom clusters, two-step cluster analysis was performed using SPSS software. Multinomial logistic regression to explore factors related to each cluster and multiple logistic regression to determine the effect of symptom clusters on treatment time delay were conducted. Three symptom clusters were identified: cluster 1 (classic MI; characterized by chest pain); cluster 2 (stress symptoms; sweating and chest pain); and cluster 3 (multiple symptoms; dizziness, sweating, chest pain, weakness, and dyspnea). Compared with patients in clusters 2 and 3, those in cluster 1 were more likely to have diabetes or prior MI. Patients in clusters 2 and 3, who predominantly showed other symptoms in addition to chest pain, had a significantly shorter DT and OTB than those in cluster 1. In conclusion, to decrease treatment time delay, it seems important that patients and clinicians recognize symptom clusters, rather than relying on chest pain alone. Further research is necessary to translate our findings into clinical practice and to improve patient education and public education campaigns.

Detection of infarct lesions from single MRI modality using inconsistency between voxel intensity and spatial location--a 3-D automatic approach.

PubMed

Shen, Shan; Szameitat, André J; Sterr, Annette

2008-07-01

Detection of infarct lesions using traditional segmentation methods is always problematic due to intensity similarity between lesions and normal tissues, so that multispectral MRI modalities were often employed for this purpose. However, the high costs of MRI scan and the severity of patient conditions restrict the collection of multiple images. Therefore, in this paper, a new 3-D automatic lesion detection approach was proposed, which required only a single type of anatomical MRI scan. It was developed on a theory that, when lesions were present, the voxel-intensity-based segmentation and the spatial-location-based tissue distribution should be inconsistent in the regions of lesions. The degree of this inconsistency was calculated, which indicated the likelihood of tissue abnormality. Lesions were identified when the inconsistency exceeded a defined threshold. In this approach, the intensity-based segmentation was implemented by the conventional fuzzy c-mean (FCM) algorithm, while the spatial location of tissues was provided by prior tissue probability maps. The use of simulated MRI lesions allowed us to quantitatively evaluate the performance of the proposed method, as the size and location of lesions were prespecified. The results showed that our method effectively detected lesions with 40-80% signal reduction compared to normal tissues (similarity index > 0.7). The capability of the proposed method in practice was also demonstrated on real infarct lesions from 15 stroke patients, where the lesions detected were in broad agreement with true lesions. Furthermore, a comparison to a statistical segmentation approach presented in the literature suggested that our 3-D lesion detection approach was more reliable. Future work will focus on adapting the current method to multiple sclerosis lesion detection.

The effect of tobacco control measures during a period of rising cardiovascular disease risk in India: a mathematical model of myocardial infarction and stroke.

PubMed

Basu, Sanjay; Glantz, Stanton; Bitton, Asaf; Millett, Christopher

2013-01-01

We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade. A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban) for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%-34%) if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent with further health system improvements. Smoke-free laws and substantially increased tobacco taxation appear to be markedly potent population measures to avert future cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular disease risk factors like hyperlipidemia and hypertension in low- and middle-income countries, tobacco control is likely to remain a highly effective strategy to reduce cardiovascular deaths.

Challenges and priorities in the management of HIV/HBV and HIV/HCV coinfection in resource-limited settings.

PubMed

Easterbrook, Philippa; Sands, Anita; Harmanci, Hande

2012-05-01

Liver disease due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is now emerging as an increasing cause of morbidity and mortality in human immunodeficiency virus- (HIV-) infected persons in resource-limited settings (RLS). Existing management guidelines have generally focused on care in tertiary level facilities in developed countries. Less than half of low-income countries have guidance, and in those that do, there are important omissions or disparities in recommendations. There are multiple challenges to delivery of effective hepatitis care in RLS, but the most important remains the limited access to antiviral drugs and diagnostic tests. In 2010, the World Health Assembly adopted a resolution calling for a comprehensive approach for the prevention, control, and management of viral hepatitis. We describe activities at the World Health Organization (WHO) in three key areas: the establishment of a global hepatitis Program and interim strategy; steps toward the development of global guidance on management of coinfection for RLS; and the WHO prequalification program of HBV and HCV diagnostic assays. We highlight key research gaps and the importance of applying the lessons learned from the public health scale-up of ART to hepatitis care. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hepatitis B vaccine immunogenicity among adults vaccinated during an outbreak response in an assisted living facility—Virginia, 2010

PubMed Central

Bender, Thomas John; Sharapov, Umid; Utah, Okey; Xing, Jian; Hu, Dale; Rybczynska, Jolanta; Drobeniuc, Jan; Kamili, Saleem; Spradling, Philip R.; Moorman, Anne C.

2017-01-01

Background Failure to adhere to infection control guidelines, especially during assisted monitoring of blood glucose, has caused multiple hepatitis B outbreaks in assisted living facilities (ALFs). In conjunction with the response to such an outbreak at an ALF (“Facility X”) where most residents had neuropsychiatric disorders, we evaluated seroprotection rates conferred by hepatitis B vaccine and assessed the influence of demographic factors on vaccine response. Methods Residents were screened for hepatitis B and C infection, and those susceptible were vaccinated against hepatitis A and hepatitis B with one dose of TWINRIX™ (GSK) given at 0, 1, and 7 months. Blood samples were collected 1–2 months after receipt of the third vaccine dose to test for antibody to hepatitis B surface antigen (anti-HBs). Results Of the 27 residents who had post-vaccination blood specimens collected, 22 (81%) achieved anti-HBs concentrations ≥10 mIU/mL. Neither age nor neuropsychiatric comorbidity was a significant determinant of seroprotection. Geometric mean concentration was lower among residents aged 60–74 years (74.3 mIU/mL) than among residents aged 46–59 years (105.3 mIU/mL) but highest among residents aged ≥75 years (122.5 mIU/mL). The effect of diabetes on vaccination response could not be examined because 16/17 (94%) diabetic residents had HBV infection by the time of investigation. Conclusions Adult vaccine recipients of all ages, even those over 60 years of age, demonstrated a robust capacity for achieving hepatitis B seroprotection in response to the combined hepatitis A/hepatitis B vaccine. The role for vaccination in interrupting HBV transmission during an outbreak remains unclear, but concerns about age-related response to hepatitis B vaccine may be insufficient to justify foregoing vaccination of susceptible residents of ALFs. PMID:24370706

[Application of diffusion tensor imaging in judging infarction time of acute ischemic cerebral infarction].

PubMed

Dai, Zhenyu; Chen, Fei; Yao, Lizheng; Dong, Congsong; Liu, Yang; Shi, Haicun; Zhang, Zhiping; Yang, Naizhong; Zhang, Mingsheng; Dai, Yinggui

2015-08-18

To evaluate the clinical application value of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in judging infarction time phase of acute ischemic cerebral infarction. To retrospective analysis DTI images of 52 patients with unilateral acute ischemic cerebral infarction (hyper-acute, acute and sub-acute) from the Affiliated Yancheng Hospital of Southeast University Medical College, which diagnosed by clinic and magnetic resonance imaging. Set the regions of interest (ROIs) of infarction lesions, brain tissue close to infarction lesions and corresponding contra (contralateral normal brain tissue) on DTI parameters mapping of fractional anisotropy (FA), volume ratio anisotropy (VRA), average diffusion coefficient (DCavg) and exponential attenuation (Exat), record the parameters values of ROIs and calculate the relative parameters value of infarction lesion to contra. Meanwhile, reconstruct the DTT images based on the seed points (infarction lesion and contra). The study compared each parameter value of infarction lesions, brain tissue close to infarction lesions and corresponding contra, also analysed the differences of relative parameters values in different infarction time phases. The DTT images of acute ischemic cerebral infarction in each time phase could show the manifestation of fasciculi damaged. The DCavg value of cerebral infarction lesions was lower and the Exat value was higher than contra in each infarction time phase (P<0.05). The FA and VRA value of cerebral infarction lesions were reduced than contra only in acute and sub-acute infarction (P<0.05). The FA, VRA and Exat value of brain tissue close to infarction lesions were increased and DCavg value was decreased than contra in hyper-acute infarction (P<0.05). There were no statistic differences of FA, VRA, DCavg and Exat value of brain tissue close to infarction lesions in acute and sub-acute infarction. The relative FA and VRA value of infarction lesion to contra gradually decreased from hyper-acute to sub-acute cerebral infarction (P<0.05), but there were no difference of the relative VRA value between acute and sub-acute cerebral infarction. The relative DCavg value of infarction lesion to contra in hyper-acute infarction than that in acute and sub-acute infarction (P<0.05), however there was also no difference between acute and sub-acute infarction. ROC curve showed the best diagnosis cut off value of relative FA, VRA and DCavg of infarction lesions to contra were 0.852, 0.886 and 0.541 between hyper-acute and acute cerebral infarction, the best diagnosis cut off value of relative FA was 0.595 between acute and sub-acute cerebral infarction, respectively. The FA, VRA, DCavg and Exat value have specific change mode in acute ischemic cerebral infarction of different infarction time phases, which can be combine used in judging infarction time phase of acute ischemic cerebral infarction without clear onset time, thus to help selecting the reasonable treatment protocols.

An Open-Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics.

PubMed

Li, Yan; Wang, Xiaomin; Liu, Liangang; Zhang, Chengyue; Gomez, Diana; Reyes, Josephine; Palmisano, Maria; Zhou, Simon

2018-05-10

Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open-label, single-dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4-mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (C max ) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4-mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), a 3-mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child-Pugh class C), a 2-mg starting daily dose (50% dose reduction). © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Colonization-Induced Host-Gut Microbial Metabolic Interaction

PubMed Central

Claus, Sandrine P.; Ellero, Sandrine L.; Berger, Bernard; Krause, Lutz; Bruttin, Anne; Molina, Jérôme; Paris, Alain; Want, Elizabeth J.; de Waziers, Isabelle; Cloarec, Olivier; Richards, Selena E.; Wang, Yulan; Dumas, Marc-Emmanuel; Ross, Alastair; Rezzi, Serge; Kochhar, Sunil; Van Bladeren, Peter; Lindon, John C.; Holmes, Elaine; Nicholson, Jeremy K.

2011-01-01

The gut microbiota enhances the host’s metabolic capacity for processing nutrients and drugs and modulate the activities of multiple pathways in a variety of organ systems. We have probed the systemic metabolic adaptation to gut colonization for 20 days following exposure of axenic mice (n = 35) to a typical environmental microbial background using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy to analyze urine, plasma, liver, kidney, and colon (5 time points) metabolic profiles. Acquisition of the gut microbiota was associated with rapid increase in body weight (4%) over the first 5 days of colonization with parallel changes in multiple pathways in all compartments analyzed. The colonization process stimulated glycogenesis in the liver prior to triggering increases in hepatic triglyceride synthesis. These changes were associated with modifications of hepatic Cyp8b1 expression and the subsequent alteration of bile acid metabolites, including taurocholate and tauromuricholate, which are essential regulators of lipid absorption. Expression and activity of major drug-metabolizing enzymes (Cyp3a11 and Cyp2c29) were also significantly stimulated. Remarkably, statistical modeling of the interactions between hepatic metabolic profiles and microbial composition analyzed by 16S rRNA gene pyrosequencing revealed strong associations of the Coriobacteriaceae family with both the hepatic triglyceride, glucose, and glycogen levels and the metabolism of xenobiotics. These data demonstrate the importance of microbial activity in metabolic phenotype development, indicating that microbiota manipulation is a useful tool for beneficially modulating xenobiotic metabolism and pharmacokinetics in personalized health care. PMID:21363910

Multipolar hepatic radiofrequency ablation using up to six applicators: preliminary results.

PubMed

Bruners, P; Schmitz-Rode, T; Günther, R W; Mahnken, A

2008-03-01

To evaluate the clinical feasibility and safety of hepatic radiofrequency (RF) ablation using a multipolar RF system permitting the simultaneous use of up to six electrodes. Ten patients (3 female, 7 male, mean age 61) suffering from 29 hepatic metastases (range: 1 - 5) of different tumors were treated with a modified multipolar RF system (CelonLab Power, Celon Medical Instruments, Teltow, Germany) operating four to six needle-shaped internally cooled RF applicators. The procedure duration, applied energy and generator output were recorded during the intervention. The treatment result and procedure-related complications were analyzed. The achieved coagulation volume was calculated on the basis of contrast-enhanced CT scans 24 hours after RF ablation. Complete tumor ablation was achieved in all cases as determined by the post-interventional lack of contrast enhancement in the target region using four applicators in five patients, five applicators in one patient and six applicators in four patients. A mean energy deposition of 353.9 +/- 176.2 kJ resulted in a mean coagulation volume of 115.9 +/- 79.5 cm (3). The mean procedure duration was 74.9 +/- 21.2 minutes. Four patients showed an intraabdominal hemorrhage which necessitated further interventional treatment (embolization; percutaneous histoacryl injection) in two patients. Multipolar RF ablation of hepatic metastasis with up to six applicators was clinically feasible. In our patient population it was associated with an increased risk of intraabdominal bleeding probably due to the multiple punctures associated with the use of multiple applicators.

Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine after intravenous and oral administration in beagle dogs.

PubMed

Kuroha, M; Shirai, Y; Shimoda, M

2004-10-01

In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.

Effect of multiple dosing of ketoconazole on pharmacokinetics of midazolam, a cytochrome P-450 3A substrate in beagle dogs.

PubMed

Kuroha, Masanori; Azumano, Akinori; Kuze, Yoji; Shimoda, Minoru; Kokue, Eiichi

2002-01-01

To evaluate effects of multiple dosing of ketoconazole (KTZ) on hepatic CYP3A, the pharmacokinetics of intravenous midazolam (MDZ, 0.5 mg/kg) before and during multiple dosing of KTZ were investigated in beagle dogs. KTZ tablets were given orally to dogs (n = 4) for 30 days (200 mg b.i.d.). With coadministration of KTZ, t(1/2beta) of MDZ were significantly increased both on day 1 (2-fold) and on day 30 (3-fold). Total body clearance (CL(tot)) of MDZ declined gradually during the first 5 days after the start of KTZ treatment, and thereafter CL(tot) appeared to reach a plateau phase (one-fourth), depending on plasma KTZ concentrations. The effects of KTZ on the biotransformation of MDZ were also investigated using dog liver microsomes (n = 5). The K(i) values of KTZ for MDZ 1'-hydroxylation and 4-hydroxylation were 0.0237 and 0.111 microM, respectively, indicating that KTZ extensively inhibits hepatic CYP3A activity in dogs. CL(tot) values estimated from in vitro K(i) values corrected by unbound fraction of KTZ and unbound concentrations of the drug in plasma were consistent with in vivo CL(tot) of MDZ. The results in this study suggest that KTZ treatment is necessary until plasma concentrations of the drug reach a steady state to evaluate the effect of multiple dosing of the drug on hepatic CYP3A in vivo. In addition, it is suggested that K(i) values corrected by unbound fraction of KTZ and unbound concentrations of the drug in plasma enable precise in vitro-in vivo scaling.

Development of multiple myeloma in a patient with chronic hepatitis C: A case report and review of the literature

PubMed Central

Lakatos, Peter Laszlo; Fekete, Sandor; Horanyi, Margit; Fischer, Simon; Abonyi, Margit E

2006-01-01

An association between chronic hepatitis C virus (HCV) infection and essential mixed cryoglobulinaemia and non-Hodgkin lymphoma (NHL) has been suggested. However, a causative role of HCV in these conditions has not been established. The authors report a case of a 50 year-old woman with chronic hepatitis C (CHC) who has been followed up since 1998 due to a high viral load, genotype 1b and moderately elevated liver function tests (LFTs). Laboratory data and liver biopsy revealed moderate activity (grade: 5/18, stage: 1/6). In April 1999, one-year interferon therapy was started. HCV-RNA became negative with normalization of LFTs. However, the patient relapsed during treatment. In September 2002, the patient was admitted for chronic back pain. A CT examination demonstrated degenerative changes. In March 2003, multiple myeloma was diagnosed (IgG-kappa, bone ma-rrow biopsy: 50% plasma cell infiltration). MRI revealed a compression fracture of the 5th lumbar vertebral body and an abdominal mass in the right lower quadrant, infiltrating the canalis spinalis. Treatment with vincristine, adriamycin and dexamethasone (VAD) was started and bisphosphonate was administered regularly. In January 2004, after six cycles of VAD therapy, the multiple myeloma regressed. Thalidomide, as a second line trea-tment of refractory multiple myeloma (MM) was initiated, and followed by peginterferon-α2b and ribavirin against the HCV infection in June. In June 2005, LFTs returned to normal, while HCV-RNA was negative, demonstrating an end of treatment response. Although a pathogenic role of HCV infection in malignant lymphoproliferative disorders has not been established, NHL and possibly MM may develop in CHC patients, supporting a role of a complex follow-up in these patients. PMID:16610042

Hepatic "BOLSA" a novel method of perihepatic wrapping for hepatic hemorrhage "BOLSA".

PubMed

Ng, Nathaniel; McLean, Susan F; Ghaleb, Melhem R; Tyroch, Alan H

2015-01-01

Severe traumatic liver hemorrhage quickly leads to exsanguination. Perihepatic packing is frequently used in damage control surgery. This method can be unsuccessful and accompanied by complications. Vicryl mesh wraps have been described in the treatment of liver hemorrhage. In this report, we describe an enhanced technique of hepatic wrapping in a case of hepatic bleeding after liver biopsy in a coagulopathic patient. The technique is called the hepatic "BOLSA" (Bag on Liver Supporting Anti-Hemorrhage). A 59 year old male presented in the recovery room after liver biopsy of a mass, followed by angio-embolization of the hepatic mass 9h earlier. The patient was acidotic, coagulopathic, and demonstrated intra-abdominal hypertension. Computed tomography demonstrated perihepatic fluid. The patient continued hemorrhaging despite attempts to correct coagulopathy by transfusion. Multiple operating room visits were required where a combination of packing and hemostatic agents could not stop hepatic venous parenchymal hemorrhage. Mesh wrap consisting of Vicryl and PDS suture were used to create the "BOLSA" to achieve hemostasis. Perihepatic packing compromises pulmonary excursion, elevates intra-abdominal pressure, is a risk factor for sepsis, and requires an additional trip to the operating room for removal. The use of Vicryl mesh wrap obviates these complications. Previously described mesh wraps require anchoring. The self-supporting structure of the BOLSA simplifies construction and application. The BOLSA is an effective tool in treatment of severe liver hemorrhage in coagulopathic patients. It is the modern simplification of hepatic wrapping and the solution to the side effects of perihepatic packing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Extracapsular hepatic adenoma. Case report and literature review].

PubMed

Vargas-Flores, Edgar; Pérez-Aguilar, Francisco; Valdez-Mendieta, Yanet

Hepatic adenomas are uncommon epithelial tumours. They usually appear in women between 20 and 44 years old. They are commonly located in the right hepatic lobe and are typically solitary masses. Multiple adenomas can present in patients with prolonged use of oral contraceptive pills, glycogen storage diseases and hepatic adenomatosis. A 35 year-old woman without any significant past medical history, with a chief complaint that started in December 2012 with oppressive, mild intensity abdominal pain located in right upper quadrant in the abdomen on deep palpation. With an abdominal ultrasound showing a mass of 91×82×65cm located in the right flank, isoechogenic with internal vascularity. Contrast computed tomography scan showing an ovoid tumour with circumscribed borders, with heterogenic intense reinforcement and displacement of adjacent structures with dimensions of 88×71×80cm. In laparotomy, excision of the tumour and cholecystectomy with the trans surgical findings of an 8cm tumour with a pedicle containing one artery and one vein coming from the hepatic free border with strong adhesions to the gallbladder. Pathologic diagnosis: Extracapsular hepatic adenoma. Incidence of hepatic adenomas has increased in the last decades, in a parallel fashion with the introduction of oral contraceptive pills, showing association with glycogen storage diseases and to a lesser degree with diabetes and pregnancy. Diagnosis is clinical with the aid of imaging studies. Prognosis of hepatic adenomas is not well established, therefore, management depends on symptoms, size, number, location and certainty of diagnosis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats.

PubMed

Morán-Ramos, Sofía; Avila-Nava, Azalia; Tovar, Armando R; Pedraza-Chaverri, José; López-Romero, Patricia; Torres, Nimbe

2012-11-01

Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

Clinical associations of hepatic stellate cell (HSC) hyperplasia.

PubMed

Mounajjed, Taofic; Graham, Rondell P; Sanderson, Schuyler O; Smyrk, Thomas C

2014-07-01

Hepatic stellate cell (HSC) hyperplasia has been principally attributed to hypervitaminosis A. There are sporadic reports of HSC hyperplasia in other conditions such as chronic biliary disease and hepatitis C, but clinical associations of this entity have not been studied in detail. We aimed to investigate the clinical associations of HSC hyperplasia aside from hypervitaminosis A. We identified 34 patients whose liver histology showed HSC hyperplasia. We reviewed the liver samples; additional histologic findings in addition to HSC hyperplasia were consolidated into a histologic diagnosis. We collected clinical, laboratory, and radiologic data; the histologic diagnosis was combined with this data to reach an "overall diagnosis." Four patients had hypervitaminosis A (all native livers). In native livers (n = 24), HSC hyperplasia also occurred in association with drug-induced hepatitis [n = 6, niacin was the most common inducing agent (n = 3)], reactive hepatitis (n = 4), chronic hepatitis C (n = 4), autoimmune hepatitis (n = 3), steatohepatitis (n = 1), chronic biliary disease (n = 1), and portal venopathy (n = 1). In liver allografts (n = 10), HSC hyperplasia was seen in protocol biopsies without other significant abnormalities (n = 5), chronic biliary disease (n = 4), and acute cellular rejection (n = 1). All patients used medications (total of 99) and 82 % were on multiple medications. HSC hyperplasia is an uncommon and relatively nonspecific finding that most commonly occurs in multimedicated patients, often in the absence of hypervitaminosis A. Associated conditions include drug toxicity (such as niacin), post-liver transplant setting, reactive hepatitis (due to systemic illness or inflammatory disorders of the gastrointestinal tract), and chronic liver disease.

Cross-talk between branched-chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease.

PubMed

Sunny, Nishanth E; Kalavalapalli, Srilaxmi; Bril, Fernando; Garrett, Timothy J; Nautiyal, Manisha; Mathew, Justin T; Williams, Caroline M; Cusi, Kenneth

2015-08-15

Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperinsulinemic clamps (insulin stimulation) were measured in 94 human subjects with varying degrees of insulin sensitivity to identify their relationships with insulin resistance. Furthermore, the impact of elevated BCAA on hepatic TCA cycle was determined in a diet-induced mouse model of NAFLD, utilizing targeted metabolomics and nuclear magnetic resonance (NMR)-based metabolic flux analysis. Insulin stimulation revealed robust relationships between human plasma BCAA and indices of insulin resistance, indicating chronic metabolic overload from BCAA. Human plasma BCAA and long-chain acylcarnitines also showed a positive correlation, suggesting modulation of mitochondrial metabolism by BCAA. Concurrently, mice with NAFLD failed to optimally induce hepatic mTORC1, plasma ketones, and hepatic long-chain acylcarnitines, following acute elevation of plasma BCAA. Furthermore, elevated BCAA failed to induce multiple fluxes through hepatic TCA cycle in mice with NAFLD. Our data suggest that BCAA are essential to mediate efficient channeling of carbon substrates for oxidation through mitochondrial TCA cycle. Impairment of BCAA-mediated upregulation of the TCA cycle could be a significant contributor to mitochondrial dysfunction in NAFLD.

Cross-talk between branched-chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease

PubMed Central

Kalavalapalli, Srilaxmi; Bril, Fernando; Garrett, Timothy J.; Nautiyal, Manisha; Mathew, Justin T.; Williams, Caroline M.; Cusi, Kenneth

2015-01-01

Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperinsulinemic clamps (insulin stimulation) were measured in 94 human subjects with varying degrees of insulin sensitivity to identify their relationships with insulin resistance. Furthermore, the impact of elevated BCAA on hepatic TCA cycle was determined in a diet-induced mouse model of NAFLD, utilizing targeted metabolomics and nuclear magnetic resonance (NMR)-based metabolic flux analysis. Insulin stimulation revealed robust relationships between human plasma BCAA and indices of insulin resistance, indicating chronic metabolic overload from BCAA. Human plasma BCAA and long-chain acylcarnitines also showed a positive correlation, suggesting modulation of mitochondrial metabolism by BCAA. Concurrently, mice with NAFLD failed to optimally induce hepatic mTORC1, plasma ketones, and hepatic long-chain acylcarnitines, following acute elevation of plasma BCAA. Furthermore, elevated BCAA failed to induce multiple fluxes through hepatic TCA cycle in mice with NAFLD. Our data suggest that BCAA are essential to mediate efficient channeling of carbon substrates for oxidation through mitochondrial TCA cycle. Impairment of BCAA-mediated upregulation of the TCA cycle could be a significant contributor to mitochondrial dysfunction in NAFLD. PMID:26058864

Multiple factors contribute to positive results for hepatitis A virus immunoglobulin M antibody.

PubMed

Alatoom, Adnan; Ansari, M Qasim; Cuthbert, Jennifer

2013-01-01

In the United States, a successful vaccination program for hepatitis A virus (HAV) infection has decreased both its incidence and the true positive rate for diagnostic immunoglobulin M (IgM) antibody to HAV in acute hepatitis. To survey positive results of HAV IgM tests and determine the effect of changing ordering options. We reviewed all positive results for IgM antibody to HAV between January 2007 and December 2010. Patient demographics, clinical history, and laboratory data were recorded and the encounter, order, and reason for test reviewed. Each result was categorized as indicating acute, recent, resolved, or indeterminate HAV infection. A total of 10,735 tests were performed; 35 patients had 49 positive results. Most positive test results were associated with outpatient visits and were ordered in the assessment of patients with liver disease, but not clinical acute hepatitis. In the final analysis, 4 patients had acute hepatitis A and 20 individual patients had recent and/or resolved hepatitis. All but 1 of the remaining 11 patients had another established cause of liver disease with a positive IgM HAV antibody test result; data to determine causality were insufficient. The total number of tests requested annually decreased more than 35% with the introduction of computerized physician order entry. Current assays for IgM HAV antibodies are overused in the absence of clinical acute hepatitis; future clinical decision support may improve patterns of order entry. Most patients have findings consistent with HAV exposure but not acute hepatitis; dormant viral infection may be a continuing source of antigen.

Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects

PubMed Central

German, Polina; Kearney, Brian P.; Yang, Cheng Yong; Brainard, Diana; Link, John; McNally, John; Han, LingLing; Ling, John; Mathias, Anita

2017-01-01

ABSTRACT Preclinical characterization of velpatasvir (VEL; GS-5816), an inhibitor of the hepatitis C virus (HCV) NS5A protein, demonstrated that it has favorable in vitro and in vivo properties, including potent antiviral activity against hepatitis C virus genotype 1 to 6 replicons, good metabolic stability, low systemic clearance, and adequate bioavailability and physicochemical properties, to warrant clinical evaluation. The phase 1 (first-in-human) study evaluated the safety, tolerability, and pharmacokinetics of VEL in healthy human subjects following administration of single and multiple (n = 7) once-daily ascending doses and of VEL in the presence and absence of food. Following administration of single and multiple doses, VEL was safe and well tolerated when administered at up to 450 mg and when administered with food. The pharmacokinetic behavior of VEL observed in humans was generally in agreement with that seen during preclinical characterization. Following administration of multiple doses, VEL trough concentrations were significantly greater than the protein-adjusted half-maximal (50%) effective concentration of VEL against HCV genotype 1 to 6 replicons at all evaluated doses greater than 5 mg. The pharmacokinetics of VEL were not significantly affected by administration with food. Collectively, the results of this study support the further clinical investigation of VEL administered once daily as part of a regimen with other pangenotypic direct-acting antivirals for the treatment of HCV infection. PMID:28193657

Recombinant Vaccinia Virus: Immunization against Multiple Pathogens

NASA Astrophysics Data System (ADS)

Perkus, Marion E.; Piccini, Antonia; Lipinskas, Bernard R.; Paoletti, Enzo

1985-09-01

The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

Levofloxacin-induced hepatotoxicity and death.

PubMed

Gulen, Muge; Ay, Mehmet Oguzhan; Avci, Akkan; Acikalin, Ayca; Icme, Ferhat

2015-01-01

Drug-induced hepatotoxicity is a major cause of hepatocellular injury in patients admitting to emergency services with acute liver failure. Hepatic necrosis may be at varying degrees from mild elevations in transaminases to fulminant hepatitis, and even death. The case of a 53-year-old female patient with toxic hepatitis due to levofloxacin and multiple organ failure secondary to toxic hepatitis is presented. Patient suffered itching, redness, and rash after receiving a single dose of 750 mg of levofloxacin tablets for pulmonary infection 10 days ago. Skin lesions had regressed within 3 days, but desquamation formed all over the body. After the fifth day of drug intake, complaints of abdominal pain, vomiting, and yellowing in skin color had started. The patient was referred to our emergency department with these complaints 10 days after drug intake. Patient was thought as a candidate for liver transplant, but cardiopulmonary arrest occurred, and the patient died before she could be referred to a transplant center. This case is important because hepatotoxicity and death due to levofloxacin is uncommon in the literature.

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies.

PubMed

Ho, V T; Revta, C; Richardson, P G

2008-02-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), remains one of the most serious and common complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the clinical triad of (1) painful hepatomegaly, (2) hyperbilirubinemia and (3) unexplained fluid retention. While milder cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide (DF), a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. Multiple studies, including a recent large international multicenter phase II clinical trial, have demonstrated 30-60% complete remission rates with DF, even among patients with severe VOD and multiorgan failure. This article will review our current understanding of hepatic VOD, and update the clinical trial experience with DF and other potential therapies for this feared transplant complication.

Hepatitis B Virus Infection, MicroRNAs and Liver Disease.

PubMed

Sarkar, Neelakshi; Chakravarty, Runu

2015-08-03

Hepatitis B virus (HBV) attacks the liver and can cause both acute as well as chronic liver diseases which might lead to liver cirrhosis and hepatocellular carcinoma. Regardless of the availability of a vaccine and numerous treatment options, HBV is a major cause of morbidity and mortality across the world. Recently,microRNAs (miRNAs) have emerged as important modulators of gene function. Studies on the role of miRNA in the regulation of hepatitis B virus gene expression have been the focus of modern antiviral research. miRNAs can regulate viral replication and pathogenesis in a number of different ways, which includefacilitation, direct or indirect inhibition, activation of immune response, epigenetic modulation, etc. Nevertheless, these mechanisms can appropriately be used with a diagnosticand/or therapeutic approach. The present review is an attempt to classify specific miRNAs that are reported to be associated with various aspects of hepatitis B biology, in order to precisely present the participation of individual miRNAs in multiple aspects relating to HBV.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

PubMed Central

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-01-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

The Effect of Lactic Acid Bacteria-fermented Soybean Milk Products on Carrageenan-induced Tail Thrombosis in Rats

PubMed Central

KAMIYA, Seitaro; OGASAWARA, Masayoshi; ARAKAWA, Masayuki; HAGIMORI, Masayori

2013-01-01

Thrombosis is characterized by congenital and acquired procatarxis. Lactic acid bacteria-fermented soybean milk products (FS-LAB) inhibit hepatic lipid accumulation and prevent atherosclerotic plaque formation. However, the therapeutic efficacy of FS-LAB against thrombosis has yet to be investigated. In this study, FS-LAB were administered subcutaneously into the tails of rats, with the subsequent intravenous administration of κ-carrageenan 12 hr after the initial injection. In general, administration of κ-carrageenan induces thrombosis. The length of the infarcted tail regions was significantly shorter in the rats administered a single-fold or double-fold concentration of the FS-LAB solution compared with the region in control rats. Therefore, FS-LAB exhibited significant antithrombotic effects. Our study is the first to characterize the properties of FS-LAB and, by testing their efficacy on an in vivo rat model of thrombosis, demonstrate the potency of their antithrombotic effect. PMID:24936368

Cystathionine beta-synthase deficiency alters hepatic phospholipid and choline metabolism: Post-translational repression of phosphatidylethanolamine N-methyltransferase is a consequence rather than a cause of liver injury in homocystinuria.

PubMed

Jacobs, René L; Jiang, Hua; Kennelly, John P; Orlicky, David J; Allen, Robert H; Stabler, Sally P; Maclean, Kenneth N

2017-04-01

Classical homocystinuria (HCU) due to inactivating mutation of cystathionine β-synthase (CBS) is a poorly understood life-threatening inborn error of sulfur metabolism. A previously described cbs-/- mouse model exhibits a semi-lethal phenotype due to neonatal liver failure. The transgenic HO mouse model of HCU exhibits only mild liver injury and recapitulates multiple aspects of the disease as it occurs in humans. Disruption of the methionine cycle in HCU has the potential to impact multiple aspect of phospholipid (PL) metabolism by disruption of both the Kennedy pathway and phosphatidylethanolamine N-methyltransferase (PEMT) mediated synthesis of phosphatidylcholine (PC). Comparative metabolomic analysis of HO mouse liver revealed decreased levels of choline, and choline phosphate indicating disruption of the Kennedy pathway. Alterations in the relative levels of multiple species of PL included significant increases in PL degradation products consistent with enhanced membrane PL turnover. A significant decrease in PC containing 20:4n6 which primarily formed by the methylation of phosphatidylethanolamine to PC was consistent with decreased flux through PEMT. Hepatic expression of PEMT in both the cbs-/- and HO models is post-translationally repressed with decreased levels of PEMT protein and activity that inversely-correlates with the scale of liver injury. Failure to induce further repression of PEMT in HO mice by increased homocysteine, methionine and S-adenosylhomocysteine or depletion of glutathione combined with examination of multiple homocysteine-independent models of liver injury indicated that repression of PEMT in HCU is a consequence rather than a cause of liver injury. Collectively, our data show significant alteration of a broad range of hepatic PL and choline metabolism in HCU with the potential to contribute to multiple aspects of pathogenesis in this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Connection of Nicotine to Diet-Induced Obesity and Non-Alcoholic Fatty Liver Disease: Cellular and Mechanistic Insights

PubMed Central

Sinha-Hikim, Amiya P.; Sinha-Hikim, Indrani; Friedman, Theodore C.

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) poses a serious health hazard affecting 20–40% of adults in the general population in the USA and over 70% of the obese and extremely obese people. In addition to obesity, nicotine is recognized as a risk factor for NAFLD, and it has been reported that nicotine can exaggerate obesity-induced hepatic steatosis. The development of NAFLD has serious clinical complications because of its potential progression from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Multiple mechanisms can be involved in nicotine plus high-fat diet-induced (HFD) hepatic steatosis. Emerging evidence now suggests that nicotine exacerbates hepatic steatosis triggered by HFD, through increased oxidative stress and hepatocellular apoptosis, decreased phosphorylation (inactivation) of adenosine-5-monophosphate-activated protein kinase and, in turn, up-regulation of sterol response-element binding protein 1-c, fatty acid synthase, and activation of acetyl-coenzyme A-carboxylase, leading to increased hepatic lipogenesis. There is also growing evidence that chronic endoplasmic reticulum stress through regulation of several pathways leading to oxidative stress, inflammation, perturbed hepatic lipid homeostasis, apoptosis, and autophagy can induce hepatic steatosis and its progression to NASH. Evidence also suggests a central role of the gut microbiota in obesity and its related disorders, including NAFLD. This review explores the contribution of nicotine and obesity to the development of NAFLD and its molecular underpinning. PMID:28239368

Chronic hepatitis B, nonalcoholic steatohepatitis and physical fitness of military males: CHIEF study.

PubMed

Chen, Yu-Jung; Chen, Kai-Wen; Shih, Yu-Leung; Su, Fang-Ying; Lin, Yen-Po; Meng, Fan-Chun; Lin, Felicia; Yu, Yun-Shun; Han, Chih-Lu; Wang, Chih-Hung; Lin, Jia-Wei; Hsieh, Tsai-Yuan; Li, Yi-Hwei; Lin, Gen-Min

2017-07-07

To investigate the association of chronic hepatitis B and nonalcoholic steatohepatitis with physical fitness in a Taiwanese military male cohort. We made a cross-sectional examination of this association using 3669 young adult military males according to cardiorespiratory fitness and hospitalization events recorded in the Taiwan Armed Forces study. Cases of chronic hepatitis B ( n = 121) were defined by personal history and positive detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis ( n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound finding of steatosis, and absence of viral hepatitis A, B or C infection. All other study participants were defined as unaffected ( n = 3419). Physical fitness was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups exercises, with all the procedures standardized by a computerized scoring system. Multiple linear regression analysis was used to determine the relationship. Chronic hepatitis B negatively correlated with 2-min push-up numbers (β = -2.49, P = 0.019) after adjusting for age, service specialty, body mass index, systolic and diastolic blood pressures, current cigarette smoking, alcohol intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic steatohepatitis was borderline positively correlated with 3000-m running time (β = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers (β = -1.47, P = 0.040). Chronic hepatitis B viral infection and nonalcoholic steatohepatitis affects different physical performances in young adult military males, and future study should determine the underlying mechanism.

Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its influence on carbohydrate metabolism.

PubMed

Altuna, María Eugenia; Lelli, Sandra Marcela; San Martín de Viale, Leonor C; Damasco, María Cristina

2006-10-01

Stress activates the synthesis and secretion of catecholamines and adrenal glucocorticoids, increasing their circulating levels. In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level. We studied the effect of 3 types of stress, 1 induced by bucogastric overload with 200 mmol/L HCl causing metabolic acidosis (HCl), the second induced by bucogastric overload with 0.45% NaCl (NaCl), and the third induced by simulated overload (cannula), on the kinetics of hepatic HSD1 of rats and their influence on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, glycemia, and glycogen deposition. Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl). Owing to these results, we suggest the following events occur when stress is induced: an increase in hepatic HSD1 activity, augmented active glucocorticoid levels, increased gluconeogenesis, and glycemia. Also involved are the multiple events indirectly related to glucocorticoids, which lead to the depletion of hepatic glycogen deposits, thereby contributing to increased glycemia. This new approach shows that stress increments the activity of hepatic HSD1 and suggests that this enzyme could be involved in the development of the Metabolic Syndrome.

Primary or metastatic hepatic carcinoma? A breast cancer patient after adjuvant chemotherapy and radiotherapy postoperatively with intrahepatic cholangiocarcinoma and review of the literature.

PubMed

Liu, Zhao-Yun; Sun, Ju-Jie; He, Ke-Wen; Zhuo, Pei-Ying; Yu, Zhi-Yong

2016-07-15

The liver is a common site of metastases, followed by the bone and lung in breast cancer. The symptoms of hepatic metastases are similar to intrahepatic cholangiocarcinoma (ICC). ICC is rare, with an overall incidence rate of 0.95 cases per 100,000 adults. The incidence of ICC for patients with breast cancer is very uncommon. Breast cancer patient with ICC is easily misdiagnosed as hepatic metastases. We report a breast cancer patient postoperatively who was hospitalized because of having continuous irregular fever for 1 month. Antibiotics were given for 1 week without any significant effect. Her admission bloods revealed elevated levels of carcino-embryonic antigen. Magnetic resonance imaging diagnosis showed multiple liver metastases. We believed that the woman had hepatic metastases until biopsy guided by computed tomography. The liver biopsy pathology analysis considered the possibility of primary intrahepatic cholangiocarcinoma. Breast cancer patient with space-occupying lesions in the liver is easily considered to be progressed hepatic metastases. Image-guided biopsy is the best diagnostic method for breast cancer with liver mass to avoid misdiagnosis and classify the molecular subtypes to make appropriate treatment.

Angiomyolipoma of the liver: case report.

PubMed

Sung, K F; Chen, T C; Hung, C F; Jeng, L B; Lien, J M

2001-05-01

Hepatic angiomyolipoma is a rare benign mesenchymal tumor of the liver. Most multiple hepatic angiomyolipomas have appeared in patients with renal angiomyolipoma and tuberous sclerosis. A 38-year-old female patient without chronic hepatitis B or C was hospitalized because of epigastric fullness for 2 months. Radiologic studies showed a large solid tumor with a small daughter nodule in the right hepatic lobe. Upon intravenous bolus injection of contrast medium, both tumors showed weak heterogeneous enhancement in the delayed phase. Although hepatocellular carcinoma was suspected by the findings of computed tomography, percutaneous transhepatic ultrasound-guided biopsy was performed for the large tumor. The histopathology showed many mature fat cells intermingled with thick-walled blood vessels, and epithelioid cells with eosinophilic cytoplasm; the epithelioid cells stained positively for HMB-45 and smooth muscle actin. Angiomyolipoma of the liver was confirmed. The main tumor enlarged considerably during a follow-up period of 3 years. Surgical resection was performed due to persistent symptoms. She had an uneventful postoperative recovery and was well when followed up 10 months after surgery. We should be aware that a hepatic angiomyolipoma can change in size during its natural course, and this finding does not necessarily indicate malignancy.

Tributyltin promoted hepatic steatosis in zebrafish (Danio rerio) and the molecular pathogenesis involved.

PubMed

Zhang, Jiliang; Sun, Ping; Kong, Tao; Yang, Fan; Guan, Wenchao

2016-01-01

Endocrine disruptor effects of tributyltin (TBT) are well established in fish. However, the adverse effects on lipid metabolism are less well understood. Since the liver is the predominant site of de novo synthesis of lipids, the present study uses zebrafish (Danio rerio) to examine lipid accumulation in the livers and hepatic gene expression associated with lipid metabolism pathways. After exposure for 90 days, we found that the livers in fish exposed to TBT were yellowish in appearance and with accumulation of lipid droplet, which is consistent with the specific pathological features of steatosis. Molecular analysis revealed that TBT induced hepatic steatosis by increasing the gene expression associated with lipid transport, lipid storage, lipiogenic enzymes and lipiogenic factors in the livers. Moreover, TBT enhanced hepatic caspase-3 activity and up-regulated genes related to apoptosis and cell-death, which indicated steatotic livers of fish exposed to TBT and the subsequent liver damage were likely due to accelerated hepatocyte apoptosis or cell stress. In short, TBT can produce multiple and complex alterations in transcriptional activity of lipid metabolism and cell damage, which provides potential molecular evidence of TBT on hepatic steatosis. Copyright © 2015 Elsevier B.V. All rights reserved.

PROSPECTIVE EVALUATION OF 18F-FDG UPTAKE IN POST-ISCHEMIC MYOCARDIUM BY SIMULTANEOUS PET/MRI AS A PROGNOSTIC MARKER OF FUNCTIONAL OUTCOME

PubMed Central

Rischpler, Christoph; Dirschinger, Ralf J.; Nekolla, Stephan G.; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P.; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

2016-01-01

Background The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by 18F-FDG PET/MRI in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI 18F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of 18F-FDG-PET/MRI in patients after AMI as a biosignal for left ventricular functional outcome. Methods and Results We prospectively enrolled 49 patients with STEMI and performed 18F-FDG-PET/MRI 5 days after PCI and follow-up cardiac MRI after 6–9 months. In a subset of patients, 99mTc-sestamibi-SPECT was performed with tracer injection prior to revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of 18F-FDG-uptake and LGE showed substantial overlap (κ=0.66), while quantitative analysis demonstrated that 18F-FDG extent exceeded LGE extent (33.2±16.2 %LV vs. 20.4±10.6 %LV, p<0.0001) and corresponded to the area-at-risk (r=0.87, p<0.0001). The peripheral blood count of CD14high/CD16+ monocytes correlated with the infarction size and 18F-FDG signal extent (r=0.53, p<0.002 and r=0.42, p<0.02, respectively). 18F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar and the SUVmean was associated with left ventricular functional outcome independent of infarct size (ΔEF: p<0.04, ΔEDV: p<0.02, ΔESV: p<0.005). Conclusions In the current study, the intensity of 18F-FDG uptake in the myocardium after AMI correlated inversely with functional outcome at 6 months. Thus, 18F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. PMID:27056601

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, B; Fujita, A; Buch, K

Purpose: To investigate the correlation between texture analysis-based model observer and human observer in the task of diagnosis of ischemic infarct in non-contrast head CT of adults. Methods: Non-contrast head CTs of five patients (2 M, 3 F; 58–83 y) with ischemic infarcts were retro-reconstructed using FBP and Adaptive Statistical Iterative Reconstruction (ASIR) of various levels (10–100%). Six neuro -radiologists reviewed each image and scored image quality for diagnosing acute infarcts by a 9-point Likert scale in a blinded test. These scores were averaged across the observers to produce the average human observer responses. The chief neuro-radiologist placed multiple ROIsmore » over the infarcts. These ROIs were entered into a texture analysis software package. Forty-two features per image, including 11 GLRL, 5 GLCM, 4 GLGM, 9 Laws, and 13 2-D features, were computed and averaged over the images per dataset. The Fisher-coefficient (ratio of between-class variance to in-class variance) was calculated for each feature to identify the most discriminating features from each matrix that separate the different confidence scores most efficiently. The 15 features with the highest Fisher -coefficient were entered into linear multivariate regression for iterative modeling. Results: Multivariate regression analysis resulted in the best prediction model of the confidence scores after three iterations (df=11, F=11.7, p-value<0.0001). The model predicted scores and human observers were highly correlated (R=0.88, R-sq=0.77). The root-mean-square and maximal residual were 0.21 and 0.44, respectively. The residual scatter plot appeared random, symmetric, and unbiased. Conclusion: For diagnosis of ischemic infarct in non-contrast head CT in adults, the predicted image quality scores from texture analysis-based model observer was highly correlated with that of human observers for various noise levels. Texture-based model observer can characterize image quality of low contrast, subtle texture changes in addition to human observers.« less

Cardiomyocyte A Disintegrin And Metalloproteinase 17 (ADAM17) Is Essential in Post-Myocardial Infarction Repair by Regulating Angiogenesis.

PubMed

Fan, Dong; Takawale, Abhijit; Shen, Mengcheng; Wang, Wang; Wang, Xiuhua; Basu, Ratnadeep; Oudit, Gavin Y; Kassiri, Zamaneh

2015-09-01

A disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound enzyme that mediates shedding of many membrane-bound molecules, thereby regulating multiple cellular responses. We investigated the role of cardiomyocyte ADAM17 in myocardial infarction (MI). Cardiomyocyte-specific ADAM17 knockdown mice (ADAM17(flox/flox)/α-MHC-Cre; f/f/Cre) and parallel controls (ADAM17(flox/flox); f/f) were subjected to MI by ligation of the left anterior descending artery. Post MI, f/f/Cre mice showed compromised survival, higher rates of cardiac rupture, more severe left ventricular dilation, and suppressed ejection fraction compared with parallel f/f-MI mice. Ex vivo ischemic injury (isolated hearts) resulted in comparable recovery in both genotypes. Myocardial vascular density (fluorescent-labeled lectin perfusion and CD31 immunofluorescence staining) was significantly lower in the infarct areas of f/f/Cre-MI compared with f/f-MI mice. Activation of vascular endothelial growth factor receptor 2 (VEGFR2), its mRNA, and total protein levels were reduced in infarcted myocardium in ADAM17 knockdown mice. Transcriptional regulation of VEGFR2 by ADAM17 was confirmed in cocultured cardiomyocyte-fibroblast as ischemia-induced VEGFR2 expression was blocked by ADAM17-siRNA. Meanwhile, ADAM17-siRNA did not alter VEGFA bioavailability in the conditioned media. ADAM17 knockdown mice (f/f/Cre-MI) exhibited reduced nuclear factor-κB activation (DNA binding) in the infarcted myocardium, which could underlie the suppressed VEGFR2 expression in these hearts. Post MI, inflammatory response was not altered by ADAM17 downregulation. This study highlights the key role of cardiomyocyte ADAM17 in post-MI recovery by regulating VEGFR2 transcription and angiogenesis, thereby limiting left ventricular dilation and dysfunction. Therefore, ADAM17 upregulation, within the physiological range, could provide protective effects in ischemic cardiomyopathy. © 2015 American Heart Association, Inc.

Spotted black snake (Pseudechis guttatus) envenomation in a maned wolf (Chrysocyon brachyurus).

PubMed

Portas, Timothy J; Montali, Richard J

2007-09-01

Envenomation by a spotted black snake (Pseudechis guttatus), following multiple bites on the buccal mucosa of a captive maned wolf (Chrysocyon brachyurus), caused the animal's collapse, hemolysis, rhabdomyolysis, local tissue necrosis, hepatic and renal failure, and subsequent death. The wolf died despite intensive supportive care including antivenom administration, fluid support, and a blood transfusion. Gross necropsy findings included myocardial and intestinal hemorrhage, pulmonary congestion, hepatomegaly, and splenomegaly. Microscopic examination of formalin-fixed tissues demonstrated pulmonary and abdominal visceral hemorrhage, acute nephrosis with casts, multifocal hepatic necrosis, and splenic congestion.

[Pharmacovigilance of hepatitis B vaccines].

PubMed

Imbs, Jean-Louis; Decker, Nicole; Welsch, Marie

2003-01-01

Since the hepatitis B vaccine are on the market in France, until the end of 2002, 1211 observations of demyelinating disease of the central nervous system (1109 cases of which 895 multiple sclerosis) or peripheral (102 cases of which 49 Guillain Barre Syndrome), have been reported to the french network of pharmacovigilance and to the AFSSAPS. It is not possible to singularize these observations, neither from a clinical nor an epidemiological point of view. No risk factor has been detected. Only the chronology could suggest a causal relationship, the vaccine preceding the pathology in all the cases notified.

Computed tomography of infantile hepatic hemangioendothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucaya, J.; Enriquez, G.; Amat, L.

1985-04-01

Computed tomography (CT) was performed on five infants with hepatic hemangioendothelioma. Precontrast scans showed solitary or multiple, homogeneous, circumscribed areas with reduced attenuation values. Tiny tumoral calcifications were identified in two patients. Serial scans, after injection of a bolus of contrast material, showed early massive enhancement, which was either diffuse or peripheral. On delayed scans, multinocular tumors became isodense with surrounding liver, while all solitary ones showed varied degrees of centripetal enhancement and persistent central cleftlike unenhanced areas. The authors believe that these CT features are characteristic and obviate arteriographic confirmation.

Rapid recovery from aphasia after infarction of Wernicke's area.

PubMed

Yagata, Stephanie A; Yen, Melodie; McCarron, Angelica; Bautista, Alexa; Lamair-Orosco, Genevieve; Wilson, Stephen M

2017-01-01

Aphasia following infarction of Wernicke's area typically resolves to some extent over time. The nature of this recovery process and its time course have not been characterized in detail, especially in the acute/subacute period. The goal of this study was to document recovery after infarction of Wernicke's area in detail in the first 3 months after stroke. Specifically, we aimed to address two questions about language recovery. First, which impaired language domains improve over time, and which do not? Second, what is the time course of recovery? We used quantitative analysis of connected speech and a brief aphasia battery to document language recovery in two individuals with aphasia following infarction of the posterior superior temporal gyrus. Speech samples were acquired daily between 2 and 16 days post stroke, and also at 1 month and 3 months. Speech samples were transcribed and coded using the CHAT system, in order to quantify multiple language domains. A brief aphasia battery was also administered at a subset of five time points during the 3 months. Both patients showed substantial recovery of language function over this time period. Most, but not all, language domains showed improvements, including fluency, lexical access, phonological retrieval and encoding, and syntactic complexity. The time course of recovery was logarithmic, with the greatest gains taking place early in the course of recovery. There is considerable potential for amelioration of language deficits when damage is relatively circumscribed to the posterior superior temporal gyrus. Quantitative analysis of connected speech samples proved to be an effective, albeit time-consuming, approach to tracking day-by-day recovery in the acute/subacute post-stroke period.

The validity of the family history method for identifying Alzheimer disease.

PubMed

Li, G; Aryan, M; Silverman, J M; Haroutunian, V; Perl, D P; Birstein, S; Lantz, M; Marin, D B; Mohs, R C; Davis, K L

1997-05-01

To examine the validity of the family history method for identifying Alzheimer disease (AD) by comparing family history and neuropathological diagnoses. Seventy-seven former residents of the Jewish Home and Hospital for the Aged, New York, NY, with neuropathological evaluations on record were blindly assessed for the presence of dementia and, if present, the type of dementia through family informants by telephone interviews. The Alzheimer's Disease Risk Questionnaire was used to collect demographic information and screen for possible dementia. If dementia was suspected, the Dementia Questionnaire was administered to assess the course and type of dementia, i.e., primary progressive dementia (PPD, likely AD), multiple infarct dementia, mixed dementia (i.e., PPD and multiple infarct dementia), and other dementias based on the modified Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria. Sixty (77.9%) of 77 elderly subjects were classified as having dementia and 17 (22.1%) were without dementia by family history evaluation. Of the 60 elderly subjects with dementia, 57 (95%) were found at autopsy to have had neuropathological changes related to dementia. The sensitivity of the family history diagnosis for dementia with related neuropathological change was 0.84 (57 of 68) and the specificity was 0.67 (6 of 9). Using family history information to differentiate the type of dementia, the sensitivity for definite or probable AD (with or without another condition) was 0.69 (36 of 51) and the specificity was 0.73 (19 of 26). The majority (9 of 15) of patients testing false negative for PPD had a history of stroke associated with onset of memory changes, excluding a diagnosis of PPD. Identifying dementia, in general, and AD, in particular, has an acceptable sensitivity and specificity. As is true for direct clinical diagnosis, the major issue associated with misclassifying AD in a family history assessment is the masking effects of a coexisting non-AD dementia or dementia-related disorders, such as stroke. Including mixed cases, ie, PPD and multiple infarct dementia in estimates of the familial risk for AD can reduce the extent of underestimation of PPD.

Gallstones in Women

MedlinePlus

... Multiple pregnancies Family history of gallstones Hispanic or American Indian heritage Obesity Rapid loss of weight What is the gallbladder ... Hepatitis C Inflammatory Bowel Disease Irritable Bowel Syndrome Obesity ©2018 American College of Gastroenterology 6400 Goldsboro Rd Ste 200 ...

The impact of irreproducibility and competing protection from P2Y12 antagonists on the discovery of cardioprotective interventions.

PubMed

Cohen, Michael V; Downey, James M

2017-09-26

Scientists and clinicians have been concerned by the lack of a clinically suitable strategy for cardioprotection in patients with acute myocardial infarction despite decades of intensive pre-clinical investigations and a surprising number of clinical trials based on those observations which have uniformly been disappointing. However, it would be a mistake to abandon this search. Rather it would be useful to examine these past efforts and determine reasons for the multiple failures. It appears that earlier clinical trials were often based on results from a single experimental laboratory, thus minimizing the importance of establishing reproducibility in multiple laboratories by multiple scientists and in multiple models. Clinical trials should be discouraged unless robust protection is demonstrated in pre-clinical testing. After approximately 2005 a loading dose of a platelet P2Y 12 receptor antagonist became increasingly widespread in patients with acute myocardial infarction prior to revascularization and quickly became standard-of-care. These agents are now thought to be a cause of failure of recent clinical trials since these pleiotropic drugs also happen to be potent postconditioning mimetics. Thus, introduction of an additional cardioprotective strategy such as ischemic postconditioning which uses the same signaling pathway as these P2Y 12 antagonists would be redundant and doomed to failure. Additive cardioprotection could be achieved only if the second intervention had a different mechanism of cardioprotection. This concept has been demonstrated in experimental animals. So lack of reproducibility of earlier studies and failure to examine interventions in experimental animals also treated with anti-platelet agents could well explain past failures. These realizations should clear the way for development of interventions which can be translated into successful clinical treatments.

Seasonality of Hepatitis: A Review Update

PubMed Central

Fares, Auda

2015-01-01

Background: Viral hepatitis is an infection that has been reported to be present throughout the year, but some particular months are associated with higher incidences. The primary objective was to review and report on the current knowledge and evidence that existed on seasonality of different type of acute viral hepatitis worldwide in order to develop recommendations for future research, prevention and control. Materials and Methods: A systematic literature review was performed to identify all the primary reports and studies published during 1970-2013 on acute hepatitis A, B, C and E (AHA, AHB, AHC and AHE) in human subjects by searching PubMed, reference lists of major articles and correspondence with scientific experts. For each report or study included, the following information was extracted (as applicable to study): Location (country and setting), study population (number of cases, patients), seasonal or monthly rate and study duration. Results: There is no definite and consistent seasonal pattern has been observed on AHA; AHB; AHE and AHC, although evidence points towards spring and summer peak for hepatitis A, B, C and E. Multiple source of transmission such as; summer travel to an endemic area, swimming habits of the population in hot months, increase sexual contact, tattoo, poor hygiene and environmental sanitation and food habits (feco-oral transmission of viral hepatitis) probably exists and should be further investigated through analytical and epidemiological. PMID:25810997

Standardized surgical techniques for adult living donor liver transplantation using a modified right lobe graft: a video presentation from bench to reperfusion.

PubMed

Hwang, Shin; Ha, Tae-Yong; Ahn, Chul-Soo; Moon, Deok-Bog; Kim, Ki-Hun; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

2016-08-01

After having experienced more than 2,000 cases of adult living donor liver transplantation (LDLT), we established the concepts of right liver graft standardization. Right liver graft standardization intends to provide hemodynamics-based and regeneration-compliant reconstruction of vascular inflow and outflow. Right liver graft standardization consists of the following components: Right hepatic vein reconstruction includes a combination of caudal-side deep incision and patch venoplasty of the graft right hepatic vein to remove the acute angle between the graft right hepatic vein and the inferior vena cava; middle hepatic vein reconstruction includes interposition of a uniform-shaped conduit with large-sized homologous or prosthetic grafts; if the inferior right hepatic vein is present, its reconstruction includes funneling and unification venoplasty for multiple short hepatic veins; if donor portal vein anomaly is present, its reconstruction includes conjoined unification venoplasty for two or more portal vein orifices. This video clip that shows the surgical technique from bench to reperfusion was a case presentation of adult LDLT using a modified right liver graft from the patient's son. Our intention behind proposing the concept of right liver graft standardization is that it can be universally applicable and may guarantee nearly the same outcomes regardless of the surgeon's experience. We believe that this reconstruction model would be primarily applied to a majority of adult LDLT cases.

Analysis of disease-associated protein expression using quantitative proteomics—fibulin-5 is expressed in association with hepatic fibrosis.

PubMed

Bracht, Thilo; Schweinsberg, Vincent; Trippler, Martin; Kohl, Michael; Ahrens, Maike; Padden, Juliet; Naboulsi, Wael; Barkovits, Katalin; Megger, Dominik A; Eisenacher, Martin; Borchers, Christoph H; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

2015-05-01

Hepatic fibrosis and cirrhosis are major health problems worldwide. Until now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. To develop noninvasive diagnostic assays for the assessment of liver fibrosis, it is urgently necessary to identify molecules that are robustly expressed in association with the disease. We analyzed biopsied tissue samples from 95 patients with HBV/HCV-associated hepatic fibrosis using three different quantification methods. We performed a label-free proteomics discovery study to identify novel disease-associated proteins using a subset of the cohort (n = 27). Subsequently, gene expression data from all available clinical samples were analyzed (n = 77). Finally, we performed a targeted proteomics approach, multiple reaction monitoring (MRM), to verify the disease-associated expression in samples independent from the discovery approach (n = 68). We identified fibulin-5 (FBLN5) as a novel protein expressed in relation to hepatic fibrosis. Furthermore, we confirmed the altered expression of microfibril-associated glycoprotein 4 (MFAP4), lumican (LUM), and collagen alpha-1(XIV) chain (COL14A1) in association to hepatic fibrosis. To our knowledge, no tissue-based quantitative proteomics study for hepatic fibrosis has been performed using a cohort of comparable size. By this means, we add substantial evidence for the disease-related expression of the proteins examined in this study.

Epidemiological and genetic analysis of a 2014 outbreak of hepatitis A in Japan.

PubMed

Ishii, Koji; Kiyohara, Tomoko; Yoshizaki, Sayaka; Kawabata, Kunio; Kanayama, Atsuhiro; Yahata, Yuichiro; Takahashi, Takuri; Kinoshita, Hitomi; Saitou, Takehito; Sunagawa, Tomimasa; Oishi, Kazunori; Uema, Masashi; Noda, Mamoru; Wakita, Takaji

2015-11-09

Hepatitis A virus (HAV) is one of the most common causes of feces-transmitted acute hepatitis worldwide. In Japan, most of HAV infections have been sporadic cases and a relatively low number of cases (approximately 100-150) of acute hepatitis A were reported in 2012 and 2013. However, in 2014, 342 cases were reported as of week 22. In order to characterize the viral agents causing this outbreak, we collected stool or sera (and both for three case) from patients with hepatitis A from many regions throughout Japan and performed genotyping of the VP1/P2A regions of HAV. We then used a multiple-alignment algorithm to compare the nucleotide sequences with those of reference strains. Phylogenetic tree analyses revealed that the 159 HAV isolates were divided into three subgenotypes: IA (137 cases), IB (4 cases), and IIIA (18 cases). The most unique feature of this outbreak was that for most subgenotype IA cases (103 out of 137 IA cases) the sequences analyzed shared 100% homology. Interestingly, the peak week for these IA infections was almost the same nationwide, suggesting that the epidemic of hepatitis A caused by this subgenotype IA strain may have expanded from a single source possibly because of one food-borne or waterborne source that was distributed nationwide at once. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sonographic findings of hepatobiliary fascioliasis accompanied by extrahepatic expansion and ectopic lesions.

PubMed

Teke, Memik; Önder, Hakan; Çiçek, Mutalip; Hamidi, Cihad; Göya, Cemil; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Ülger, Burak Veli

2014-12-01

The aim of the study was to describe the sonographic findings of hepatobiliary fascioliasis with extrahepatic expansion and ectopic lesions. The study included 45 patients with fascioliasis. All diagnoses were confirmed via serologic enzyme-linked immunosorbent assays. Sonographic findings in the hepatobiliary system, extrahepatic expansion, and ectopic lesions were defined. The most common hepatic lesions were subcapsular localized, small, confluent, multiple hypoechoic nodules with poorly defined borders. We also detected ectopic lesion in 5 patients (11.1%) and live parasites in the gallbladder and bile duct in 11 (24.4%). The large spectrum of entities in the differential diagnosis of hepatobiliary fascioliasis may lead to misdiagnosis and incorrect treatment. However, the diagnosis can be made when the characteristic sonographic features are seen, such as heterogeneity of the liver with multiple poorly defined hypoechoic-isoechoic lesions and multiple echogenic nonshadowing particles in the gallbladder or common bile ducts. Nonetheless, the differential diagnosis of fascioliasis versus other hepatic lesions may still be difficult. In these situations, pathologic confirmation should be performed to exclude the possibility of malignancy. © 2013 by the American Institute of Ultrasound in Medicine.

Construction, expression, purification and biotin labeling of a single recombinant multi-epitope antigen for double-antigen sandwich ELISA to detect hepatitis C virus antibody.

PubMed

He, Jing; Xiu, Bingshui; Wang, Guohua; Chen, Kun; Feng, Xiaoyan; Song, Xiaoguo; Zhu, Cuixia; Yang, Xiqin; Bai, Guanzhong; Ling, Shigan; Zhang, Heqiu

2011-08-01

Based on B cell epitope predictions, a recombinant antigen with multiple epitopes from four Hepatitis C Virus fragments (C, NS3, NS4 and NS5) were engineered. The recombinant gene was then highly expressed in E. coli. The non-modified and C-terminal-modified recombinant proteins were used for coating and biotin labeling, respectively, to establish the double-antigen sandwich ELISA. Ten positive reference samples confirmed by the CHIRON RIBA HCV 3.0 SIA kit were detected positive, Forty one plasma samples were positive among samples from 441 volunteers, which indicated that the recombinant antigen could readily react well with plasma HCV antibody. As critical reagents of double-antigen sandwich ELISA, the recombinant multi-epitope antigen and the C-terminal-modified and biotin-conjugated antigen show good antigenicity. In this study, we provide a simple approach to produce multiple epitopes within one recombinant protein in order to avoid the costly expression of less-effective pools of multiple proteins, which is the conventional strategy of diagnostic antigen production for HCV antibody detection.

Application of the HeartLander Crawling Robot for Injection of a Thermally Sensitive Anti-Remodeling Agent for Myocardial Infarction Therapy

PubMed Central

Chapman, Michael P.; López González, Jose L.; Goyette, Brina E.; Fujimoto, Kazuro L.; Ma, Zuwei; Wagner, William R.; Zenati, Marco A.; Riviere, Cameron N.

2011-01-01

The injection of a mechanical bulking agent into the left ventricular (LV) wall of the heart has shown promise as a therapy for maladaptive remodeling of the myocardium after myocardial infarct (MI). The HeartLander robotic crawler presented itself as an ideal vehicle for minimally-invasive, highly accurate epicardial injection of such an agent. Use of the optimal bulking agent, a thermosetting hydrogel developed by our group, presents a number of engineering obstacles, including cooling of the miniaturized injection system while the robot is navigating in the warm environment of a living patient. We present herein a demonstration of an integrated miniature cooling and injection system in the HeartLander crawling robot, that is fully biocompatible and capable of multiple injections of a thermosetting hydrogel into dense animal tissue while the entire system is immersed in a 37°C water bath. PMID:21096276

Management of Neurologic Manifestations in Patients with Liver Disease.

PubMed

Ferro, José M; Viana, Pedro; Santos, Patrícia

2016-08-01

Liver disease, both in its acute and chronic forms, can be associated with a wide spectrum of neurologic manifestations, both central and peripheral, ranging in severity from subclinical changes to neurocritical conditions. Neurologists are frequently consulted to participate in their management. In this review, we present an overview of management strategies for patients with hepatic disease whose clinical course is complicated by neurologic manifestations. Type A hepatic encephalopathy (HE), which occurs in acute liver failure, is a neurologic emergency, and multiple measures should be taken to prevent and treat cerebral edema. In Type C HE, which occurs in chronic liver disease, management should be aimed at correcting precipitant factors and hyperammonemia. There is an increasing spectrum of drug treatments available to minimize ammonia toxicity. Acquired hepatocerebral degeneration is a rare complication of the chronic form of HE, with typical clinical and brain MRI findings, whose most effective treatment is liver transplantation. Epilepsy is frequent and of multifactorial cause in patients with hepatic disease, and careful considerations should be made regarding choice of the appropriate anti-epileptic drugs. Several mechanisms increase the risk of stroke in hepatic disease, but many of the drugs used to treat and prevent stroke are contraindicated in severe hepatic failure. Hepatitis C infection increases the risk of ischemic stroke. Hemorrhagic stroke is more frequent in patients with liver disease of alcoholic etiology. Viral hepatitis is associated with a wide range of immune-mediated complications, mostly in the peripheral nervous system, which respond to different types of immunomodulatory treatment. Several drugs used to treat hepatic disease, such as the classical and the new direct-acting antivirals, may have neurologic complications which in some cases preclude its continued use.

Clinical Features and Transmission Pattern of Hepatitis A: An Experience from a Hepatitis A Outbreak Caused by Two Cocirculating Genotypes in Sri Lanka.

PubMed

Dahanayaka, Niroshana J; Kiyohara, Tomoko; Agampodi, Suneth B; Samaraweera, Pradeep K; Kulasooriya, Gayani K; Ranasinghe, Jagath C; Semage, Saveen N; Yoshizaki, Sayaka; Wakita, Takaji; Ishii, Koji

2016-10-05

Sri Lanka is one of the intermediate-endemic areas for hepatitis A virus (HAV), and concerns exist about the increasing HAV-susceptible population. In fact, Sri Lanka recorded a large hepatitis outbreak, possibly hepatitis A, around the end of the Sri Lankan war. It included more than 14,000 patients consisting of local residents, internally displaced personnel, and military personnel in the main combat zone. The outbreak had slowed down by October 2009; however, acute viral hepatitis continued to occur sequentially among military personnel. We obtained clinical information and serum samples from 222 patients with acute hepatitis who visited the Military Hospital Anuradhapura between January and September 2010. Samples were subjected to laboratory testing including HAV-immunoglobulin M and genotyping. Most patients (98.2%) were confirmed as having hepatitis A belonging to two subgenotypes: IA and IIIA. We did not observe any differences in clinical or biochemical features among patients with subgenotypes IA and IIIA except for pale stools and upper abdominal discomfort. During the investigation period, we observed a serial outbreak caused by identical HAV strains with an interval in line with that of typical HAV incubation periods. Most patients in the first outbreak were found in the training center, and patients in the second outbreak were found in multiple places where soldiers were assigned after the training center. These findings indicate that a strain of HAV diffused from one place to another along with movement of infected persons among the HAV-susceptible population. HAV vaccination for high-risk groups, such as young soldiers, is necessary. © The American Society of Tropical Medicine and Hygiene.

Clinical Features and Transmission Pattern of Hepatitis A: An Experience from a Hepatitis A Outbreak Caused by Two Cocirculating Genotypes in Sri Lanka

PubMed Central

Dahanayaka, Niroshana J.; Kiyohara, Tomoko; Agampodi, Suneth B.; Samaraweera, Pradeep K.; Kulasooriya, Gayani K.; Ranasinghe, Jagath C.; Semage, Saveen N.; Yoshizaki, Sayaka; Wakita, Takaji; Ishii, Koji

2016-01-01

Sri Lanka is one of the intermediate-endemic areas for hepatitis A virus (HAV), and concerns exist about the increasing HAV-susceptible population. In fact, Sri Lanka recorded a large hepatitis outbreak, possibly hepatitis A, around the end of the Sri Lankan war. It included more than 14,000 patients consisting of local residents, internally displaced personnel, and military personnel in the main combat zone. The outbreak had slowed down by October 2009; however, acute viral hepatitis continued to occur sequentially among military personnel. We obtained clinical information and serum samples from 222 patients with acute hepatitis who visited the Military Hospital Anuradhapura between January and September 2010. Samples were subjected to laboratory testing including HAV-immunoglobulin M and genotyping. Most patients (98.2%) were confirmed as having hepatitis A belonging to two subgenotypes: IA and IIIA. We did not observe any differences in clinical or biochemical features among patients with subgenotypes IA and IIIA except for pale stools and upper abdominal discomfort. During the investigation period, we observed a serial outbreak caused by identical HAV strains with an interval in line with that of typical HAV incubation periods. Most patients in the first outbreak were found in the training center, and patients in the second outbreak were found in multiple places where soldiers were assigned after the training center. These findings indicate that a strain of HAV diffused from one place to another along with movement of infected persons among the HAV-susceptible population. HAV vaccination for high-risk groups, such as young soldiers, is necessary. PMID:27382079

The Role of Bioactive Lipids in Stem Cell Mobilization and Homing: Novel Therapeutics for Myocardial Ischemia

PubMed Central

Klyachkin, Yuri M.; Karapetyan, Anush V.; Ratajczak, Mariusz Z.; Abdel-Latif, Ahmed

2014-01-01

Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI) and ischemic heart disease (IHD) remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM)-derived stem/progenitor cells (SPCs). This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and homing to a highly proteolytic microenvironment, such as the ischemic/infarcted myocardium, is currently being challenged. Recent evidence suggests a pivotal role for bioactive lipids in the mobilization of BMSPCs at the early stages following AMI and their homing towards ischemic myocardium. This review highlights the recent advances in our understanding of the mechanisms of stem cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC mobilization and differentiation, and discusses their potential as therapeutic agents in the treatment of IHD. PMID:24672794

A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β

PubMed Central

Arima, Masaru; Iwata, Youhei; Morita, Yusuke; Kobayashi, Tsukane; Sasaki, Ryousuke; Suzuki, Kayoko; Matsunaga, Kayoko

2014-01-01

A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion. PMID:24707255

Relationship of Early Spontaneous Type V Blood Pressure Fluctuation after Thrombolysis in Acute Cerebral Infarction Patients and the Prognosis

PubMed Central

Zuo, Lian; Wan, Ting; Xu, Xiahong; Liu, Feifeng; Li, Changsong; Li, Ying; Zhang, Yue; Zhang, Jing; Bao, Huan; Li, Gang

2016-01-01

We examined the relationship between an early spontaneous type V blood pressure fluctuation and the post-thrombolysis prognosis of patients with acute cerebral infarction. Patients were admitted consecutively. All patients were categorized into the type V blood pressure fluctuation group or non-type V blood pressure group. Their blood pressure was monitored before thrombolysis and until 6 h after thrombolysis. Baseline data and clinical outcomes were compared. Of 170 patients, 43 (25.2%) had an early type V blood pressure fluctuation. The National Institute of Health Stroke Scale (NIHSS) score before thrombolysis and 24 h after thrombolysis, and the modified Rankin scale score at 90 days differed significantly between the two groups (P < 0.05). Multiple logistic regression analysis showed that an unfavorable prognosis at 3 months was associated with the NIHSS score before thrombolysis (P = 0.000) but probably not with this blood pressure fluctuation (P = 0.058). An early spontaneous type V blood pressure fluctuation is common in patients with acute cerebral infarction who received venous thrombolysis, especially if they have a higher NIHSS score before thrombolysis. The type V blood pressure fluctuation may not influence patients’ prognosis; however, this needs to be confirmed in future trials. PMID:27278121

A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β.

PubMed

Arima, Masaru; Iwata, Youhei; Morita, Yusuke; Kobayashi, Tsukane; Sasaki, Ryousuke; Suzuki, Kayoko; Matsunaga, Kayoko

2014-01-01

A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion.

Comparative Testing of Hemostatic Dressing in a Large Animal Model (Sus Scorofa) with Severe hepatic Injuries

DTIC Science & Technology

2013-12-02

applicable terms in EACH column) ___ Training: Live Animal ___ Medical Readiness ___ Prolonged Restraint ___ Training: non-Live Animal ... Health Promotion ___ Multiple Survival Surgery ___ Research: Survival (chronic) ___ Prevention ___ Behavioral Study _X__ Research

T-cell count

MedlinePlus

... or multiple myeloma Infections, such as hepatitis or mononucleosis Lower than normal T-cell levels may be due to: Acute viral infections Aging Cancer Immune system diseases, such as HIV/AIDS Radiation therapy Steroid treatment Risks Risks associated with having blood ...

Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study).

PubMed

Sigurdsson, Sigurdur; Aspelund, Thor; Kjartansson, Olafur; Gudmundsson, Elias F; Jonsdottir, Maria K; Eiriksdottir, Gudny; Jonsson, Palmi V; van Buchem, Mark A; Gudnason, Vilmundur; Launer, Lenore J

2017-09-01

The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3-2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9-3.4). Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels. © 2017 American Heart Association, Inc.

Computed tomography and magnetic resonance imaging of multiple focal nodular hyperplasias of the liver with congenital absence of the portal vein in a Chinese girl: case report and review of the literature.

PubMed

Zhang, Kun; Wang, Qingjun; Wang, Haiyi; Ye, Huiyi; Guo, Aitao; Duan, Weidong

2014-11-26

Patients with congenital absence of the portal vein (CAPV) often suffer from additional medical complications such as hepatic tumors and cardiac malformations. Congenital absence of the portal vein (CAPV) is a rare malformation. We present a case of a 16-year-old Chinese girl with CAPV with multiple pathology-proven hepatic focal nodular hyperplasias (FNHs) and ventricular septal defect (VSD). The CT and MRI features of this case are described, and previously reported cases are reviewed. CAPV is a rare congenital anomaly and in such patients, clarifying the site of portosystemic shunts, liver disease, and other anomalies is critical for appropriate treatment selection and accurate prognosis determination. Close follow-up, including laboratory testing and radiologic imaging, is recommended for all CAPV patients.

Specificity, cross-talk and adaptation in Interferon signaling

NASA Astrophysics Data System (ADS)

Zilman, Anton

Innate immune system is the first line of defense of higher organisms against pathogens. It coordinates the behavior of millions of cells of multiple types, achieved through numerous signaling molecules. This talk focuses on the signaling specificity of a major class of signaling molecules - Type I Interferons - which are also used therapeutically in the treatment of a number of diseases, such as Hepatitis C, multiple sclerosis and some cancers. Puzzlingly, different Interferons act through the same cell surface receptor but have different effects on the target cells. They also exhibit a strange pattern of temporal cross-talk resulting in a serious clinical problem - loss of response to Interferon therapy. We combined mathematical modeling with quantitative experiments to develop a quantitative model of specificity and adaptation in the Interferon signaling pathway. The model resolves several outstanding experimental puzzles and directly affects the clinical use of Type I Interferons in treatment of viral hepatitis and other diseases.

Hepatocyte Polarity

PubMed Central

Treyer, Aleksandr; Müsch, Anne

2013-01-01

Hepatocytes, like other epithelia, are situated at the interface between the organism’s exterior and the underlying internal milieu and organize the vectorial exchange of macromolecules between these two spaces. To mediate this function, epithelial cells, including hepatocytes, are polarized with distinct luminal domains that are separated by tight junctions from lateral domains engaged in cell-cell adhesion and from basal domains that interact with the underlying extracellular matrix. Despite these universal principles, hepatocytes distinguish themselves from other nonstriated epithelia by their multipolar organization. Each hepatocyte participates in multiple, narrow lumina, the bile canaliculi, and has multiple basal surfaces that face the endothelial lining. Hepatocytes also differ in the mechanism of luminal protein trafficking from other epithelia studied. They lack polarized protein secretion to the luminal domain and target single-spanning and glycosylphosphatidylinositol-anchored bile canalicular membrane proteins via transcytosis from the basolateral domain. We compare this unique hepatic polarity phenotype with that of the more common columnar epithelial organization and review our current knowledge of the signaling mechanisms and the organization of polarized protein trafficking that govern the establishment and maintenance of hepatic polarity. The serine/threonine kinase LKB1, which is activated by the bile acid taurocholate and, in turn, activates adenosine monophosphate kinase-related kinases including AMPK1/2 and Par1 paralogues has emerged as a key determinant of hepatic polarity. We propose that the absence of a hepatocyte basal lamina and differences in cell-cell adhesion signaling that determine the positioning of tight junctions are two crucial determinants for the distinct hepatic and columnar polarity phenotypes. PMID:23720287

Expression of toll-like receptors in hepatic cirrhosis and hepatocellular carcinoma.

PubMed

Sun, L; Dai, J J; Hu, W F; Wang, J

2016-07-14

Toll-like receptors (TLRs) can specifically identify pathogen-associated molecular patterns (PAMPs) by recognizing structural patterns in diverse microbial molecules, and can provide an effective defense against multiple microbial infectious. A variety of TLRs can be expressed on the surface of liver parenchymal as well as nonparenchymal cells. Kupffer cells are a type of hepatic nonparenchymal macrophage, and are positively associated with the severity of liver fibrosis. They play an important role in the synthesis and deposition of the extracellular matrix by upregulating the expression of tissue inhibitor of metalloproteinases and downregulating the activity of matrix metalloproteinases. Cirrhosis, a chronic diffuse lesion usually accompanying extensive liver fibrosis and nodular regeneration, is caused by liver parenchymal cells repeating injury-repair following reconstruction of organizational structure in the hepatic lobules. Hepatocellular carcinoma is caused by repeated and persistent chronic severe liver injury, and partial hepatocytes can eventually transform into hepatoma cells. Multiple TLRs such as TLR2, TLR3, TLR4, and TLR9, as well as other receptors, can be expressed in cirrhosis and hepatocellular carcinoma. About 53 and 85% of hepatocellular carcinoma patients frequently express TLR3 and TLR9, respectively. The chronic and repeated liver injury caused by alcohol, and HBV, HCV, or other pathogens can be recognized by TLRs through the PAMP pathway, which directly increases the risk for hepatic cirrhosis and hepatocellular carcinoma. In this review, we briefly present evidence that the novel cellular molecular mechanisms of TLRs may provide more information about new therapeutics targets of the anti-inflammatory immune response.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome.

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

Hepatic encephalopathy: An approach to its multiple pathophysiological features

PubMed Central

Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

2012-01-01

Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in order to clarify, at least partially, controversial topics. PMID:22489256

T-cell antigenic determinants within hepatitis C virus nonstructural protein 3 and cytokine production profiles in hepatitis C.

PubMed

Pan, C-H; Yang, P-M; Hwang, L-H; Kao, Shing-F; Chen, P-J; Chiang, B-L; Chen, D-S

2002-07-01

The aim of this study was to further investigate the role of T-helper cells in hepatitis C virus (HCV) infection, focusing on the T-cell antigenic determinants and cytokine profiles of nonstructural 3 (NS3) protein-stimulated peripheral blood mononuclear cells (PBMCs) of HCV patients. A total of 12 recombinant proteins of theNS3 region were purified and used to test T-cell proliferative response and antigenic determinants of HCV-seropositive patients. In addition, cytokines produced by antigen stimulated PBMCs were measured. Our data showed that PBMCs from 55.7% (34/61) of HCV patients proliferated to at least one antigen, but PBMCs of HCV seronegative patients did not. In addition, PBMCs from about 82.0% (32/39) HCV-seropositive patients produced significant amounts of cytokines (10 pg/mL). Interestingly, PBMCs from 66% of patients produced TH2-related cytokines such as interleukin (IL)-4 and IL-5. In mappingexperiments, the data showed multiple T-cell antigenic determinants. Our data demonstrated that NS3 antigen-stimulated PBMCs of HCV patients recognized multiple T-cell antigenic determinants and produced significant amounts of TH0 or TH2-related cytokines, which might play a critical role in the chronicity of HCV infection.

Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1).

PubMed

Fuller, Michael J; Callendret, Benoit; Zhu, Baogong; Freeman, Gordon J; Hasselschwert, Dana L; Satterfield, William; Sharpe, Arlene H; Dustin, Lynn B; Rice, Charles M; Grakoui, Arash; Ahmed, Rafi; Walker, Christopher M

2013-09-10

Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells that express the inhibitory receptor programmed cell death 1 (PD-1). Blockade of PD-1 signaling improves in vitro proliferation of HCV-specific T lymphocytes, but whether antiviral function can be restored in infected individuals is unknown. To address this question, chimpanzees with persistent HCV infection were treated with anti-PD-1 antibodies. A significant reduction in HCV viremia was observed in one of three treated animals without apparent hepatocellular injury. Viremia rebounded in the responder animal when antibody treatment was discontinued. Control of HCV replication was associated with restoration of intrahepatic CD4+ and CD8+ T-cell immunity against multiple HCV proteins. The responder animal had a history of broader T-cell immunity to multiple HCV proteins than the two chimpanzees that did not respond to PD-1 therapy. The results suggest that successful PD-1 blockade likely requires a critical threshold of preexisting virus-specific T cells in liver and warrants consideration of therapeutic vaccination strategies in combination with PD-1 blockade to broaden narrow responses. Anti-PD-1 immunotherapy may also facilitate control of other persistent viruses, notably the hepatitis B virus where options for long-term control of virus replication are limited.

Adverse Outcome Pathway (AOP) Network Development for ...

EPA Pesticide Factsheets

Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk research. According to the Organization for Economic Co-operation and Development guidelines, AOPs are pathways with one MIE anchored to an adverse outcome (AO) by key events (KEs) and key event relationships (KERs). However, this approach does not always capture the cumulative impacts of multiple MIEs on the AO. For example, hepatic lipid flux due to chemical-induced toxicity initiates from multiple ligand-activated receptors and signaling pathways that cascade across biology to converge upon a common fatty liver (FL, also known as steatosis) outcome. To capture this complexity, a top-down strategy was used to develop a FL AOP network (AOPnet). Literature was queried based on the terms steatosis, fatty liver, cirrhosis, and hepatocellular carcinoma. Search results were analyzed for physiological and pathophysiological organ level, cellular and molecular processes, as well as pathway intermediates, to identify potential KEs and MIEs that are key for hepatic lipid metabolism, maintenance, and dysregulation. The analysis identified four apical KE nodes (hepatic fatty acid uptake, de novo fatty acid and lipid synthesis, fatty acid oxidation, and lipid efflux) juxtaposed to the FL AO. The apic

Machine-learning-based classification of real-time tissue elastography for hepatic fibrosis in patients with chronic hepatitis B.

PubMed

Chen, Yang; Luo, Yan; Huang, Wei; Hu, Die; Zheng, Rong-Qin; Cong, Shu-Zhen; Meng, Fan-Kun; Yang, Hong; Lin, Hong-Jun; Sun, Yan; Wang, Xiu-Yan; Wu, Tao; Ren, Jie; Pei, Shu-Fang; Zheng, Ying; He, Yun; Hu, Yu; Yang, Na; Yan, Hongmei

2017-10-01

Hepatic fibrosis is a common middle stage of the pathological processes of chronic liver diseases. Clinical intervention during the early stages of hepatic fibrosis can slow the development of liver cirrhosis and reduce the risk of developing liver cancer. Performing a liver biopsy, the gold standard for viral liver disease management, has drawbacks such as invasiveness and a relatively high sampling error rate. Real-time tissue elastography (RTE), one of the most recently developed technologies, might be promising imaging technology because it is both noninvasive and provides accurate assessments of hepatic fibrosis. However, determining the stage of liver fibrosis from RTE images in a clinic is a challenging task. In this study, in contrast to the previous liver fibrosis index (LFI) method, which predicts the stage of diagnosis using RTE images and multiple regression analysis, we employed four classical classifiers (i.e., Support Vector Machine, Naïve Bayes, Random Forest and K-Nearest Neighbor) to build a decision-support system to improve the hepatitis B stage diagnosis performance. Eleven RTE image features were obtained from 513 subjects who underwent liver biopsies in this multicenter collaborative research. The experimental results showed that the adopted classifiers significantly outperformed the LFI method and that the Random Forest(RF) classifier provided the highest average accuracy among the four machine algorithms. This result suggests that sophisticated machine-learning methods can be powerful tools for evaluating the stage of hepatic fibrosis and show promise for clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic hepatitis B, nonalcoholic steatohepatitis and physical fitness of military males: CHIEF study

PubMed Central

Chen, Yu-Jung; Chen, Kai-Wen; Shih, Yu-Leung; Su, Fang-Ying; Lin, Yen-Po; Meng, Fan-Chun; Lin, Felicia; Yu, Yun-Shun; Han, Chih-Lu; Wang, Chih-Hung; Lin, Jia-Wei; Hsieh, Tsai-Yuan; Li, Yi-Hwei; Lin, Gen-Min

2017-01-01

AIM To investigate the association of chronic hepatitis B and nonalcoholic steatohepatitis with physical fitness in a Taiwanese military male cohort. METHODS We made a cross-sectional examination of this association using 3669 young adult military males according to cardiorespiratory fitness and hospitalization events recorded in the Taiwan Armed Forces study. Cases of chronic hepatitis B (n = 121) were defined by personal history and positive detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis (n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound finding of steatosis, and absence of viral hepatitis A, B or C infection. All other study participants were defined as unaffected (n = 3419). Physical fitness was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups exercises, with all the procedures standardized by a computerized scoring system. Multiple linear regression analysis was used to determine the relationship. RESULTS Chronic hepatitis B negatively correlated with 2-min push-up numbers (β = -2.49, P = 0.019) after adjusting for age, service specialty, body mass index, systolic and diastolic blood pressures, current cigarette smoking, alcohol intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic steatohepatitis was borderline positively correlated with 3000-m running time (β = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers (β = -1.47, P = 0.040). CONCLUSION Chronic hepatitis B viral infection and nonalcoholic steatohepatitis affects different physical performances in young adult military males, and future study should determine the underlying mechanism. PMID:28740347

Severity of CIND and MCI predict incidence of dementia in an ischemic stroke cohort

PubMed Central

Narasimhalu, K; Ang, S; De Silva, D A.; Wong, M -C.; Chang, H -M.; Chia, K -S.; Auchus, A P.; Chen, C

2009-01-01

Background: The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population. Methods: A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia. Results: A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7. Conclusion: Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia. GLOSSARY AD = Alzheimer disease; AUC = area under the curve; CI = confidence interval; CIND = cognitive impairment no dementia; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; ESPRIT = European Australasian Stroke Prevention in Reversible Ischemia Trial; ESPRIT-Cog = European Australasian Stroke Prevention in Reversible Ischemia Trial, cognitive substudy; HR = hazard ratio; LACI = lacunar infarct; MCI = mild cognitive impairment; mRS = modified Rankin scale; NCI = no cognitive impairment; OCSP = Oxfordshire Community Stroke Project; PACI = partial anterior circulation infarct; POCI = posterior circulation infarct; ROC = receiver operating curve; TACI = total anterior circulation infarct; VaD = vascular dementia; WAIS-R = Wechsler Adult Intelligence Scale–Revised; WMS-R = Wechsler Memory Scale–Revised. PMID:19949033

Right ventricular myocardial infarction: presentation and acute outcomes.

PubMed

Chockalingam, Anand; Gnanavelu, G; Subramaniam, T; Dorairajan, Smrita; Chockalingam, V

2005-01-01

Acute inferior wall myocardial infarction can be complicated by right ventricular myocardial infarction (RVMI), and the excess mortality cannot be fully explained by mechanical reasons. The authors try to systematically assess the incidence, clinical presentation and early outcomes of right ventricular infarction in a tertiary-care setup. Their study was a prospective observational series of consecutive patients with RVMI. All patients with acute inferior myocardial infarction (n=135) were enlisted. RVMI was diagnosed by > or = 1 mm ST elevation in lead V(4R) in a right-sided electrocardiogram. Right ventricular (RV) infarction occurred in 37% (n=50) of patients with acute inferior infarctions. Patients with isolated inferior infarction served as controls (n=85). Echocardiography was performed within 24 hours of admission. From both groups, 66% qualified for thrombolysis. The incidence of hypotension-bradycardia and heart blocks requiring pacing support was much higher in right ventricular infarction (n=21) than in inferior infarction (n=13). Clinically manifest RV dysfunction (raised jugular venous pulse [JVP], hypotension, tricuspid regurgitation) and right ventricular dilation detected by echocardiography were seen in only 13 patients. The in-hospital mortality rate was significantly higher (n=8, 16%) in right ventricular infarction group than in inferior infarction group (n=3, 3.5%). Right ventricular infarction was seen in a third of inferior myocardial infarctions (IMIs), but hemodynamically evident right ventricular dysfunction occurred in only a tenth of acute IMIs. Nevertheless, the acute in-hospital mortality rate of patients with right ventricular infarction was much higher than in those with inferior infarction owing to arrhythmic and mechanical complications.

A pilot study on the correlation of tongue manifestation with the site of cerebral infarction in patients with stroke.

PubMed

Liu, Ping; Gao, Li; Song, Jue-Xian; Zhao, Hai-Ping; Wu, Xiao-Guang; Xu, Chang-Min; Huang, Li-Yuan; Wang, Ping-Ping; Luo, Yu-Min

2014-11-01

To discuss the correlation of tongue manifestation with the site of cerebral infarction in patients with acute cerebral infarction. From March 2008 to February 2009, 200 cases of hospitalized patients with first unilateral cerebral infarction were chosen in the Department of Neurology, Xuanwu Hospital. The correlation of different tongue color, fur texture, fur color with the site of cerebral infarction was analyzed. The site of cerebral infarction in patients were compared between different tongue color by Chisquare test (P=0.314), and further correspondence analysis demonstrated that there was correlation between red tongue and cortical-subcortical infarction group. The site of cerebral infarction in patients were compared between thick fur group and thin fur group, cortical-subcortical infarction occurred more frequently in the former (P=0.0008). The site of cerebral infarction in patients were compared between dry fur group, moist fur group and smooth fur group, correspondence analysis demonstrated there was correlation between dry fur and cortical-subcortical group. The site of cerebral infarction in the patients were compared between white fur group, white-yellow fur group and yellow fur group (P=0.010), and correspondence analysis demonstrated there was correlation between white fur and brainstem infarction; white-yellow fur has relationship with cortical infarction; subcortical infarction was weakly related with white-yellow fur; there was closer relationship between yellow fur and cortical-subcortical infarction. The change of tongue manifestation was associated with the site of cerebral infarction in patients, providing a new combining site for diagnosing cerebrovascular diseases by integrative medicine.

Clonazepam-associated Bradycardia in a Disabled Elderly Woman with Multiple Complications

PubMed Central

Maruyoshi, Hidetomo; Maruyoshi, Natsue; Hirosue, Motone; Ikeda, Komei; Shimamoto, Masaaki

2017-01-01

We herein report an 87-year-old woman who was taking clonazepam at 1.5 mg/day. She was hospitalized with an old cerebral infarction complicated with symptomatic epilepsy, dementia, dyslipidemia, and chronic cholecystitis. Electrocardiogram revealed severe bradycardia at 31 beats/min. The bradycardia disappeared on day 3 after clonazepam withdrawal, although the serum clonazepam level had been within normal limits. She was diagnosed with clonazepam-associated bradycardia, which was likely related to the potential calcium channel-blocking properties of clonazepam. Because of age-related pharmacokinetic and pharmacodynamic changes, the adverse effects of clonazepam should be considered, especially in disabled elderly individuals with multiple comorbidities. PMID:28794360

Clonazepam-associated Bradycardia in a Disabled Elderly Woman with Multiple Complications.

PubMed

Maruyoshi, Hidetomo; Maruyoshi, Natsue; Hirosue, Motone; Ikeda, Komei; Shimamoto, Masaaki

2017-09-01

We herein report an 87-year-old woman who was taking clonazepam at 1.5 mg/day. She was hospitalized with an old cerebral infarction complicated with symptomatic epilepsy, dementia, dyslipidemia, and chronic cholecystitis. Electrocardiogram revealed severe bradycardia at 31 beats/min. The bradycardia disappeared on day 3 after clonazepam withdrawal, although the serum clonazepam level had been within normal limits. She was diagnosed with clonazepam-associated bradycardia, which was likely related to the potential calcium channel-blocking properties of clonazepam. Because of age-related pharmacokinetic and pharmacodynamic changes, the adverse effects of clonazepam should be considered, especially in disabled elderly individuals with multiple comorbidities.

ADULT WITH CHICKENPOX COMPLICATED BY SYSTEMIC VASCULITIS AND BILATERAL RETINAL VASCULITIS WITH RETINAL VASCULAR OCCLUSIONS.

PubMed

Murdock, Jennifer; Carvounis, Petros E

2017-01-01

To describe an adult with chickenpox resulting in systemic vasculitis and bilateral retinal vascular occlusions. Single case report. A 58-year-old man with chickenpox complicated by disseminated varicella-zoster systemic and retinal vasculitis resulting in a combined arterial and venous occlusion in one eye with multiple branch retinal vein occlusions in the other eye. There was no evidence of retinitis. The patient systemically improved after treatment with acyclovir and steroids; however, his vision remained poor. Chickenpox can be associated with systemic vasculopathy and may rarely result in multiple systemic and ocular infarcts, including severe retinal vascular occlusions.

[A case of fat embolism syndrome associated with pathological femoral fracture caused by metastatic adenocarcinoma of the lung].

PubMed

Sato, Takashi; Soejima, Kenzo; Nakayama, Sohei; Satomi, Ryosuke; Sayama, Koichi; Asano, Koichiro

2010-10-01

A 76-year-old woman with multiple bone metastases from lung adenocarcinoma was admitted due to a pathological femoral fracture. On the night after admission, her consciousness deteriorated rapidly and she developed progressive respiratory failure. Computed tomography of the chest revealed diffuse ground glass opacities in both lungs, and magnetic resonance imaging of the brain showed multiple acute infarctions. Her condition improved after several days of supportive treatment with oxygen, corticosteroids and diuretics. Fat embolism syndrome should be considered as a differential diagnosis if consciousness disturbance and respiratory failure occur in patients with metastatic bone carcinoma and pathological long bone fractures.

The Effect of Tobacco Control Measures during a Period of Rising Cardiovascular Disease Risk in India: A Mathematical Model of Myocardial Infarction and Stroke

PubMed Central

Basu, Sanjay; Glantz, Stanton; Bitton, Asaf; Millett, Christopher

2013-01-01

Background We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade. Methods and Findings A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban) for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%–34%) if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent with further health system improvements. Conclusions Smoke-free laws and substantially increased tobacco taxation appear to be markedly potent population measures to avert future cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular disease risk factors like hyperlipidemia and hypertension in low- and middle-income countries, tobacco control is likely to remain a highly effective strategy to reduce cardiovascular deaths. Please see later in the article for the Editors' Summary PMID:23874160

Polymorphisms in IRG1 gene associated with immune responses to hepatitis B vaccination in a Chinese Han population and function to restrain the HBV life cycle.

PubMed

Liu, Xing; Zhang, Li; Wu, Xiao-Pan; Zhu, Xi-Lin; Pan, Li-Ping; Li, Tao; Yan, Bing-Yu; Xu, Ai-Qiang; Li, Hui; Liu, Ying

2017-07-01

Vaccination against the hepatitis B virus (HBV) is extensively used as an effective method to prevent HBV infection. However, nearly 10% of healthy adults fail to produce a protective level of antibodies against the hepatitis B vaccine, and multiple genetic variants are known to affect the immune response to the hepatitis B vaccine. The aim of the present study was to investigate the association between polymorphisms in immunoresponsive gene 1 (IRG1) gene and the immune response to hepatitis B vaccination in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) located in the IRG1 gene were genotyped in 1230 high-responders and 451 non-responders to hepatitis B vaccination. The SNPs rs17470171 and rs17385627 were associated with the immune response to hepatitis B vaccination (P = 0.014 and 0.029, respectively). In addition, the haplotypes G-A-A-A (rs614171-rs17470171-rs9530614-rs17385627, P = 0.0042, OR = 0.68) and A-A (rs17470171-rs17385627, P = 0.0065, OR = 0.72) exerted a protective role in the immune response to hepatitis B vaccination. Allele 'A' of rs17470171 and allele 'A' of rs17385627 show higher levels of expression for the IRG1 gene compared with allele 'C' of rs17470171 and allele 'T' of rs17385627 as demonstrated by luciferase reporter and overexpression assays. In addition, we observed that IRG1 inhibited the HBV life cycle and that IRG1 rs17385627 allele 'A' was more effective than rs17385627 allele 'T' at eliminating HBV in HepG2.2.15 cells. These findings suggest that polymorphisms in the IRG1 gene are associated with the immune response to hepatitis B vaccination. The antiviral effect of IRG1 was confirmed using HBV infection cell models. © 2017 Wiley Periodicals, Inc.

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction.

PubMed

van Zutphen, Tim; Ciapaite, Jolita; Bloks, Vincent W; Ackereley, Cameron; Gerding, Albert; Jurdzinski, Angelika; de Moraes, Roberta Allgayer; Zhang, Ling; Wolters, Justina C; Bischoff, Rainer; Wanders, Ronald J; Houten, Sander M; Bronte-Tinkew, Dana; Shatseva, Tatiana; Lewis, Gary F; Groen, Albert K; Reijngoud, Dirk-Jan; Bakker, Barbara M; Jonker, Johan W; Kim, Peter K; Bandsma, Robert H J

2016-12-01

Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. Peroxisomes and mitochondria play key roles in various hepatic metabolic functions including lipid metabolism and energy production. To investigate the involvement of these organelles in the mechanisms underlying malnutrition-induced hepatic dysfunction we developed a rat model of malnutrition. Weanling rats were placed on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Peroxisomal and mitochondrial structural features were characterized using immunofluorescence and electron microscopy. Mitochondrial function was assessed using high-resolution respirometry. A novel targeted quantitative proteomics method was applied to analyze 47 mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle and fatty acid β-oxidation pathways. Low protein diet-fed rats developed hypoalbuminemia and hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated peroxisomal dysfunction. This was followed by changes in mitochondrial ultrastructure and increased mitochondrial content. Mitochondrial function was impaired due to multiple defects affecting respiratory chain complex I and IV, pyruvate uptake and several β-oxidation enzymes, leading to strongly reduced hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial β-oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. Malnutrition leads to severe impairments in hepatic peroxisomal and mitochondrial function, and hepatic metabolic dysfunction. We discuss the potential future implications of our findings for the clinical management of malnourished children. Severe malnutrition in children is associated with metabolic disturbances that are poorly understood. In order to study this further, we developed a malnutrition animal model and found that severe malnutrition leads to an impaired function of liver mitochondria which are essential for energy production and a loss of peroxisomes, which are important for normal liver metabolic function. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hepatic trauma management in polytraumatised patients.

PubMed

Pop, P Axentii; Pop, M; Iovan, C; Boancã, C

2012-01-01

The specialty literature of the last decade presents the nonoperative management of the closed abdominal trauma as the treatment of choice. The purpose of this study is to highlight the importance of the optimal management of hepatic lesions considering the clinical, paraclinical and therapeutic approach. Our study is based on the analysis of the clinical and paraclinical data and also on the evaluation of the treatment results in 1671 patients with abdominal trauma affecting multiple organs who were treated at the Clinic of Surgery, County Hospital of Oradea from 2008 to 2011. The non-operative approach of the hepatic trauma, applied in 52% of the patients, was indicated in stable hemodynamic status, non-bleeding hepatic lesions on the abdominal CT, and the absence of other significant abdominal lesions. The remaining 48% were treated surgically. The postoperative evolution was free of complications in 72% of the patients while the rest of 28% presented one or more postoperative complications. CT = Computer Tomography; ISS= Injury Severity Score; AIS = Abbreviated Index of Severity; AAST = American Association for the Surgery of Trauma; ARDS = Adult Respiratory Distress Syndrome. RevistaChirurgia.

A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region.

PubMed

Png, Eileen; Thalamuthu, Anbupalam; Ong, Rick T H; Snippe, Harm; Boland, Greet J; Seielstad, Mark

2011-10-01

We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363; P= 6.53 × 10(-22); odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35-1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P= 2.91 × 10(-12); OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 × 10(-17); OR = 2.05, CI = 1.64-2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.

Hepatic Steatosis as a Marker of Metabolic Dysfunction

PubMed Central

Fabbrini, Elisa; Magkos, Faidon

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the complex metabolic derangements associated with obesity. NAFLD is characterized by excessive deposition of fat in the liver (steatosis) and develops when hepatic fatty acid availability from plasma and de novo synthesis exceeds hepatic fatty acid disposal by oxidation and triglyceride export. Hepatic steatosis is therefore the biochemical result of an imbalance between complex pathways of lipid metabolism, and is associated with an array of adverse changes in glucose, fatty acid, and lipoprotein metabolism across all tissues of the body. Intrahepatic triglyceride (IHTG) content is therefore a very good marker (and in some cases may be the cause) of the presence and the degree of multiple-organ metabolic dysfunction. These metabolic abnormalities are likely responsible for many cardiometabolic risk factors associated with NAFLD, such as insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Understanding the factors involved in the pathogenesis and pathophysiology of NAFLD will lead to a better understanding of the mechanisms responsible for the metabolic complications of obesity, and hopefully to the discovery of novel effective treatments for their reversal. PMID:26102213

Apoptosis induction in duck tissues during duck hepatitis A virus type 1 infection.

PubMed

Sheng, X D; Zhang, W P; Zhang, Q R; Gu, C Q; Hu, X Y; Cheng, G F

2014-03-01

To investigate the role of apoptosis in duck viral hepatitis pathogenesis, 4- and 21-d-old ducks were inoculated with duck hepatitis A virus serotype 1 and killed at 2, 6, 12, 24, and 48 h postinfection. TdT-mediated dUTP nick-end labeling was used to detect apoptosis cells. Expression profiles of apoptosis-related genes including caspase-3, -8, -9, and Bcl-2 in spleen, bursa of Fabricius, liver, and the quantity of virus in blood were examined using real-time PCR. The TdT-mediated dUTP nick-end labeling analysis indicated there was a significant difference of apoptotic cells between treatments and controls. The same difference also appeared in virus amount variation in blood during infection. Gene expression analysis revealed that the apoptosis-related gene expression profile was different in the 2 groups, and also different between various organs. This study suggested that apoptosis may play an important role in duck hepatitis A virus serotype 1 infection, and apoptosis suppression might facilitate virus multiplication, resulting in the highest virus concentration in the host.

Berberine-induced activation of AMPK increases hepatic FGF21 expression via NUR77.

PubMed

Zhou, Feiye; Bai, Mengyao; Zhang, Yuqing; Zhu, Qin; Zhang, Linlin; Zhang, Qi; Wang, Shushu; Zhu, Kecheng; Liu, Yun; Wang, Xiao; Zhou, Libin

2018-01-08

Fibroblast growth factor 21 (FGF21), a hormone-like protein mainly derived from liver, exhibits multiple beneficial effect on energy metabolism. Similar to FGF21, berberine exerts anti-hyperglycemic and anti-dyslipidemic properties. Previous studies revealed that the beneficial metabolic effect of berberine was attributed to the activation of AMP-activated protein kinase (AMPK). Here we investigated the effect of berberine on FGF21 expression in primary mouse hepatocytes. As expected, berberine induced hepatic FGF21 expression in a dose-dependent and time-dependent manner, along with the increased expression of NUR77, a proved transcription factor of FGF21. Berberine stimulated the phosphorylations of AMPK and acetyl-CoA carboxylase in primary mouse hepatocytes. Adenovirus-mediated overexpression of constitutively active AMPK triggered hepatic FGF21 and NUR77 expressions. The inhibition of AMPK by compound C abolished berberine-stimulated FGF21 and NUR77 expressions. These results suggest that berberine-induced activation of AMPK may contribute to hepatic FGF21 expression via NUR77. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-pre-S responses and viral clearance in chronic hepatitis B virus infection.

PubMed

Budkowska, A; Dubreuil, P; Poynard, T; Marcellin, P; Loriot, M A; Maillard, P; Pillot, J

1992-01-01

Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S1 and pre-S2 antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S1 and anti-pre-S2 antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B virus from serum.

Second window of protection against infarction in conscious rabbits: real or artifactual.

PubMed

Miki, T; Swafford, A N; Cohen, M V; Downey, J M

1999-04-01

To date, most studies of the second window of protection against infarction (SWOP) have evaluated infarct size by staining with triphenyltetrazolium chloride (TTC) soon after reperfusion. However, early TTC staining has been found to be an unreliable indicator of the ultimate infarct size following some interventions. Therefore, we tested whether SWOP could induce a sustained limitation of infarct size. Instrumented, conscious rabbits underwent 30 min of coronary occlusion. Infarct size was determined by either TTC staining after 3 h of reperfusion or conventional histology after 72 h of reperfusion. In the TTC study, 43.5+/-3.1% of the risk zone infarcted in the control group. Four cycles of 5 min ischemia/10 min reperfusion 24 h prior to 30 min ischemia significantly reduced infarct size measured by TTC to 32.5+/-2.3% (P<0.05 v control). In the histological study 57.8+/-3.6% of the risk zone infarcted in the control group. However, ischemic preconditioning 24 h prior to the 30 min ischemia did not protect the heart (59.3+/-4.4% infarction). Thus the infarct-limiting effect of SWOP evaluated with early TTC staining could not be demonstrated when infarction was assessed by histology after 3 days of reperfusion. These data suggest that SWOP may not have a sustained anti-infarct effect, but rather may simply delay the progression to infarction. Copyright 1999 Academic Press.

Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation.

PubMed

Corbacioglu, Selim; Richardson, Paul G

2017-10-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile. In children and adults following HSCT, defibrotide is approved for the treatment of hepatic VOD/SOS with concomitant renal or pulmonary dysfunction in the United States and for the treatment of severe hepatic VOD/SOS in the European Union. Day +100 survival rates with defibrotide are superior to those of historical controls receiving best supportive care only, and safety profiles are similar. Expert commentary: Defibrotide appears to act through multiple mechanisms to restore thrombo-fibrinolytic balance and protect endothelial cells, and there are promising data on the use of defibrotide for VOD/SOS prophylaxis in high-risk children undergoing HSCT. An ongoing randomized controlled trial in children and adults will better assess the clinical value of defibrotide as a preventive medication.

Use of PCR in resolving diagnostic difficulties potentially caused by genetic variation of hepatitis B virus.

PubMed Central

van Deursen, F J; Hino, K; Wyatt, D; Molyneaux, P; Yates, P; Wallace, L A; Dow, B C; Carman, W F

1998-01-01

AIMS: To assess the relevance of genetic variants of hepatitis B virus (HBV) and to demonstrate the usefulness of the polymerase chain reaction (PCR) in cases of HBV diagnostic difficulty. METHODS: Five serum samples from patients that presented diagnostic difficulty in routine laboratories were sent to a research laboratory for PCR, and if appropriate, S gene sequencing, in vitro expression, and antigenic analysis. RESULTS: The demonstration of HBV in serum by PCR allowed a definitive diagnosis of current infection. One serum sample with poor reactivity in a diagnostic assay had a minor hepatitis B surface antigen (HBsAg) variant and another with very poor reactivity had multiple variants of HBsAg. Transient HBsAg reactivity was observed in a recently vaccinated patient. A hepatitis Be antigen (HBeAg) false positive reaction was noted in a patient from a well defined risk group for HBV. One patient who was strongly HBsAg/HBeAg positive, but anti-hepatitis B core antibody negative, was viraemic. CONCLUSIONS: PCR may become the gold standard for the diagnosis of current HBV infection. HBV variants are responsible for a proportion of diagnostically difficult cases. Modification of commercial assays is necessary to increase the sensitivity of detection of such variants. PMID:9602690

Amyloidosis and spontaneous hepatic bleeding, transcatheter therapy for hepatic parenchymal bleeding with massive intraperitoneal hemorrhage: a case report and review of the literature.

PubMed

Mousa, Albeir Y; Abu-Halimah, Shadi; Alhalbouni, Saadi; Hass, Stephen M; Yang, Calvin; Gill, Gurpreet; AbuRahma, Ali F; Bates, Mark

2014-10-01

Hepatic hemorrhage can be devastating, especially in patients with underlying hepatic pathology. This is a case report of a 50-year-old man who presented to the emergency room with Stage 3 shock as evidenced by a systolic blood pressure of 90 mmHg, a heart rate of 125 beats per minute, respiration of 32, with delayed capillary refill and agitation. At this time, he was found to have a massive spontaneous intra-abdominal hemorrhage with an advanced stage of amyloidosis with multiple organ malfunctions. The initial diagnosis was based on an abdominal computed tomography scan and the patient was taken expeditiously to a hybrid angiography suite for a celiac angiogram. An intraoperative diagnosis of extravasation from amyloid related vasculopathy was made based on the angiographic appearance of hepatic circulation. Coil embolization of the feeding branch of the bleeder was achieved using the interlock coil system and a completion angiogram was done showing complete cessation of active bleeding. The postoperative phase was uneventful and the patient was discharged home on postoperative day three. His postoperative visit at five months later was unremarkable. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration.

PubMed

Formiga, Fabio R; Pelacho, Beatriz; Garbayo, Elisa; Imbuluzqueta, Izaskun; Díaz-Herráez, Paula; Abizanda, Gloria; Gavira, Juan J; Simón-Yarza, Teresa; Albiasu, Edurne; Tamayo, Esther; Prósper, Felipe; Blanco-Prieto, Maria J

2014-01-10

Acidic fibroblast growth factor (FGF1) and neuregulin-1 (NRG1) are growth factors involved in cardiac development and regeneration. Microparticles (MPs) mediate cytokine sustained release, and can be utilized to overcome issues related to the limited therapeutic protein stability during systemic administration. We sought to examine whether the administration of microparticles (MPs) containing FGF1 and NRG1 could promote cardiac regeneration in a myocardial infarction (MI) rat model. We investigated the possible underlying mechanisms contributing to the beneficial effects of this therapy, especially those linked to endogenous regeneration. FGF1- and NRG1-loaded MPs were prepared using a multiple emulsion solvent evaporation technique. Seventy-three female Sprague-Dawley rats underwent permanent left anterior descending coronary artery occlusion, and MPs were intramyocardially injected in the peri-infarcted zone four days later. Cardiac function, heart tissue remodeling, revascularization, apoptosis, cardiomyocyte proliferation, and stem cell homing were evaluated one week and three months after treatment. MPs were shown to efficiently encapsulate FGF1 and NRG1, releasing the bioactive proteins in a sustained manner. Three months after treatment, a statistically significant improvement in cardiac function was detected in rats treated with growth factor-loaded MPs (FGF1, NRG1, or FGF1/NRG1). The therapy led to inhibition of cardiac remodeling with smaller infarct size, a lower fibrosis degree and induction of tissue revascularization. Cardiomyocyte proliferation and progenitor cell recruitment were detected. Our data support the therapeutic benefit of NRG1 and FGF1 when combined with protein delivery systems for cardiac regeneration. This approach could be scaled up for use in pre-clinical and clinical studies. © 2013.

A modular, prospective, semi-automated drug safety monitoring system for use in a distributed data environment.

PubMed

Gagne, Joshua J; Wang, Shirley V; Rassen, Jeremy A; Schneeweiss, Sebastian

2014-06-01

The aim of this study was to develop and test a semi-automated process for conducting routine active safety monitoring for new drugs in a network of electronic healthcare databases. We built a modular program that semi-automatically performs cohort identification, confounding adjustment, diagnostic checks, aggregation and effect estimation across multiple databases, and application of a sequential alerting algorithm. During beta-testing, we applied the system to five databases to evaluate nine examples emulating prospective monitoring with retrospective data (five pairs for which we expected signals, two negative controls, and two examples for which it was uncertain whether a signal would be expected): cerivastatin versus atorvastatin and rhabdomyolysis; paroxetine versus tricyclic antidepressants and gastrointestinal bleed; lisinopril versus angiotensin receptor blockers and angioedema; ciprofloxacin versus macrolide antibiotics and Achilles tendon rupture; rofecoxib versus non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and myocardial infarction; telithromycin versus azithromycin and hepatotoxicity; rosuvastatin versus atorvastatin and diabetes and rhabdomyolysis; and celecoxib versus ns-NSAIDs and myocardial infarction. We describe the program, the necessary inputs, and the assumed data environment. In beta-testing, the system generated four alerts, all among positive control examples (i.e., lisinopril and angioedema; rofecoxib and myocardial infarction; ciprofloxacin and tendon rupture; and cerivastatin and rhabdomyolysis). Sequential effect estimates for each example were consistent in direction and magnitude with existing literature. Beta-testing across nine drug-outcome examples demonstrated the feasibility of the proposed semi-automated prospective monitoring approach. In retrospective assessments, the system identified an increased risk of myocardial infarction with rofecoxib and an increased risk of rhabdomyolysis with cerivastatin years before these drugs were withdrawn from the market. Copyright © 2014 John Wiley & Sons, Ltd.

Predictors of physical and mental health-related quality of life outcomes among myocardial infarction patients

PubMed Central

2013-01-01

Background Health-related quality of life (HRQoL) is an important outcome for patients diagnosed with coronary heart disease. This report describes predictors of physical and mental HRQoL at six months post-hospitalisation for myocardial infarction. Methods Participants were myocardial infarction patients (n=430) admitted to two tertiary referral centres in Brisbane, Australia who completed a six month coronary heart disease secondary prevention trial (ProActive Heart). Outcome variables were HRQoL (Short Form-36) at six months, including a physical and mental summary score. Baseline predictors included demographics and clinical variables, health behaviours, and psychosocial variables. Stepwise forward multiple linear regression analyses were used to identify significant independent predictors of six month HRQoL. Results Physical HRQoL was lower in participants who: were older (p<0.001); were unemployed (p=0.03); had lower baseline physical and mental HRQoL scores (p<0.001); had lower confidence levels in meeting sufficient physical activity recommendations (p<0.001); had no intention to be physically active in the next six months (p<0.001); and were more sedentary (p=0.001). Mental HRQoL was lower in participants who: were younger (p=0.01); had lower baseline mental HRQoL (p<0.001); were more sedentary (p=0.01) were depressed (p<0.001); and had lower social support (p=0.001). Conclusions This study has clinical implications as identification of indicators of lower physical and mental HRQoL outcomes for myocardial infarction patients allows for targeted counselling or coronary heart disease secondary prevention efforts. Trial registration Australian Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, CTRN12607000595415. PMID:24020831

Education, income, and occupational class cannot be used interchangeably in social epidemiology. Empirical evidence against a common practice

PubMed Central

Geyer, Siegfried; Hemström, Örjan; Peter, Richard; Vågerö, Denny

2006-01-01

Study objective Education, income, and occupational class are often used interchangeably in studies showing social inequalities in health. This procedure implies that all three characteristics measure the same underlying phenomena. This paper questions this practice. The study looked for any independent effects of education, income, and occupational class on four health outcomes: diabetes prevalence, myocardial infarction incidence and mortality, and finally all cause mortality in populations from Sweden and Germany. Design Sweden: follow up of myocardial infarction mortality and all cause mortality in the entire population, based on census linkage to the Cause of Death Registry. Germany: follow up of myocardial infarction morbidity and all cause mortality in statutory health insurance data, plus analysis of prevalence data on diabetes. Multiple regression analyses were performed to calculate the effects of education, income, and occupational class before and after mutual adjustments. Setting and participants Sweden (all residents aged 25–64) and Germany (Mettman district, Nordrhein‐Westfalen, all insured persons aged 25–64). Main results Correlations between education, income, and occupational class were low to moderate. Which of these yielded the strongest effects on health depended on type of health outcome in question. For diabetes, education was the strongest predictor and for all cause mortality it was income. Myocardial infarction morbidity and mortality showed a more mixed picture. In mutually adjusted analyses each social dimension had an independent effect on each health outcome in both countries. Conclusions Education, income, and occupational class cannot be used interchangeably as indicators of a hypothetical latent social dimension. Although correlated, they measure different phenomena and tap into different causal mechanisms. PMID:16905727

Rapid recovery from aphasia after infarction of Wernicke's area

PubMed Central

Yagata, Stephanie A.; Yen, Melodie; McCarron, Angelica; Bautista, Alexa; Lamair-Orosco, Genevieve

2017-01-01

Background Aphasia following infarction of Wernicke's area typically resolves to some extent over time. The nature of this recovery process and its time course have not been characterized in detail, especially in the acute/subacute period. Aims The goal of this study was to document recovery after infarction of Wernicke's area in detail in the first 3 months after stroke. Specifically, we aimed to address two questions about language recovery. First, which impaired language domains improve over time, and which do not? Second, what is the time course of recovery? Methods & Procedures We used quantitative analysis of connected speech and a brief aphasia battery to document language recovery in two individuals with aphasia following infarction of the posterior superior temporal gyrus. Speech samples were acquired daily between 2 and 16 days post stroke, and also at 1 month and 3 months. Speech samples were transcribed and coded using the CHAT system, in order to quantify multiple language domains. A brief aphasia battery was also administered at a subset of five time points during the 3 months. Outcomes & Results Both patients showed substantial recovery of language function over this time period. Most, but not all, language domains showed improvements, including fluency, lexical access, phonological retrieval and encoding, and syntactic complexity. The time course of recovery was logarithmic, with the greatest gains taking place early in the course of recovery. Conclusions There is considerable potential for amelioration of language deficits when damage is relatively circumscribed to the posterior superior temporal gyrus. Quantitative analysis of connected speech samples proved to be an effective, albeit time-consuming, approach to tracking day-by-day recovery in the acute/subacute post-stroke period. PMID:29051682

Time course of degradation of cardiac troponin I in patients with acute ST-elevation myocardial infarction: the ASSENT-2 troponin substudy.

PubMed

Madsen, Lene H; Christensen, Geir; Lund, Terje; Serebruany, Victor L; Granger, Chris B; Hoen, Ingvild; Grieg, Zanina; Alexander, John H; Jaffe, Allan S; Van Eyk, Jennifer E; Atar, Dan

2006-11-10

Although measurement of troponin is widely used for diagnosing acute myocardial infarction (AMI), its diagnostic potential may be increased by a more complete characterization of its molecular appearance and degradation in the blood. The aim of this study was to define the time course of cardiac troponin I (cTnI) degradation in patients with acute ST-elevation myocardial infarction (STEMI). In the ASSENT-2 substudy, 26 males hospitalized with STEMI were randomized to 2 different thrombolytic drugs within 6 hours after onset of symptoms. Blood samples were obtained just before initiation of thrombolysis and at 30 minutes intervals (7 samples per patient). Western blot analysis was performed using anti-cTnI antibodies and compared with serum concentrations of cTnI. All patients exceeded the cTnI cutoff for AMI during the sampling period; at initiation of therapy, 23 had elevated cTnI values. All patients demonstrated 2 bands on immunoblot: intact cTnI and a single degradation product as early as 90 minutes after onset of symptoms. On subsequent samples, 15 of 26 patients showed multiple degradation products with up to 7 degradation bands. The appearance of fragments was correlated with higher levels of cTnI (P<0.001) and time to initiation of treatment (P=0.058). This study defines for the first time the initial time course of cTnI degradation in STEMI. Intact cTnI and a single degradation product were detectable on immunoblot as early as 90 minutes after onset of symptoms with further degradation after 165 minutes. Infarct size and time to initiation of treatment was the major determinant for degradation.

Predictors of malignant brain edema in middle cerebral artery infarction observed on CT angiography.

PubMed

Kim, Hoon; Jin, Seon Tak; Kim, Young Woo; Kim, Seong Rim; Park, Ik Seong; Jo, Kwang Wook

2015-03-01

Patients with middle cerebral artery (MCA) infarction accompanied by MCA occlusion with or without internal carotid artery (ICA) occlusion have a poor prognosis, as a result of brain cell damage caused by both the infarction and by space-occupying and life-threatening edema formation. Multiple treatments can reduce the likelihood of edema formation, but tend to show limited efficacy. Decompressive hemicraniectomy with duroplasty has been promising for improving functional outcomes and reducing mortality, particularly improved functional outcomes can be achieved with early decompressive surgery. Therefore, identifying patients at risk for developing fatal edema is important and should be performed as early as possible. Sixty-four patients diagnosed with major MCA infarction with MCA occlusion within 8 hours of symptom onset were retrospectively reviewed. Early clinical, laboratory, and computed tomography angiography (CTA) parameters were analyzed for malignant brain edema (MBE). Twenty of the 64 patients (31%) had MBE, and the clinical outcome was poor (3month modified Rankin Scale >2) in 95% of them. The National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomography Score, Clot Burden Score, and Collateral Score (CS) showed statically significant differences in both groups. Multivariable analyses adjusted for age and sex identified the independent predictors of MBE: NIHSS score >18 (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 1.2-16.0, p=0.023) and CS on CTA <2 (OR: 7.28, 95% CI: 1.7-30.3,p=0.006). Our results provide useful information for selecting patients in need of aggressive treatment such as decompressive surgery. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease.

PubMed

Schatz, J; Brown, R T; Pascual, J M; Hsu, L; DeBaun, M R

2001-04-24

The authors evaluated education attainment and neuropsychological deficits in children with sickle cell disease (SCD) and silent cerebral infarcts. Children with silent infarcts had twice the rate of school difficulties as children without infarcts. Eighty percent of silent infarct cases had clinically significant cognitive deficits, whereas 35% had deficits in academic skills. Children with silent cerebral infarcts show high rates of poor educational attainment, cognitive deficits, and frontal lobe injury. Poor school performance in SCD is one indicator of silent infarcts.

‘Extreme’ vasculobiliary injuries: association with fundus-down cholecystectomy in severely inflamed gallbladders

PubMed Central

Strasberg, Steven M; Gouma, Dirk J

2012-01-01

Objectives Extreme vasculobiliary injuries usually involve major hepatic arteries and portal veins. They are rare, but have severe consequences, including rapid infarction of the liver. The pathogenesis of these injuries is not well understood. The purpose of this study was to elucidate the mechanism of injury through an analysis of clinical records, particularly the operative notes of the index procedure. Methods Biliary injury databases in two institutions were searched for data on extreme vasculobiliary injuries. Operative notes for the index procedure (cholecystectomy) were requested from the primary institutions. These notes and the treatment records of the tertiary centres to which the patients had been referred were examined. Radiographs from the primary institutions, when available, as well as those from the tertiary centres, were studied. Results Eight patients with extreme vasculobiliary injuries were found. Most had the following features in common. The operation had been started laparoscopically and converted to an open procedure because of severe chronic or acute inflammation. Fundus-down cholecystectomy had been attempted. Severe bleeding had been encountered as a result of injury to a major portal vein and hepatic artery. Four patients have required right hepatectomy and one had required an orthotopic liver transplant. Four of the eight patients have died and one remains under treatment. Conclusions Extreme vasculobiliary injuries tend to occur when fundus-down cholecystectomy is performed in the presence of severe inflammation. Contractive inflammation thickens and shortens the cystic plate, making separation of the gallbladder from the liver hazardous. PMID:22151444

Toxicogenomic Effects Common to Triazole Antifungals and Conserved Between Rats and Humans

EPA Science Inventory

The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple time-points and various study d...

Dietary Zinc Deficiency Exaggerates Ethanol-Induced Liver Injury in Mice: Involvement of Intrahepatic and Extrahepatic Factors

PubMed Central

Sun, Xinguo; Song, Zhenyuan; McClain, Craig J.; Zhou, Zhanxiang

2013-01-01

Clinical studies have demonstrated that alcoholics have a lower dietary zinc intake compared to health controls. The present study was undertaken to determine the interaction between dietary zinc deficiency and ethanol consumption in the pathogenesis of alcoholic liver disease. C57BL/6N mice were subjected to 8-week feeding of 4 experimental liquid diets: (1) zinc adequate diet, (2) zinc adequate diet plus ethanol, (3) zinc deficient diet, and (4) zinc deficient diet plus ethanol. Ethanol exposure with adequate dietary zinc resulted in liver damage as indicated by elevated plasma alanine aminotransferase level and increased hepatic lipid accumulation and inflammatory cell infiltration. Dietary zinc deficiency alone increased hepatic lipid contents, but did not induce hepatic inflammation. Dietary zinc deficiency showed synergistic effects on ethanol-induced liver damage. Dietary zinc deficiency exaggerated ethanol effects on hepatic genes related to lipid metabolism and inflammatory response. Dietary zinc deficiency worsened ethanol-induced imbalance between hepatic pro-oxidant and antioxidant enzymes and hepatic expression of cell death receptors. Dietary zinc deficiency exaggerated ethanol-induced reduction of plasma leptin, although it did not affect ethanol-induced reduction of white adipose tissue mass. Dietary zinc deficiency also deteriorated ethanol-induced gut permeability increase and plasma endotoxin elevation. These results demonstrate, for the first time, that dietary zinc deficiency is a risk factor in alcoholic liver disease, and multiple intrahepatic and extrahepatic factors may mediate the detrimental effects of zinc deficiency. PMID:24155903

Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat.

PubMed

Peeters, Geert; Debbaut, Charlotte; Friebel, Adrian; Cornillie, Pieter; De Vos, Winnok H; Favere, Kasper; Vander Elst, Ingrid; Vandecasteele, Tim; Johann, Tim; Van Hoorebeke, Luc; Monbaliu, Diethard; Drasdo, Dirk; Hoehme, Stefan; Laleman, Wim; Segers, Patrick

2018-03-01

Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions. © 2017 Anatomical Society.

Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat

PubMed Central

Chiu, Huan-Wen; Hua, Kuo-Feng

2016-01-01

Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and has multiple biological functions, including hepatoprotective and immune-modulatory effects. Currently, the commercially available A. cinnamomea are mainly liquid- and solid-state fermented A. cinnamomea. However, the hepatoprotective effect of solid-state fermented A. cinnamomea has never been reported. Here we evaluate the ability of air-dried, ground and non-extracted wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo. The results showed that oral administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the increase in plasma aspartate aminotransferase and alanine aminotransferase levels caused by chronic repeated CCl4 intoxication in rats. WFAC significantly reduced the CCl4-induced increase in hepatic lipid peroxidation levels and hydroxyproline contents, as well as reducing the spleen weight and water content of the liver. WFAC also restored the hepatic soluble protein synthesis and plasma albumin concentration in CCl4-intoxicated rats, but it did not affect the activities of superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic morphological analysis showed that the hepatic fibrosis and necrosis induced by CCl4 were significantly ameliorated by WFAC. Furthermore, the body weights of control rats and WFAC-administered rats were not significantly different, and no adverse effects were observed in WFAC-administered rats. These results indicate that WFAC is a nontoxic hepatoprotective agent against chronic CCl4-induced hepatic injury. PMID:27046059

Unexplained hepatitis following halothane.

PubMed Central

Walton, B; Simpson, B R; Strunin, L; Doniach, D; Perrin, J; Appleyard, A J

1976-01-01

Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur. PMID:1268612

Single‐Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment

PubMed Central

Karim, Aziz; Zhao, Zhen; Alonso, Alberto B.; Garg, Dyal; Preston, Richard A.

2017-01-01

Abstract Azilsartan medoxomil (AZL‐M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose‐dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M‐II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single‐center, open‐label, phase 1 parallel‐group study that examined the single‐dose (day 1) and multiple‐dose (days 4–8) — 40 mg — pharmacokinetics of AZL and M‐II in 16 subjects with mild and moderate hepatic impairment by Child‐Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M‐II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M‐II. Single and multiple doses of AZL‐M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL‐M is required for subjects with mild and moderate hepatic impairment. PMID:28750149

[Clinical implications and angiographic and electrocardiographic correlation of ST segment elevation in leads V7-V9 in patients with ST elevation myocardial infarction].

PubMed

Adawi, Khaled; Atar, Shaul

2008-07-01

The clinical significance and clinical characteristics of patients with myocardial infarction involving the posterior wall of the left ventricle is not well-defined. The angiographic findings and their correlation with the eletrocardiographic (ECG) findings may be of high therapeutic importance. We retrospectively studied consecutive patients with ST elevation myocardial infarction on the admission ECG to the intensive cardiac care. We studied the clinical and demographic characteristics, the clinical course in-hospital and the clinical outcome (including infarct size, congestive heart failure and significant mitral insufficiency). All patients underwent coronary angiography during the index admission. We correlated the ECG findings on admission to the angiographic findings. We studied 198 patients with mean age of 57 +/- 12 years (range 30-88 years), 158 men (79.8%) and 40 women (20.2%). Myocardial infarction involving the inferior wall was noted in 119 patients, of whom 68 had inferior wall myocardial infarction only, and 51 had inferior and lateral wall involvement (leads I, AVL and/or V5-V6). Only 4 patients (2%) had ST elevation in leads V7-V9 only. The left ventricular ejection fraction was lowest in patients with anterior wall myocardial infarction (41% +/- 6) compared to myocardial infarction with the posterior wall involved (44% +/- 8) or myocardial infarction with the inferior wall only (54% +/- 6) (p = 0.023). The largest infarct size by peak creatine phosphokinase was found in the inferoposterior myocardial infarction group, significantly larger from inferior infarction only, and similar to that of anterior myocardial infarction. The incidence of congestive heart failure was slightly more in anterior myocardial infarction; however, significant mitral valve insufficiency was higher in patients with posterior wall involvement, yet with no statistical significance. The infarct related artery causing posterior myocardial infarction was significantly more frequent in the right coronary artery (57.1%) compared to the left circumflex artery (37.5%) (p < 0.01). The major artery causing involvement of the posterior wall is the right coronary artery. In patients with myocardial infarction involving the posterior wall, infarct size is similar to that of anterior wall myocardial infarction, and with similar complications rate. However, the incidence of significant mitral valve insufficiency and congestive heart failure is high in patients with posterior wall involvement. Posterior leads assessment should be conducted routinely in patients with suspected myocardial infarction.

Femoral medullary infarction secondary to canine total hip arthroplasty.

PubMed

Sebestyen, P; Marcellin-Little, D J; DeYoung, B A

2000-01-01

To evaluate the prevalence of femoral intramedullary infarction after total hip arthroplasty (THA) and to determine whether any specific femoral morphology predisposes to bone infarction. Retrospective clinical study. All dogs from our hospital population undergoing THA between 1984 and 1997 with radiographic follow-up available at 1 year or more postoperatively. A case control study was conducted within the THA group to determine risk factors predisposing to femoral infarction after THA. Medical records and radiographs were reviewed. Data were collected on clinical parameters, femoral morphology, prosthesis, and bone changes. Radiographic diagnosis was confirmed using histopathology in 11 femora. Radiographs of 50 age-matched control dogs weighing more than 20 kg with coxofemoral degenerative joint disease were randomly chosen to determine the prevalence of bone infarction in nonoperated dogs. Ninety-one dogs with 110 THA were included in the study. Fifteen of the 110 femora with THA had radiographic evidence of infarction (14%). Infarction was not present in any femora in the control group. There was no significant difference in the prevalence of infarction between dogs that received cemented or uncemented prostheses. Clinical signs were not reported in any patient that developed femoral infarction. Young age (P = .03) and a distance between the greater trochanter and nutrient foramen greater than 79 mm (P = .008) predisposed dogs to femoral infarction. Over time, three infarcts decreased in size radiographically, five remained unchanged, and three expanded. An osteosarcoma developed at the site of a bone infarct in one dog. Femoral intramedullary infarction occurred in 15 of 110 THA. Young age at the time of THA and a greater distance between the greater trochanter and the nutrient foramen predisposed to infarction. Intramedullary infarction occurs after canine THA. These bone infarcts do not appear to cause clinical signs; however, they may present a diagnostic challenge. Malignant transformation could potentially result from medullary infarction.

Differential MR Delayed Enhancement Patterns of Chronic Myocardial Infarction between Extracellular and Intravascular Contrast Media

PubMed Central

Wang, Jian; Xiang, Bo; Lin, Hung Yu; Liu, Hongyu; Freed, Darren; Arora, Rakesh C.; Tian, Ganghong

2015-01-01

Objectives Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media. Materials and Methods Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson's trichrome method. Results Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn’t significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen. Conclusions Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn’t provide delayed enhancement. PMID:25816056

Hepatic encephalopathy in acute-on-chronic liver failure.

PubMed

Lee, Guan-Huei

2015-10-01

The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

Molecular Characterization of Hepatitis A Virus Isolates from a Transcontinental Shellfish-Borne Outbreak

PubMed Central

Sánchez, Glòria; Pintó, Rosa M.; Vanaclocha, Hermelinda; Bosch, Albert

2002-01-01

One hundred eighty-four serologically confirmed cases of hepatitis A were reported in eastern Spain in 1999. A matched case-control study implicated imported coquina clams complying with European Union shellfish standards as the source of infection; this implication was confirmed by the detection by reverse transcription-PCR of hepatitis A virus (HAV) RNA in shellfish samples. In spite of the recognized low variability of HAV, genetic characterization of the complete capsid region of virus isolates from patient serum samples revealed the existence of both synonymous and nonsynonymous variants. Two antigenic variants were detected, one in a discontinuous epitope defined by monoclonal antibody K3-4C8 and a second in a linear VP1 epitope of the virus. In spite of these antigenic variants, all isolates were assigned to genotype IB, providing further evidence that the outbreak originated from a common source, although multiple strains were likely to be involved. PMID:12409389

Polycystic Liver Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linda, Nguyen, E-mail: nguyenli@einstein.edu

A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations.more » The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.« less

A renal transplant patient with abdominal discomfort, vomiting and diarrhoea for 1 week

PubMed Central

Lutwak, Nancy; Dill, Curt

2011-01-01

The patient is a 61-year-old diabetic male with history of renal transplant who presented to the emergency department with complaints of intermittent abdominal discomfort accompanied by multiple episodes of vomiting and diarrhoea. He had delayed seeking medical attention until his friends insisted that he come to the emergency department, since the abdominal discomfort was worsening. The patient’s ECG revealed an ST-segment elevation myocardial infarction. PMID:22678945

A renal transplant patient with abdominal discomfort, vomiting and diarrhoea for 1 week.

PubMed

Lutwak, Nancy; Dill, Curt

2011-08-24

The patient is a 61-year-old diabetic male with history of renal transplant who presented to the emergency department with complaints of intermittent abdominal discomfort accompanied by multiple episodes of vomiting and diarrhoea. He had delayed seeking medical attention until his friends insisted that he come to the emergency department, since the abdominal discomfort was worsening. The patient's ECG revealed an ST-segment elevation myocardial infarction.

Variables Affecting the Reporting of Pain Following an Acute Myocardial Infarction

DTIC Science & Technology

1991-05-01

research found which investigated the phenomenon of unreported CP. The experience of pain is a highly complex human experience with a multiplicity of...occur, and is persistent (Greer & Hoyt, 1990). Nociceptive fibers have cell bodies in the spinal ganglia , which enter the dorsal horn posteriorly, and...via the spinothalamic pathway, and stimulate somatic motor neurons on the anterior horn, or preganglionic neurons of the autonomic nervous system in the

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease.

PubMed

Larsen, Sanne Bøjet; Grove, Erik Lerkevang; Neergaard-Petersen, Søs; Würtz, Morten; Hvas, Anne-Mette; Kristensen, Steen Dalby

2017-08-05

Increased platelet aggregation during antiplatelet therapy may predict cardiovascular events in patients with coronary artery disease. The majority of these patients receive aspirin monotherapy. We aimed to investigate whether high platelet-aggregation levels predict cardiovascular events in stable coronary artery disease patients treated with aspirin. We included 900 stable coronary artery disease patients with either previous myocardial infarction, type 2 diabetes mellitus, or both. All patients received single antithrombotic therapy with 75 mg aspirin daily. Platelet aggregation was evaluated 1 hour after aspirin intake using the VerifyNow Aspirin Assay (Accriva Diagnostics) and Multiplate Analyzer (Roche; agonists: arachidonic acid and collagen). Adherence to aspirin was confirmed by serum thromboxane B 2 . The primary end point was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At 3-year follow-up, 78 primary end points were registered. The primary end point did not occur more frequently in patients with high platelet-aggregation levels (first versus fourth quartile) assessed by VerifyNow (hazard ratio: 0.5 [95% CI, 0.3-1.1], P =0.08) or Multiplate using arachidonic acid (hazard ratio: 1.0 [95% CI, 0.5-2.1], P =0.92) or collagen (hazard ratio: 1.4 [95% CI, 0.7-2.8], P =0.38). Similar results were found for the composite secondary end point (nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and all-cause death) and the single end points. Thromboxane B 2 levels did not predict any end points. Renal insufficiency was the only clinical risk factor predicting the primary and secondary end points. This study is the largest to investigate platelet aggregation in stable coronary artery disease patients receiving aspirin as single antithrombotic therapy. We found that high platelet-aggregation levels did not predict cardiovascular events. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Deriving the Intrahepatic Arteriovenous Shunt Rate from CT Images and Biochemical Data Instead of from Arterial Perfusion Scintigraphy in Hepatic Arterial Infusion Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozaki, Toshiro, E-mail: ganronbun@amail.plala.or.jp; Seki, Hiroshi; Shiina, Makoto

2009-09-15

The purpose of the present study was to elucidate a method for predicting the intrahepatic arteriovenous shunt rate from computed tomography (CT) images and biochemical data, instead of from arterial perfusion scintigraphy, because adverse exacerbated systemic effects may be induced in cases where a high shunt rate exists. CT and arterial perfusion scintigraphy were performed in patients with liver metastases from gastric or colorectal cancer. Biochemical data and tumor marker levels of 33 enrolled patients were measured. The results were statistically verified by multiple regression analysis. The total metastatic hepatic tumor volume (V{sub metastasized}), residual hepatic parenchyma volume (V{sub residual};more » calculated from CT images), and biochemical data were treated as independent variables; the intrahepatic arteriovenous (IHAV) shunt rate (calculated from scintigraphy) was treated as a dependent variable. The IHAV shunt rate was 15.1 {+-} 11.9%. Based on the correlation matrixes, the best correlation coefficient of 0.84 was established between the IHAV shunt rate and V{sub metastasized} (p < 0.01). In the multiple regression analysis with the IHAV shunt rate as the dependent variable, the coefficient of determination (R{sup 2}) was 0.75, which was significant at the 0.1% level with two significant independent variables (V{sub metastasized} and V{sub residual}). The standardized regression coefficients ({beta}) of V{sub metastasized} and V{sub residual} were significant at the 0.1 and 5% levels, respectively. Based on this result, we can obtain a predicted value of IHAV shunt rate (p < 0.001) using CT images. When a high shunt rate was predicted, beneficial and consistent clinical monitoring can be initiated in, for example, hepatic arterial infusion chemotherapy.« less

New diagnostic and therapeutic techniques in the management of pyogenic liver abscesses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ranson, J.H.C.; Madayag, M.A.; Localio, S.A.

1975-05-01

An unexplained increase in the frequency of pyogenic liver abscesses of unknown etiology has, fortunately, been paralleled by significant advances in diagnostic and therapeutic methods. This report reviews experience with 14 patients operated upon at NYU Medical Center since 1971. Eight cases (57 percent) were cryptogenic. Other abscesses were associated with biliary disease (3); abdominal sepsis (2); and trauma (1). Abscesses were present on hospitalization in 12 patients. Clinical findings included fever (101 to 108 F), 100 percent; leucocytosis, 71 percent; anorexia and vomiting, 50 percent; localized tenderness and hepatomegaly, 50 percent; hypoalbuminemia; 86 percent; hypocholesterolemia, 78 percent; elevated SGOT,more » 71 percent; and elevated aikaline phosphatase, 43 percent. Technetium hepatic scintiscans showed focal defects in 10 of 12 patients (83 percent), but did not detect multiple abscesses in 2 of these. Hepatic arteriography performed in 10 patients was highly accurate, outlining single abscesses in 6 and multiple abscesses in 4. Furthermore, in one patient a false positive scintiscan was demonstrated by negative arteriography, confirmed by autopsy. In 4 patients, arteriography indicated an abscess in the posterior-superior area of the right hepatic lobe. With precise anatomical localization, a transthoracic approach permitted uncomplicated drainage in each case. This approach provides excellent exposure and direct drainage for abscesses in this area. An additional therapeutic adjunct in two patients, with 4 and 11 abscesses each, was postoperative intraportal infusion of antibiotics through the umbilical vein. Thirteen patients (83 percent) recovered, one dying from pulmonary embolism. Primary hepatic abscesses occur with increasing frequency. The methods described allow more precise preoperative diagnosis and direct surgical drainage. (auth)« less

Adiponectin inhibits leptin signaling via multiple mechanisms to exert protective effects against hepatic fibrosis

PubMed Central

HANDY, Jeffrey A.; FU, Ping P.; KUMAR, Pradeep; MELLS, Jamie E.; SHARMA, Shvetank; SAXENA, Neeraj K.; ANANIA, Frank A.

2011-01-01

SYNOPSIS Adiponectin is protective against hepatic fibrosis, while leptin promotes fibrosis. In hepatic stellate cells (HSCs), leptin signals via a Janus Kinase 2/Signal Transducers and Activators of Transcription 3 (Jak2/Stat3) pathway, producing effects that enhance extracellular matrix deposition. Suppressors of Cytokine Signaling-3 (SOCS-3) and Protein Tyrosine Phosphatase-1B (PTP1B) are both negative regulators of Jak/Stat signaling, and recent studies demonstrated a role for adiponectin in regulating SOCS-3 expression. In this study we investigated mechanisms whereby adiponectin dampens leptin signaling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad−/−) and wild-type mice with leptin and/or carbon tetrachloride (CCl4), or saline. We analyzed Jak2 and Ob-Rb phosphorylation, and PTP1B expression and activity. We also explored potential mechanisms through which adiponectin regulates SOCS-3/Ob-Rb association. Adiponectin inhibited leptin-stimulated Jak2 activation and Ob-Rb phosphorylation in HSCs, while both were increased in Ad−/− mice. Adiponectin stimulated PTP1B expression and activity, in vitro, while PTP1B expression was lower in Ad−/−mice than in wild-type mice. Adiponectin also promoted SOCS-3/Ob-R association, and blocked leptin-stimulated formation of extracellular TIMP-1/MMP-1 complexes, in vitro. These data suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: by promoting binding of SOCS-3 to Ob-Rb, and stimulating PTP1B expression and activity, thus inhibiting Jak2-Stat3 signaling at multiple points. PMID:21846328

Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis.

PubMed

Handy, Jeffrey A; Fu, Ping P; Kumar, Pradeep; Mells, Jamie E; Sharma, Shvetank; Saxena, Neeraj K; Anania, Frank A

2011-12-15

Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression. In the present study we investigate mechanisms whereby adiponectin dampens leptin signalling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad-/-) and wild-type mice with leptin and/or carbon tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the leptin receptor) phosphorylation, and PTP1B expression and activity. We also explore potential mechanisms through which adiponectin regulates SOCS-3-Ob-Rb association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb phosphorylation in HSCs, whereas both were increased in Ad-/- mice. Adiponectin stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was lower in Ad-/-mice than in wild-type mice. Adiponectin also promotes SOCS-3-Ob-R association and blocks leptin-stimulated formation of extracellular TIMP-1 (tissue inhibitor of metalloproteinases-1)-MMP-1 (matrix metalloproteinase-1) complexes in vitro. These results suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob-Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting JAK2/STAT3 signalling at multiple points.

Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids.

PubMed

Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Placko, R

1989-03-01

The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies). The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool. While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001). Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function. The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group. At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients. These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs.

Measurement of acute Q-wave myocardial infarct size with single photon emission computed tomography imaging of indium-111 antimyosin.

PubMed

Antunes, M L; Seldin, D W; Wall, R M; Johnson, L L

1989-04-01

Myocardial infarct size was measured by single photon emission computed tomography (SPECT) following injection of indium-111 antimyosin in 27 patients (18 male and 9 female; mean age 57.4 +/- 10.5 years, range 37 to 75) who had acute transmural myocardial infarction (MI). These 27 patients represent 27 of 35 (77%) consecutive patients with acute Q-wave infarctions who were injected with indium-111 antimyosin. In the remaining 8 patients either tracer uptake was too faint or the scans were technically inadequate to permit infarct sizing from SPECT reconstructions. In the 27 patients studied, infarct location by electrocardiogram was anterior in 15 and inferoposterior in 12. Nine patients had a history of prior infarction. Each patient received 2 mCi of indium-111 antimyosin followed by SPECT imaging 48 hours later. Infarct mass was determined from coronal slices using a threshold value obtained from a human torso/cardiac phantom. Infarct size ranged from 11 to 87 g mean 48.5 +/- 24). Anterior infarcts were significantly (p less than 0.01) larger (60 +/- 20 g) than inferoposterior infarcts (34 +/- 21 g). For patients without prior MI, there were significant inverse correlations between infarct size and ejection fraction (r = 0.71, p less than 0.01) and wall motion score (r = 0.58, p less than 0.01) obtained from predischarge gated blood pool scans. Peak creatine kinase-MB correlated significantly with infarct size for patients without either reperfusion or right ventricular infarction (r = 0.66). Seven patients without prior infarcts had additional simultaneous indium-111/thallium-201 SPECT studies using dual energy windows.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis

PubMed Central

Song, Zhenyuan; Deaciuc, Ion; Zhou, Zhanxiang; Song, Ming; Chen, Theresa; Hill, Daniell; McClain, Craig J.

2014-01-01

Although simple steatosis was originally thought to be a pathologically inert histological change, fat accumulation in the liver may play a critical role not only in disease initiation, but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Therefore, prevention of fat accumulation in the liver may be an effective therapy for multiple stages of nonalcoholic fatty liver disease (NAFLD). Promising beneficial effects of betaine supplementation on human NAFLD have been reported in some pilot clinical studies; however, data related to betaine therapy in NAFLD are limited. In this study, we examined the effects of betaine on fat accumulation in the liver induced by high-sucrose diet and evaluated mechanisms by which betaine could attenuate or prevent hepatic steatosis in this model. Male C57BL/6 mice weighing 20 ± 0.5 g (means ± SE) were divided into four groups (8 mice per group) and started on one of four treatments: standard diet (SD), SD+betaine, high-sucrose diet (HS), and HS + betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Long-term feeding of high-sucrose diet to mice caused significant hepatic steatosis accompanied by markedly increased lipogenic activity. Betaine significantly attenuated hepatic steatosis in this animal model, and this change was associated with increased activation of hepatic AMP-activated protein kinase (AMPK) and attenuated lipogenic capability (enzyme activities and gene expression) in the liver. Our findings are the first to suggest that betaine might serve as a therapeutic tool to attenuate hepatic steatosis by targeting the hepatic AMPK system. PMID:17702954

Fontan-associated liver disease: Spectrum of US findings.

PubMed

Bae, Jung Min; Jeon, Tae Yeon; Kim, Jung Sun; Kim, Seokhwi; Hwang, Sook Min; Yoo, So-Young; Kim, Ji Hye

2016-04-01

To describe ultrasonography (US) findings of Fontan-associated liver disease (FALD) and to determine whether screening US examinations can identify FALD before biochemical hepatic dysfunction. This retrospective study included 55 patients who underwent Fontan procedure over a 20-year period. Hepatobiliary US findings (n=55), CT or MRI findings (n=19), biochemical hepatic function tests (n=49), and histopathological results (n=4) were analyzed. Images were reviewed focusing on the hepatic parenchymal changes, presence of focal lesions, and signs of portal hypertension. Hepatic parenchymal changes (either heterogeneous echotexture or surface nodularity) evident on US were present in 67% (37/55) and showed positive correlation with the Fontan duration. Hyper-echoic lesions were noted in 35% (19/55) and showed a predilection for multiplicity, small size, right lobe location, and irregular margin on high-frequency transducer. These lesions were not demonstrated by CT or MRI or by low-frequency transducer. Histopathological results of targeted biopsy for hyper-echoic lesions revealed lesser degree of patchy sinusoidal and portal fibrosis than seen in cases with surface nodularity. Abnormal parenchymal enhancement was commonly seen with CT or MRI in 63% (12/19) and hypervascular nodules in 21% (4/19). Most patients (82%, 40/49) showed normal biochemical hepatic function tests, despite the presence of hepatic parenchymal changes on imaging. The common US findings of FALD included heterogeneous parenchymal echotexture, surface nodularity, and hyper-echoic lesions. We suggest that hyper-echoic lesions without surface nodularity detected by high-frequency transducer may represent the early stage of fibrosis. US examination may be useful for identifying the progression of FALD before biochemical hepatic dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model.

PubMed

Zhang, Chi; Lu, Xuemian; Tan, Yi; Li, Bing; Miao, Xiao; Jin, Litai; Shi, Xue; Zhang, Xiang; Miao, Lining; Li, Xiaokun; Cai, Lu

2012-01-01

Zinc (Zn) deficiency often occurs in the patients with diabetes. Effects of Zn deficiency on diabetes-induced hepatic injury were investigated. Type 1 diabetes was induced in FVB mice with multiple low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with and without Zn chelator, N,N,N',N'-tetrakis (2-pyridylemethyl) ethylenediamine (TPEN), at 5 mg/kg body-weight daily for 4 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level and liver histopathological and biochemical changes. Hepatic Zn deficiency (lower than control level, p<0.05) was seen in the mice with either diabetes or TPEN treatment and more evident in the mice with both diabetes and TPEN. Zn deficiency exacerbated hepatic injuries, shown by further increased serum ALT, hepatic lipid accumulation, inflammation, oxidative damage, and endoplasmic reticulum stress-related cell death in Diabetes/TPEN group compared to Diabetes alone. Diabetes/TPEN group also showed a significant decrease in nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and transcription action along with significant increases in Akt negative regulators, decrease in Akt and GSK-3β phosphorylation, and increase in nuclear accumulation of Fyn (a Nrf2 negative regulator). In vitro study with HepG2 cells showed that apoptotic effect of TPEN at 0.5-1.0 µM could be completely prevented by simultaneous Zn supplementation at the dose range of 30-50 µM. Zn is required for maintaining Akt activation by inhibiting the expression of Akt negative regulators; Akt activation can inhibit Fyn nuclear translocation to export nuclear Nrf2 to cytoplasm for degradation. Zn deficiency significantly enhanced diabetes-induced hepatic injury likely through down-regulation of Nrf2 function.

A survey of bloodborne viruses and associated risk behaviours in Greek prisons.

PubMed

Malliori, M; Sypsa, V; Psichogiou, M; Touloumi, G; Skoutelis, A; Tassopoulos, N; Hatzakis, A; Stefanis, C

1998-02-01

To determine HIV and hepatitis infection prevalence and correlates with risk behaviour. Cross-sectional study: voluntary, anonymous HIV, hepatitis (HCV, HBV and HDV) surveillance and questionnaire on risk factors. Korydallos Prison, Athens and Ag. Stefanos Prison, Patra, Greece. Of 544 drug users imprisoned for drug related offences, all completed the questionnaire and 533 blood samples were collected. HIV (by anti-HIV-1), HCV (by anti-HCV), HBV (by anti-HBc, HBsAg) and HDV (by anti-HDV) prevalence. Data on demography, legal status, drug use, sharing of injecting equipment. Of the 544 drug users, 375 (68.9%) had injected drugs (IDUs) at some time, 35% of whom had injected whilst in that prison. Of the 533 blood samples tested, one was positive for anti-HIV-1 (0.19%), 310 for anti-HCV (58.2%), 306/531 (57.6%) for anti-HBc, 34/527 (6.5%) for HBsAg and 12/527 (2.3%) for anti-HDV. Prevalence rates for IDUs only were 0.27% for HIV-1, 80.6% for hepatitis C, 62.7% for hepatitis B and 3.3% for hepatitis D. Ninety-two per cent of IDUs injecting in prison shared needles, indicating that IDUs inject less but share more during incarceration. Multiple logistic regression revealed needle-sharing as the most important risk factor for HCV infection in IDUs. Prior knowledge of a positive hepatitis result did not appear to inhibit IDUs from practising risky behaviours in prison. The epidemic of hepatitis B and C among imprisoned IDUs identified by this study constitutes a major public health problem. Prevention programmes, such as counselling, HBV vaccination, community-based methadone maintenance treatment and syringe exchange schemes, are necessary in order to prevent a further spread.

Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver

PubMed Central

Sekiguchi, Satoshi; Kimura, Kiminori; Chiyo, Tomoko; Ohtsuki, Takahiro; Tobita, Yoshimi; Tokunaga, Yuko; Yasui, Fumihiko; Tsukiyama-Kohara, Kyoko; Wakita, Takaji; Tanaka, Toshiyuki; Miyasaka, Masayuki; Mizuno, Kyosuke; Hayashi, Yukiko; Hishima, Tsunekazu; Matsushima, Kouji; Kohara, Michinori

2012-01-01

Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29(+/−)/MxCre(+/−) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine. PMID:23284733

Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver.

PubMed

Sekiguchi, Satoshi; Kimura, Kiminori; Chiyo, Tomoko; Ohtsuki, Takahiro; Tobita, Yoshimi; Tokunaga, Yuko; Yasui, Fumihiko; Tsukiyama-Kohara, Kyoko; Wakita, Takaji; Tanaka, Toshiyuki; Miyasaka, Masayuki; Mizuno, Kyosuke; Hayashi, Yukiko; Hishima, Tsunekazu; Matsushima, Kouji; Kohara, Michinori

2012-01-01

Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid-polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29((+/-))/MxCre((+/-)) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine.

Quantification of myocardial infarction: a comparison of single photon-emission computed tomography with pyrophosphate to serial plasma MB-creatine kinase measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jansen, D.E.; Corbett, J.R.; Wolfe, C.L.

1985-08-01

Single photon-emission computed tomography (SPECT) with /sup 99m/Tc-pyrophosphate (PPi) has been shown to estimate size of myocardial infarction accurately in animals. The authors tested the hypothesis that SPECT with /sup /sup 99m//Tc-PPi and blood pool subtraction can provide prompt and accurate estimates of size of myocardial infarction in patients. SPECT estimates are potentially available early after the onset of infarction and should correlate with estimates of infarct size calculated from serial measurements of plasma MB-creatine kinase (CK) activity. Thirty-three patients with acute myocardial infarction and 16 control patients without acute myocardial infarction were studied. Eleven of the patients had transmuralmore » anterior myocardial infarction, 16 had transmural inferior myocardial infarction, and six had nontransmural myocardial infarction. SPECT was performed with a commercially available rotating gamma camera. Identical projection images of the distribution of 99mTc-PPi and the ungated cardiac blood pool were acquired sequentially over 180 degrees. Reconstructed sections were color coded and superimposed for purposes of localization of infarct. Areas of increased PPi uptake within myocardial infarcts were thresholded at 65% of peak activity. The blood pool was thresholded at 50% and subtracted to determine the endocardial border for the left ventricle. Myocardial infarcts ranged in size from 1 to 126 gram equivalents (geq) MB-CK. The correlation of MB-CK estimates of size of infarct with size determined by SPECT (both in geq) was good (r = .89 with a regression line of y = 13.1 + 1.5x).« less

78 FR 3005 - Creating an Alternative Approval Pathway for Certain Drugs Intended to Address Unmet Medical Need...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... major advances in the treatment of conditions such as cystic fibrosis, HIV, hepatitis C, and multiple sclerosis. In some cases, however, the resource-intensive programs needed for approval of drugs to treat a...

Effects of myocardial infarction on the distribution and transport of nutrients and oxygen in porcine myocardium.

PubMed

Davis, Bryce H; Morimoto, Yoshihisa; Sample, Chris; Olbrich, Kevin; Leddy, Holly A; Guilak, Farshid; Taylor, Doris A

2012-10-01

One of the primary limitations of cell therapy for myocardial infarction is the low survival of transplanted cells, with a loss of up to 80% of cells within 3 days of delivery. The aims of this study were to investigate the distribution of nutrients and oxygen in infarcted myocardium and to quantify how macromolecular transport properties might affect cell survival. Transmural myocardial infarction was created by controlled cryoablation in pigs. At 30 days post-infarction, oxygen and metabolite levels were measured in the peripheral skeletal muscle, normal myocardium, the infarct border zone, and the infarct interior. The diffusion coefficients of fluorescein or FITC-labeled dextran (0.3-70 kD) were measured in these tissues using fluorescence recovery after photobleaching. The vascular density was measured via endogenous alkaline phosphatase staining. To examine the influence of these infarct conditions on cells therapeutically used in vivo, skeletal myoblast survival and differentiation were studied in vitro under the oxygen and glucose concentrations measured in the infarct tissue. Glucose and oxygen concentrations, along with vascular density were significantly reduced in infarct when compared to the uninjured myocardium and infarct border zone, although the degree of decrease differed. The diffusivity of molecules smaller than 40 kD was significantly higher in infarct center and border zone as compared to uninjured heart. Skeletal myoblast differentiation and survival were decreased stepwise from control to hypoxia, starvation, and ischemia conditions. Although oxygen, glucose, and vascular density were significantly reduced in infarcted myocardium, the rate of macromolecular diffusion was significantly increased, suggesting that diffusive transport may not be inhibited in infarct tissue, and thus the supply of nutrients to transplanted cells may be possible. in vitro studies mimicking infarct conditions suggest that increasing nutrients available to transplanted cells may significantly increase their ability to survive in infarct.

Clinicoradiological Correlation of Infarct Patterns on Diffusion-weighted Magnetic Resonance Imaging in Stroke.

PubMed

Hussain, Zainab; Hilal, Kiran; Ahmad, Muhammad; Sajjad, Zafar; Sayani, Raza

2018-03-02

Diffusion-weighted magnetic resonance imaging (DW-MRI) represents a major advance in the early diagnosis of acute ischemic stroke. It can detect edema due to ischemia in the brain tissue. It not only establishes the presence and location of ischemic brain injury but also a relatively new concept is the determination of infarct patterns seen on diffusion imaging and its clinical correlation. Objective To determine the frequency of various infarct patterns and their relationship with functional outcome of the patient. Materials and methods A total of 108 patients with acute stroke were enrolled by purposive sampling. Magnetic resonance imaging (MRI) was obtained with departmental protocol and diffusion-weighted sequences. The clinical data was collected from medical records and functional outcome was assessed at the time of admission using Barthel Index (BI) which was dichotomized into poor and favorable outcomes. The radiological data was collected and three infarct patterns (cortical, subcortical, and territorial infarcts) were recorded from diffusion-weighted images. Association of other risk factors such as age, gender, diabetes, hypertension (HTN), hyperlipidemia, and smoking were also evaluated. Results Amongst the three infarct patterns, subcortical infarcts were noted with the highest proportion of 62% (67/108). The highest proportion of territorial infarcts (78.6%) was significantly associated with a poor outcome in comparison to cortical and subcortical infarcts. Cortical infarcts (61.5%) were significantly associated with good outcomes followed by subcortical and then territorial infarcts (p-value < 0.002). Amongst the risk factors, HTN was found to be highly prevalent followed by diabetes mellitus (DM). Conclusion Subcortical infarct pattern was the most common, followed by territorial and cortical infarct. The highest proportion of infarct pattern with good outcomes was seen with cortical infarcts followed by subcortical and then territorial infarct pattern. HTN and coronary artery disease (CAD) were the effect modifiers showing significant association with poor outcomes.

Three-dimensional rotational angiography fused with multimodal imaging modalities for targeted endomyocardial injections in the ischaemic heart.

PubMed

Dauwe, Dieter Frans; Nuyens, Dieter; De Buck, Stijn; Claus, Piet; Gheysens, Olivier; Koole, Michel; Coudyzer, Walter; Vanden Driessche, Nina; Janssens, Laurens; Ector, Joris; Dymarkowski, Steven; Bogaert, Jan; Heidbuchel, Hein; Janssens, Stefan

2014-08-01

Biological therapies for ischaemic heart disease require efficient, safe, and affordable intramyocardial delivery. Integration of multiple imaging modalities within the fluoroscopy framework can provide valuable information to guide these procedures. We compared an anatomo-electric method (LARCA) with a non-fluoroscopic electromechanical mapping system (NOGA(®)). LARCA integrates selective three-dimensional-rotational angiograms with biplane fluoroscopy. To identify the infarct region, we studied LARCA-fusion with pre-procedural magnetic resonance imaging (MRI), dedicated CT, or (18)F-FDG-PET/CT. We induced myocardial infarction in 20 pigs by 90-min LAD occlusion. Six weeks later, we compared peri-infarct delivery accuracy of coloured fluospheres using sequential NOGA(®)- and LARCA-MRI-guided vs. LARCA-CT- and LARCA-(18)F-FDG-PET/CT-guided intramyocardial injections. MRI after 6 weeks revealed significant left ventricular (LV) functional impairment and remodelling (LVEF 31 ± 3%, LVEDV 178 ± 15 mL, infarct size 17 ± 2% LV mass). During NOGA(®)-procedures, three of five animals required DC-shock for major ventricular arrhythmias vs. one of ten during LARCA-procedures. Online procedure time was shorter for LARCA than NOGA(®) (77 ± 6 vs. 130 ± 3 min, P < 0.0001). Absolute distance of injection spots to the infarct border was similar for LARCA-MRI (4.8 ± 0.5 mm) and NOGA(®) (5.4 ± 0.5 mm). LARCA-CT-integration allowed closer approximation of the targeted border zone than LARCA-PET (4.0 ± 0.5 mm vs. 6.2 ± 0.6 mm, P < 0.05). Three-dimensional -rotational angiography fused with multimodal imaging offers a new, cost-effective, and safe strategy to guide intramyocardial injections. Endoventricular procedure times and arrhythmias compare favourably to NOGA(®), without compromising injection accuracy. LARCA-based fusion imaging is a promising enabling technology for cardiac biological therapies. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study.

PubMed

Gurbel, Paul A; Bliden, Kevin P; Saucedo, Jorge F; Suarez, Thomas A; DiChiara, Joseph; Antonino, Mark J; Mahla, Elisabeth; Singla, Anand; Herzog, William R; Bassi, Ashwani K; Hennebry, Thomas A; Gesheff, Tania B; Tantry, Udaya S

2009-02-24

The primary objective of this study was to compare the effect of therapy with bivalirudin alone versus bivalirudin plus eptifibatide on platelet reactivity measured by turbidometric aggregometry and thrombin-induced platelet-fibrin clot strength (TIP-FCS) measured by thrombelastography in percutaneous coronary intervention (PCI) patients. The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction. Bivalirudin is commonly administered alone to clopidogrel naïve (CN) patients and to patients on maintenance clopidogrel therapy (MT) undergoing elective stenting. The effect of adding eptifibatide to bivalirudin on platelet reactivity (PR) and TIP-FCS, and their relation to periprocedural infarction in these patients are unknown. Patients (n = 200) stratified to clopidogrel treatment status were randomly treated with bivalirudin (n = 102) or bivalirudin plus eptifibatide (n = 98). One hundred twenty-eight CN patients were loaded with 600 mg clopidogrel immediately after stenting, and 72 MT patients were not loaded. The PR, TIP-FCS, and myonecrosis markers were serially determined. In CN and MT patients, bivalirudin plus eptifibatide was associated with markedly lower PR at all times (5- and 20-microM adenosine diphosphate-induced, and 15- and 25-microM thrombin receptor activator peptide-induced aggregation; p < 0.001 for all) and reduced mean TIP-FCS (p < 0.05). Patients who had a periprocedural infarction had higher mean 18-h PR (p < 0.0001) and TIP-FCS (p = 0.002). For elective stenting, the addition of eptifibatide to bivalirudin lowered PR to multiple agonists and the tensile strength of the TIP-FCS, 2 measurements strongly associated with periprocedural myonecrosis. Future studies of PR and TIP-FCS for elective stenting may facilitate personalized antiplatelet therapy and enhance the selection of patients for glycoprotein IIb/IIIa blockade. (Peri-Procedural Myocardial Infarction, Platelet Reactivity, Thrombin Generation, and Clot Strength: Differential Effects of Eptifibatide + Bivalirudin Versus Bivalirudin [CLEAR PLATELETS-2]; NCT00370045.

Evidence of extensive atherosclerosis, coronary artery disease and myocardial infarction in the ApoE-/-:Ins2+/Akita mouse fed a western diet.

PubMed

Venegas-Pino, Daniel E; Lagrotteria, Andrew; Wang, Pei-Wen; Morphet, Jaiya; Clapdorp, Cassaundra; Shi, Yuanyuan; Werstuck, Geoff H

2018-05-23

Diabetic patients with no history of cardiac infarction have a prevalence of coronary atherosclerosis and a risk of heart attack equivalent to euglycemic patients who have coronary atherosclerosis and have suffered a prior myocardial infarction. Although several murine models of diabetes have been established, none of these show indications of cardiac events. In an attempt to establish a diabetic mouse model with coronary atherosclerosis and myocardial injury, we have fed hyperglycemic ApoE -/- :Ins2 +/Akita mice a western diet to enhance the dyslipidemic phenotype. Five-week-old ApoE -/- :Ins2 +/Akita mice and ApoE -/- controls were fed a diet, 0.15% cholesterol and 21% anhydrous milk lipids, until 25 weeks of age. Changes in lifespan, clinical and metabolic parameters were evaluated as well as atherosclerosis and heart injury. In comparison to male ApoE -/- , male ApoE -/- :Ins2 +/Akita mice presented with chronic hyperglycemia (30.8 ± 1.2 mM vs. 9.3 ± 0.5 mM) accompanied by extremely high levels of total plasma cholesterol (49.3 ± 6.3 mM vs. 30.1 ± 1.5 mM) and triglycerides (11.6 ± 1.7 mM vs. 2.36 ± 0.18 mM). These mice have atherosclerosis at multiple vascular sites, including aortic sinus, ascending and descending aorta, brachiocephalic artery and coronary arteries. In addition, myocardial infarcts and a significant reduction of the lifespan (close to 20% of survival vs. other groups) were observed. Distinctively, both strains of female mice presented a parallel increase in plasma lipids, atherosclerosis, and no effects on mortality. We have established a diabetic mouse model, the western-diet-fed male ApoE -/- :Ins2 +/Akita mouse, with profound cardiovascular disease involving extensive atherosclerosis, coronary artery disease and myocardial infarct resulting in shortened lifespan. Copyright © 2018 Elsevier B.V. All rights reserved.

Myocardial infarct sizing by late gadolinium-enhanced MRI: Comparison of manual, full-width at half-maximum, and n-standard deviation methods.

PubMed

Zhang, Lin; Huttin, Olivier; Marie, Pierre-Yves; Felblinger, Jacques; Beaumont, Marine; Chillou, Christian DE; Girerd, Nicolas; Mandry, Damien

2016-11-01

To compare three widely used methods for myocardial infarct (MI) sizing on late gadolinium-enhanced (LGE) magnetic resonance (MR) images: manual delineation and two semiautomated techniques (full-width at half-maximum [FWHM] and n-standard deviation [SD]). 3T phase-sensitive inversion-recovery (PSIR) LGE images of 114 patients after an acute MI (2-4 days and 6 months) were analyzed by two independent observers to determine both total and core infarct sizes (TIS/CIS). Manual delineation served as the reference for determination of optimal thresholds for semiautomated methods after thresholding at multiple values. Reproducibility and accuracy were expressed as overall bias ± 95% limits of agreement. Mean infarct sizes by manual methods were 39.0%/24.4% for the acute MI group (TIS/CIS) and 29.7%/17.3% for the chronic MI group. The optimal thresholds (ie, providing the closest mean value to the manual method) were FWHM30% and 3SD for the TIS measurement and FWHM45% and 6SD for the CIS measurement (paired t-test; all P > 0.05). The best reproducibility was obtained using FWHM. For TIS measurement in the acute MI group, intra-/interobserver agreements, from Bland-Altman analysis, with FWHM30%, 3SD, and manual were -0.02 ± 7.74%/-0.74 ± 5.52%, 0.31 ± 9.78%/2.96 ± 16.62% and -2.12 ± 8.86%/0.18 ± 16.12, respectively; in the chronic MI group, the corresponding values were 0.23 ± 3.5%/-2.28 ± 15.06, -0.29 ± 10.46%/3.12 ± 13.06% and 1.68 ± 6.52%/-2.88 ± 9.62%, respectively. A similar trend for reproducibility was obtained for CIS measurement. However, semiautomated methods produced inconsistent results (variabilities of 24-46%) compared to manual delineation. The FWHM technique was the most reproducible method for infarct sizing both in acute and chronic MI. However, both FWHM and n-SD methods showed limited accuracy compared to manual delineation. J. Magn. Reson. Imaging 2016;44:1206-1217. © 2016 International Society for Magnetic Resonance in Medicine.

An experimental investigation of bubble splitting through multiple bifurcations

NASA Astrophysics Data System (ADS)

Bull, Joseph L.; Eshpuniyani, Brijesh; Fowlkes, J. Brian

2004-11-01

A bench top vascular bifurcation model is used to investigate the splitting of long bubbles in a series of liquid-filled bifurcations. These experiments are motivated by a gas embolotherapy technique for the potential treatment of cancer by using gas emboli to infarct tumors. The gas bubbles originate as perfluorocarbon droplets that are small enough to pass through capillaries and are injected into the bloodstream. Low intensity ultrasound is used to track their motion, and they are vaporized at the desired location for treatment via high intensity ultrasound to produce gas bubbles whose volumes are approximately 125 to 150 times the droplet volume. Achieving complete tumor necrosis requires infarction of most of the tumor. Understanding the transport and splitting of the gas bubbles, which can be long enough to extend through more than one bifurcation, is necessary to design delivery strategies. The current experiments investigate the behavior of a bubble as it passes through a series of two geometrically symmetric bifurcations, for different values of effective Bond number, which depends on gravity and the positioning of the bifurcation, capillary number, and bubble volume. The experiments are designed to match the Reynolds, Bond and capillary numbers to the physiological values for arterioles, and to provide guidance in achieving uniform tumor infarction. This work is supported by NSF grant BES-0301278 and NIH grant EB003541-01.

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

PubMed Central

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-01-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials. PMID:27184924

Fish consumption and risk of subclinical brain abnormalities on MRI in older adults.

PubMed

Virtanen, J K; Siscovick, D S; Longstreth, W T; Kuller, L H; Mozaffarian, D

2008-08-05

To investigate the association between fish consumption and subclinical brain abnormalities. In the population-based Cardiovascular Health Study, 3,660 participants age > or =65 underwent an MRI scan in 1992-1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish > or =3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54-1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits.

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

NASA Astrophysics Data System (ADS)

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-05-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

PubMed Central

Yoon, Young-sup; Wecker, Andrea; Heyd, Lindsay; Park, Jong-Seon; Tkebuchava, Tengiz; Kusano, Kengo; Hanley, Allison; Scadova, Heather; Qin, Gangjian; Cha, Dong-Hyun; Johnson, Kirby L.; Aikawa, Ryuichi; Asahara, Takayuki; Losordo, Douglas W.

2005-01-01

We have identified a subpopulation of stem cells within adult human BM, isolated at the single-cell level, that self-renew without loss of multipotency for more than 140 population doublings and exhibit the capacity for differentiation into cells of all 3 germ layers. Based on surface marker expression, these clonally expanded human BM-derived multipotent stem cells (hBMSCs) do not appear to belong to any previously described BM-derived stem cell population. Intramyocardial transplantation of hBMSCs after myocardial infarction resulted in robust engraftment of transplanted cells, which exhibited colocalization with markers of cardiomyocyte (CMC), EC, and smooth muscle cell (SMC) identity, consistent with differentiation of hBMSCs into multiple lineages in vivo. Furthermore, upregulation of paracrine factors including angiogenic cytokines and antiapoptotic factors, and proliferation of host ECs and CMCs, were observed in the hBMSC-transplanted hearts. Coculture of hBMSCs with CMCs, ECs, or SMCs revealed that phenotypic changes of hBMSCs result from both differentiation and fusion. Collectively, the favorable effect of hBMSC transplantation after myocardial infarction appears to be due to augmentation of proliferation and preservation of host myocardial tissues as well as differentiation of hBMSCs for tissue regeneration and repair. To our knowledge, this is the first demonstration that a specific population of multipotent human BM-derived stem cells can induce both therapeutic neovascularization and endogenous and exogenous cardiomyogenesis. PMID:15690083

[NOTCH3 gene mutations in two Chinese families featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy].

PubMed

Sun, Qiying; Li, Wenwen; Zhou, Yafang; Yi, Fang; Wang, Jianfeng; Hu, Yacen; Yao, Lingyan; Zhou, Lin; Xu, Hongwei

2017-12-10

To analyze potential mutations of the NOTCH3 gene in two Chinese families featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL). The two probands and related family members and 100 healthy controls were recruited. Potential mutations of the NOTCH3 gene were screened by PCR and direct sequencing. PolyPhen-2 and SIFT software were used to predict the protein function. The conditions of both probands were adult-onset, with main clinical features including recurrent transient ischemic attacks and/or strokes, cognitive impairment. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A heterozygous mutation c.328C>T (p.Arg110Cys), which was located in exon 3 of the NOTCH3 gene and known as a causative mutation, was identified in proband 1. A novel heterozygous mutation c.1013 G>C (p.Cys338Ser) located in exon 6 of the NOTCH3 gene was identified in the proband 2, which was not reported previously. The same mutations were not detected among the 100 unrelated healthy controls. Function analysis suggested that heterozygous mutation c.1013G>C can severely affect the functions of NOTCH3 protein. Two heterozygous missense mutations in the NOTCH3 gene have been identified in two families affected with CADASIL. The novel heterozygous Cys338Ser mutation in exon 6 of the NOTCH3 gene probably underlies the CADASIL.

Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis.

PubMed

Choudhuri, K; Gregorio, G V; Mieli-Vergani, G; Vergani, D

1998-11-01

We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.

The association of exposure to hepatitis B and C viruses with lung function and respiratory disease: a population based study from the NHANES III database.

PubMed

Goh, Li Yen; Card, Tim; Fogarty, Andrew W; McKeever, Tricia M

2014-12-01

Globally, 500 million people are chronically infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV). While these viruses are notorious for their detrimental effect on the liver they are also known to affect multiple organs in the body including the lungs. To investigate if exposure to HBV and HCV is associated with lung function and respiratory diseases. Data from the Third National Health and Nutrition Examination Survey (NHANES III) was analysed using multiple linear regressions to investigate the association between exposure to HBV and HCV with the various measures of lung function, while multiple logistic regressions were used to evaluate the association with the respiratory diseases asthma and chronic obstructive pulmonary disease (COPD). Exposure to HCV was significantly associated with an increase in Forced Expiratory Volume in 1 s, FEV1 (Coef: 97.94 ml, 95% CI: 38.87 to 157.01) and Full Vital Capacity, FVC (Coef: 90 ml, 95% CI: 14.50 to 166.24). Individuals who had been exposed to both HBV and HCV also had a significantly higher FEV1 (Coef: 145.82, CI: 60.68 to 230.94) and FVC (Coef: 195.09, CI: 78.91 to 311.26). There was also a significant association between exposure to HBV and asthma (OR: 1.28, 95% CI: 1.05 to 1.58). These associations were no longer significant after additionally adjusting for cocaine and marijuana use as well as poverty income ratio. Our research implies that hepatotropic viruses may affect the respiratory system, but more work at a population level is needed to further explore these associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dysphagia in a patient with bilateral medial medullary infarcts.

PubMed

Paliwal, Vimal K; Kalita, Jayanti; Misra, Usha K

2009-09-01

Bilateral medial medullary infarct is a rare stroke syndrome and only a handful of cases have been described. Dysphagia as a manifestation of medullary infarcts is well recognized but often associated with lateral medullary infarct. Bilateral medial medullary infarcts are commonly associated with severe dysphagia in addition to a number of other signs and symptoms. We describe a patient who had bilateral medial medullary infarct with severe dysphagia in addition to quadriplegia and respiratory difficulty, and analyze infarct topography with respect to dysphagia, risk factors, vascular territories involved, and prognosis in view of previously reported cases.

Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles.

PubMed Central

Nisini, R; Paroli, M; Accapezzato, D; Bonino, F; Rosina, F; Santantonio, T; Sallusto, F; Amoroso, A; Houghton, M; Barnaba, V

1997-01-01

The T-cell-mediated immune response plays a crucial role in defense against hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides. However, very little is known about the role of specific T cells during hepatitis delta virus (HDV) infection in humans. In this study, the T-cell response to HDV in chronic hepatitis B virus (HBV) carriers with HDV superinfection was investigated at different levels. Analysis of peripheral blood mononuclear cell (PBMC) proliferation in response to a recombinant form of large hepatitis delta antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically responded to HDAg. By employing synthetic peptides spanning the entire HDAg sequence, we found that T-cell recognition was directed against different antigenic determinants, with patient-to-patient variation in the pattern of response to peptides. Interestingly, all responders had signs of inactive HDV-induced disease, while none of the patients with active disease and none of the control subjects showed any significant proliferation. More accurate information about the specific T-cell response was obtained at the clonal level. A panel of HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine-specificity analysis revealed that the clones tested individually recognized four epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106 to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells in association with multiple class II molecules. In addition, peptide 26 to 41 was efficiently generated after processing of HDAg through the endogenous processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell clones assayed were able to produce high levels of gamma interferon (IFN-gamma), belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were cytotoxic in a specific assay. This study provides the first evidence that detection of a specific T-cell response to HDAg in the peripheral blood of individuals with hepatitis delta is related to the decrease of HDV-induced disease activity. The HDAg epitopes identified here and particularly those recognized by CD4+ T cells in association with multiple major histocompatibility complex class II molecules may be potentially exploited for the preparation of a vaccine for prophylaxis and therapy of HDV infection. PMID:9032359

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification.

PubMed

Allen, Richard J; Musante, Cynthia J

2017-01-01

Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing 'transfer function'. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole.

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification

PubMed Central

Allen, Richard J; Musante, Cynthia J

2017-01-01

Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing ‘transfer function’. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole. PMID:28469410

Covert Hepatic Encephalopathy: Can My Patient Drive?

PubMed Central

Shaw, Jawaid; Bajaj, Jasmohan S

2016-01-01

Liver cirrhosis is a public health problem and hepatic encephalopathy (HE) is one of its main complications, which can be either overt meaning thereby evident and readily diagnosed, or covert/minimal (CHE) needing psychometric testing for diagnosis. Patients with CHE hepatic encephalopathy have deficits in multiple domains including visuo-spatial assessment, attention, response inhibition, working memory, along with psychomotor speed to name a few areas. These patients have poor navigational skills, get fatigued easily and demonstrate poor insight into their driving deficits. The combination of all these leads them to have poor driving skills leading to traffic violations and crashes as demonstrated not only on the simulation testing but also in real life driving events. There are multiple psychometric tests for CHE testing but these are not easily available and there is no uniform consensus on the gold standard testing as of yet. It does not automatically connote that all patients who test positive on driving simulation testing are unfit to drive. The physicians are encouraged to take driving history from the patient and the care- givers on every encounter and focus their counseling efforts more on patients with recent history of traffic crashes, with abnormal simulation studies and history of alcohol cessation within last year. As physicians are not trained to determine fitness to drive, their approach towards CHE patients in regards to driving restrictions should be driven by ethical principles while as respecting the local laws. PMID:28027071

Zebrafish as a disease model for studying human hepatocellular carcinoma.

PubMed

Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

2015-11-14

Liver cancer is one of the world's most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury.

Zebrafish as a disease model for studying human hepatocellular carcinoma

PubMed Central

Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

2015-01-01

Liver cancer is one of the world’s most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury. PMID:26576090

Host-regulated Hepatitis B Virus Capsid Assembly in a Mammalian Cell-free System.

PubMed

Liu, Kuancheng; Hu, Jianming

2018-04-20

The hepatitis B virus (HBV) is an important global human pathogen and represents a major cause of hepatitis, liver cirrhosis and liver cancer. The HBV capsid is composed of multiple copies of a single viral protein, the capsid or core protein (HBc), plays multiple roles in the viral life cycle, and has emerged recently as a major target for developing antiviral therapies against HBV infection. Although several systems have been developed to study HBV capsid assembly, including heterologous overexpression systems like bacteria and insect cells, in vitro assembly using purified protein, and mammalian cell culture systems, the requirement for non-physiological concentrations of HBc and salts and the difficulty in manipulating host regulators of assembly presents major limitations for detailed studies on capsid assembly under physiologically relevant conditions. We have recently developed a mammalian cell-free system based on the rabbit reticulocyte lysate (RRL), in which HBc is expressed at physiological concentrations and assembles into capsids under near-physiological conditions. This system has already revealed HBc assembly requirements that are not anticipated based on previous assembly systems. Furthermore, capsid assembly in this system is regulated by endogenous host factors that can be readily manipulated. Here we present a detailed protocol for this cell-free capsid assembly system, including an illustration on how to manipulate host factors that regulate assembly.

Behavioral and Healthcare-Associated Risk Factors for Chronic Hepatitis C Virus Infection in Korea

PubMed Central

Kim, Jong Yeop; Cho, Juhee; Hwang, Sung Ho; Kil, Ho; Bae, Si Hyun; Kim, Young Seok; Lee, Han Chu

2012-01-01

The risk factors related to hepatitis C virus (HCV) infection showed geographic and temporal differences. We investigated HCV-related risk factors in Korea where intravenous drug use (IVDU) is uncommon. The HCV-related risk factors were investigated in a prospective, multicenter chronic HCV cohort (n = 711) using a standardized questionnaire in four university hospitals. The results were compared with those of 206 patients with chronic liver diseases not related to either of HCV or hepatitis B virus infection (comparison group). The IVDU was found in 3.9% and remote blood transfusion (≥ 20 yr ago) in 18.3% in HCV cohort group, while that in comparison group was in none and 5.3%, respectively. In a multivariate logistic analysis, transfusion in the remote past (odds ratio [OR], 2.99), needle stick injury (OR, 4.72), surgery (OR, 1.89), dental procedures (OR, 2.96), tattooing (OR, 2.07), and multiple sexual partners (2-3 persons; OR, 2.14, ≥ 4 persons; OR, 3.19), were independent risk factors for HCV infection. In conclusion, the major risk factors for HCV infection in Korea are mostly related to conventional or alterative healthcare procedures such as blood transfusion in the remote past, needle stick injury, surgery, dental procedure, and tattooing although multiple sex partners or IVDU plays a minor role. PMID:23166420

Imaging and radiological interventions in extra-hepatic portal vein obstruction

PubMed Central

Pargewar, Sudheer S; Desai, Saloni N; Rajesh, S; Singh, Vaibhav P; Arora, Ankur; Mukund, Amar

2016-01-01

Extrahepatic portal vein obstruction (EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension (PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt (PSS) and revision of PSS. PMID:27358683

Adverse events after endovascular treatment of chronic cerebro-spinal venous insufficiency (CCSVI) in patients with multiple sclerosis.

PubMed

Ghezzi, A; Annovazzi, P; Amato, M P; Capello, E; Cavalla, P; Cocco, E; Falcini, M; Gallo, A; Patti, F; Perini, P; Rodegher, M E; Rovaris, M; Rottoli, M R; Comi, G

2013-06-01

Although it is debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients undergo endovascular treatment (ET) of CCSVI. A study is ongoing in Italy to evaluate the clinical outcome of ET. Severe adverse events (AEs) occurred in 15/462 subjects at a variable interval after ET: jugular thrombosis in seven patients, tetraventricular hydrocephalus, stroke, paroxysmal atrial fibrillation, status epilepticus, aspiration pneumonia, hypertension with tachicardia, or bleeding of bedsore in the remaining seven cases. One patient died because of myocardial infarction 10 weeks after ET. The risk of severe AEs related to ET for CCSVI must be carefully considered.

Simulating Chemical-Induced Injury Using Virtual Hepatic Tissues

EPA Science Inventory

Chemical-induced liver injury involves a dynamic sequence of events that span multiple levels of biological organization. Current methods for testing the toxicity of a single chemical can cost millions of dollars, take up to two years and sacrifice thousands of animals. It is dif...

Multiple infections and associated risk factors among non-injecting cocaine users in Argentina.

PubMed

Rossi, Diana; Radulich, Graciela; Muzzio, Estela; Naveira, Jorge; Sosa-Estani, Sergio; Rey, Jorge; Griemberg, Gloria; Friedman, Samuel R; Martínez-Peralta, Liliana; Weissenbacher, Mercedes

2008-05-01

The aim of this study was to estimate the seroprevalence rates of human immunodeficiency virus (HIV), hepatitis B virus (HBV, core antibody), hepatitis C virus (HCV), and syphilis infections and analyze associated risk factors among 504 non-injecting cocaine users (NICU) in Buenos Aires, Argentina. Participants were interviewed in face-to-face sessions through a short structured questionnaire. Using venipuncture, 10 mL of blood was collected. Seroprevalence rates were: HIV (6.3%), HBV (9%), HCV (7.5%), and VDRL (4.2%). The risk of being infected with HIV, HBV, and HCV was significantly associated with having had a sex partner who was either a drug injector or who was known to be HIV positive. HIV and HCV infections were associated with former imprisonment, and HCV was associated with having been tattooed. Because of the rising number of NICU and the multiple infections detected, it is essential to implement prevention strategies focused on this population.

Multiple primary malignancies of the liver and the colon: a complex diagnostic and decisional process with a final unanswered question.

PubMed

Portolani, Nazario; Baiocchi, Gianluca; Baronchelli, Carla; Gheza, Federico; Giulini, Stefano Maria

2014-03-29

We herein present the case of a 78-year-old man with an incidental finding of a solid hepatic mass without symptoms and only a laparotomic cholecystectomy for acute cholecystitis in the past surgical history. A colonoscopy, a magnetic resonance imaging scan, a positron emission tomography scan, and a computed tomography scan completed the preoperative workup: a neoplastic lesion 4.3×3 cm in size was diagnosed at segments IV and V, associated with a neoplastic involvement of the splenic flexure without signs of colonic occlusion. After colonic resection, a frozen section on a granulomatous-like tissue at gastric border suggested a diagnosis of an adenocarcinoma of bilio-pancreatic type, changing the surgical strategy to include gastric resection and hepatic pedicle node dissection. The discussion turns around the idea that a final diagnosis of colon cancer with regional nodal involvement (pT3N1) and metastatic gallbladder cancer with multiple peritoneal seedings cannot be excluded.

Different Causes of Death in Patients with Myocardial Infarction Type 1, Type 2, and Myocardial Injury.

PubMed

Lambrecht, Sascha; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Hosbond, Susanne; Diederichsen, Axel C P; Thygesen, Kristian; Mickley, Hans

2018-05-01

Data outlining the mortality and the causes of death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and those with myocardial injury are limited. During a 1-year period from January 2010 to January 2011, all hospitalized patients who had cardiac troponin I measured on clinical indication were prospectively studied. Patients with at least one cardiac troponin I value >30 ng/L underwent case ascertainment and individual evaluation by an experienced adjudication committee. Patients were classified as having type 1 myocardial infarction, type 2 myocardial infarction, or myocardial injury according to the criteria of the universal definition of myocardial infarction. Follow-up was ensured until December 31, 2014. Data on mortality and causes of death were obtained from the Danish Civil Registration System and the Danish Register of Causes of Death. Overall, 3762 consecutive patients were followed for a mean of 3.2 years (interquartile range 1.3-3.6 years). All-cause mortality differed significantly among categories: Type 1 myocardial infarction 31.7%, type 2 myocardial infarction 62.2%, myocardial injury 58.7%, and 22.2% in patients with nonelevated troponin values (log-rank test; P < .0001). In patients with type 1 myocardial infarction, 61.3% died from cardiovascular causes, vs 42.6% in patients with type 2 myocardial infarction (P = .015) and 41.2% in those with myocardial injury (P < .0001). The overall mortality and the causes of death did not differ substantially between patients with type 2 myocardial infarction and those with myocardial injury. Patients with type 2 myocardial infarction and myocardial injury exhibit a significantly higher long-term mortality compared with patients with type 1 myocardial infarction . However, most patients with type 1 myocardial infarction die from cardiovascular causes in contrast to patients with type 2 myocardial infarction and myocardial injury, in whom noncardiovascular causes of death predominate. Copyright © 2018 Elsevier Inc. All rights reserved.

Hepatic enzyme decline after pediatric blunt trauma: a tool for timing child abuse?

PubMed

Baxter, Amy L; Lindberg, Daniel M; Burke, Bonnie L; Shults, Justine; Holmes, James F

2008-09-01

Previous research in adult patients with blunt hepatic injuries has suggested a pattern of serum hepatic transaminase concentration decline. Evaluating this decline after pediatric blunt hepatic trauma could establish parameters for estimating the time of inflicted injuries. Deviation from a consistent transaminase resolution pattern could indicate a developing complication. Retrospective review of pediatric patients with injuries including blunt liver trauma admitted to one of four urban level 1 trauma centers from 1990 to 2000. Cases were excluded for shock, death within 48 h, complications, or inability to determine injury time. Transaminase concentration decline was modeled by individual patients, by injury grade, and as a ratio with regard to injury time. One hundred and seventy-six patients met inclusion criteria. The rate of aspartate aminotransferase (AST) clearance changed significantly over time. Alanine aminotransferase (ALT) fell more slowly. Of the 118 patients who had multiple measurements of AST, for 112 (95%) the first concentration obtained was the highest. When ALT was greater than AST, the injury was older than 12h (97% specificity (95% CI, 95-99%), sensitivity 42% (95% CI, 33-50%)). Patients with enzymes that rose after 14 h post-injury were more likely to develop complications (RR=24, 95% CI 10-58). Hepatic transaminases rise rapidly after uncomplicated blunt liver injury, then fall predictably. Persistently stable or increasing concentrations may indicate complications. ALT>AST indicates subacute injury.

Rates of HIV and Hepatitis Infections in Clients Entering Heroin-Assisted Treatment between 2003 and 2013 and Risk Factors for Hepatitis C Infection.

PubMed

Dickson-Spillmann, Maria; Haug, Severin; Uchtenhagen, Ambros; Bruggmann, Philip; Schaub, Michael P

2016-01-01

We report on the rates of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in 1,313 clients entering heroin-assisted treatment (HAT) in Switzerland from 2003 to 2013. We identify predictors of HCV infection. Data were collected using questionnaires within 2 weeks of clients' first entry into HAT. Prevalence of HAV, HBV, HCV and HIV was calculated using laboratory test results collected at entry or using reports of older test results. Predictors of HCV status were identified through multiple logistic regression analysis. Results show stable rates of HIV-positive clients and decreasing proportions of HAV- and HBV-infected clients. In 2013, there were 12% (n = 8) HIV-, 20% (n = 12) HAV-, 20% (n = 12) HBV- and 52% HCV- (n = 34) positive clients. Vaccination against HAV and HBV had become more frequent. Predictors of positive HCV status included older age, female gender, earlier year of entry, having spent 1 month or more in detention or prison, use of injected heroin and more years of intravenous use. Our results highlight the fact that efforts to prevent and test for infections and to promote vaccination against HAV and HBV in heroin users need to be continued. © 2015 S. Karger AG, Basel.

Physicians, nonphysician healthcare providers, and patients communicating in hepatitis C: an in-office sociolinguistic study.

PubMed

Hamilton, Heidi E; Gordon, Cynthia; Nelson, Meaghan; Kerbleski, Marian

2006-01-01

In-office conversations about hepatitis C can impact patients' perceptions of outcomes, as well as medication adherence. This study analyzed interactions between physicians, nonphysician healthcare providers (including nurses), and patients with hepatitis C virus infection in order to examine differences based on number and type of providers participating. Gastroenterologists, nonphysician healthcare providers, and patients with hepatitis C virus infection were video- and audio-recorded during regularly scheduled visits. Recordings were transcribed and analyzed using validated sociolinguistic techniques. Thirty-four visits took place with a physician only, 4 with a nonphysician healthcare provider only, and 25 with both providers (9 concurrent and 16 consecutive). Differences among the participant schema included visit length, patient "talk-time," and motivation provided. When providers saw patients consecutively, differing information was sometimes provided. In visits where providers saw the patient concurrently, competing authority between providers and exclusion of the patient through use of medical jargon were obstacles to ideal communication. Differences in hepatitis C-related interactions based on the number and type of participants suggest opportunities for improved communication. In visits with multiple providers, physicians and nurses should attempt to ensure that they (a) avoid supplying differing information, (b) present a "unified front" to avoid competing authority, and (c) minimize the use of medical jargon, which excludes patients from participating in their own healthcare.

Recent advances in the diagnosis and treatment of primary biliary cholangitis

PubMed Central

Huang, Ying-Qiu

2016-01-01

Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients. PMID:27957241

[Efficacy of the combination therapy in early stage of recurrent cholangio celluler carcinoma (CCC)].

PubMed

Fujiwara, Shinichi; Hasuike, Yasunori; Fukuchi, Nariaki; Hayashi, Nobuyasu; Kida, Hiroyuki; Tsujie, Masaki; Yoshida, Tetsuya; Ebisui, Chikara; Sakita, Isao; Fujimoto, Takayoshi

2005-10-01

We report a case of cholangio celluler carcinoma (CCC) with a good quality of life, in spite of the recurrence of peritoneum and portal hepatic lymph nodes (PHLN), due to the combination therapy that consisted of hepatic arterial infusion, systemic chemotherapy, radiation therapy and an insertion of a metallic stent into the bile duct. The patient was a 61-year-old man. Left hepatectomy was done due to multiple CCC. For the purpose of preventing the recurrence of CCC in residual liver, we performed an arterial infusion therapy. Ten months later, metastases to peritoneum and portal hepatic lymph nodes were found, so the resection of the peritoneum was performed, and cells in ascites were defined to be positive with cytology. After 2 years from the first operation, the size of portal hepatic lymph nodes had grown and both the billilbin and tumor marker levels had increased, so we started systemic chemotherapy, radiation therapy and insertion of a metallic stent into the bile duct. The tumor marker level decreased in a short time. Consequently, we inserted a metallic stent into the bile duct and radiation therapy was performed. Until the patient's death due to peritonitis carcinomatosa, the recurrence in residual liver occurred only once in three years after the first operation, and portal hepatic lymph nodes did not grow for two years after the recurrence.

Evaluation of the In Vivo Therapeutic Effects of Radix Paeoniae Rubra Ethanol Extract with the Hypoglycemic Activities Measured from Multiple Cell-Based Assays

PubMed Central

Chang, Chia-Chuan; Yuan, Wei; Lin, Yun-Lian; Liu, Ren-Shyan; Juan, Yi-Chen; Sun, Wan-Hua; Tsay, Huey Jen; Lee, Yu-Ching

2016-01-01

Background. Radix Paeoniae Rubra (Chi Shao) contains several phytochemicals with hypoglycemic actions. Current research aims to explore potential insulinotropic effects and long-term therapeutic efficacy of such herb against type 2 diabetes. Methods. Composition analysis for the ethanol extract (PRExt) was executed by high performance liquid chromatography. Polyphenol-enriched fraction was characterized by high pressure size exclusion chromatography. Multiple cell platforms were employed to evaluate hypoglycemic bioactivities. In animal experiments, blood glucose, the homeostasis model assessment (HOMA)-index assessment, glucose tolerance test, and in vivo glucose uptake were all measured. Additional effects of PRExt on obesity and hepatic steatosis were evaluated by serum and histological analysis. Results. PRExt provides multiple hypoglycemic effects including the enhancement of glucose-mediated insulin secretion. Pentagalloylglucose and polyphenol-enriched fraction are two insulinotropic constituents. Moreover, PRExt intraperitoneal injection causes acute hypoglycemic effects on fasted db/db mice. Oral administration of PRExt (200 mg/kg b.w.) gradually reduces blood glucose in db/db mice to the level similar to that in C57J/B6 mice after 30 days. The improvement of glucose intolerance, HOMA-index, and in vivo glucose uptake is evident in addition to the weight loss effect and attenuation of hepatic steatosis. Conclusion. PRExt is an effective antidiabetic herbal extract with multiple hypoglycemic bioactivities. PMID:28018473

Blood transfusion transmitted infections in multiple blood transfused patients of Beta thalassaemia.

PubMed

Vidja, Prakash J; Vachhani, J H; Sheikh, S S; Santwani, P M

2011-06-01

Transfusion Transmitted Infection (TTI) continue to be a problem in many parts of world and multi-transfused patients of beta thalassaemia major are at a particularly increased risk of TTI. This study is aimed to estimate the prevalence of blood TTI in multiple blood transfused patients of beta thalassaemia major. Cross-sectional study of 200 multi-transfused patients of beta thalassaemia major, who were interviewed using a structured questionnaire and history was taken regarding sero-status of HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) infection from their case papers. This study was conducted at the department of Pathology, M.P. Shah medical college, Jamnagar and Thalassemia ward, G.G. Hospital, Jamnagar (Gujarat, India) from March to May 2010. Out of 200 multiple blood transfused patients 7% patients were infected with TTI. Total 9 male patients and 5 female patients were infected with TTI. The seroreactivity for HIV was 3% (06/200); 1% (02/200) were males and 2% (04/200) were females. The seroreactivity for HBV was 2% (04/200) all were males. The seroreactivity for HCV was 2% (04/200); 1.5% (03/200) were males and 0.5% (01/200) was female. HIV, HBV, HCV infections are most prevalent TTI among multiple blood transfused patients of beta thalassemia major, and remains a major health problem for these patients.

Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach

PubMed Central

Broessner, Gregor; Beer, Ronny; Franz, Gerhard; Lackner, Peter; Engelhardt, Klaus; Brenneis, Christian; Pfausler, Bettina; Schmutzhard, Erich

2005-01-01

Introduction We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. Methods A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Results Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. Conclusion In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result. PMID:16285034

Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers

ClinicalTrials.gov

2017-12-08

Acute Myocardial Infarction (AMI); Acute Coronary Syndrome (ACS); ST Elevation (STEMI) Myocardial Infarction; Ischemic Reperfusion Injury; Non-ST Elevation (NSTEMI) Myocardial Infarction; Angina, Unstable

Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

PubMed

Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

2014-01-01

Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

Mechanical regulation of fibroblast migration and collagen remodelling in healing myocardial infarcts

PubMed Central

Rouillard, Andrew D; Holmes, Jeffrey W

2012-01-01

Effective management of healing and remodelling after myocardial infarction is an important problem in modern cardiology practice. We have recently shown that the level of infarct anisotropy is a critical determinant of heart function following a large anterior infarction, which suggests that therapeutic gains may be realized by controlling infarct anisotropy. However, factors regulating infarct anisotropy are not well understood. Mechanical, structural and chemical guidance cues have all been shown to regulate alignment of fibroblasts and collagen in vitro, and prior studies have proposed that each of these cues could regulate anisotropy of infarct scar tissue, but understanding of fibroblast behaviour in the complex environment of a healing infarct is lacking. We developed an agent-based model of infarct healing that accounted for the combined influence of these cues on fibroblast alignment, collagen deposition and collagen remodelling. We pooled published experimental data from several sources in order to determine parameter values, then used the model to test the importance of each cue for predicting collagen alignment measurements from a set of recent cryoinfarction experiments. We found that although chemokine gradients and pre-existing matrix structures had important effects on collagen organization, a response of fibroblasts to mechanical cues was critical for correctly predicting collagen alignment in infarct scar. Many proposed therapies for myocardial infarction, such as injection of cells or polymers, alter the mechanics of the infarct region. Our modelling results suggest that such therapies could change the anisotropy of the healing infarct, which could have important functional consequences. This model is therefore a potentially important tool for predicting how such interventions change healing outcomes. PMID:22495588

Optimizing image registration and infarct definition in stroke research.

PubMed

Harston, George W J; Minks, David; Sheerin, Fintan; Payne, Stephen J; Chappell, Michael; Jezzard, Peter; Jenkinson, Mark; Kennedy, James

2017-03-01

Accurate representation of final infarct volume is essential for assessing the efficacy of stroke interventions in imaging-based studies. This study defines the impact of image registration methods used at different timepoints following stroke, and the implications for infarct definition in stroke research. Patients presenting with acute ischemic stroke were imaged serially using magnetic resonance imaging. Infarct volume was defined manually using four metrics: 24-h b1000 imaging; 1-week and 1-month T2-weighted FLAIR; and automatically using predefined thresholds of ADC at 24 h. Infarct overlap statistics and volumes were compared across timepoints following both rigid body and nonlinear image registration to the presenting MRI. The effect of nonlinear registration on a hypothetical trial sample size was calculated. Thirty-seven patients were included. Nonlinear registration improved infarct overlap statistics and consistency of total infarct volumes across timepoints, and reduced infarct volumes by 4.0 mL (13.1%) and 7.1 mL (18.2%) at 24 h and 1 week, respectively, compared to rigid body registration. Infarct volume at 24 h, defined using a predetermined ADC threshold, was less sensitive to infarction than b1000 imaging. 1-week T2-weighted FLAIR imaging was the most accurate representation of final infarct volume. Nonlinear registration reduced hypothetical trial sample size, independent of infarct volume, by an average of 13%. Nonlinear image registration may offer the opportunity of improving the accuracy of infarct definition in serial imaging studies compared to rigid body registration, helping to overcome the challenges of anatomical distortions at subacute timepoints, and reducing sample size for imaging-based clinical trials.

Endovascular Exclusion of Visceral Artery Aneurysms with Stent-Grafts: Technique and Long-Term Follow-up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossi, Michele; Rebonato, Alberto, E-mail: albertorebonato@libero.it; Greco, Laura

This paper describes four cases of visceral artery aneurysms (VAAs) successfully treated with endovascular stent-grafts and discusses the endovascular approach to VAAs and the long-term results. Four balloon expandable stent-grafts were used to treat three splenic artery aneurysms and one bleeding common hepatic artery pseudoaneurysm. The percutaneous access site and the materials were chosen on the basis of CT angiography findings. In all cases the aneurysms were successfully excluded. In one case a splenic infarction occurred, with nonrelevant clinical findings. At 16- to 24-month follow-up three patients had patent stents and complete exclusion and shrinkage of the aneurysms. One patientmore » died due to pancreatitis and sepsis, 16 days after successful stenting and exclusion of a bleeding pseudoaneurysm. We conclude that endovascular treatment using covered stent-grafts is a valid therapeutic option for VAAs. Multislice CT preoperative study helps in planning stent-graft positioning.« less

Streptococcus agalactiae septicemia in a patient with diabetes and hepatic cirrhosis

PubMed Central

Ferreira, Cristiane Rúbia

2015-01-01

Streptococcus agalactiae is a well-known pathogen during pregnancy and in neonates. Among non-pregnant adults, invasive infection, although rare, is showing increasing frequency, especially in chronically ill, immunosuppressed, or older patients. Although rare, the clinical features of meningeal infection caused by S. agalactiae are similar to other bacterial meningitis. The authors report the case of a middle-aged man previously diagnosed with hypertension, diabetes mellitus, and alcoholic liver cirrhosis, who was admitted at the emergency department with a Glasgow Coma Scale of 11/12, generalized spasticity, bilateral Babinski sign, and hypertension. The clinical outcome was bad, with refractory shock and death within 24 hours of hospitalization. The bacteriological work-up isolated S. agalactiae in the cerebral spinal fluid (CSF), blood, and urine. An autopsy revealed meningoencephalitis, acute myocardial infarction, and pyelonephritis due to septic emboli. The authors point out the atypical CSF findings, the rapid fatal outcome, and the importance of including this pathogen among the etiologic possibilities of invasive infections in this group of patients. PMID:26894044

Check-up and cardiovascular risk progression: is there a room for innovation?

PubMed Central

Conceição, Raquel Dilguerian de Oliveira; Laurinavicius, Antonio Gabriele; Kashiwagi, Nea Miwa; de Carvalho, José Antonio Maluf; Oliva, Carlos Alberto Garcia; Santos, Raul Dias

2015-01-01

ABSTRACT Objective: To evaluate the impact of traditional check-up appointment on the progression of the cardiovascular risk throughout time. Methods: This retrospective cohort study included 11,126 medical records of asymptomatic executives who were evaluated between January, 2005 and October, 2008. Variables included participants’ demographics characteristics, smoking habit, history of cardiovascular diseases, diabetes, dyslipidemia, total cholesterol, HDL, triglycerides, glucose, c-reactive protein, waist circumference, hepatic steatosis, Framingham score, metabolic syndrome, level of physical activity, stress, alcohol consumption, and body mass index. Results: A total of 3,150 patients was included in the final analysis. A worsening was observed in all risk factors, excepting in smoking habit, incidence of myocardial infarction or stroke and in the number of individuals classified as medium or high risk for cardiovascular events. In addition, a decrease in stress level and alcohol consumption was also seen. Conclusion: The adoption of consistent health policies by companies is imperative in order to reduce the risk factors and the future costs associated with illness and absenteeism. PMID:26154540

Myocardial infarction in the elderly.

PubMed

Carro, Amelia; Kaski, Juan Carlos

2011-04-01

Advances in pharmacological treatment and effective early myocardial revascularization have -in recent years- led to improved clinical outcomes in patients with acute myocardial infarction (AMI). However, it has been suggested that compared to younger subjects, elderly AMI patients are less likely to receive evidence-based treatment, including myocardial revascularization therapy. Several reasons have been postulated to explain this trend, including uncertainty regarding the true benefits of the interventions commonly used in this setting as well as increased risk mainly associated with comorbidities. The diagnosis, management, and post-hospitalization care of elderly patients presenting with an acute coronary syndrome pose many difficulties at present. A complex interplay of variables such as comorbidities, functional and socioeconomic status, side effects associated with multiple drug administration, and individual biologic variability, all contribute to creating a complex clinical scenario. In this complex setting, clinicians are often required to extrapolate evidence-based results obtained in cardiovascular trials from which older patients are often, implicitly or explicitly, excluded. This article reviews current recommendations regarding management of AMI in the elderly.

A Nationwide Assessment of the Association of Smoking Bans and Cigarette Taxes With Hospitalizations for Acute Myocardial Infarction, Heart Failure, and Pneumonia

PubMed Central

Ho, Vivian; Ross, Joseph S.; Steiner, Claudia A.; Mandawat, Aditya; Short, Marah; Ku-Goto, Meei-Hsiang; Krumholz, Harlan M.

2016-01-01

Multiple studies claim that public place smoking bans are associated with reductions in smoking-related hospitalization rates. No national study using complete hospitalization counts by area that accounts for contemporaneous controls including state cigarette taxes has been conducted. We examine the association between county-level smoking-related hospitalization rates and comprehensive smoking bans in 28 states from 2001 to 2008. Differences-in-differences analysis measures changes in hospitalization rates before versus after introducing bans in bars, restaurants, and workplaces, controlling for cigarette taxes, adjusting for local health and provider characteristics. Smoking bans were not associated with acute myocardial infarction or heart failure hospitalizations, but lowered pneumonia hospitalization rates for persons ages 60 to 74 years. Higher cigarette taxes were associated with lower heart failure hospitalizations for all ages and fewer pneumonia hospitalizations for adults aged 60 to 74. Previous studies may have overestimated the relation between smoking bans and hospitalizations and underestimated the effects of cigarette taxes. PMID:27624634

Curbing Inflammation in the Ischemic Heart Disease

PubMed Central

Evora, Paulo Roberto B.; Nather, Julio; Tubino, Paulo Victor; Albuquerque, Agnes Afrodite S.; Celotto, Andrea Carla; Rodrigues, Alfredo J.

2013-01-01

A modern concept considers acute coronary syndrome as an autoinflammatory disorder. From the onset to the healing stage, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Inflammatory response following acute myocardial infarction has been well documented since the 1940s and 1950s, including increased erythrocyte sedimentation rate, the C-reactive protein analysis, and the determination of serum complement. It is surprising to note, based on a wide literature overview including the following 30 years (decades of 1960, 1970, and 1980), that the inflammatory acute myocardium infarction lost its focus, virtually disappearing from the literature reports. The reversal of this historical process occurs in the 1990s with the explosion of studies involving cytokines. Considering the importance of inflammation in the pathophysiology of ischemic heart disease, the aim of this paper is to present a conceptual overview in order to explore the possibility of curbing this inflammatory process. PMID:23819098

Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment.

PubMed Central

Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.

2007-01-01

The aim of this study was to determine whether intravenously-administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group was significantly improved compared with that in controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion. PMID:17257581

Myocardial Infarction in the Elderly

PubMed Central

Carro, Amelia; Kaski, Juan Carlos

2011-01-01

Advances in pharmacological treatment and effective early myocardial revascularization have –in recent years- led to improved clinical outcomes in patients with acute myocardial infarction (AMI). However, it has been suggested that compared to younger subjects, elderly AMI patients are less likely to receive evidence-based treatment, including myocardial revascularization therapy. Several reasons have been postulated to explain this trend, including uncertainty regarding the true benefits of the interventions commonly used in this setting as well as increased risk mainly associated with comorbidities. The diagnosis, management, and post-hospitalization care of elderly patients presenting with an acute coronary syndrome pose many difficulties at present. A complex interplay of variables such as comorbidities, functional and socioeconomic status, side effects associated with multiple drug administration, and individual biologic variability, all contribute to creating a complex clinical scenario. In this complex setting, clinicians are often required to extrapolate evidence-based results obtained in cardiovascular trials from which older patients are often, implicitly or explicitly, excluded. This article reviews current recommendations regarding management of AMI in the elderly. PMID:22396870

A Nationwide Assessment of the Association of Smoking Bans and Cigarette Taxes With Hospitalizations for Acute Myocardial Infarction, Heart Failure, and Pneumonia.

PubMed

Ho, Vivian; Ross, Joseph S; Steiner, Claudia A; Mandawat, Aditya; Short, Marah; Ku-Goto, Meei-Hsiang; Krumholz, Harlan M

2017-12-01

Multiple studies claim that public place smoking bans are associated with reductions in smoking-related hospitalization rates. No national study using complete hospitalization counts by area that accounts for contemporaneous controls including state cigarette taxes has been conducted. We examine the association between county-level smoking-related hospitalization rates and comprehensive smoking bans in 28 states from 2001 to 2008. Differences-in-differences analysis measures changes in hospitalization rates before versus after introducing bans in bars, restaurants, and workplaces, controlling for cigarette taxes, adjusting for local health and provider characteristics. Smoking bans were not associated with acute myocardial infarction or heart failure hospitalizations, but lowered pneumonia hospitalization rates for persons ages 60 to 74 years. Higher cigarette taxes were associated with lower heart failure hospitalizations for all ages and fewer pneumonia hospitalizations for adults aged 60 to 74. Previous studies may have overestimated the relation between smoking bans and hospitalizations and underestimated the effects of cigarette taxes.

[Effective combination therapy of plasma exchange and subsequent cyclophosphamide pulses for catastrophic antiphospholipid antibody syndrome: a case report].

PubMed

Miyamae, T; Imagawa, T; Ito, S; Katakura, S; Mori, M; Ibe, M; Mitsuda, T; Aihara, Y; Nakanishi, S; Kohri, T; Yokota, S

1999-06-01

A 7-year-old girl with catastrophic antiphospholipid antibody syndrome was described. She firstly admitted to the local hospital with the complaints of persistent fever and abdominal pain, and was diagnosed as systemic lupus erythematosus with the laboratory findings as follows; positive for antinuclear antibody, anti-DNA antibody, and platelet-associated IgG, thrombocytopenia, and hypocomplementemia. 10 days after the initiation of oral prednisolone, she suddenly manifested tonic convulsion and unconsciousness accompanied by high fever. Because of the unresponsiveness to the methylprednisolone pulse therapy for supposed CNS lupus, she was transferred to our hospital. Her unconsciousness persisted, and pulsation on dorsalis pedis was not palpable on admission. Laboratory investigation revealed the falsely positive VDRL, a prolonged aPTT, positive for lupus-anticoagulant and antiphospholipid antibody. The magnetic resonance image demonstrated multiple spotty hyperintensity (T2) in the brain consistent with multiple hemorrhagic infarcts. Arteriogram demonstrated the infarct of dorsalis pedis, and coronary aneurysms. These findings were compatible with the criteria of catastrophic antiphospholipid antibody syndrome, she was diagnosed as catastrophic antiphospholipid antibody syndrome. The plasma exchange and subsequent cyclophosphamide-pulse therapy, which was given once a month for first 6 months, and later, at 3 months intervals, was effectively administered. This combination and oral anti-thrombotic therapy revealed effective for this kind of fatal disorder.

Magnetic resonance imaging reveals altered distribution of hepatic fat in children with type 1 diabetes compared to controls.

PubMed

Regnell, Simon E; Peterson, Pernilla; Trinh, Lena; Broberg, Per; Leander, Peter; Lernmark, Åke; Månsson, Sven; Elding Larsson, Helena

2015-08-01

Children with type 1 diabetes have been identified as a risk group for non-alcoholic fatty liver disease (NAFLD). The aim was to compare total hepatic fat fraction and fat distribution across Couinaud segments in children with type 1 diabetes and controls and the relation of hepatic fat to plasma and anthropometric parameters. Hepatic fat fraction and fat distribution across Couinaud segments were measured with magnetic resonance imaging (MRI) in 22 children with type 1 diabetes and 32 controls. Blood tests and anthropometric data were collected. No children had NAFLD. Children with type 1 diabetes had a slightly lower hepatic fat fraction (median 1.3%) than controls (median 1.8%), and their fat had a different segmental distribution. The fat fraction of segment V was the most representative of the liver as a whole. An incidental finding was that diabetes patients treated with multiple daily injections of insulin (MDI) had a fat distribution more similar to controls than patients with continuous subcutaneous insulin infusion (CSII). In children with type 1 diabetes, NAFLD may be less common than recent studies have suggested. Children with type 1 diabetes may have a lower fat fraction and a different fat distribution in the liver than controls. Diabetes treatment with MDI or CSII may affect liver fat, but this needs to be confirmed in a larger sample of patients. The heterogeneity of hepatic fat infiltration may affect results when liver biopsy is used for diagnosing fatty liver. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical presentation and management of Fasciola hepatica infection: Single-center experience

PubMed Central

Kaya, Muhsin; Beştaş, Remzi; Çetin, Sedat

2011-01-01

AIM: To identify the characteristic clinical, laboratory and radiological findings and response to treatment in patients with fascioliasis. METHODS: Patients who were diagnosed with Fasciola hepatica infection were included in this prospective study. Initial clinical, laboratory and radiological findings were recorded. All patients were followed until a complete response was achieved or for 6 mo after treatment discontinuation. RESULTS: Fasciola hepatica infection was diagnosed in 30 patients (24 females; mean age: 42.6 years) between January 2008 and February 2011. Twenty-two (73%) patients had hepatic phase fascioliasis, 5 patients had biliary phase, and 3 patients had biliary phase associated with acute pancreatitis. Of the 8 patients with biliary phase fascioliasis, 2 patients displayed features that overlapped with both hepatic and biliary phase. Abdominal pain and right upper abdominal tenderness were the most prominent signs and symptoms in all patients. Eosinophilia was the most prominent laboratory abnormality in both patients with hepatic and biliary phase (100% and 50%, respectively). Multiple nodular lesions like micro-abscesses on abdominal computerized tomography were the main radiological findings in patients with hepatic phase. Small linear filling defects in the distal choledochus were the main endoscopic retrograde cholangiopancreatography (ERCP) findings in patients with biliary phase. Patients with hepatic phase were treated with triclabendazole alone, and patients with biliary phase were treated with triclabendazole and had live Fasciola hepatica extracted from the bile ducts during ERCP. CONCLUSION: Fasciola hepatica infection should be considered in the differential diagnosis of patients with hepatic or biliary disease and/or acute pancreatitis associated with eosinophilia. PMID:22171131

Molecular confirmation of oysters as the vector for hepatitis A in a 2005 multistate outbreak.

PubMed

Shieh, Y C; Khudyakov, Y E; Xia, G; Ganova-Raeva, L M; Khambaty, F M; Woods, J W; Veazey, J E; Motes, M L; Glatzer, M B; Bialek, S R; Fiore, A E

2007-01-01

Numerous hepatitis A outbreaks were linked to the consumption of raw molluscan shellfish in the United States between 1960 and 1989. However, there had been no major molluscan shellfish-associated hepatitis A outbreaks reported in the United States for more than a decade (1989 to 2004). Beginning in late August 2005, at least 10 clusters of hepatitis A illnesses, totaling 39 persons, occurred in four states among restaurant patrons who ate oysters. Epidemiologic data indicated that oysters were the source of the outbreak. Traceback information showed that the implicated oysters were harvested from specific Gulf Coast areas. A voluntary recall of oysters was initiated in September. Hepatitis A virus (HAV) was detected in multiple 25-g portions in one of two recalled samples, indicating that as many as 1 of every 15 oysters from this source was contaminated. Comparing 315 nucleotides within the HAV VPl-2B region, 100% homology was found among four amplicons recovered from a total of six independent experiments of the implicated oysters, and an identical HAV sequence was detected in sera from all 28 patient serum specimens tested. Ten percent heterogeneity over 315 nucleotides (31 variants) was observed between the outbreak strain (subgenotype 1A) and an HM-175 strain (subgenotype 1B) used in the laboratory where the oysters were processed. To our knowledge, this investigation is the first in the United States to identify an HAV-identical strain in persons with hepatitis A as well as in the food that was implicated as the source of their infections.

The influence of myocardial substrate on ventricular fibrillation waveform: A swine model of acute and postmyocardial infarction

PubMed Central

Indik, Julia H.; Donnerstein, Richard L.; Hilwig, Ronald W.; Zuercher, Mathias; Feigelman, Justin; Kern, Karl B.; Berg, Marc D.; Berg, Robert A.

2009-01-01

Objective In cardiac arrest resulting from ventricular fibrillation, the ventricular fibrillation waveform may be a clue to its duration and predict the likelihood of shock success. However, ventricular fibrillation occurs in different myocardial substrates such as ischemia, heart failure, and structurally normal hearts. We hypothesized that ventricular fibrillation is altered by myocardial infarction and varies from the acute to postmyocardial infarction periods. Design An animal intervention study was conducted with comparison to a control group. Setting This study took place in a university animal laboratory. Subjects Study subjects included 37 swine. Interventions Myocardial infarction was induced by occlusion of the midleft anterior descending artery. Ventricular fibrillation was induced in control swine, acute myocardial infarction swine, and in postmyocardial infarction swine after a 2-wk recovery period. Measurements and Main Results Ventricular fibrillation was recorded in 11 swine with acute myocardial infarction, ten post-myocardial infarction, and 16 controls. Frequency (mean, median, dominant, and bandwidth) and amplitude-related content (slope, slope-amp [slope divided by amplitude], and amplitude–spectrum area) were analyzed. Frequencies at 5 mins of ventricular fibrillation were altered in both acute myocardial infarction (p < .001 for all frequency characteristics) and postmyocardial infarction swine (p = .015 for mean, .002 for median, .002 for dominant frequency, and <.001 for bandwidth). At 5 mins, median frequency was highest in controls, 10.9 ± .4 Hz; lowest in acute myocardial infarction, 8.4 ± .5 Hz; and intermediate in postmyocardial infarction, 9.7 ± .5 Hz (p < .001 for acute myocardial infarction and p = .002 for postmyocardial infarction compared with control). Slope and amplitude–spectrum area were similar among the three groups with a shallow decline after minute 2, whereas slope-amp remained significantly altered for acute myocardial infarction swine at 5 mins (p = .003). Conclusions Ventricular fibrillation frequencies depend on myocardial substrate and evolve from the acute through healing phases of myocardial infarction. Amplitude related measures, however, are similar among these groups. It is unknown how defibrillation may be affected by relying on the ventricular fibrillation waveform without considering myocardial substrate. PMID:18552696

Differences in symptoms, first medical contact and pre-hospital delay times between patients with ST- and non-ST-elevation myocardial infarction.

PubMed

Ängerud, Karin H; Sederholm Lawesson, Sofia; Isaksson, Rose-Marie; Thylén, Ingela; Swahn, Eva

2017-11-01

In ST-elevation myocardial infarction, time to reperfusion is crucial for the prognosis. Symptom presentation in myocardial infarction influences pre-hospital delay times but studies about differences in symptoms between patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction are sparse and inconclusive. The aim was to compare symptoms, first medical contact and pre-hospital delay times in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction. This multicentre, observational study included 694 myocardial infarction patients from five hospitals. The patients filled in a questionnaire about their pre-hospital experiences within 24 h of hospital admittance. Chest pain was the most common symptom in ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (88.7 vs 87.0%, p=0.56). Patients with cold sweat (odds ratio 3.61, 95% confidence interval 2.29-5.70), jaw pain (odds ratio 2.41, 95% confidence interval 1.04-5.58), and nausea (odds ratio 1.70, 95% confidence interval 1.01-2.87) were more likely to present with ST-elevation myocardial infarction, whereas the opposite was true for symptoms that come and go (odds ratio 0.58, 95% confidence interval 0.38-0.90) or anxiety (odds ratio 0.52, 95% confidence interval 0.29-0.92). Use of emergency medical services was higher among patients admitted with ST-elevation myocardial infarction. The pre-hospital delay time from symptom onset to first medical contact was significantly longer in non-ST-elevation myocardial infarction (2:05 h vs 1:10 h, p=0.001). Patients with ST-elevation myocardial infarction differed from those with non-ST-elevation myocardial infarction regarding symptom presentation, ambulance utilisation and pre-hospital delay times. This knowledge is important to be aware of for all healthcare personnel and the general public especially in order to recognise symptoms suggestive of ST-elevation myocardial infarction and when to decide if there is a need for an ambulance.

Systemic Multiple Aneurysms Caused by Vascular Ehlers-Danlos Syndrome.

PubMed

Gui, Xinyu; Li, Fangda; Wu, Lingeer; Zheng, Yuehong

2016-07-01

Systemic multiple aneurysms are rare and usually associated with collagen tissue disease, such as Ehlers-Danlos syndrome (EDS) or Marfan syndrome. In the present case, we describe a 39-year-old male patient with systemic multiple aneurysms and acute intraperitoneal hemorrhage who was clinically diagnosed with vascular EDS. Coil embolization of the distal segment of the common hepatic artery was performed, which resolved the patient's symptoms. With this case presentation, we aim to increase the awareness of vascular EDS among clinicians and emphasize the extreme fragility of the arteries in patients with vascular EDS. © The Author(s) 2016.

The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity.

PubMed

Bowen, David G; Zen, Monica; Holz, Lauren; Davis, Thomas; McCaughan, Geoffrey W; Bertolino, Patrick

2004-09-01

Hepatic immunobiology is paradoxical: although the liver possesses unusual tolerogenic properties, it is also the site of effective immune responses against multiple pathogens and subject to immune-mediated pathology. The mechanisms underlying this dichotomy remain unclear. Following previous work demonstrating that the liver may act as a site of primary T cell activation, we demonstrate here that the balance between immunity and tolerance in this organ is established by competition for primary activation of CD8+ T cells between the liver and secondary lymphoid tissues, with the immune outcome determined by the initial site of activation. Using a transgenic mouse model in which antigen is expressed within both liver and lymph nodes, we show that while naive CD8+ T cells activated within the lymph nodes were capable of mediating hepatitis, cells undergoing primary activation within the liver exhibited defective cytotoxic function and shortened half-life and did not mediate hepatocellular injury. The implications of these novel findings may pertain not only to the normal maintenance of peripheral tolerance, but also to hepatic allograft tolerance and the immunopathogenesis of chronic viral hepatitis.

Simultaneous Occurrence of Varicella Zoster Virus-Induced Pancreatitis and Hepatitis in a Renal Transplant Recipient: A Case Report and Review of Literature

PubMed Central

Chhabra, Puneet; Ranjan, Priyadarshi; Bhasin, Deepak K

2017-01-01

Introduction: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. Case Presentation: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella. Liver enzyme levels were also elevated. He was started on a regimen of acyclovir. His pain improved in 24 hours, and liver enzyme levels returned to normal in 48 hours. Discussion: There is a paucity of literature on the simultaneous occurrence of varicella zoster virus-induced hepatitis and pancreatitis in both immunocompetent and immunocompromised patients. Our case highlights the gastrointestinal complications of varicella infection in immunocompromised patients that may precede the characteristic dermatologic manifestations, and the fact that rarely both hepatitis and pancreatitis may be seen. PMID:28333601

Nephrolithiasis and Osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B.

PubMed

Lin, Jueying; Zhuo, Yufeng; Zhang, Dongdong

2017-08-29

An increasing number of case reports suggest that acquired renal Fanconi syndrome may be associated with prolonged use of adefovir against hepatitis B virus. Renal Fanconi syndrome is an uncommon disease, and its complication with nephrolithiasis is quite rare. Herein, we report a rare coexistence of nephrolithiasis and acquired renal Fanconi syndrome in a chronic hepatitis B-positive patient with prolonged adefovir therapy. The patient presented with osteomalacia and nephrolithiasis. Consequently, extracorporeal shock-wave lithotripsy and left double-J ureteral stent insertion were considered for obstructive nephropathy, which was caused by nephrolithiasis. However, osteomalacia had been misdiagnosed as osteoporosis before admission to our hospital. On admission, a complexity of multiple fractures, hypophosphataemia, glycosuria without hyperglycaemia and non-anion-gap metabolic acidosis indicated a diagnosis of acquired renal Fanconi syndrome induced by adefovir. After switching from adefovir to entecavir, the patient's symptoms and laboratory findings improved significantly. The mechanism responsible for nephrolithiasis in renal Fanconi syndrome is still unclear. We recommend regularly monitoring renal function and serum calcium and serum phosphate to prevent renal Fanconi syndrome during the prolonged use of adefovir for hepatitis B virus.

Long-term outcomes after hepatic resection combined with radiofrequency ablation for initially unresectable multiple and bilobar liver malignancies.

PubMed

Qiu, Jianguo; Chen, Shuting; Wu, Hong

2014-05-01

Hepatic resection (HRE) combined with radiofrequency ablation (RFA) offers a surgical option to a group of patients with multiple and bilobar liver malignancies who are traditionally unresectable for inadequate functional hepatic reserve. The aims of the present study were to assess the perioperative outcomes, recurrence, and long-term survival rates for patients treated with HRE plus RFA in the management of primary hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC). Data from all consecutive patients with primary and secondary hepatic malignancies who were treated with HRE combined with RFA between 2007 and 2013 were prospectively collected and retrospectively reviewed. A total of 112 patients, with 368 hepatic tumors underwent HRE combined with ultrasound-guided RFA, were included in the present study. There were 40 cases of HCC with 117 tumors and 72 cases of MLC with 251 metastases. Most cases of liver metastases originated from the gastrointestinal tract (44, 61.1%). Other uncommon lesions included breast cancer (5, 6.9%), pancreatic cancer (3, 4.2%), lung cancer (4, 5.6%), cholangiocarcinoma (4, 5.6%), and so on. The ablation success rates were 93.3% for HCC and 96.7% for MLC. The 1-, 2-, 3-, 4-, and 5-y overall recurrence rates were 52.5%, 59.5%, 72.3%, 75%, and 80% for the HCC group and 44.4%, 52.7%, 56.1%, 69.4%, and 77.8% for the MLC group, respectively. The 1-, 2-, 3-, 4-, and 5-y overall survival rates for the HCC patients were 67.5%, 50%, 32.5%, 22.5%, and 12.5% and for the MLC patients were 66.5%, 55.5%, 50%, 30.5%, and 19.4%, respectively. The corresponding recurrence-free survival rates for the HCC patients were 52.5%, 35%, 22.5%, 15%, and 10% and for the MLC patients were 58.3%, 41.6%, 23.6%, 16.9%, and 12.5%, respectively. HRE combined with RFA provides an effective treatment approach for patients with primary and secondary liver malignancies who are initially unsuitable for radical resection, with high local tumor control rates and promising survival data. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein

PubMed Central

Yang, Jia-Ming; Ip, Siu-Po; Xian, Yanfang; Zhao, Ming; Lin, Zhi-Xiu; Yeung, John Hok Keung; Chan, Raphael Chiu Yeung; Lee, Shui-Shan; Che, Chun-Tao

2012-01-01

Sophora flavescens is a Chinese medicinal herb used for the treatment of gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral hepatitis. In this study the herb-drug interactions between S. flavescens and indinavir, a protease inhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg, p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a dose-dependent decrease of plasma indinavir concentrations, with 55%–83% decrease in AUC0-∞ and 38%–78% reduction in Cmax. The CL (Clearance)/F (fraction of dose available in the systemic circulation) increased up to 7.4-fold in Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased indinavir concentrations, while the ethyl acetate fraction of Sophora extract had no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir in faeces was increased after Sophora treatment. Compared to the controls, multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp in the small intestine and liver. In addition, Sophora treatment increased intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2 expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats. All available data demonstrated that Sophora flavescens reduced plasma indinavir concentration after multiple concomitant doses, possibly through hepatic CYP3A activity and induction of intestinal and hepatic P-gp. The animal study would be useful for predicting potential interactions between natural products and oral pharmaceutics and understanding the mechanisms prior to human studies. Results in the current study suggest that patients using indinavir might be cautioned in the use of S. flavescens extract or Sophora-derived products. PMID:22359586

Impact of the herbal medicine Sophora flavescens on the oral pharmacokinetics of indinavir in rats: the involvement of CYP3A and P-glycoprotein.

PubMed

Yang, Jia-Ming; Ip, Siu-Po; Xian, Yanfang; Zhao, Ming; Lin, Zhi-Xiu; Yeung, John Hok Keung; Chan, Raphael Chiu Yeung; Lee, Shui-Shan; Che, Chun-Tao

2012-01-01

Sophora flavescens is a Chinese medicinal herb used for the treatment of gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral hepatitis. In this study the herb-drug interactions between S. flavescens and indinavir, a protease inhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg, p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a dose-dependent decrease of plasma indinavir concentrations, with 55%-83% decrease in AUC(0-∞) and 38%-78% reduction in C(max). The CL (Clearance)/F (fraction of dose available in the systemic circulation) increased up to 7.4-fold in Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased indinavir concentrations, while the ethyl acetate fraction of Sophora extract had no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir in faeces was increased after Sophora treatment. Compared to the controls, multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp in the small intestine and liver. In addition, Sophora treatment increased intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2 expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats. All available data demonstrated that Sophora flavescens reduced plasma indinavir concentration after multiple concomitant doses, possibly through hepatic CYP3A activity and induction of intestinal and hepatic P-gp. The animal study would be useful for predicting potential interactions between natural products and oral pharmaceutics and understanding the mechanisms prior to human studies. Results in the current study suggest that patients using indinavir might be cautioned in the use of S. flavescens extract or Sophora-derived products.

Diffuse corpus callosum infarction - Rare vascular entity with differing etiology.

PubMed

Mahale, Rohan; Mehta, Anish; Buddaraju, Kiran; John, Aju Abraham; Javali, Mahendra; Srinivasa, Rangasetty

2016-01-15

Infarctions of the corpus callosum are rare vascular events. It is relatively immune to vascular insult because of its rich vascular supply from anterior and posterior circulations of brain. Report of 3 patients with largely diffuse acute corpus callosum infarction. 3 patients with largely diffuse acute corpus callosum infarction were studied and each of these 3 patients had 3 different aetiologies. The 3 different aetiologies of largely diffuse acute corpus callosum infarction were cardioembolism, tuberculous arteritis and takayasu arteritis. Diffuse corpus callosum infarcts are rare events. This case series narrates the three different aetiologies of diffuse acute corpus callosum infarction which is a rare vascular event. Copyright © 2015 Elsevier B.V. All rights reserved.

72 FR 56765 - Proposed Consolidated Vaccine Information Materials for Multiple Infant Vaccines

Federal Register 2010, 2011, 2012, 2013, 2014

2007-10-04

... to meningitis (infection of the brain and spinal cord coverings); pneumonia; infections of the blood... vaccines: DTaP, Haemophilus influenzae type b, inactivated polio vaccine, pneumococcal conjugate vaccine... to administration of any of these vaccines. Hepatitis B, Haemophilus influenzae type b (Hib...

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

PubMed

Mahaffey, K W; Puma, J A; Barbagelata, N A; DiCarli, M F; Leesar, M A; Browne, K F; Eisenberg, P R; Bolli, R; Casas, A C; Molina-Viamonte, V; Orlandi, C; Blevins, R; Gibbons, R J; Califf, R M; Granger, C B

1999-11-15

The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Laser microdissection and capture of pure cardiomyocytes and fibroblasts from infarcted heart regions: perceived hyperoxia induces p21 in peri-infarct myocytes.

PubMed

Kuhn, Donald E; Roy, Sashwati; Radtke, Jared; Khanna, Savita; Sen, Chandan K

2007-03-01

Myocardial infarction caused by ischemia-reperfusion in the coronary vasculature is a focal event characterized by an infarct-core, bordering peri-infarct zone and remote noninfarct zone. Recently, we have reported the first technique, based on laser microdissection pressure catapulting (LMPC), enabling the dissection of infarction-induced biological responses in multicellular regions of the heart. Molecular mechanisms in play at the peri-infarct zone are central to myocardial healing. At the infarct site, myocytes are more sensitive to insult than robust fibroblasts. Understanding of cell-specific responses in the said zones is therefore critical. In this work, we describe the first technique to collect the myocardial tissue with a single-cell resolution. The infarcted myocardium was identified by using a truncated hematoxylin-eosin stain. Cell elements from the infarct, peri-infarct, and noninfarct zones were collected in a chaotropic RNA lysis solution with micron-level surgical precision. Isolated RNA was analyzed for quality by employing microfluidics technology and reverse transcribed to generate cDNA. Purity of the collected specimen was established by real-time PCR analyses of cell-specific genes. Previously, we have reported that the oxygen-sensitive induction of p21/Cip1/Waf1/Sdi1 in cardiac fibroblasts in the peri-infarct zone plays a vital role in myocardial remodeling. Using the novel LMPC technique developed herein, we confirmed that finding and report for the first time that the induction of p21 in the peri-infarct zone is not limited to fibroblasts but is also evident in myocytes. This work presents the first account of an analytical technique that applies the LMPC technology to study myocardial remodeling with a cell-type specific resolution.

Effects of endovascular cooling on infarct size in ST-segment elevation myocardial infarction: A patient-level pooled analysis from randomized trials.

PubMed

Dae, Michael; O'Neill, William; Grines, Cindy; Dixon, Simon; Erlinge, David; Noc, Marko; Holzer, Michael; Dee, Anne

2018-06-01

This study sought to examine the relationship between temperature at reperfusion and infarct size. Hypothermia consistently reduces infarct size when administered prior to reperfusion in animal studies, however, clinical results have been inconsistent. We performed a patient-level pooled analysis from six randomized control trials of endovascular cooling during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in 629 patients in which infarct size was assessed within 1 month after randomization by either single-photon emission computed tomography (SPECT) or cardiac magnetic resonance imaging (cMR). In anterior infarct patients, after controlling for variability between studies, mean infarct size in controls was 21.3 (95%CI 17.4-25.3) and in patients with hypothermia <35°C it was 14.8 (95%CI 10.1-19.6), which was a statistically significant absolute reduction of 6.5%, or a 30% relative reduction in infarct size (P = 0.03). There was no significant difference in infarct size in anterior ≥35°C, or inferior infarct patients. There was no difference in the incidence of death, ventricular arrhythmias, or re-infarction due to stent thrombosis between hypothermia and control patients. The present study, drawn from a patient-level pooled analysis of six randomized trials of endovascular cooling during primary PCI in STEMI, showed a significant reduction in infarct size in patients with anterior STEMI who were cooled to <35°C at the time of reperfusion. The results support the need for trials in patients with anterior STEMI using more powerful cooling devices to optimize the delivery of hypothermia prior to reperfusion. © 2017 The Authors. Journal of Interventional Cardiology Published by Wiley Periodicals, Inc.

Evaluating blood-brain barrier permeability in delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

PubMed

Ivanidze, J; Kesavabhotla, K; Kallas, O N; Mir, D; Baradaran, H; Gupta, A; Segal, A Z; Claassen, J; Sanelli, P C

2015-05-01

Patients with SAH are at increased risk of delayed infarction. Early detection and treatment of delayed infarction remain challenging. We assessed blood-brain barrier permeability, measured as permeability surface area product, by using CTP in patients with SAH with delayed infarction. We performed a retrospective study of patients with SAH with delayed infarction on follow-up NCCT. CTP was performed before the development of delayed infarction. CTP data were postprocessed into permeability surface area product, CBF, and MTT maps. Coregistration was performed to align the infarcted region on the follow-up NCCT with the corresponding location on the CTP maps obtained before infarction. Permeability surface area product, CBF, and MTT values were then obtained in the location of the subsequent infarction. The contralateral noninfarcted region was compared with the affected side in each patient. Wilcoxon signed rank tests were performed to determine statistical significance. Clinical data were collected at the time of CTP and at the time of follow-up NCCT. Twenty-one patients with SAH were included in the study. There was a statistically significant increase in permeability surface area product in the regions of subsequent infarction compared with the contralateral control regions (P < .0001). However, CBF and MTT values were not significantly different in these 2 regions. Subsequent follow-up NCCT demonstrated new delayed infarction in all 21 patients, at which time 38% of patients had new focal neurologic deficits. Our study reveals a statistically significant increase in permeability surface area product preceding delayed infarction in patients with SAH. Further investigation of early permeability changes in SAH may provide new insights into the prediction of delayed infarction. © 2015 by American Journal of Neuroradiology.

Neuroimaging findings in cryptogenic stroke patients with and without patent foramen ovale.

PubMed

Thaler, David E; Ruthazer, Robin; Di Angelantonio, Emanuele; Di Tullio, Marco R; Donovan, Jennifer S; Elkind, Mitchell S V; Griffith, John; Homma, Shunichi; Jaigobin, Cheryl; Mas, Jean-Louis; Mattle, Heinrich P; Michel, Patrik; Mono, Marie-Luise; Nedeltchev, Krassen; Papetti, Federica; Serena, Joaquín; Weimar, Christian; Kent, David M

2013-03-01

Patent foramen ovale (PFO) and cryptogenic stroke are commonly associated but some PFOs are incidental. Specific radiological findings associated with PFO may be more likely to indicate a PFO-related cause. We examined whether specific radiological findings are associated with PFO among subjects with cryptogenic stroke and known PFO status. We analyzed the Risk of Paradoxical Embolism(RoPE) Study database of subjects with cryptogenic stroke and known PFO status, for associations between PFO and: (1) index stroke seen on imaging, (2) index stroke size, (3) index stroke location, (4) multiple index strokes, and (5) prior stroke on baseline imaging. We also compared imaging with purported high-risk echocardiographic features. Subjects (N=2680) were significantly more likely to have a PFO if their index stroke was large (odds ratio [OR], 1.36; P=0.0025), seen on index imaging (OR, 1.53; P=0.003), and superficially located (OR, 1.54; P<0.0001). A prior stroke on baseline imaging was associated with not having a PFO (OR, 0.66; P<0.0001). Finding multiple index strokes was unrelated to PFO status (OR, 1.21; P=0.161). No echocardiographic variables were related to PFO status. This is the largest study to report the radiological characteristics of patients with cryptogenic stroke and known PFO status. Strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiological infarcts were more likely to be PFO-associated than were unapparent, smaller, or deep strokes, and those accompanied by chronic infarcts. There was no association between PFO and multiple acute strokes nor between specific echocardiographic PFO features with neuroimaging findings.

Cardiovascular disease and perceived weight, racial, and gender discrimination in U.S. adults.

PubMed

Udo, Tomoko; Grilo, Carlos M

2017-09-01

To date, most research on perceived discrimination and cardiovascular disease (CVD) has examined racial discrimination although other forms of discrimination may also impact physical and mental health. The current study investigated the relationship between three forms of discrimination (weight, race, and gender) and 3-year incidence of CVD in a large national sample of U.S. adults. 26,992 adults (55.5% women) who participated in the 2001-2002 and 2004-2005 National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) were included in this study. Multiple logistic regression analyses were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for three forms of perceived discrimination (simultaneously included in equations after adjusting for relevant potential confounds) for predicting CVD incidence at Wave 2. Perceived weight and racial discrimination were associated with significantly greater likelihood of reporting myocardial infarction (OR=2.56 [95% CI=1.31-4.98], OR=1.84 [95% CI=1.19-2.84], respectively) and minor heart conditions (OR=1.48 [95% CI=1.11-1.98], OR=1.41 [95% CI=1.18-1.70], respectively). Perceived racial discrimination was also significantly associated with greater likelihood of reporting arteriosclerosis (OR=1.61 [95% CI=1.11-2.34]). Odds ratios for diagnoses of arteriosclerosis, myocardial infarction, and other minor heart disease were largest for individuals reporting multiple forms of discrimination. Adults who experience weight and racial discrimination, and especially multiple forms of discrimination, may be at heightened risk for CVD. Perceived discrimination may be important to consider during assessment of life stressors by health providers. Future research should address the mechanisms that link discrimination and CVD to assist public health and policy efforts to reduce discrimination. Copyright © 2017. Published by Elsevier Inc.

Regional mechanics determine collagen fiber structure in healing myocardial infarcts.

PubMed

Fomovsky, Gregory M; Rouillard, Andrew D; Holmes, Jeffrey W

2012-05-01

Following myocardial infarction, the mechanical properties of the healing infarct are an important determinant of heart function and the risk of progression to heart failure. In particular, mechanical anisotropy (having different mechanical properties in different directions) in the healing infarct can preserve pump function of the heart. Based on reports of different collagen structures and mechanical properties in various animal models, we hypothesized that differences in infarct size, shape, and/or location produce different patterns of mechanical stretch that guide evolving collagen fiber structure. We tested the effects of infarct shape and location using a combined experimental and computational approach. We studied mechanics and collagen fiber structure in cryoinfarcts in 53 Sprague-Dawley rats and found that regardless of shape or orientation, cryoinfarcts near the equator of the left ventricle stretched primarily in the circumferential direction and developed circumferentially aligned collagen, while infarcts at the apex stretched similarly in the circumferential and longitudinal directions and developed randomly oriented collagen. In a computational model of infarct healing, an effect of mechanical stretch on fibroblast and collagen alignment was required to reproduce the experimental results. We conclude that mechanical environment determines collagen fiber structure in healing myocardial infarcts. Our results suggest that emerging post-infarction therapies that alter regional mechanics will also alter infarct collagen structure, offering both potential risks and novel therapeutic opportunities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patent Foramen Ovale in Patients with Cerebral Infarction: A Transesophageal Echocradigraphy Study

NASA Technical Reports Server (NTRS)

Petty, George W.; Khandheria, Bijoy K.; Chu, Chu-Pin; Sicks, JoRean D.; Whisnant, Jack P.

1997-01-01

Patent foramen ovale was detected in 37 patients (32%). Mean age was similar in those with (60 years) and those without (64 years) PFO. Patent foramen ovale was more frequent among men (39%) than women (20%, P=.03). Patients with PFO had a lower frequency of atrial fibrillation, diabetes me!litus, hypertension, and peripheral vascular disease compared with those without PFO. There was no difference in frequency of the following characteristics in patients with PFO compared with those without PFO: pulmonary embolus, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral embolism, prior cerebral infarction, nosocomial cerebral infarction, Valsalva maneuver at the time of cerebral infarction, recent surgery, or hemorrhagic transformation of cerebral infarction. Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of uncertain cause and in 15 (25%) of 61 with infarcts of known cause (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P=.08). When the analysis was restricted to patients who underwent Valsalva maneuver, PFO with right to left or bidirectional shunt was found in 19 (50%) of 38 patients with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known cause (P=.Ol). Conclusion: Although PFO was over-represented in patients with infarcts of uncertain cause in our and other studies, it has a high frequency among patients with cerebral infarction of all types. The relation between PFO and stroke requires further study.