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Sample records for ischaemic hepatic failure

  1. Ischaemic Markers in Acute Hepatic Injury

    PubMed Central

    Jena, Sushanta Kumar; Nanda, Rachita; Mangaraj, Manaswini; Nayak, Parsuram

    2016-01-01

    Introduction Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT-LDH ratio and ALT-LDH index have been suggested for its detection at early stage. Aim To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. Materials and Methods Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1st day and 7th day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. Result Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1st day of admission. ALT-LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7th day registered a rise in comparison to the 1st day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. Conclusion Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID:27190791

  2. Acute hepatic failure in children.

    PubMed Central

    Riely, C. A.

    1984-01-01

    Many diseases may present as acute hepatic failure in the pediatric age group, including viral hepatitis A and B, adverse drug reactions, both toxic and "hepatitic," and inherited metabolic disorders such as tyrosinemia, alpha 1 antitrypsin deficiency, and Wilson's disease. Management is primarily supportive, with care taken to anticipate the known complications of hepatic failure. Few "curative" therapies are known, although attempts at stimulating hepatic regeneration may be helpful. Images FIG. 1 FIG. 3 FIG. 4 PMID:6433587

  3. Multimodal brain monitoring in fulminant hepatic failure

    PubMed Central

    Paschoal Jr, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2016-01-01

    Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

  4. Multimodal brain monitoring in fulminant hepatic failure.

    PubMed

    Paschoal, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2016-08-01

    Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

  5. Evaluation of Encapsulated Liver Cell Spheroids in a Fluidised-Bed Bioartificial Liver for Treatment of Ischaemic Acute Liver Failure in Pigs in a Translational Setting

    PubMed Central

    Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram; Gautier, Aude; Sharratt, Peter; Fuller, Barry; Hodgson, Humphrey

    2013-01-01

    Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell

  6. Fulminant hepatic failure from hepatitis E in a non-pregnant female traveller.

    PubMed

    Chris, Robert B; Keystone, Jay S

    2016-04-01

    A non-pregnant Canadian woman returning from India presented with a 1-week history of jaundice and malaise. Subsequently, she developed fulminant hepatic failure caused by hepatitis E virus (HEV). HEV can cause fulminant hepatic failure, most commonly in pregnant women and those with chronic liver disease; however, all travellers are at risk. PMID:27069000

  7. Fulminant hepatic failure in children and adolescents in Northern Brazil.

    PubMed

    Fonseca, José Carlos F; Souza, Rita A B; Brasil, Leila M; Araújo, José R; Ferreira, Luiz Carlos L

    2004-01-01

    The histological findings of fulminant hepatic failure were correlated to the demographic, clinical, biochemical and virological features in children and adolescents, native to the Amazonas State in Northern Brazil. 96.2% had evidence of infection by primary hepatotrophic viruses. Histological analysis revealed three distinct patterns of fulminant hepatic failure. PMID:15042190

  8. Regenerative cells for transplantation in hepatic failure.

    PubMed

    Ishikawa, Tetsuya; Banas, Agnieszka; Teratani, Takumi; Iwaguro, Hideki; Ochiya, Takahiro

    2012-01-01

    Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have an enormous potential; however, their potential clinical application is being arrested due to various limitations such as teratoma formation followed by tumorigenesis, emergent usage, and the quality control of cells, as well as safety issues regarding long-term culture are also delaying their clinical application. In addition, human ES cells have two crucial issues: immunogenicity and ethical issues associated with their clinical application. The efficient generation of human iPS cells requires gene transfer, yet the mechanism underlying pluripotent stem cell induction has not yet been fully elucidated. Otherwise, although human adult regenerative cells including mesenchymal stem cells have a limited capacity for differentiation, they are nevertheless promising candidates for tissue regeneration in a clinical setting. This review highlights the use of regenerative cells for transplantation in hepatic failure. PMID:22793046

  9. Review article: liver support systems in acute hepatic failure.

    PubMed

    Rahman, T M; Hodgson, H J

    1999-10-01

    The treatment of acute hepatic failure has developed rapidly over the last 40 years, reducing morbidity and mortality from this syndrome. Whilst this has been partly attributed to significant improvements in the specialist medical management of these patients, advances in surgical techniques and pharmaceutical developments have led to the establishment of successful liver transplantation programmes, which have improved mortality significantly. This review will examine the clinical impact of alternative methods that have been used to provide extra-corporeal hepatic support. Non-biological, bio- logical and hybrid hepatic extra-corporeal support will be explored, offering a comprehensive historical overview and an appraisal of present and future advances. PMID:10540040

  10. Idiopathic neonatal giant cell hepatitis presenting with acute hepatic failure on postnatal day one.

    PubMed

    Correa, Kimberley K; Nanjundiah, Prathiba; Wirtschafter, David D; Alshak, Najeeb S

    2002-01-01

    We report a term male infant presenting on postnatal day 1 with fulminant hepatic failure. Described congenital infection, metabolic disorders, and cardiovascular etiologies of acute neonatal liver failure were assessed and eliminated. A liver biopsy on postnatal day 10 showed neonatal giant cell hepatitis (NGCH) with an unusual degree of fibrosis for this early postnatal age. NGCH is a clinical diagnosis of cholestatic disorders of unknown etiology in the newborn, and, to our knowledge, has not been previously associated with immediate neonatal hepatic failure. The giant cell transformation is a common response to a variety of insults and only rarely occurs beyond the neonatal period. Most cases present with cholestatic jaundice and varying degrees of coagulopathy, and, many, as in this case, show progressive resolution. PMID:11948391

  11. Acute Hepatic Failure in a Dog after Xylitol Ingestion.

    PubMed

    Schmid, Renee D; Hovda, Lynn R

    2016-06-01

    Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations. PMID:26691320

  12. Missed opportunities: Peripartum hepatic failure in a Chinese immigrant

    PubMed Central

    Gandhi, Shital

    2014-01-01

    Hepatitis B surface antigen (HBsAg) positivity presents unique management challenges in pregnancy. We present the case of a 26-year-old HBsAg-positive woman who presented at 35 weeks gestational age with nausea, vomiting, and abdominal pain with markedly elevated liver enzymes. An elevated alpha feto-protein on antenatal screening had been misconstrued as fetal in origin. Magnetic resonance imaging and liver biopsy confirmed hepatocellular carcinoma. She died of fulminant hepatic failure two weeks after emergent delivery. This case highlights the importance of adequate evaluation and management of pregnant patients testing positive for HBsAg on routine antenatal testing.

  13. Hepatic encephalopathy: effects of liver failure on brain function.

    PubMed

    Felipo, Vicente

    2013-12-01

    Liver failure affects brain function, leading to neurological and psychiatric alterations; such alterations are referred to as hepatic encephalopathy (HE). Early diagnosis of minimal HE reveals an unexpectedly high incidence of mild cognitive impairment and psychomotor slowing in patients with liver cirrhosis - conditions that have serious health, social and economic consequences. The mechanisms responsible for the neurological alterations in HE are beginning to emerge. New therapeutic strategies acting on specific targets in the brain (phosphodiesterase 5, type A GABA receptors, cyclooxygenase and mitogen-activated protein kinase p38) have been shown to restore cognitive and motor function in animal models of chronic HE, and NMDA receptor antagonists have been shown to increase survival in acute liver failure. This article reviews the latest studies aimed at understanding how liver failure affects brain function and potential ways to ameliorate these effects. PMID:24149188

  14. Scintigraphic study of regenerative nodules due to fulminant hepatic failure.

    PubMed

    Watanabe, Tomohiro; Kondo, Masahiko; Hirasa, Masahiro; Shirane, Hirofumi; Okabe, Yoshihiro; Ibuki, Yasuyoshi; Tomita, Shusuke; Orino, Akio; Todo, Akio; Wakatsuki, Yoshio; Chiba, Tsutomu; Kudo, Masatoshi

    2003-01-01

    We report the case of a 25-year-old woman with fulminant hepatic failure (FHF). Liver scintigraphy using (99m)Tc-galactosyl human serum albumin (GSA) and (99m)Tc-phytate produced interesting findings; regenerative nodules appeared as nodules of increased accumulation of (99m)Tc-GSA, whereas these nodules were expressed as defects of accumulation of (99m)Tc-phytate. These scintigraphic findings suggested that the functions of hepatocytes in regenerative nodules were maintained, whereas those of Kupffer cells were impaired. Although (99m)Tc-GSA scintigraphy indicated hepatic functional reserve enough to survive, she died despite intensive therapy including plasma exchange. Based on this case, it is recommended that not only (99m)Tc-GSA scintigraphy but also (99m)Tc-phytate scintigraphy is required to evaluate the prognosis of patients with FHF. PMID:12898364

  15. Hepatitis E and Acute-on-Chronic Liver Failure

    PubMed Central

    Kumar, Ashish; Saraswat, Vivek A.

    2013-01-01

    Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials. PMID:25755504

  16. Flupirtine-induced hepatic failure requiring orthotopic liver transplant.

    PubMed

    Klein, Fritz; Glanemann, Matthias; Rudolph, Birgit; Seehofer, Daniel; Neuhaus, Peter

    2011-08-01

    We present the case of a 48-year-old otherwise healthy man who required an urgent liver transplant owing to acute liver failure after flupirtine treatment. After 3 months of daily flupirtine intake as treatment for pseudoradicular pain syndrome, he presented at our institution with signs of jaundice and hepatic encephalopathy. Laboratory results showed elevated liver transaminases, and the liver histopathology supported the assumed drug-induced liver injury. After listing him for an urgent liver transplant, he was given a liver graft from a 21-year-old man. Despite a rejection episode on day 11 after the surgery (which was successfully treated by steroid pulse therapy), the postoperative course was uneventful and the patient recovered completely. To the best of our knowledge, this is the first report of a liver transplant for acute liver failure after taking flupirtine. PMID:21819373

  17. Association between β-blocker therapy and outcomes in patients hospitalised with acute exacerbations of chronic obstructive lung disease with underlying ischaemic heart disease, heart failure or hypertension

    PubMed Central

    Stefan, Mihaela S; Rothberg, Michael B; Priya, Aruna; Pekow, Penelope S; Au, David H; Lindenauer, Peter K

    2015-01-01

    Background β-Blocker therapy has been shown to improve survival among patients with ischaemic heart disease (IHD) and congestive heart failure (CHF) and is underused among patients with chronic obstructive pulmonary disease (COPD). Evidence regarding the optimal use of β-blocker therapy during an acute exacerbation of COPD is particularly weak. Methods We conducted a retrospective cohort study of patients aged ≥40 years with IHD, CHF or hypertension who were hospitalised for an acute exacerbation of COPD from 1 January 2006 to 1 December 2007 at 404 acute care hospitals throughout the USA. We examined the association between β-blocker therapy and in-hospital mortality, initiation of mechanical ventilation after day 2 of hospitalisation, 30-day all-cause readmission and length of stay. Results Of 35 082 patients who met the inclusion criteria, 29% were treated with β blockers in the first two hospital days, including 22% with β1-selective and 7% with non-selective β blockers. In a propensity-matched analysis, there was no association between β-blocker therapy and in-hospital mortality (OR 0.88, 95% CI 0.71 to 1.09), 30-day readmission (OR 0.96, 95% CI 0.89 to 1.03) or late mechanical ventilation (OR 0.98, 95% CI 0.77 to 1.24). However, when compared with β1 selective β blockers, receipt of non-selective β blockers was associated with an increased risk of 30-day readmission (OR 1.25, 95% CI 1.08 to 1.44). Conclusions Among patients with IHD, CHF or hypertension, continuing β1-selective β blockers during hospitalisation for COPD appears to be safe. Until additional evidence becomes available, β1-selective β blockers may be superior to treatment with a non-selective β blocker. PMID:22941975

  18. The effect of bone marrow- and adipose tissue-derived mesenchymal stem cell transplantation on myocardial remodelling in the rat model of ischaemic heart failure.

    PubMed

    Karpov, Andrey A; Uspenskaya, Yulia K; Minasian, Sarkis M; Puzanov, Maxim V; Dmitrieva, Renata I; Bilibina, Anna A; Anisimov, Sergey V; Galagudza, Michael M

    2013-06-01

    This study aimed to investigate the effect of bone marrow- and adipose tissue-derived mesenchymal stem cell (BM-MSC and AD-MSC respectively) transplantation on left ventricular function and infarct area (IA) in the rat model of ischaemic heart failure. In anaesthetized Wistar rats, the left coronary artery (LCA) was occluded for 40 min with subsequent reperfusion for 7 days. Seven days following surgery, the animals with LCA occlusion/reperfusion were randomized into three groups: (i) Controls received intramyocardial injection of vehicle at three different locations within the peri-infarct zone, (ii) BM-MSC: cells were injected in the same way as in previous group (10(6) ), (iii) AD-MSC: using the same protocol as used in the BM-MSC group. In addition there was also a sham-treated group that had no injection. Two weeks following MSC transplantation, the hearts were isolated and perfused according to the Langendorff method followed by 30-min global ischaemia and 90-min reperfusion. After this IA was determined histologically. During Langendorff perfusion initial and postischaemic LV functions were the same in all groups although LV pressure at the 10th minute of reperfusion was higher in the AD-MSC group compared to controls. However, LV pressure during 30-min global ischaemia was significantly higher in BM-MSC as compared to controls and AD-MSC. The sham treated animals showed the same results as those seen with BM-MSC. Thus, BM-MSC transplantation, in contrast to transplantation of AD-MSC, resulted in better preservation of the LV ability to contract during ischaemia. Furthermore, IA was significantly smaller in BM-MSC group as compared to the controls and the AD-MSC groups. Thus this study has demonstrated that treatment with BM-MSC both ameliorates LV function and reduces histological scar size. PMID:23560418

  19. Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation

    PubMed Central

    Mourad, Moustafa Mabrouk; Algarni, Abdullah; Liossis, Christos; Bramhall, Simon R

    2014-01-01

    Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts. PMID:24876737

  20. Compressed spectral arrays of patients with fulminant hepatic failure in hepatic coma undergoing liver transplantation.

    PubMed

    Takeichi, Takayuki; Asonuma, Katsuhiro; Kim, Ildeok; Inomata, Yukihiro; Kasahara, Mureo; Ohwada, Susumu; Morishita, Yasuo; Tanaka, Koichi

    2002-08-01

    Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on-line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III-IV) who underwent living-related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE-72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological recovery

  1. Livedoid Vasculopathy and Mononeuritis Multiplex, with a Fulminant Hepatic Failure which was caused by Herpes Simplex Hepatitis: A Case Report

    PubMed Central

    Pai B, Sathish; Pai, Kanthilatha

    2013-01-01

    Livedoid vasculopathy with mononeuritis multiplex is a rare association. We are presenting a case of an unusual association of livedoid vasculopathy with mononeuritis multiplex, who developed fulminant hepatic failure which was secondary to Herpes simplex virus (HSV) hepatitis, while she was on treatment with immunosuppressants. Her skin biopsy and immunofluorescence studies showed the features of vasculitis. A biopsy from the sural nerve showed the features of chronic vasculitis. PMID:23814745

  2. Resolution of hypophosphatemia is associated with recovery of hepatic function in children with fulminant hepatic failure.

    PubMed

    Quirós-Tejeira, Rubén E; Molina, Ricardo A; Katzir, Lirona; Lie, Angela; Vargas, Jorge H; Ament, Marvin E; McDiarmid, Sue V; Martín, Martín G

    2005-09-01

    Fulminant hepatic failure (FHF) is a rare but often fatal disease in children. Clinical and laboratory predictors of liver regeneration and recovery, however, have not been well established. We hypothesized that hypophosphatemia may indicate recovery of liver synthetic function in children with FHF. We retrospectively reviewed the medical records of children with FHF who were admitted to UCLA and recovered hepatic function either spontaneously or by liver transplantation (LTx). Serum phosphate (Ph) and prothrombin time or international normalized ratio (INR) were compared over the patient's clinical course. Records of 39 children who spontaneously recovered experienced profound hypophosphatemia that resolved as liver synthetic function improved. Similar patterns were seen in the 84 children who recovered after LTx. We found that hypophosphatemia precedes the recovery of liver synthetic function in children with FHF who recovered with or without transplantation, and that Ph levels return to normal as liver synthetic function improves. These data suggest that hypophosphatemia may be a useful laboratory indicator of recovering liver function in children with FHF. PMID:16101727

  3. Possible roxithromycin-induced fulminant hepatic failure in a child.

    PubMed

    Easton-Carter, K L; Hardikar, W; Smith, A L

    2001-07-01

    A pediatric formulation of roxithromycin is a relatively new addition to the antibiotic market in Australia. A previously healthy 5-year-old boy with no significant medical history was treated with roxithromycin 50 mg twice/day for cough, fever, and anorexia. After completing a 5-day course of the agent, he developed a nonpruritic, nonurticarial, erythematous, maculopapular, generalized rash and occasional vomiting. Three days later his symptoms included jaundice, dark urine, and pale stools. Laboratory results revealed acute hepatitis, and the patient was admitted to the hospital. His hepatic function continued to deteriorate, so the boy was transferred to a tertiary pediatric hospital. His condition continued to worsen, and 6 days after transfer, he underwent liver transplantation. Clinicians should be aware of potential hepatic complications associated with the use of roxithromycin. PMID:11444584

  4. N-acetylcysteine for the treatment of clove oil-induced fulminant hepatic failure.

    PubMed

    Eisen, Jeffrey S; Koren, Gideon; Juurlink, David N; Ng, Vicky L

    2004-01-01

    We present a 3-month-old female who developed fulminant hepatic failure after ingesting less than 8 mL of clove oil. Initial treatment involved gastrointestinal decontamination, supportive measures, and admission to hospital. She subsequently developed fulminant hepatic failure and was treated with intravenous N-acetylcysteine (N-AC) according to a protocol used for acetaminophen poisoning. Over the next 72 h her liver synthetic function and clinical status improved, and she made a complete recovery. Previous reported cases of clove oil toxicity and the potential role of N-AC therapy are reviewed. PMID:15083943

  5. Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure

    PubMed Central

    Poley, Rachel A.; Snowdon, Jaime F.; Howes, Daniel W.

    2011-01-01

    Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated. PMID:24826316

  6. SURVIVAL IN INFECTION-RELATED ACUTE-ON-CHRONIC LIVER FAILURE IS DEFINED BY EXTRA-HEPATIC ORGAN FAILURES

    PubMed Central

    Bajaj, Jasmohan S; O’Leary, Jacqueline G; Reddy, K Rajender; Wong, Florence; Biggins, Scott W.; Patton, Heather; Fallon, Michael B; Garcia-Tsao, Guadalupe; Maliakkal, Benedict; Malik, Raza; Subramanian, Ram M; Thacker, Leroy R; Kamath, Patrick S

    2014-01-01

    Background Infections worsen survival in cirrhosis; however, simple predictors of survival in infection-related acute-on-chronic liver failure (I-ACLF) derived from multi-center studies are required in order to improve prognostication and resource allocation. Methods Using the NACSELD database, data from 18 centers were collected for survival analysis of prospectively enrolled cirrhotic patients hospitalized with an infection. We defined organ failures as (i) shock, (ii) grade III/IV hepatic encephalopathy(HE), (iii) need for dialysis (iv) mechanical ventilation. Determinants of survival with these organ failures were analyzed. Results 507 patients were included (55 yrs, 52% HCV, 15.8% nosocomial infection, 96% Child score≥7) and 30-day evaluations were available in 453 patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial peritonitis (SBP) (22.5%) were most prevalent. During hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal replacement, and 15.8% needed ventilation; 23% died within 30-days and 21.6% developed second infections. Admitted patients developed none (38.4%), one (37.3%), two (10.4%), three (10%) or four (4%) organ failures. 30-day survival worsened with higher number of extra-hepatic organ failures, none (92%), one (72.6%), two (51.3%), three (36%) and all four (23%). I-ACLF was defined as ≥2 organ failures given the significant change in survival probability associated at this cutoff. Baseline independent predictors for development of ACLF were nosocomial infections, MELD score, low mean arterial pressure (MAP), and non-SBP infections. Independent predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high MELD, low MAP, high white blood count and low albumin. In conclusion, using multi-center study data in hospitalized decompensated infected cirrhotic patients, I-ACLF defined by the presence of two or more organ failures using simple definitions is predictive of poor

  7. [Glutamate metabolism in cerebral cortex obtained from chronic hepatic failure rats].

    PubMed

    Ito, M; Matsumoto, H; Kikuchi, S; Yachi, A

    1986-09-01

    The present investigation was carried out in order to elucidate the amino acid metabolism in hepatic failure with particular emphasis placed on glutamate. For this purpose, chronic hepatic failure models were produced in adult male Wistar rats by successive carbontetrachloride injection (0.20 ml/100 g. B. W., twice/week) for 13 weeks. They were confirmed to develop chemical changes compartible with hepatic failure, showing markedly elevated serum levels of NH3, GOT and ALP. Animals were killed by decapitation during fasting and the brains were removed immediately. After the parietal cortical slices were incubated for 45 min at 37 degrees C together with L-(U-14C) glutamate in O2-saturated Gey's balanced salt solution, they were homogenized in 75% ethanol and deproteinized with water saturated chloroform. The radioactivities of liberated CO2, glutamate and its metabolites (glutamine, aspartate and GABA) obtained from the slices were measured. The amount of radioactivity recovered from CO2, glutamine and aspartate revealed a significant increase (p less than 0.001), while that of glutamate and GABA remained unchanged. The main source of the CO2 is believed to originate from TCA cycle rather than the decarboxylation of glutamate to form GABA, and glutamate forms glutamine when it fixes ammonia. Furthermore, glutamate is converted into aspartate via TCA cycle when the carbon was labeled. Therefore, the results indicate that in chronic hepatic failure brains glutamate metabolism is enhanced through TCA cycle as well as ammonia fixation mechanism. PMID:3790365

  8. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents: A Case Report.

    PubMed

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule

  9. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents

    PubMed Central

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians

  10. Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats

    PubMed Central

    Fujimoto, Yoshitaka; Urashima, Takashi; Shimura, Daisuke; Ito, Reiji; Kawachi, Sadataka; Kajimura, Ichige; Akaike, Toru; Kusakari, Yoichiro; Fujiwara, Masako; Ogawa, Kiyoshi; Goda, Nobuhito; Ida, Hiroyuki; Minamisawa, Susumu

    2016-01-01

    Background Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB)-induced right heart failure model and investigated whether cardiac output (CO) is responsible for the progression of hepatic fibrosis. Methods and Results Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01). Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01). Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-β1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2) were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05). Conclusions Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats. PMID:26863419

  11. Two Cases of Fulminant Hepatic Failure from Amanita phalloides Poisoning Treated Additively by Homeopathy

    PubMed Central

    Frass, Michael; Zagorchev, Petko; Yurukova, Vasilka; Wulkersdorfer, Beatrix; Thieves, Karin; Zedtwitz-Liebenstein, Konstantin; Bursch, Willfried; Kaye, Alan David

    2014-01-01

    Background Intoxication with Amanita phalloides is associated with high morbidity and mortality. Treatment therapies include general support, toxin elimination, pharmacotherapy with agents such as the hepatoprotective agent silibinin, and, in extreme states, liver transplantation. Despite these therapeutic interventions, mortality remains relatively high. Case Reports We present reports of 2 patients with severe hepatic failure following intoxication with Amanita phalloides. Both patients were admitted to the intensive care unit; 1 patient suffered from hepatic failure solely, and the second patient experienced severe 5-organ failure. In addition to conventional intensive care treatment, both patients were treated additively with classical homeopathy. The 2 patients survived without any residual pathological sequelae. Conclusion Based on the 2 cases, including 1 extreme situation, we suggest that adjunctive homeopathic treatment has a role in the treatment of acute Amanita phalloides–induced toxicity following mushroom poisoning. Additional studies may clarify a more precise dosing regimen, standardization, and better acceptance of homeopathic medicine in the intensive care setting. PMID:24940137

  12. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure

    PubMed Central

    Colpitts, Che C.; Baumert, Thomas F.

    2016-01-01

    Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs) revolutionized hepatitis C virus (HCV) treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed. PMID:27537906

  13. Causes of death in fulminant hepatic failure and relationship to quantitative histological assessment of parenchymal damage.

    PubMed

    Gazzard, B G; Portmann, B; Murray-Lyon, I M; Williams, R

    1975-10-01

    The clinical course and causes of death in 132 consecutive patients with fulminant hepatic failure and grade III or IV encephalopathy have been reviewed. 105 patients died and in 96 of these an autopsy examination was performed. In 36 patients there was cerebral oedema and the mean age of this group was significantly younger than the other fatal cases. In 28 patients death was attributed to major haemorrhage which originated in the gastrointestinal tract in 25. The prothrombin time ratio was not significantly greater in patients with major bleeding than in those without but they did have a significantly lower platelet count. Sepsis contributed to death in 12 patients. In 25 patients massive hepatic necrosis only was found at autopsy and death was considered to be due solely to hepatic failure. The degree of hepatocyte loss was assessed in 80 fatal cases by a histological morphometric technique on a needle specimen of liver taken immediately post-mortem. The proportion of the liver volume occupied by hepatocytes (hepatocyte volume fraction, HVF) was greatly reduced in all patients (normal 85+/-SD 5 percent) but the mean value was significantly higher in the patients dying with sepsis, cerebral oedema or haemorrhage than in the group in whom death was attributed solely to hepatic failure. There were ten patients in whom liver function was improving at the time of death which was due to cerebral (9) or haemorrhage (1). These observations suggest that many patients presently dying from fulminant hepatic failure may be expected to survive, once more effective therapy is available for the complications of the illness. PMID:172938

  14. Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

    PubMed Central

    Chu, Chi-Jen; Hsiao, Ching-Chin; Wang, Teh-Fang; Chan, Cho-Yu; Lee, Fa-Yauh; Chang, Full-Young; Chen, Yi-Chou; Huang, Hui-Chun; Wang, Sun-Sang; Lee, Shou-Dong

    2005-01-01

    AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg.d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg.d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α (TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs 5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-α (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the

  15. The association of consumptive hypothyroidism secondary to hepatic hemangioma and severe heart failure in infancy.

    PubMed

    Emir, Suna; Ekici, Filiz; İkiz, Mehmet Alper; Vidinlisan, Sadi

    2016-03-01

    Although hemangiomas are the most common vascular tumors of the liver in infancy, data regarding hypothyroidism and heart failure related to hepatic hemangiomas are limited. Here, we present a 15- day -old girl who presented with prolonged jaundice at the age of 15 days. Because her TSH level was found to be 74 μIU/mL, she was initially diagnosed with congenital hypothyroidism and L-Thyroxine replacement therapy was initiated. On follow-up examination performed two months later, it was observed that her TSH level was not suppressed and a mass was noticed in the right upper abdomen on physical examination. Abdominal ultrasonography revealed multiple masses with sizes of about 3-3,5 cm covering the whole liver. When evaluated with clinical and radiological appearance, oral methylprednisolone at a dose of 5 mg/kg/day and propranolol at a dose of 2 mg/kg were initiated with a diagnosis of hepatic hemagioma/hemangioendothelioma. Consumptive hypothyroidism due to hepatic hemangioma and congestive heart failure were considered in the patient who had findings of heart failure. The dose of L-Thyroxine was increased 2-fold. The patient received intensive care treatment for severe heart failure. Because his findings resolved, he was started to be followed up with propranolol, steroid and L-Thyroxine treatment. PMID:27103866

  16. Micro-RNA-122 Levels in Acute Liver Failure and Chronic Hepatitis C

    PubMed Central

    Dubin, Perry H.; Yuan, Hejun; Devine, Robert K.; Hynan, Linda S.; Jain, Mamta K.; Lee, William M.

    2016-01-01

    MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV–HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P<0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P<0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. PMID:24895202

  17. What factors determine the severity of hepatitis A-related acute liver failure?

    PubMed Central

    Ajmera, V.; Xia, G.; Vaughan, G.; Forbi, J. C.; Ganova-Raeva, L. M.; Khudyakov, Y.; Opio, C. K.; Taylor, R.; Restrepo, R.; Munoz, S.; Fontana, R. J.; Lee, W. M.

    2016-01-01

    SUMMARY The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were subgenotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare subgenotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes. PMID:21143345

  18. Secondary preventive potential of nitrates in ischaemic heart disease.

    PubMed

    Thadani, U

    1996-12-01

    Nitrates exert their anti-anginal activity by a number of mechanisms. By reducing venous return and left ventricular end-diastolic pressure they lower myocardial oxygen demand and at the same time enhance blood flow to the sub-endocardium. They also directly increase myocardial oxygen supply by dilating the coronary artery stenoses and increasing collateral blood flow. These pharmacodynamic attributes are clinically efficacious in all the ischaemic myocardial syndromes. In stable angina pectoris, nitrates reduce myocardial ischaemia and ischaemic pain and increase exercise tolerance. In unstable angina, nitrates similarly reduce electrocardiographic evidence of myocardial ischaemia and relieve anginal pain. Following acute myocardial infarction, nitrates reduce ventricular dilatation and by so doing reduce pulmonary congestion and mitral regurgitation. The weak anti-aggregatory effect of nitrates on platelets may also play an adjuvant role in their anti-ischaemic activity. Early small-scale studies with both intravenous and oral nitrates demonstrated a trend to reduced mortality and reinfarction in survivors of acute myocardial infarction. However, the later and larger ISIS-4 and GISSI-3 trials have not confirmed this trend possibly due to the smaller doses of nitrates used and the diluting effect of the widespread use of open-label nitrates in the placebo group. In patients with congestive heart failure, including those of ischaemic aetiology, nitrates together with hydralazine have clearly demonstrated a significant reduction in the medium term mortality risk. Nitrates have the undoubted ability, probably greater than any other single anti-anginal drug, to rapidly and often completely relieve the pain and breathlessness associated with myocardial ischaemia. They are haemodynamically efficacious in reducing dilatation of the ischaemic left ventricle and enhancing coronary blood flow to ischaemic areas. Although their preventative impact in survivors of acute

  19. Cordyceps sinensis prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.

    PubMed

    Cheng, Yu-Jung; Cheng, Shiu-Min; Teng, Yi-Hsien; Shyu, Woei-Cherng; Chen, Hsiu-Ling; Lee, Shin-Da

    2014-01-01

    Cordyceps sinensis (C. sinensis) has long been considered to be an herbal medicine and has been used in the treatment of various inflammatory diseases. The present study examined the cytoprotective properties of C. sinensis on D(+)-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were randomly assigned into control, GalN/LPS, CS 20 mg and CS 40 mg groups (C. sinensis, oral gavage, five days/week, four weeks). After receiving saline or C. sinensis, mice were intraperitoneally given GalN (800 mg/kg)/LPS (10 μg/kg). The effects of C. sinensis on TNF-α, IL-10, AST, NO, SOD, and apoptoticrelated proteins after the onset of endotoxin intoxication were determined. Data demonstrated that GalN/LPS increased hepatocyte degeneration, circulating AST, TNF-α, IL-10, and hepatic apoptosis and caspase activity. C. sinensis pre-treatment reduced AST, TNF-α, and NO and increased IL-10 and SOD in GalN/LPS induced fulminant hepatic failure. C. sinensis attenuated the apoptosis of hepatocytes, as evidenced by the TUNEL and capase-3, 6 activity analyses. In summary, C. sinensis alleviates GalN/LPS-induced liver injury by modulating the cytokine response and inhibiting apoptosis. PMID:24707872

  20. Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure.

    PubMed

    McCarthy, M; Ellis, A J; Wendon, J A; Heaton, N; Rela, M; Buxton-Thomas, M; Hughes, R D; Portmann, B C; Williams, R

    1997-04-01

    The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting. PMID:9160207

  1. Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient.

    PubMed

    Haas, Christopher; Ziccardi, Mary Rodriguez; Borgman, Jody

    2015-01-01

    Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen. PMID:26670894

  2. Hepatitis C treatment failure is associated with increased risk of hepatocellular carcinoma.

    PubMed

    Lu, Mei; Li, Jia; Rupp, Loralee B; Holmberg, Scott D; Moorman, Anne C; Spradling, Philip R; Teshale, Eyasu H; Zhou, Yueren; Boscarino, Joseph A; Schmidt, Mark A; Lamerato, Lois E; Trinacty, Connie; Trudeau, Sheri; Gordon, Stuart C

    2016-09-01

    Sustained virological response (SVR) to antiviral therapy for hepatitis C (HCV) reduces risk of hepatocellular carcinoma (HCC), but there is little information regarding how treatment failure (TF) compares to lack of treatment. We evaluated the impact of treatment status on risk of HCC using data from the Chronic Hepatitis Cohort Study (CHeCS-an observational study based in four large US health systems, with up to 7 years of follow-up on patients). Multivariable analyses were used to adjust for bias in treatment selection, as well as other covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681 (36%) received treatment, 2099 (57%) experienced treatment failure (TF), and 1582 (43%) of these achieved sustained virological response (SVR). TF patients demonstrated almost twice the risk of HCC than untreated patients [adjusted hazard ratio (aHR) = 1.95, 95% confidence interval (CI) 1.50-2.53]; this risk persisted across all stages of fibrosis. Several sensitivity analyses validated these results. Although African Americans were at increased risk of treatment failure, they were at lower risk for HCC and all-cause mortality compared to White patients. SVR patients had lower risk of HCC than TF patients (aHR = 0.48, CI 0.31-0.73), whereas treatment - regardless of outcome - reduced all-cause mortality (aHR = 0.45, CI 0.34-0.60 for SVR patients; aHR = 0.78, CI 0.65-0.93 for TF patients). PMID:27028626

  3. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

    PubMed Central

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687

  4. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

    PubMed

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687

  5. Effect of experimentally induced hepatic and renal failure on the pharmacokinetics of topiramate in rats.

    PubMed

    Matar, Kamal M; Tayem, Yasin I

    2014-01-01

    We aimed to investigate the effect of induced hepatic and renal failure on the pharmacokinetics of topiramate (TPM) in rats. Twenty-four Sprague-Dawley rats were used in this study. Renal or hepatic failure was induced by a single i.p. dose of 7.5 mg/kg cisplatin (n = 8) or 0.5 mL/kg carbon tetrachloride (CCl4) (n = 8), respectively. Three days after cisplatin dose or 24 h after CCl4 dose, the rats were administered a single oral dose of 20 mg/kg TPM. The plasma samples were quantified by LC-MS/MS method. Compared to control, plasma concentration-time profile in CCl4-treated and, to a lesser extent, in cisplatin-treated rats decreased more slowly particularly in the elimination phase. TPM oral clearance (CL/F) in CCl4-treated group was significantly lower than that in control (P < 0.001), whereas AUC0-∞, T1/2, and Vd/F were significantly higher in CCl4-treated rats compared to the control (P < 0.01). The CL/F was not significantly different between cisplatin-treated rats and control (P > 0.05). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group (P < 0.01). Both conditions failed to cause a significant effect on Cmax or Tmax. The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat. PMID:25009818

  6. Effect of Experimentally Induced Hepatic and Renal Failure on the Pharmacokinetics of Topiramate in Rats

    PubMed Central

    Matar, Kamal M.; Tayem, Yasin I.

    2014-01-01

    We aimed to investigate the effect of induced hepatic and renal failure on the pharmacokinetics of topiramate (TPM) in rats. Twenty-four Sprague-Dawley rats were used in this study. Renal or hepatic failure was induced by a single i.p. dose of 7.5 mg/kg cisplatin (n = 8) or 0.5 mL/kg carbon tetrachloride (CCl4) (n = 8), respectively. Three days after cisplatin dose or 24 h after CCl4 dose, the rats were administered a single oral dose of 20 mg/kg TPM. The plasma samples were quantified by LC-MS/MS method. Compared to control, plasma concentration-time profile in CCl4-treated and, to a lesser extent, in cisplatin-treated rats decreased more slowly particularly in the elimination phase. TPM oral clearance (CL/F) in CCl4-treated group was significantly lower than that in control (P < 0.001), whereas AUC0−∞, T1/2, and Vd/F were significantly higher in CCl4-treated rats compared to the control (P < 0.01). The CL/F was not significantly different between cisplatin-treated rats and control (P > 0.05). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group (P < 0.01). Both conditions failed to cause a significant effect on Cmax or Tmax. The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat. PMID:25009818

  7. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  8. Sorbent suspensions vs. sorbent columns for extracorporeal detoxification in hepatic failure.

    PubMed

    Ash, Stephen R; Sullivan, Thomas A; Carr, David J

    2006-04-01

    Hepatic failure is a significant medical problem which has been unsuccessfully treated by hemodialysis. However, similar therapies using recirculated dialysate regenerated by sorbents in place of single-pass dialysate have been beneficial in treating acute-on-chronic liver failure. The advantages of sorbent-based treatments include some selectivity of toxin removal and improved removal of protein-bound toxins. Activated carbon has been extensively used in detoxification systems, but has often had insufficient toxin capacity. Powdered activated carbon, because of its large surface area, can provide greater binding capacity for bilirubin and other toxins than granular carbon commonly used in detoxifying columns. Methods of using powdered carbon in extracorporeal blood treatment devices are reviewed in the present paper, including liver dialysis and a new sorbent suspension reactor (SSR); and the abilities and limitations of the SSR and columns to process protein solutions are discussed. PMID:16684216

  9. Dibromosulphophthalein: its pharmacokinetics and binding to hepatic cytosol proteins in rats with acute renal failure.

    PubMed Central

    Silberstein, D. J.; Bowmer, C. J.; Yates, M. S.

    1988-01-01

    1. The pharmacokinetics, biliary excretion and binding of dibromosulphophthalein (DBSP) to plasma proteins and hepatic cytosol proteins have been studied in male rats with glycerol-induced acute renal failure (ARF). 2. The rate constants for hepatic uptake, efflux from liver to plasma and excretion into bile were all significantly decreased in rats with ARF. Furthermore, the plasma clearance of DBSP was also reduced. 3. The initial (0-10 min) and maximum biliary excretion rates of DBSP were both diminished in animals with ARF. The maximum excretion rate occurred between 5-10 min in control rats and 10-15 min in rats with ARF. However, there was no statistically significant change in the percentage dose recovered from bile after 30 min. 4. The plasma-protein binding of DBSP was decreased in rats with ARF and this change was due to a significant reduction in the association constant for the primary binding sites. 5. The binding of DBSP to ligandin (Y protein) was reduced by about 38% in rats with ARF but no change was noted in binding to Z protein. Reduced binding to ligandin was accompanied by decreased total liver glutathione S-transferase (GST) activity and a 36% reduction in the GST activity of ligandin. 6. The results support the contention that altered hepatic handling of cholephilic dyes in rats with ARF may be due to reduced binding to ligandin. PMID:3228667

  10. Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion.

    PubMed Central

    Vollmar, B.; Glasz, J.; Leiderer, R.; Post, S.; Menger, M. D.

    1994-01-01

    Hepatic ischemia-reperfusion (I/R) is characterized by circulatory and metabolic derangements, liver dysfunction, and tissue damage. However, little is known about the causative role of I/R-induced microcirculatory disturbance on the manifestation of postischemic reperfusion injury. Therefore, the intention of the study was to assess changes of hepatic microvascular perfusion (intravital fluorescence microscopy) as related to hepatic morphology (light/electron microscopy), hepatocellular integrity (serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities), and excretory function (bile flow). Sprague-Dawley rats were subjected to 20 minutes (group B, n = 9) and 60 minutes (group C, n = 9) of left hepatic lobar ischemia followed by 60 minutes of reperfusion. Sham-operated animals without ischemia served as controls (group A, n = 10). Lobar ischemia for 20 minutes followed by reperfusion resulted in a significant reduction of sinusoidal perfusion rate (93.9 +/- 1.4%; P < 0.05) and a decrease in erythrocyte flux (90.0 +/- 5.6%) when compared with controls (99.4 +/- 0.2 and 97.9 +/- 2.7%). This was accompanied by a significant increase of serum AST and ALT activities (P < 0.05) and a reduction of bile flow (P < 0.05). Prolongation of lobar ischemia (group C, 60 minutes) aggravated postischemic reperfusion injury (sinusoidal perfusion rate: 87.4 +/- 2.9%; erythrocyte flux: 62.1 +/- 8.4%) and was paralleled by severed hepatocellular damage. Electron microscopy of postischemic tissue demonstrated alteration of nonparenchymal cells (swelling of sinusoidal lining cells and widening of Disse's space) and substantial parenchymal cell damage (swelling of mitochondria, disarrangement of rough endoplasmatic reticulum, vacuolization, complete cytoplasmic degeneration). Initial postischemic increase in serum AST and ALT activities and reduction of bile flow directly correlated with the extent of microcirculatory failure (P < 0.01), ie, impairment of

  11. Unusual Severe Complication Following Transarterial Chemoembolization for Metastatic Malignant Melanoma: Giant Intrahepatic Cyst and Fatal Hepatic Failure

    SciTech Connect

    Ataergin, Selmin; Tasar, Mustafa; Solchaga, Luis; Ozet, Ahmet; Arpaci, Fikret

    2009-03-15

    We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.

  12. Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

    PubMed

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.(1-3) The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.(4) In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.(5-6) We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor's portal vein was carried out via the recipient's right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient's aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. (7) In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft's weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  13. Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

    PubMed Central

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  14. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

    PubMed Central

    Tuñón, María Jesús; Alvarez, Marcelino; Culebras, Jesús M; González-Gallego, Javier

    2009-01-01

    Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed. PMID:19575487

  15. Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients.

    PubMed

    Morsiani, E; Pazzi, P; Puviani, A C; Brogli, M; Valieri, L; Gorini, P; Scoletta, P; Marangoni, E; Ragazzi, R; Azzena, G; Frazzoli, E; Di Luca, D; Cassai, E; Lombardi, G; Cavallari, A; Faenza, S; Pasetto, A; Girardis, M; Jovine, E; Pinna, A D

    2002-03-01

    Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients. PMID:11999191

  16. Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir

    PubMed Central

    Mutimer, D; Feraz-Neto, B; Harrison, R; O'Donnell, K; Shaw, J; Cane, P; Pillay, D

    2001-01-01

    BACKGROUND—Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure.
CASE REPORT—A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the devlopment of graft failure.
OUTCOME—A rapid exponential decline in serum HBV titre was observed. Liver function tests normalised and signs of liver failure resolved.
CONCLUSION—The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent inhibitor of lamivudine resistant HBV, should be used when failure of prophylaxis is associated with graft hepatitis.


Keywords: hepatitis B virus; adefovir; liver graft; lamivudine PMID:11709523

  17. Defective opsonisation and complement deficiency in serum from patients with fulminant hepatic failure.

    PubMed Central

    Wyke, R J; Rajkovic, I A; Eddleston, A L; Williams, R

    1980-01-01

    Serum from 23 of 26 patients with fulminant hepatic failure and grade IV encephalopathy had defective opsonisation of E. coli and yeast (S. cerevisiae). No toxic serum factors acting on the polymorphonuclear leucocytes or inactivators of the normal serum opsonisation factors were found. Complement deficiency was shown to be the most likely cause of the defect in opsonisation. The addition of a heat-labile fraction of normal serum at low concentration corrected the defect and factors of both the classical and the alternative pathways of complement were reduced to below 40% of the activity of the control serum. During the early stages of clinical recovery serum opsonisation and complement activity returned to normal with statistically significant correlations between tests of opsonisation and total haemolytic complement CH50, C3 and total alternative pathway activity. Defective serum opsonisation and complement deficiency represent major defects in the body's defences against infection. PMID:7000632

  18. Mechanism of the serum defect in yeast opsonization in children with fulminant hepatic failure (FHF).

    PubMed Central

    Larcher, V F; Wyke, R J; Mowat, A P; Williams, R

    1981-01-01

    Defective opsonization of heat-killed baker's yeast was found in all 14 children with fulminant hepatic failure (FHF) but returned to normal in two who recovered and was normal in six mothers of patients. Yeast opsonization was significantly correlated with factor B activity of FHF serum but not with other components of classical or alternative pathways of complement. Reconstitution and family studies suggested that defective yeast opsonization in FHF is secondary and, although dependent on factor B activity, is qualitatively and quantitatively similar to that of primary yeast opsonization deficiency. These findings suggest that the factors responsible for opsonization of yeasts, or their regulation, are synthesized or controlled by the liver. PMID:7039888

  19. Protective Effects of Platycodon grandiflorum Aqueous Extract on Thioacetamide-induced Fulminant Hepatic Failure in Mice.

    PubMed

    Lim, Jong-Hwan; Kim, Tae-Won; Park, Sang-Jin; Song, In-Bae; Kim, Myoung-Seok; Kwon, Hyo-Jung; Cho, Eun-Sang; Son, Hwa-Young; Lee, Sang-Wook; Suh, Joo-Won; Kim, Jong-Woo; Yun, Hyo-In

    2011-12-01

    The aim of the present study was to evaluate the protective activity of aqueous extract from Platycodon grandiflorum (BC703) on thioacetamide (TA)-induced hepatotoxicity in mice. We found that BC703 significantly decreased mortality and the change in serum transaminase following TA administration. The group treated with BC703 at doses of 1, 5, and 10 mg/kg produced significant hepatoprotective effects against TA-induced liver damage by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation in dose-dependent manners. Histopathological studies further substantiated the protective effect of BC703. These results show the hepatoprotective activity of aqueous extract from Platycodon grandiflorum on thioacetamide-induced fulminant hepatic failure. PMID:22319234

  20. Fulminant liver failure: clinical and experimental study.

    PubMed

    Slapak, M

    1975-11-01

    Clinical experience of some newer methods of hepatic support is described. The results are unpredictable and far from satisfactory. The need for an animal model in which potential therapeutic methods can be studied is emphasized. Such a model based on carefully imposed ischaemic insult to the liver in the absence of portacaval shunting is described. It is suggested that bacterial presence in the bowel together with a depression of the liver reticuloendothelial function plays an important part in the early and rapid mortality of acute liver failure. Temporary auxiliary liver transplantation using an allograft or a closely related primate heterograft seem to be the 2 best available methods of hepatic support for potentially reversible acute liver failure. PMID:812415

  1. Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure

    PubMed Central

    Chen, En-Qiang; Zeng, Fan; Zhou, Ling-Yun; Tang, Hong

    2015-01-01

    Hepatitis B virus (HBV) associated acute-on-chronic liver failure (ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B (CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field. PMID:26576085

  2. Auxiliary liver transplantation in patients with fulminant hepatic failure: hepatobiliary scintigraphic follow-up.

    PubMed

    Buyck, D; Bonnin, F; Bernuau, J; Belghiti, J; Bok, B

    1997-02-01

    Auxiliary liver transplantation (ALT), retaining in place the liver of the recipient, has been proposed as an alternative to liver replacement in patients with fulminant hepatic failure (FHF). Hepatobiliary scintigraphy (HS) has proved a unique tool for the separate assessment of graft and native liver function. Forty-eight HS scans were performed, following the injection of technetium-99m trimethyl-bromo-imino-diacetic acid, in six patients who underwent ALT for FHF. Quantitative parameters were derived from the time-activity curves of both the graft and the native liver. The function of the graft remained normal as long as the patients remained under immunosuppressive therapy (IST). The function of the native liver was almost completely absent in the 1st month in five patients, but it improved gradually in four of them. IST was then decreased in four patients and finally withdrawn in three. Spontaneous graft atrophy occurred in two patients and the graft was removed in two. All of the patients in whom IST was reduced had a normal global hepatic function and selective uptake (RU) >30% at that time. In ALT patients with FHF, HS can distinguish non-invasively the functional performance of both the donor and the recipient liver and its evolution with time. PMID:9021110

  3. Psychrobacter immobilis septicemia in a boy with X-linked chronic granulomatous disease and fulminant hepatic failure.

    PubMed

    Sriaroon, Panida; Elizalde, Araceli; Perez, Elena E; Leiding, Jennifer W; Aldrovandi, Grace M; Sleasman, John W

    2014-01-01

    A 16-year old boy with chronic granulomatous disease (CGD) developed Psychrobacter immobilis septicemia during a course of fulminant hepatic failure. The patient died despite aggressive management with antimicrobials and corticosteroids. While Psychrobacter immobilis rarely affects humans, it should be considered an organism that can cause sepsis in patients with CGD. PMID:24217814

  4. Fulminate Hepatic Failure in a 5 Year Old Female after Inappropriate Acetaminophen Treatment

    PubMed Central

    Kasmi, Irena; Sallabanda, Sashenka; Kasmi, Gentian

    2015-01-01

    BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses. CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day. The blood level of acetaminophen after 10 hours of the last administered dose was 32 mg/l. The patient presented with high fever, jaundice, lethargic, agitating with abdominal pain accompanied by encephalopathy. The liver function test revealed with high level of alanine aminotransferase 5794 UI/l and aspartate aminotransferase 6000 UI/l. Early initiation of oral N-acetylcysteine (NAC) after biochemical evidence of liver toxicity was beneficial with rapid improvement of liver enzymes, hepatic function and encephalopathy. During the course of the illness the child developed acute pancreatitis with hyperamylasemia 255 UI/L and hyperlypasemia 514 UI/L. Patient totally recovered within 29 days. CONCLUSION: Healthcare providers should considered probable acetaminophen toxicity in any child who has received the drug and presented with liver failure. When there is a high index of suspicion of acetaminophen toxicity NAC should be initiated and continued until there are no signs of hepatic dysfunction.

  5. Antagonistic interaction between cordyceps sinensis and exercise on protection in fulminant hepatic failure.

    PubMed

    Cheng, Yu-Jung; Shyu, Woei-Cherng; Teng, Yi-Hsien; Lan, Yu-Hsuan; Lee, Shin-Da

    2014-01-01

    Herb supplements are widely used by Asian athletes; however, there are no studies evaluated the co-effects of exercise and herb supplements on hepatic failure. In this study, D-GalN/LPS-induced fulminant hepatic failure was used to examine whether there are synergistic or antagonistic effects of exercise and Cordyceps sinensis (CS). Mice were randomly divided into eight groups: control, swimming exercise for four weeks, D-GalN/LPS challenge, swimming exercise plus D-GalN/LPS, 20 mg/kg or 40 mg/kg CS pretreated for four weeks plus D-GalN/LPS, and swimming exercise combined with 20 mg/kg or 40 mg/kg CS pretreatment plus D-GalN/LPS. Either exercise or 40 mg/kg CS pretreatment alone significantly decreased D-GalN/LPS-induced TNF-α, AST, NO, apoptotic-related proteins, and hepatocyte apoptosis. Exercise or 40 mg/kg CS alone increased the IL-10 and D-GalN/LPS-suppressed Superoxide Dismutase (SOD) level. However, no protective or worse effect was observed in the mice treated with exercise preconditioning combined 40 mg/kg CS compared to those receive exercise alone or CS alone. TNF-α, AST, NO level, caspase-3 activity, and hepatocytes apoptosis were not significantly different in the exercise combined with 40 mg/kg CS compared to mice challenged with D-GalN/LPS. The IL-10 level was significantly decreased after D-GalN/LPS stimulation in the mice received exercise combined with 40 mg/kg CS, indicating the combination strongly reduced the anti-inflammatory effect. In summary, preconditioning exercise or CS pretreatment alone can protect mice from septic liver damage, but in contrast, the combination of exercise and CS does not produce any benefit. The antagonistic interactions between exercise and CS imply taking CS is not recommended for people who undertake regular exercise. PMID:25242080

  6. Infantile Hepatic Hemangioendothelioma Associated With Congestive Heart Failure: Two Case Reports With Different Outcomes.

    PubMed

    Wang, Tao; Wang, Yibin; Liang, Yun; Lu, Guoyan

    2015-12-01

    Infantile hepatic hemangioendothelioma (IHH) is rare which can regress spontaneously. Arteriovenous shunts within hemangiomas, however, may result in pulmonary artery hypertension (PAH) and congestive heart failure (CHF).The authors report 2 young infants suffering from multifocal IHH associated with CHF were both treated with glucocorticoid and transcatheter arterial embolization (TAE), but had different outcomes. The PAH decreased immediately and the symptoms of CHF were alleviated after TAE for both of them. For the Tibetan infant, the development was normal with tumor regression by follow-up. For the Han ethnic neonate, PAH increased again in the seventh day with progressive cardiovascular insufficiency. Ultrasound showed a persisting perfusion caused by collateralization around occluded main feeders. Furthermore, a pulmonary infection occurred and ventilation was performed. As a result, the infant died from multiorgan failure caused by CHF and infection.TAE is a treatment of reducing shunting for hemangiomas. Fistula recanalization in multifocal IHH, however, might be an important risk factor affecting the outcome of TAE. TAE should be further evaluated with special attention to anatomy of feeding and draining vessels, and cardiopulmonary conditions. In addition, the patients were susceptible to secondary pulmonary infection because of lung congestion. As well, the infant from the high altitude area showed better adaptability to hypoxia. PMID:26717373

  7. Association between Plasma Fibrinogen Levels and Mortality in Acute-on-Chronic Hepatitis B Liver Failure

    PubMed Central

    Shao, Zhexin; Zhao, Ying; Feng, Limin; Feng, Guofang; Zhang, Juanwen; Zhang, Jie

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672–0.820, P < 0.001), and the fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094–0.983; P = 0.047). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients. PMID:25960593

  8. Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure

    PubMed Central

    Saracyn, Marek; Brytan, Marek; Zdanowski, Robert; Ząbkowski, Tomasz; Dyrla, Przemysław; Patera, Janusz; Wojtuń, Stanisław; Kozłowski, Wojciech; Wańkowicz, Zofia

    2014-01-01

    AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF). METHODS: An experimental rat model of galactosamine-induced AHF was used. An inhibitor of NO synthase, nitroarginine methyl ester, or an NO donor, arginine, were administered at various doses prior to or after the induction of AHF. RESULTS: All tested groups developed AHF. Following inhibition of the endogenous NO pathway, most liver parameters improved, regardless of the inhibitor dose before the induction of liver damage, and depending on the inhibitor dose after liver damage. Prophylactic administration of the inhibitor was more effective in improving liver function parameters than administration of the inhibitor after liver damage. An attempt to activate the endogenous NO pathway prior to the induction of liver damage did not change the observed liver function parameters. Stimulation of the endogenous NO pathway after liver damage, regardless of the NO donor dose used, improved most liver function parameters. CONCLUSION: The endogenous NO pathway plays an important role in the development of experimental galactosamine-induced AHF. PMID:25516652

  9. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  10. Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

    PubMed

    Anholt, H; Himsworth, C; Britton, A

    2016-07-01

    Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat. PMID:26792845

  11. Is it right to promote living donor liver transplantation for fulminant hepatic failure in pediatric recipients?

    PubMed

    Reding, Raymond

    2005-07-01

    Good clinical results are currently achieved in elective pediatric liver transplantation (LT) with living-related donors. However, the question whether such therapeutic approach may also be promoted in case of fulminant hepatic failure (FHF) remains a matter of debate. This work briefly reviews the ethical background and overall medical results of living-related donation in pediatric LT. When considering FHF, success is essentially conditioned by the availability of a suitable organ donor before the onset of irreversible brain damage and death of the transplant candidate on the waiting list. Accordingly, living donor LT provides several advantages for patients with FHF, including the short waiting time and the access to a transplant with reduced ischemic injury and optimal graft quality; however, living donation is also characterized by several drawbacks to be carefully considered, particularly the possibility of coercion to the recipient's family as well as the operative risks of the emergency donor hepatectomy. The ethical soundness of living parental donor LT for FHF is discussed, with emphasis to the type of medical context, with or without access to an efficient emergency postmortem organ sharing system. PMID:15943615

  12. Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study.

    PubMed

    Zhou, Pengcheng; Shao, Li; Zhao, Lifu; Lv, Guoliang; Pan, Xiaoping; Zhang, Anye; Li, Jianzhou; Zhou, Ning; Chen, Deying; Li, Lanjuan

    2016-01-01

    Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h. Serum samples were assayed using ultra-performance liquid chromatography-mass spectrometry. The difference in survival time (51.6 ± 7.9 h vs. 49.3 ± 6.6 h) and serum metabolome was negligible between the S and C groups, whereas FBBAL treatment significantly prolonged survival time (70.4 ± 11.5h, P < 0.01) and perturbed the serum metabolome, resulting in a marked decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelinase, and fatty acids and an increase in conjugated bile acids. The FBBAL exhibits some liver functions and may exert its therapeutic effect by altering the serum metabolome of FHF pigs. Moreover, alginate-chitosan capsules have less influence on serum metabolites. Nevertheless, the alterations were not universally beneficial, revealing that much should be done to improve the FBBAL. PMID:27194381

  13. Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study

    PubMed Central

    Zhou, Pengcheng; Shao, Li; Zhao, Lifu; Lv, Guoliang; Pan, Xiaoping; Zhang, Anye; Li, Jianzhou; Zhou, Ning; Chen, Deying; Li, Lanjuan

    2016-01-01

    Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h. Serum samples were assayed using ultra-performance liquid chromatography-mass spectrometry. The difference in survival time (51.6 ± 7.9 h vs. 49.3 ± 6.6 h) and serum metabolome was negligible between the S and C groups, whereas FBBAL treatment significantly prolonged survival time (70.4 ± 11.5h, P < 0.01) and perturbed the serum metabolome, resulting in a marked decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelinase, and fatty acids and an increase in conjugated bile acids. The FBBAL exhibits some liver functions and may exert its therapeutic effect by altering the serum metabolome of FHF pigs. Moreover, alginate–chitosan capsules have less influence on serum metabolites. Nevertheless, the alterations were not universally beneficial, revealing that much should be done to improve the FBBAL. PMID:27194381

  14. Acute liver failure secondary to khat (Catha edulis)-induced necrotic hepatitis requiring liver transplantation: case report.

    PubMed

    Roelandt, P; George, C; d'Heygere, F; Aerts, R; Monbaliu, D; Laleman, W; Cassiman, D; Verslype, C; van Steenbergen, W; Pirenne, J; Wilmer, A; Nevens, F

    2011-11-01

    We describe the case of a 26-year-old man with acute liver failure secondary to ingestion of khat (Catha edulis) leaves. In fact, this is the first case of acute liver failure due to khat reported outside the United Kingdom. The combination of specific epidemiologic data (young man of East African origin) and clinical features (central nervous system stimulation, withdrawal reactions, toxic autoimmune-like hepatitis) led to the diagnosis. Mechanisms of action and potential side effects of khat are elaborated on. PMID:22099826

  15. Liver myofibroblasts up-regulate monocyte CD163 expression via PGE2 during hepatitis B induced liver failure

    PubMed Central

    2014-01-01

    Background Although patients with liver failure exhibit a generalized inflammatory-imbalance status, substantial evidence indicates that this immunosuppressive or anti-inflammatory state may be deleterious. Increased expression of CD163 (known to be involved in several anti-inflammatory functions of the immune system) in patients with liver failure is significantly correlated with a fatal outcome. However, little is known of the regulatory mechanisms that influence the expression of CD163. Methods We assessed the expression of CD163 on monocytes from both circulating cells and the liver tissues of patients with hepatitis B induced liver failure using flow cytometry and isolated the myofibroblasts from diseased livers. The ability of human liver myofibroblasts to regulate CD163 expression on monocytes was studied in vitro. Results We showed that CD163+ monocytes were enriched primarily in diseased livers and that they were associated with liver myofibroblasts in the same area. Accordingly, liver myofibroblasts were significantly superior to normal skin fibroblasts in inducing the expression of CD163 on monocytes in vitro. Moreover, we found that liver myofibroblasts triggered the activation of monocytes by secreting PGE2. Inhibition of PGE2 production in liver myofibroblasts using NS-398 markedly reduced CD163 expression in vitro. Conclusion These results suggest that liver myofibroblasts play a direct role in regulating the expression of CD163 on monocytes in human liver tissues and thereby may regulate monocyte function during hepatitis B induced liver failure. PMID:24597777

  16. A novel prognostic score for acute-on-chronic hepatitis B liver failure.

    PubMed

    Yi, Zhao-quan; Lu, Meng-hou; Xu, Xu-wen; Fu, Xiao-yu; Tan, De-ming

    2015-02-01

    Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (Δ scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930 ± 0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF. PMID:25673199

  17. Systemic Inflammatory Response and Serum Lipopolysaccharide Levels Predict Multiple Organ Failure and Death in Alcoholic Hepatitis

    PubMed Central

    Michelena, Javier; Altamirano, José; Abraldes, Juan G.; Affò, Silvia; Morales-Ibanez, Oriol; Sancho-Bru, Pau; Dominguez, Marlene; García-Pagán, Juan Carlos; Fernández, Javier; Arroyo, Vicente; Ginès, Pere; Louvet, Alexandre; Mathurin, Philippe; Mehal, Wajahat Z.; Caballería, Juan; Bataller, Ramón

    2015-01-01

    Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P <0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P=0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone. Conclusion In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids. PMID:25761863

  18. Hepatitis

    MedlinePlus

    ... be serious. Some can lead to scarring, called cirrhosis, or to liver cancer. Sometimes hepatitis goes away by itself. If it does not, it can be treated with drugs. Sometimes hepatitis lasts a lifetime. Vaccines can help prevent some viral forms.

  19. Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

    PubMed

    Li, Hai; Chen, Liu-Ying; Zhang, Nan-Nan; Li, Shu-Ting; Zeng, Bo; Pavesi, Marco; Amorós, Àlex; Mookerjee, Rajeshwar P; Xia, Qian; Xue, Feng; Ma, Xiong; Hua, Jing; Sheng, Li; Qiu, De-Kai; Xie, Qing; Foster, Graham R; Dusheiko, Geoffrey; Moreau, Richard; Gines, Pere; Arroyo, Vicente; Jalan, Rajiv

    2016-01-01

    The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were 'hepatic' and 'coagulation'. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles. PMID:27146801

  20. Serum from patients with hepatitis E virus-related acute liver failure induces human liver cell apoptosis

    PubMed Central

    WU, FAN; WANG, MINXIN; TIAN, DEYING

    2014-01-01

    The pathogenesis of acute liver failure has not been fully elucidated. The present study investigated the effects of the serum from patients with hepatitis E virus (HEV)-related acute liver failure on human liver cell survival and apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS) antibody recognizing core polysaccharide against acute liver failure serum-induced apoptosis. Serum was collected from patients with HEV-related acute liver failure. The levels of endotoxin (LPS) in the serum were measured using a quantitative tachypleus amebocyte lysate endotoxin detection kit with a chromogenic endpoint. Serum with a mean concentration of LPS was incubated with L02 human liver cells and the rate of apoptosis was detected by flow cytometry. The apoptotic rate was also evaluated in liver cells incubated with antibody and the HEV-related acute liver failure serum. The results indicated that the concentration of LPS in the serum of patients with HEV-related acute liver failure was 0.26±0.02 EU/ml, which was significantly higher than that of the control group (P<0.05). The rate of apoptosis in the human liver cells induced by acute liver failure serum was 5.83±0.42%, which was significantly increased compared with that in the cells treated with the serum of healthy individuals (P<0.05). The apoptotic rate of the cells incubated with antibody and the acute liver failure serum was 5.53±0.51%, which was lower than that of the cells incubated with acute liver failure serum alone (P>0.05). These results indicate that the serum of patients with HEV-related acute liver failure induces the apoptosis of human liver cells. LPS may be directly involved in the apoptosis of human liver cells. Moreover, the presence of the antibody did not significantly reduce the level of apoptosis of liver cells exposed to HEV-related acute liver failure serum. PMID:24348810

  1. Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure.

    PubMed

    Wang, Jing-Bo; Wang, Dong-Lei; Wang, Hai-Tao; Wang, Zhao-Han; Wen, Ying; Sun, Cui-Ming; Zhao, Yi-Tong; Wu, Jian; Liu, Pei

    2014-07-01

    The mechanism of renal failure during fulminant hepatic failure (FHF) or end-stage of liver disease is not fully understood. The present study aims to delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute hepatic failure. A rat model of renal insufficiency in severe liver injury was established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR was evaluated by continuous infusion of fluorescein isothiocyanate-inulin with implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe hepatocyte toxicity as evidenced by liver histology and biochemical tests, whereas renal morphology remained normal. GFR was reduced by 33% of the controls 12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a marked increase in serum TNF-α and ET-1 levels as well as significantly upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression. The upregulated IP3R1 expression was abrogated by the treatment of anti-TNF-α antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either TNF-α antibodies or 2-APB also significantly improved the compromised GFR, elevated serum urea nitrogen and creatinine levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT levels was much more attenuated by anti-TNF-α antibodies than by 2-APB. Liver histology further confirmed that anti-TNF-α antibodies conferred better protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-α over-production is responsible for decreased GFR through IP3R1 overexpression, and the compromised GFR resulted in the development of acute renal failure in rats with FHF. PMID:24887412

  2. Tim-3 alters the balance of IL-12/IL-23 and drives TH17 cells: role in hepatitis B vaccine failure during hepatitis C infection.

    PubMed

    Wang, Jia M; Ma, Cheng J; Li, Guang Y; Wu, Xiao Y; Thayer, Penny; Greer, Pamela; Smith, Ashley M; High, Kevin P; Moorman, Jonathan P; Yao, Zhi Q

    2013-04-26

    Hepatitis B virus (HBV) vaccination is recommended for individuals with hepatitis C virus (HCV) infection given their shared risk factors and increased liver-related morbidity and mortality upon super-infection. Vaccine responses in this setting are often blunted, with poor response rates to HBV vaccinations in chronically HCV-infected individuals compared to healthy subjects. In this study, we investigated the role of T cell immunoglobulin mucin domain-3 (Tim-3)-mediated immune regulation in HBV vaccine responses during HCV infection. We found that Tim-3, a marker for T cell exhaustion, was over-expressed on monocytes, leading to a differential regulation of IL-12/IL-23 production which in turn TH17 cell accumulation, in HCV-infected HBV vaccine non-responders compared to HCV-infected HBV vaccine responders or healthy subjects (HS). Importantly, ex vivo blockade of Tim-3 signaling corrected the imbalance of IL-12/IL-23 as well as the IL-17 bias observed in HBV vaccine non-responders during HCV infection. These results suggest that Tim-3-mediated dysregulation of innate to adaptive immune responses is involved in HBV vaccine failure in individuals with chronic HCV infection, raising the possibility that blocking this negative signaling pathway might improve the success rate of HBV immunization in the setting of chronic viral infection. PMID:23499521

  3. Tim-3 alters the balance of IL-12/IL-23 and drives TH17 cells: role in hepatitis B vaccine failure during hepatitis C infection

    PubMed Central

    Wang, Jia M.; Ma, Cheng J.; Li, Guang Y.; Wu, Xiao Y.; Thayer, Penny; Greer, Pamela; Smith, Ashley M.; High, Kevin P.; Moorman, Jonathan P; Yao, Zhi Q.

    2013-01-01

    Hepatitis B virus (HBV) vaccination is recommended for individuals with hepatitis C virus (HCV) infection given their shared risk factors and increased liver-related morbidity and mortality upon super-infection. Vaccine responses in this setting are often blunted, with poor response rates to HBV vaccinations in chronically HCV-infected individuals compared to healthy subjects. In this study, we investigated the role of T cell immunoglobulin mucin domain-3 (Tim-3)-mediated immune regulation in HBV vaccine responses during HCV infection. We found that Tim-3, a marker for T cell exhaustion, was over-expressed on monocytes, leading to a differential regulation of IL-12/IL-23 production with in turn TH17 cell accumulation, in HCV-infected HBV vaccine non-responders compared to HCV-infected HBV vaccine responders or healthy subjects (HS). Importantly, ex vivo blockade of Tim-3 signaling corrected the imbalance of IL-12/IL-23 as well as the IL-17 bias observed in HBV vaccine non-responders during HCV infection. These results suggest that Tim-3-mediated dysregulation of innate to adaptive immune responses is involved in HBV vaccine failure in individuals with chronic HCV infection, raising the possibility that blocking this negative signaling pathway might improve the success rate of HBV immunization in the setting of chronic viral infection. PMID:23499521

  4. Feasibility of progesterone treatment for ischaemic stroke.

    PubMed

    Gibson, Claire L; Bath, Philip M

    2016-03-01

    Two multi-centre phase III clinical trials examining the protective potential of progesterone following traumatic brain injury have recently failed to demonstrate any improvement in outcome. Thus, it is timely to consider how this impacts on the translational potential of progesterone treatment for ischaemic stroke. A wealth of experimental evidence supports the neuroprotective properties of progesterone, and associated metabolites, following various types of central nervous system injury. In particular, for ischaemic stroke, studies have also begun to reveal possible mechanisms of such neuroprotection. However, the results in traumatic brain injury now question whether further clinical development of progesterone for ischaemic stroke is relevant. PMID:26661235

  5. Feasibility of progesterone treatment for ischaemic stroke

    PubMed Central

    Bath, Philip M

    2015-01-01

    Two multi-centre phase III clinical trials examining the protective potential of progesterone following traumatic brain injury have recently failed to demonstrate any improvement in outcome. Thus, it is timely to consider how this impacts on the translational potential of progesterone treatment for ischaemic stroke. A wealth of experimental evidence supports the neuroprotective properties of progesterone, and associated metabolites, following various types of central nervous system injury. In particular, for ischaemic stroke, studies have also begun to reveal possible mechanisms of such neuroprotection. However, the results in traumatic brain injury now question whether further clinical development of progesterone for ischaemic stroke is relevant. PMID:26661235

  6. Fulminant hepatic failure attributed to infection with human herpesvirus 6 (HHV-6) in an immunocompetent woman: A case report and review of the literature.

    PubMed

    Charnot-Katsikas, Angella; Baewer, David; Cook, Linda; David, Michael Z

    2016-02-01

    Mild disease due to human herpesvirus-6 (HHV-6) has been reported in healthy children. Severe disease due to this virus can occur in immunocompromised patients but is rarely reported in previously healthy adults. We report the case of a previously healthy woman who presented with a skin rash, mild upper respiratory symptoms, and abdominal pain and succumbed to fulminant hepatic failure attributed to infection with HHV-6B. HHV-6 may be more commonly associated with fulminant hepatitis in immunocompetent patients than previously thought and should be considered in the differential diagnosis of patients presenting with skin rash, upper respiratory symptoms, and unexplained hepatitis. PMID:26745830

  7. Hypertension and the ischaemic myocardium.

    PubMed

    Fox, K M; Levy, R D; Mockus, L; Wright, C

    1987-08-01

    Hypertension and ischaemic heart disease often co-exist. Recent studies, using ambulatory ST-segment and haemodynamic monitoring, have shown that myocardial ischaemia may not necessarily be accompanied by angina pectoris. Unless transient myocardial ischaemia is actively sought it may, therefore, be missed and this may have important prognostic and therapeutic implications. Studies investigating the use of beta-blockers, calcium antagonists and nitrates in angina pectoris have shown that these agents have an equal effect on painless as opposed to painful myocardial ischaemia. While there are no currently completed studies demonstrating the prognostic implication of silent ischaemia in stable angina, it is well known that approximately one-quarter of all myocardial infarctions occur without chest pain. Recent investigation in unstable angina showed that silent ischaemia was an important predictor of future coronary events. PMID:3312524

  8. Failure to detect hepatitis B surface antigen (HBsAg) in certified shellfish from New England.

    PubMed Central

    Koff, R S; Connelly, L J

    1976-01-01

    In this study, hard- and soft-shell clams harvested during a one-year period from state approved (certified) clam beds in Maine, Massachusetts, and Rhode Island were tested for HBsAg by radioimmunoassay. HBsAg could not be detected in clam viscera. The role of bivalve mollusk ingestion in transmission of Hepatitis B remains speculative. PMID:1251953

  9. Circulating endothelin in acute ischaemic syndromes.

    PubMed Central

    Ray, S G; McMurray, J J; Morton, J J; Dargie, H J

    1992-01-01

    BACKGROUND--Endothelin is an extremely potent vasoconstrictor that may have a role in the pathogenesis of acute myocardial ischaemia. Atrial natriuretic factor is an endogenous antagonist of endothelin. To find the pattern and possible importance of circulating endothelin in ischaemic heart disease, concentrations in normal controls and those in patients with stable and unstable angina, acute myocardial infarction, and chronic cardiac failure were compared. The relation between circulating concentrations of endothelin and atrial natriuretic factor in the aftermath of myocardial infarction was also examined. METHODS--Eighteen patients with acute myocardial infarction, 10 with unstable angina, 10 with stable angina, 12 with chronic cardiac failure, and 10 normal controls were studied. Endothelin concentration was measured in venous plasma by radioimmunoassay. In patients with acute myocardial infarction simultaneous concentrations of endothelin and atrial natriuretic factor were measured on admission and at one, four, and 24 hours. RESULTS--Mean concentrations (SEM) of endothelin were 5.72 (0.19) fmol/ml in controls, 6.56 (0.48) fmol/ml in stable angina, 6.41 (0.48) fmol/ml in unstable angina, and 13.83 (0.95) fmol/ml in chronic cardiac failure. In acute myocardial infarction concentrations were 8.81 (0.69) fmol/ml on admission, 11.85 (1.02) fmol/ml at one hour, 11.88 (1.10) fmol/ml at four hours, and 7.30 (0.49) fmol/ml at 24 hours. Concentrations of atrial natriuretic factor at the same times were 68.1 (13.1) pg/ml, 8.4 (1.5) pg/ml, 24.4 (4.1) pg/ml, and 42.0 (6.9) pg/ml. CONCLUSIONS--Plasma endothelin is raised in chronic heart failure and in the aftermath of acute myocardial infarction but not in stable or unstable angina. After myocardial infarction endothelin concentrations are raised whereas concentrations of atrial natriuretic factor are relatively low. The role of endothelin in the pathogenesis of acute myocardial infarction and its interactions with other

  10. Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

    PubMed Central

    Li, Hai; Chen, Liu-Ying; Zhang, Nan-nan; Li, Shu-Ting; Zeng, Bo; Pavesi, Marco; Amorós, Àlex; Mookerjee, Rajeshwar P; Xia, Qian; Xue, Feng; Ma, Xiong; Hua, Jing; Sheng, Li; Qiu, De-kai; Xie, Qing; Foster, Graham R; Dusheiko, Geoffrey; Moreau, Richard; Gines, Pere; Arroyo, Vicente; Jalan, Rajiv

    2016-01-01

    The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles. PMID:27146801

  11. Entecavir Versus Lamivudine Therapy for Patients With Chronic Hepatitis B-Associated Liver Failure: A Meta-Analysis

    PubMed Central

    Zhang, Xiaoguo; An, Yong; Jiang, Xuemei; Xu, Minling; Xu, Linlin; Chen, Shijun; Xi, Yaguang

    2014-01-01

    Background: Nucleoside analogues are recommended as antiviral treatments for patients with hepatitis B virus (HBV)-associated liver failure. Clinical data comparing entecavir (ETV) and lamivudine (LAM) are inconsistent in this setting. Objectives: To compare the efficacy and safety of ETV and LAM in patients with chronic hepatitis B (CHB)-associated liver failure. Patients and Methods: A literature search was performed on articles published until January 2014 on therapy with ETV and LAM for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was the primary efficacy measure, while total bilirubin (TBIL), prothrombin activity (PTA) changes and HBV DNA negative change rates were secondary efficacy measures. A quantitative meta-analysis was performed to compare the efficacy of the two drugs. Safety of ETV and LAM was observed. Results: Four randomized controlled trials and nine retrospective cohort studies comprising a total of 1549 patients were selected. Overall analysis revealed comparable survival rates between patients received ETV and those received LAM (4 weeks: RR = 1.03, 95%CI [0.89, 1.18], P = 0.73; 8 weeks: RR = 0.98, 95% CI [0.85, 1.14], P = 0.84; 12 weeks: RR = 0.98, 95% CI [0.90, 1.08], P = 0.70; 24 weeks: RR = 1.02, 95% CI [0.94, 1.10], P = 0.66). After 24 weeks of treatment, patients treated with ETV had a significantly lower TBIL levels (MD = -37.34, 95% CI [-63.57, -11.11], P = 0.005), higher PTA levels (MD = 11.10, 95% CI [2.47, 19.73], P = 0.01) and higher HBV DNA negative rates (RR = 2.76, 95% CI [1.69, 4.51], P < 0.0001) than those treated with LAM. In addition, no drug related adverse effects were observed in the two treatment groups. Conclusions: ETV and LAM treatments had similar effects to improve 24 weeks survival rate of patients with CHB-associated liver failure, but ETV was associated with greater clinical improvement. Both drugs were tolerated well during

  12. The ischaemic constellation: an alternative to the ischaemic cascade—implications for the validation of new ischaemic tests

    PubMed Central

    Maznyczka, Annette; Sen, Sayan; Cook, Christopher; Francis, Darrel P

    2015-01-01

    The ischaemic cascade is the concept that progressive myocardial oxygen supply–demand mismatch causes a consistent sequence of events, starting with metabolic alterations and followed sequentially by myocardial perfusion abnormalities, wall motion abnormalities, ECG changes, and angina. This concept would suggest that investigations that detect expressions of ischaemia earlier in the cascade should be more sensitive tests of ischaemia than those that detect expressions appearing later in the cascade. However, careful review of the studies on which the ischaemic cascade is based suggests that the ischaemic cascade concept may be less well supported by the literature than assumed. In this review we explore this, discuss an alternative method for conceptualising ischaemia, and discuss the potential implications of this new approach to clinical studies and clinical practice. PMID:26196015

  13. The ischaemic constellation: an alternative to the ischaemic cascade-implications for the validation of new ischaemic tests.

    PubMed

    Maznyczka, Annette; Sen, Sayan; Cook, Christopher; Francis, Darrel P

    2015-01-01

    The ischaemic cascade is the concept that progressive myocardial oxygen supply-demand mismatch causes a consistent sequence of events, starting with metabolic alterations and followed sequentially by myocardial perfusion abnormalities, wall motion abnormalities, ECG changes, and angina. This concept would suggest that investigations that detect expressions of ischaemia earlier in the cascade should be more sensitive tests of ischaemia than those that detect expressions appearing later in the cascade. However, careful review of the studies on which the ischaemic cascade is based suggests that the ischaemic cascade concept may be less well supported by the literature than assumed. In this review we explore this, discuss an alternative method for conceptualising ischaemia, and discuss the potential implications of this new approach to clinical studies and clinical practice. PMID:26196015

  14. Ischaemic heart disease in pregnancy

    PubMed Central

    Bondagji, Nabeel S.

    2012-01-01

    Ischaemic heart disease (IHD) in pregnancy, particularly myocardial infarction (MI), is a rare yet potentially fatal condition for the mother and the foetus. With delays in the age of conception, the changes in some social habits among females including cigarette and shisha smoking in addition to an increased prevalence of diabetes mellitus, IHD may represent a real hazard among pregnant women in the near future. The difficulty in the diagnosis emerges from the similarity of the signs and symptoms of ischaemia and infarct to some of the physiological adaptations that occur in a normal pregnancy. The physiological changes that are normal in pregnancy may aggravate pre-existing disease and may unmask some underlying unrecognized coronary vascular changes; therefore, the diagnosis requires a high index of suspicion and careful assessment of the underlying risk factors. The management of IHD always requires a multidisciplinary team approach. The management of each patient should be individualized according to the clinical condition, the risk factors, and the availability of the necessary support. Pregnancy after MI may be an acceptable and reasonably safe option provided the cited criteria are met. A systematic PubMed search was performed to identify all published data including cases reports, small series and systematic reviews in the existing literature. These publications were comprised of both retrospective and cross sectional population studies to maximize the number of cases considered in order to reach conclusions and make recommendations based on the best available evidence considering the rare occurrence of this event. The epidemiology, diagnosis, medical and surgical treatment, and prognosis of IHD in pregnancy are the subjects of the present review. PMID:23960678

  15. New Point Mutations in Surface and Core Genes of Hepatitis B Virus Associated with Acute on Chronic Liver Failure Identified by Complete Genomic Sequencing

    PubMed Central

    Lou, Guohua; Zheng, Min; Cao, Qingyi; Chen, Zhi

    2015-01-01

    The objective of this study was to identify new viral biomarkers associated with acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV. Hepatitis B virus mutations associated with ACLF were screened by Illumina high-throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic hepatitis B patients, which were validated in 438 chronic hepatitis B patients (80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The results of Illumina sequencing showed that the mutations at 7 sites (T216C, G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were significantly higher than those of 12 controls. In the validation cohorts, a significantly higher ratio of genotype B to C was found in patients with ACLF than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A, C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any combination, A/G1913 in any combination, and G/C2159 in any combination had high specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors independently associated with ACLF. Combined mutations in hepatitis B cases could play important roles in ACLF development. PMID:25849554

  16. Protective effect of Amaranthus spinosus against D-galactosamine/lipopolysaccharide-induced hepatic failure.

    PubMed

    Zeashan, Hussain; Amresh, G; Singh, Satyawan; Rao, Chandana Venkateswara

    2010-10-01

    The current study is an effort to identify the hepatoprotective activity of the 50% ethanol extract of the whole plant of Amaranthus spinosus Linn. (Amaranthaceae) against d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced liver injury in rats. d-GalN/LPS (300 mg/kg body weight/30 µg/kg body weight)-induced hepatic damage was manifested by a significant (p <0.05) increase in the activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase) and bilirubin level in serum while phospholipids significantly decreased. All other parameters, i.e. cholesterol, triglycerides and free fatty acids were increased significantly in both serum and liver compared to the control group. Pretreatment of rats with A. spinosus extract (400 mg/kg) significantly (p <0.05) reversed these altered parameters to normal compared to the intoxicated group. The biochemical observations were supplemented by histopathological examination of liver sections. There were no significant changes in the activities of marker enzymes, bilirubin level and lipids in the rats treated with A. spinosus extract alone. Results of this study revealed that A. spinosus extract could afford a significant protection against d-GalN/LPS-induced hepatocellular injury. PMID:20860438

  17. Emergency ABO-incompatible liver transplant secondary to fulminant hepatic failure: outcome, role of TPE and review of the literature.

    PubMed

    Maitta, Robert W; Choate, Jacquelyn; Emre, Sukru H; Luczycki, Stephen M; Wu, Yanyun

    2012-01-01

    The increasing demand for solid organ transplants has brought to light the need to utilize organs in critical situations despite ABO-incompatibility. However, these transplantations are complicated by pre-existing ABO antibodies which may be potentially dangerous and makes the transplantation prone to failure due to rejection with resulting necrosis or intrahepatic biliary complications. We report the clinical outcome of an emergency ABO-incompatible liver transplant (due to fulminant hepatic failure with sudden and rapidly deteriorating mental status) using a modified therapeutic plasma exchange (TPE) protocol. The recipient was O-positive with an initial anti-B titer of 64 and the cadaveric organ was from a B-positive donor. The patient underwent initial TPE during the peri-operative period, followed by a series of postoperative daily TPE, and later a third series of TPE for presumptive antibody-mediated rejection. The latter two were performed in conjunction with the use of IVIg and rituximab. The recipient's anti-B titer was reduced and maintained at 8 or less 8 months post-op. However, an elevation of transaminases 3 months post-transplant triggered a biopsy which was consistent with cellular rejection and with weak C4d positive staining suggestive of antibody mediated rejection. Additional plasma exchange procedures were performed. The patient improved rapidly after modification of her immunosuppression regimen and treatment with plasma exchange. This case illustrates that prompt and aggressive plasma exchange, in conjunction with immunosuppression, is a viable approach to prevent and treat antibody mediated transplant rejection in emergency ABO-incompatible liver transplant. PMID:22833397

  18. Recent development of ischaemic heart disease in sex difference

    PubMed Central

    Shu, Wang; Lei, Wang; Peng, Song

    2007-01-01

    Despite a dramatic decline in mortality over the past years, coronary heart disease is the leading cause of death and disability in the world. At the same time, with the great improvement of medical science, there is a growing population of postmyocardial infarction, postrevascularisation and heart failure survivors. Furthermore, there are rising rates of cigarette smoking, obesity, hypertension and the metabolic syndrome in the world. All the above contribute to the rising incidence rates of ischaemic heart disease (IHD) among women and men. This review highlights sex‐specific issues in IHD presentation, evaluation and outcomes, with several new results published from the Women's Ischemia Syndrome Evaluation study. New evidence on traditional and novel risk markers as well as sex‐specific differences in symptoms and diagnostic approaches have also been discussed. PMID:17403950

  19. Acute Q fever presenting as fever of unknown origin with rapidly progressive hepatic failure in a patient with alcoholism.

    PubMed

    Lin, Po-Han; Lo, Yi-Chun; Chiang, Fu-Tien; Wang, Jiun-Ling; Jeng, Yung-Ming; Fang, Chi-Tai; Chang, Shan-Chwen

    2008-11-01

    We report a case of fulminant acute Q fever presenting as fever of unknown origin with rapidly progressive hepatic failure in a patient with alcoholism. A 51-year-old electrician, who was a habitual drinker, presented with a 2-week history of intermittent high fever, acute hepatomegaly and rapidly progressive jaundice after being accidentally exposed to dust from bird nests when he was repairing electrical equipment and circuitry at an abandoned factory in Taipei County. Ascites and prolonged prothrombin time were noted at admission. Transjugular liver biopsy and bone marrow biopsy found multiple small fibrinoid-ring granulomas in liver parenchyma and bone marrow. Doxycycline therapy was empirically started. The fever gradually subsided over a 2-week period, along with the recovery of liver function. The diagnosis of acute Q fever was confirmed by high titers of antibodies against Coxiella burnetii (phase I IgM 1:160 and IgG 1:2560, phase II IgM > 1:320 and IgG 1:5120) and a four-fold elevation of phase II IgG titer in the paired serum. The experience of this case shows that the possibility of Q fever should not be overlooked in patients who have an unexplained febrile illness and severe liver function impairment following exposure to a contaminated environment in Taiwan. PMID:18971160

  20. Bacterial and fungal infection in children with fulminant hepatic failure: possible role of opsonisation and complement deficiency.

    PubMed Central

    Larcher, V F; Wyke, R J; Mowat, A P; Williams, R

    1982-01-01

    Serious bacterial infection, including eight episodes of bacteraemia, developed in seven of 15 (47%) children with fulminant hepatic failure. Those with infections had a slightly higher leucocyte response than those who did not. Serum immunoglobulin concentrations were normal or raised in all patients. Opsonisation of heat-killed baker's yeast, functionally measured total haemolytic complement, C4, C5, total alternative pathway activity, factor B and D activity, and C3 concentrations were all significantly (p less than 0.005) reduced at presentation but returned to normal in those who survived. The severity of defects in yeast opsonisation, C4, and factor B activity at presentation were significantly correlated with the subsequent development of infection. In five patients bacteraemia occurred at a time when opsonisation and complement components were defective. Plasma infusions in vivo improved opsonisation in vitro and only one bacterial isolate was obtained within four days of such an infusion. Those patients who developed infection had received significantly (p less than 0.05) fewer plasma infusions than those who did not. Our findings suggest that both alternative and classical pathways of complement are defective in children with severe liver disease and may contribute to the susceptibility of such patients to infections. Plasma infusions might be useful in reducing the incidence of bacterial infection in such conditions. PMID:6757064

  1. Altering the sphingolipid acyl chain composition prevents LPS/GLN-mediated hepatic failure in mice by disrupting TNFR1 internalization

    PubMed Central

    Ali, M; Fritsch, J; Zigdon, H; Pewzner-Jung, Y; Schütze, S; Futerman, A H

    2013-01-01

    The involvement of ceramide in death receptor-mediated apoptosis has been widely examined with most studies focusing on the role of ceramide generated from sphingomyelin hydrolysis. We now analyze the effect of the ceramide acyl chain length by studying tumor necrosis factor α receptor-1 (TNFR1)-mediated apoptosis in a ceramide synthase 2 (CerS2) null mouse, which cannot synthesize very-long acyl chain ceramides. CerS2 null mice were resistant to lipopolysaccharide/galactosamine-mediated fulminant hepatic failure even though TNFα secretion from macrophages was unaffected. Cultured hepatocytes were also insensitive to TNFα-mediated apoptosis. In addition, in both liver and in hepatocytes, caspase activities were not elevated, consistent with inhibition of TNFR1 pro-apoptotic signaling. In contrast, Fas receptor activation resulted in the death of CerS2 null mice. Caspase activation was blocked because of the inability of CerS2 null mice to internalize the TNFR1; whereas Fc-TNFα was internalized to a perinuclear region in hepatocytes from wild-type mice, no internalization was detected in CerS2 null mice. Our results indicate that altering the acyl chain composition of sphingolipids inhibits TNFR1 internalization and inhibits selective pro-apoptotic downstream signaling for apoptosis. PMID:24263103

  2. Protective effects of lupeol against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

    PubMed

    Kim, So-Jin; Cho, Hong-Ik; Kim, Seok-Joo; Kim, Joon-Sung; Kwak, Jong-Hwan; Lee, Dong-Ung; Lee, Sang Kook; Lee, Sun-Mee

    2014-11-26

    This study examined the hepatoprotective effects of lupeol (1, a major active triterpenoid isolated from Adenophora triphylla var. japonica) against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were orally administered 1 (25, 50, and 100 mg/kg; dissolved in olive oil) 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) treatment. Treatment with GalN/LPS resulted in increased levels of serum alanine aminotransferase, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as increased mortality, all of which were attenuated by treatment with 1. In addition, levels of toll-like receptor (TLR)4, myeloid differentiation primary response gene 88, TIR-domain-containing adapter-inducing interferon-β (TRIF), IL-1 receptor-associated kinase (IRAK)-1, and TNF receptor associated factor 6 protein expression were increased by GalN/LPS. These increases, except TRIF, were attenuated by 1. Interestingly, 1 augmented GalN/LPS-mediated increases in the protein expression of IRAK-M, a negative regulator of TLR signaling. Following GalN/LPS treatment, nuclear translocation of nuclear factor-κB and the levels of TNF-α and IL-6 mRNA expression increased, which were attenuated by 1. Together, the present findings suggest that lupeol (1) ameliorates GalN/LPS-induced liver injury, which may be due to inhibition of IRAK-mediated TLR inflammatory signaling. PMID:25325613

  3. Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats.

    PubMed

    Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Martinez-Perez, Yoalli; Lezama-Palacios, Ruth; Franco-Colin, Margarita; Ortiz-Butron, Rocio

    2015-10-01

    The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment. PMID:26238033

  4. Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015.

    PubMed

    Mochida, Satoshi; Nakayama, Nobuaki; Ido, Akio; Takikawa, Yasuhiro; Yokosuka, Osamu; Sakaida, Isao; Moriwaki, Hisataka; Genda, Takuya; Takikawa, Hajime

    2016-03-01

    In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure. PMID:26615003

  5. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

    2015-10-01

    The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management. PMID:25500531

  6. Protective effect of an improved immunization practice of mother-to-infant transmission of hepatitis B virus and risk factors associated with immunoprophylaxis failure.

    PubMed

    Wang, Chong; Wang, Chuan; Jia, Zhi-Fang; Wu, Xing; Wen, Si-Min; Kong, Fei; Hu, Ke-Qin; Li, Jie; Jiang, Jing; Niu, Jun-Qi

    2016-08-01

    Although routine immunoprophylaxis has been known to reduce hepatitis B virus (HBV) transmission, immunoprophylaxis failure still occurs. The study aimed to investigate the protective efficacy of an improved immunoprophylaxis protocol to prevent mother-to-infant transmission of HBV and to explore the potential risk factors associated with immunoprophylaxis failure and low antibody response.A prospective observational cohort study was conducted from July 2012 to April 2015. A total of 863 HBsAg-positive mothers and their 871 infants (8 pairs of twins) were included in the study. Two different hepatitis B vaccine doses (20 or 10 μg) were administered to the infants based on the hepatitis B e-antigen (HBeAg) status of their mothers. Simultaneously, hepatitis B immunoglobulin (HBIG) was administered to the infants. Initial injections of HBIG and the hepatitis vaccine were given within 2 hours after birth. Rates of HBV infections among the infants were evaluated at 7 months of age. Factors associated with immunoprophylaxis failure and low responses to vaccination were analyzed by unconditional logistic regression..At 7 months of age, no immunoprophylaxis failure was observed in the 565 infants born to HBeAg-negative mothers. Among the 306 infants born to HBeAg-positive mothers, immunoprophylaxis failed in 16 infants (5.2%) of the infants and they were found to be HBsAg-positive. Further analysis showed that HBV DNA levels ≥10 IU/mL [odds ratio (OR) = 4.53, 95% confidence interval (95% CI): 1.19-17.34], delayed vaccination (OR = 4.14, 95% CI: 1.00-17.18), and inadequate initial injections (OR = 7.69, 95% CI: 1.71-34.59) were independently associated with immunoprophylaxis failure. Adequate titers of antibody to HBsAg (anti-HBs, ≥100 mIU/mL) were present in 96.5% of immunoprophylaxis-successful infants. For full-term infants, birth weights <3000 g were correlated with low immune responses to vaccination.This improved immunoprophylaxis protocol

  7. Right hepatectomy with extra-hepatic vascular division prior to transection: intention-to-treat analysis of a standardized policy

    PubMed Central

    Boleslawski, Emmanuel; Decanter, Gauthier; Truant, Stéphanie; Bouras, Ahmed Fouad; Sulaberidze, Lasha; Oberlin, Olivier; Pruvot, François-René

    2012-01-01

    Background Right hepatectomy (RH) is the most common type of major hepatectomy and can be achieved without portal triad clamping (PTC) in non-cirrhotic liver. The present study reviews our standardized policy of performing RH without systematic PTC. Methods One hundred and eighty-one consecutive RH were performed in non-cirrhotic patients, with division of the right afferent and efferent blood vessels prior to transection, without systematically using PTC. Prospectively collected data were analysed, focusing on the following endpoints: need for salvage PTC, ischaemic time, blood loss and post-operative outcome. Results Extra-hepatic division of the right hepatic vessels was feasible in all patients, but was ineffective in 48 patients (26.5%) who required salvage PTC during transection. In those patients, the median ischaemic time was 20 min. The median blood loss was 500 ml (50–3000). Six patients (3.3%) experienced post-operative liver failure. Overall morbidity, severe morbidity and mortality were 42%, 12.1% and 1.6%, respectively, with peri-operative transfusion rate (16.6%) being the only factor associated with morbidity. Discussion By performing RH with extra-hepatic vascular division prior to transection, PTC can be safely avoided in the majority of patients. PMID:22954006

  8. Rapid liver enlargement and hepatic failure secondary to radiographic occult tumor invasion: two case reports and review of the literature

    PubMed Central

    2012-01-01

    Introduction Unfamiliarity with certain clinical presentations, as illustrated in these cases, can lead to delayed diagnoses that in turn cause increased morbidity, prolonged hospitalization, and the need for autopsy. Case presentation In Case 1, a 63-year-old Caucasian woman presented with hepatic enlargement and insufficiency which progressed and resulted in her death over a period of less than 2 weeks. The patient underwent a detailed workup included magnetic resonance imaging and computed tomography scan of her liver, which did not reveal the source of her liver enlargement. Due to her progressive liver enlargement and insufficiency, she developed a life-threatening esophageal variceal bleeding during her hospital stay which further delayed the attainment of her diagnosis. She finally underwent a videoscopic laparotomy and liver biopsy which revealed complete replacement and filling in of the liver sinuous with Indian filing lobular breast cancer. The patient died shortly after her diagnosis and before she could be discharged. In Case 2, a 68-year-old Caucasian woman with non-small-cell lung cancer was admitted to our Oncology in-patient service with a presentation of rapid hepatic insufficiency and severe liver enlargement. Like the patient in Case 1, during her hospitalization, this patient underwent a thorough radiographic evaluation, including computed tomography and magnetic resonance imaging, to identify the source of her symptoms. Radiographic imaging showed only hepatomegaly and no discrete focal lesions. As the multiple imaging studies over a period of a week did not reveal a clear cause for her symptoms, she finally underwent an interventional radiology core biopsy which showed complete replacement of her liver with non-small-cell lung cancer. Her condition rapidly progressed due to continued liver enlargement and she died due to frank liver failure before her diagnosis was affirmed and she could be discharged. Conclusion Both of these cases

  9. Autophagic response in the Rabbit Hemorrhagic Disease, an animal model of virally-induced fulminant hepatic failure

    PubMed Central

    2014-01-01

    The Rabbit Hemorrhagic Disease Virus (RHDV) induces a severe disease that fulfils many requirements of an animal model of fulminant hepatic failure. However, a better knowledge of molecular mechanisms contributing to liver damage is required, and it is unknown whether the RHDV induces liver autophagy and how it relates to apoptosis. In this study, we attempted to explore which signalling pathways were involved in the autophagic response induced by the RHDV and to characterize their role in the context of RHDV pathogenesis. Rabbits were infected with 2 × 104 hemmaglutination units of a RHDV isolate. The autophagic response was measured as presence of autophagic vesicles, LC3 staining, conversion of LC3-I to autophagosome-associated LC3-II and changes in expression of beclin-1, UVRAG, Atg5, Atg12, Atg16L1 and p62/SQSTM1. RHDV-triggered autophagy reached a maximum at 24 hours post-infection (hpi) and declined at 30 and 36 hpi. Phosphorylation of mTOR also augmented in early periods of infection and there was an increase in the expression of the endoplasmic reticulum chaperones BiP/GRP78, CHOP and GRP94. Apoptosis, measured as caspase-3 activity and expression of PARP-1, increased significantly at 30 and 36 hpi in parallel to the maximal expression of the RHDV capsid protein VP60. These data indicate that RHDV infection initiates a rapid autophagic response, perhaps in an attempt to protect liver, which associates to ER stress development and is independent from downregulation of the major autophagy suppressor mTOR. As the infection continues and the autophagic response declines, cells begin to exhibit apoptosis. PMID:24490870

  10. [Chronic ischaemic heart disease in the elderly].

    PubMed

    Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa

    2016-04-15

    It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging. PMID:26965220

  11. [Chronic ischaemic heart disease in the elderly].

    PubMed

    Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa

    2016-01-01

    It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging. PMID:27102136

  12. Central regions of keloids are severely ischaemic.

    PubMed

    Touchi, Ryoma; Ueda, Koichi; Kurokawa, Norifumi; Tsuji, Motomu

    2016-02-01

    We classified scars as keloids, hypertrophic scars and mature scars, and then examined the scars for differences in central and marginal vascularization. We found significant differences in localized hypoxia-induced factor-1α (HIF-1α) expression and vascular density in keloids, but no localized differences in hypertrophic or mature scars. The central areas of keloids exhibited higher HIF-1α expression and lower vascular density than marginal areas, suggesting that the former are severely ischaemic. PMID:26794626

  13. Remote ischaemic conditioning and remodelling following myocardial infarction: current evidence and future perspectives.

    PubMed

    Vanezis, A P; Rodrigo, G C; Squire, I B; Samani, N J

    2016-09-01

    Remote ischaemic conditioning (rIC) has demonstrated its effectiveness as a powerful cardioprotective tool in number of preclinical and limited clinical settings. More recently, ischaemic postconditioning given after an ischaemic event such as a myocardial infarction (MI) has shown not only to reduce infarct size but also to have beneficial effects on acute remodelling post-MI and to reduce the burden of heart failure and other detrimental outcomes. Building on this platform, repeated rIC over a number of days has the potential to augment the protective process even further. This review considers the current evidence base from which the concept of rIC in the setting of post-MI remodelling has grown. It also discusses the ongoing and planned clinical trials which are attempting to elucidate whether the protection imparted by rIC in the preclinical setting can be translated to the clinic and become a realistic weapon in the clinician's armoury to tackle acute remodelling and heart failure post-MI. PMID:27177446

  14. Target hepatic artery regional chemotherapy and bevacizumab perfusion in liver metastatic colorectal cancer after failure of first-line or second-line systemic chemotherapy.

    PubMed

    Chen, Hui; Zhang, Ji; Cao, Guang; Liu, Peng; Xu, Haifeng; Wang, Xiaodong; Zhu, Xu; Gao, Song; Guo, Jianhai; Zhu, Linzhong; Zhang, Pengjun

    2016-02-01

    Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer. TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials. PMID:26566233

  15. To Revascularise or Not To Revascularise, That Is the Question: the Diagnostic and Management Conundrum of Ischaemic Cardiomyopathy.

    PubMed

    Briceno, Natalia; Perera, Divaka

    2016-06-01

    Ischaemic cardiomyopathy is an important cardiovascular condition that has differing pathophysiological substrates and clinical manifestations. Contemporary management involves the administration of heart failure pharmacotherapy and device therapy where indicated, which has good prognostic data to support it. Whilst the role of revascularisation is clear in those patients presenting with an acute coronary syndrome or angina, the role in those patients presenting either incidentally, with predominant heart failure symptoms, or in those presenting with acute heart failure with an associated elevated troponin is less well defined and lacks randomised outcome data to support its adoption. The aim of this review is therefore to discuss the challenges in the diagnosis of ischaemic cardiomyopathy with a review of the existing imaging modalities that can facilitate, and to revisit the variety of clinical presentations that can occur, with particular emphasis on the contemporary role of revascularisation in these cohorts of patients. PMID:27115418

  16. Acute ischaemic colitis associated with oral phenylephrine decongestant use.

    PubMed

    Ward, Paul W; Shaneyfelt, Terrence M; Roan, Ronald M

    2014-01-01

    In this case, the authors have presented for the first time that ischaemic colitis may be associated with phenylephrine use. Since phenylephrine is the more common active ingredient in over-the-counter (OTC) cold medications, other presentations may follow this case. A MEDLINE search was performed for all case reports or case series of ischaemic colitis secondary to pseudoephedrine or phenylephrine use published between 1966 and 2013. The search resulted in four case reports and one case series describing patients with acute onset ischaemic colitis with exposure to pseudoephedrine immediately prior to onset. However, we found no case reports of ischaemic colitis associated with phenylephrine use. We present this case as an unexpected clinical outcome of phenylephrine, which has not been associated with ischaemic colitis in the literature. Also, this case serves as a reminder of the important clinical lesson to question all patients' use of OTC and prescribed medications. PMID:24895387

  17. Acute ischaemic colitis associated with oral phenylephrine decongestant use

    PubMed Central

    Ward, Paul W; Shaneyfelt, Terrence M; Roan, Ronald M

    2014-01-01

    In this case, the authors have presented for the first time that ischaemic colitis may be associated with phenylephrine use. Since phenylephrine is the more common active ingredient in over-the-counter (OTC) cold medications, other presentations may follow this case. A MEDLINE search was performed for all case reports or case series of ischaemic colitis secondary to pseudoephedrine or phenylephrine use published between 1966 and 2013. The search resulted in four case reports and one case series describing patients with acute onset ischaemic colitis with exposure to pseudoephedrine immediately prior to onset. However, we found no case reports of ischaemic colitis associated with phenylephrine use. We present this case as an unexpected clinical outcome of phenylephrine, which has not been associated with ischaemic colitis in the literature. Also, this case serves as a reminder of the important clinical lesson to question all patients’ use of OTC and prescribed medications. PMID:24895387

  18. Protective effects of protostemonine on LPS/GalN-induced acute liver failure: Roles of increased hepatic expression of heme oxygenase-1.

    PubMed

    Cheng, Zhuo; Yue, Ling; Zhao, Wenhao; Yang, Xinzhou; Shu, Guangwen

    2015-12-01

    Here, we explored protective effects of protostemonine (PSN), on mouse acute liver failure induced by lipopolysaccharide/d-galactosamine (LPS/GalN). PSN dose-dependently declined LPS/GalN-induced lethality of mice as well as increase of ALT/AST activities in their serum. Hepatoprotective effects of PSN were also supported by liver histopathological examinations. After LPS/GalN treatment, severe oxidative stresses in the liver could be detected by boosted MDA and ROS as well as decreased GSH. Moreover, hepatic expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, were sharply elevated. These symptoms were dose-dependently ameliorated by PSN. Mechanistically, PSN promoted the transcription and translation of heme oxygenase-1 (HO-1) in hepatocytes and liver Kupffer cells. Nrf2 is a master transcription factor contributing to the expression of HO-1. PSN elevated Nrf2 nuclear accumulation and enhanced Nrf2/HO-1 promoter interaction. Suppressing enzyme activity of HO-1 by co-treating mice with HO-1 inhibitor ZnPP abolished protective effects of PSN. ZnPP also abrogated alleviative impacts of PSN on LPS/GalN-mediated hepatic oxidative stresses and inflammatory responses. Finally, we showed that PSN exhibited undetectable toxic effects on vital organs of mice. Our findings suggested that PSN is able to attenuate LPS/GalN-induced acute liver failure and upregulating HO-1 expression is implicated in its hepatoprotective activity. PMID:26363973

  19. Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

    PubMed Central

    Kim, Yu Ri; Ban, Jung Ok; Yoo, Hwan Soo; Lee, Yong Moon; Yoon, Yeo Pyo; Eum, So Young; Jeong, Heon Sang; Yoon, Do-young; Han, Sang Bae; Hong, Jin Tae

    2013-01-01

    High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity. PMID:23935693

  20. Total hepatectomy and liver transplantation as a two-stage procedure for fulminant hepatic failure: A safe procedure in exceptional circumstances

    PubMed Central

    Sanabria Mateos, Rebeca; Hogan, Niamh M; Dorcaratto, Dimitri; Heneghan, Helen; Udupa, Venkatesh; Maguire, Donal; Geoghegan, Justin; Hoti, Emir

    2016-01-01

    AIM: To evaluate the outcomes of two-stage liver transplant at a single institution, between 1993 and March 2015. METHODS: We reviewed our institutional experience with emergency hepatectomy followed by transplantation for fulminant liver failure over a twenty-year period. A retrospective review of a prospectively maintained liver transplant database was undertaken at a national liver transplant centre. Demographic data, clinical presentation, preoperative investigations, cardiocirculatory parameters, operative and postoperative data were recorded. RESULTS: In the study period, six two-stage liver transplants were undertaken. Indications for transplantation included acute paracetamol poisoning (n = 3), fulminant hepatitis A (n = 1), trauma (n = 1) and exertional heat stroke (n = 1). Anhepatic time ranged from 330 to 2640 min. All patients demonstrated systemic inflammatory response syndrome in the first post-operative week and the incidence of sepsis was high at 50%. There was one mortality, secondary to cardiac arrest 12 h following re-perfusion. Two patients required re-transplantation secondary to arterial thrombosis. At a median follow-up of 112 mo, 5 of 6 patients are alive and without evidence of graft dysfunciton. CONCLUSION: Two-stage liver transplantation represents a safe and potentially life-saving treatment for carefully selected exceptional cases of fulminant hepatic failure. PMID:26855693

  1. Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia.

    PubMed

    Menezes, Minal J; Guo, Yiran; Zhang, Jianguo; Riley, Lisa G; Cooper, Sandra T; Thorburn, David R; Li, Jiankang; Dong, Daoyuan; Li, Zhijun; Glessner, Joseph; Davis, Ryan L; Sue, Carolyn M; Alexander, Stephen I; Arbuckle, Susan; Kirwan, Paul; Keating, Brendan J; Xu, Xun; Hakonarson, Hakon; Christodoulou, John

    2015-04-15

    Functional defects of the mitochondrial translation machinery, as a result of mutations in nuclear-encoded genes, have been associated with combined oxidative phosphorylation (OXPHOS) deficiencies. We report siblings with congenital sensorineural deafness and lactic acidemia in association with combined respiratory chain (RC) deficiencies of complexes I, III and IV observed in fibroblasts and liver. One of the siblings had a more severe phenotype showing progressive hepatic and renal failure. Whole-exome sequencing revealed a homozygous mutation in the gene encoding mitochondrial ribosomal protein S7 (MRPS7), a c.550A>G transition that encodes a substitution of valine for a highly conserved methionine (p.Met184Val) in both affected siblings. MRPS7 is a 12S ribosomal RNA-binding subunit of the small mitochondrial ribosomal subunit, and is required for the assembly of the small ribosomal subunit. Pulse labeling of mitochondrial protein synthesis products revealed impaired mitochondrial protein synthesis in patient fibroblasts. Exogenous expression of wild-type MRPS7 in patient fibroblasts rescued complexes I and IV activities, demonstrating the deleterious effect of the mutation on RC function. Moreover, reduced 12S rRNA transcript levels observed in the patient's fibroblasts were also restored to normal levels by exogenous expression of wild-type MRPS7. Our data demonstrate the pathogenicity of the identified MRPS7 mutation as a novel cause of mitochondrial RC dysfunction, congenital sensorineural deafness and progressive hepatic and renal failure. PMID:25556185

  2. Vitamin D and ischaemic heart disease.

    PubMed

    Lund, B; Badskjaer, J; Lund, B; Soerensen, O H

    1978-11-01

    Vitamin D has been proposed as a risk factor of ischaemic heart disease. In 12 patients with acute myocardial infarction the major circulating vitamin D metabolite, 25-hydroxy-cholecalciferol (25-HCC), did not show any fluctuations during the first 4 days after onset of symptoms. The serum 25-HCC level was then measured in 128 patients consecutively admitted because of chest pain, 53 of whom had myocardial infarction and 75 had angina pectoris. The values found did not differ from those measured in 409 normal persons. The seasonal variations of serum 25-HCC were less pronounced in heart patients than in normals, probably due to less sun exposure in the summer months. The levels of serum 25-HCC did not correlate with the concentrations of serum cholesterol, glycerides, calcium or magnesium. Low serum calcium and magnesium were observed in all patients. Serum calcium was further reduced in the course of acute myocardial infarctions while serum parathyroid hormone rose significantly. We conclude that patients with ischaemic heart disease are not ingesting or producing in their skin elevated amount of vitamin D. PMID:744575

  3. Continuous-flow left ventricular assist device therapy in patients with preoperative hepatic failure: are we pushing the limits too far?

    PubMed

    Weymann, Alexander; Patil, Nikhil P; Sabashnikov, Anton; Mohite, Phrashant N; Garcia Saez, Diana; Bireta, Christian; Wahlers, Thorsten; Karck, Matthias; Kallenbach, Klaus; Ruhparwar, Arjang; Fatullayev, Javid; Amrani, Mohamed; De Robertis, Fabio; Bahrami, Toufan; Popov, Aron-Frederik; Simon, Andre R

    2015-04-01

    The purpose of this study was to evaluate the effects and outcome of continuous-flow left ventricular assist device (cf-LVAD) therapy in patients with preoperative acute hepatic failure. The study design was a retrospective review of prospectively collected data. Included were 42 patients who underwent cf-LVAD implantation (64.3% HeartMate II, 35.7% HeartWare) between July 2007 and May 2013 with preoperative hepatic failure defined as elevation of greater than or equal to two liver function parameters above twice the upper normal range. Mean patient age was 35 ± 12.5 years, comprising 23.8% females. Dilated cardiomyopathy was present in 92.9% of patients (left ventricular ejection fraction 17.3 ± 5.9%). Mean support duration was 511 ± 512 days (range: 2-1996 days). Mean preoperative laboratory parameters for blood urea nitrogen, serum creatinine, total bilirubin, and alanine aminotransferase were 9.5 ± 5.4 mg/dL, 110.3 ± 42.8 μmol/L, 51.7 ± 38.3 mmol/L, and 242.1 ± 268.6 U/L, respectively. All parameters decreased significantly 1 month postoperatively. The mean preoperative modified Model for Endstage Liver Disease excluding international normalized ratio score was 16.03 ± 5.57, which improved significantly after cf-LVAD implantation to 10.62 ± 5.66 (P < 0.001) at 7 days and 5.83 ± 4.98 (P < 0.001) at 30 days postoperatively. One-year and 5-year survival was 75.9 and 48.1%, respectively. 21.4% of the patients underwent LVAD explantation for myocardial recovery, 16.7% were successfully transplanted, and 7.1% underwent LVAD exchange for device failure over the follow-up period. Patients with preexisting acute hepatic failure are reasonable candidates for cf-LVAD implantation, with excellent rates of recovery and survival, suggesting that cf-LVAD therapy should not be denied to patients merely on grounds of "preoperative elevated liver enzymes/hepatopathy." PMID:25345547

  4. Environmental stress, reactivity and ischaemic heart disease.

    PubMed

    Krantz, D S; Raisen, S E

    1988-03-01

    This article provides an overview of work in two areas of biobehavioural research: the effects of environmental stress and the role of psychophysiologic reactivity in the development of ischaemic heart disease. Attention is given first to evidence that low socio-economic status, low social support, and occupational settings characterized by high demands and low levels of control over the job are associated with increased coronary risk. Also discussed is a promising animal primate model of social stress and its role in development of coronary atherosclerosis. Next, we discuss physiological responsiveness (reactivity) to emotional stress, which is being studied as a marker of processes involved in the development of cardiovascular disease. Stress and psychophysiological reactivity constitute promising targets for research on biobehavioural antecedents of coronary disease and for clinical intervention studies. However, further evidence is needed before these variables can be regarded as proven coronary risk factors. PMID:3129010

  5. Upregulated Expression of A20 on Monocytes is Associated With Increased Severity of Acute-on-Chronic Hepatitis B Liver Failure: A Case-Control Study.

    PubMed

    Guo, Yonghong; He, Yu; Zhang, Ying; Zhou, Yun; Qin, Yuan; Fan, Chao; Ji, Guangxi; Zhang, Peixin; Jia, Zhansheng

    2015-09-01

    A20 expression is increased in various inflammatory diseases. However, the role of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate A20 expression on monocytes and its associations with the severity of acute-on-chronic hepatitis B liver failure (ACHBLF). Thirty-seven patients with ACHBLF, 20 patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were enrolled in this case-control study. A20-positive monocytes were identified using flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-α were determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1 cells stimulated by lipopolysaccharide (LPS). The frequency of A20+ monocytes was significantly increased in patients with ACHBLF compared with HC (median [interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased monocyte A20 expression was detected during the progression phase (including the mild/moderate and severe grades of ACHBLF) compared with patients in the recovery phase (both P < 0.05), and in the ACHBLF worsening group compared with patients in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10 expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and inversely with prothrombin activity (r = -0.33, P = 0.046). IL-10 and TLR4 expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF-α were increased in patients with ACHBLF compared with patients with CHB and HC. Increased A20 expression on monocytes was associated with the severity of ACHBLF. PMID:26426612

  6. Prevalence of ischaemic heart disease in middle aged British men.

    PubMed Central

    Shaper, A G; Cook, D G; Walker, M; Macfarlane, P W

    1984-01-01

    The prevalence of ischaemic heart disease was determined by an administered questionnaire and electrocardiography in 7735 men aged 40-59 years drawn at random from general practices in 24 British towns. Overall, one quarter of these men had some evidence of ischaemic heart disease on questionnaire or electrocardiogram or both. On questionnaire, 14% of men had possible myocardial infarction or angina, with considerable overlap of the two syndromes. The prevalence of possible myocardial infarction combined with angina and of definite angina only showed a fourfold increase over the age range studied. Electrocardiographic evidence of ischaemic heart disease (definite or possible) was present in 15% of men, there being myocardial infarction in 4.2% and myocardial ischaemia in 10.3%. Electrocardiographic evidence of myocardial infarction increased fourfold over the age range studied. There was considerable overlap of questionnaire and electrocardiographic evidence of ischaemic heart disease. Nevertheless, more than half of those with possible myocardial infarction combined with angina had no resting electrocardiographic evidence of ischaemic heart disease, and half of those with definite myocardial infarction on electrocardiogram had no history of chest pain at any time. This national population based study strongly suggests that the prevalence of ischaemic heart disease in middle aged British men is greater than has been indicated by previous studies based on occupational groups. PMID:6732989

  7. Invasive intracranial pressure monitoring is a useful adjunct in the management of severe hepatic encephalopathy associated with pediatric acute liver failure

    PubMed Central

    Kamat, Pradip; Kunde, Sachin; Vos, Miriam; Vats, Atul; Heffron, Thomas; Romero, Rene; Fortenberry, James D.

    2011-01-01

    Introduction Pediatric acute liver failure (ALF) is often accompanied by hepatic encephalopathy, cerebral edema and raised intracranial pressure (ICP). Elevated ICP can be managed more effectively with intracranial monitoring, but ALF-associated coagulopathy is often considered a contraindication for invasive monitoring due to risk for intracranial bleeding. We reviewed our experience with use of early ICP monitoring in ALF in children listed for liver transplantation. Methods Retrospective review of all intubated pediatric ALF patients with Grade 3 and Grade 4 encephalopathy requiring intracranial pressure monitoring and evaluated for potential liver transplant were identified from an institutional liver transplant patient database from 1999 to 2009. Result 14 patients were identified that met inclusion criteria. Age ranged from 7 months to 20 yrs. Diagnoses of ALF were infectious (3), drug induced (7), autoimmune hepatitis (2) and indeterminate (2). Grade 3 and 4 encephalopathy was seen in 10 (71%) and 4 (29%) patients respectively. CT scans prior to ICP monitor placement showed cerebral edema in 5 (35.7%) patients. Prior to ICP monitor placement, fresh frozen plasma, Vitamin K and activated recombinant factor VIIa were given to all 14 patients with significant improvement in coagulopathy (p<.04). Initial ICP ranged from 5 – 50 cmH2O; ICP was significantly higher in patients with cerebral edema by CT (p<.05). 11/14 (78%) patients received hypertonic saline and 3 (22%) received mannitol for elevated ICP. 8 of 14 (56%) monitored patients were managed to liver transplant with 100% surviving neurologically intact. 4/14 (28%) patients had spontaneous recovery without liver transplant. 2 of 14 (14%) patients died due to multiple organ failure prior to transplant. One patient had a small 9mm intracranial hemorrhage but survived after receiving a liver transplant. No patient developed intracranial infection. Conclusion In our series of patients, ICP monitoring had a

  8. A Randomized Controlled Trial of Rituximab Following Failure of Antiviral Therapy for Hepatitis C-Associated Cryoglobulinemic Vasculitis

    PubMed Central

    Sneller, Michael C.; Hu, Zonghui; Langford, Carol A.

    2011-01-01

    OBJECTIVES To report on the results of a randomized controlled trial of rituximab in hepatitis C virus (HCV)-associated mixed cryoglobulinemic vasculitis. METHODS We conducted an open-label single center randomized controlled trial of rituximab (375 mg/m2 per week for 4 weeks) compared to best available therapy for treatment of patients with HCV-associated cryoglobulinemic vasculitis in whom antiviral therapy failed to induce remission. The primary endpoint was remission at 6 months from study entry. RESULTS A total of 24 patients were enrolled. Baseline disease activity and organ involvement were similar in the two groups. Ten patients in the rituximab group (83%) were in remission at study month 6, compared with 1 patient in the control group (8%), a result that met criterion for stopping the study (P<0.001). The median duration of remission for rituximab-treated patients reaching the primary endpoint was 7 months. No adverse effect of rituximab on HCV plasma viremia or hepatic transaminase levels was observed. CONCLUSIONS Therapy with rituximab was well tolerated and effective treatment for patients with HCV-associated cryoglobulinemic vasculitis in whom antiviral therapy fails to induce remission. PMID:22147444

  9. KLRG1 impairs CD4+ T cell responses via p16ink4a and p27kip1 pathways: role in hepatitis B vaccine failure in individuals with hepatitis C virus infection.

    PubMed

    Shi, Lei; Wang, Jia M; Ren, Jun P; Cheng, Yong Q; Ying, Ruo S; Wu, Xiao Y; Lin, Shu M; Griffin, Jeddidiah W D; Li, Guang Y; Moorman, Jonathan P; Yao, Zhi Q

    2014-01-15

    Coinfection of hepatitis B virus (HBV) with hepatitis C virus (HCV) is quite common, leading to an increase in morbidity and mortality. As such, HBV vaccination is recommended in HCV-infected individuals. However, HBV vaccine responses in HCV-infected individuals are often blunted compared with uninfected populations. The mechanism for this failure of vaccine response in HCV-infected subjects remains unclear. In this study, we investigated the expression and function of an inhibitory receptor, killer cell lectin-like receptor subfamily G member 1 (KLRG1), in the regulation of CD4(+) T cells and HBV vaccine responses during HCV infection. We demonstrated that KLRG1 was overexpressed on CD4(+) T cells from HCV-infected, HBV vaccine nonresponders compared with HBV vaccine responders. The capacity of CD4(+) T cells to proliferate and secrete IL-2 cytokine was inversely associated with the level of KLRG1 expression. Importantly, blocking KLRG1 signaling resulted in a significant improvement in CD4(+) T cell proliferation and IL-2 production in HCV-infected, HBV vaccine nonresponders in response to TCR stimulation. Moreover, blockade of KLRG1 increased the phosphorylation of Akt (Ser(473)) and decreased the expression of cell cycle inhibitors p16(ink4a) and p27(kip1), which subsequently enhanced the expression of cyclin-dependent kinase 2 and cyclin E. These results suggest that the KLRG1 pathway impairs CD4(+) T cell responses to neoantigen and induces a state of immune senescence in individuals with HCV infection, raising the possibility that blocking this negative-signaling pathway might improve HBV vaccine responses in the setting of chronic viral infection. PMID:24337749

  10. KLRG1 impairs CD4+ T cell responses via p16ink4a and p27kip1 pathways - Role in hepatitis B vaccine failure in individuals with hepatitis C virus infection

    PubMed Central

    Shi, Lei; Wang, Jia M.; Ren, Jun P.; Cheng, Yong Q.; Ying, Ruo S.; Wu, Xiao Y.; Lin, Shu M.; Griffin, Jeddidiah WD; Li, Guang Y.; Moorman, Jonathan P.; Yao, Zhi Q.

    2014-01-01

    Co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) is quite common, leading to an increase in morbidity and mortality. As such, HBV vaccination is recommended in HCV-infected individuals. HBV vaccine responses in HCV-infected individuals, however, are often blunted when compared to uninfected populations. The mechanism for this failure of vaccine response in HCV-infected subjects remains unclear. In this study, we investigated the expression and function of an inhibitory receptor, killer cell lectin-like receptor subfamily G member 1 (KLRG1), in regulation of CD4+ T cells and HBV vaccine responses during HCV infection. We demonstrated that KLRG1 was over-expressed on CD4+ T cells from HCV-infected, HBV vaccine non-responders (HBV-NR) compared to those responders (HBV-R). The capacity of CD4+ T cell to proliferate and secrete IL-2 cytokine was inversely associated with the level of KLRG1 expression. Importantly, blocking KLRG1 signaling resulted in a significant improvement of CD4+ T cell proliferation and IL-2 production in HCV-infected, HBV-NR in response to T cell receptor (TCR) stimulation. Moreover, blockade of KLRG1 increased the phosphorylation of Akt (Ser473) and decreased the expression of cell cycle inhibitors p16ink4a and p27kip1, which subsequently enhanced CDK 2 and cyclin E expressions. These results suggest that the KLRG1 pathway impairs CD4+ T cell responses to neo-antigen and induces a state of immune senescence in individuals with HCV infection, raising the possibility that blocking this negative signaling pathway might improve HBV vaccine responses in the setting of chronic viral infection. PMID:24337749

  11. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  12. Elevated on-treatment levels of serum IFN-gamma is associated with treatment failure of peginterferon plus ribavirin therapy for chronic hepatitis C

    PubMed Central

    Lu, Ming-Ying; Huang, Ching-I; Dai, Chia-Yen; Wang, Shu-Chi; Hsieh, Ming-Yen; Hsieh, Meng-Hsuan; Liang, Po-Cheng; Lin, Yi-Hung; Hou, Nai-Jen; Yeh, Ming-Lun; Huang, Chung-Feng; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Jee-Fu; Chuang, Wan-Long; Yu, Ming-Lung

    2016-01-01

    Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response. PMID:26965318

  13. A model to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure using artificial neural network.

    PubMed

    Zheng, M-H; Shi, K-Q; Lin, X-F; Xiao, D-D; Chen, L-L; Liu, W-Y; Fan, Y-C; Chen, Y-P

    2013-04-01

    Model for end-stage liver disease (MELD) scoring was initiated using traditional statistical technique by assuming a linear relationship between clinical features, but most phenomena in a clinical situation are not linearly related. The aim of this study was to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure (ACHBLF) on an individual patient level using an artificial neural network (ANN) system. The ANN model was built using data from 402 consecutive patients with ACHBLF. It was trained to predict 3-month mortality by the data of 280 patients and validated by the remaining 122 patients. The area under the curve of receiver operating characteristic (AUROC) was calculated for ANN and MELD-based scoring systems. The following variables age (P < 0.001), prothrombin activity (P < 0.001), serum sodium (P < 0.001), total bilirubin (P = 0.015), hepatitis B e antigen positivity rate (P < 0.001) and haemoglobin (P < 0.001) were significantly related to the prognosis of ACHBLF and were selected to build the ANN. The ANN performed significantly better than MELD-based scoring systems both in the training cohort (AUROC = 0.869 vs 0.667, 0.591, 0.643, 0.571 and 0.577; P < 0.001, respectively) and in the validation cohort (AUROC = 0.765 vs 0.599, 0.563, 0.601, 0.521 and 0.540; P ≤ 0.006, respectively). Thus, the ANN model was shown to be more accurate in predicting 3-month mortality of ACHBLF than MELD-based scoring systems. PMID:23490369

  14. Establishment and validation of ALPH-Q score to predict mortality risk in patients with acute-on-chronic hepatitis B liver failure: a prospective cohort study.

    PubMed

    Wu, Sheng-Jie; Yan, Hua-Dong; Zheng, Zai-Xing; Shi, Ke-Qing; Wu, Fa-Ling; Xie, Yao-Yao; Fan, Yu-Chen; Ye, Bo-Zhi; Huang, Wei-Jian; Chen, Yong-Ping; Zheng, Ming-Hua

    2015-01-01

    Currently, there are no robust models for predicting the outcome of acute-on-chronic hepatitis B liver failure (ACHBLF). We aimed to establish and validate a new prognostic scoring system, named ALPH-Q, that integrates electrocardiography parameters that may be used to predict short-term mortality of patients with ACHBLF. Two hundred fourteen patients were included in this study. The APLH-Q score was constructed by Cox proportional hazard regression analysis and was validated in an independent patient cohort. The area under the receiver-operating characteristic curve was used to compare the performance of different models, including APLH-Q, Child-Pugh score (CPS), model of end-stage liver disease (MELD), and a previously reported logistic regression model (LRM). The APLH-Q score was constructed with 5 independent risk factors, including age (HR = 1.034, 95% CI: 1.007-1.061), liver cirrhosis (HR = 2.753, 95% CI: 1.366-5.548), prothrombin time (HR = 1.031, 95% CI: 1.002-1.062), hepatic encephalopathy (HR = 2.703, 95% CI: 1.630-4.480), and QTc (HR = 1.008, 95% CI: 1.001-1.016). The performance of the ALPH-Q score was significantly better than that of MELD and CPS in both the training (0.896 vs 0.712, 0.896 vs 0.738, respectively, both P < 0.05) and validation cohorts (0.837 vs 0.689, 0.837 vs 0.585, respectively, both P < 0.05). Compared with LRM, APLH-Q also showed a better performance (0.896 vs 0.825, 0.837 vs 0.818, respectively).We have developed a novel APLH-Q score with greater performance than CPS, MELD, and LRM for predicting short-term mortality of patients with ACHBLF. PMID:25590846

  15. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    PubMed Central

    van Haelst, P.L.; Schot, B.; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute leukaemia. The pathophysiological mechanisms of acute leukaemia leading to ischaemic heart disease are discussed. ImagesFigure 1AFigure 1BFigure 2 PMID:25696595

  16. Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up.

    PubMed

    Donati, Gabriele; La Manna, Gaetano; Cianciolo, Giuseppe; Grandinetti, Valeria; Carretta, Elisa; Cappuccilli, Maria; Panicali, Laura; Iorio, Mario; Piscaglia, Fabio; Bolondi, Luigi; Colì, Luigi; Stefoni, Sergio

    2014-02-01

    Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In

  17. [Follow-up of newborns with hypoxic-ischaemic encephalopathy].

    PubMed

    Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S

    2014-07-01

    Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed. PMID:24290154

  18. Hypoxic-ischaemic encephalopathy after near miss sudden infant death syndrome.

    PubMed

    Constantinou, J E; Gillis, J; Ouvrier, R A; Rahilly, P M

    1989-05-01

    Between 1982 and 1985, 14 infants aged 3-26 weeks presented with severe hypoxic episodes as a result of the 'near miss' sudden infant death syndrome (SIDS). They all had metabolic acidosis, cardiovascular instability, acute renal failure, ischaemic colitis, or acute neurological dysfunction. Investigation of the cause excluded infection and trauma, or a primary metabolic, pulmonary, cardiac, or seizure disorder. Seven infants were deeply comatose on admission, never regained consciousness, and died within 60 hours. A characteristic evolution of hypoxic-ischaemic encephalopathy not previously clearly described after near miss SIDS was seen in the seven who lived. Five of the seven were conscious within one hour of resuscitation and showed a striking interval of near normality before neurological deterioration that was characterised by status epilepticus, deep coma, and brain stem dysfunction from 36-96 hours after the event. A biphasic course was not apparent in the remaining two, each of whom was comatose on admission, though refractory seizures did develop. Computed tomograms of the brain more than a week after the event showed cortical infarction or cerebral atrophy. Six of the survivors, followed up from 16-55 months, have serious residual deficits including spastic quadriplegia, delayed development, cortical blindness, or infantile spasms. PMID:2730124

  19. Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation.

    PubMed Central

    Meldrum, D R; Cain, B S; Cleveland, J C; Meng, X; Ayala, A; Banerjee, A; Harken, A H

    1997-01-01

    Tumour necrosis factor-alpha (TNF-alpha) is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischaemia-reperfusion injury (I/R), sepsis, chronic heart failure and cardiac allograft rejection. Cardiac resident macrophages, infiltrating leucocytes, and cardiomyocytes themselves produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF-alpha in a crystalloid-perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF-alpha and protects function after I/R. To study this, isolated rat hearts were crystalloid-perfused using the Langendorff method and subjected to I/R, with or without adenosine pretreatment. Post-ischaemic cardiac TNF-alpha (enzyme-linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF-alpha and impaired myocardial function. Adenosine decreased cardiac TNF-alpha and improved post-ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF-alpha in a crystalloid-perfused model: second, adenosine decreases cardiac TNF-alpha and improves post-ischaemic myocardial function; third, decreased cardiac TNF-alpha may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine-induced suppression of cardiac TNF-alpha may provide an anti-inflammatory link to preconditioning and have implications for cardiac allograft preservation. PMID:9497488

  20. Early phase combined therapeutic management of acute ischaemic stroke.

    PubMed

    Bassi, P; Lattuada, P; Tonietti, S

    2005-05-01

    An adequate treatment of ischaemic stroke in the early phase (28-48 h) is the most important factor for a better outcome. Thrombolysis with rTPA (within 3 h) and oral ASA 300 mg/days are the first therapeutic misures. Continuous monitoring of cardiological and haemodinamic parameters allows early detection of cardiac disturbances. Treatment of hypertension, low haematic oxigenation, hyperglicaemia, seizures and hypertermia is basic to improve outcome. Pharmacological therapy is only one of the components of effective multidisciplinary integrated management of ischaemic stroke; we remind also the precocity of rehabilitation procedures and an accurate psychological assessment. PMID:15883687

  1. The mechanism of renin release from the ischaemic kidney

    PubMed Central

    Labal, S.E.; Pola, J.L.; Seeber, A. Martinez; Taquini, A.C.

    1974-01-01

    The re-establishment of blood flow to an ischaemic kidney produced an elevation of blood pressure in the rat. This response did not occur in animals with a pithed spinal cord or in rats with low blood pressure produced by haemorrhage. When the blood pressure was raised in rats with pithed spinal cords, by the intravenous infusion of noradrenaline, the response was restored. Occlusion of the subclavian arteries did not prevent the response. It is considered that the increase in blood pressure, produced by renin release, after re-establishment of the blood flow in an ischaemic kidney is a 'washout' phenomenon independent of the integrity of the nervous system. PMID:4447861

  2. Hepatitis B in Pregnancy.

    PubMed

    Tran, Tram T

    2016-06-01

    Chronic hepatitis B virus (HBV) infection is estimated to affect >350 million people worldwide and represents a significant cause of morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Mother-to-child transmission (MTCT) of HBV remains an important source of incident cases of HBV. Current barriers to eradication of incident HBV infections via MTCT include underutilization of immunoprophylaxis with hepatitis B vaccination and hepatitis B immune globulin in certain endemic regions as well as failure of immunoprophylaxis. PMID:27190321

  3. A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic-ischaemic brain injury in mice.

    PubMed

    Rousset, Catherine I; Leiper, Fiona C; Kichev, Anton; Gressens, Pierre; Carling, David; Hagberg, Henrik; Thornton, Claire

    2015-04-01

    Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term infants and the devastating consequences range from cerebral palsy, epilepsy and neurological deficit to death. Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. AMP-activated protein kinase (AMPK) is a sensor of cellular stress resulting from ATP depletion and/or calcium dysregulation, hallmarks of the neuronal cell death observed after HIE. AMPK activation has been implicated in the models of adult ischaemic injury but, as yet, there have been no studies defining its role in neonatal asphyxia. Here, we find that in an in vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose deprivation in neurons, there is pathological activation of the calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-AMPKα1 signalling pathway. Pharmacological inhibition of AMPK during the insult promotes neuronal survival but, conversely, inhibiting AMPK activity prior to the insult sensitizes neurons, exacerbating cell death. Our data have pathological relevance for neonatal HIE as prior sensitization such as exposure to bacterial infection (reported to reduce AMPK activity) produces a significant increase in injury. We show that in an in vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose deprivation in neurons, there is a pathological activation of the CaMKKβ-AMPKα1 signalling pathway. Inhibiting AMPK during OGD promotes neuronal survival; conversely, inhibiting AMPK prior to OGD exacerbates cell death. Our data have clinical relevance as prior sensitization (e.g. exposure to bacterial infection reducing AMPK activity) increases injury. AMPK, AMP-activated protein kinase; HI, hypoxia-ischaemia; OGD, oxygen-glucose deprivation. PMID:25598140

  4. NS5A resistance leading to failure of 24-week therapy with sofosbuvir/ledipasvir and ribavirin for the treatment of hepatitis C genotype 1a infection in a HIV-1 co-infected patient.

    PubMed

    Sevastianova, Ksenia; Dean, Jonathan; Bannan, Ciaran; Coghlan, Miriam; Farrell, Gillian; Murray, Catherine; De Gascun, Cillian F; Bergin, Colm

    2016-09-01

    Herein we report a previously undescribed case of treatment-emergent non-structural protein 5A (NS5A) resistance mutations, Q30H and Y93C, leading to a failure of 24-week course of sofosbuvir/ledipasvir+ribavirin therapy for the treatment of hepatitis C virus (HCV) genotype 1a in interferon-experienced, human immunodeficiency virus type 1 (HIV-1) co-infected patient with cirrhosis. PMID:27454231

  5. Functional magnetic resonance imaging in chronic ischaemic stroke.

    PubMed

    Lake, Evelyn M R; Bazzigaluppi, Paolo; Stefanovic, Bojana

    2016-10-01

    Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression. Stroke affects each of the physiological parameters underlying the BOLD contrast, markedly complicating the interpretation of BOLD fMRI data. This review summarizes current progress on application of BOLD fMRI in the chronic stage of ischaemic injury progression and discusses means by which more information may be gained from such BOLD fMRI measurements. Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function. The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574307

  6. Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure

    PubMed Central

    Zheng, Su-Jun; Liu, Shuang; Liu, Mei; McCrae, Malcolm A; Li, Jun-Feng; Han, Yuan-Ping; Xu, Chun-Hui; Ren, Feng; Chen, Yu; Duan, Zhong-Ping

    2014-01-01

    AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC ≥ 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in

  7. Establishment and Validation of ALPH-Q Score to Predict Mortality Risk in Patients With Acute-on-Chronic Hepatitis B Liver Failure

    PubMed Central

    Wu, Sheng-Jie; Yan, Hua-Dong; Zheng, Zai-Xing; Shi, Ke-Qing; Wu, Fa-Ling; Xie, Yao-Yao; Fan, Yu-Chen; Ye, Bo-Zhi; Huang, Wei-Jian; Chen, Yong-Ping; Zheng, Ming-Hua

    2015-01-01

    Abstract Currently, there are no robust models for predicting the outcome of acute-on-chronic hepatitis B liver failure (ACHBLF). We aimed to establish and validate a new prognostic scoring system, named ALPH-Q, that integrates electrocardiography parameters that may be used to predict short-term mortality of patients with ACHBLF. Two hundred fourteen patients were included in this study. The APLH-Q score was constructed by Cox proportional hazard regression analysis and was validated in an independent patient cohort. The area under the receiver-operating characteristic curve was used to compare the performance of different models, including APLH-Q, Child–Pugh score (CPS), model of end-stage liver disease (MELD), and a previously reported logistic regression model (LRM). The APLH-Q score was constructed with 5 independent risk factors, including age (HR = 1.034, 95% CI: 1.007–1.061), liver cirrhosis (HR = 2.753, 95% CI: 1.366–5.548), prothrombin time (HR = 1.031, 95% CI: 1.002–1.062), hepatic encephalopathy (HR = 2.703, 95% CI: 1.630–4.480), and QTc (HR = 1.008, 95% CI: 1.001–1.016). The performance of the ALPH-Q score was significantly better than that of MELD and CPS in both the training (0.896 vs 0.712, 0.896 vs 0.738, respectively, both P < 0.05) and validation cohorts (0.837 vs 0.689, 0.837 vs 0.585, respectively, both P < 0.05). Compared with LRM, APLH-Q also showed a better performance (0.896 vs 0.825, 0.837 vs 0.818, respectively). We have developed a novel APLH-Q score with greater performance than CPS, MELD, and LRM for predicting short-term mortality of patients with ACHBLF. PMID:25590846

  8. Multiple risk factors and ischaemic stroke in the elderly Asian population with and without atrial fibrillation. An analysis of 425,600 Chinese individuals without prior stroke.

    PubMed

    Guo, Yutao; Wang, Hao; Tian, Yingchun; Wang, Yutang; Lip, Gregory Y H

    2016-01-01

    Ischaemic stroke risk rises with the increasing cardiovascular risk factors. How atrial fibrillation (AF) incrementally contributes to the risk for ischaemic stroke with increasing age and multiple cardiovascular risk factors is unclear. In an individual patient with AF the mechanism of ischaemic stroke may be related directly to AF itself or to risk factors associated with AF. It was this study's objective to investigate incident ischaemic stroke in relation to age and increasing cardiovascular risk factor(s), and the incremental impact of AF on stroke rates. We studied a 5% random sampling from Chinese medical insurance data covering more than 10 million individuals, for the years 2001 to 2012. The rate of ischaemic stroke was calculated amongst the individuals with no prior history of ischaemic stroke, in relation to age groups (aged < 65, 65-74, ≥ 75 years old; n = 348,431, n = 56,952, n = 20,217, respectively), and increasing risk factors using the CHA2DS2-VASc score. Among the randomly sampled 425,600 individuals with total follow-up of 1,864,232 patient-years [63.8% male, mean age 60 years; 880 with AF, vs 424,720 non-AF], there were 13,242 (3.1%) ischaemic strokes after 64,834 person-years follow-up. Overall, ischaemic stroke incidence (per 100 person-years) was 0.35 (95%CI 0.34-0.35) in the non-AF population and 1.11 (0.84-1.45) with AF. The AF population age < 65 and 65-74 had higher CHA2DS2-VASc scores than the non-AF population (p< 0.001), but this was non-significant between the non-AF and AF population age ≥ 75 (p=0.086). For the population age ≥ 75 years, incident stroke rates were 2.07 (0.86-4.76) and 4.29 (4.08-4.51) in non-AF and AF populations, respectively. The non-AF population age ≥ 65 years with ≥ 2 additional comorbidities (hypertension, vascular disease, diabetic, or heart failure) had ischaemic stroke rates similar to an AF population with CHA2DS2-VASc ≥ 4. In both non-AF and AF populations, those with CHA2DS2

  9. Echocardiographic Assessment of Ischaemic Mitral Regurgitation, Mechanism, Severity, Impact on Treatment Strategy and Long Term Outcome

    PubMed Central

    Naser, Nabil; Dzubur, Alen; Kusljugic, Zumreta; Kovacevic, Katarina; Kulic, Mehmed; Sokolovic, Sekib; Terzic, Ibrahim; Haxihibeqiri-Karabdic, Ilirijana; Hondo, Zorica; Brdzanovic, Snjezana; Miseljic, Sanja

    2016-01-01

    echocardiography for detection and assessment of ischaemic mitral regurgitation (IMR) with baseline age (62 ± 9), ejection fraction (EF 41±12%), the regurgitant volume (RV) were 42±21 mL/beat, and effective regurgitant orifice area (EROA) 20±16 mm2, the regurgitant fraction (RF) were 48±10%, Jet/LA area 47±12%. Also we measured the of vena contracta width (VC width cm) 0,4±0,6 for assessment of IMR severity. During 5 years follow up, total mortality for patients with moderate/severe IMR–grade II-IV (54.2±1.8%) were higher than for those with mild IMR–grade I (30.4±2.9%) (P<0.05), the total mortality for patients with EROA ≥20 mm2(54±1.9%) were higher than for those with EROA <20 mm2(27.2±2.7%) (P<0.05), and the total mortality for patients with RVol ≥30 mL (56.8±1.7%) were higher than for those with RVol<30ml (29.4±2.9%) (P<0.05). After assessment of IMR and during follow up period 64 patients (46%) underwent CABG alone or combined CABG with mitral valve repair or replacement. In this study, the procedure of concomitant down-sized ring annuloplasty at the time if CABG surgery has a failure rate around 24% in terms of high late recurrence rate of IMR during the follow period especially after 18–42 months. Conclusion: The presence of ischaemic MR is associated with increased morbidity and mortality. Chronic IMR, an independent predictor of mortality with a reported survival of 40–60% at 5 years. Ischaemic mitral regurgitation has important prognosis implications in patients with coronary heart disease. Recognizing the mechanism of valve incompetence is an essential point for the surgical planning and for a good result of the mitral repair. It is important that echocardiographers understand the complex nature of the condition. Despite remarkable progress in reparative surgery, further investigation is still necessary to find the best approach to treat ischaemic mitral regurgitation. PMID:27482130

  10. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.

    PubMed

    Chouchani, Edward T; Pell, Victoria R; Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y; Robb, Ellen L; Logan, Angela; Nadtochiy, Sergiy M; Ord, Emily N J; Smith, Anthony C; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J; James, Andrew M; Rogatti, Sebastian; Hartley, Richard C; Eaton, Simon; Costa, Ana S H; Brookes, Paul S; Davidson, Sean M; Duchen, Michael R; Saeb-Parsy, Kourosh; Shattock, Michael J; Robinson, Alan J; Work, Lorraine M; Frezza, Christian; Krieg, Thomas; Murphy, Michael P

    2014-11-20

    Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia

  11. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

    PubMed Central

    Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S.H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P.

    2014-01-01

    Ischaemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses through generation of mitochondrial reactive oxygen species (ROS)1-5. Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion1,3. Here, we developed a comparative in vivo metabolomic analysis and unexpectedly identified widely conserved metabolic pathways responsible for mitochondrial ROS production during IR. We showed that selective accumulation of the citric acid cycle (CAC) intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase (SDH), which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. Upon reperfusion, the accumulated succinate is rapidly re-oxidised by SDH, driving extensive ROS generation by reverse electron transport (RET) at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo IR injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of IR injury. Furthermore, these findings reveal a novel pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation upon subsequent reperfusion is a potential therapeutic target to decrease IR injury in a range of pathologies. PMID:25383517

  12. Hepatic encephalopathy: a review.

    PubMed

    Lizardi-Cervera, Javier; Almeda, Paloma; Guevara, Luis; Uribe, Misael

    2003-01-01

    Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy. PMID:15115963

  13. Classification of ischaemic episodes with ST/HR diagrams.

    PubMed

    Faganeli Pucer, Jana; Demšar, Janez; Kukar, Matjaž

    2012-01-01

    Coronary artery disease is the developed world's premier cause of mortality and the most probable cause of myocardial ischaemia. More advanced diagnostic tests aside, in electrocardiogram (ECG) analysis it manifests itself as a ST segment deviation, targeted by both exercise ECG and ambulatory ECG. In ambulatory ECG, besides ischaemic ST segment deviation episodes there are also non-ischaemic heart rate related episodes which aggravate real ischaemia detection. We present methods to transform the features developed for the heart rate adjustment of ST segment depression in exercise ECG for use in ambulatory ECG. We use annotations provided by the Long-Term ST Database to plot the ST/HR diagrams and then estimate the overall and maximal slopes of the diagrams in the exercise and recovery phase for each ST segment deviation episode. We also estimate the angle at the extrema of the ST/HR diagrams. Statistical analysis shows that ischaemic ST segment deviation episodes have significantly steeper overall and maximal slopes than heart rate related episodes, which indicates the explored features' utility for distinguishing between the two types of episodes. This makes the proposed features very useful in automated ECG analysis. PMID:22874369

  14. Pharmacological therapy of acute ischaemic stroke: Achievements and problems.

    PubMed

    Moretti, Antonio; Ferrari, Federica; Villa, Roberto F

    2015-09-01

    Acute ischaemic stroke (AIS) is a leading cause of death and disability worldwide. Its incidence and prevalence increase considerably with age and numbers will grow with an ageing population. Consequently, the impact of AIS on costs is soaring. AIS is caused by the abrupt occlusion of an intracranial vessel resulting in reduced blood flow to the brain region supplied. The ischaemic core (which is irreversibly lesioned) is surrounded by the penumbra region with less severe flow reduction, lower functional impairment and potential recovery. Therefore, the fundamental treatment of AIS relies on prompt recanalisation and reperfusion of the threatened, but potentially salvageable, ischaemic penumbra. With this aim, intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) remains the current strategy. However, thrombolysis is underused, owing to various exclusion criteria that limit the number of treated patients. Other thrombolytics are under investigation. Endovascular therapy with mechanical recanalisation devices is also increasingly applied, though definite evidence of its benefit is lacking. Moreover, hypertension and hyperglycaemia are acute complications to be treated in AIS. This review analyses the current status, the problems, the perspectives and the cost-effectiveness of the pharmacological therapy for AIS. PMID:26079382

  15. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  16. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  17. Dobutamine echocardiography and thallium-201 imaging predict functional improvement after revascularisation in severe ischaemic left ventricular dysfunction.

    PubMed Central

    Senior, R.; Glenville, B.; Basu, S.; Sridhara, B. S.; Anagnostou, E.; Stanbridge, R.; Edmondson, S. J.; Handler, C. E.; Raftery, E. B.; Lahiri, A.

    1995-01-01

    OBJECTIVES--To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup. PATIENTS AND METHODS--45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation. RESULTS--Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting "recoverable" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS). CONCLUSIONS--Dobutamine echocardiography and 201Tl imaging may be used to predict mechanical improvement in dysynergic segments after revascularisation in patients with chronic ischaemic left ventricular dysfunction. Images PMID:7488446

  18. Dengue causing fulminant hepatitis in a hepatitis B virus carrier.

    PubMed

    Agarwal, M P; Giri, S; Sharma, V; Roy, U; Gharsangi, K

    2011-01-01

    Dengue is an acute febrile illness resulting from infection by a flavivirus transmitted by the Aedes mosquito. It is characterized by bleeding manifestations and a plasma leak syndrome. Hepatic involvement in the form of elevation in transaminases is common. However, acute hepatic failure is uncommon. It is not known how the presence of an underlying chronic hepatitis or liver disease affects the likelihood of severity of hepatitis from dengue. The present report is of a 33-year-old man, a carrier of hepatitis B virus, who presented with fever, altered sensorium, thrombocytopenia, and coagulopathy. He was diagnosed to have developed acute hepatic failure due to dengue. The patient improved with supportive measures. PMID:21422600

  19. Update on Alcoholic Hepatitis

    PubMed Central

    Torok, Natalie J.

    2015-01-01

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%–50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies. PMID:26540078

  20. NKP30-B7-H6 Interaction Aggravates Hepatocyte Damage through Up-Regulation of Interleukin-32 Expression in Hepatitis B Virus-Related Acute-On-Chronic Liver Failure

    PubMed Central

    Pan, Xingfei; Lu, Ying; Liao, Sihong; Wang, Xicheng; Wang, Guoying; Lin, Dongjun

    2015-01-01

    Background and Aims Previous work conducted by our group has shown that the accumulation of hepatic natural killer (NK) cells and the up-regulation of natural cytotoxicity receptors (NKP30 and NKP46) on NK cells from patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) were correlated with disease progression in HBV-ACLF. The natural cytotoxicity receptors expressed on NK cells are believed to be probable candidates involved in the NK cell-mediated hepatocyte damage in HBV-ACLF. However, the underlying mechanisms remain to be elucidated. In the present study, we aimed to discover the role of NKP30-B7-H6 interaction in NK cells-mediated hepatocyte damage in HBV-ACLF. Methods Hepatic expressions of B7-H6 and interleukin-32 (IL-32) were examined by immunochemistry staining in samples from patients with HBV-ACLF or mild chronic hepatitis B (CHB). The cytotoxicity of NK-92 cell against target cells (Huh-7 and LO2) was evaluated by CCK8 assay. Expression of IL-32 in liver NK cell, T cells and NK-92 cell line was detected by the flow cytometric analysis. The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis. Results An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF. And there was a positive association between hepatic B7-H6 and IL-32 expression. Expressions of IL-32 in liver NK cells and T cells were increased in HBV-ACLF patients. In vitro NK-92 cells are highly capable of killing the high B7-H6 expressing Huh7 cells and B7-H6-tansfected hepatocyte line LO2 cells dependent on NKP30 and B7-H6 interaction. Furthermore, NK-92 cells exhibited elevated IL-32 expression when stimulated with anti-NKP30 antibodies or when co-cultured with Huh7 cells. IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner. Conclusion Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up

  1. Myocardial structure, function and ischaemic tolerance in a rodent model of obesity with insulin resistance.

    PubMed

    Wensley, I; Salaveria, K; Bulmer, A C; Donner, D G; du Toit, E F

    2013-11-01

    Obesity and its comorbidities (dyslipidaemia, insulin resistance and hypertension) that together constitute the metabolic syndrome are all risk factors for ischaemic heart disease. Although obesity has been reported to be an independent risk factor for congestive heart failure, whether obesity-induced heart failure develops in the absence of increased afterload (induced by hypertension) is not clear. We have previously shown that obesity with insulin resistance decreases myocardial tolerance to ischaemia-reperfusion, but the mechanism for this decreased tolerance remains unclear. We hypothesize that obesity with insulin resistance induces adverse cardiac remodelling and pump dysfunction, as well as adverse changes in myocardial prosurvival reperfusion injury salvage kinase (RISK) pathway signalling to reduce myocardial tolerance to ischaemia-reperfusion. Wistar rats were fed an obesogenic (obese group) or a standard rat chow diet (control group) for 32 weeks. Echocardiography was performed over the 32 weeks before isolated Langendorff-perfused hearts were subjected to 40 min coronary artery ligation followed by reperfusion, and functional recovery (rate-pressure product), infarct size and RISK pathway function were assessed (Western blot analysis). Obesity with insulin resistance increased myocardial lipid accumulation but had no effect on in vivo or ex vivo left ventricular structure/function. Hearts from obese rats had lower reperfusion rate-pressure products (13115 ± 562 beats min(-1) mmHg for obese rats versus 17781 ± 1109 beats min(-1) mmHg for control rats, P < 0.05) and larger infarcts (36.3 ± 5.6% of area at risk in obese rats versus 14.1 ± 2.8% of area at risk in control rats, P < 0.01) compared with control hearts. These changes were associated with reductions in RISK pathway function, with 30-50 and 40-60% reductions in Akt and glycogen synthase kinase 3 beta (GSK-3β) expression and phosphorylation, respectively, in obese rat hearts compared with

  2. Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease.

    PubMed Central

    Bridges, A B; McLaren, M; Scott, N A; Pringle, T H; McNeill, G P; Belch, J J

    1993-01-01

    OBJECTIVES--To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. DESIGN--Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. PATIENTS--Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. RESULTS--There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. CONCLUSION--Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning. PMID:8435236

  3. Erythropoietic and hepatic porphyrias.

    PubMed

    Gross, U; Hoffmann, G F; Doss, M O

    2000-11-01

    Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased

  4. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury.

    PubMed

    Rocha-Ferreira, Eridan; Hristova, Mariya

    2016-01-01

    Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI) of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity. PMID:27047695

  5. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

    PubMed Central

    Rocha-Ferreira, Eridan

    2016-01-01

    Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI) of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity. PMID:27047695

  6. Ischaemic conditioning: pitfalls on the path to clinical translation

    PubMed Central

    Przyklenk, Karin

    2015-01-01

    The development of novel adjuvant strategies capable of attenuating myocardial ischaemia-reperfusion injury and reducing infarct size remains a major, unmet clinical need. A wealth of preclinical evidence has established that ischaemic ‘conditioning’ is profoundly cardioprotective, and has positioned the phenomenon (in particular, the paradigms of postconditioning and remote conditioning) as the most promising and potent candidate for clinical translation identified to date. However, despite this preclinical consensus, current phase II trials have been plagued by heterogeneity, and the outcomes of recent meta-analyses have largely failed to confirm significant benefit. As a result, the path to clinical application has been perceived as ‘disappointing’ and ‘frustrating’. The goal of the current review is to discuss the pitfalls that may be stalling the successful clinical translation of ischaemic conditioning, with an emphasis on concerns regarding: (i) appropriate clinical study design and (ii) the choice of the ‘right’ preclinical models to facilitate clinical translation. PMID:25560903

  7. Cyclin-dependent kinase-5 targeting for ischaemic stroke.

    PubMed

    Slevin, Mark; Krupinski, Jerzy

    2009-04-01

    Recovery from ischaemic stroke is dependent on survival of neurones, particularly in peri-infarcted regions. Angiogenesis is critical for the development of new microvessels resulting in the re-formation of collateral circulation associated with enhanced neuronal survival and reduced morbidity and mortality. Recently, the identification of a neurovascular niche has been described, where the co-ordinated effects of angiogenesis and migration of neuroprogenitor cells to damaged stroke regions were shown to be vital in the process of tissue remodelling. Cdk5, a serine/threonine kinase is highly expressed in the central nervous system, particularly following ischaemic stroke and its aberrant activation is directly associated with neuronal apoptosis and death. In contrast, recent evidence suggests that increased expression of Cdk5 by endothelium might be protective against cell death and/or promote angiogenesis leading to increased vessel formation and reperfusion. Owing to its known interaction with over 20 substrates including caspase-3, MEF2, Tau and p53, Cdk5 could be a master switch controlling both neuronal survival and revascularisation. Therefore its cell-specific pharmacological or genetic modulation using novel nanotechnology-based delivery systems could be of benefit when considering future stroke therapies. PMID:18983942

  8. Time to Talk: 5 Things You Should Know about Dietary Supplements for Hepatitis C

    MedlinePlus

    ... You Should Know About Dietary Supplements for Hepatitis C Share: Hepatitis C is a liver disease caused by a virus. ... years to happen. Without medical treatment, chronic hepatitis C can eventually cause liver cancer or liver failure. ...

  9. Serum Interleukin (IL)-9 and IL-10, but not T-Helper 9 (Th9) Cells, are Associated With Survival of Patients With Acute-on-Chronic Hepatitis B Liver Failure.

    PubMed

    Yu, Xueping; Zheng, Yijuan; Deng, Yong; Li, Julan; Guo, Ruyi; Su, Milong; Ming, Desong; Lin, Zhenzhong; Zhang, Jiming; Su, Zhijun

    2016-04-01

    CD4 T helper (Th) cells are reported to be essential for initiating and maintaining an effective immune response to hepatitis B virus (HBV) infection. Th9 cells are a new subset of CD4 Th cells that produce interleukin (IL)-9 and IL-10. The present study aimed to investigate the percentage of Th9 cells relative to the number of CD4 cells in peripheral blood.We also measured serum IL-9 and IL-10 levels in different stages of HBV infection and their relationship with progress and prognosis of liver disease. Whole blood samples from 111 patients with HBV infection, including 39 chronic hepatitis B (CHB), 25 HBV-liver cirrhosis (HBV-LC), 21 acute-on-chronic liver failure (ACLF) patients, and 26 healthy controls were collected.The percentage of Th9 cells and serum IL-9 and IL-10 levels were determined. There was no significant difference in the percentage of Th9 cells and serum IL-9 and IL-10 levels among different groups, nor were these related to hepatitis B e antigen status, complications of cirrhosis, inflammation index, or prognosis indexes. There was no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients. There was no correlation of Th9 cells with survival of ACLF patients. However, IL-9 and IL-10 levels were significantly higher in the nonsurvived ACLF patients compared to survived ACLF patients. Furthermore, baseline IL-9 level predicted the prognosis of ACLF patients with 87.5% sensitivity and 61.5% specificity.Thus, our data indicate that Th9 cells were unlikely involved in the pathogenesis of HBV infection, but elevation in IL-9 and IL-10 may signal poor prognosis for ACLF. PMID:27100428

  10. Serum Interleukin (IL)-9 and IL-10, but not T-Helper 9 (Th9) Cells, are Associated With Survival of Patients With Acute-on-Chronic Hepatitis B Liver Failure

    PubMed Central

    Yu, Xueping; Zheng, Yijuan; Deng, Yong; Li, Julan; Guo, Ruyi; Su, Milong; Ming, Desong; Lin, Zhenzhong; Zhang, Jiming; Su, Zhijun

    2016-01-01

    Abstract CD4+ T helper (Th) cells are reported to be essential for initiating and maintaining an effective immune response to hepatitis B virus (HBV) infection. Th9 cells are a new subset of CD4+ Th cells that produce interleukin (IL)-9 and IL-10. The present study aimed to investigate the percentage of Th9 cells relative to the number of CD4+ cells in peripheral blood. We also measured serum IL-9 and IL-10 levels in different stages of HBV infection and their relationship with progress and prognosis of liver disease. Whole blood samples from 111 patients with HBV infection, including 39 chronic hepatitis B (CHB), 25 HBV-liver cirrhosis (HBV-LC), 21 acute-on-chronic liver failure (ACLF) patients, and 26 healthy controls were collected. The percentage of Th9 cells and serum IL-9 and IL-10 levels were determined. There was no significant difference in the percentage of Th9 cells and serum IL-9 and IL-10 levels among different groups, nor were these related to hepatitis B e antigen status, complications of cirrhosis, inflammation index, or prognosis indexes. There was no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients. There was no correlation of Th9 cells with survival of ACLF patients. However, IL-9 and IL-10 levels were significantly higher in the nonsurvived ACLF patients compared to survived ACLF patients. Furthermore, baseline IL-9 level predicted the prognosis of ACLF patients with 87.5% sensitivity and 61.5% specificity. Thus, our data indicate that Th9 cells were unlikely involved in the pathogenesis of HBV infection, but elevation in IL-9 and IL-10 may signal poor prognosis for ACLF. PMID:27100428

  11. Heart Failure

    MedlinePlus

    ... version of this page please turn Javascript on. Heart Failure What is Heart Failure? In heart failure, the heart cannot pump enough ... failure often experience tiredness and shortness of breath. Heart Failure is Serious Heart failure is a serious and ...

  12. The Difficult Diagnosis of Ischaemic Papillary Muscle Rupture

    PubMed Central

    Braun, Christian T.; Ricklin, Meret E.; Exadaktylos, Aristomenis K.

    2016-01-01

    We present a rare case of severe ischaemic papillary muscle rupture in a 67-year-old male patient who was admitted to the Emergency Department of the University Hospital Bern, Switzerland, in November 2013 with acute chest pain. On admission, the patient’s blood pressure was 60/40 mm/Hg, his pulse was 110 beats per minute and his respiratory rate was 20 breaths per minute. An electrocardiogram was normal and focused assessment with sonography in trauma was negative. Transthoracic echocardiography showed possible thickening of the mitral valve leaflet with no indications of severe mitral insufficiency or wall motion abnormalities. Triple-rule-out computed tomography angiography revealed no pulmonary emboli or aortic dissection, although coronary atherosclerosis was present. Finally, severe insufficiency of the mitral valve with rupture of the papillary muscle, likely due to ischaemia, was observed via transoesophageal echocardiography. The patient underwent a successful surgical intervention and was discharged 10 days later in stable condition. PMID:27226917

  13. Isolated asymptomatic pulmonary arteriovenous malformation presenting with ischaemic stroke.

    PubMed

    Bertram, Kelly L; Madan, Anoop; Frayne, Judith

    2016-07-01

    Young onset stroke is uncommon, and may be due to conditions other than traditional vascular risk factors. A 42-year-old woman with an ischaemic stroke was found to have left atrial bubble study positivity on transthoracic echocardiogram (TTE) suggestive of patent foramen ovale, however she also had low peripheral oxygen saturation. Investigation revealed an isolated pulmonary arteriovenous malformation (PAVM), visible on admission chest radiograph. This can cause embolic stroke and is an alternate cause of the TTE findings. The PAVM was able to be closed via endovascular intervention, removing the shunt and therefore removing her risk of recurrent stroke events. This is a rare cause of embolic stroke in young people which can be easily missed on investigation yet is amenable to treatment. PMID:26896908

  14. Ischaemic stroke with intact atrial septum--exclude arteriovenous malformations.

    PubMed

    Doering, Friederike; Eicken, Andreas; Hess, John

    2014-02-01

    A 44-year-old woman was referred to our centre for interventional cardiac catheterisation. The diagnostic work-up after a preceding ischaemic stroke led to the assumption of a patent foramen ovale due to a positive bubble study. Before the planned percutaneous closure of the patent foramen ovale, we performed a second bubble study, which showed an intact atrial septum. However, after two to three heart cycles bubbles could be detected in the left atrium, assuming a right-to-left shunt of an extracardiac origin most likely in the lung. We therefore performed cardiac catheterisation, yielding a pulmonary arteriovenous malformation in the lower lobe of the right lung. This was successfully closed interventionally by placing a Cook coil, as well as several plugs into the malformation and feeding vessels. PMID:23347820

  15. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg), you have ...

  16. Hepatitis C and HIV

    MedlinePlus

    ... Problems : Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living ...

  17. Hepatitis B and HIV

    MedlinePlus

    ... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  18. Molsidomine prevents post-ischaemic ventricular fibrillation in dogs.

    PubMed Central

    Cano, J. P.; Guillen, J. C.; Jouve, R.; Langlet, F.; Puddu, P. E.; Rolland, P. H.; Serradimigni, A.

    1986-01-01

    Forty anaesthetized dogs were subjected to left circumflex coronary artery ligation followed by reperfusion. Molsidomine was randomly administered to 20 dogs (50 micrograms kg-1 as an i.v. bolus - 15 min prior to coronary occlusion - followed by an infusion of 0.05 micrograms kg-1 min-1. Standard electrocardiographic leads 2 and 3 were continuously recorded to measure ST segment and delta R% changes and to document both the number of ventricular premature beats and the onset of ventricular fibrillation; aortic pressure and cardiac output were measured; thromboxane B2 plasma levels, platelet aggregation produced by ADP, and molsidomine plasma levels were determined before and at 10, 30 and 75 min after the start of the drug protocol. Molsidomine protected the treated animals from early (10 min) post-ischaemic ventricular fibrillation (0 of 20 vs 6 of 20, P = 0.0202), reduced the incidence of overall post-occlusion ventricular fibrillation (3 of 20 vs 10 of 20, P = 0.0407) and improved the total survival rate (P = 0.0067). In molsidomine treated dogs: mean aortic pressure and the rate-pressure product were lowered 10 min after the start of the drug; immediate post-occlusion (3 min) ST segment changes (0.82 +/- 0.52 vs 1.52 +/- 0.78 mV, P less than 0.025) and delta R% changes (37 +/- 50 vs 90 +/- 84%, P less than 0.025) were less marked; the number of ventricular premature beats was lowered and finally, a progressive decline of platelet aggregation produced by ADP was achieved after 75 min of drug infusion. These results were obtained in the presence of mean plasma levels of molsidomine ranging from 20 to 28 ng ml-1. The time-action curve of the antifibrillatory effect of molsidomine parallels those at the level of post-ischaemic electrocardiographic changes. Images Figure 2 PMID:3755634

  19. A 3-year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color Doppler US evaluation of cerebral perfusion.

    PubMed

    Novelli, Gilnardo; Rossi, Massimo; Pretagostini, Renzo; Novelli, Luigi; Poli, Luca; Ferretti, Giancarlo; Iappelli, Massimo; Berloco, Pasquale; Cortesini, Raffaello

    2003-01-01

    In our 3-year experience, we treated 63 patients with Molecular Adsorbent Recirculating System (MARS). The patients were divided as follows: 10 primary non-function (PNF) 16%, 10 delayed non-function (DNF) 16%, 16 Fulminant hepatitis (FH) 24%, 23 acute decompensation of chronic liver disease (ACLF) 38%, and 4 hepatic resection 6%. All patients who underwent MARS treatment had bilirubin >15 mg/dL, Glasgow Coma Score between 9 and 11, ammonium >160 microg/dL and non-coagulability. The determining factors taken into consideration for the continuation of MARS treatment were: an improvement in Glasgow Coma Score, and a decrease in ammonium and bilirubin. We also monitored hemodynamic parameters, acid-base equilibrium, and blood gas analysis before and after each treatment. In order to determine patients' neurological conditions, we not only took into account the Glasgow Coma Score, which does not give mathematically precise results but also took into account the fact that patients with hepatic coma had lower cerebral mean velocity in the cerebral arteries than patients without encephalopathy. For this reason, in the last 22 patients we monitored cerebral perfusion, determined by mean flow velocity (Vmean) in the middle cerebral artery. Our results were expressed as mean +/- SD and we analyzed the differences between mean values for each variable, before and after treatment by means of Student's t-test. At the end of treatment, we obtained significant P-values for bilirubin, ammonium, Glasgow Coma Score and creatinine. In 16/20 patients, we could demonstrate a clear correlation between the improvement in clinical conditions (especially neurological status) and improvement in cerebral perfusion, measured by color Doppler US. PMID:12950955

  20. Hepatitis Testing

    MedlinePlus

    ... caused by viruses. They include hepatitis A, hepatitis B, and hepatitis C. To diagnose hepatitis, your health care provider will ask you about your medical history and symptoms, do a physical exam, and order blood tests. There are blood tests for each type of ...

  1. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus.

    PubMed

    Matoq, Amr; Salahuddin, Asma

    2016-01-01

    Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection. PMID:27340581

  2. Fulminant hepatitis following chemotherapy treatment for breast cancer

    PubMed Central

    Shoushtari, Ali Hakim; Shaw, Robert A

    2013-01-01

    A woman in her early 50s was admitted to the intensive care unit with nausea, altered mental status and hepatic failure. She had a history of asymptomatic chronic hepatitis B and recently received chemotherapy for breast cancer. A diagnosis of hepatitis B reactivation (HBR) was made, but unfortunately she died of liver failure. Controversies around testing for hepatitis B prior to giving immunosuppressive treatments and the use of prophylactic antiviral therapy to prevent HBR are discussed. PMID:23307451

  3. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus

    PubMed Central

    Salahuddin, Asma

    2016-01-01

    Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection. PMID:27340581

  4. Ischaemic Priapism and Glucose-6-Phosphate Dehydrogenase Deficiency: A Mechanism of Increased Oxidative Stress?

    PubMed Central

    Morrison, BF; Thompson, EB; Shah, SD; Wharfe, GH

    2014-01-01

    ABSTRACT Ischaemic priapism is a devastating urological condition that has the potential to cause permanent erectile dysfunction. The disorder has been associated with numerous medical conditions and the use of pharmacotherapeutic agents. The aetiology is idiopathic in a number of cases. There are two prior case reports of the association of ischaemic priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report on a third case of priapism associated with G6PD deficiency and review recently described molecular mechanisms of increased oxidative stress in the pathophysiology of ischaemic priapism. The case report of a 32-year old Afro-Caribbean male with his first episode of major ischaemic priapism is described. Screening for common causes of ischaemic priapism, including sickle cell disease was negative. Glucose-6-phosphate dehydrogenase deficiency was discovered on evaluation for priapism. Penile aspiration was performed and erectile function was good post treatment. Glucose-6-phosphate dehydrogenase deficiency is a cause for ischaemic priapism and should be a part of the screening process in idiopathic causes of the disorder. Increased oxidative stress occurs in G6PD deficiency and may lead to priapism. PMID:25803385

  5. Aplastica Anemia And Viral Hepatitis

    PubMed Central

    Cudillo, Laura

    2009-01-01

    Acquired aplastic anemia (aAA) is a severe and rare disease, characterized by hematopoietic bone marrow failure and peripheral cytopenia. The pathophysiology is immune mediated in most cases, activated T1 lymphocytes have been identified as effector cells. The disease can be successfully treated with combined immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation. Hepatitis-associated aplastic anemia (HAA) is a syndrome of bone marrow failure following the development of acute seronegative hepatitis. HAA syndrome most often affects young males who presented severe pancytopenia two to three months after an episode of acute hepatitis. The clinical course of hepatitis is more frequently benign but a fulminant severe course is also described. The bone marrow failure can be explosive and severe and it is usually fatal if untreated, no correlations have been observed between severity of hepatitis and AA. In none of the studies a specific virus could be identified and most cases are seronegative for known hepatitis viruses. The clinical characteristics and response to immunotherapy indicate a central role for immune-mediated mechanism in the pathogenesis of HAA. The initial target organ of the immune response is the liver as suggested by the time interval between hepatitis and the onset of bone marrow failure. Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis. Recently in HAA it has been demonstrated intrahepatic and blood lymphocytes with T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia. PMID:21415960

  6. Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs.

    PubMed Central

    Sassen, L. M.; den Boer, M. O.; Rensen, R. J.; Saxena, P. R.; Verdouw, P. D.

    1988-01-01

    1. The ability of the cardioselective beta-adrenoceptor antagonist bisoprolol ((+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropyl-amino -2-propanol hemifumarate, EMD 33512) to suppress isoprenaline-induced increases in heart rate and maximal rate of rise in left ventricular pressure (LVdP/dtmax) was studied in 6 anaesthetized pigs given 4 cumulative doses (16, 64, 256 and 1024 micrograms kg-1). Bisoprolol was about 2 times more effective in suppressing isoprenaline-induced increases in LVdP/dtmax than those in heart rate. 2. In 8 animals which had a partial stenosis of the left anterior descending coronary artery (LADCA), the effects of 3 consecutive doses (50, 200 and 750 micrograms kg-1) of bisoprolol were studied on systemic haemodynamics, regional myocardial perfusion and function. The effects of the drug were compared with those obtained in a group of 9 animals with LADCA stenosis which did not receive any treatment. 3. The lowest dose of bisoprolol (50 micrograms kg-1) increased perfusion of the ischaemic myocardium (which had been reduced from 123 +/- 20 ml min-1 100 g-1 to 42 +/- 11 ml min-1 100 g-1) by 21 +/- 10 ml min-1 100 g-1 (P less than 0.05). In particular the subendocardial layers, which were most severely affected by the stenosis (a decrease from 128 +/- 19 ml min-1 100 g-1 to 20 +/- 6 ml min-1 100 g-1) benefited from the administration of the drug (an increase of 30 +/- 10 ml min-1 100 g-1). Perfusion of the subepicardium was not significantly affected. With the higher dose only a minor additional improvement in perfusion of the ischaemic myocardium was observed. 4. The negative chronotropic response is the most likely factor leading to the improvement in perfusion. 5. Myocardial wall thickening, which decreased from 41 +/- 2% to 9 +/- 4% (P less than 0.05) due to the hypoperfusion, did not improve after administration of the drug. This lack of improvement may possibly be due to the duration of ischaemia before and the magnitude of the

  7. Hepatitis B and Hepatitis C in Pregnancy

    MedlinePlus

    ... infected with the hepatitis B virus, can I breastfeed? • If I am infected with the hepatitis B ... infected with the hepatitis C virus, can I breastfeed? • Glossary What are hepatitis B and hepatitis C ...

  8. Ischaemia and reperfusion injury of rat liver increases expression of glutathione S-transferase A1/A2 in zone 3 of the hepatic lobule.

    PubMed Central

    Branum, G D; Selim, N; Liu, X; Whalen, R; Boyer, T D

    1998-01-01

    Effects of ischaemia-reperfusion injury (I/R) of liver on expression of rat glutathione S-transferase (rGST) isoenzymes that metabolize products of oxidative stress were examined. Rats underwent lobar liver ischaemia for 30 min followed by reperfusion. In ischaemic lobes, rGSTA1/A2 transcript levels increased significantly 12 h after I/R (2.94-fold) and protein levels increased significantly at 24 h (1.45-fold); increased transcript levels were also observed in nonischaemic lobes (1.78-fold). Superoxide dismutase prevented I/R and the increases in transcript and protein levels in ischaemic and non-ischaemic lobes. By in-situ hybridization, increases in transcript levels at 6 h were present in zones 2 and 3 of the ischaemic lobes and peaked at 12 h (2.5-fold zone 2, 4.5-fold zone 3). Significant increases in transcript levels also were observed at 24 h in zones 2 (2.0-fold) and 3 (2.9-fold) of non-ischaemic lobes. Nuclear run-off assays showed a 1.8-fold increase in rGSTA1/A2 transcription rates in ischaemic lobes at 3 h. We conclude that I/R causes increased rGSTA1/A2 expression in the zone of the hepatic lobule most susceptible to oxidative injury and that this expression may be an important defence against injury. PMID:9461493

  9. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... There are different tests for hepatitis A and B. A positive test is ... may mean: You currently have a hepatitis infection. This may ...

  10. Hepatitis C and Incarceration

    MedlinePlus

    HEPATITIS C & INCARCERATION What is hepatitis? “Hepatitis” means inflammation or swelling of the liver. The liver is an important ... viral hepatitis: Hepatitis A, Hepatitis B, and Hepatitis C. They are all different from each other and ...

  11. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  12. Hepatitis B and Hepatitis C Reactivation in the Biologic Era

    PubMed Central

    Bojito-Marrero, Lizza; Pyrsopoulos, Nikolaos

    2014-01-01

    Hepatitis B (HBV) and hepatitis C (HCV) reactivation may occur after the use of biologic agents. During the last decade, utilization of biologics has changed the fate of many treated for cancer, autoimmune and connective tissue disease, maintenance of transplanted organs, and the prevention of graft-versus-host disease among others. HBV reactivation has been reported in up to 50% of HBV carriers undergoing immunosuppressive therapy, and there is emerging data pointing towards an increased risk for HCV reactivation. If reactivation of HBV and HCV occurs, the spectrum of clinical manifestations can range from asymptomatic hepatitis flares to hepatic decompensation, fulminant hepatic failure, and death. Therefore, identifying patients at risk and early diagnosis are imperative to decrease significant morbidity and mortality. The purpose of this article is to review the pathophysiology of the reactivation of HBV and HCV infection in patients receiving biologic therapies and the approaches used to diagnose, prevent, and treat HBV and HCV reactivation. PMID:26355300

  13. Hepatic ischemia

    MedlinePlus

    Hepatic ischemia is a condition in which the liver does not get enough blood or oxygen, causing injury to ... pressure from any condition can lead to hepatic ischemia. Such conditions may include: Abnormal heart rhythms Dehydration ...

  14. Hepatic Encephalopathy

    MedlinePlus Videos and Cool Tools

    ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that ... medical care is an important factor in staying as healthy as possible. The American Liver Foundation is ...

  15. Hepatitis D

    MedlinePlus

    ... if the hepatitis B virus is also present. Transmission Hepatitis D can be found in the blood, ... other body fluids of people who are infected. Transmission happens when infected body fluid enters another person’s ...

  16. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  17. Hepatitis C

    MedlinePlus

    ... 2014 Select a Language: Fact Sheet 507 Hepatitis C WHAT IS HEPATITIS C? HOW IS IT DIAGNOSED? ... treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure ...

  18. Hepatitis A

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  19. Hepatitis B

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000279.htm Hepatitis B To use the sharing features on this page, please enable JavaScript. Hepatitis B is irritation and swelling (inflammation) of the ...

  20. Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms.

    PubMed

    Thijssen, Dick H J; Maxwell, Joseph; Green, Daniel J; Cable, N Timothy; Jones, Helen

    2016-06-01

    What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact

  1. Monophasic action potentials and Ca2+ transients in ischaemically preconditioned rabbit ventricular muscle

    PubMed Central

    Dekker, L.R.C.; van Bavel, E.; Opthof, T.; Coronel, R.; Janse, M.J.

    2003-01-01

    Background ATP-sensitive K+ (KATP) channels play an important role in the protective mechanism underlying ischaemic preconditioning. Ample evidence indicates, however, that action potential shortening is not a prerequisite for the cardioprotective effect of preconditioning. Methods Monophasic action potential duration (MAPD), tissue resistance, intracellular Ca2+ (Indo-1) and mechanical activity were simultaneously assessed in arterially perfused rabbit papillary muscles. We studied four experimental protocols preceding sustained ischaemia: 1. control perfusion (n=6), 2. ischaemic preconditioning (PC; n=4), 3. pretreatment with a KATP channel blocker, glibenclamide (15 μmol/1), prior to ischaemic preconditioning (PC+glib; n=3), 4. glibenclamide pretreatment only (Glib; n=2). Results In the PC group an increase in the diastolic Ca2+ level and a prolongation of the Ca2+ transient just prior to the induction of sustained ischaemia correlate to the postponement of the onset of irreversible ischaemic damage, as established by a rise in [Ca2+]i, electrical uncoupling and contracture. Glibenclamide antagonised these changes in the Ca2+ transient and the cardioprotection induced by preconditioning. MAPD was equal in all experimental groups. Conclusions Prolongation of the Ca2+ transient and increase of diastolic [Ca2+]i just prior to the induction of sustained ischaemia and not action potential shortening are involved in the cardioprotective effect of ischaemic preconditioning. Therefore, a glibenclamide-sensitive mechanism, other than the sarcolemmal KATP channels, is involved in the protective effect of ischaemic preconditioning. Changes in Ca2+ metabolism may play a crucial role in ischaemic preconditioning. ImagesFigure 1 PMID:25696182

  2. Motor recovery after acute ischaemic stroke: a metabolic study.

    PubMed Central

    Di Piero, V; Chollet, F M; MacCarthy, P; Lenzi, G L; Frackowiak, R S

    1992-01-01

    The metabolic changes occurring after ischaemic stroke were measured to investigate the functional anatomy of clinical motor recovery. Positron emission tomography (PET) and the steady-state 15O technique was used to compare resting relative metabolic distributions at the onset of functional deficit with those following recovery. Ten patients were studied with repeat scans. Motor recovery was associated in some patients with an increase of relative oxygen metabolism in anatomical structures normally involved in motor function in the affected hemisphere, particularly in the cortical motor areas. In those patients without such metabolic changes in the cortex of the diseased hemisphere, relative increases in cortical metabolism in the contralateral hemisphere were associated with better motor recovery than in patients with no relative cortical metabolic increase in either hemisphere. There was no correlation between the degree of improvement in motor function and the severity of motor deficit at onset, the size and site of the lesion and the metabolic changes in the infarcted zone. No particular pattern of global metabolic changes was observed after recovery. Thus different relative patterns of metabolic recovery were seen in patients with different lesions and evidence was found for the participation of contralateral structures in the recovery process in some patients. Images PMID:1469418

  3. Desmoteplase: discovery, insights and opportunities for ischaemic stroke

    PubMed Central

    Medcalf, Robert L

    2012-01-01

    Nature has provided a vast array of bioactive compounds that have been exploited for either diagnostic or therapeutic use. The field of thrombosis and haemostasis in particular has enjoyed much benefit from compounds derived from nature, notably from snakes and blood-feeding animals. Indeed, the likelihood that blood-feeding animals would harbour reagents with relevant pharmacology and with potential pharmaceutical benefit in haemostasis was not too far-fetched. Blood-feeding animals including leeches and ticks have evolved a means to keep blood from clotting or to at least maintain the liquid state, and some of these have been the subject of clinical development. A more recent example of this has been the saliva of the common vampire bat Desmodus rotundus, which has proven to harbour a veritable treasure trove of novel regulatory molecules. Among the bioactive compounds present is a fibrinolytic compound that was shown over 40 years ago to be a potent plasminogen activator. Studies of this vampire bat-derived plasminogen activator, more recently referred to as desmoteplase, revealed that this protease shared a number of structural and functional similarities to the human fibrinolytic protease, tissue-type plasminogen activator (t-PA) yet harboured critically important differences that have rendered this molecule attractive for clinical development for patients with ischaemic stroke. PMID:21627637

  4. Desmoteplase: discovery, insights and opportunities for ischaemic stroke.

    PubMed

    Medcalf, Robert L

    2012-01-01

    Nature has provided a vast array of bioactive compounds that have been exploited for either diagnostic or therapeutic use. The field of thrombosis and haemostasis in particular has enjoyed much benefit from compounds derived from nature, notably from snakes and blood-feeding animals. Indeed, the likelihood that blood-feeding animals would harbour reagents with relevant pharmacology and with potential pharmaceutical benefit in haemostasis was not too far-fetched. Blood-feeding animals including leeches and ticks have evolved a means to keep blood from clotting or to at least maintain the liquid state, and some of these have been the subject of clinical development. A more recent example of this has been the saliva of the common vampire bat Desmodus rotundus, which has proven to harbour a veritable treasure trove of novel regulatory molecules. Among the bioactive compounds present is a fibrinolytic compound that was shown over 40 years ago to be a potent plasminogen activator. Studies of this vampire bat-derived plasminogen activator, more recently referred to as desmoteplase, revealed that this protease shared a number of structural and functional similarities to the human fibrinolytic protease, tissue-type plasminogen activator (t-PA) yet harboured critically important differences that have rendered this molecule attractive for clinical development for patients with ischaemic stroke. PMID:21627637

  5. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

    PubMed Central

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

    2016-01-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  6. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure.

    PubMed

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves

    2016-04-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  7. Platelet function testing in transient ischaemic attack and ischaemic stroke: A comprehensive systematic review of the literature.

    PubMed

    Lim, Soon Tjin; Coughlan, Catherine A; Murphy, Stephen J X; Fernandez-Cadenas, Israel; Montaner, Joan; Thijs, Vincent; Marquardt, Lars; McCabe, Dominick J H

    2015-01-01

    The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition of platelet function ex vivo on antiplatelet therapy, using laboratory tests that correlate with the clinical effectiveness of these agents, would potentially enable physicians to tailor antiplatelet therapy to suit individuals. A systematic review of the literature was performed to collate all available data on ex vivo platelet function/reactivity in CVD patients, especially those treated with aspirin, dipyridamole or clopidogrel. Particular emphasis was paid to information from commonly available whole blood platelet function analysers (PFA-100®, VerifyNow® and Multiplate®). Data on pharmacogenetic mechanisms potentially influencing high on-treatment platelet reactivity (HTPR) on antiplatelet therapy in CVD were reviewed. Two-hundred forty-nine potentially relevant articles were identified; 93 manuscripts met criteria for inclusion. The prevalence of ex vivo HTPR in CVD varies between 3-62% with aspirin monotherapy, 8-61% with clopidogrel monotherapy and 56-59% when dipyridamole is added to aspirin in the early, subacute or late phases after TIA/stroke onset. The prevalence of HTPR on aspirin was higher on the PFA-100 than on the VerifyNow in one study (p < 0.001). Furthermore, the prevalence of HTPR on aspirin was lower when one used 'novel longitudinal' rather than 'cross-sectional, case-control' definitions of HTPR on the PFA early after TIA or stroke (p = 0.003; 1 study). Studies assessing the influence of genetic polymorphisms on HTPR in CVD patients are limited, and need validation in large multicentre studies. Available data illustrate that an important proportion of CVD patients have ex vivo HTPR on their prescribed antiplatelet regimen, and that the prevalence varies depending on the definition and assay used. Large, adequately-sized, prospective multicentre collaborative studies are

  8. The effect of warm liver ischaemia & reperfusion injury on circulating plasma lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic preconditioning

    PubMed Central

    Lanitis, Sophocles; Lolis, Evangelos; Dafnios, Nikolaos; Sgourakis, George; Voros, Dionysios C.; Vassiliou, Ioannis

    2012-01-01

    Background & objectives: Ischaemia/reperfusion (I/R) associated with major liver surgery compromises liver function. Ischaemic preconditioning (IPC) may be effective in minimizing hepatic I/R injury. This study aimed to investigate the impact of liver ischaemic manipulations on lipid metabolism in rat during the process of liver recovery after liver surgery. Methods: Sixty three male Wistar rats were assigned to three groups: the sham group, the I/R group which underwent warm ischaemia and reperfusion (I/R), and the IPC group. The animals were subdivided in 3 groups [1st, 3rdand 7th postoperative day (PO)]. Hepatic lipase (HL) and total lipase (TL) activity and the levels of aspartate and alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were measured in plasma. Results: There was no significant difference in the activity of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were observed in the IPC group when compared to the other groups on the 3rd PO day. Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the sham group on the 7th PO day while HDL was also higher in the I/R group. Significantly higher cholesterol levels were found in the I/R and IPC groups on the 7th PO day, which were not observed in the sham group. There was a similar curve for triglycerides in the sham and IPC groups while there were significantly higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in the IPC group were higher on the 3rd and 7th PO day, compared to day 1. Interpretation & conclusion: Warm ischaemia and I/R injury do not seem to affect lipolytic enzyme activity after the 1st PO day despite the effects on plasma lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in plasma. PMID:22960895

  9. Hepatitis A

    MedlinePlus

    ... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

  10. Hepatitis C

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  11. Hepatitis A

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Español Hepatitis A Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is hepatitis A? Hepatitis * A is a virus , or infection, ...

  12. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  13. Hepatic haemangiomata: diagnosis and management.

    PubMed Central

    Larcher, V F; Howard, E R; Mowat, A P

    1981-01-01

    Five cases of hepatic haemangioma are described, and a sixth (previously reported) is reviewed. Clinical features, investigation, and management are described to show the great variability of the complications and prognosis. Five children presented in the first 10 weeks of life with hepatomegaly; 4 developed congestive cardiac failure; 3 had cutaneous haemangiomata. One child presented at age 4 years with hepatomegaly and anaemia, and on investigation had features of chronic disseminated intravascular coagulation. Focal decrease or patchiness in hepatic uptake of technetium-99m colloid, and abnormal intrahepatic circulation was shown in all cases. In 3 children liver biopsy was performed to exclude malignant disease. In one patient there was spontaneous regression of the tumour by age 3 years. In 3 cases hepatic artery ligation was necessary to control congestive cardiac failure which had persisted despite treatment with digoxin, diuretics, and oral corticosteroids, a procedure which was without complications after up to 8 years. One infant with intractable portal hypertension, hepatic vein obstruction, and severe cholestasis died with persisting alimentary haemorrhage and intra-abdominal sepsis. One child aged 4 years showed no immediate response to hepatic artery ligation but the size of her tumour got smaller and the clinical features diminished after irradiation. These tumours cause considerable morbidity and have a high reported mortality. If congestive cardiac failure is not rapidly controlled, hepatic artery ligation should be performed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7469456

  14. Automatic classification of transient ischaemic and transient non-ischaemic heart-rate related ST segment deviation episodes in ambulatory ECG records.

    PubMed

    Faganeli, J; Jager, F

    2010-03-01

    In ambulatory ECG records, besides transient ischaemic ST segment deviation episodes, there are also transient non-ischaemic heart-rate related ST segment deviation episodes present, which appear only due to a change in heart rate and thus complicate automatic detection of true ischaemic episodes. The goal of this work was to automatically classify these two types of episodes. The tested features to classify the ST segment deviation episodes were changes of heart rate, changes of the Mahalanobis distance of the first five Karhunen-Loève transform (KLT) coefficients of the QRS complex, changes of time-domain morphologic parameters of the ST segment and changes of the Legendre orthonormal polynomial coefficients of the ST segment. We chose Legendre basis functions because they best fit typical shapes of the ST segment morphology, thus allowing direct insight into the ST segment morphology changes through the feature space. The classification was performed with the help of decision trees. We tested the classification method using all records of the Long-Term ST Database on all ischaemic and all non-ischaemic heart-rate related deviation episodes according to annotation protocol B. In order to predict the real-world performance of the classification we used second-order aggregate statistics, gross and average statistics, and the bootstrap method. We obtained the best performance when we combined the heart-rate features, the Mahalanobis distance and the Legendre orthonormal polynomial coefficient features, with average sensitivity of 98.1% and average specificity of 85.2%. PMID:20130344

  15. Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

    PubMed

    Mursu, Jaakko; Voutilainen, Sari; Nurmi, Tarja; Tuomainen, Tomi-Pekka; Kurl, Sudhir; Salonen, Jukka T

    2008-10-01

    The role of flavonoids in CVD, especially in strokes, is unclear. Our aim was to study the role of flavonoids in CVD. We studied the association between the intakes of five subclasses (flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins), a total of twenty-six flavonoids, on the risk of ischaemic stroke and CVD mortality. The study population consisted of 1950 eastern Finnish men aged 42-60 years free of prior CHD or stroke as part of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up time of 15.2 years, 102 ischaemic strokes and 153 CVD deaths occurred. In the Cox proportional hazards model adjusted for age and examination years, BMI,systolic blood pressure, hypertension medication, serum HDL- and LDL-cholesterol, serum TAG, maximal oxygen uptake, smoking, family history of CVD, diabetes, alcohol intake, energy-adjusted intake of folate, vitamin E, total fat and saturated fat intake (percentage of energy), men in the highest quartile of flavonol and flavan-3-ol intakes had a relative risk of 0.55 (95% CI 0.31, 0.99) and 0.59 (95% CI 0.30, 1.14) for ischaemic stroke, respectively, as compared with the lowest quartile. After multivariate adjustment, the relative risk for CVD death in the highest quartile of flavanone and flavone intakes were 0.54 (95% CI 0.32, 0.92) and 0.65 (95% CI 0.40, 1.05), respectively. The present results suggest that high intakes of flavonoids may be associated with decreased risk of ischaemic stroke and possibly with reduced CVD mortality. PMID:18377681

  16. Treating hepatitis C - what's new?

    PubMed

    Thompson, Alex J; Holmes, Jacinta A

    2015-12-01

    Chronic hepatitis C infection causes cirrhosis, liver failure and hepatocellular carcinoma, and is the most common indication for liver transplantation. Hepatitis C is curable and complications can be prevented. Until recently, treatment regimens involved peginterferon alfa. Although effective, their widespread use is limited by treatment-related toxicity. A number of direct-acting drugs for hepatitis C, such as sofosbuvir, have recently been developed and target multiple steps in the viral life cycle. These drugs are used in combination in interferon-free regimens. Short courses are highly effective with minimal toxicity. PMID:26843711

  17. The effect of uraemia on the duration of arrhythmias in the context of cardioprotective ischaemic conditioning strategies

    PubMed Central

    McCafferty, Kieran; Byrne, Conor J; Kieswich, Julius; Raftery, Martin; Thiemermann, Christoph; Yaqoob, Muhammad M

    2014-01-01

    Background Sudden cardiac death is a leading cause of death in patients with chronic kidney disease and end stage renal disease. Ischaemic conditioning strategies confer profound myocardial protection and, in the absence of uraemia, have been reported to reduce myocardial dysrhythmias. Recent data confirms that ischaemic conditioning can protect the uraemic heart. However, the effect of uraemia on myocardial arrhythmogenesis in the context of ischaemia-reperfusion injury and whether ischaemic conditioning can modulate this is unknown. Objective We investigated the effect of underling chronic uraemia on the duration of arrhythmias in the context of cardioprotective ischaemic conditioning strategies. Methods We examined the effect of chronic uraemia on arrhythmias occurring in the context of myocardial ischaemia-reperfusion injury and the ability of ischaemic preconditioning (IPC), remote ischaemic preconditioning (RIPC) and ischaemic postconditioning (iPOST) to suppress arrhythmogenesis in uraemic and non-uraemic animals. Results IPC led to a reduction in the frequency and duration of arrhythmias occurring during ischaemia and reperfusion. Neither RIPC nor iPOST affected the duration or frequency of ischaemic or reperfusion arrhythmias. Underlying uraemia did not alter the frequency or duration of ischaemic arrhythmias in any of the experiments however it was associated with a reduction in reperfusion arrhythmia duration in the IPC and iPOST experiments. Conclusions These studies demonstrate that underlying chronic uraemia does not reduce the threshold for arrhythmia timing or duration resulting from myocardial ischaemia-reperfusion and underlying uraemia did not alter the effects of these cardioprotective ischaemic conditioning strategies in the context of arrhythmia duration. Summary This novel work in a rodent model of chronic uraemia establishes that underlying uraemia does not increase the susceptibility to myocardial ischaemia-reperfusion induced arrhythmias

  18. Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging.

    PubMed

    Harston, George W J; Tee, Yee Kai; Blockley, Nicholas; Okell, Thomas W; Thandeswaran, Sivarajan; Shaya, Gabriel; Sheerin, Fintan; Cellerini, Martino; Payne, Stephen; Jezzard, Peter; Chappell, Michael; Kennedy, James

    2015-01-01

    The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke. PMID:25564491

  19. Polyphenols: Potential source of drugs for the treatment of ischaemic heart disease.

    PubMed

    Du, Guanhua; Sun, Lan; Zhao, Rui; Du, Lida; Song, Junke; Zhang, Li; He, Guorong; Zhang, Yongxiang; Zhang, Juntian

    2016-06-01

    Polyphenols, which are naturally present in plants, have been studied for their chemical and pharmacological properties. Polyphenols have been found to exhibit various bioactivities such as antioxidant, free radical scavenging and anti-inflammatory effects, in addition to regulating the intracellular free calcium levels. These bioactivities are related to the underlying mechanisms of ischaemic heart diseases. Pharmacological studies have proven polyphenols to be effective in treating cardiovascular diseases in various ways, particularly ischaemic heart diseases. Based on their mode of action, we propose that some polyphenols can be developed as drugs to treat ischaemic heart diseases. For this purpose, a strategy to evaluate the therapeutic value of drugs for ischaemic heart diseases is needed. Despite several advances in percutaneous coronary intervention (PCI), the incidence of myocardial infarction and deaths due to cardiovascular diseases has not decreased markedly in China. Due to their pleiotropic properties and structural diversity, polyphenols have been of great interest in pharmacology. In the present review, we summarize the pharmacological effects and mechanisms of polyphenols reported after 2000, and we analyse the benefits or druggability of these compounds for ischaemic heart diseases. PMID:27113411

  20. Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging

    PubMed Central

    Harston, George W. J.; Tee, Yee Kai; Blockley, Nicholas; Okell, Thomas W.; Thandeswaran, Sivarajan; Shaya, Gabriel; Sheerin, Fintan; Cellerini, Martino; Payne, Stephen; Jezzard, Peter; Chappell, Michael

    2015-01-01

    The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke. PMID:25564491

  1. The hepatic-arterial/portal-venous scintiangiogram in alcoholic hepatitis

    SciTech Connect

    Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.

    1984-01-01

    This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.

  2. Fialuridine Induces Acute Liver Failure in Chimeric TK-NOG Mice: A Model for Detecting Hepatic Drug Toxicity Prior to Human Testing

    PubMed Central

    Xu, Dan; Nishimura, Toshi; Nishimura, Sachiko; Zhang, Haili; Zheng, Ming; Guo, Ying-Ying; Masek, Marylin; Michie, Sara A.; Glenn, Jeffrey; Peltz, Gary

    2014-01-01

    Background Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers. Methods and Findings Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers. Conclusions FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in

  3. Risk of stroke and transient ischaemic attack after herpes zoster.

    PubMed

    Kwon, S U; Yun, S-C; Kim, M-C; Kim, B J; Lee, S H; Lee, S-O; Choi, S-H; Kim, Y S; Woo, J H; Kim, S-H

    2016-06-01

    We assessed the association of herpes zoster (HZ) with stroke/transient ischaemic attack (TIA) in the general population according to age with controlling risk factors for stroke, using a nationwide representative cohort. The study was based on a prospective dynamic cohort consisting of 1 million Koreans representing all age groups, genders and geographical areas in the Korea Health Insurance Database. New events of stroke/TIA and HZ were identified using the diagnostic codes in the International Classification of Diseases, tenth revision. The risk for stroke/TIA after HZ was compared with HZ-free stroke/TIA individuals according to age group. A total of 766 179 adults were followed up for 11 years from 2003. The incidence of the first-diagnosed HZ cases was 9.40 per 1000 person-years, and that of the first-diagnosed stroke/TIA cases was 9.77 per 1000 person-years. The risk for stroke/TIA was higher in patients who had previous HZ episodes than in those who had never experienced HZ (incidence rate ratio 1.90; 95% CI 1.85-1.95). In addition, this risk persisted for several years after HZ. The risk of stroke/TIA after HZ gradually decreased with age; adjusted hazard ratio (HR) 2.04 in 18- to 30-year-olds, HR 1.74 in 30- to 40-year-olds, HR 1.43 in 40- to 50-year-olds, HR 1.23 in 50- to 60-year-olds, HR 1.24 in 60- to 70-year-olds, and HR 1.29 in those >70 years old, after controlling risk factors for stroke/TIA. Our findings provide evidence that HZ carries an increased risk of stroke or TIA and that the effect of HZ on stroke decreases with increasing age. PMID:26992774

  4. Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat.

    PubMed Central

    Curtis, M. J.; MacLeod, B. A.; Walker, M. J.

    1984-01-01

    The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. Verapamil (2-20 mg kg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-1. This dose was effective when given immediately post-occlusion. Severe arrhythmias, as opposed to PVC, were preferentially reduced. In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-1) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20 mg kg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre- or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 +/- 0.8 mumol l-1 and 0.6 +/- 0.1 mumol l-1 (mean +/- s.e. mean), respectively following post-occlusion administration vs. 2.7 +/- 1.2 and 0.24 +/- 0.04 for pre-occlusion administration. Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug. PMID:6487902

  5. Mechanical Thrombectomy for Ischaemic Stroke: The First UK Case Series

    PubMed Central

    Ahmad, Nasar; Nayak, Sanjeev; Jadun, Changez; Natarajan, Indira; Jain, Palbha; Roffe, Christine

    2013-01-01

    Background and Purpose Endovascular treatments have the potential to accelerate reperfusion in acute ischaemic stroke with large vessel occlusion. In the UK only a few stroke centres offer this interventional option. The University Hospital of North Staffordshire (UHNS) has treated the largest number of cases in the UK. Results of the first 106 endovascular treatments (EVT) are presented here. Methods All patients treated with EVT (intra-arterial thrombolysis (IAT), mechanical thrombectomy (MT) or both, or an attempt at intervention) for acute stroke at UHNS, Stoke-on-Trent, UK, were entered into a prospective register. Baseline demographic and clinical data, the National Institutes for Health Stroke Scale (NIHSS), imaging results including Thrombolysis in Cerebral Infarction (TICI) score, and complications were recorded. Mortality, and modified Rankin score (mRS) were assessed at 90 days. Results From December 2009 to January 2013 106 patients (mean age 64 years, median baseline NIHSS 18) were treated with EVT (thrombectomy ± IAT 83%, IAT alone 13%, neither 4%). Seventy-eight per cent of occlusions were in the anterior circulation. Intravenous bridging thrombolysis was performed in 81%. Revascularization was successful (TICI 2b/3) in 84%. The median time from stroke onset to the end of the procedure was 6 h 03 min. A good outcome (mRS≤2) at 90 days was achieved in 48% with a mortality of 15%. Fatal or nonfatal symptomatic intracranial haemorrhage (sICH) within 10 days occurred in 9%. The median length of stay was 14 days (31% discharged home ≤7 days). Conclusions EVT led to good clinical outcomes in almost 50% of patients with severe strokes. PMID:24386090

  6. Endogenous chemical mediators of ventricular arrhythmias in ischaemic heart disease.

    PubMed

    Curtis, M J; Pugsley, M K; Walker, M J

    1993-05-01

    The causes of ventricular arrhythmias in the acute setting of coronary artery disease (myocardial ischaemia and reperfusion) may be approached using two paradigms. One, the electrophysiological paradigm (disturbance of ionic homeostasis, electrogenesis, and conduction) has not been addressed in detail here. Instead, we have focused on the concept of a chemical paradigm of arrhythmogenesis. Many endogenous chemical substances (derived from the myocardium, nerves, blood plasma, platelets, leucocytes, and endothelium) accumulate in the ischaemic tissue or are produced during reperfusion and many of these have been suggested to modulate ventricular arrhythmias. Some substances may be arrhythmogenic and others may be antiarrhythmic. Together they determine whether or not arrhythmias occur. Potentially arrhythmogenic substances include potassium, catecholamines, cAMP, histamine, 5-HT, lysophosphatidylcholine, palmitylcarnitine, platelet activating factor, prostaglandins, leukotrienes, thromboxane A2, angiotensin II, endothelin, opioids, protons, calcium, and free radicals. We have considered each of these, with the objective of evaluating which are important in arrhythmogenesis in acute ischaemia and reperfusion. Two alternative models of arrhythmogenesis are possible in the context of the chemical paradigm: a series model (where one substance or its effects determines the arrhythmogenicity of another) and a parallel model (where numerous substances operate independently to cause ventricular arrhythmias). It is not yet clear which model is most appropriate; a combination of the two is possible, so a working prototype has been constructed which accommodates both. A set of criteria (hitherto lacking) for establishing whether a substance is sufficient and necessary for arrhythmogenesis is proposed. Some generalisations are given on approaches to establishment of these criteria for putative arrhythmogenic substances. Finally, we have considered how arrhythmogenic drug

  7. Antiplatelet regimens in the long-term secondary prevention of transient ischaemic attack and ischaemic stroke: an updated network meta-analysis

    PubMed Central

    Niu, Peng-Peng; Guo, Zhen-Ni; Jin, Hang; Xing, Ying-Qi; Yang, Yi

    2016-01-01

    Objective To examine the comparative efficacy and safety of different antiplatelet regimens in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack. Design Systematic review and network meta-analysis. Data sources As on 31 March 2015, all randomised controlled trials that investigated the effects of antiplatelet agents in the long-term (≥3 months) secondary prevention of non-cardioembolic transient ischaemic attack or ischaemic stroke were searched and identified. Outcome measures The primary outcome measure of efficacy was serious vascular events (non-fatal stroke, non-fatal myocardial infarction and vascular death). The outcome measure of safety was any bleeding. Results A total of 36 randomised controlled trials (82 144 patients) were included. Network meta-analysis showed that cilostazol was significantly more effective than clopidogrel (OR 0.77, 95% credible interval 0.60–0.98) and low-dose (75–162 mg daily) aspirin (0.69, 0.55–0.86) in the prevention of serious vascular events. Aspirin (50 mg daily) plus dipyridamole (400 mg daily) and clopidogrel reduced the risk of serious vascular events compared with low-dose aspirin; however, the difference was not statistically significant. Furthermore, low-dose aspirin was as effective as higher daily doses. Cilostazol was associated with a significantly lower bleeding risk than most of the other regimens. Moreover, aspirin plus clopidogrel was associated with significantly more haemorrhagic events than other regimens. Direct comparisons showed similar results as the network meta-analysis. Conclusions Cilostazol was significantly more effective than aspirin and clopidogrel alone in the long-term prevention of serious vascular events in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack. Cilostazol was associated with a significantly lower bleeding risk than low-dose aspirin (75–162 mg daily) and aspirin (50 mg daily) plus

  8. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  9. Hepatitis Vaccines.

    PubMed

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  10. The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology.

    PubMed

    Yamada, Yohei; Hoshino, Ken; Irie, Rie; Tomita, Hirofumi; Kato, Mototoshi; Shimojima, Naoki; Fujino, Akihiro; Hibi, Taizo; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kawachi, Shigeyuki; Tanabe, Minoru; Sakamoto, Michiie; Kitagawa, Yuko; Kuroda, Tatsuo

    2016-08-01

    The outcome of LTx in pediatric patients with FHF of unknown etiology remains inferior to that of LTx in pediatric patients with cholestatic diseases. A higher incidence of steroid-resistant severe rejection has been increasingly recognized among the responsible factors. We assessed the efficacy of the administration of steroids and PGE1 via PVI in the management of LTx for FHF in pediatric patients. In our early cohort (1995-2007), seven patients who underwent LTx for FHF of unknown etiology were treated with conventional immunosuppressive therapy (calcineurin inhibitor and a steroid). Seven of eight grafts (one patient underwent re-LTx) sustained CV and/or CPV associated with ACR, and four patients died of a graft failure or infectious complications that were associated with the treatment for rejection. Of note, the pathological incidence of CV/CPV was significantly higher in recipients with FHF of unknown etiology than in recipients with biliary cholestatic disease during the same study period (87.5% vs. 13.7%, p < 0.00001). From 2008, three patients underwent LTx for cryptogenic FHF with PVI and conventional IS. PVI was well tolerated, and no relevant severe complications were observed. More strikingly, the patients who received PVI overcame biopsy-proven immunological events and are all currently doing well with excellent graft function after more than five yr. We conclude that PVI is technically safe and effective for preventing severe rejection in pediatric patients who undergo LTx for FHF of unknown etiology and that it does not increase the risk of fatal infectious complications. PMID:27090203

  11. The Transforming Growth Factor β1/Interleukin-31 Pathway Is Upregulated in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure and Is Associated with Disease Severity and Survival

    PubMed Central

    Yu, Xueping; Guo, Ruyi; Ming, Desong; Deng, Yong; Su, Milong; Lin, Chengzu; Li, Julan; Lin, Zhenzhong

    2015-01-01

    The transforming growth factor β1/interleukin-31 (TGF-β1/IL-31) pathway plays an important role in the process of cell injury and inflammation. The purpose of this work was to explore the role of the TGF-β1/IL-31 pathway in the cytopathic process of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). The quantitative serum levels of TGF-β1, IL-9, IL-10, IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were analyzed among chronic hepatitis B (CHB) patients (n = 17), ACLF patients (n = 18), and normal control (NC) subjects (n = 18). Disease severity in patients with ACLF was assessed using the model for end-stage liver disease (MELD) and Child-Pugh scores. Serum TGF-β1 levels were strongly positively correlated with IL-31 in all subjects, and both of them were positively correlated with IL-17, IL-22, and IL-33. In CHB and ACLF patients, serum levels of TGF-β1 and IL-31 were both increased significantly compared with those in NC subjects and positively correlated with total bilirubin (TBil) and alpha-fetoprotein (AFP) levels. ACLF patients showed the highest levels of TGF-β1 and IL-31, which were positively correlated with Child-Pugh scores. Furthermore, the recovery from the liver injury in CHB was accompanied by decreased TGF-β1 and IL-31 levels. More importantly, serum levels of TGF-β1 and IL-31 were markedly upregulated in ACLF nonsurvivors, and IL-31 displayed the highest sensitivity and specificity (85.7% and 100.0%, respectively) in predicting nonsurvival of ACLF patients. Increasing activity of the TGF-β1/IL-31 pathway is well correlated with the extent of liver injury, disease severity, and nonsurvival of ACLF patients, while reducing activity is detected along the recovery from liver injury in CHB, suggesting its potential role in the pathogenesis of liver injury during chronic HBV infection. PMID:25716231

  12. Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating D-Galactosamine induced fulminant hepatic failure in Wistar rats

    SciTech Connect

    Ganai, Ajaz A. Khan, Athar A. Malik, Zainul A. Farooqi, Humaira

    2015-03-01

    Genistein is an isoflavanoid abundantly found in soy. It has been found to play an important role in the prevention of various chronic diseases including cancer. In this study, we evaluated potential therapeutic properties of Genistein against D-Galactosamine (D-GalN) induced inflammation and hepatotoxicity in male Wistar rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal injection of D-GalN (700 mg/kgBW). Genistein (5 mg/kgBW/day) was given as pre-treatment for 30 days via intra-gastric route followed by D-GalN (700 mg/kgBW) injection. The hepatoprotective and curative effects of Genistein were evident from a significant decrease in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as prevention of histological damage by pre-treatment of Genistein. Genistein pre-treatment significantly inhibited the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly suppressed the production of D-GalN-induced proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. These inhibitory effects were associated with the suppression of nuclear factor-kappa B (NF-ĸB) activation, IKKα/β and Mitogen activated protein kinase (MAPK) phosphorylation by Genistein in D-GalN-treated animals. In conclusion, our results suggest that Genistein may serve as a potential supplement in the prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to maintain the redox potential and strengthens the antioxidant defense system of a cell. - Highlights: • First study to evaluate hepatoprotective effect of Genistein against D-GalN • Genistein prevents oxidative damage induced by D-GalN. • Genistein blunts iNOS, COX-2, NF-ĸB, IKKα/β and MAPK expression. • Genistein prevents D-GalN induced apoptosis and

  13. Ischaemic stroke in the setting of glioblastoma: A case series and review of the literature.

    PubMed

    Lasocki, Arian; Gaillard, Frank

    2016-06-01

    Ischaemic strokes are an uncommon occurrence in the setting of glioblastoma, and clinically challenging due to co-existing deficits from the tumour, but important to consider as a possible cause of clinical deterioration. Modern therapies and their associated improvements in survival may lead to a greater overall incidence. The possible underlying causes of ischaemia are multiple, and several factors may contribute in a given patient. This review discusses the causative mechanisms of ischaemic strokes in the setting of glioblastoma, with some illustrative cases. PMID:26988080

  14. Major ischaemic stroke caused by an air embolism from a ruptured giant pulmonary bulla.

    PubMed

    Gudmundsdottir, Johanna F; Geirsson, Arnar; Hannesson, Petur; Gudbjartsson, Tomas

    2015-01-01

    We report an extremely rare complication of a major ischaemic cerebral event caused by an air embolism due to spontaneous rupture of a giant pulmonary bulla that occurred during an airline flight. Shortly after take-off, the patient experienced sudden right-sided hemiplegia and dyspnoea. Following an emergency landing in Reykjavik, a CT scan of the brain showed minute air bubbles consistent with air emboli within the left-sided intracerebral arteries, and MRI showed signs of acute ischaemic cerebral infarction in the left hemisphere. The patient later underwent a pulmonary lobectomy and survived this life-threatening complication with relatively mild neurological sequelae. PMID:25743863

  15. Change in alcohol consumption and risk of death from all causes and from ischaemic heart disease.

    PubMed Central

    Lazarus, N B; Kaplan, G A; Cohen, R D; Leu, D J

    1991-01-01

    OBJECTIVE--To examine the association between alcohol consumption and mortality from all causes and from ischaemic heart disease with a focus on differentiating between long term abstainers and more recent non-drinkers. DESIGN--Cohort study of changes in alcohol consumption from 1965 to 1974 and mortality from all causes and ischaemic heart disease during 1974-84. SETTING--Population based study of adult residents of Alameda County, California. SUBJECTS--2225 women and 1845 men aged 35 and over in 1965. MAIN OUTCOME MEASURES--Alcohol consumption in 1964 and 1974 and mortality from all causes and from ischaemic heart disease during 1974-84. RESULTS--There was a significantly higher risk of death from all causes and from ischaemic heart disease in women who gave up drinking between 1965 and 1974 than in women who continued to drink (relative risk 1.72, 95% confidence interval 1.11 to 2.66, and 2.75, 1.44 to 5.23, for all causes and ischaemic heart disease respectively). A significant increase in risk was not seen in men who gave up drinking (1.32, 0.87 to 2.01, and 0.95, 0.41 to 2.20, respectively). Among men, long term abstainers compared with drinkers were at increased risk of death from all causes and from ischaemic heart disease, though the associations were not significant (1.40, 0.98 to 2.00, and 1.40, 0.76 to 2.58, for all causes and ischaemic heart disease respectively). CONCLUSION--Some of the increased risk of death from all causes and from ischaemic heart disease associated with not drinking in women seems to be accounted for by higher risks among those who gave up drinking. Men who are long term abstainers may also be at an increased risk of death. The heterogeneity of the non-drinking group should be considered when comparisons are made with drinkers. PMID:1912885

  16. Hepatitis B Vaccine

    MedlinePlus

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  17. Hepatitis A Vaccine

    MedlinePlus

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis A?Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in ...

  18. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  19. Autoimmune hepatitis

    MedlinePlus

    ... diseases. These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family ...

  20. Hepatitis B

    MedlinePlus

    ... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

  1. Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats

    PubMed Central

    Tjen-A-Looi, Stephanie C; Pan, Hui-Lin; Longhurst, John C

    1998-01-01

    Activity of ischaemically sensitive cardiac visceral afferents during myocardial ischaemia induces both angina and cardiovascular reflexes. Increased production of bradykinin (BK) and cyclo-oxygenase products (i.e. prostaglandins (PGs)) occurs during myocardial ischaemia. However, the role of these agents in activation of ischaemically sensitive cardiac afferents has not been established. The present study tested the hypothesis that BK produced during ischaemia activates cardiac afferents through kinin B2 receptors. Single-unit activity of cardiac afferents innervating the left ventricle was recorded from the left thoracic sympathetic chain (T1–T4) of anaesthetized cats. Ischaemically sensitive cardiac afferents were identified according to their response to 5 min of myocardial ischaemia. The mechanism of BK in activation of ischaemically sensitive cardiac afferents was determined by injection of BK (1 μg kg−1 i.a.), des-Arg9-BK (1 μg kg−1 i.a., a specific kinin B1 receptor agonist), kinin B2 receptor antagonists: HOE140 (30 μg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.), cyclo-oxygenase inhibition with indomethacin (5 mg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.) after pretreatment with indomethacin (5 mg kg−1 i.v.). We observed that BK increased the discharge rate of all eleven ischaemically sensitive cardiac afferents from 0.39 ± 0.12 to 1.47 ± 0.37 impulses s−1 (P < 0.05). Conversely, des-Arg9-BK did not significantly increase the activity of eleven ischaemically sensitive fibres (0.58 ± 0.02 vs. 0.50 ± 0.18 impulses s−1). HOE140 significantly attenuated the response of twelve afferents to ischaemia (0.61 ± 0.22 to 1.85 ± 0.5 vs. 0.53 ± 0.16 to 1.09 ± 0.4 impulses s−1). NPC-17731, another kinin B2 receptor antagonist, had similar inhibitory effects on six other ischaemically sensitive cardiac afferents (0.35 ± 0.14 to 1.19 ± 0.29 vs. 0.22 ± 0.08 to 0.23 ± 0.07 impulses s−1). Indomethacin significantly reduced the

  2. Distinct cardioprotective mechanisms of immediate, early and delayed ischaemic postconditioning.

    PubMed

    Barsukevich, Veronika; Basalay, Marina; Sanchez, Jenifer; Mrochek, Alexander; Whittle, John; Ackland, Gareth L; Gourine, Alexander V; Gourine, Andrey

    2015-01-01

    Cardioprotection against ischaemia/reperfusion injury in mice can be achieved by delayed ischaemic postconditioning (IPost) applied as late as 30 min after the onset of reperfusion. We determined the efficacy of delayed IPost in a rat model of myocardial infarction (MI) and investigated potential underlying mechanisms of this phenomenon. Rats were subjected to 20, 30 or 45 min of coronary artery occlusion followed by 120 min of reperfusion (I/R). Immediate and early IPost included six cycles of I/R (10/10 s) applied 10 s or 10 min after reperfusion onset. In the second series of experiments, the rats were subjected to 30 min of coronary occlusion followed by IPost applied 10 s, 10, 30, 45 or 60 min after the onset of reperfusion. Immediate and early IPost (applied 10 s or 10 min of reperfusion) established cardioprotection only when applied after a period of myocardial ischaemia lasting 30 min. Delayed IPost applied after 30 or 45 min of reperfusion reduced infarct sizes by 36 and 41 %, respectively (both P < 0.01). IPost applied 60 min after reperfusion onset was ineffective. Inhibition of RISK pathway (administration of ERK1/2 inhibitor PD-98059 or PI3K inhibitor LY-294002) abolished cardioprotection established by immediate IPost but had no effect on cardioprotection conferred by early IPost. Blockade of SAFE pathway using JAK/STAT inhibitor AG490 had no effect on the immediate or early IPost cardioprotection. Blockade of mitochondrial KATP (mitoKATP) channels (with 5-Hydroxydecanoate) abolished cardioprotection achieved by immediate and early IPost, but had no effect on cardioprotection when IPost was applied 30 or 45 min into the reperfusion period. Immediate IPost increased phosphorylation of PI3K-AKT and ERK1/2. Early or delayed IPost had no effect on phosphorylation of PI3K-AKT, ERK1/2 or STAT3. These data show that in the rat model, delayed IPost confers significant cardioprotection even if applied 45 min after onset of reperfusion. Cardioprotection

  3. Serum erythropoietin and outcome after ischaemic stroke: a prospective study

    PubMed Central

    Åberg, N David; Stanne, Tara M; Jood, Katarina; Schiöler, Linus; Blomstrand, Christian; Andreasson, Ulf; Blennow, Kaj; Zetterberg, Henrik; Isgaard, Jörgen; Jern, Christina; Svensson, Johan

    2016-01-01

    Objectives Erythropoietin (EPO), which is inversely associated with blood haemoglobin (Hb), exerts neuroprotective effects in experimental ischaemic stroke (IS). However, clinical treatment trials have so far been negative. Here, in patients with IS, we analysed whether serum EPO is associated with (1) initial stroke severity, (2) recovery and (3) functional outcome. Design Prospective. Controls available at baseline. Setting A Swedish hospital-initiated study with outpatient follow-up after 3 months. Participants Patients (n=600; 64% males, mean age 56 years, controls n=600) were included from the Sahlgrenska Academy Study on IS (SAHLSIS). Primary and secondary outcome measures In addition to EPO and Hb, initial stroke severity was assessed by the Scandinavian Stroke Scale (SSS) and compared with SSS after 3 months (follow-up) as a measure of recovery. Functional outcome was evaluated using the modified Rankin Scale (mRS) at follow-up. Serum EPO and SSS were divided into quintiles in the multivariate regression analyses. Results Serum EPO was 21% and 31% higher than in controls at the acute phase of IS and follow-up, respectively. In patients, acute serum EPO was 19.5% higher in severe versus mild IS. The highest acute EPO quintile adjusted for sex, age and Hb was associated with worse stroke severity quintile (OR 1.70, 95% CI 1.00 to 2.87), better stroke recovery quintile (OR 1.93, CI 1.09 to 3.41) and unfavourable mRS 3–6 (OR 2.59, CI 1.15 to 5.80). However, the fourth quintile of EPO increase (from acute to follow-up) was associated with favourable mRS 0–2 (OR 3.42, CI 1.46 to 8.03). Only the last association withstood full adjustment. Conclusions The crude associations between EPO and worse stroke severity and outcome lost significance after multivariate modelling. However, in patients in whom EPO increased, the association with favourable outcome remained after adjustment for multiple covariates. PMID:26916692

  4. Eradication Strategies for Chronic Hepatitis B Infection.

    PubMed

    Wilson, Eleanor M P; Tang, Lydia; Kottilil, Shyam

    2016-06-01

    Chronic hepatitis B infection affects >300 million people worldwide and is a leading cause of liver failure and cancer. Current approaches to treatment for chronic hepatitis B involve suppression of hepatitis B virus (HBV) DNA with the use of nucleoside analogues. Chronic suppressive therapy rarely results in a "functional cure" or absence of detectable HBV DNA in plasma and loss of detectable hepatitis B surface antigen after cessation of therapy. The major obstacles to achieving a functional cure are the presence of covalently closed circular DNA and ineffective/exhaustive immune system. This review focuses on novel approaches to target viral life cycle and host immunity to achieve a functional cure. PMID:27190322

  5. Kidney Failure

    MedlinePlus

    ... if You Have Kidney Disease Kidney Failure Expand Dialysis Kidney Transplant Preparing for Kidney Failure Treatment Choosing Not to Treat with Dialysis or Transplant Paying for Kidney Failure Treatment Contact ...

  6. Acute hepatitis after amiodarone infusion

    PubMed Central

    Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco

    2015-01-01

    Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients. PMID:26488027

  7. The Pathology of Acute Liver Failure.

    PubMed

    Lefkowitch, Jay H

    2016-05-01

    Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies. PMID:27058243

  8. Epilepsy in Hemiplegic Cerebral Palsy Due to Perinatal Arterial Ischaemic Stroke

    ERIC Educational Resources Information Center

    Wanigasinghe, Jithangi; Reid, Susan M.; Mackay, Mark T.; Reddihough, Dinah S.; Harvey, A. Simon; Freeman, Jeremy L.

    2010-01-01

    Aim: The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS). Method: The study group comprised 63 participants (41 males, 22 females) from a population-based CP register whose brain imaging showed…

  9. CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury.

    PubMed

    Akahori, Hirokuni; Karmali, Vinit; Polavarapu, Rohini; Lyle, Alicia N; Weiss, Daiana; Shin, Eric; Husain, Ahsan; Naqvi, Nawazish; Van Dam, Richard; Habib, Anwer; Choi, Cheol Ung; King, Adrienne L; Pachura, Kimberly; Taylor, W Robert; Lefer, David J; Finn, Aloke V

    2015-01-01

    Macrophages are an essential component of the immune response to ischaemic injury and play an important role in promoting inflammation and its resolution, which is necessary for tissue repair. The type I transmembrane glycoprotein CD163 is exclusively expressed on macrophages, where it acts as a receptor for haemoglobin:haptoglobin complexes. An extracellular portion of CD163 circulates in the blood as a soluble protein, for which no physiological function has so far been described. Here we show that during ischaemia, soluble CD163 functions as a decoy receptor for TWEAK, a secreted pro-inflammatory cytokine of the tumour necrosis factor family, to regulate TWEAK-induced activation of canonical nuclear factor-κB (NF-κB) and Notch signalling necessary for myogenic progenitor cell proliferation. Mice with deletion of CD163 have transiently elevated levels of TWEAK, which stimulate muscle satellite cell proliferation and tissue regeneration in their ischaemic and non-ischaemic limbs. These results reveal a role for soluble CD163 in regulating muscle regeneration after ischaemic injury. PMID:26242746

  10. CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury

    PubMed Central

    Akahori, Hirokuni; Karmali, Vinit; Polavarapu, Rohini; Lyle, Alicia N.; Weiss, Daiana; Shin, Eric; Husain, Ahsan; Naqvi, Nawazish; Van Dam, Richard; Habib, Anwer; Choi, Cheol Ung; King, Adrienne L.; Pachura, Kimberly; Taylor, W. Robert; Lefer, David J.; Finn, Aloke V.

    2015-01-01

    Macrophages are an essential component of the immune response to ischaemic injury and play an important role in promoting inflammation and its resolution, which is necessary for tissue repair. The type I transmembrane glycoprotein CD163 is exclusively expressed on macrophages, where it acts as a receptor for haemoglobin:haptoglobin complexes. An extracellular portion of CD163 circulates in the blood as a soluble protein, for which no physiological function has so far been described. Here we show that during ischaemia, soluble CD163 functions as a decoy receptor for TWEAK, a secreted pro-inflammatory cytokine of the tumour necrosis factor family, to regulate TWEAK-induced activation of canonical nuclear factor-κB (NF-κB) and Notch signalling necessary for myogenic progenitor cell proliferation. Mice with deletion of CD163 have transiently elevated levels of TWEAK, which stimulate muscle satellite cell proliferation and tissue regeneration in their ischaemic and non-ischaemic limbs. These results reveal a role for soluble CD163 in regulating muscle regeneration after ischaemic injury. PMID:26242746

  11. The Course and Outcome of Unilateral Intracranial Arteriopathy in 79 Children with Ischaemic Stroke

    ERIC Educational Resources Information Center

    Braun, K. P. J.; Bulder, M. M. M.; Chabrier, S.; Kirkham, F. J.; Uiterwaal, C. S. P.; Tardieu, M.; Sebire, G.

    2009-01-01

    Arteriopathies are the commonest cause of arterial ischaemic stroke (AIS) in children. Repeated vascular imaging in children with AIS demonstrated the existence of a "transient cerebral arteriopathy" (TCA), characterized by lenticulostriate infarction due to non-progressive unilateral arterial disease affecting the supraclinoid internal carotid…

  12. Hepatitis B immunization in adolescents.

    PubMed

    Lawrence, M H; Goldstein, M A

    1995-10-01

    This article reviews the epidemiology of hepatitis B in the United States, previous vaccination strategy, and reasons for its failure and issues leading to the recommendation to vaccinate all adolescents. A review of specific hepatitis B virus risk behaviors of adolescents and barriers to vaccinating adolescents is covered. Strategies that favor successful completion of the immunization series are also examined. Hepatitis B infection is an important public health concern for adolescents. The previous vaccine strategy to immunize only individuals though to be at high risk was unsuccessful, especially because providers of care could not identify these individuals. Furthermore, many individuals thought not to be at high risk for infection were exposed through contacts which could not be identified. Challenges to immunization of adolescents include logistical issues, patient education, cost of the vaccine, and patient compliance. Several of these issues can be addressed by a school-based hepatitis B immunization program. The body of evidence and national policy is rapidly changing to support the recommendation that all adolescents receive the hepatitis B immunization series. The series would be most effective if administered during the middle-school years. A universal adolescent hepatitis B vaccination program would result in the most immediate health benefits and acceleration toward the eradication of hepatitis B in the United States. PMID:8580124

  13. Know HBV: What Every Asian and Pacific Islander Should Know About Hepatitis B and Liver Cancer

    MedlinePlus

    ... 2006 Asian Liver Center What every Asian and Pacific Islander should know about hepatitis B and liver ... or liver failure. » 1 in 10 Asian and Pacific Islanders is living with chronic (life-long) hepatitis ...

  14. Haemodynamic events and localised parenchymal changes following transcatheter arterial chemoembolisation for hepatic malignancy: interpretation of imaging findings

    PubMed Central

    Chung, J; Yu, J-S; Chung, J-J; Kim, J H; Kim, K W

    2010-01-01

    Following transcatheter arterial chemoembolisation (TACE), the appearances on CT or MR images are largely related to the chemical and ischaemic insults to the portal tract. Understanding the mechanism of TACE-induced changes is essential for radiologists in order to determine the therapeutic effect as well as to distinguish these changes from recurrent tumours. This pictorial review illustrates the haemodynamic and substantial parenchymal changes related to TACE for hepatic malignancy. PMID:19581309

  15. "Playboy bunny" sign of congestive heart failure.

    PubMed

    Hokama, Akira; Arakaki, Shingo; Shibata, Daisuke; Maeshiro, Tatsuji; Kinjo, Fukunori; Fujita, Jiro

    2011-11-01

    In emergency, ultrasound has been widely used as a noninvasive and effective examination to evaluate congestive heart failure. We highlight "Playboy Bunny" sign as a reliable marker and an important clue to the diagnosis of passive hepatic congestion, caused by congestive heart failure. PMID:22224133

  16. Hepatic Encephalopathy

    PubMed Central

    Bleibel, Wissam; Al-Osaimi, Abdullah M. S.

    2012-01-01

    Chronic liver disease and cirrhosis affect hundreds of millions of patients all over the world. The majority of patients with cirrhosis will eventually develop complications related to portal hypertension. One of these recurrent and difficult to treat complications is hepatic encephalopathy. Studies have indicated that overt hepatic encephalopathy affects 30 to 45% of patients with cirrhosis and a higher percentage may be affected by minimal degree of encephalopathy. All of these factors add to the impact of hepatic encephalopathy on the healthcare system and presents a major challenge to the gastroenterologist, hospitalist and primary care physician. PMID:23006457

  17. Hepatitis B

    MedlinePlus

    ... and Change Plan Wallet card for patients to record their alcohol use over a 4-week period as a way to monitor and reduce their drinking behavior. Glossary Definitions of terms commonly used with viral hepatitis and ...

  18. Hepatitis B

    MedlinePlus

    ... U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2014;161(1):58-66. PMID 24863637 ... Development Conference Statement: Management of hepatitis B. Ann Intern Med . 2009;150:104-10. PMID: 19124811 www. ...

  19. Acute Alcoholic Hepatitis: Therapy.

    PubMed

    Phillips, Paulina K; Lucey, Michael R

    2016-08-01

    Alcoholic hepatitis (AH) causes great morbidity and mortality in the United States and throughout the world. Advances in therapy have proven difficult. In part, this reflects challenges in diagnosis, including the distinction between AH and acute-on-chronic liver failure. Liver biopsy is the best method to clarify the cause in circumstances whereby conflicting clinical data confound the diagnosis. All treatment of AH begins with abstinence from alcohol. All patients with AH should be given sufficient nutrition. Prednisolone has become the principal agent for treating patients with severe AH. PMID:27373613

  20. In vivo bioimpedance measurement of healthy and ischaemic rat brain: implications for stroke imaging using electrical impedance tomography.

    PubMed

    Dowrick, T; Blochet, C; Holder, D

    2015-06-01

    In order to facilitate the imaging of haemorrhagic and ischaemic stroke using frequency difference electrical impedance tomography (EIT), impedance measurements of normal and ischaemic brain, and clotted blood during haemorrhage, were gathered using a four-terminal technique in an in vivo animal model, a first for ischaemic measurements. Differences of 5-10% in impedance were seen between the frequency spectrums of healthy and ischaemic brain, over the frequency range 0-3 kHz, while the spectrum of blood was predominately uniform. The implications of imaging blood/ischaemia in the brain using electrical impedance tomography are discussed, supporting the notion that it will be possible to differentiate stroke from haemorrhage. PMID:26006171

  1. Hepatitis C and liver transplantation

    NASA Astrophysics Data System (ADS)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

  2. Hepatitis B Foundation

    MedlinePlus

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 10 Other Languages . Resource Video See ...

  3. Hepatitis C - children

    MedlinePlus

    ... virus (HCV). Other common hepatitis virus infections include hepatitis A and hepatitis B . ... Elisofon SA, Jonas MMF. Viral hepatitis in children. In: Boyer TD, Manns MP, Sanyal AJ, eds. Zakim & Boyer's Hepatology: A Textbook of Liver Disease. 6th ed. ...

  4. Hepatitis A FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis A FAQs for the Public Recommend on Facebook ...

  5. Delta agent (Hepatitis D)

    MedlinePlus

    Hepatitis D virus ... Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make liver ... B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs ...

  6. Hepatitis C FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis C FAQs for the Public Recommend on Facebook ...

  7. Hepatitis B FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis B FAQs for the Public Recommend on Facebook ...

  8. Hepatitis A Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Hepatitis A Testing Share this page: Was this page ... HAV-Ab total; Anti-HAV Formal name: Viral Hepatitis A Antibody Related tests: Hepatitis B Testing ; Hepatitis ...

  9. Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis.

    PubMed Central

    Ehata, T; Omata, M; Chuang, W L; Yokosuka, O; Ito, Y; Hosoda, K; Ohto, M

    1993-01-01

    Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis, and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as an asymptomatic chronic carrier state. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes. To investigate the reason why the extreme immunological attack occurred in fulminant hepatitis and severe exacerbation patients, the entire precore and core region of hepatitis B virus DNA was sequenced in 24 subjects (5 fulminant, 10 severe fatal exacerbation, and 9 self-limited acute hepatitis patients). No significant change in the nucleotide sequence and deduced amino acid residue was noted in the nine self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of 16 amino acids (codon 84-99 from the start of the core gene) in all seven adr subtype infected fulminant and severe exacerbation patients was found. A different segment with clustering substitutions (codon 48-60) was also found in seven of eight adw subtype infected fulminant and severe exacerbation patients. Of the 15 patients, 2 lacked precore stop mutation which was previously reported to be associated with fulminant hepatitis. These data suggest that these core regions with mutations may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage. Images PMID:8450049

  10. Age at menarche, total mortality and mortality from ischaemic heart disease and stroke: the Adventist Health Study, 1976–88

    PubMed Central

    Jacobsen, B K; Oda, K; Knutsen, S F; Fraser, G E

    2009-01-01

    Background Little is known about the relationship between age at menarche and total mortality and mortality from ischaemic heart disease and stroke. Methods A cohort study of 19 462 Californian Seventh-Day Adventist women followed-up from 1976 to 1988. A total of 3313 deaths occurred during follow-up, of which 809 were due to ischaemic heart disease and 378 due to stroke. Results An early menarche was associated with increased total mortality (P-value for linear trend <0.001), ischaemic heart disease (P-value for linear trend = 0.01) and stroke (P-value for linear trend = 0.02) mortality. There were, however, also some indications of an increased ischaemic heart disease mortality in women aged 16–18 at menarche (5% of the women). When assessed as a linear relationship, a 1-year delay in menarche was associated with 4.5% (95% CI 2.3–6.7) lower total mortality. The association was stronger for ischaemic heart disease [6.0% (95% CI 1.2–10.6)] and stroke [8.6% (95% CI 1.6–15.1)] mortality. Conclusions The results suggest that there is a linear, inverse relationship between age at menarche and total mortality as well as with ischaemic heart disease and stroke mortality. PMID:19188208

  11. Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

    MedlinePlus

    ... Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 Table of ... Stomach ache Nausea Diarrhea No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will ...

  12. Liver steatosis associated with chronic hepatitis C.

    PubMed

    Irimia, Eugenia; Mogoantă, Laurentiu; Predescu, Ion Octavian; Efrem, Ion Cristian; Stănescu, Casiana; Streba, Letitia Adela Maria; Georgescu, Anca Meda

    2014-01-01

    Hepatic steatosis is a common histological finding in chronic liver diseases. One of the pathological entities in which hepatic steatosis has been found is chronic hepatitis C. The prevalence of steatosis in these patients ranges from 40% to 86%, with an average of 55%, which is two times higher than the steatosis seen in adults uninfected with hepatitis C. Many studies have shown that hepatic steatosis is a medical condition that may progress to steatohepatitis, progressive hepatic failure, hepatic cirrhosis, and is a risk factor for development of hepatocellular carcinoma. We have proposed to evaluate the severity of steatosis in patients with chronic hepatitis C and to correlate it with necroinflammatory processes and fibrosis. We included 259 patients diagnosed with chronic hepatitis C and proven histological steatosis. Age of patients with hepatic steatosis varied from 20 to 69 years. Most cases of steatosis associated with chronic hepatitis C (47.87%) were diagnosed in the age group 50-59 years. Of 259 patients, 141 (54.44%) were female and 118 (45.56%) male. Slight steatosis was identified in 130 cases (50.19%), moderate fatty changes were present in 54 (20.85%) patients and severe steatosis in 75 (28.96%) patients. The appearance of steatosis was macrovesicular and predominantly affected the third zone of the hepatic lobe. Most cases of hepatic steatosis were associated with necroinflammatory activity and low and moderate fibrosis. Cases of marked steatosis associated with intense activity accounted for about 10%, while marked steatosis was associated with severe fibrosis in less than 5% of cases. PMID:24969985

  13. Nutritional support during liver failure.

    PubMed

    Gecelter, G R; Comer, G M

    1995-07-01

    Critically ill patients in varying degrees of liver failure are catabolic and consequently require expeditious caloric support. Unique problems in this group of patients essentially revolve around the diagnosis and management of hepatic encephalopathy. From the overview provided in this text, it can be concluded that, only in overt hepatic coma, should all nitrogen products be withheld while precipitating causes are evaluated. Protein should be reintroduced as rapidly as possible to avoid the consequences of protein deprivation. Once the acute intercurrent illness has resolved, the cirrhotic patient returns to baseline energy and protein requirements indistinguishable from the population at large. PMID:7552976

  14. Hepatic Encephalopathy-the Old and the New.

    PubMed

    Kandiah, Prem A; Kumar, Gagan

    2016-07-01

    Hepatic encephalopathy occurs ubiquitously in all causes of advanced liver failure, however, its implications on mortality diverge and vary depending upon acuity and severity of liver failure. This associated mortality has decreased in subsets of liver failure over the last 20 years. Aside from liver transplantation, this improvement is not attributable to a single intervention but likely to a combination of practical advances in critical care management. Misconceptions surrounding many facets of hepatic encephalopathy exists due to heterogeneity in presentation, pathophysiology and outcome. This review is intended to highlight the important concepts, rationales and strategies for managing hepatic encephalopathy. PMID:27339673

  15. Cardiac arrhythmia and ischaemic events after combination chemotherapy for testicular cancer.

    PubMed

    Villani, F; Misrachi, D; Galimberti, M

    1994-11-01

    The aim of the present investigation was to evaluate the type and the incidence of cardiac arrhythmias and ischaemic events in patients suffering from testicular cancer and submitted to combination chemotherapy with cisplatin, bleomycin and vinblastine (PVB) or etoposide (PEB). Forty-seven patients took part in the study; 23 were treated with PVB and 24 with PEB. Holter monitoring was performed in each patient before chemotherapy and on the 1st, 2nd and 5th day of the first cycle of drug administration. The results showed that combination chemotherapy with PVB or PEB was accompanied by the appearance of, or an increase in, the incidence of supraventricular ectopic beats. No significant difference was found between the two groups. No significant conduction disturbances were recorded. These results show that combination chemotherapy with PVB or PEB, at least during the first cycle, has no significant ventricular arrhythmogenic or ischaemic potency in young people with no history of cardiac disease. PMID:7530660

  16. Risk factors for ischaemic heart disease in patients with dermatitis herpetiformis.

    PubMed Central

    Lear, J T; Neary, R H; Jones, P; Fitzgerald, D A; English, J S

    1997-01-01

    For reasons that are unclear, patients with dermatitis herpetiformis (DH) have a lower than expected mortality rate from ischaemic heart disease. We have compared risk factors for ischaemic heart disease (lipids, fibrinogen levels, smoking history and social class) in 29 DH patients and 57 controls matched for age and sex. Patients with DH had significantly lower cholesterol, triglycerides, apolipoprotein B and fibrinogen and higher HDL2; they also smoked less and were of higher social class. The mechanisms underlying these observations merit further investigation. Intestinal abnormalities or gluten-free diet may account for differences in lipid fractions, and the immunomodulatory properties of cigarette smoke may protect against the development of DH. PMID:9204017

  17. Standardized Minnesota coding of electrocardiographic findings for purposes of cooperative research on ischaemic heart disease.

    PubMed

    Misjavicene, I S; Glazunov, I S; Balavadze, M B; Reklaitene, R A

    1981-01-01

    For purposes of cooperative research on multifactorial prevention of ischaemic heart disease, a standardization system was elaborated in the USSR for classification of ECG findings according to the Minnesota code. The system includes instruction about the coding rules, experimental coding, analysis of faulty codings, and finally a control test consisting in encoding several series of 200 ECG findings each. For assessing the encoder's qualification the criterion was accepted of less than 20% cases of discordance with the standard code of "ischaemic" ECG changes. It was found that after the initial instructive course it was necessary to gain experience with encoding at least 1 000 ECG to qualify the candidate for the specified expert level. The necessity is emphasized of continual surveillance of the quality of ECG classification by the encoders in different centres, and the possibility of reaching a satisfactory level of unification is declared. PMID:7261597

  18. Diagnostic and prognostic value of cardiovascular magnetic resonance in non-ischaemic cardiomyopathies

    PubMed Central

    2012-01-01

    Cardiovascular Magnetic Resonance (CMR) is recognised as a valuable clinical tool which in a single scan setting can assess ventricular volumes and function, myocardial fibrosis, iron loading, flow quantification, tissue characterisation and myocardial perfusion imaging. The advent of CMR using extrinsic and intrinsic contrast-enhanced protocols for tissue characterisation have dramatically changed the non-invasive work-up of patients with suspected or known cardiomyopathy. Although the technique initially focused on the in vivo identification of myocardial necrosis through the late gadolinium enhancement (LGE) technique, recent work highlighted the ability of CMR to provide more detailed in vivo tissue characterisation to help establish a differential diagnosis of the underlying aetiology, to exclude an ischaemic substrate and to provide important prognostic markers. The potential application of CMR in the clinical approach of a patient with suspected non-ischaemic cardiomyopathy is discussed in this review. PMID:22857649

  19. Motor cortex excitability changes within 8 hours after ischaemic stroke may predict the functional outcome.

    PubMed

    Di Lazzaro, V; Oliviero, A; Profice, P; Saturno, E; Pilato, F; Tonali, P

    1999-06-01

    Motor evoked potentials after magnetic transcranial stimulation and the excitability of the motor cortex to increasing magnetic stimulus intensities were evaluated in six patients with hemiparesis after ischaemic stroke within 8 hours after stroke. The latencies of motor evoked potentials were normal in all patients. After stimulation of the ischaemic hemisphere we obtained responses comparable with the contralateral ones in two patients (mean NIH score 2 (SD 0)) and this group was completely asymptomatic after 15 days (NIH score 0). In four patients the excitability of the motor cortex involved by the ischaemia was reduced and magnetic motor threshold was higher than that of the spared motor cortex. This finding was associated with a poor motor recovery and the NIH score after 15 days was unchanged (NIH score 1.75 (SD 1.5)). The present data suggest that the evaluation of the excitability of motor cortex may offer a mean of predicting functional outcome following stroke. PMID:10461555

  20. Thrombolytics in acute ischaemic stroke: a guide to patient selection and optimum use.

    PubMed

    Adams, H P

    2000-02-01

    Intravenously administered alteplase (recombinant tissue plasminogen activator; rtPA) is the only medical treatment that has been approved for the management of acute ischaemic stroke. Although rtPA has demonstrated efficacy in improving outcomes of patients with a wide range of neurological impairments, it cannot be given with impunity. Thrombolytic therapy is associated with a considerable risk of intracranial bleeding that is likely to be catastrophic. Careful selection of patients to treat and intensive ancillary care are the keys for successful administration of rtPA. An algorithm for selection is based on the interval from the onset of stroke, history of recent medical illnesses or use of medications, findings of the medical and neurological examinations and the results of laboratory and brain imaging studies. Because rtPA must be given within 3 hours of onset of stroke, most patients cannot be treated. Thus, additional therapies are needed for treatment of patients with acute ischaemic stroke. PMID:18034518

  1. Ischaemic colitis in the experimental animal. II. Role of hypovolaemia in the production of the disease.

    PubMed Central

    Matthews, J G; Parks, T G

    1976-01-01

    Hypovolaemia alone did not lead to ischaemic colitis but when venesection was induced immediately after the acute ligation of the common colic artery large bowel ischaemia ensued. Similarly, hypovolaemia induced one month after two major blood vessels had been occluded led to ischaemic colitis. These findings suggest that states of low blood flow in the presence of previous arterial constriction or blockage may lead to enough reduction in mesenteric perfusion for intestinal ischaemia to develop. Using an electromagnetic flowmeter placed in the cranial mesenteric artery of the dog, it was shown that hypovolaemia may lead to 50-75% reduction in mesenteric blood flow without producing any significant change in the systemic blood pressure. Images Fig. 5 Fig. 6 Fig. 7 Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:976807

  2. Respiratory Failure

    MedlinePlus

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, such ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can't ...

  3. Kidney Failure

    MedlinePlus

    ... enough red blood cells. This is called kidney failure. If your kidneys fail, you need treatment to ... providers, family, and friends, most people with kidney failure can lead full and active lives. NIH: National ...

  4. Late onset Leber's optic neuropathy: a case confused with ischaemic optic neuropathy.

    PubMed Central

    Borruat, F X; Green, W T; Graham, E M; Sweeney, M G; Morgan-Hughes, J A; Sanders, M D

    1992-01-01

    A case is reported of a 63-year-old man with progressive central visual loss in one eye followed 11 months later by involvement of the fellow eye. A diagnosis of chronic ischaemic optic neuropathy was considered. However, despite a negative family history, the absence of electrocardiographic abnormalities, and minimal fundus changes a diagnosis of Leber's optic neuropathy was made on the basis of magnetic resonance imaging findings and the mitochondrial DNA mutation at base pair 11778. Images PMID:1420066

  5. Myocarditis along with acute ischaemic cerebellar, pontine and lacunar infarction following viper bite.

    PubMed

    Bhatt, Alok; Menon, Aravind Ajakumar; Bhat, Rama; Ramamoorthi, Kusugodlu

    2013-01-01

    Cerebrovascular complications are rare following viper bites. A 65-year-old man presented with loss of consciousness and developed haemiparesis following a viper bite. Coagulation parameters were severely deranged. MRI showed acute ischaemic infarction on the left side in the precentral and postcentral gyrus, hemipons and cerebellum. Troponin T was elevated and transient left bundle branch block was seen. The patient had a good outcome following treatment with Anti Snake Venom and supportive therapy. Possible mechanisms of infarction are discussed. PMID:24014571

  6. Hunting mimics and chameleons: diagnostic difficulties in atypical acute ischaemic stroke

    PubMed Central

    Plummer, Nicholas Russell; Hari-Bhaskar, Kemparaju

    2014-01-01

    The seemingly straightforward diagnosis of acute ischaemic stroke can be complicated by the presence of conditions presenting similarly to stroke, and atypical strokes presenting with confusing and non-classical signs. We present a diagnostic quest to disentangle the effects of a number of stroke mimics from those of an underlying bilateral cerebrovascular phenomena, where with appropriate treatment of the non-stroke conditions the patient was able to make a near complete neurological recovery. PMID:24891484

  7. [Outcomes of carotid endarterectomy performed in acute stage of ischaemic stroke].

    PubMed

    Shatravka, A V; Sokurenko, G Yu; Suvorov, S A; Rizakhanova, M R; Loginov, I A; Alekseeva, N V

    2016-01-01

    Recent years have witnessed several studies concerning optimal terms of performing carotid endarterectomy after endured acute cerebral circulation disorder (ACCD). However up to now there is no common opinion regarding feasibility and safety of performing carotid endarterectomy in the acute period of ischaemic stroke. The 2013 Russian National Guidelines on surgical management of diseases of extracranial arteries point to feasibility of performing carotid endarterectomy at terms within up to 2 weeks after endured ischaemic stroke (level B evidence). At the same time, there is no data concerning possibility of performing this type of operation in patients with neurological deficit scoring 4 points according to the Rankin scale. Analysing the results of 110 carotid endarterectomies performed in patients with haemodynamically meaningful stenosis of carotid arteries at terms varying from 2 to 14 days after the development of ipsilateral ACCD showed safety of the operation (the rate of postoperative cerebral circulation disorders amounted to 0.9% - 1 patient) and its efficacy in prevention of recurrent ischaemic complications, also determining regression of neurological symptomatology in the overwhelming majority - 86 (78%) patients. Despite the absence of recommendations on possibility to perform carotid endarterectomy in patients after endured ACCD with neurological deficiency scoring 4 points according to the modified Rankin scale we proved efficiency and feasibility of performing this type of operation in the cohort of patients concerned. There was not a single case of transformation of the ischaemic focus into haemorrhagic one. One patient developed fatal ACCD. During the follow up period (12 months) regression of neurological symptomatology was observed in 16 (66.7%) patients of 24 operated patients with baseline deficit of stage 4 according to the Rankin scale. PMID:27336345

  8. Myocarditis along with acute ischaemic cerebellar, pontine and lacunar infarction following viper bite

    PubMed Central

    Bhatt, Alok; Menon, Aravind Ajakumar; Bhat, Rama; Ramamoorthi, Kusugodlu

    2013-01-01

    Cerebrovascular complications are rare following viper bites. A 65-year-old man presented with loss of consciousness and developed haemiparesis following a viper bite. Coagulation parameters were severely deranged. MRI showed acute ischaemic infarction on the left side in the precentral and postcentral gyrus, hemipons and cerebellum. Troponin T was elevated and transient left bundle branch block was seen. The patient had a good outcome following treatment with Anti Snake Venom and supportive therapy. Possible mechanisms of infarction are discussed. PMID:24014571

  9. Effects of ischaemic training on local aerobic muscle performance in man.

    PubMed

    Sundberg, C J; Eiken, O; Nygren, A; Kaijser, L

    1993-05-01

    The aim of the study was to compare the effects of ischaemic and non-ischaemic training on aerobic performance. In 10 subjects, peak oxygen uptake (peak VO2) and time to fatigue (TTF) for one-legged exercise were measured before and after 4 weeks (4 times week-1) of one-legged training. Each training session started with one leg training for 45 min with 20% blood-flow reduction induced by local application of a supra-atmospheric external pressure of 50 mmHg (ischaemic leg; I-leg). We have previously shown that this decreases leg blood flow by about 20%. The contralateral leg (non-restricted-flow leg; N-leg), serving as a control, then trained with an identical power-output profile for 45 min but without flow restriction. In the I-leg the average training-induced increments in TTF and peak VO2 were 27 and 24%, respectively. In the N-trained leg TTF and peak-VO2 increased 10 and 14%, respectively. Both increments were significantly greater (P < 0.05) in the I-trained leg. Moreover, the performance increase in the I-trained leg was exaggerated (P < 0.05) in the ischaemic test condition, i.e. there was a specificity in the training response. In conclusion, ischaemia acts as an additive stimulus to training leading to an exaggerated increase in endurance and peak-VO2 compared to identical training without blood-flow restriction. The main explanation is probably an enhanced local adaptation in the I-trained leg. PMID:8333292

  10. Susceptible and protective associations of HLA DRB1*/DQB1* alleles and haplotypes with ischaemic stroke.

    PubMed

    Murali, V; Rathika, C; Ramgopal, S; Padma Malini, R; Arun Kumar, M J; Neethi Arasu, V; Jeyaram Illiayaraja, K; Balakrishnan, K

    2016-06-01

    Stroke has emerged as the second commonest cause of mortality worldwide and is a major public health problem. For the first time, we present here the association of human leucocyte antigen (HLA)-DRB1*/DQB1* alleles and haplotypes with ischaemic stroke in South Indian patients. Ischaemic stroke (IS) cases and controls were genotyped for HLA-DRB1*/DQB1* alleles by polymerase chain reaction sequence-specific primers (PCR-SSP) method. The frequencies of HLA class II alleles such as DRB1*04, DRB1*07, DRB1*11, DRB1*12, DRB1*13, DQB1*02 and DQB1*07 were high in IS patients than in the age- and gender-matched controls, suggesting that the individuals with these alleles are susceptible to ischaemic stroke in South India. The frequencies of alleles such as DRB1*03, DRB1*10, DRB1*14, DQB1*04 and DQB1*05 were less in IS cases than in the controls, suggesting a protective association. Haplotypes DRB1*04-DQB1*0301, DRB1*07-DQB1*02, DRB1*07-DQB1*0301, DRB1*11-DQB1*0301 and DRB1*13-DQB1*06 were found to be high in IS patients conferring susceptibility. The frequency of haplotype DRB1*10-DQB1*05 was high in controls conferring protection. IS-LVD and gender-stratified analysis too confirmed these susceptible and protective associations. Thus, HLA-DRB1*/DQB1* alleles and haplotypes strongly predispose South Indian population to ischaemic stroke. Further studies in different populations with large sample size or the meta-analysis are needed to explain the exact mechanism of associations of HLA gene(s) with IS. PMID:27105925

  11. Hepatitis C: Sex and Sexuality

    MedlinePlus

    ... with Hepatitis » Sex and Sexuality: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... hepatitis C virus through sex. Can you pass hepatitis C to a sex partner? Yes, but it ...

  12. Use of telemedicine to manage severe ischaemic strokes in a rural area with an elderly population.

    PubMed

    Richard, Sébastien; Lavandier, K; Zioueche, Y; Pelletier, S; Vezain, A; Ducrocq, X

    2014-05-01

    The rural district of the Meuse (East France) has a high number of elderly patients for whom prognosis of ischaemic strokes is poor with high-haemorrhagic transformation risk of intravenous tissue plasminogen activator (rt-PA). This disadvantage is made worse by the distances a patient has to travel to the nearest stroke unit. We set out to assess the effectiveness of a telestroke system implemented in this area. Between October 2010 and February 2012, data from each "tele-expertised" patient were collected. 53 patients were examined. Diagnosis of ischaemic stroke was confirmed in 43 cases (81 %), and intravenous rt-PA treatment performed in 21 cases (40 %). In the treated patient group, median age was 73 years, with 29 % of octogenarians. Baseline National Institutes of Health Stroke Scale (NIHSS) was 16, with 29 % ≥ 20. The median onset to needle time was 169 min, and the median door to needle time was 69 min. Intracranial haemorrhage occurred in 3 cases (14 %), and was symptomatic in two (10 %). At 3 months, median NIHSS was 6, 6 patients (29 %) presented a favourable outcome (modified Rankin scale ≤ 1) and 3 (14 %) had died. In rural areas, for elderly patients with severe ischaemic strokes, telemedicine appears to be a way of improving accessibility and benefits of rt-PA treatment. PMID:24277200

  13. Ischaemic and haemorrhagic brain lesions in newborns with seizures and normal Apgar scores.

    PubMed Central

    Mercuri, E.; Cowan, F.; Rutherford, M.; Acolet, D.; Pennock, J.; Dubowitz, L.

    1995-01-01

    Serial ultrasound scans and conventional and diffusion weighted magnetic resonance imaging (MRI) were performed on 16 neonates who presented with seizures. The Apgar scores were normal and subsequently no metabolic or infective cause could be found. The aim of the study was to evaluate the extent to which early sequential imaging can elucidate the cause of seizures in apparently neurologically normal infants. Fourteen of the infants had haemorrhagic or ischaemic lesions on MRI and these were detected by ultrasound scanning in 11. Early ultrasound scanning detected the haemorrhagic lesions but the ischaemic lesions were often not seen until the end of the first week of life. Early MRI, however, was able to detect all the ischaemic lesions. The evolution of the insult could be timed by using serial ultrasound scans and a combination of diffusion weighted and conventional MRI during the first week of life, confirming a perinatal insult even in the absence of fetal distress. Although the aetiology of these lesions remains obscure, serial ultrasound scans will detect the presence of cerebral lesions in neonates presenting with isolated seizures but additional MRI sequences will give better definition on type, site, and extent of the pathology. Images Figures 5 and 6 Figure 2 Figures 3 and 4 Figure 1 PMID:7583609

  14. Prognostic value of continuous electroencephalographic recording in full term infants with hypoxic ischaemic encephalopathy

    PubMed Central

    Wertheim, D; Mercuri, E; Faundez, Jc; Rutherford, M; Acolet, D; Dubowitz, L

    1994-01-01

    The prognostic value of early neonatal continuous electroencephalographic recordings in hypoxic ischaemic encephalopathy was evaluated. Thirty seven full term infants with hypoxic ischaemic encephalopathy were studied. The electroencephalogram (EEG) was recorded using four or eight channel Oxford Medilog recorders and was started as soon as possible after birth. The recordings were initially visually analysed and divided into four categories: three in relation to the grade of discontinuity of the background activity (continuous, discontinuous, and maximum depression) and an additional fourth category to include status epilepticus. The EEGs with discontinuous activity were then analysed by computer to obtain a more objective assessment of discontinuity. The results were related to neurological outcome. Continuous background activity was associated with a normal outcome in all but the three infants who had continuous, but asymmetrical EEGs and who developed contralateral hemiplegia. In the eight infants with discontinuous activity, the outcome appeared to be related to the grade of continuity and the presence of clear convulsions on the EEG. The 10 infants with maximum depression and status epilepticus had severe impairment. These preliminary results suggest that continuous recording of EEGs could be used routinely in term infants with hypoxic ischaemic encephalopathy. Computer analysis can improve the value of this technique, allowing the identification of infants who might benefit from early therapeutic intervention. PMID:7979486

  15. Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury

    PubMed Central

    Ito, Minako; Shichita, Takashi; Okada, Masahiro; Komine, Ritsuko; Noguchi, Yoshiko; Yoshimura, Akihiko; Morita, Rimpei

    2015-01-01

    Inflammasome activation has been implicated in various inflammatory diseases including post-ischaemic inflammation after stroke. Inflammasomes mediate activation of caspase-1, which subsequently induces secretion of pro-inflammatory cytokines such as IL-1β and IL-18, as well as a form of cell death called pyroptosis. In this study, we report that Bruton's tyrosine kinase (BTK) is an essential component of the NLRP3 inflammasome, in which BTK physically interacts with ASC and NLRP3. Inhibition of BTK by pharmacological or genetic means severely impairs activation of the NLRP3 inflammasome. The FDA-approved BTK inhibitor ibrutinib (PCI-32765) efficiently suppresses infarct volume growth and neurological damage in a brain ischaemia/reperfusion model in mice. Ibrutinib inhibits maturation of IL-1β by suppressing caspase-1 activation in infiltrating macrophages and neutrophils in the infarcted area of ischaemic brain. Our study indicates that BTK is essential for NLRP3 inflammasome activation and could be a potent therapeutic target in ischaemic stroke. PMID:26059659

  16. Regulation of pyruvate dehydrogenase activity and glucose metabolism in post-ischaemic myocardium.

    PubMed

    Schöder, H; Knight, R J; Kofoed, K F; Schelbert, H R; Buxton, D B

    1998-02-27

    Pyruvate dehydrogenase (PDH) is regulated both by covalent modification and through modulation of the active enzyme by metabolites. In the isolated heart, post-ischaemic inhibition of PDH, leading to uncoupling of glycolysis and glucose oxidation and a decrease in cardiac efficiency, has been described. In vivo, post-ischaemic reperfusion leads to metabolic abnormalities consistent with PDH inhibition, but the effects of ischaemia/reperfusion on PDH are not well characterized. We therefore investigated PDH regulation following transient ischaemia in vivo. In 33 open-chest dogs, the left anterior descending (LAD) was occluded for 20 min followed by 4 h reperfusion. In 17 dogs, dichloroacetate (DCA) was injected prior to reperfusion, while 16 dogs served as controls. In dogs without DCA, glucose oxidation and lactate uptake were lower in reperfused than in remote tissue, suggesting reduced flux through PDH. However, percent active and total PDH measured in myocardial biopsies were similar in both territories, excluding covalent enzyme modification or loss of functional enzyme. DCA activated PDH activity similarly in both regions and abolished differences in glucose oxidation and lactate uptake. Thus, decreased PDH flux in reperfused myocardium does not result from covalent modification or loss of total enzyme activity, but more likely from metabolite inhibition of the active enzyme. DCA leads to essentially complete activation of PDH, increases overall glucose utilization and abolishes post-ischaemic inhibition of glucose oxidation. PMID:9545535

  17. Remote ischaemic conditioning-a new paradigm of self-protection in the brain.

    PubMed

    Hess, David C; Blauenfeldt, Rolf A; Andersen, Grethe; Hougaard, Kristina D; Hoda, Md Nasrul; Ding, Yuchuan; Ji, Xunming

    2015-12-01

    Remote ischaemic conditioning (RIC) triggers endogenous protective pathways in distant organs such as the kidney, heart and brain, and represents an exciting new paradigm in neuroprotection. RIC involves repetitive inflation and deflation of a blood pressure cuff on the limb, and is safe and feasible. The exact mechanism of signal transmission from the periphery to the brain is not known, but both humoral factors and an intact nervous system seem to have critical roles. Early-phase clinical trials have already been conducted to test RIC in the prehospital setting in acute ischaemic stroke, and in subarachnoid haemorrhage for the prevention of delayed cerebral ischaemia. Furthermore, two small randomized clinical trials in patients with symptomatic intracranial atherosclerosis have shown that RIC can reduce recurrence of stroke and have neuroprotective activity. RIC represents a highly practical and translatable therapy for acute, subacute, and chronic neurological diseases with an ischaemic or inflammatory basis. In this Review, we consider the principles and mechanisms of RIC, evidence from preclinical models and clinical trials that RIC is beneficial in neurological disease, and how the procedure might be used in the future in disorders such as vascular cognitive impairment and traumatic brain injury. PMID:26585977

  18. Hepatitis C

    PubMed Central

    Mehta, Bharti; Kumar Dharma, Vijay; Chawla, Sumit; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Hepatitis C Virus (HCV) infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following acute infection, 20% of people eliminate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of which approximately 20% will eventually develop liver cirrhosis and 1–5% will develop liver cancer. About 150 million people are chronically infected with HCV, and more than 350 000 people die every year from hepatitis C related liver diseases. The economic cost of hepatitis C is significant both to the individual and to the society. In the United States the average lifetime cost of the disease was estimated at $33 407 USD with the cost of a liver transplant approximately $200 000 USD. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB £7000 in the UK for a treatment course, is unaffordable in developing countries. Hepatitis C, not only brings down the quality of the life of individuals but also affect progress of the nation by adding financial burden. If we prevent the disease from occurring or find a perfect cure of the disease, in form of a prophylactic or therapeutic vaccine, it will be a boon to not only to the individual but to the nation as a whole. PMID:24165512

  19. Hepatitis E vaccines: progress and prospects.

    PubMed

    Worm, Harald Claus; Wirnsberger, Gerhard

    2004-01-01

    Hepatitis E accounts for the major part of enterally transmitted non-A, non-B hepatitis worldwide. Its agent, the hepatitis E virus (HEV), is a small, single-stranded RNA virus. Only one serotype of HEV is recognised. Infection results in protective immunity with long-lived neutralising antibodies. In developing countries with poor sanitary conditions and high population density, hepatitis E causes water-borne epidemics with substantial mortality rates in pregnant women. In addition, more than 50% of cases of acute hepatic failure and sporadic acute hepatitis are due to hepatitis E. The overall prevalence rates of antibodies to the HEV in populations native to these areas rarely exceed 25%. Hence, many individuals remain susceptible to hepatitis E infection, making hepatitis E an important public health concern. In this context, the development of an HEV vaccine is warranted. Because HEV does not grow adequately in cell cultures the development of a vaccine based on inactivated or attenuated whole-virus particles is not feasible. HEV vaccines currently under study are based on recombinant proteins derived from immunogenic parts of the HEV capsid gene. Other approaches such as DNA-based vaccines or transgenic tomatoes have also been developed. Several recombinant protein-based vaccines elicited neutralising antibodies and protective immunity in vaccinated non-human primates. One such vaccine has passed phase I trial and is currently under further evaluation in field trials. Even so, several questions remain to be answered before vaccination programmes could be implemented. PMID:15233590

  20. Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial

    PubMed Central

    Jacobsen, Rikke Kart; Toft, Ulla; Aadahl, Mette; Glümer, Charlotte; Pisinger, Charlotta

    2014-01-01

    Objective To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. Design Randomised controlled community based trial. Setting Suburbs of Copenhagen, Denmark Participants 59 616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n=11 629) and a control group (n=47 987). Intervention The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening. Main outcome measures The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality. Results 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58 308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58 940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the

  1. Hepatic encephalopathy.

    PubMed

    Córdoba, Juan; Mínguez, Beatriz

    2008-02-01

    Hepatic encephalopathy is a severe complication of cirrhosis that is related to the effects of ammonia. Analysis of interorgan ammonia trafficking has identified an important role of skeletal muscle in ammonia removal and has highlighted the importance of the nutritional status. Ammonia causes neurotransmitter abnormalities and induces injury to astrocytes that is partially mediated by oxidative stress. These disturbances lead to astrocyte swelling and brain edema, which appear to be involved in the pathogenesis of neurological manifestations. Inflammatory mediators worsen brain disturbances. New methods for assessing hepatic encephalopathy include clinical scales, neuropsychological tests, imaging of portal-systemic circulation, and magnetic resonance of the brain. Reappraisal of current therapy indicates the need for performing placebo-controlled trials and the lack of evidence for administering diets with restricted protein content. Liver transplant should be considered in selected patients with hepatic encephalopathy. Future prospects include new drugs that decrease plasma ammonia, measures to reduce brain edema, and liver-support devices. PMID:18293278

  2. [Hepatic encephalopathy].

    PubMed

    Córdoba, Juan; Mur, Rafael Esteban

    2014-07-01

    Hepatic encephalopathy (EH) is a severe complication of hepatic cirrhosis that is characterized by multiple neuropsychiatric manifestations. EH is usually triggered by a precipitating factor and occurs in patients with severely impaired hepatic function. Minimal EH is characterized by minor cognitive impairments that are difficult to specify but represent a risk for the patients. The primary pathophysiological mechanism of EH is considered to be an increase in blood ammonia with an impairment in the patency of the blood-brainbarrier and its metabolism to glutamine in astrocytes. The diagnosis is clinical and neuroimaging techniques can be complementary. The diagnosis of minimal EH requires specific neurocognitive tests. The clinical evaluation should be directed towards identifying the trigger. Nonabsorbable disaccharides and rifaximin constitute the treatment of choice, along with prophylaxis for new episodes. PMID:25087716

  3. Management of chronic hepatitis C: Consensus guidelines

    PubMed Central

    Sherman, Morris; Shafran, Stephen; Burak, Kelly; Doucette, Karen; Wong, Winnie; Girgrah, Nigel; Yoshida, Eric; Renner, Eberhard; Wong, Philip; Deschênes, Marc

    2007-01-01

    Since the last consensus conference on the management of chronic viral hepatitis, a number of studies looking at modifications of the standard course of treatment have been published. These changes have been sufficiently substantive to warrant review to determine whether any changes in the recommended treatment algorithms are needed. A consensus development conference was held in January 2007, and the present document highlights the results of the presentations and discussion about these issues. It reviews the epidemiology of hepatitis C in Canada, treatment of acute hepatitis C and new algorithms in chronic hepatitis C, including retreatment of previous treatment failures. In addition, sections on management of hepatitis C in special populations have been updated. There is also a section on the use of hematopoietic growth factors to help manage patients on therapy. The document should be read in conjunction with the previous document to identify changes. Some recommendations made in the previous document remain and are not discussed here. PMID:17568824

  4. Hepatitis A

    MedlinePlus

    ... Low-grade fever Nausea and vomiting Pale or clay-colored stools Yellow skin (jaundice) ... The virus does not remain in the body after the infection is gone. Most people with hepatitis A recover within 3 months. Nearly all people get better within 6 months. There ...

  5. Autoimmune Hepatitis

    MedlinePlus

    ... provider will closely monitor and manage any side effects that may occur, as high doses of prednisone are often prescribed to treat autoimmune hepatitis. Immune system suppressors. Medications that suppress the immune system prevent the body from making autoantibodies and block the immune reaction ...

  6. Hepatitis A

    MedlinePlus

    ... Advisory Board Sponsors Sponsorship Opporunities Spread the Word Shop AAP Find a Pediatrician ... Body Hepatitis means “inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There ...

  7. Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors

    PubMed Central

    Ali, Syed Asad; Donahue, Rafe M.J.; Qureshi, Huma; Vermund, Sten H.

    2009-01-01

    Summary Background Pakistan carries one of the world’s highest burdens of chronic hepatitis and mortality due to liver failure and hepatocellular carcinomas. However, national level estimates of the prevalence of and risk factors for hepatitis B and hepatitis C are currently not available. Methods We reviewed the medical and public health literature over a 13-year period ([Au?1] 1994–September 2007) to estimate the prevalence of active hepatitis B and chronic hepatitis C in Pakistan, analyzing data separately for the general and high-risk populations and for each of the four provinces. We included 84 publications with 139 studies (42 studies had two or more sub-studies). Results Methodological differences in studies made it inappropriate to conduct a formal meta-analysis to determine accurate national prevalence estimates, but we estimated the likely range of prevalence in different population sub-groups. A weighted average of hepatitis B antigen prevalence in pediatric populations was 2.4% (range 1.7–5.5%) and for hepatitis C antibody was 2.1% (range 0.4–5.4%). A weighted average of hepatitis B antigen prevalence among healthy adults (blood donors and non-donors) was 2.4% (range 1.4–11.0%) and for hepatitis C antibody was 3.0% (range 0.3–31.9% [Au?2]). Rates in the high-risk subgroups were far higher. Conclusions Data suggest a moderate to high prevalence of hepatitis B and hepatitis C in different areas of Pakistan. The published literature on the modes of transmission of hepatitis B and hepatitis C in Pakistan implicate contaminated needle use in medical care and drug abuse and unsafe blood and blood product transfusion as the major causal factors. PMID:18835208

  8. Natural variability of transient myocardial ischaemia during daily life: an obstacle when assessing efficacy of anti-ischaemic agents?

    PubMed Central

    Patel, D. J.; Mulcahy, D.; Norrie, J.; Wright, C.; Clarke, D.; Ford, I.; Fox, K. M.

    1996-01-01

    OBJECTIVE: To assess the degree of variability of transient myocardial ischaemia during daily life in patients with coronary artery disease, which could confound the interpretation of trials of the therapeutic effects of anti-ischaemic agents. DESIGN: Prospective method evaluation. SETTING: Tertiary referral centre, outpatient clinic. PATIENTS: Patients with stable angina, confirmed coronary artery disease, and a positive treadmill exercise test for ischaemia. Patients were not preselected on the basis of prior documented transient ischaemia during ambulatory ST segment monitoring. INTERVENTIONS: A simulated drug-study with 4 monitoring phases in 16 subjects. To minimise variability in ischaemic activity, patients underwent weekly 48 hour ambulatory ST segment monitoring outside hospital off all prophylactic therapy on the same weekdays for 4 weeks. MAIN OUTCOME MEASURE: Variability in the frequency and duration of transient myocardial ischaemia. RESULTS: There was marked variability in both ischaemic activity and mean duration of ischaemia in patients with confirmed ischaemia, the greatest degree of variability being between patients and from day to day within weeks within patients, with a further contribution to variability being noted between fortnights within patients. CONCLUSIONS: Despite assessment off all therapy and an adequate period of monitoring (48 hours) with small intervals between monitoring periods (5 days), marked variability in ischaemic activity was noted, and regression towards the mean was clearly shown. Ambulatory ST segment monitoring outside hospital is not a reliable method for assessing the therapeutic effects of anti-ischaemic agents. PMID:9014794

  9. Productive Failure

    ERIC Educational Resources Information Center

    Kapur, Manu

    2008-01-01

    This study demonstrates an existence proof for "productive failure": engaging students in solving complex, ill-structured problems without the provision of support structures can be a productive exercise in failure. In a computer-supported collaborative learning setting, eleventh-grade science students were randomly assigned to one of two…

  10. Design, methodology and baseline characteristics of Tai Chi and its protective effect against ischaemic stroke risk in an elderly community population with risk factors for ischaemic stroke: a randomised controlled trial

    PubMed Central

    Zheng, Guohua; Zheng, Xin; Li, Junzhe; Duan, Tingjin; Qi, Dalu; Ling, Kun; He, Jian; Chen, Lidian

    2015-01-01

    Introduction Controlling risk factors with regular exercise is effective and cost-effective for the primary prevention of ischaemic stroke. As a traditional Chinese form of exercise, Tai Chi might be beneficial in decreasing ischaemic stroke, but the evidence remains insufficient. We hypothesise that elderly community adults with risk factors for ischaemic stroke will decrease their ischaemic stroke risk by improving cerebral haemodynamic parameters, cardiopulmonary function, motor function, plasma risk indices, physical parameters or psychological outcomes after receiving 12 weeks of regular Tai Chi training compared with those who maintained their original physical activities. Therefore, we designed a randomised controlled trial that will systematically evaluate the protective effects of Tai Chi exercise on ischaemic stroke risk in an elderly community population with risk factors for ischaemic stroke. Methods and analysis A total of 170 eligible participants were randomly allocated into either the Tai Chi training group or the usual physical activity group. This paper reports on the design, intervention development and baseline characteristics of the participants. There were no significant differences between comparison groups in demographic characteristics or the baseline data of primary or secondary outcomes. Participants in the Tai Chi training group will receive 12 weeks of Tai Chi training with a frequency of 5 days/week and 60 min/day, while those in the usual physical activities group will maintain their original activities. Primary and secondary outcomes will be measured at the 12-week and 24-week follow-ups. Ethics and dissemination Ethical approval has been obtained from the Medical Ethics Committee of The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine (number 2013-020-02). The findings of this study will be communicated to healthcare professionals, participants and the public through peer

  11. Efficient therapy of ischaemic lesions with VEGF121-fibrin in an animal model of systemic sclerosis

    PubMed Central

    Allipour Birgani, Shadab; Mailänder, Marion; Wasle, Ines; Dietrich, Hermann; Gruber, Johann; Distler, Oliver; Sgonc, Roswitha

    2016-01-01

    Background In systemic sclerosis (SSc), chronic and uncontrolled overexpression of vascular endothelial growth factor (VEGF) results in chaotic vessels, and intractable fingertip ulcers. Vice versa, VEGF is a potent mediator of angiogenesis if temporally and spatially controlled. We have addressed this therapeutic dilemma in SSc by a novel approach using a VEGF121 variant that covalently binds to fibrin and gets released on demand by cellular enzymatic activity. Using University of California at Davis (UCD)-206 chickens, we tested the hypothesis that cell-demanded release of fibrin-bound VEGF121 leads to the formation of stable blood vessels, and clinical improvement of ischaemic lesions. Methods Ninety-one early and late ischaemic comb and neck skin lesions of UCD-206 chickens were treated locally with VEGF121-fibrin, fibrin alone, or left untreated. After 1 week of treatment the clinical outcome was assessed. Angiogenesis was studied by immunofluorescence staining of vascular markers quantitatively analysed using TissueQuest. Results Overall, 79.3% of the lesions treated with VEGF121-fibrin showed clinical improvement, whereas 71.0% of fibrin treated controls, and 93.1% of untreated lesions deteriorated. This was accompanied by significantly increased growth of stable microvessels, upregulation of the proangiogenic VEGFR-2 and its regulator TAL-1, and increase of endogenous endothelial VEGF expression. Conclusions Our findings in the avian model of SSc suggest that cell-demanded release of VEGF121 from fibrin matrix induces controlled angiogenesis by differential regulation of VEGFR-1 and VEGFR-2 expression, shifting the balance towards the proangiogenic VEGFR-2. The study shows the potential of covalently conjugated VEGF-fibrin matrices for the therapy of ischaemic lesions such as fingertip ulcers. PMID:26362758

  12. Oxidative Stress and C-Reactive Protein in Patients with Cerebrovascular Accident (Ischaemic Stroke)

    PubMed Central

    Thanoon, Imad A-J; Abdul-Jabbar, Hilmy AS; Taha, Dhia A

    2012-01-01

    Objectives: This study aimed to investigate the presence of oxidative stress and inflammation in ischaemic stroke patients by measuring malondialdehyde (MDA), total antioxidant status (TAS), and highly-sensitivity C-reactive protein (hsCRP) in the early post-ischaemic period, and to determine the role of Ginkgo biloba therapy in correcting the markers of oxidative stress and inflammation. Methods: This study was conducted at Ibn Seena Hospital, Mosul City, Iraq and included 31 cerebrovascular accident (CVA) patients and 30 healthy controls. Ischaemic stroke patients were divided into two groups: group I (n = 15) received conventional therapy; group II (n = 16) received conventional therapy with G. biloba (1500 mg/day) for 30 days. Blood samples were obtained from patients and controls before treatment and assays done of serum levels of MDA, TAS, and hsCRP. For CVA patients, a post-treatment blood sample was taken and the same parameters reassessed. Results: Compared with the controls, patients’ serum levels of MDA, and hsCRP were significantly higher (P ≤0.001) and TAS significantly lower. Group I and II patients reported a significant reduction in serum levels of MDA and hsCRP and a significant increase in serum levels of TAS, in comparison with pre-treatment levels. There was no significant difference (P = 0.19) in serum MDA levels between groups I and II, whereas, serum TAS levels were significantly higher (P ≤0.01) and hsCRP significantly lower (P ≤0.01) in group II. Conclusion: Acute stroke is associated with oxidative stress and inflammatory response in the early period. G. biloba plays a potential role in reducing oxidative damage and inflammatory response. PMID:22548139

  13. [Pathogenetic justification of statin use in ischaemic stroke prevention according to inflammatory theory in development of atherosclerosis].

    PubMed

    Kotlęga, Dariusz; Ciećwież, Sylwester; Turowska-Kowalska, Jolanta; Nowacki, Przemysław

    2012-01-01

    There is an inflammatory component in the pathogenesis of ischaemic stroke, which plays an important role in inducing atherothrombotic and embolic stroke. Statins, HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme A) reductase inhibitors are widely used in the primary and secondary prevention of ischaemic stroke. It has been proved that beyond their main effect on inhibition of endogenous cholesterol, they also modify the inflammatory process. Additional benefits from the use of statins result from their effect on the immune system. Increased risk of recurrent vascular episodes and risk of death after statin withdrawal in patients with vascular disorders is connected with termination of the anti-inflammatory effect of these drugs. The authors highlight that because of the anti-inflammatory effect of statins it is reasonable to use them in all patients at risk of ischaemic stroke, including those with atrial fibrillation. PMID:22581600

  14. [Hepatic encephalopathy].

    PubMed

    Jacques, Jérémie; Carrier, Paul; Debette-Gratien, Marilyne; Sobesky, Rodolphe; Loustaud-Ratti, Véronique

    2016-01-01

    Hepatic encephalopathy is a severe complication of liver cirrhosis and is an important therapeutic challenge, with a social and economic issue. If, now, the pathophysiology is not totally understood (main role of ammonia, but a better understanding of cerebral mechanisms), the clinical presentation is well-known. Some treatments are useful (disaccharides, treatment of the trigger) but their efficiency is limited. Nevertheless, the emergence of new treatments, such as non-absorbable antibiotics (rifaximin essentially), is an interesting therapeutic tool. PMID:26597584

  15. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  16. Hepatitis A - children

    MedlinePlus

    ... have the virus and do not practice good hygiene. Other common hepatitis virus infections include hepatitis B ... where diapers are changed to ensure that proper hygiene is followed. If your child gets hepatitis A, ...

  17. Hepatitis B virus (image)

    MedlinePlus

    Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

  18. Preventing hepatitis A

    MedlinePlus

    Hepatitis A is inflammation (irritation and swelling) of the liver caused by the hepatitis A virus. You can take several steps to ... reduce your risk of spreading or catching the hepatitis A virus: Always wash your hands thoroughly after ...

  19. What Is Hepatitis?

    MedlinePlus

    ... Twitter Facebook Google + iTunes Play Store What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Know hepatitis - Act now Event notice Key ...

  20. Ischaemic necrosis of the tongue as a rare complication of cardiogenic shock.

    PubMed

    Hulstaert, E; Roggeman, E; Beeckman, A-S; Moerman, M; Vanderstraeten, E; Rasquin, K; Monsaert, E; Baert, D; Dewint, P; Burvenich, P; Van Steenkiste, C

    2015-12-01

    Ischaemic necrosis of the tongue is an unusual clinical finding. In most cases it is associated with vasculitis, particularly giant cell arteritis (GCA). Other causes include profound cardiogenic shock. We report a case of tongue necrosis in an 81-year-old Caucasian woman. The patient was admitted to the intensive care unit (ICU) for cardiogenic shock. Swelling of the tongue was reported before intubation and evolved into tongue ischaemia and necrosis of the tip of the tongue. After surgical debridement the patient recovered. To our knowledge, this is the second report of a patient surviving tongue necrosis resulting from cardiogenic shock. PMID:26790554

  1. Non-ketotic hyperglycaemia hemichorea-hemiballismus and acute ischaemic stroke.

    PubMed

    Carrion, Diego M; Carrion, Andres F

    2013-01-01

    Here we describe a patient with a rare movement disorder, hemichorea-hemiballismus, which is described as a complication of non-ketotic hyperglycaemia. This complication may be seen in individuals with poorly controlled long-standing diabetes mellitus. Proper diagnosis is established with CT and MRI of the brain, which typically show classic findings in the basal ganglia. Treatment focuses on improvement of glycaemic control and usually results in rapid resolution of the movement disorder. Nevertheless, recurrent episodes of hemichorea-hemiballismus, and even more ominous complications such as ischaemic stroke may occur. PMID:23470671

  2. Persistent trigeminal artery as a rare cause of ischaemic lesion and migraine-like headache.

    PubMed

    Uhlig, S; Kurzepa, J; Czekajska-Chehab, E; Staśkiewicz, G; Polar, M K; Nastaj, M; Stochmal, E; Drop, A

    2015-01-01

    The persistent trigeminal artery (PTA) is a rare remnant of the embryonic intracranial circulatory system that forms a carotid-vertebrobasilar anastomosis. In most cases PTA does not have clear clinical implications. However, some authors report the association of PTA occurrence with vertigo, dizziness and nerve palsy, resulting in diplopia, strabismus or trigeminal neuralgia in patients. In rare cases it may also be related to posterior cerebral circulation strokes. This work reports the case of a female patient who presented with migraine-like headache and an ischaemic lesion in the left temporal lobe in association with PTA. PMID:25792408

  3. Acute ischaemic stroke during short-term travel to high altitude.

    PubMed

    Chan, T; Wong, Winnie W Y; Chan, Jonathan K C; Ma, Johnny K F; Mak, Henry K F

    2012-02-01

    This is a case report of a young healthy adult who had acute cerebral infarcts after a short-term visit to high-altitude area. He developed acute onset of right-sided limb weakness and right hemianopia a few hours after arrival at an altitude of 3600 m by train. He was initially treated for high-altitude cerebral oedema but later computed tomography and magnetic resonance imaging confirmed ischaemic infarcts in the medial left occipital lobe and left thalamus. Subsequent investigations, including laboratory tests and imaging including an echocardiogram, revealed no culpable predisposing factors. PMID:22302915

  4. Occupational exposure to particulate air pollution and mortality due to ischaemic heart disease and cerebrovascular disease

    PubMed Central

    Torén, Kjell; Bergdahl, Ingvar A; Nilsson, Tohr; Järvholm, Bengt

    2007-01-01

    Objectives A growing number of epidemiological studies are showing that ambient exposure to particulate matter air pollution is a risk factor for cardiovascular disease; however, whether occupational exposure increases this risk is not clear. The aim of the present study was to examine whether occupational exposure to particulate air pollution increases the risk for ischaemic heart disease and cerebrovascular disease. Methods The study population was a cohort of 176 309 occupationally exposed Swedish male construction workers and 71 778 unexposed male construction workers. The definition of exposure to inorganic dust (asbestos, man‐made mineral fibres, dust from cement, concrete and quartz), wood dust, fumes (metal fumes, asphalt fumes and diesel exhaust) and gases and irritants (organic solvents and reactive chemicals) was based on a job‐exposure matrix with focus on exposure in the mid‐1970s. The cohort was followed from 1971 to 2002 with regard to mortality to ischaemic heart disease and cerebrovascular disease. Relative risks (RR) were obtained by the person‐years method and from Poisson regression models adjusting for baseline values of blood pressure, body mass index, age and smoking habits. Results Any occupational particulate air pollution was associated with an increased risk for ischemic heart disease (RR 1.13, 95% CI 1.07 to 1.19), but there was no increased risk for cerebrovascular disease (RR 0.97, 95% CI 0.88 to 1.07). There was an increased risk for ischaemic heart disease and exposure to inorganic dust (RR 1.07, 95% CI 1.03 to 1.12) and exposure to fumes (RR 1.05, 95% CI 1.00 to 1.10), especially diesel exhaust (RR 1.18, 95% CI 1.13 to 1.24). There was no significantly increased risk for cerebrovascular disease and exposure to inorganic dust, fumes or wood dust. Conclusions Occupational exposure to particulate air pollution, especially diesel exhaust, among construction workers increases the risk for ischaemic heart disease. PMID

  5. Hepatitis C

    MedlinePlus

    ... damage that may lead to liver failure or liver cancer . Your provider will monitor you by checking liver ... be recommended for people who develop cirrhosis and liver cancer. Your provider can tell you more about liver ...

  6. Hepatitis B

    MedlinePlus

    ... HBV, which lasts a lifetime. Chronic HBV can lead to cirrhosis (scarring of the liver), liver failure, or liver cancer. There is a vaccine for HBV. It requires three shots. All babies should get the vaccine, but older ...

  7. Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts

    PubMed Central

    Palmer, Tom M; Nordestgaard, Børge G; Benn, Marianne; Tybjærg-Hansen, Anne; Davey Smith, George; Lawlor, Debbie A

    2013-01-01

    Objectives To assess the associations between both uric acid levels and hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore the potentially confounding role of body mass index. Design Mendelian randomisation analysis, using variation at specific genes (SLC2A9 (rs7442295) as an instrument for uric acid; and FTO (rs9939609), MC4R (rs17782313), and TMEM18 (rs6548238) for body mass index). Setting Two large, prospective cohort studies in Denmark. Participants We measured levels of uric acid and related covariables in 58 072 participants from the Copenhagen General Population Study and 10 602 from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic heart disease, respectively. Main outcome Blood pressure and prospectively assessed ischaemic heart disease. Results Estimates confirmed known observational associations between plasma uric acid and hyperuricaemia with risk of ischaemic heart disease and diastolic and systolic blood pressure. However, when using genotypic instruments for uric acid and hyperuricaemia, we saw no evidence for causal associations between uric acid, ischaemic heart disease, and blood pressure. We used genetic instruments to investigate body mass index as a potentially confounding factor in observational associations, and saw a causal effect on uric acid levels. Every four unit increase of body mass index saw a rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%). Conclusion By contrast with observational findings, there is no strong evidence for causal associations between uric acid and ischaemic heart disease or blood pressure. However, evidence supports a causal effect between body mass index and uric acid level and hyperuricaemia. This finding strongly suggests body mass index as a confounder in observational associations, and suggests a role for elevated body mass index or obesity in the development of

  8. NMDA receptors in hyperammonemia and hepatic encephalopathy.

    PubMed

    Llansola, Marta; Rodrigo, Regina; Monfort, Pilar; Montoliu, Carmina; Kosenko, Elena; Cauli, Omar; Piedrafita, Blanca; El Mlili, Nisrin; Felipo, Vicente

    2007-12-01

    The NMDA type of glutamate receptors modulates learning and memory. Excessive activation of NMDA receptors leads to neuronal degeneration and death. Hyperammonemia and liver failure alter the function of NMDA receptors and of some associated signal transduction pathways. The alterations are different in acute and chronic hyperammonemia and liver failure. Acute intoxication with large doses of ammonia (and probably acute liver failure) leads to excessive NMDA receptors activation, which is responsible for ammonia-induced death. In contrast, chronic hyperammonemia induces adaptive responses resulting in impairment of signal transduction associated to NMDA receptors. The function of the glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic liver failure or hyperammonemia and in homogenates from brains of patients died in hepatic encephalopathy. The impairment of this pathway leads to reduced cGMP and contributes to impaired cognitive function in hepatic encephalopathy. Learning ability is reduced in animal models of chronic liver failure and hyperammonemia and is restored by pharmacological manipulation of brain cGMP by administering phosphodiesterase inhibitors (zaprinast or sildenafil) or cGMP itself. NMDA receptors are therefore involved both in death induced by acute ammonia toxicity (and likely by acute liver failure) and in cognitive impairment in hepatic encephalopathy. PMID:17701332

  9. CT analysis of the upper end of the femur: The asterisk sign and ischaemic bone necrosis of the femoral head

    SciTech Connect

    Dihlmann, W.

    1982-08-01

    In computed tomography (CT) of the head of the femur, a star-shaped structure can be seen which we refer to as the asterisk or asterisk sign. The asterisk is formed by thickened weight-bearing bone trabeculae. It can be shown by CT that the asterisk exhibits a characteristic change in ischaemic bone necrosis of the femoral head, even when the disease is in an early stage. CT of the hip joint is therefore an important examination for early diagnosis of ischaemic diesease of the femoral head.

  10. Comparison of trends in ischaemic heart disease between North Karelia, Finland, and Kaunas, Lithuania, from 1971 to 1987

    PubMed Central

    Rastenyte, Daiva; Salomaa, Veikko; Mustaniemi, Harri; Rasteniene, Dalia; Grazuleviciene, Regina; Cepaitis, Zygimantas; Kankaanpää, Jari; Kuulasmaa, Kari; Torppa, Jorma; Bluzhas, Juozas; Tuomilehto, Jaakko

    1992-01-01

    Objective—To compare the long-term trends in mortality and attack rate of ischaemic heart disease in North Karelia, Finland, and in Kaunas, Lithuania, from 1971 to 1987. Design—Data on routine mortality statistics were obtained from the Central Statistical Office of Finland and from the Central City Archives of Kaunas. In addition, data from the community based myocardial infarction registers were used. The registers used similar diagnostic criteria and had operated in both areas during the entire study period. Setting—The province of North Karelia in Finland and the city of Kaunas in Lithuania. Subjects—The target populations were the people of North Karelia and Kaunas aged 35–64 years. Main outcome measures—Mortality from ischaemic heart disease and the attack rate of acute myocardial infarction. Results—In North Karelia mortality from ischaemic heart disease and the attack rate of acute myocardial infarction declined steeply both in men and women. This decline was accompanied by a decrease in total mortality. In Kaunas, both mortality and the attack rate increased in men but remained unchanged in women. In 1985 to 1987, age standardised total mortality per 100 000 inhabitants was similar in the two populations in men (1081 (95% confidence interval (CI) 1013 to 1149), in North Karelia; 1082 (95% CI 1032 to 1132), in Kaunas). The proportional mortality from ischaemic heart disease was considerably higher in North Karelia (40%) than in Kaunas (28%). In women, age standardised total mortality was lower in North Karelia (350 (95% CI 312–388)) than in Kaunas (440 (95% CI 413 to 467)). The proportional mortality from ischaemic heart disease in women was also higher in North Karelia (28%) than in Kaunas (13%). Conclusions—Despite the remarkable decline in the occurrence of ischaemic heart disease, it still remains the most important cause of premature mortality in North Karelia. In Kaunas ischaemic heart disease mortality and attack rate increased in

  11. Postpriapism erectile dysfunction and shunt-related urethral stricture: long-term morbidity after proximal shunt for ischaemic priapism

    PubMed Central

    Bello, Jibril Oyekunle

    2014-01-01

    Recent guidelines have advocated for step-wise treatment of increasing invasiveness in the management of ischaemic priapism though with low-level evidences. In the past, proximal shunts were favoured as first-line treatment. We present an African man who had proximal shunt (cavernoso-spongiosal) three decades ago for ischaemic priapism and subsequently had long-term morbidity over the three decades with adverse effect on his quality of life. Recent guidelines appear to be sound despite their limitations and more invasive cavernoso-spongiosal shunts may be associated with significant long-term morbidities and poor quality of life. PMID:25709730

  12. Auto immune hepatitis.

    PubMed

    van Gerven, Nicole Mf; de Boer, Ynto S; Mulder, Chris Jj; van Nieuwkerk, Carin Mj; Bouma, Gerd

    2016-05-21

    To provide an update of the latest trends in epidemiology, clinical course, diagnostics, complications and treatment of auto immune hepatitis (AIH). A search of the MEDLINE database was performed using the search terms: "auto immune hepatitis", "clinical presentation", "symptoms", "signs", "diagnosis", "auto antibodies", "laboratory values", "serology", "histopathology", "histology", "genetics", "HLA genes", "non-HLA genes", "environment", "epidemiology", "prevalence", "incidence", "demographics", "complications", "HCC", "PBC", "PSC", "corticosteroid", "therapy", "treatment", "alternative treatment". English-language full-text articles and abstracts were considered. Articles included reviews, meta-analysis, prospective retrospective studies. No publication date restrictions were applied. AIH is an immune meditated progressive inflammatory liver disease that predominantly affects middle-aged females but may affect people of all ages. The clinical spectrum of AIH is wide, ranging from absent or mild symptoms to fulminant hepatic failure. The aetiology of AIH is still unknown, but is believed to occur as the consequence of an aberrant immune response towards an un-known trigger in a genetically susceptible host. In the absence of a gold standard, diagnosis is based on the combination of clinical, biochemical and histopathological criteria. Immunosuppressive treatment has been the cornerstone of treatment since the earliest description of the disease in 1950 by Waldenström. Such treatment is often successful at inducing remission and generally leads to normal life expectancy. Nevertheless, there remain significant areas of unmet aetiological a clinical needs including fundamental insight in disease pathogenesis, optimal therapy, duration of treatment and treatment alternatives in those patients unresponsive to standard treatment regimens. PMID:27217697

  13. Liver failure in total artificial heart therapy

    PubMed Central

    Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero

    2016-01-01

    Background Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. Methods A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Results Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. Conclusions TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality. PMID:27499942

  14. Hepatitis C, stigma and cure

    PubMed Central

    Marinho, Rui Tato; Barreira, David Pires

    2013-01-01

    The infection with hepatitis C virus (HCV) is one of the most important global chronic viral infections worldwide. It is estimated to affect around 3% of the world population, about 170-200 million people. Great part of the infections are asymptomatic, the patient can be a chronic carrier for decades without knowing it. The most severe consequences of the chronic infection are liver cirrhosis and hepatocellular carcinoma, which appears in 20%-40% of the patients, leading to hepatic failure and death. The HCV was discovered 25 years ago in 1989, is a RNA virus and classified by the World Health Organization as an oncogenic one. Hepatocellular carcinoma is one of the most important cancers, the fifth worldwide in terms of mortality. It has been increasing in the Ocidental world, mainly due to chronic hepatitis C. Hepatitis C is not only a liver disease and a cause of cirrhosis, but also a mental, psychological, familiar, and social disease. The stigma that the infected person sometimes carries is tremendous having multiple consequences. The main cause is lack of adequate information, even in the health professionals setting. But, besides the “drama” of being infected, health professionals, family, society and the infected patients, must be aware of the chance of real cure and total and definitive elimination of the virus. The treatment for hepatitis C has begun in the last 80´s with a percentage of cure of 6%. Step by step the efficacy of the therapy for hepatitis C is rapidly increasing and nowadays with the very new medications, the so called Direct Antiviral Agents-DAAs of new generation, is around 80%-90%. PMID:24187444

  15. Current Knowledge on Hepatitis E.

    PubMed

    Pérez-Gracia, María Teresa; García, Mario; Suay, Beatriz; Mateos-Lindemann, María Luisa

    2015-06-28

    Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin(®). PMID:26355220

  16. Current Knowledge on Hepatitis E

    PubMed Central

    Pérez-Gracia, María Teresa; García, Mario; Suay, Beatriz; Mateos-Lindemann, María Luisa

    2015-01-01

    Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin®. PMID:26355220

  17. Heart Failure

    MedlinePlus

    ... together. About Rise Above HF Rise Above Heart Failure seeks to increase the dialogue about HF and improve the lives of people affected by the condition through awareness, education and support. Through the initiative, AHA strives to ...

  18. Testicular failure

    MedlinePlus

    ... Blood tests may show a low level of testosterone and high levels of prolactin, FSH , and LH . ... testes will be ordered. Testicular failure and low testosterone level may be hard to diagnose in older ...

  19. Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

    MedlinePlus

    ... of chronic liver disease, cirrhosis, viral hepatitis, and liver cancer make liver disease one of the 10 leading ... disease are decreasing, those for viral hepatitis and liver cancer are on the rise, both in the U.S. ...

  20. Modelling of the physiological response of the brain to ischaemic stroke

    PubMed Central

    Orlowski, Piotr; O'Neill, David; Grau, Vicente; Ventikos, Yiannis; Payne, Stephen

    2013-01-01

    Identification of salvageable brain tissue is a major challenge when planning the treatment of ischaemic stroke. As the standard technique used in this context, the perfusion–diffusion mismatch, has not shown total accuracy, there is an ongoing search for new imaging protocols that could better identify the region of the brain at risk and for new physiological models that could, on the one hand, incorporate the imaged parameters and predict the evolution of the condition for the individual, and, on the other hand, identify future biomarkers and thus suggest new directions for the design of imaging protocols. Recently, models of cellular metabolism after stroke and blood–brain barrier transport at tissue level have been introduced. We now extend these results by developing a model of the propagation of key metabolites in the brain's extracellular space owing to stroke-related oedema and chemical concentration gradients between the ischaemic and normal brain. We also couple the resulting chemical changes in the extracellular space with cellular metabolism. Our work enables the first patient-specific simulations of stroke progression with finite volume models to be made. PMID:24427526

  1. Protective role of methylprednisolone and heparin in ischaemic-reperfusion injury of the rat testicle.

    PubMed

    Mertoğlu, C; Senel, U; Cayli, S; Tas, U; Küskü Kiraz, Z; Özyurt, H

    2016-09-01

    This study evaluated the therapeutic efficacy of heparin and methylprednisolone in the treatment of ischaemic reperfusion (IR) injury of the testis. Twenty-four male Sprague-Dawley rats were allocated equally into three groups of eight animals each. The left testes were rotated 720° for 2 h in the rats in the torsion-detorsion group. Rats in the treatment groups underwent the same surgical procedure as the torsion-detorsion group but were also given methylprednisolone (group II) or heparin (group III) by an intraperitoneal route 30 min prior to detorsion. Left orchiectomy was performed in all rats from each experimental animal at 2 h after detorsion, and the tissue was harvested for the measurement of malondialdehyde (MDA), protein carbonyl (PC) and nitric oxide (NO) and the endogenous antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase. Additional tissue was evaluated using histopathological and immunohistochemical changes. PC and MDA levels were significantly reduced in the treated groups compared to the control group. There was no statistically significant difference in NO level or SOD, GSH-Px and catalase activity among the treatment groups. Histopathological and immunohistochemical findings supported biochemical changes. It is concluded that pre-treatment with methylprednisolone or heparin protects the testis in ischaemic reperfusion injury caused by testicular torsion-detorsion. PMID:26626546

  2. Angiogenesis gene therapy to rescue ischaemic tissues: achievements and future directions

    PubMed Central

    Emanueli, Costanza; Madeddu, Paolo

    2001-01-01

    Ischaemic diseases are characterized by an impaired supply of blood resulting from narrowed or blocked arteries that starve tissues of needed nutrients and oxygen. Coronary-atherosclerosis induced myocardial infarction is one of the leading causes of mortality in developed countries. Ischaemic disease also affects the lower extremities. Considerable advances in both surgical bypassing and percutaneous revascularization techniques have been reached. However, many patients cannot benefit from these therapies because of the extension of arterial occlusion and/or microcirculation impairment. Consequently, the need for alternative therapeutic strategies is compelling. An innovative approach consists of stimulating collateral vessel growth, a natural host defence response that intervenes upon occurrence of critical reduction in tissue perfusion (Isner & Asahara, 1999). This review will debate the relevance of therapeutic angiogenesis for promotion of tissue repair. The following issues will receive attention: (a) vascular growth patterns, (b) delivery systems for angiogenesis gene transfer, (c) achievements of therapeutic angiogenesis in myocardial and peripheral ischaemia, and (d) future directions to improve effectiveness and safety of vascular gene therapy. PMID:11487503

  3. Commentary on a GWAS: HDAC9 and the risk for ischaemic stroke.

    PubMed

    Hacke, Werner; Grond-Ginsbach, Caspar

    2012-01-01

    Modifiable risk factors like obesity, hypertension, smoking, physical inactivity or atrial fibrillation account for a significant proportion of the risk for ischaemic stroke, but genetic variation is also believed to contribute to the risk, although few genetic risk variants were identified to date. Common clinical subtypes of stroke are caused by cardiac embolism, large artery atherosclerosis and small cerebral vessel disease. Each of these underlying pathologies may have a specific genetic architecture.Previous genome-wide association studies (GWAS) showed association of variants near PITX2 and ZFHX3 with atrial fibrillation and stroke. ANRIL (antisense Non-coding RNA in the INK4 Locus (harboring the CDKN2A/B genes)) variants were related to a variety of vascular diseases (myocardial infarction, aortic and intracranial aneurysm), including ischaemic stroke. Now a recent GWAS published in Nature Genetics confirmed these previous associations, analyzed the specificity of the previous associations with particular stroke subtypes and identified a new association between HDAC9 and large vessel stroke. The findings suggest that well-recognized clinical stroke subtypes correspond to distinct aetiological entities. However, the molecular pathways that are affected by the identified genetic variants are not yet pinpointed, and the observed associations apply only for some, but not all victims of a specific stroke aetiology. PMID:22776031

  4. Studies of acidosis in the ischaemic heart by phosphorus nuclear magnetic resonance.

    PubMed Central

    Garlick, P B; Radda, G K; Seeley, P J

    1979-01-01

    1. Phosphorus-nuclear-magnetic-resonance measurements were made on perfused rat hearts at 37 degrees C. 2. With the improved sensitivity obtained by using a wide-bore 4.3 T superconducting magnet, spectra could be recorded in 1 min. 3. The concentrations of ATP, phosphocreatine and Pi and, from the position of the Pi resonance, the intracellular pH (pHi) were measured under a variety of conditions. 4. In a normal perfused heart pHi = 7.05 +/- 0.02 (mean +/- S.E.M. for seven hearts). 5. During global ischaemia pHi drops to 6.2 +/- 0.06 (mean +/- S.E.M.) in 13 min in a pseudoexponential decay with a rate constant of 0.25 min-1. 6. The relation between glycogen content and acidosis in ischaemia is studied in glycogen-depleted hearts. 7. Perfusion of hearts with a buffer containing 100 mM-Hepes before ischaemia gives a significant protective effect on the ischaemic myocardium. Intracellular pH and ATP and phosphocreatine concentrations decline more slowly under these conditions and metabolic recovery is observed on reperfusion after 30min of ischaemia at 37 degrees C. 8. The relation between acidosis and the export of protons is discussed and the significance of glycogenolysis in ischaemic acid production is evaluated. PMID:44193

  5. Locally induced hypothermia for treatment of acute ischaemic stroke: a physical feasibility study.

    PubMed

    Slotboom, J; Kiefer, C; Brekenfeld, C; Ozdoba, C; Remonda, L; Nedeltchev, K; Arnold, M; Mattle, H; Schroth, G

    2004-11-01

    During the treatment of stroke by local intra-arterial thrombolysis (LIT) it is frequently possible to pass the blood clot with a micro-catheter, allowing perfusion of brain tissue distally to the occlusion. This possibility allows for new early treatments of ischaemic brain tissue, even before the blood clot has been removed. One potential new approach to preserve brain tissue at risk may be locally induced endovascular hypothermia. Physical parameters such as the required micro-catheter input pressure, output velocity and flow rates, and a heat exchange model, applicable in the case of a micro-catheter placed within a guiding catheter, are presented. Also, a simple cerebral temperature model is derived that models the temperature response of the brain to the perfusion with coolant fluids. Based on this model, an expression has been derived for the time needed to reach a certain cerebral target temperature. Experimental in vitro measurements are presented that confirm the usability of standard commercially available micro-catheters to induce local hypothermia of the brain. If applied in vivo, the model predicts a local cooling rate of ischaemic brain tissue of 300 g of approximately 1 degrees C in 1 min, which is up to a factor 30-times faster than the time-consuming systemic hypothermia via the skin. Systemic body temperature is only minimally affected by application of local hypothermia, thus avoiding many limitations and complications known in systemic hypothermia. PMID:15551092

  6. Minimising time to treatment: targeted strategies to minimise time to thrombolysis for acute ischaemic stroke.

    PubMed

    Tai, Y J; Yan, B

    2013-11-01

    Time to thrombolysis is a critical determinant of favourable outcomes in acute ischaemic stroke. It is not infrequent that patient outcomes are compromised due to out-of-hospital and in-hospital time delays. On the other hand, time delays could be minimised through the identification of barriers and the implementation of targeted solutions. This review outlines the different strategies in minimising treatment delays and offers recommendations. Literature search in PubMed, Medline and EBSCO Host was conducted to identify studies that are relevant to reduction of time to treatment from January 1995 to December 2012. Strategies to reduce time to thrombolysis are categorised into pre-hospital strategies, in-hospital strategies and post-treatment decision strategies. Proposed pre-hospital strategies include public education on stroke symptoms awareness, prioritising stroke by emergency medical services, increasing ease of access to medical records, pre-hospital notification, and mobile computed tomography scanning. In-hospital strategies include a streamlined code stroke system, computed tomography scanner co-location with emergency department, 24/7 availability of stroke physicians, point-of-care laboratory testing and access to expert neuroimaging interpretation. Post-decision strategies include increasing availability of intravenous thrombolysis and simplification of informed consent procurement. Time to thrombolysis delays is multifactorial. Effective reduction of time delays for acute ischaemic stroke requires the correct identification of and targeted strategies to overcome time barriers. PMID:23734983

  7. Reconsidering the back door approach by targeting the coronary sinus in ischaemic heart disease.

    PubMed

    De Maria, Giovanni Luigi; Kassimis, George; Raina, Tushar; Banning, Adrian P

    2016-08-15

    Coronary sinus interventions (CSI) are a class of invasive techniques (surgical and percutaneous) originally proposed in the first half of the 20th century, aiming to treat ischaemic heart disease by acting on the venous coronary system. Three main classes of CSI have been proposed and tested: (1) retroperfusion technique, (2) retroinfusion technique and (3) coronary sinus occlusion techniques. They all share the principle that a controlled increased pressure within the coronary sinus may promote a retrograde perfusion of the ischaemic myocardium with consequent cardioprotection. Development of arterial treatments including coronary aortic bypass grafting and then percutaneous coronary intervention deflected interest from interventions on the coronary venous system. However, CSI may still have a possible niche role today in specific and selected clinical contexts in which existing therapies are insufficient. In this review paper, we aim to revise the rationale for CSI, describing the details and the evidence collected so far about these techniques and to provide insights about the main clinical scenarios in which these strategies may find a contemporary application in combination or as an alternative to existing approaches. PMID:27288281

  8. The third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke

    PubMed Central

    Sandercock, Peter; Lindley, Richard; Wardlaw, Joanna; Dennis, Martin; Lewis, Steff; Venables, Graham; Kobayashi, Adam; Czlonkowska, Anna; Berge, Eivind; Slot, Karsten Bruins; Murray, Veronica; Peeters, Andre; Hankey, Graeme; Matz, Karl; Brainin, Michael; Ricci, Stefano; Celani, Maria Grazia; Righetti, Enrico; Cantisani, Teresa; Gubitz, Gord; Phillips, Steve; Arauz, Antonio; Prasad, Kameshwar; Correia, Manuel; Lyrer, Phillippe

    2008-01-01

    Background Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit. Design International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit. Trial procedures Patients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24–48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol). Trial registration ISRCTN25765518 PMID:18559104

  9. Protect Yourself from Hepatitis

    MedlinePlus

    ... develop yellowish eyes and skin. All the hepatitis viruses can cause acute, or short-term, hepatitis. Some can also cause chronic hepatitis, in which the infection lasts a long time, sometimes for your whole life. Chronic hepatitis can eventually lead to scarring of ...

  10. Hepatic osteodystrophy.

    PubMed

    Gatta, Angelo; Verardo, Alberto; Di Pascoli, Marco; Giannini, Sandro; Bolognesi, Massimo

    2014-09-01

    Metabolic disturbances of bone are frequent in patients with chronic liver disease. The prevalence of osteoporosis among patients with advanced chronic liver disease is reported between 12% and 55%; it is higher in primary biliary cirrhosis. All patients with advanced liver disease should be screened for osteoporosis with a densitometry, especially if the etiology is cholestatic and in the presence of other risk factors. Clinical relevance of hepatic osteodystrophy increases after liver transplantation. After liver transplant, a rapid loss of bone mineral density can be detected in the first 6 months, followed by stabilization and slight improvement of the values. At the time of transplantation, bone density values are very important prognostic factors. Therapy of hepatic osteodystrophy is based primarily on the control of risk factors: cessation of tobacco and alcohol assumption, reduction of caffeine ingestion, exercise, supplementation of calcium and vitamin D, limitation of drugs such as loop diuretics, corticosteroids, cholestyramine. Bisphosphonates have been proposed for the therapy of osteoporosis in patients with liver disease, particularly after liver transplantation. The possible side effects of oral administration of bisphosphonates, such as the occurrence of esophageal ulcerations, are of particular concern in patients with liver cirrhosis and portal hypertension, due to the risk of gastrointestinal hemorrhage from ruptured esophageal varices, although this risk is probably overestimated. PMID:25568651

  11. [Hepatic encephalopathy].

    PubMed

    Festi, Davide; Marasco, Giovanni; Ravaioli, Federico; Colecchia, Antonio

    2016-07-01

    Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and it can manifest with a broad spectrum of neuropsychiatric abnormalities of varying severity, acuity and time course with important clinical implications. According to recent guidelines, HE has been classified into different types, depending on the severity of hepatic dysfunction, the presence of porto-systemic shunts and the number of previous episodes or persistent manifestations. From a clinical point of view, HE can be recognized as unimpaired, covert (that deals with minimal and grade 1 according to the grading of mental state), and overt (that is categorized from grade 2 to grade 4). Different and only partially known pathogenic mechanisms have been identified, comprising ammonia, inflammatory cytokines, benzodiazepine-like compounds and manganese deposition. Different therapeutic strategies are available for treating HE, in particular the overt HE, since covert HE needs to be managed case by case. Recognition and treatment of precipitating factors represent fundamental part of the management. The more effective treatments, which can be performed separately or combined, are represented by non-absorbable disaccharides (lactulose and lactitol) and the topic antibiotic rifaximin; other possible therapies, mainly used in patients non responders to previous treatments, are represented by branched chain amino acids and metabolic ammonia scavengers. PMID:27571468

  12. Is valve repair preferable to valve replacement in ischaemic mitral regurgitation? A systematic review and meta-analysis.

    PubMed

    Salmasi, Mohammad Yousuf; Acharya, Metesh; Humayun, Nada; Baskaran, Dinnish; Hubbard, Stephanie; Vohra, Hunaid

    2016-07-01

    Ischaemic mitral regurgitation (MR) is associated with poor survival. The favoured surgical option remains debatable. Our aim was to perform a meta-analysis to compare the outcomes of mitral valve repair (MVRp) with replacement (MVR). A literature search was conducted in PubMed, Medline and Ovid using the terms 'ischaemic mitral regurgitation', 'repair' and 'replacement'. The primary outcome measure was 30-day survival. The secondary outcome measures were MR recurrence and reoperation. Out of 310 articles, 18 fulfilled the inclusion criteria. A total of 3978 patients were included: 2563 (64%) MVRp cases and 1415 (36%) MVR cases. Operative techniques included annuloplasty for MVRp and subvalvular apparatus-sparing MVR techniques. Thirty-day mortality was lower after MVRp compared with MVR [OR 0.42; (95% CI 0.33-0.54; P = 0.0001)]. There was no difference in long-term survival ranging 1-5 years (HR 0.85, 95% CI 0.65-1.12). Recurrence of MR was significantly higher in the MVRp group (OR 4.26, 95% CI 2.52-7.22), as was the rate of reoperation (OR 2.03, 95% CI 1.49-2.77). Although MVR for ischaemic MR has a higher 30-day mortality rate compared with MVRp, MVRp is associated with the higher rate of MR recurrence and the need for reoperation. MVR remains an attractive option for ischaemic MR. PMID:27009102

  13. The – 148 C/T fibrinogen gene polymorphism and fibrinogen levels in ischaemic stroke: a case–control study

    PubMed Central

    van Goor, M P J; Gomez-Garcia, E; Leebeek, F; Brouwers, G; Koudstaal, P; Dippel, D

    2005-01-01

    Design: A case–control study of patients with first ever ischaemic stroke, confirmed by computed tomography. Methods: Venous blood samples were collected for fibrinogen and routine coagulation tests one week after the stroke, and after three months in about half the patients. Population controls were age and sex matched. –148 C/T fibrinogen polymorphism was determined by polymerase chain reaction followed by digestion with restriction enzymes HindIII/AluI. Results: There were 124 patients and 125 controls, mean age 56 years (range 18 to 75); 34 patients (27%) and 41 controls (33%) were heterozygous for –148 C/T fibrinogen polymorphism; six patients (5%) and five controls (4%) had the T/T genotype. The odds ratio of ischaemic stroke associated with CC homozygotes v T carriers was 0.8 (95% confidence interval, 0.5 to 1.4). Relative risk for ischaemic stroke associated with fibrinogen levels in the highest quartile was 3.9 (1.9 to 8.4) at one week, decreasing to 1.4 (0.6 to 3.3) at three months. Conclusions: –148 C/T fibrinogen gene polymorphism was not a strong risk factor for ischaemic stroke. High fibrinogen levels early after acute stroke probably represent an acute phase response. PMID:15608011

  14. A novel technique for hepatic vein reconstruction during hepatectomy.

    PubMed

    Surjan, Rodrigo C; Basseres, Tiago; Pajecki, Denis; Puzzo, Daniel B; Makdissi, Fabio F; Machado, Marcel A C; Battilana, Alexandre Gustavo Bellorio

    2016-01-01

    Surgical resection is the treatment of choice for malignant liver tumours. Nevertheless, surgical approach to tumours located close to the confluence of the hepatic veins is a challenging issue. Trisectionectomies are considered the first curative option for treatment of these tumours. However, those procedures are associated with high morbidity and mortality rates primarily due to post-operative liver failure. Thus, maximal preservation of functional liver parenchyma should always be attempted. We describe the isolated resection of Segment 8 for the treatment of a tumour involving the right hepatic vein and in contact with the middle hepatic vein and retrohepatic vena cava with immediate reconstruction of the right hepatic vein with a vascular graft. This is the first time this type of reconstruction was performed, and it allowed to preserve all but one of the hepatic segments with normal venous outflow. This innovative technique is a fast and safe method to reconstruct hepatic veins. PMID:27076622

  15. A novel technique for hepatic vein reconstruction during hepatectomy

    PubMed Central

    Surjan, Rodrigo C.; Basseres, Tiago; Pajecki, Denis; Puzzo, Daniel B.; Makdissi, Fabio F.; Machado, Marcel A.C.; Battilana, Alexandre Gustavo Bellorio

    2016-01-01

    Surgical resection is the treatment of choice for malignant liver tumours. Nevertheless, surgical approach to tumours located close to the confluence of the hepatic veins is a challenging issue. Trisectionectomies are considered the first curative option for treatment of these tumours. However, those procedures are associated with high morbidity and mortality rates primarily due to post-operative liver failure. Thus, maximal preservation of functional liver parenchyma should always be attempted. We describe the isolated resection of Segment 8 for the treatment of a tumour involving the right hepatic vein and in contact with the middle hepatic vein and retrohepatic vena cava with immediate reconstruction of the right hepatic vein with a vascular graft. This is the first time this type of reconstruction was performed, and it allowed to preserve all but one of the hepatic segments with normal venous outflow. This innovative technique is a fast and safe method to reconstruct hepatic veins. PMID:27076622

  16. “Playboy Bunny” Sign of Congestive Heart Failure

    PubMed Central

    Hokama, Akira; Arakaki, Shingo; Shibata, Daisuke; Maeshiro, Tatsuji; Kinjo, Fukunori; Fujita, Jiro

    2011-01-01

    In emergency, ultrasound has been widely used as a noninvasive and effective examination to evaluate congestive heart failure. We highlight “Playboy Bunny” sign as a reliable marker and an important clue to the diagnosis of passive hepatic congestion, caused by congestive heart failure. PMID:22224133

  17. Management of blunt hepatic trauma.

    PubMed

    Letoublon, C; Amariutei, A; Taton, N; Lacaze, L; Abba, J; Risse, O; Arvieux, C

    2016-08-01

    For the last 20 years, nonoperative management (NOM) of blunt hepatic trauma (BHT) has been the initial policy whenever this is possible (80% of cases), i.e., in all cases where the hemodynamic status does not demand emergency laparotomy. NOM relies upon the coexistence of three highly effective treatment modalities: radiology with contrast-enhanced computerized tomography (CT) and hepatic arterial embolization, intensive care surveillance, and finally delayed surgery (DS). DS is not a failure of NOM management but rather an integral part of the surgical strategy. When imposed by hemodynamic instability, the immediate surgical option has seen its effectiveness transformed by development of the concept of abbreviated (damage control) laparotomy and wide application of the method of perihepatic packing (PHP). The effectiveness of these two conservative and cautious strategies for initial management is evidenced by current experience, but the management of secondary events that may arise with the most severe grades of injury must be both rapid and effective. PMID:27519150

  18. Role of risk stratification by SPECT, PET, and hybrid imaging in guiding management of stable patients with ischaemic heart disease: expert panel of the EANM cardiovascular committee and EACVI.

    PubMed

    Acampa, Wanda; Gaemperli, Oliver; Gimelli, Alessia; Knaapen, Paul; Schindler, Thomas H; Verberne, Hein J; Zellweger, Michael J

    2015-12-01

    Risk stratification has become increasingly important in the management of patients with suspected or known ischaemic heart disease (IHD). Recent guidelines recommend that these patients have their care driven by risk assessment. The purpose of this position statement is to summarize current evidence on the value of cardiac single-photon emission computed tomography, positron emission tomography, and hybrid imaging in risk stratifying asymptomatic or symptomatic patients with suspected IHD, patients with stable disease, patients after coronary revascularization, heart failure patients, and specific patient population. In addition, this position statement evaluates the impact of imaging results on clinical decision-making and thereby its role in patient management. The document represents the opinion of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee and of the European Association of Cardiovascular Imaging (EACVI) and intends to stimulate future research in this field. PMID:25902767

  19. Left ventricular angiography on exercise. A new method of assessing left ventricular function in ischaemic heart disease.

    PubMed Central

    Sharma, B; Goodwin, J F; Raphael, M J; Steiner, R E; Rainbow, R G; Taylor, S H

    1976-01-01

    Left ventricular function was studied in 17 patients with ischaemic heart disease and compared with 4 patients with normal left ventricular function. The patients in the homogeneous group of ischaemic heart disease were further subdivided into those 'without angina' (n=5) and those 'with angina' (n=12), depending upon the presence of angina during supine leg exercise at the time of definitive study. At rest there was no significant difference in the heart rate, cardiac output, stroke volume, and left ventricular end-diastolic pressure (LVEDP) in the three groups. During exercise the cardiac output and stroke volume were significantly depressed and LVEDP was significantly raised in the ischaemic heart disease group as a whole but within this group failed to show any significant difference in patients with and without angina. The left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) measurements showed clear separation of these three groups only on exercise. On exercise, there was decrease in LVEDV and LVESV (P less than 0.05; P less than 0.02) in the group with normal left ventricular function, no change in the group with ischaemic heart disease without angina, and striking increase in LVEDV and LVESV in the group with ischaemic heart disease and angina (P less than 0.01 and P less than 0.02, respectively). This angiographic method of assessing left ventricular function shows clear separation of the three groups and also highlights the significance of angina. Ejection fraction (EF), a commonly measured parameter of left ventricular function, failed to reflect consistent changes on exercise as compared to values at rest which emphasizes the limitations of the measurement of ejection fraction at rest. Images PMID:1082766

  20. Quantifying the risk of heart disease following acute ischaemic stroke: a meta-analysis of over 50 000 participants

    PubMed Central

    Gunnoo, Trishna; Hasan, Nazeeha; Khan, Muhammad Saleem; Slark, Julia; Bentley, Paul; Sharma, Pankaj

    2016-01-01

    Objective Following an acute stroke, there is a high risk of recurrence. However, the leading cause of mortality following a stroke is due to coronary artery disease (CAD) and myocardial infarction (MI) but that risk has not been robustly quantified. We sought to reliably quantify the risk of ischaemic heart disease (IHD) in patients presenting with acute ischaemic stroke (AIS) in the absence of a known cardiac history. Setting A meta-analysis study. PubMed, MEDLINE, EMBASE and Google Scholar were searched for potential studies up to October 2015. Included studies reported an acute cerebral ischaemic event and followed for CAD or MI within 1 year in patients without known IHD. Using arcsine transformed proportions for meta-analysis, studies were combined using a generic inverse variance random-effects model to calculate the pooled standardised mean difference and 95% CIs. These were interpreted as the percentage prevalence of CAD or incidence of MI following AIS. Results 17 studies with 4869 patients with AIS demonstrated a mean average of asymptomatic CAD in 52%. Anatomical methods of CAD detection revealed a prevalence of asymptomatic ≥50% coronary stenosis in 32% (95% CI 19% to 47%; p<0.00001). 8 studies with 47229 patients with ischaemic stroke revealed an overall risk of MI in the year following stroke of 3% (95% CI 1% to 5%; p<0.00001) despite the absence of any cardiac history. Conclusions One-third of patients with ischaemic stroke with no cardiac history have more than 50% coronary stenosis and 3% are at risk of developing MI within a year. Our findings provide a reliable quantitative measure of the risk of IHD following AIS in patients with no cardiac history. PMID:26792217

  1. Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation.

    PubMed

    Hao, J X; Xu, X J; Aldskogius, H; Seiger, A; Wiesenfeld-Hallin, Z

    1991-05-01

    We report behaviours suggesting the presence of allodynia elicited by non-noxious brushing and mechanical pressure following photochemically induced ischaemic spinal cord injury in the rat. Female rats were intravenously injected with Erythrosin B and the T10 vertebra was irradiated with a laser beam for 1, 5 or 10 min. These procedures initiated an intravascular photochemical reaction, resulting in ischaemic spinal cord injury. After irradiation a clear allodynia was observed in most rats. The animals vocalized intensely to light touch during gentle handling and were clearly agitated to light brushing of the flanks. The vocalization threshold in response to the mechanical pressure measured with von Frey hairs was markedly decreased during this period. In some animals the existence of spontaneous pain was suggested by spontaneous vocalization. The duration of the allodynia varied among animals from several hours to several days. The severity and duration of allodynia seemed not to be related to the duration of irradiation. In sham-operated rats a slight, transient allodynia was also noted around the wound within a few hours after surgery, which was effectively relieved by systemic morphine (2 mg/kg, i.p.). Morphine (2 mg/kg, i.p.) also partially relieved the allodynia in spinally injured rats 4 h after irradiation. However, morphine, even at a higher dose (5 mg/kg, i.p.), failed to alleviate the allodynia in spinally injured rats 24-48 h after the injury. Systemic injection of the GABAB agonist baclofen (0.01-0.1 mg/kg, i.p.), but not the GABAA agonist muscimol (1 mg/kg, i.p.), effectively relieved allodynia during this period. Pretreatment with guanethidine 24 h and just prior to the irradiation (20 mg/kg, s.c.) did not prevent the occurrence of allodynia in spinal cord injured rats. The present observation is the first to show that ischaemic spinal cord injury could result in cutaneous mechanical allodynia. This phenomenon is resistant to morphine and may not

  2. Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis

    PubMed Central

    Neves, Joana Briosa; Caldeira, Daniel; Ferro, José M; Ferreira, Joaquim J; Costa, João

    2016-01-01

    Objectives To evaluate the efficacy and safety of endovascular treatment, particularly adjunctive intra-arterial mechanical thrombectomy, in patients with ischaemic stroke. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, SciELO, LILACS, and clinical trial registries from inception to December 2015. Reference lists were crosschecked. Eligibility criteria for selecting studies Randomised controlled trials in adults aged 18 or more with ischaemic stroke comparing endovascular treatment, including thrombectomy, with medical care alone, including intravenous recombinant tissue plasminogen activator (rt-PA). Trial endpoints were functional outcome (modified Rankin scale scores of ≤2) and mortality at 90 days after onset of symptoms. No language or time restrictions applied. Results 10 randomised controlled trials (n=2925) were included. In pooled analysis endovascular treatment, including thrombectomy, was associated with a higher proportion of patients experiencing good (modified Rankin scale scores ≤2) and excellent (scores ≤1) outcomes 90 days after stroke, without differences in mortality or rates for symptomatic intracranial haemorrhage, compared with patients randomised to medical care alone, including intravenous rt-PA. Heterogeneity was high among studies. The more recent studies (seven randomised controlled trials, published or presented in 2015) proved better suited to evaluate the effect of adjunctive intra-arterial mechanical thrombectomy on its index disease owing to more accurate patient selection, intravenous rt-PA being administered at a higher rate and earlier, and the use of more efficient thrombectomy devices. In most of these studies, more than 86% of the patients were treated with stent retrievers, and rates of recanalisation were higher (>58%) than previously reported. Subgroup analysis of these seven studies yielded a risk ratio of 1.56 (95

  3. Aspirin failure in patients presenting with acute cerebrovascular ischaemia.

    PubMed

    Halawani, Saeed H M; Williams, David J P; Adefurin, Abiodun; Webster, John; Greaves, Michael; Ford, Isobel

    2011-08-01

    Aspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke. In order to determine the prevalence and nature of aspirin failure, we studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin. Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods. All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients. Following in-hospital aspirin administration, there was a significant decrease in AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission. However, residual aggregation (10-15%) persisted in 11 subjects - suggesting alternative causes. In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Intervention studies are required to determine the clinical relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness of improved pharmacotherapy for stroke prevention. PMID:21544317

  4. Heart Failure

    MedlinePlus

    ... Tiredness and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and diabetes. It is more common in people who are 65 years old or older, African Americans, people who are overweight, and people who have ...

  5. Respiratory Failure

    MedlinePlus

    ... from inhaling smoke or harmful fumes Treatment for respiratory failure depends on whether the condition is acute (short-term) or chronic (ongoing) and how severe it is. It also depends on the underlying cause. You may receive oxygen therapy and other treatment to help you breathe. NIH: ...

  6. Hepatitis A: Old and New

    PubMed Central

    Cuthbert, Jennifer A.

    2001-01-01

    The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis worldwide. Spread of infection is generally person to person or by oral intake after fecal contamination of skin or mucous membranes; less commonly, there is fecal contamination of food or water. Hepatitis A is endemic in developing countries, and most residents are exposed in childhood. In contrast, the adult population in developed countries demonstrates falling rates of exposure with improvements in hygiene and sanitation. The export of food that cannot be sterilized, from countries of high endemicity to areas with low rates of infection, is a potentially important source of infection. After ingestion and uptake from the gastrointestinal tract, the virus replicates in the liver and is excreted into the bile. Cellular immune responses to the virus lead to destruction of infected hepatocytes with consequent development of symptoms and signs of disease. Humoral immune responses are the basis for diagnostic serologic assays. Acute HAV infection is clinically indistinguishable from other causes of acute viral hepatitis. In young children the disease is often asymptomatic, whereas in older children and adults there may be a range of clinical manifestations from mild, anicteric infection to fulminant hepatic failure. Clinical variants include prolonged, relapsing, and cholestatic forms. Management of the acute illness is supportive, and complete recovery without sequelae is the usual outcome. Research efforts during World War II led to the development of passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the prevention and attenuation of disease in exposed individuals. More recently, active immunoprophylaxis by vaccination has been accomplished. Future eradication of this disease can now be contemplated. PMID:11148002

  7. Experimental models of hepatic encephalopathy: ISHEN guidelines.

    PubMed

    Butterworth, Roger F; Norenberg, Michael D; Felipo, Vicente; Ferenci, Peter; Albrecht, Jan; Blei, Andres T

    2009-07-01

    Objectives of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism Commission were to identify well-characterized animal models of hepatic encephalopathy (HE) and to highlight areas of animal modelling of the disorder that are in need of development. Features essential to HE modelling were identified. The best-characterized animal models of HE in acute liver failure, the so-called Type A HE, were found to be the hepatic devascularized rat and the rat with thioacetamide-induced toxic liver injury. In case of chronic liver failure, surgical models in the rat involving end-to-side portacaval anastomosis or bile duct ligation were considered to best model minimal/mild (Type B) HE. Unfortunately, at this time, there are no satisfactory animal models of Type C HE resulting from end-stage alcoholic liver disease or viral hepatitis, the most common aetiologies encountered in patients. The commission highlighted the urgent need for such models and of improved models of HE in chronic liver failure in general as well as a need for models of post-transplant neuropsychiatric disorders. Studies of HE pathophysiology at the cellular and molecular level continue to benefit from in vitro and or ex vivo models involving brain slices or exposure of cultured cells (principally cultured astrocytes) to toxins such as ammonia, manganese and pro-inflammatory cytokines. More attention could be paid in the future to in vitro models involving the neurovascular unit, microglia and neuronal co-cultures in relation to HE pathogenesis. PMID:19638106

  8. Athetoid cerebral palsy with cysts in the putamen after hypoxic-ischaemic encephalopathy.

    PubMed Central

    Rutherford, M A; Pennock, J M; Murdoch-Eaton, D M; Cowan, F M; Dubowitz, L M

    1992-01-01

    Three cases of athetoid cerebral palsy after hypoxic-ischaemic encephalopathy (HIE) are reported. All three neonates had haemorrhagic lesions in the basal ganglia and thalami on magnetic resonance imaging (MRI). Prior cranial ultrasound had detected the lesions in only two cases. In all three children athetoid movements began within the first year of life. Follow up MRI scans showed bilateral symmetrical cystic lesions in the posterior putamen. Although haemorrhagic lesions within the basal ganglia are a common MRI finding in neonates with HIE, few of these babies develop athetoid cerebral palsy. We believe this to be the first report of discrete cystic lesions found in the basal ganglia of children with athetoid cerebral palsy. Images Figure 1 Figure 2 Figure 3 PMID:1519987

  9. The meteorological sensitivity of ischaemic heart disease mortality events in Birmingham, UK

    NASA Astrophysics Data System (ADS)

    McGregor, G. R.

    Winter ischaemic heart disease (IHD) mortality events (ME) were identified in order to establish their degree of meteorological sensitivity. Sensitivity was evaluated using regression of surface meteorological and large-scale atmospheric circulation variables on daily mortality for each mortality event. Critical meteorological variables affecting IHD mortality appear to be local surface dry-bulb and dew-point temperature and large-scale southerly and westerly wind components, atmospheric pressure and vorticity. The rate of change and departure from normal conditions of these variables appear to be especially important for engendering IHD mortality events. Associated with IHD mortality are two broad types of weather conditions: (1) blustery westerly flows and rapidly changing weather from the west and (2) climatologically strong northeasterly to southeasterly flows of cold air, which bring rapidly changing and anomalous thermal conditions to the study area. The general atmospheric circulation patterns that produce these conditions are identified and the implications of results for weather and health studies are discussed.

  10. Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

    PubMed

    Nuttall, T J; Burrow, R; Fraser, I; Kipar, A

    2005-05-01

    An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition. PMID:15909448

  11. Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases

    PubMed Central

    Eltzschig, Holger K.; Bratton, Donna L.; Colgan, Sean P.

    2014-01-01

    Hypoxia-inducible factors (HIFs) are stabilized during adverse inflammatory processes associated with disorders such as inflammatory bowel disease, pathogen infection and acute lung injury, as well as during ischaemia–reperfusion injury. HIF stabilization and hypoxia-induced changes in gene expression have a profound impact on the inflamed tissue microenvironment and on disease outcomes. Although the mechanism that initiates HIF stabilization may vary, the final molecular steps that control HIF stabilization converge on a set of oxygen-sensing prolyl hydroxylases (PHDs) that mark HIFs for proteasomal degradation. PHDs are therefore promising therapeutic targets. In this Review, we discuss the emerging potential and associated challenges of targeting the PHD–HIF pathway for the treatment of inflammatory and ischaemic diseases. PMID:25359381

  12. [Pregnancy in patients with a history of ischaemic heart disease - Case series and literature review].

    PubMed

    Matura-Bedouhene, M; Maatouk, A; Moulin, F; Welter, E; Morel, O; Perdriolle-Galet, E

    2016-04-01

    Heart diseases complicate 1 to 3% of pregnancies and are the leading cause of indirect maternal deaths. Prior ischaemic heart event in pregnant patients is increasing. Most knowledge is based on few reports and there are no French nor international recommendations about the specific management of these patients. The specificity of the management of these patients during pregnancy, delivery and post-partum depends on the severity of the prior cardiac event and its consequences. This will be illustrated by the report of four recent cases managed in our hospital. First patient had myocardial infarction with normal left ventricular ejection fraction (LVEF). Second patient had a Tako-Tsubo syndrome with LVEF 45%. Third patient had ischemic cardiopathy with LVEF 30%. Fourth patient had myocardial infarction with LVEF 20%. A multidisciplinary follow-up should be required, especially in patients with severe ventricular dysfunction. The risk of fetal growth restriction appears to be increased, suggesting that closer ultrasound monitoring is necessary. PMID:26321610

  13. Pseudo-ischaemic ECG in a patient with amyotrophic lateral sclerosis surviving for a decade

    PubMed Central

    Zhang, Jian; Yang, Shi-Wei; Wang, Zheng; Wei, Guang-Ru; Zhou, Yu-Jie

    2012-01-01

    A 58-year-old female with no history of heart disease was admitted to our hospital for abnormal ECG mimicking myocardial ischaemia. The ECG revealed persistent T-wave inversion in almost all leads, especially in precordial leads V2–V6. The patient had no complaints of chest pain, chest distress, short of breath or other atypical myocardial ischaemia symptoms. She had a history of amyotrophic lateral sclerosis (ALS) with a disease course more than 20 years. Examinations help rule out other diseases causing persistent T-wave inversion. Importantly, cardiac catheterisation showed nearly normal coronary arteries that could rule out myocardial ischaemia. Accordingly, the authors presumed that the pseudo-ischaemic ECG was associated with ALS in this patient. The findings of the present case provide new evidence that autonomic nervous system may involve in the pathophysiological progress of ALS. PMID:22665549

  14. Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation. Correlation with ischaemic events.

    PubMed

    Lenti, Massimo; Falcinelli, Emanuela; Pompili, Marcella; de Rango, Paola; Conti, Valentina; Guglielmini, Giuseppe; Momi, Stefania; Corazzi, Teresa; Giordano, Giuseppe; Gresele, Paolo

    2014-06-01

    Purified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events. PMID:24499865

  15. ASTRAL-R score predicts non-recanalisation after intravenous thrombolysis in acute ischaemic stroke.

    PubMed

    Vanacker, Peter; Heldner, Mirjam R; Seiffge, David; Mueller, Hubertus; Eskandari, Ashraf; Traenka, Christopher; Ntaios, George; Mosimann, Pascal J; Sztajzel, Roman; Mendes Pereira, Vitor; Cras, Patrick; Engelter, Stefan; Lyrer, Philippe; Fischer, Urs; Lambrou, Dimitris; Arnold, Marcel; Michel, Patrik

    2015-05-01

    Intravenous thrombolysis (IVT) as treatment in acute ischaemic strokes may be insufficient to achieve recanalisation in certain patients. Predicting probability of non-recanalisation after IVT may have the potential to influence patient selection to more aggressive management strategies. We aimed at deriving and internally validating a predictive score for post-thrombolytic non-recanalisation, using clinical and radiological variables. In thrombolysis registries from four Swiss academic stroke centres (Lausanne, Bern, Basel and Geneva), patients were selected with large arterial occlusion on acute imaging and with repeated arterial assessment at 24 hours. Based on a logistic regression analysis, an integer-based score for each covariate of the fitted multivariate model was generated. Performance of integer-based predictive model was assessed by bootstrapping available data and cross validation (delete-d method). In 599 thrombolysed strokes, five variables were identified as independent predictors of absence of recanalisation: Acute glucose > 7 mmol/l (A), significant extracranial vessel STenosis (ST), decreased Range of visual fields (R), large Arterial occlusion (A) and decreased Level of consciousness (L). All variables were weighted 1, except for (L) which obtained 2 points based on β-coefficients on the logistic scale. ASTRAL-R scores 0, 3 and 6 corresponded to non-recanalisation probabilities of 18, 44 and 74 % respectively. Predictive ability showed AUC of 0.66 (95 %CI, 0.61-0.70) when using bootstrap and 0.66 (0.63-0.68) when using delete-d cross validation. In conclusion, the 5-item ASTRAL-R score moderately predicts non-recanalisation at 24 hours in thrombolysed ischaemic strokes. If its performance can be confirmed by external validation and its clinical usefulness can be proven, the score may influence patient selection for more aggressive revascularisation strategies in routine clinical practice. PMID:25589216

  16. Remote ischaemic preconditioning does not alter perioperative cytokine production in high-risk cardiac surgery

    PubMed Central

    Williams, Jenni M; Young, Paul; Pilcher, Janine; Weatherall, Mark; Miller, John Holmes; Beasley, Richard; La Flamme, Anne Camille

    2012-01-01

    Rationale Remote ischaemic preconditioning (RIPC) is a novel cardioprotective strategy that uses brief intermittent limb ischaemia to protect the myocardium and other organs from perioperative ischaemic damage. The precise mechanism through which this protective effect occurs is unknown, but potentially could be related to changes in blood-borne mediators such as cytokines. Objective To determine whether RIPC alters inflammatory cytokine expression in a double-blind, randomised, controlled trial of patients undergoing high-risk cardiac surgery. Methods and results Serum interleukin (IL)-6, IL-8, and IL-10 levels from 95 patients randomised to RIPC (n=47) or control treatment (n=48) were measured preoperatively, and 1, 2, 3, 6 and 12 h after cross-clamp removal. Systemic concentrations of all cytokines were increased from baseline following surgery, and, compared with simple procedures, complex surgeries were associated with significantly higher release of IL-6 (ratio of mean area under the curves 1.54 (95% CI 1.02 to 2.34), p=0.04) and IL-10 (1.97 (1.16 to 3.35), p=0.012). No significant difference in mean cytokine levels between the RIPC and control groups was detected at any time point, irrespective of the type of surgery undergone. Conclusions High levels of IL-6, IL-8 and IL-10 are produced during high-risk cardiac surgery, and RIPC does not alter these elevated perioperative cytokine concentrations. Identification of factors that influence the ability to induce RIPC-mediated cardioprotection should be the priority of future research. Trial registration is in the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au; ACTRN12609000965202)

  17. Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management.

    PubMed

    Kaur, C; Foulds, W S; Ling, E A

    2008-11-01

    The blood-retinal barrier (BRB) plays an important role in the homeostatic regulation of the microenvironment in the retina. It consists of inner and outer components, the inner BRB (iBRB) being formed by the tight junctions between neighbouring retinal capillary endothelial cells and the outer barrier (oBRB) by tight junctions between retinal pigment epithelial cells. Astrocytes, Müller cells and pericytes contribute to the proper functioning of the iBRB. In many clinically important conditions including diabetic retinopathy, ischaemic central retinal vein occlusion, and some respiratory diseases, retinal hypoxia results in a breakdown of the iBRB. Disruption of the iBRB associated with increased vascular permeability, results in vasogenic oedema and tissue damage, with consequent adverse effects upon vision. Factors such as enhanced production of vascular endothelial growth factor (VEGF), NO, oxidative stress and inflammation underlie the increased permeability of the iBRB and inhibition of these factors is beneficial. Experimental studies in our laboratory have shown melatonin to be a protective agent for the iBRB in hypoxic conditions. Although oBRB breakdown can occur in conditions such as accelerated hypertension and the toxaemia of pregnancy, both of which are associated with choroidal ischaemia and in age-related macular degeneration (ARMD), and is a feature of exudative (serous) retinal detachment, our studies have shown that the oBRB remains intact in hypoxic/ischaemic conditions. Clinically, anti-VEGF therapy has been shown to improve vision in diabetic maculopathy and in neovascular ARMD. The visual benefit in both conditions appears to arise from the restoration of BRB integrity with a reduction of retinal oedema. PMID:18940262

  18. Effects of Bordetella pertussis toxin pretreatment on the antiarrhythmic action of ischaemic preconditioning in anaesthetized rats.

    PubMed Central

    Piacentini, L; Wainwright, C L; Parratt, J R

    1995-01-01

    1. Bordetella pertussis toxin, which catalyses the ADP-ribosylation of certain guanine nucleotide binding proteins (G proteins), thus functionally uncoupling them from associated receptors, was examined to determine whether it modified the antiarrhythmic effect of ischaemic preconditioning in anaesthetized rats. 2. Pertussis toxin (25 micrograms kg-1, i.p., 48 h prior to heart isolation) attenuated the negative chronotropic effect of acetylcholine (ACh) in rat isolated Langendorff perfused hearts. ACh (10 microM) reduced heart rate by 4% in hearts taken from pertussis toxin-treated animals, compared to a reduction of 57% in hearts taken from animals treated only with vehicle. 3. In anaesthetized rats, ischaemic preconditioning (a single 3 min occlusion of the left main coronary artery followed by 10 min reperfusion) had a pronounced antiarrhythmic effect during a subsequent 30 min period of regional myocardial ischaemia. Compared to hearts receiving only a 30 min period of left coronary occlusion, there was a reduced mortality (67% and 0% for control and preconditioned groups, respectively; P < 0.01) and decreased incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF). Pretreatment with pertussis toxin (25 micrograms kg-1, i.p., 48 h previously) did not modify the arrhythmias associated with a 30 min period of regional myocardial ischaemia, neither did it modify the reduction in mortality (from 56% to 0%; P < 0.05) associated with preconditioning. Furthermore, the decrease in total ventricular premature beat count induced by preconditioning seen in controls (from 427 +/- 130 to 95 +/- 45) was also seen in pertussis toxin-treated rats (from 252 +/- 190 to 57 +/- 25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7773535

  19. Transient ischaemic attacks: which patients are at high (and low) risk of serious vascular events?

    PubMed Central

    Hankey, G J; Slattery, J M; Warlow, C P

    1992-01-01

    The aims of this study were to determine the important prognostic factors at presentation which identify patients with transient ischaemic attacks (TIA) who are at high risk (and low risk) of serious vascular events and to derive a prediction model (equation) for each of the major vascular outcome events. A cohort of 469 TIA patients referred to a University hospital, without prior stroke, were evaluated prospectively and followed up over a mean period of 4.1 years (range 1-10 years). The major outcome events of interest were 1) stroke 2) coronary event and 3) stroke, myocardial infarction or vascular death (whichever occurred first). Prognostic factors and their hazard ratios were identified by means of the Cox proportional hazards multiple regression analysis. The significant adverse prognostic factors (in order of strength of association) for stroke were an increasing number of TIAs in the three months before presentation, increasing age, peripheral vascular disease, left ventricular hypertrophy and TIAs of the brain (compared with the eye); the prognostic factors for coronary event were increasing age, ischaemic heart disease, male sex, and a combination of carotid and vertebrobasilar TIAs at presentation; and for stroke, myocardial infarction or vascular death they were increasing age, peripheral vascular disease, increasing number of TIAs in the three months before presentation, male sex, a combination of carotid and vertebrobasilar TIAs at presentation, TIAs of the brain (compared with the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the presence of residual neurological signs after the TIA. Prediction models (equations) of both the relative risk and absolute risk of each of the major outcome events were produced, based on the presence or level of the significant prognostic factors and their hazard. Before it can be concluded that our equations accurately predict prognosis and

  20. An outbreak of pyrimethamine toxicity in patients with ischaemic heart disease in Pakistan.

    PubMed

    Khan Assir, Muhammad Zaman; Ahmad, Hafiz Ijaz; Akram, Javed; Yusuf, Noshin Wasim; Kamran, Umair

    2014-09-01

    We investigated an outbreak of darkening of skin, bleeding from multiple sites, leucopenia and thrombocytopenia in ischaemic heart disease patients. Case patients were defined as patients who had received medicines from the pharmacy of Punjab Institute of Cardiology between 1 December 2011 and 12 January 2012 and who developed any one of the following: darkening of skin, bleeding from any site, thrombocytopenia and leucopenia. Clinical and drug-related data were abstracted. All 664 case patients had received iso-sorbide-mono-nitrate contaminated with about 50 mg of pyrimethamine, and 151 (23%) died. The median age of 117 patients admitted at Jinnah Hospital Lahore was 57 years (range, 37-100) and 92 (79%) were male. The median time from intake of medicine to presentation was 37 days (range 13-72). Symptoms and signs included bleeding (in 95% of the patients), skin hyperpigmentation (in 61%), diarrhoea (in 53%) and abdominal pain (in 48%). At presentation, the median white cell count was 2.3 × 10(9) /L (range, 0.1 × 10(9) -16.0 × 10(9) ), the median hemoglobin concentration was 109 g/L (range 58-169) and the median platelet count was 18 × 10(9) /L (range, 0 × 10(9) -318 × 10(9) ). Bone marrow examination revealed trileneage dysplasia and severe megaloblastosis. The predictors of mortality included presentation prior to 15 January 2012, age more than 57 years, hypotension and leukocyte count less than 1.5 × 10(9) /L. None of the patients who died received Calcium folinate because all deaths occurred prior to contaminant identification. We describe an outbreak of pyrimethamine toxicity in ischaemic heart disease patients receiving medicines from a single pharmacy due to accidental contamination of iso-sorbide mono-nitrate tablets at industrial level. Late recognition of illness resulted in high mortality. PMID:24490639

  1. Effects of ischaemic training on force development and fibre-type composition in human skeletal muscle.

    PubMed

    Eiken, O; Sundberg, C J; Esbjörnsson, M; Nygren, A; Kaijser, L

    1991-01-01

    Force (peak torque) of m. quadriceps femoris was measured during 60 repeated, voluntary dynamic knee extensions in 10 men before and after a 4-week training regimen of one-legged cycle exercise. Biopsies for histochemical analysis were obtained from the lateral vastus muscle after the training period. One leg was trained with the blood flow to the leg muscles reduced by local supra-atmospheric external pressure of 50 mmHg ('Ischaemic leg, I-leg'). Employing the same work-load profile the other leg was trained at normal atmospheric pressure ('Non-restricted-flow leg, N-leg'). In response to I-training, Maximum Peak Torqued (MPT; the highest torque produced in any contraction) and Initial Peak Torque (IPT; the average peak torque of the initial 12 contractions) decreased by 8% (P less than 0.01) and 9% (P less than 0.001), respectively. Final Peak Torque (FPT; the average peak torque of the final 12 contractions) increased by 13% (P less than 0.05) after I-training. No changes in MPT, IPT or FPT occurred following N-training. After training the proportion of slow-twitch fibres was higher (P less than 0.05) and the mean slow-twitch fibre area was larger (P less than 0.05) in the I-than in the N-trained leg. The results indicate that blood flow-restricted training, in contrast to non-restricted-flow training, decreases maximum voluntary dynamic force, possibly by inducing an increase in the share of the muscle cross-sectional area consisting of slow-twitch fibres. That flow-restricted training improves maintenance of force during short-term local exercise may reflect ischaemically induced changes in the metabolic characteristics of skeletal muscle. PMID:2019077

  2. Viral hepatitis: Indian scenario.

    PubMed

    Satsangi, Sandeep; Chawla, Yogesh K

    2016-07-01

    Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India. PMID:27546957

  3. Diabetes and Hepatitis B Vaccination

    MedlinePlus

    Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

  4. Hepatitis B Blood Tests: FAQ

    MedlinePlus

    ... 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working on ... people living with hepatitis B. Learn About Hepatitis B in 10 Other Languages . Resource Video See More ...

  5. Hepatitis Information for the Public

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...

  6. Resistance to leptin action is the major determinant of hepatic triglyceride accumulation in vivo.

    PubMed

    Fishman, Sigal; Muzumdar, Radhika H; Atzmon, Gil; Ma, Xiaohui; Yang, Xiaoman; Einstein, Francine H; Barzilai, Nir

    2007-01-01

    Impairment of both insulin and leptin action has been implicated in the pathogenesis of nonalcoholic fatty liver disease. By assessing hepatic triglyceride (TG) stores in response to modulation of leptin action (by leptin infusion), we attempted to determine whether leptin has the major role in hepatic TG accumulation. TG were markedly decreased (by 63%, P<0.05) in young animals treated with leptin. However, this was also associated with improvement in hepatic insulin action (2-fold decrease in HGP during clamp, P<0.05). These effects on hepatic TG stores and insulin action were abolished in old rats who demonstrate leptin resistance. Since these experiments could not discern the role of leptin from the role of hepatic insulin action on hepatic TG stores, we further examined the effect of improvement of hepatic insulin action by visceral fat removal (VF-). Enhancement of hepatic insulin action in old VF-rats was associated with reduced hepatic TG stores (by 64% P<0.01). Because this manipulation may have induced an improvement in leptin action as well, we studied VF removal in a genetically leptin-resistant model (Zucker Diabetic Fatty rats, ZDF). Only in this mode was exclusive improvement of hepatic insulin action by VF removal not associated with reduced hepatic TG stores, suggesting that improved hepatic insulin action is not necessary for modulation of hepatic TG stores. By dissociating action of leptin from that of insulin, we suggest that the failure of leptin action is the major physiological mechanism for hepatic steatosis. PMID:17099068

  7. Left ventricular partitioning in systolic heart failure subjects: addressing a mechanistic void with current therapies.

    PubMed

    Schäfer, Ulrich

    2016-05-17

    ICD patients with narrow QRS, CRT non-responders, and functional MR patients all have one mechanistic failure mode that is left untreated - the scar left behind following an MI. ICDs, CRTs, and MitraClip implantation are all well-proven therapies, but the Parachute device may address the mechanistic void that remains after each of these therapies has been used and may further improve patients' outcomes. A pooled analysis of 134 subjects was conducted using the first three clinical trials which included subjects with symptomatic ischaemic HF with LV wall motion abnormalities secondary to MI, and an LV ejection fraction less than 40%. The two-year cumulative mortality rate was 12.9%, with 8.7% in the first year and an increment of 4.2% in the second, which is a 53% reduction as compared to the first year. There is a significant proportion of patients with ischaemic heart failure being excluded from cardiac rhythm management (CRT, etc.), leaving a large treatment gap until mechanical support devices (LVAD) or heart transplantation in progressive heart failure are indicated. Along with other heart failure devices, Parachute may be a useful treatment modality, addressing a mechanistic void in the treatment of this disease. Current data support improvements in haemodynamics, functional capacity, six-minute walk distance, quality of life and a promising decline in mortality two years after Parachute implantation. PMID:27174122

  8. Auto immune hepatitis

    PubMed Central

    van Gerven, Nicole MF; de Boer, Ynto S; Mulder, Chris JJ; van Nieuwkerk, Carin MJ; Bouma, Gerd

    2016-01-01

    To provide an update of the latest trends in epidemiology, clinical course, diagnostics, complications and treatment of auto immune hepatitis (AIH). A search of the MEDLINE database was performed using the search terms: “auto immune hepatitis”, “clinical presentation”, “symptoms”, “signs”, “diagnosis”, “auto antibodies”, “laboratory values”, “serology”, “histopathology”, “histology”, “genetics”, “HLA genes”, “non-HLA genes”, “environment”, “epidemiology”, “prevalence”, “incidence”, “demographics”, “complications”, “HCC”, “PBC”, “PSC”, “corticosteroid”, “therapy”, “treatment”, “alternative treatment”. English-language full-text articles and abstracts were considered. Articles included reviews, meta-analysis, prospective retrospective studies. No publication date restrictions were applied. AIH is an immune meditated progressive inflammatory liver disease that predominantly affects middle-aged females but may affect people of all ages. The clinical spectrum of AIH is wide, ranging from absent or mild symptoms to fulminant hepatic failure. The aetiology of AIH is still unknown, but is believed to occur as the consequence of an aberrant immune response towards an un-known trigger in a genetically susceptible host. In the absence of a gold standard, diagnosis is based on the combination of clinical, biochemical and histopathological criteria. Immunosuppressive treatment has been the cornerstone of treatment since the earliest description of the disease in 1950 by Waldenström. Such treatment is often successful at inducing remission and generally leads to normal life expectancy. Nevertheless, there remain significant areas of unmet aetiological a clinical needs including fundamental insight in disease pathogenesis, optimal therapy, duration of treatment and treatment alternatives in those patients unresponsive to standard treatment regimens. PMID:27217697

  9. Metallization failures

    NASA Technical Reports Server (NTRS)

    Beatty, R.

    1971-01-01

    Metallization-related failure mechanisms were shown to be a major cause of integrated circuit failures under accelerated stress conditions, as well as in actual use under field operation. The integrated circuit industry is aware of the problem and is attempting to solve it in one of two ways: (1) better understanding of the aluminum system, which is the most widely used metallization material for silicon integrated circuits both as a single level and multilevel metallization, or (2) evaluating alternative metal systems. Aluminum metallization offers many advantages, but also has limitations particularly at elevated temperatures and high current densities. As an alternative, multilayer systems of the general form, silicon device-metal-inorganic insulator-metal, are being considered to produce large scale integrated arrays. The merits and restrictions of metallization systems in current usage and systems under development are defined.

  10. A new transmissible agent causing acute hepatitis, chronic hepatitis and cirrhosis in dogs.

    PubMed

    Jarrett, W F; O'Neil, B W

    1985-06-15

    There is a hepatitis of dogs which occurs in acute, persistent and chronic forms. Histological studies of spontaneous cases suggested that several apparently diverse hepatic diseases might be stages of one process. This was also implied by follow up studies and case histories: acute non-lethal episodes were followed later by the development of chronic hepatitis, cirrhosis and liver failure. Serum was taken and homogenates of liver were made from three field cases representing different putative temporal stages of the complex. These were injected into experimental dogs and a hepatitis was induced in all. The cytopathological and histological changes were the same in all animals and were identical to field cases. Acute lethal disease and persistent infections were produced. Two second passages were carried out and an identical condition was induced, characterised by recurrent episodes of subclinical hepatitis and persistent infection. It is suggested that the disease might be named canine acidophil cell hepatitis in view of the pathognomonic cytopathology. Specific morphological criteria have been established for this hepatitis. PMID:4024428

  11. Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy.

    PubMed

    Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade

    2016-09-01

    Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties. PMID:27337989

  12. [Viral hepatitis in travellers].

    PubMed

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  13. Hepatic abscesses

    PubMed Central

    Rajagopalan, S.; Langer, V.

    2012-01-01

    Hepatic abscesses are potentially lethal diseases if early diagnosis and treatment are not instituted. They are prevalent all over the globe and pyogenic abscesses are predominant over amoebic. With better control of intra abdominal and systemic infections by a spectrum of antibiotics, aetiology of pyogenic abscesses are secondary to interventions and diseases in the biliary tree to a large extent today. The common organisms isolated are the Gram negative group. Amoebic abscesses continue to plague some regions of the world where hygiene and sanitation are questionable. Over the years, diagnosis, treatment and prognosis have evolved remarkably. Imaging modalities like ultrasonography and CT scan have become the cornerstone of diagnosis. The absence of ionizing radiation makes MRI an attractive alternative in patients who require multiple follow up scans. Serological testing in amoebic abscesses has become more reliable. Though antibiotics have remained the principal modality of management, percutaneous drainage of abscesses have vastly improved the chances of cure and bring down the morbidity drastically in pyogenic abscesses. Amoebic abscesses respond well to medical treatment with nitroimidazoles, and minimally invasive surgical drainage is an option in cases where open surgery is indicated. PMID:24532886

  14. Hepatitis B Test

    MedlinePlus

    ... IgM; anti-HBe; Hepatitis B e Antibody; HBV DNA Formal name: Hepatitis B Virus Testing Related tests: ... produced by the virus, and others detect viral DNA . The main uses for HBV tests include: To ...

  15. Hepatitis Foundation International

    MedlinePlus

    ... partner – it's your best friend. Welcome. The Hepatitis Foundation International (HFI) is a 501 (c) 3 non- ... and cures is your participation in the Hepatitis Foundation International Registry. Whether you are affected, a caregiver, ...

  16. Hepatitis A - children

    MedlinePlus

    ... hepatitis A. Children can get hepatitis A at day care center from other children or from child care ... treatment with immunoglobulin therapy. If your child attends day care: Make sure the children and staff at the ...

  17. Hepatitis C (image)

    MedlinePlus

    Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs ...

  18. The impact of the variation in death certification and coding practices on trends in mortality from ischaemic heart disease.

    PubMed

    Chen, Linping; Walker, Sue; Tong, Shilu

    2002-01-01

    This review examines the literature relating to the effect of death certification practices, coding and the terminology used by certifiers on trends in mortality from ischaemic heart disease (IHD). The review identifies factors that affect mortality trends in a number of countries and discusses methods for assessing the impact of these issues on trends in mortality from IHD. The review found that although the magnitude of the effects of the issues on trends in mortality from ischaemic heart disease varied among countries and sub-populations, miscertification and the resultant assignment of misleading ICD codes, particularly for ill-defined cardiovascular conditions, were important factors affecting the IHD mortality trends. In light of these findings, it is essential to monitor regularly the accuracy of death certificates for IHD and consider necessary adjustments in analysing mortality trends from IHD. PMID:12404982

  19. Myocardial ischaemia reperfusion injury: the challenge of translating ischaemic and anaesthetic protection from animal models to humans.

    PubMed

    Xia, Z; Li, H; Irwin, M G

    2016-09-01

    Myocardial ischaemia reperfusion injury is the leading cause of death in patients with cardiovascular disease. Interventions such as ischaemic pre and postconditioning protect against myocardial ischaemia reperfusion injury. Certain anaesthesia drugs and opioids can produce the same effects, which led to an initial flurry of excitement given the extensive use of these drugs in surgery. The underlying mechanisms have since been extensively studied in experimental animal models but attempts to translate these findings to clinical settings have resulted in contradictory results. There are a number of reasons for this such as dose response, the intensity of the ischaemic stimulus applied, the duration of ischaemia and lost or diminished cardioprotection in common co-morbidities such as diabetes and senescence. This review focuses on current knowledge regarding myocardial ischaemia reperfusion injury and cardioprotective interventions both in experimental animal studies and in clinical trials. PMID:27566808

  20. Management in Acute Liver Failure

    PubMed Central

    Shalimar; Acharya, Subrat K.

    2015-01-01

    Acute liver failure (ALF) is a rare, potentially fatal complication of severe hepatic illness resulting from various causes. In a clinical setting, severe hepatic injury is usually recognised by the appearance of jaundice, encephalopathy and coagulopathy. The central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a central role in the pathogenesis. The role of newer ammonia lowering agents is still evolving. Liver transplant is the only effective therapy that has been identified to be of promise in those with poor prognostic factors, whereas in the others, aggressive intensive medical management has been documented to salvage a substantial proportion of patients. A small fraction of patients undergo liver transplant and the remaining are usually treated with medical therapy. Therefore, identification of the complications and causes of death in such patients, and use of appropriate prognostic models to identify those who need liver transplant and those who can be managed with medical treatment is a vital component of therapeutic strategy. In this review, we discuss the various pathogenetic mechanisms and treatment options available. PMID:26041950

  1. Hepatitis E Pathogenesis.

    PubMed

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  2. Treating hepatitis C.

    PubMed

    Hanson, Karmen

    2014-10-01

    (1) New treatments for hepatitis C are curing more people than before. (2) Baby boomers make up an estimated 75 percent of all cases of hepatitis C. (3) Medicare and some insurance plans cover screening for hepatitis C as a preventive service without a copayment. PMID:25514812

  3. Hepatitis E Pathogenesis

    PubMed Central

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  4. Hepatitis B (HBV)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) Print A A A Text Size ... Prevented? How Is It Treated? What Is It? Hepatitis (pronounced: hep-uh-TIE-tiss) is a disease ...

  5. A novel snake venom-derived GPIb antagonist, anfibatide, protects mice from acute experimental ischaemic stroke and reperfusion injury

    PubMed Central

    Li, Ting-Ting; Fan, Man-Li; Hou, Shi-Xiang; Li, Xiao-Yi; Barry, Devin M; Jin, Hui; Luo, Sheng-Yong; Kong, Feng; Lau, Lit-Fui; Dai, Xiang-Rong; Zhang, Guo-Hui; Zhou, Lan-Lan

    2015-01-01

    Background and Purpose Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice. Experimental Approach Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 μg·kg−1), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control. Key Results Twenty-four hours after MCAO, anfibatide-treated mice showed significantly improved ischaemic lesions in a dose-dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide-treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban-treated mice. Conclusions and Implications Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke. PMID:25917571

  6. Increased dispersion of ventricular repolarization and ventricular tachyarrhythmias in the globally ischaemic rabbit heart.

    PubMed

    Kurz, R W; Xiao-Lin, R; Franz, M R

    1993-11-01

    Contemporary concepts of ischaemic ventricular tachyarrhythmias (VTA) are based on increased electrophysiological heterogeneity of the myocardium. We developed a multi-site monophasic action potential recording system for an isolated rabbit heart to study the effects of global ischaemia on the electrophysiological properties at different ventricular sites simultaneously. The hearts were paced from the right ventricle (RV), and conduction time (CT), action potential duration (APD) and total repolarization time (TRT = [CT + APD]) were measured during normal perfusion and ischaemia. The dispersion of these parameters was calculated as the maximal difference between simultaneous recordings. Inducibility of VTA by programmed extrastimulation (ES) was investigated under normal and ischaemic conditions. During global ischaemia, CT increased progressively, showing a faster and greater increase at the left ventricle (LV) than at the RV. After 10 min the prolongation of CT reached a plateau at the LV while it continued to rise in the RV. The dispersion of CT increased from 14.5 +/- 2.7 ms during normal perfusion to a maximum of 79.8 +/- 17.2 ms after 14 min of ischaemia (P < 0.0001). APD was uniform at the three sites (190.9 +/- 10.2, 185.0 +/- 8.6 and 179.3 +/- 9.8 ms, ns) during normal perfusion but changed non-uniformly during ischaemia. There was a transient lengthening of APD until 1 and 3 min of ischaemia at the LV sites followed by a rapid shortening of APD. At the RV site, APD continued to increase until 5 min of ischaemia and then shortened gradually. Consequently, dispersion of APD showed a rapid initial rise from 17.7 +/- 2.7 ms to 77.8 +/- 10.2 ms (P < 0.0001) followed by a slower final increase. TRT was uniform during normal perfusion (210.4 +/- 10.3, 213.1 +/- 7.8, 212.1 +/- 10.3 ms, ns) but became non-uniform during global ischaemia. The dispersion of TRT increased from 15.4 +/- 4.2 ms to 92.6 +/- 23.2 ms (P < 0.0001) during 14 min of global ischaemia. Both CT

  7. The role of Toll-like receptor 4 (TLR4) in cardiac ischaemic-reperfusion injury, cardioprotection and preconditioning.

    PubMed

    Lee, Sam Man; Hutchinson, Mark; Saint, David A

    2016-09-01

    Cardiac ischaemic-reperfusion injury (IRI) remains the primary cause of mortality throughout the developed world. Molecular mechanisms underlying IRI are complex and are often interlinked with each other driving a synergistic response. Toll-like receptor 4 (TLR4), an immunosurveillance receptor, is known to enhance tissue injury during IRI by enhancing the inflammatory response. The release of endogenous components during IRI bind onto TLR4 leading to the activation of multiple signalling kinases. Once this event occurs these proteins are defined as danger associated molecular patterns molecules (DAMPs) or alarmins. Examples include heat shock proteins, high mobility group box one (HMGB1) and extracellular matrix proteins, all of which are involved in IRI. However, literature in the last two decades suggests that transient stimulation of TLR4 may suppress IRI and thus improve cardiac recovery. Furthermore, it remains to be seen what role TLR4 plays during ischaemic-preconditioning where acute bouts of ischaemia, preceding a harmful bout of ischaemic-reperfusion, is cardioprotective. The other question which also needs to be considered is that if transient TLR4 signalling drives a preconditioning response then what are the ligands which drive this? Hence the second part of this review explores the possible TLR4 ligands which may promote cardioprotection against IRI. PMID:27249055

  8. Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia.

    PubMed

    Lopes, Rosana S; Cardoso, Marcelo M; Sampaio, Arthur O; Barbosa, Mario Santos; Souza, Celice C; DA Silva, Michelle C; Ferreira, Elane Magno N; Freire, Marco Aurelio M; Lima, Rafael Rodrigues; Gomes-Leal, Walace

    2016-09-01

    Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1+ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX+ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN+ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke. PMID:27581930

  9. Acute hepatitis E complicated by acute pancreatitis and multiorgan dysfunction

    PubMed Central

    Karanth, Suman S; Khan, Zohaib; Rau, Nileshwar Radhakrishna; Rao, Karthik

    2014-01-01

    We report this rare case of a 27-year-old man who presented with acute hepatitis E and went on to develop acute epigastric pain. He was diagnosed to have acute severe pancreatitis with shock and acute renal failure due to hepatitis E. Such a phenomenon has rarely been reported in the literature, with patients following a benign course and complete recovery after conservative management and analgesia. Awareness of this potentially life-threatening complication, especially in young men from endemic areas with acute hepatitis E presenting with abdomen pain has been highlighted. PMID:24899005

  10. Role of the parasympathetic nervous system in cardioprotection by remote hindlimb ischaemic preconditioning.

    PubMed

    Donato, Martín; Buchholz, Bruno; Rodríguez, Manuel; Pérez, Virginia; Inserte, Javier; García-Dorado, David; Gelpi, Ricardo J

    2013-02-01

    This investigation was designed to determine the participation of the vagus nerve and muscarinic receptors in the remote ischaemic preconditioning (rIPC) mechanism. New Zealand rabbits were anaesthetized, and the femoral artery was dissected. After 30 min of monitoring, the hearts were isolated and subjected to 30 min of global no-flow ischaemia and 180 min of reperfusion (non-rIPC group). The ventricular function was evaluated, considering the left ventricular developed pressure and the left ventricular end-diastolic pressure. In the rIPC group, the rabbits were subjected to three cycles of hindlimb ischaemia (5 min) and reperfusion (5 min), and the same protocol as that used in non-rIPC group was then repeated. In order to evaluate the afferent neural pathway during the rIPC protocol we used two groups, one in which the femoral and sciatic nerves were sectioned and the other in which the spinal cord was sectioned (T9-T10 level). To study the efferent neural pathway during the rIPC protocol, the vagus nerve was sectioned and, in another group, atropine was administered. The effect of vagal stimulation was also evaluated. An infarct size of 40.8 ± 3.1% was obtained in the non-rIPC group, whereas in rIPC group the infarct size decreased to 16.4 ± 3.5% (P < 0.05). During the preconditioning protocol, the vagus nerve section and the atropine administration each abolished the effect of rIPC on infarct size. Vagal stimulation mimicked the effect of rIPC, decreasing infarct size to 15.2 ± 4.7% (P < 0.05). Decreases in infarct size were accompanied by improved left ventricular function. We demonstrated the presence of a neural afferent pathway, because the spinal cord section completely abolished the effect of rIPC on infarct size. In conclusion, rIPC activates a neural afferent pathway, the cardioprotective signal reaches the heart through the vagus nerve (efferent pathway), and acetylcholine activates the ischaemic preconditioning phenomenon when acting on the

  11. The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration

    PubMed Central

    Lim, Kelvin H H; Javadov, Sabzali A; Das, Manika; Clarke, Samantha J; Suleiman, M-Saadeh; Halestrap, Andrew P

    2002-01-01

    Studies with different ATP-sensitive potassium (KATP) channel openers and blockers have implicated opening of mitochondrial KATP (mitoKATP) channels in ischaemic preconditioning (IPC). It would be predicted that this should increase mitochondrial matrix volume and hence respiratory chain activity. Here we confirm this directly using mitochondria rapidly isolated from Langendorff-perfused hearts. Pre-ischaemic matrix volumes for control and IPC hearts (expressed in μl per mg protein ± s.e.m., n = 6), determined with 3H2O and [14C]sucrose, were 0.67 ± 0.02 and 0.83 ± 0.04 (P < 0.01), respectively, increasing to 1.01 ± 0.05 and 1.18 ± 0.02 following 30 min ischaemia (P < 0.01) and to 1.21 ± 0.13 and 1.26 ± 0.25 after 30 min reperfusion. Rates of ADP-stimulated (State 3) and uncoupled 2-oxoglutarate and succinate oxidation increased in parallel with matrix volume until maximum rates were reached at volumes of 1.1 μl ml−1 or greater. The mitoKATP channel opener, diazoxide (50 μm), caused a similar increase in matrix volume, but with inhibition rather than activation of succinate and 2-oxoglutarate oxidation. Direct addition of diazoxide (50 μm) to isolated mitochondria also inhibited State 3 succinate and 2-oxoglutarate oxidation by 30 %, but not that of palmitoyl carnitine. Unexpectedly, treatment of hearts with the mitoKATP channel blocker 5-hydroxydecanoate (5HD) at 100 or 300 μm, also increased mitochondrial volume and inhibited respiration. In isolated mitochondria, 5HD was rapidly converted to 5HD-CoA by mitochondrial fatty acyl CoA synthetase and acted as a weak substrate or inhibitor of respiration depending on the conditions employed. These data highlight the dangers of using 5HD and diazoxide as specific modulators of mitoKATP channels in the heart. PMID:12482899

  12. The Pleiotropic Effects of Simvastatin on Retinal Microvascular Endothelium Has Important Implications for Ischaemic Retinopathies

    PubMed Central

    Medina, Reinhold J.; O'Neill, Christina L.; Devine, Adrian B.; Gardiner, Tom A.; Stitt, Alan W.

    2008-01-01

    Background Current guidelines encourage the use of statins to reduce the risk of cardiovascular disease in diabetic patients; however the impact of these drugs on diabetic retinopathy is not well defined. Moreover, pleiotropic effects of statins on the highly specialised retinal microvascular endothelium remain largely unknown. The objective of this study was to investigate the effects of clinically relevant concentrations of simvastatin on retinal endothelium in vitro and in vivo. Methods and Findings Retinal microvascular endothelial cells (RMECs) were treated with 0.01–10 µM simvastatin and a biphasic dose-related response was observed. Low concentrations enhanced microvascular repair with 0.1 µM simvastatin significantly increasing proliferation (p<0.05), and 0.01 µM simvastatin significantly promoting migration (p<0.05), sprouting (p<0.001), and tubulogenesis (p<0.001). High concentration of simvastatin (10 µM) had the opposite effect, significantly inhibiting proliferation (p<0.01), migration (p<0.01), sprouting (p<0.001), and tubulogenesis (p<0.05). Furthermore, simvastatin concentrations higher than 1 µM induced cell death. The mouse model of oxygen-induced retinopathy was used to investigate the possible effects of simvastatin treatment on ischaemic retinopathy. Low dose simvastatin(0.2 mg/Kg) promoted retinal microvascular repair in response to ischaemia by promoting intra-retinal re-vascularisation (p<0.01). By contrast, high dose simvastatin(20 mg/Kg) significantly prevented re-vascularisation (p<0.01) and concomitantly increased pathological neovascularisation (p<0.01). We also demonstrated that the pro-vascular repair mechanism of simvastatin involves VEGF stimulation, Akt phosphorylation, and nitric oxide production; and the anti-vascular repair mechanism is driven by marked intracellular cholesterol depletion and related disorganisation of key intracellular structures. Conclusions A beneficial effect of low-dose simvastatin on ischaemic

  13. The risk of ischaemic colitis in irritable bowel syndrome patients treated with serotonergic therapies.

    PubMed

    Lewis, James H

    2011-07-01

    Ischaemic colitis (IC) is the most common form of ischaemic injury to the gastrointestinal (GI) tract. IC typically presents with the sudden onset of lower abdominal pain, cramping and rectal bleeding, and is usually self-limited with low morbidity, although it may cause gangrenous or fulminant colitis, especially when the right colon is involved. Multiple medical conditions, as well as several pharmacological agents, are associated with IC, including irritable bowel syndrome (IBS) and drugs used for its treatment that act on gut serotonin 5-HT receptors. These include the selective 5-HT(3) receptor antagonist alosetron, currently approved for the treatment of severe diarrhoea-predominant IBS in women who fail to respond to conventional treatment, and cilansetron, another 5-HT(3) receptor antagonist that is no longer in clinical development. In addition, the 5-HT(4) receptor partial agonist tegaserod, which was approved for the treatment of constipation-predominant IBS in women, was associated with IC in the postmarketing setting, as was renzapride, a 5-HT(4) agonist/5-HT(3) antagonist. Although several hypotheses have been proposed, the pathophysiological basis for development of IC with 5-HT(3) receptor antagonists or 5-HT(4) receptor agonists remains unknown. Of interest, several population-based studies demonstrated that a diagnosis of IBS (independent of serotonergic therapies) increases the risk of developing IC 2- to 4-fold. As a result, IBS patients with the acute onset of abdominal pain, tenderness, diarrhoea or lower intestinal bleeding, especially those with predisposing conditions or medications, should be evaluated promptly for IC. The management of IC remains supportive; most cases of non-gangrenous IC, as seen in the alosetron and tegaserod databases, have been transient and have resolved spontaneously without complications or death. Despite the small number of deaths associated with alosetron in patients with complications of constipation and

  14. Infantile Hepatic Hemangioendothelioma: An Uncommon Cause of Persistent Pulmonary Hypertension in a Newborn Infant

    PubMed Central

    Chatmethakul, Trassanee; Bhat, Ramachandra; Alkaabi, Maryam; Siddiqui, Abdul; Peevy, Keith; Zayek, Michael

    2016-01-01

    Multifocal and diffuse infantile hepatic hemangioendotheliomas commonly present with signs of high-output congestive heart failure. In addition, prolonged persistent pulmonary overcirculation eventually leads to the development of pulmonary hypertension at a later age. We report a 2-day old, full-term infant with multifocal, large infantile hepatic hemangioendothelioma, who presented with an early onset of pulmonary hypertension, managed successfully with supportive care and systemic therapy directed toward the involution of infantile hepatic hemangioendothelioma. PMID:27468364

  15. Hepatitis: protecting BMETs & CEs.

    PubMed

    Baker, S A

    1994-01-01

    Hepatitis is the primary occupational hazard for healthcare workers. Not until the 1970s were hepatitis viruses isolated and identified as types A and B. In the late 1970s, hepatitis D was discovered as a major cause of fulminant hepatitis. Soon, it was evident that another type was also at work. Because testing was only available for types A and B, the new category was referred to as non-A, non-B. In the 1980s, scientists identified two more viruses from this non-A, non-B group, namely hepatitis E and hepatitis C. These five types of hepatitis have different modes of transmission. The fecal-to-oral route is the mode of transmission for hepatitis types A and E. But, types B and D are bloodborne pathogens. With the advent of a safe vaccine for hepatitis B, this category is declining. To date, hepatitis C appears to have multiple routes of transmission, with half the cases being posttransfusion. In the United States, 85,000 people per year develop chronic hepatitis C, which ultimately leads to severe liver damage. This paper addresses each of the five viruses that have been grouped by routes of transmission, prevention techniques for BMETs and CEs, and statistics of reported cases to the Centers for Disease Control and Prevention (CDCP) over the last 20 years. PMID:10139739

  16. Raynaud's phenomenon and bilateral olecranon bursitis co-existing in a patient with chronic hepatitis B and D treated with pegylated interferon.

    PubMed

    Arain, Shafique Rehman; Umer, Tahira Perveen

    2016-06-01

    Pegylated interferon remains the first line treatment for patients with hepatitis D virus and more than one year therapy may be necessary. Interferon a has the most extensive clinical application and is used for the treatment of chronic hepatitis B and D virus as well as HCV infections. The attachment of polyethylene glycol to interferon increases its half-life. Treatment with peg interferon is associated with many troublesome and occasionally with serious or even life-threatening side effects. In this case report, we have described a patient with chronic hepatitis B and D, who developed Raynaud's phenomenon, ischaemic digital necrosis and bilateral olecranon bursitis during Pegylated interferon therapy. The patient underwent a very extensive workup in order to determine the underlying cause of his digital ischaemia and olecranon bursitis, which was finally determined to be secondary to the use of Pegylated interferon. PMID:27339587

  17. Hepatitis B viral infection of hepatic progenitor cells. Resolving unresolved questions?

    PubMed

    Minuk, G Y; Baruch, Y

    2016-06-01

    Accumulated data to date do not entirely explain the; propensity of the hepatitis B virus (HBV) to cause chronic infections in newborns; failure of antiviral agents to resolve infections or precise mechanism whereby HBV causes hepatocellular carcinoma (HCC). Based on the increased numbers of hepatic stem/progenitor cells (HPCs) present within the neonatal liver, the refractoriness of these cells to the effects of interferons and xenobiotics and their ability to undergo malignant transformation, we hypothesize that HBV infection of HPCs could explain these and perhaps other clinical features of chronic HBV. PMID:27142136

  18. Liver transplantation for viral hepatitis in 2015

    PubMed Central

    Ferrarese, Alberto; Zanetto, Alberto; Gambato, Martina; Bortoluzzi, Ilaria; Nadal, Elena; Germani, Giacomo; Senzolo, Marco; Burra, Patrizia; Russo, Francesco Paolo

    2016-01-01

    Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release. PMID:26819523

  19. Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure.

    PubMed

    Karvellas, Constantine J; Subramanian, Ram M

    2016-07-01

    Artificial (nonbiological) extracorporeal liver support devices aim to remove albumin-bound and water-soluble toxins to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. The following beneficial effects have been documented: improvement of jaundice, amelioration of hemodynamic instability, reduction of portal hypertension, and improvement of hepatic encephalopathy. The only randomized prospective multicenter controlled trial to show an improvement in transplant-free survival was for high-volume plasmapheresis. Biological (cell-based) extracorporeal liver support systems aim to support the failing liver through detoxification and synthetic function and warrant further study for safety and benefit. PMID:27339682

  20. Personal experience with 411 hepatic resections.

    PubMed Central

    Iwatsuki, S; Starzl, T E

    1988-01-01

    Over a 24-year period, 411 partial hepatic resections were performed: 142 right or left trisegmentectomies, 158 lobectomies, 25 segmentectomies, and 86 local excisions. The operations were performed for benign lesions in 182 patients, for primary hepatic malignancies in 106, and for hepatic metastases in 123, including 90 from colorectal cancers. The 30-day (operative) mortality rate was 3.2%, and there were an additional six late deaths (1.5%) due to hepatic failure caused by the resection. The highest operative mortality rate (6.3%) resulted from the trisegmentectomies, but this merely reflected the extent of the disease being treated. A mortality rate of 8.5% for patients with primary hepatic malignancy was associated not only with the extensiveness of lesions, but also with cirrhosis in the remaining liver fragment. There was no mortality for 123 patients with metastatic disease, 100 patients with cavernous hemangioma, 22 with liver cell adenoma, 17 with focal nodular hyperplasia, 16 with congenital cystic disease, and five with hydatid cysts. Trauma, pre-existing iatrogenic injury, and cirrhosis were the only conditions that had lethal portent in patients with benign disease. Furthermore, patients with benign disease who survived operation had minimal liability from recurrence of their original disease and none from the resection per se. By contrast, tumor recurrence dominated the actuarial survival rates for cancer patients, which at 1 and 5 years were 68.5% and 31.9%, respectively, after resection for primary hepatic malignancy, and 84.2% and 29.5%, respectively, for hepatic metastases. In this report, the expanding role of partial hepatectomy in the treatment of liver disease was emphasized, as well as the need for considering, in some cases, the alternative of total hepatectomy and liver replacement. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 9. PMID:3178330

  1. Placental weight and foetal growth rate as predictors of ischaemic heart disease in a Swedish cohort.

    PubMed

    Heshmati, A; Koupil, I

    2014-06-01

    Studies on placental size and cardiovascular disease have shown inconsistent results. We followed 10,503 men and women born in Uppsala, Sweden, 1915-1929 from 1964 to 2008 to assess whether birth characteristics, including placental weight and placenta/birth weight ratio, were predictive of future ischaemic heart disease (IHD). Adjustments were made for birth cohort, age, sex, mother's parity, birth weight, gestational age and social class at birth. Placental weight and birth weight were negatively associated with IHD. The effect of placental weight on IHD was stronger in individuals from medium social class at birth and in those with low education. Men and women from non-manual social class at birth had the lowest risk for IHD as adults. We conclude that low foetal growth rate rather than placental weight was more predictive of IHD in the Swedish cohort. However, the strong effect of social class at birth on risk for IHD did not appear to be mediated by foetal growth rate. PMID:24901654

  2. Current concepts in the diagnosis, pathogenesis and management of nonarteritic anterior ischaemic optic neuropathy

    PubMed Central

    Miller, N R; Arnold, A C

    2015-01-01

    Nonarteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Patients typically present with acute, painless, unilateral loss of vision associated with a variable visual field defect, a relative afferent pupillary defect, a swollen, hyperaemic optic disc, and one or more flame-shaped peripapillary retinal haemorrhages. The pathogenesis of this condition is unknown, but it occurs primarily in patients with structurally small optic discs that have little or no cup and a variety of underlying vascular disorders that may or may not be known at the time of visual loss. There is no consistently beneficial medical or surgical treatment for the condition, but there are now animal models that allow testing of various potential therapies. About 40% of patients experience spontaneous improvement in visual acuity. Patients in whom NAION occurs in one eye have a 15–19% risk of developing a similar event in the opposite eye over the subsequent 5 years. PMID:24993324

  3. Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome.

    PubMed Central

    Rutherford, M; Pennock, J; Schwieso, J; Cowan, F; Dubowitz, L

    1996-01-01

    Sixteen infants with hypoxic-ischaemic encephalopathy (HIE) were studied using serial magnetic resonance imaging (MRI) up to the age of 2 years. The infants had regular neurological and developmental assessments. An nuclear magnetic resonance (NMR) score was devised to quantify the early and late MRI findings and a neurological optimality score was used to quantify abnormal neurological signs at the time of the final examination. The follow up MRI score was compared with the neonatal MRI score and the outcome of the child. There was a strong positive correlation between the neonatal and follow up MRI scores and between MRI scores and optimality score. All infants with a normal outcome had patchy white matter abnormalities. All infants with an abnormal outcome had extensive white matter abnormalities. The outcome was most severe in those infants with additional basal ganglia atrophy with or without cyst formation. Infants with mild HIE who are developmentally normal at the age of 2 years do not have normal MRI scans and may be at risk of minor neurological problems by school age. Bilateral basal ganglia abnormalities are associated with severe developmental delay, but infants with mainly white matter and cortical abnormalities have less severe problems despite extensive tissue loss. Images PMID:8976678

  4. Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome.

    PubMed

    Rutherford, M; Pennock, J; Schwieso, J; Cowan, F; Dubowitz, L

    1996-11-01

    Sixteen infants with hypoxic-ischaemic encephalopathy (HIE) were studied using serial magnetic resonance imaging (MRI) up to the age of 2 years. The infants had regular neurological and developmental assessments. An nuclear magnetic resonance (NMR) score was devised to quantify the early and late MRI findings and a neurological optimality score was used to quantify abnormal neurological signs at the time of the final examination. The follow up MRI score was compared with the neonatal MRI score and the outcome of the child. There was a strong positive correlation between the neonatal and follow up MRI scores and between MRI scores and optimality score. All infants with a normal outcome had patchy white matter abnormalities. All infants with an abnormal outcome had extensive white matter abnormalities. The outcome was most severe in those infants with additional basal ganglia atrophy with or without cyst formation. Infants with mild HIE who are developmentally normal at the age of 2 years do not have normal MRI scans and may be at risk of minor neurological problems by school age. Bilateral basal ganglia abnormalities are associated with severe developmental delay, but infants with mainly white matter and cortical abnormalities have less severe problems despite extensive tissue loss. PMID:8976678

  5. Hypercoagulability Is a Stronger Risk Factor for Ischaemic Stroke than for Myocardial Infarction: A Systematic Review

    PubMed Central

    Maino, Alberto; Rosendaal, Frits R.; Algra, Ale; Peyvandi, Flora; Siegerink, Bob

    2015-01-01

    Background and Purpose Hypercoagulability increases the risk of arterial thrombosis; however, this effect may differ between various manifestations of arterial disease. Methods In this study, we compared the effect of coagulation factors as measures of hypercoagulability on the risk of ischaemic stroke (IS) and myocardial infarction (MI) by performing a systematic review of the literature. The effect of a risk factor on IS (relative risk for IS, RRIS) was compared with the effect on MI (RRMI) by calculating their ratio (RRR = RRIS/RRMI). A relevant differential effect was considered when RRR was >1+ its own standard error (SE) or <1−SE. Results We identified 70 publications, describing results from 31 study populations, accounting for 351 markers of hypercoagulability. The majority (203/351, 58%) had an RRR greater than 1. A larger effect on IS risk than MI risk (RRE>1+1SE) was found in 49/343 (14%) markers. Of these, 18/49 (37%) had an RRR greater than 1+2SE. On the opposite side, a larger effect on MI risk (RRR<1-1SE) was found in only 17/343 (5%) markers. Conclusions These results suggest that hypercoagulability has a more pronounced effect on the risk of IS than that of MI. PMID:26252207

  6. The influence of "hylase" on the ultrastructure of ischaemic heart muscle changes.

    PubMed

    David, H; Lindenau, K F; Behrisch, D

    1980-01-01

    A two-hour acute ischaemia of the myocardium was induced in dogs by ligature of the coronary arteries and the effect produced on the qualitative and quantitative ultrastructure of heart muscle cells by infusing "hylase", a hyaluronidase preparation, was examined. The changes in both the central and peripheral ischaemic zones following hylase infusion are more severe than after ischaemia alone. Particularly the mitochondria showed an increased dissolution of the outer membrane. In the case of ischaemia the percentage of mitochondria in the peripheral zone is 29.6%, in the central zone 27.6%; after hylase infusion it is 25.9% in the peripheral zone and 32.3% in the central zone. After hylase infusion, the percentage of sarcoplasm in the central zone rises to 120.7% and to 186.8% in the peripheral zone. In view of the fact that macroscopic, histological and histochemical findings also show negative effects, the infusion of hyaluronidase is not recommended. PMID:7398839

  7. Interventions addressing risk factors of ischaemic heart disease in sub-Saharan Africa: a systematic review

    PubMed Central

    Ebireri, Jennifer; Aderemi, Adewale V; Omoregbe, Nicholas; Adeloye, Davies

    2016-01-01

    Background Ischaemic heart disease (IHD) is currently ranked eighth among the leading causes of deaths in sub-Saharan Africa (sSA). Yet, effective population-wide preventive measures targeting risks in the region are still largely unavailable. We aimed to review population-wide and individual-level interventions addressing risk factors of IHD among adults in sSA. Methods A systematic search of MEDLINE, EMBASE, Global Health and AJOL was conducted to identify studies focusing on population-wide and individual-level interventions targeting risks of IHD among adults in sSA. We conducted a detailed synthesis of basic findings of selected studies. Results A total of 2311 studies were identified, with only 9 studies meeting our selection criteria. 3 broad interventions were identified: dietary modifications, physical activity and community-based health promotion measures on tobacco and alcohol cessation. 3 studies reported significant reduction in blood pressure (BP), and another study reported statistically significant reduction in mean total cholesterol. Other outcome measures observed ranged from mild to no reduction in BP, blood glucose, body mass index and total cholesterol, respectively. Conclusions We cannot specify with all certainty contextually feasible interventions that can be effective in modifying IHD risk factors in population groups across sSA. We recommend more research on IHD, particularly on the understanding of the burden, geared towards developing and/or strengthening preventive and treatment interventions for the disease in sSA. PMID:27381212

  8. [Ingestion of anabolic steroids and ischaemic stroke. A clinical case report and review of the literature].

    PubMed

    García-Esperón, Carlos; Hervás-García, José Vicente; Jiménez-González, Marta; Pérez de la Ossa-Herrero, Natalia; Gomis-Cortina, Meritxell; Dorado-Bouix, Laura; López-Cancio Martinez, Elena; Castaño-Duque, Carlos H; Millán-Torné, Mónica; Dávalos, Antonio

    2013-03-16

    INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers. PMID:23483467

  9. EEG in ischaemic stroke: quantitative EEG can uniquely inform (sub-)acute prognoses and clinical management.

    PubMed

    Finnigan, Simon; van Putten, Michel J A M

    2013-01-01

    Investigations of (sub-)acute ischaemic stroke (IS) employing quantitative electroencephalographic (QEEG) methods, in concert with other assessments, are reviewed. Numerous outcomes from hundreds of patients collectively indicate that (sub-)acute QEEG indices from standard systems can uniquely inform clinical management, particularly prognostication of outcomes from IS. Two classes of QEEG indices have proven particularly informative. The first quantifies the power of abnormal, slow activity relative to that of faster activity and the second, interhemispheric voltage asymmetry (broadband). Both have been identified as statistically significant predictors of outcomes assessed (via routine clinical scales) in the weeks and months following IS. Furthermore both have demonstrated higher predictive value than concomitant neurological assessments and scales, and to improve upon outcome prediction afforded by neuroimaging alone. These indices also may continuously provide unique, real-time insights into the efficacy of thrombolytic therapy, prior to clinical changes. Two key applications of QEEG which should prove valuable for future clinical management of IS are: (1) continuous, acute monitoring to inform about the efficacy of thrombolysis and decisions about potential additional interventions, and; (2) brief, subacute recording to inform outcome prognostication and clinical decisions about, for example, rehabilitation strategies. Ongoing research and technological developments will continue to facilitate clinical translation of QEEG investigations reviewed herein. PMID:22858178

  10. An automated system for grading EEG abnormality in term neonates with hypoxic-ischaemic encephalopathy.

    PubMed

    Stevenson, N J; Korotchikova, I; Temko, A; Lightbody, G; Marnane, W P; Boylan, G B

    2013-04-01

    Automated analysis of the neonatal EEG has the potential to assist clinical decision making for neonates with hypoxic-ischaemic encephalopathy. This paper proposes a method of automatically grading the degree of abnormality in an hour long epoch of neonatal EEG. The automated grading system (AGS) was based on a multi-class linear classifier grading of short-term epochs of EEG which were converted into a long-term grading of EEG using a majority vote operation. The features used in the AGS were summary measurements of two sub-signals extracted from a quadratic time-frequency distribution: the amplitude modulation and instantaneous frequency. These sub-signals were based on a model of EEG as a multiplication of a coloured random process with a slowly varying pseudo-periodic waveform and may be related to macroscopic neurophysiological function. The 4 grade AGS had a classification accuracy of 83% compared to human annotation of the EEG (level of agreement, κ = 0.76). Features estimated on the developed sub-signals proved more effective at grading the EEG than measures based solely on the EEG and the incorporation of additional sub-grades based on EEG states into the AGS also improved performance. PMID:23519533

  11. The involvement of cytokines in the second window of ischaemic preconditioning.

    PubMed

    Yamashita, N; Hoshida, S; Otsu, K; Taniguchi, N; Kuzuya, T; Hori, M

    2000-10-01

    We utilized a rat model of myocardial infarction to investigate whether manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, and tumour necrosis factor- alpha (TNF-alpha) and/or interleukin-1beta (IL-1beta) are involved in the late phase of ischaemic preconditioning (IP). IP was induced in anaesthetized rats by four 3-min left coronary artery (LCA) occlusions, each separated by 10 min of reperfusion. Twenty-four hours after the repetitive brief ischaemia, the LCA was occluded for 20 min followed by reperfusion for 48 h. IP reduced the infarct size by approximately 46% as determined after 48 h of reperfusion. Antisense oligodeoxynucleotides to Mn-SOD inhibited the increases in Mn-SOD content and activity, and abolished the expected decrease in myocardial infarct size. Sense or scrambled oligodeoxynucleotides did not abolish either Mn-SOD induction or tolerance to ischaemia/reperfusion. The simultaneous administration of the antibodies to TNF-alpha (0.5 ml) and IL-1beta (0.5 mg) prior to IP abolished the cardioprotection and the increase in Mn-SOD activity induced by IP. We conclude that the induction and activation of Mn-SOD, mediated by TNF-alpha and IL-1beta after IP, plays an important role in the acquisition of late-phase cardioprotection against ischaemia/reperfusion injury in rats. PMID:11015290

  12. Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

    PubMed Central

    Deanfield, John E.; Sellier, Phillipe; Thaulow, Erik; Bultas, Jan; Yunis, Carla; Shi, Harry; Buch, Jan; Beckerman, Bruce

    2010-01-01

    Aims The DoUble-blind Atorvastatin AmLodipine (DUAAL) trial investigated whether atorvastatin decreases ischaemia by a vascular benefit, independent of low-density lipoprotein cholesterol lowering, in patients with coronary artery disease (CAD), both alone and in combination with the traditional anti-anginal therapy, amlodipine. Methods and results Randomized, double-blind, parallel-group, multicountry trial (2 weeks run-in and 24 weeks active therapy) comparing three treatments: amlodipine, atorvastatin, and amlodipine + atorvastatin; in 311 patients (78% male; mean age 62 years) with stable angina (≥2 attacks/week), CAD history, ≥3 transient myocardial ischaemia (TMI) episodes, and/or ≥15 min ischaemia on 48 h ambulatory electrocardiographic (AECG) monitoring. Efficacy variables were change in TMI by AECG, exercise ischaemia, angina diary data, and inflammatory biomarkers at Week 26. There was a comparable, highly significant decrease in TMI with amlodipine and atorvastatin, but no additional benefit for the combination. More than 50% of patients became TMI-free in all three groups and this was accompanied by a comparable, marked reduction in angina and nitroglycerin consumption. High-sensitivity C-reactive protein fell by 40% in patients receiving atorvastatin but there was no change with amlodipine. Adverse events were comparable among groups. Conclusion Atorvastatin was as potent an anti-ischaemic agent as amlodipine. Future studies of combination therapies will be instructive. Clinical trial registration information: National clinical trial number: NCT00159718, protocol number A0531031 listed on http://clinicaltrials.gov/. PMID:20494902

  13. Bacterial endotoxin sensitizes the immature brain to hypoxic--ischaemic injury.

    PubMed

    Eklind, S; Mallard, C; Leverin, A L; Gilland, E; Blomgren, K; Mattsby-Baltzer, I; Hagberg, H

    2001-03-01

    Epidemiological studies show a markedly increased risk of cerebral palsy following the combined exposure of infection and birth asphyxia. However, the underlying mechanisms of this increased vulnerability remain unclear. We have examined the effects of a low dose of bacterial endotoxin on hypoxic--ischaemic injury in the immature brain of rats. Bacterial endotoxin (lipopolysaccharide 0.3 mg/kg) was administered to 7-day-old rats 4 h prior to unilateral hypoxia--ischaemia and the neurological outcome was determined 3 days later. Rectal temperature and cerebral blood flow was measured during the study and the expression of CD14 and toll-like receptor-4 mRNA in the brain was examined. We found that a low dose of endotoxin dramatically sensitizes the immature brain to injury and induces cerebral infarction in response to short periods of hypoxia--ischaemia that by themselves caused no or little injury. This effect could not be explained by a reduction in cerebral blood flow or hyperthermia. In association with the sensitization of injury we found an altered expression of CD14 mRNA and toll-like receptor-4 mRNA in the brain. These results suggest that the innate immune system may be involved in the vulnerability of the immature brain following the combination of infection and hypoxia--ischaemia. PMID:11285007

  14. Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain.

    PubMed Central

    Asano, T.; Ikegaki, I.; Satoh, S.; Mochizuki, D.; Hidaka, H.; Suzuki, Y.; Shibuya, M.; Sugita, K.

    1991-01-01

    1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal neurones in the hippocampus of the Mongolian gerbil brain occurred 7 days after transient bilateral occlusion of the common carotid arteries. 2. A single injection of HA1077 (1 and 3 mg kg-1, i.p.) 5 min after the occlusion led to a dose-dependent protection of the CA1 neurones. Repeated administrations of HA1077 (1 and 3 mg kg-1, i.p., twice daily for 7 days post-ischaemia) revealed an increase in the number of normal cells, compared to findings with a single administration. 3. In contrast to HA1077, nicardipine (0.3 and 1 mg kg-1, i.p.) did not reduce neuronal degeneration. 4. HA1077 did not interact with the ion channel within which MK-801 binds, as determined by receptor binding. 5. The calcium ionophore, A23187, caused a tonic contraction in canine cerebral arterial strips. HA1077, but not nicardipine, relaxed the A23187-induced contraction, concentration-dependently. 6. These results suggest that blockade of the intracellular actions of calcium may provide protection against ischaemic damage in the brain. Images Figure 1 PMID:1912980

  15. Bovine ischaemic teat necrosis: a further potential role for digital dermatitis treponemes.

    PubMed

    Clegg, S R; Carter, S D; Stewart, J P; Amin, D M; Blowey, R W; Evans, N J

    2016-01-16

    A recent outbreak of ischaemic teat necrosis (ITN) on mainland UK has resulted in large economic losses for dairy farmers. Typical cases start as an area of dry, thickened and encrusted skin on the medial aspect of the base of the teat, where the teat joins the udder, often with a fetid odour. The erosion spreads down the teat, often causing intense irritation, which in turn leads to more severely affected animals removing the entire teat. Due to the severity of ITN and the substantial economic costs to the industry, analyses were undertaken to ascertain if an infectious agent might be involved in the pathology. The study has considered a role for digital dermatitis (DD) treponemes in the aetiopathogenesis of ITN because, as well as being the prime bacteria associated with infectious lameness, they have been associated with a number of emerging skin diseases of cattle, including udder lesions. A high association between presence of DD-associated treponemes and incidence of ITN (19/22), compared with absence in the control population is reported. Furthermore, sequencing of the 16S rRNA gene of treponeme isolates supports the hypothesis that the identified treponemes are similar or identical to those isolated from classical foot DD lesions in cattle (and sheep). Further studies are required to allow effective targeted prevention measures and/or treatments to be developed. PMID:26743503

  16. Source-specific fine particulate air pollution and systemic inflammation in ischaemic heart disease patients

    PubMed Central

    Siponen, Taina; Yli-Tuomi, Tarja; Aurela, Minna; Dufva, Hilkka; Hillamo, Risto; Hirvonen, Maija-Riitta; Huttunen, Kati; Pekkanen, Juha; Pennanen, Arto; Salonen, Iiris; Tiittanen, Pekka; Salonen, Raimo O; Lanki, Timo

    2015-01-01

    Objective To compare short-term effects of fine particles (PM2.5; aerodynamic diameter <2.5 µm) from different sources on the blood levels of markers of systemic inflammation. Methods We followed a panel of 52 ischaemic heart disease patients from 15 November 2005 to 21 April 2006 with clinic visits in every second week in the city of Kotka, Finland, and determined nine inflammatory markers from blood samples. In addition, we monitored outdoor air pollution at a fixed site during the study period and conducted a source apportionment of PM2.5 using the Environmental Protection Agency's model EPA PMF 3.0. We then analysed associations between levels of source-specific PM2.5 and markers of systemic inflammation using linear mixed models. Results We identified five source categories: regional and long-range transport (LRT), traffic, biomass combustion, sea salt, and pulp industry. We found most evidence for the relation of air pollution and inflammation in LRT, traffic and biomass combustion; the most relevant inflammation markers were C-reactive protein, interleukin-12 and myeloperoxidase. Sea salt was not positively associated with any of the inflammatory markers. Conclusions Results suggest that PM2.5 from several sources, such as biomass combustion and traffic, are promoters of systemic inflammation, a risk factor for cardiovascular diseases. PMID:25479755

  17. Dramatic decline of ischaemic heart disease mortality in post communist central Europe: recovery from totality.

    PubMed

    Ginter, Emil; Simko, Vlado

    2012-06-01

    After 1970 the preexisting gap in population health between democratic Europe and communist countries became even more prominent. While in the democratic Europe there was a progressive rise in life expectancy associated with the decline in ischaemic heart disease (IHD), the trend on the other side of the iron curtain was exactly reverse. After the fall of communism in 1989 population health in the post-communist central Europe (CE) rapidly signalled a favourable recovery. This biphasic trend in post-communist countries is very remarkable. Most remarkably the decline in IHD mortality started soon after the demise of totality, even before the modernization of health care (new more effective medications and diagnostic technology), public campaign against smoking and improved supply of protective nutrients got chance to attain an important role. The decades-long psychosocial depression of communism was rapidly replaced with a promise of a better future. It is generally accepted that psychosocial factors are powerfool tools in the pathogenesis of IHD. PMID:22966731

  18. Differential Modulation of Angiogenesis by Erythropoiesis-Stimulating Agents in a Mouse Model of Ischaemic Retinopathy

    PubMed Central

    McVicar, Carmel M.; Colhoun, Liza M.; Abrahams, Jodie L.; Kitson, Claire L.; Hamilton, Ross; Medina, Reinhold J.; Durga, Dash; Gardiner, Tom A.; Rudd, Pauline M.; Stitt, Alan W.

    2010-01-01

    Background Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. Methodology/Principal Findings The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1–20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFα and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001). Conclusions This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs. PMID:20686695

  19. Carotid Anatomy Does Not Predict the Risk of New Ischaemic Brain Lesions on Diffusion-Weighted Imaging after Carotid Artery Stenting in the ICSS-MRI Substudy

    PubMed Central

    Doig, D.; Hobson, B.M.; Müller, M.; Jäger, H.R.; Featherstone, R.L.; Brown, M.M.; Bonati, L.H.; Richards, T.

    2016-01-01

    Introduction The International Carotid Stenting Study (ICSS, ISRCTN25337470) randomized patients with recently symptomatic carotid artery stenosis > 50% to carotid artery stenting (CAS) or endarterectomy. CAS increased the risk of new brain lesions visible on diffusion-weighted magnetic resonance imaging (DWI-MRI) more than endarterectomy in the ICSS-MRI Substudy. The predictors of new post-stenting DWI lesions were assessed in these patients. Methods ICSS-MRI Substudy patients allocated to CAS were studied. Baseline or pre-stenting catheter angiograms were rated to determine carotid anatomy. Baseline patient demographics and the influence of plaque length, plaque morphology, internal carotid angulation, and external or common carotid atheroma were examined in negative binomial regression models. Results A total of 115 patients (70% male, average age 70.4) were included; 50.4% had at least one new DWI-MRI-positive lesion following CAS. Independent risk factors increasing the number of new lesions were a left-sided stenosis (incidence risk ratio [IRR] 1.59, 95% CI 1.04–2.44, p = .03), age (IRR 2.10 per 10-year increase in age, 95% CI 1.61–2.74, p < .01), male sex (IRR 2.83, 95% CI 1.72–4.67, p < .01), hypertension (IRR 2.04, 95% CI 1.25–3.33, p < .01) and absence of cardiac failure (IRR 6.58, 95% CI 1.23–35.07, p = .03). None of the carotid anatomical features significantly influenced the number of post-procedure lesions. Conclusion Carotid anatomy seen on pre-stenting catheter angiography did not predict of the number of ischaemic brain lesions following CAS. PMID:26481656

  20. Alcoholic hepatitis.

    PubMed

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (< 84 days after diagnosis), patients with AH were likely to die from liver-related events and infections. In the long-term (≥ 84 days after diagnosis), those who developed cirrhosis mainly died from liver-related causes, and

  1. Prevention and Treatment of Recurrent Hepatitis B after Liver Transplantation

    PubMed Central

    Maiwall, Rakhi; Kumar, Manoj

    2016-01-01

    Chronic hepatitis B is a global health problem that leads to development of various complications, such as cirrhosis, liver cancer, and liver failure requiring liver transplantation. The recurrence of hepatitis B virus (HBV) post-liver transplantation is a major cause of allograft dysfunction, cirrhosis of the allograft, and graft failure. Patients with high viral load at the time of transplantation, hepatitis B e antigen (HBeAg) positivity, or those with a history of anti-viral drug resistance are considered as high-risk for recurrent HBV post-liver transplantation, while patients with low viral load, including HBeAg negative status, acute liver failure, and hepatitis D virus (HDV) co-infection are considered to be at low-risk for recurrent HBV post-liver transplantation. Antivirals for patients awaiting liver transplantation(LT) cause suppression of HBV replication and reduce the risk of recurrent HBV infection of the allograft and, therefore, all HBV patients with decompensated cirrhosis should be treated with potent antivirals with high genetic barrier to resistance (entecavir or tenofovir) prior to liver transplantation. Prevention of post-liver transplantation recurrence should be done using a combination of hepatitis B immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence. Low dose HBIG, HBIG-free protocols, and monoprophylaxis with high potency antivirals can still be considered in patients at low risk of recurrence. Even, marginal grafts from anti-HBc positive donors can be safely used in hepatitis B surface antigen (HBsAg) negative, preferably in anti-hepatitis B core (HBc)/anti-hepatitis B surface (HBs) positive recipients. In this article, we aim to review the mechanisms and risk factors of HBV recurrence post-LT in addition to the various treatment strategies proposed for the prevention of recurrent HBV infection PMID:27047773

  2. Diurnal variation of pulmonary artery pressure in chronic heart failure.

    PubMed Central

    Gibbs, J S; Cunningham, D; Shapiro, L M; Park, A; Poole-Wilson, P A; Fox, K M

    1989-01-01

    Variation in pulmonary artery pressure has important consequences for the interpretation of isolated pressure measurements in patients with chronic heart failure. To investigate the nature of diurnal variation in pulmonary artery pressure in chronic heart failure, eight angina-free men (aged 50-72 years) with treated chronic heart failure caused by ischaemic heart disease underwent continuous ambulatory pulmonary artery pressure recording by a transducer tipped catheter. The mean (1 SD) daytime pulmonary artery pressure was 29.6 (5.0) mm Hg systolic and 13.7 (5.6) mm Hg diastolic. The mean change in pressure from day to night was +5.1 (3.2) mm Hg systolic and +3.8 (1.7) mm Hg diastolic; and the mean change from standing to lying +9.3 (2.3) mm Hg systolic and +6.4 (2.1) mm Hg diastolic. In six of the eight patients there was considerable rise in pulmonary artery pressure at night, but in the two patients with the most severe symptoms there was no nocturnal rise. In patients with chronic heart failure, nocturnal pulmonary artery pressure is not determined by postural change alone. But interpretation of isolated pulmonary artery pressure measurements must take the posture of the patient into account. PMID:2757872

  3. Feature Hepatitis: Hepatitis Can Strike Anyone

    MedlinePlus

    ... please turn Javascript on. From Hollywood's "Walk of Stars" to Main Street, USA, people from all walks ... that includes many well-known names: Legendary television star Larry Hagman was diagnosed with advanced hepatitis C ...

  4. Is Remodelling of Corticospinal Tract Terminations Originating in the Intact Hemisphere Associated with Recovery following Transient Ischaemic Stroke in the Rat?

    PubMed Central

    Mitchell, Emma J.; Dewar, Deborah; Maxwell, David J

    2016-01-01

    Following large strokes that encompass the cerebral cortex, it has been suggested that the corticospinal tract originating from the non-ischaemic hemisphere reorganises its pattern of terminal arborisation within the spinal cord to compensate for loss of function. However many strokes in humans predominantly affect subcortical structures with minimal involvement of the cerebral cortex. The aim of the present study was to determine whether remodelling of corticospinal terminals arising from the non-ischaemic hemisphere was associated with spontaneous recovery in rats with subcortical infarcts. Rats were subjected to transient middle cerebral artery occlusion or sham surgery and 28 days later, when animals exhibited functional recovery, cholera toxin b subunit was injected into the contralesional, intact forelimb motor cortex in order to anterogradely label terminals within cervical spinal cord segments. Infarcts were limited to subcortical structures and resulted in partial loss of corticospinal tract axons from the ischaemic hemisphere. Quantitative analysis revealed there was no significant difference in the numbers of terminals on the contralesional side of the spinal grey matter between ischaemic and sham rats. The results indicate that significant remodelling of the corticospinal tract from the non-ischaemic hemisphere is not associated with functional recovery in animals with subcortical infarcts. PMID:27014870

  5. Preventing hepatitis B or C

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000401.htm Preventing hepatitis B or C To use the sharing features on this page, please enable JavaScript. Hepatitis B and hepatitis C infections cause irritation and ...

  6. Hepatitis C: Information on Testing and Diagnosis

    MedlinePlus

    HEPATITIS C Information on Testing & Diagnosis What is Hepatitis C? Hepatitis C is a serious liver disease that results from infection with the Hepatitis C virus. Hepatitis C has been called a silent ...

  7. [Treatment for hepatic osteodystrophy].

    PubMed

    Kaji, Hiroshi

    2015-11-01

    Chronic liver diseases, including liver cirrhosis, are caused by various pathogenesis, such as viral hepatitis, primary biliary cirrhosis, autoimmune hepatitis and steatohepatitis. There have not been enough clinical evidence about the treatment of hepatic osteodystrophy at the present time. Several reports suggested that bisphosphonates, such as alendronate, are effective for an increase in bone mineral density in patients with chronic liver disease. Vitamin D treatment might be useful for the frequent prevalence of vitamin D deficiency in the pathogenesis of hepatic oseodystrophy. The use of estrogens will be limited for the risk of liver dysfunction and hepatocellular carcinoma. PMID:26503875

  8. Remote ischaemic conditioning in percutaneous coronary intervention: a meta-analysis of randomised trials

    PubMed Central

    Niu, Xiaowei; Zhang, Jingjing; Chen, De; Wan, Guozhen; Zhang, Yiming

    2014-01-01

    Introduction It remains uncertain whether remote ischaemic conditioning (RIC) using cycles of limb ischaemia-reperfusion as a conditioning stimulus benefits patients undergoing percutaneous coronary intervention (PCI). Aim We performed a meta-analysis toassessthe effect of RIC in PCI. Material and methods The PubMed, EMBASE, Web of Science, and CENTRAL databases were searched for randomised controlled trials (RCTs) comparing RIC with controls. The treatment effects were measured as a pooled odds ratio (OR), standardised mean difference (SMD), and corresponding 95% confidence intervals (95% CIs) using random-effects models. Results Fourteen RCTs, including 2,301 patients, were analysed. Compared to the controls, RIC significantly reduced the cardiac enzyme levels (SMD = –0.21; 95% CI: –0.39 to –0.04; p = 0.015; heterogeneity test, I 2 = 75%), and incidence of PCI-related myocardial infarction (OR = 0.70; 95% CI, 0.51–0.98; p = 0.037). There was a trend toward an improvement in the complete ST-segment resolution rate with RIC (OR = 1.83; 95% CI: 0.99–3.40; p = 0.054). No significant difference could be detected between the two groups regarding the risk for acute kidney injury after PCI. Univariate meta-regression analysis suggested that the major source of significant heterogeneity was the PCI type (primary or non-emergent) for the myocardial enzyme levels (adjusted R 2 = 0.44). Subsequent subgroup analysis confirmed the results. Conclusions The present meta-analysis showed that RIC could confer cardioprotection for patients undergoing coronary stent implantation. Moreover, the decrease in the myocardial enzyme levels was more pronounced in the patients treated with primary PCI. PMID:25489323

  9. Fatigue, psychological and cognitive impairment following transient ischaemic attack and minor stroke: a systematic review.

    PubMed

    Moran, G M; Fletcher, B; Feltham, M G; Calvert, M; Sackley, C; Marshall, T

    2014-10-01

    Transient ischaemic attack (TIA) and minor stroke are characterized by short-lasting symptoms; however, anecdotal and empirical evidence suggests that these patients experience ongoing cognitive/psychological impairment for which they are not routinely treated. The aims were (i) to investigate the prevalence and time course of fatigue, anxiety, depression, post-traumatic stress disorder(PTSD) and cognitive impairment following TIA/minor stroke; (ii) to explore the impact on quality of life (QoL), change in emotions and return to work; and (iii) to identify where further research is required and potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PSYCINFO, CINAHL, the Cochrane libraries and the grey literature between January 1993 and April 2013 was undertaken. Literature was screened and data were extracted by two independent reviewers. Studies were included of adult TIA/minor stroke participants with any of the outcomes of interest: fatigue, anxiety, depression, PTSD, cognitive impairment, QoL, change in emotions and return to work. Random-effects meta-analysis pooled outcomes by measurement tool. Searches identified 5976 records, 289 were assessed for eligibility and 31 studies were included. Results suggest high levels of cognitive impairment and depression post-TIA/minor stroke which decreased over time. However, frequencies varied between studies. Limited information was available on anxiety, PTSD and fatigue. Meta-analysis revealed that the measurement tool administered influenced the prevalence of cognitive impairment: Mini-Mental State Examination 17% [95% confidence interval (CI) 7, 26]; neuropsychological test battery 39% (95% CI 28, 50); Montreal Cognitive Assessment 54% (95% CI 43, 66). There is evidence to suggest that TIA/minor stroke patients may experience residual impairments; however, results should be interpreted with caution because of the few high quality studies. Notwithstanding, it is important to raise awareness

  10. Gene variations of ROCKs and risk of ischaemic stroke: the Women’s Genome Health Study

    PubMed Central

    CHASMAN, Daniel I.; RIDKER, Paul M; LIAO, James K.

    2014-01-01

    Recent animal and human studies have demonstrated the importance of the ROCK (RhoA/Rho-associated kinase) pathway in IsST (ischaemic stroke). Whether the genetic variation within ROCK-associated genes modulates the risk of IsST remains elusive. The association between 66 tSNPs [tagging SNPs (single nucleotide polymorphisms)] of three ROCK-associated genes [ROCK1, ROCK2 and ARHGEF10 (Rho guanine-nucleotide-exchange factor 10)] and the incidence of IsST was investigated in 23 294 Caucasian female participants of the prospective WGHS (Women’s Genome Health Study). All were free of known cancer and cardiovascular disease at baseline. During a 15-year follow-up period, 323 participants developed their first ever IsST. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and risk of IsST assuming an additive genetic model. Haplotype-block analysis was also performed. A total of ten tSNPs were associated with the risk of IsST (three in ARHGEF10 and seven in ROCK1; P < 0.050). Further investigation using the haplotype-block analysis revealed a similar significant association of pre-specified haplotypes of ROCK1 with the risk of IsST (P = 0.005). If corroborated in other large prospective studies, the findings of the present study suggest that genetic variation within the ROCK-associated pathway gene loci examined, and in particular ROCK1 gene variation, may influence the risk of IsST. PMID:24351102

  11. Mechanical thrombectomy in acute ischaemic stroke: a review of the literature, clinical effectiveness and future use.

    PubMed

    Lally, Frank; Grunwald, Iris Q; Sanyal, Ranjan; Natarajan, Indira; Roffe, Christine

    2013-03-01

    The only effective treatment licensed for acute ischaemic stroke is intravenous thrombolysis within 4.5 hours from stroke onset. An alternative method of restoring blood flow is mechanical thrombectomy (MT). Although this is highly effective at recanalization, it remains unclear whether it is more effective than thrombolysis in improving clinical outcomes. This review examines key clinical outcomes from published studies and reviews ongoing studies to identify devices, patient population, and stated outcomes of MT. We discuss the issues when comparing clinical outcomes from different trials and suggest measures to help standardize reporting. We used routine review methodology to search relevant databases for stroke and MT published between 1999 - 2012 and active trials between August 2011 - May 2012. The studies in this review had an overall patient population of 8354. The most widely used primary outcome (94% of studies) was successful recanalization. The mean mortality across the studies was 17% (range 7 - 44), 64% of studies reported neurological improvement and 97% reported functional outcome with 42% (range 15 - 54)] achieving independence in activities of daily living. Mean symptomatic intracerebral haemorrhage was 11% (range 0 - 45%). There were significant differences in outcome reporting between studies. Evidence from published studies shows a strong relationship between recanalization and good outcomes although non-standardization makes comparisons difficult. There is a trend towards higher recanalization, lower mortality, and better functional outcome in more recent studies. To examine effectiveness of MT vs thrombolysis, randomized controlled trials are needed. Several are currently in progress but it remains to be seen if procedures and outcomes are reported in a standardized manner. PMID:23394538

  12. Transient ischaemic attack clinic: an evaluation of diagnoses and clinical decision making.

    PubMed

    Lee, Will; Frayne, Judith

    2015-04-01

    The diagnosis of transient ischaemic attack (TIA) is based largely on the patient's symptom recall and clinical judgement. This decision-making process is highly subjective and the inter-observer reliability of TIA diagnosis is at best moderate, even among neurologists. The aim of this study is to examine the presenting features and final diagnoses of referrals to a TIA clinic and to evaluate characteristics that favoured the diagnosis of TIA over other TIA "mimics". Consecutive new referrals to a tertiary metropolitan hospital TIA clinic over a 9month period were examined. Characteristics between TIA and non-TIA diagnoses were compared and analysed. Eighty-two patients were recruited. Eighteen (22%) were given a final diagnosis of TIA or stroke. Major alternative diagnoses included migraine (n=17, 21%), presyncope/syncope (n=13, 16%) and anxiety (n=7, 9%). Four (5%) patients had unclassifiable symptoms with no clear final diagnosis. Mean age was 67±a standard deviation of 17years and patients diagnosed with TIA/stroke were on average older than those with non-TIA diagnoses (77±10 versus 64±17years, p=0.003). A diagnosis of TIA/stroke was favoured in the presence of moderate to severe weakness (p=0.032), dysphasia (p=0.037) or dysarthria (p=0.005). Unclassifiable symptoms (for example, palpitations, confusion, headache) were reported in 27 patients (33%) and their presence favoured non-TIA diagnoses (p=0.0003). TIA constituted a minority of the referrals to our clinic. Accurate clinical diagnosis of TIA facilitates early stroke prevention and avoids unnecessary investigations and prescriptions. Attempts to improve diagnostic accuracy of TIA should target improving the education and awareness of frontline medical practitioners. PMID:25669115

  13. Phosphate metabolite concentrations and ATP hydrolysis potential in normal and ischaemic hearts

    PubMed Central

    Wu, Fan; Zhang, Eric Y; Zhang, Jianyi; Bache, Robert J; Beard, Daniel A

    2008-01-01

    To understand how cardiac ATP and CrP remain stable with changes in work rate – a phenomenon that has eluded mechanistic explanation for decades – data from 31phosphate-magnetic resonance spectroscopy (31P-MRS) are analysed to estimate cytoplasmic and mitochondrial phosphate metabolite concentrations in the normal state, during high cardiac workstates, during acute ischaemia and reactive hyperaemic recovery. Analysis is based on simulating distributed heterogeneous oxygen transport in the myocardium integrated with a detailed model of cardiac energy metabolism. The model predicts that baseline myocardial free inorganic phosphate (Pi) concentration in the canine myocyte cytoplasm – a variable not accessible to direct non-invasive measurement – is approximately 0.29 mm and increases to 2.3 mm near maximal cardiac oxygen consumption. During acute ischaemia (from ligation of the left anterior descending artery) Pi increases to approximately 3.1 mm and ATP consumption in the ischaemic tissue is reduced quickly to less than half its baseline value before the creatine phosphate (CrP) pool is 18% depleted. It is determined from these experiments that the maximal rate of oxygen consumption of the heart is an emergent property and is limited not simply by the maximal rate of ATP synthesis, but by the maximal rate at which ATP can be synthesized at a potential at which it can be utilized. The critical free energy of ATP hydrolysis for cardiac contraction that is consistent with these findings is approximately −63.5 kJ mol−1. Based on theoretical findings, we hypothesize that inorganic phosphate is both the primary feedback signal for stimulating oxidative phosphorylation in vivo and also the most significant product of ATP hydrolysis in limiting the capacity of the heart to hydrolyse ATP in vivo. Due to the lack of precise quantification of Piin vivo, these hypotheses and associated model predictions remain to be carefully tested experimentally. PMID:18617566

  14. Managerial leadership and ischaemic heart disease among employees: the Swedish WOLF study

    PubMed Central

    Nyberg, A; Alfredsson, L; Theorell, T; Westerlund, H; Vahtera, J; Kivimäki, M

    2009-01-01

    Objective: To investigate the association between managerial leadership and ischaemic heart disease (IHD) among employees. Methods: Data on 3122 Swedish male employees were drawn from a prospective cohort study (WOLF). Baseline screening was carried out in 1992–1995. Managerial leadership behaviours (consideration for individual employees, provision of clarity in goals and role expectations, supplying information and feedback, ability to carry out changes at work successfully, and promotion of employee participation and control) were rated by subordinates. Records of employee hospital admissions with a diagnosis of acute myocardial infarction or unstable angina and deaths from IHD or cardiac arrest to the end of 2003 were used to ascertain IHD. Cox proportional-hazards analyses were used to calculate hazard ratios for incident IHD per 1 standard deviation increase in standardised leadership score. Results: 74 incident IHD events occurred during the mean follow-up period of 9.7 years. Higher leadership score was associated with lower IHD risk. The inverse association was stronger the longer the participant had worked in the same workplace (age-adjusted hazard ratio 0.76 (95% CI 0.61 to 0.96) for employment for 1 year, 0.77 (0.61 to 0.97) for 2 years, 0.69 (0.54 to 0.88) for 3 years, and 0.61 (0.47 to 0.80) for 4 years); this association was robust to adjustments for education, social class, income, supervisory status, perceived physical load at work, smoking, physical exercise, BMI, blood pressure, lipids, fibrinogen and diabetes. The dose–response association between perceived leadership behaviours and IHD was also evident in subsidiary analyses with only acute myocardial infarction and cardiac death as the outcome. Conclusion: If the observed associations were causal then workplace interventions should focus on concrete managerial behaviours in order to prevent IHD in employees. PMID:19039097

  15. The burden of hypoxic-ischaemic encephalopathy in Malaysian neonatal intensive care units

    PubMed Central

    Boo, Nem-Yun; Cheah, Irene Guat-Sim

    2016-01-01

    INTRODUCTION This study aimed to determine the incidence of hypoxic-ischaemic encephalopathy (HIE) and predictors of HIE mortality in Malaysian neonatal intensive care units (NICUs). METHODS This was a retrospective study of data from 37 NICUs in the Malaysian National Neonatal Registry in 2012. All newborns with gestational age ≥ 36 weeks, without major congenital malformations and fulfilling the criteria of HIE were included. RESULTS There were 285,454 live births in these hospitals. HIE was reported in 919 newborns and 768 of them were inborn, with a HIE incidence of 2.59 per 1,000 live births/hospital (95% confidence interval [CI] 2.03, 3.14). A total of 144 (15.7%) affected newborns died. Logistic regression analysis showed that the significant predictors of death were: chest compression at birth (adjusted odds ratio [OR] 2.27, 95% CI 1.27, 4.05; p = 0.003), being outborn (adjusted OR 2.65, 95% CI 1.36, 5.13; p = 0.004), meconium aspiration syndrome (MAS) (adjusted OR 2.16, 95% CI 1.05, 4.47; p = 0.038), persistent pulmonary hypertension of the newborn (PPHN) (adjusted OR 4.39, 95% CI 1.85, 10.43; p = 0.001), sepsis (adjusted OR 4.46, 95% CI 1.38, 14.40; p = 0.013), pneumothorax (adjusted OR 4.77, 95% CI 1.76, 12.95; p = 0.002) and severe HIE (adjusted OR 42.41, 95% CI 18.55, 96.96; p < 0.0001). CONCLUSION The incidence of HIE in Malaysian NICUs was similar to that reported in developed countries. Affected newborns with severe grade of HIE, chest compression at birth, MAS, PPHN, sepsis or pneumothorax, and those who were outborn were more likely to die before discharge. PMID:27549510

  16. [Hemophagocytic syndrome associated to hepatitis].

    PubMed

    Sandoval-Ramírez, Eunice; Camacho-Meza, Ignacio; Eduardo-Solís, Nery; Plascencia-Tabares, Oswaldo; Navarro-Olivos, Efraín; Ortiz-Aldana, Francisco Ignacio

    2016-01-01

    Hemophagocytic syndrome is characterized by increased proliferation and activation of antigen presenting cells (histiocytes) in bone marrow and other organs of the reticuloendothelial system as well as CD8+ T cells that threatens life of patients. The predominant clinical manifestations such as fever, cytopenia, hepatitis, coagulopathy, neurological symptoms and multiple organ failure are related to systemic inflammation. We report the case of an infant who started with jaundice, abdominal pain, vomiting and malaise, at admission, hepatomegaly, splenomegaly and biochemically with features suggestive of hepatocellular inflammation and progressive cholestasis with poor outcome, it was added persistent fever, seizures, anemia, thrombocytopenia, leukopenia, elevated ferritin and hypertriglyceridemia integrating hemophagocytic syndrome with fatal outcome despite immunosuppressive therapy. PMID:26943833

  17. Treatment of Severe Alcoholic Hepatitis.

    PubMed

    Thursz, Mark; Morgan, Timothy R

    2016-06-01

    Alcoholic hepatitis (AH) is a syndrome of jaundice and liver failure that occurs in a minority of heavy consumers of alcohol. The diagnosis usually is based on a history of heavy alcohol use, findings from blood tests, and exclusion of other liver diseases by blood and imaging analyses. Liver biopsy specimens, usually collected via the transjugular route, should be analyzed to confirm a diagnosis of AH in patients with an atypical history or presentation. The optimal treatment for patients with severe AH is prednisolone, possibly in combination with N-acetyl cysteine. At present, only short-term increases in survival can be expected-no treatment has been found to increase patient survival beyond 3 months. Abstinence is essential for long-term survival. New treatment options, including liver transplantation, are being tested in trials and results eagerly are awaited. PMID:26948886

  18. Acupuncture treatment for ischaemic stroke in young adults: protocol for a randomised, sham-controlled clinical trial

    PubMed Central

    Chen, Lifang; Fang, Jianqiao; Jin, Xiaoming; Keeler, Crystal Lynn; Gao, Hong; Fang, Zhen; Chen, Qin

    2016-01-01

    Introduction Stroke in young adults is not uncommon. Although the overall incidence of stroke has been recently declining, the incidence of stroke in young adults is increasing. Traditional vascular risk factors are the main cause of young ischaemic stroke. Acupuncture has been shown to benefit stroke rehabilitation and ameliorate the risk factors for stroke. The aims of this study were to determine whether acupuncture treatment will be effective in improving the activities of daily living (ADL), motor function and quality of life (QOL) in patients of young ischaemic stroke, and in preventing stroke recurrence by controlling blood pressure, lipids and body weight. Methods and analysis In this randomised, sham-controlled, participant-blinded and assessor-blinded clinical trial, 120 patients between 18 and 45 years of age with a recent (within 1 month) ischaemic stroke will be randomised for an 8-week acupuncture or sham acupuncture treatment. The primary outcome will be the Barthel Index for ADL. The secondary outcomes will include the Fugl-Meyer Assessment for motor function; the World Health Organization Quality of Life BREF (WHOQOL-BREF) for QOL; and risk factors that are measured by ambulatory blood pressure, the fasting serum lipid, body mass index and waist circumference. Incidence of adverse events and long-term mortality and recurrence rate during a 10-year and 30-year follow-up will also be investigated. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University. Protocol V.3 was approved in June 2013. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone during follow-up calls enquiring on the patient's post-study health status. Trial registration number ChiCTR-TRC- 13003317; Pre-results. PMID:26739742

  19. Erythropoietin attenuates the sequels of ischaemic spinal cord injury with enhanced recruitment of CD34+ cells in mice

    PubMed Central

    Hirano, Koji; Wagner, Klaus; Mark, Peter; Pittermann, Erik; Gäbel, Ralf; Furlani, Dario; Li, Wenzhong; Vollmar, Brigitte; Yamada, Tomomi; Steinhoff, Gustav; Ma, Nan

    2012-01-01

    Abstract Erythropoietin has been shown to promote tissue regeneration after ischaemic injury in various organs. Here, we investigated whether Erythropoietin could ameliorate ischaemic spinal cord injury in the mouse and sought an underlying mechanism. Spinal cord ischaemia was developed by cross-clamping the descending thoracic aorta for 7 or 9 min. in mice. Erythropoietin (5000 IU/kg) or saline was administrated 30 min. before aortic cross-clamping. Neurological function was assessed using the paralysis score for 7 days after the operation. Spinal cords were histologically evaluated 2 and 7 days after the operation. Immunohistochemistry was used to detect CD34+ cells and the expression of brain-derived neurotrophic factor and vascular endothelial growth factor. Each mouse exhibited either mildly impaired function or complete paralysis at day 2. Erythropoietin-treated mice with complete paralysis demonstrated significant improvement of neurological function between day 2 and 7, compared to saline-treated mice with complete paralysis. Motor neurons in erythropoietin-treated mice were more preserved at day 7 than those in saline-treated mice with complete paralysis. CD34+ cells in the lumbar spinal cord of erythropoietin-treated mice were more abundant at day 2 than those of saline-treated mice. Brain-derived neurotrophic factor and vascular endothelial growth factor were markedly expressed in lumbar spinal cords in erythropoietin-treated mice at day 7. Erythropoietin demonstrated neuroprotective effects in the ischaemic spinal cord, improving neurological function and attenuating motor neuron loss. These effects may have been mediated by recruited CD34+ cells, and enhanced expression of brain-derived neurotrophic factor and vascular endothelial growth factor. PMID:22145921

  20. Gαi2-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart

    PubMed Central

    Waterson, Rachael E.; Thompson, Corbin G.; Mabe, Nathaniel W.; Kaur, Kuljeet; Talbot, Jeffery N.; Neubig, Richard R.; Rorabaugh, Boyd R.

    2011-01-01

    Aims Regulator of G protein signalling (RGS) proteins act as molecular ‘off switches’ that terminate G protein signalling by catalyzing the hydrolysis of Gα-bound GTP to GDP. Many different Gαi-coupled receptors have been implicated in the cardioprotective effects of ischaemic preconditioning. However, the role of RGS proteins in modulating cardioprotection has not been previously investigated. We used mice that were homozygous (GS/GS) or heterozygous (GS/+) for a mutation in Gαi2 rendering it RGS-insensitive (G184S) to determine whether interactions between endogenous RGS proteins and Gαi2 modulate Gαi-mediated protection from ischaemic injury. Methods and results Langendorff-perfused mouse hearts were subjected to 30 min global ischaemia and 2 h reperfusion. Infarcts in GS/GS (14.5% of area at risk) and GS/+ (22.6% of AAR) hearts were significantly smaller than those of +/+ hearts (37.2% of AAR) and recovery of contractile function was significantly enhanced in GS/GS and GS/+ hearts compared with +/+ hearts. The cardioprotective phenotype was not reversed by wortmannin or U0126 but was reversed by 5-hydroxydecanoic acid and HMR 1098, indicating that RGS-insensitive Gαi2 protects the heart through a mechanism that requires functional ATP-dependent potassium channels but does not require acute activation of extracellular-regulated kinase or Akt signalling pathways. Conclusions This is the first study to demonstrate that Gαi2-mediated cardioprotection is suppressed by RGS proteins. These data suggest that RGS proteins may provide novel therapeutic targets to protect the heart from ischaemic injury. PMID:21349876

  1. In vivo bioimpedance changes during haemorrhagic and ischaemic stroke in rats: towards 3D stroke imaging using electrical impedance tomography.

    PubMed

    Dowrick, T; Blochet, C; Holder, D

    2016-06-01

    Electrical impedance tomography (EIT) could be used as a portable non-invasive means to image the development of ischaemic stroke or haemorrhage. The purpose of this study was to examine if this was possible using time difference imaging, in the anesthetised rat using 40 spring-loaded scalp electrodes with applied constant currents of 50-150 μA at 2 kHz. Impedance changes in the largest 10% of electrode combinations were  -12.8%  ±  12.0% over the first 10 min for haemorrhage and  +46.1%  ±  37.2% over one hour for ischaemic stroke (mean  ±  SD, n  =  7 in each group). The volume of the pathologies, assessed by tissue section and histology post-mortem, was 12.6 μl  ±  17.6 μl and 12.6 μl  ±  17.6 μl for haemorrhage and ischaemia respectively. In time difference EIT images, there was a correspondence with the pathology in 3/7 cases of haemorrhage and none of the ischaemic strokes. Although the net impedance changes were physiologically reasonable and consistent with expectations from the literature, it was disappointing that it was not possible to obtain reliable EIT images. The reason for this are not clear, but probably include confounding effects of secondary ischaemia for haemorrhage and tissue and cerebrospinal fluid shifts for the stroke model. With this method, it does not appear that EIT with scalp electrodes is yet ready for clinical use. PMID:27200510

  2. Nox2 Knockout Delays Infarct Progression and Increases Vascular Recovery through Angiogenesis in Mice following Ischaemic Stroke with Reperfusion

    PubMed Central

    McCann, Sarah K.; Dusting, Gregory J.; Roulston, Carli L.

    2014-01-01

    Evidence suggests the NADPH oxidases contribute to ischaemic stroke injury and Nox2 is the most widely studied subtype in the context of stroke. There is still conjecture however regarding the benefits of inhibiting Nox2 to improve stroke outcome. The current study aimed to examine the temporal effects of genetic Nox2 deletion on neuronal loss after ischaemic stroke using knockout (KO) mice with 6, 24 and 72 hour recovery. Transient cerebral ischaemia was induced via intraluminal filament occlusion and resulted in reduced infarct volumes in Nox2 KO mice at 24 h post-stroke compared to wild-type controls. No protection was evident at either 6 h or 72 h post-stroke, with both genotypes exhibiting similar volumes of damage. Reactive oxygen species were detected using dihydroethidium and were co-localised with neurons and microglia in both genotypes using immunofluorescent double-labelling. The effect of Nox2 deletion on vascular damage and recovery was also examined 24 h and 72 h post-stroke using an antibody against laminin. Blood vessel density was decreased in the ischaemic core of both genotypes 24 h post-stroke and returned to pre-stroke levels only in Nox2 KO mice by 72 h. Overall, these results are the first to show that genetic Nox2 deletion merely delays the progression of neuronal loss after stroke but does not prevent it. Additionally, we show for the first time that Nox2 deletion increases re-vascularisation of the damaged brain by 72 h, which may be important in promoting endogenous brain repair mechanisms that rely on re-vascularisation. PMID:25375101

  3. Current concepts on magnetic resonance imaging (MRI) perfusion-diffusion assessment in acute ischaemic stroke: a review & an update for the clinicians.

    PubMed

    Roldan-Valadez, Ernesto; Lopez-Mejia, Mariana

    2014-12-01

    Recently, several medical societies published joint statements about imaging recommendations for acute stroke and transient ischaemic attack patients. In following with these published guidelines, we considered it appropriate to present a brief, practical and updated review of the most relevant concepts on the MRI assessment of acute stroke. Basic principles of the clinical interpretation of diffusion, perfusion, and MRI angiography (as part of a global MRI protocol) are discussed with accompanying images for each sequence. Brief comments on incidence and differential diagnosis are also included, together with limitations of the techniques and levels of evidence. The purpose of this article is to present knowledge that can be applied in day-to-day clinical practice in specialized stroke units or emergency rooms to attend patients with acute ischaemic stroke or transient ischaemic attack according to international standards. PMID:25758570

  4. [Fatal hepatic necrosis during treatment with sodium valproate].

    PubMed

    Miguil, M; Chlihi, A; Mjahed, K; Sarf, I; Moutawakkil, S; Benaguida, M

    1995-01-01

    The authors report a case of fatal hepatic failure in a 19-year old young man suffering from absence seizures and treated for two months with valproic acid (VPA). The duration of VPA therapy before onset of clinical manifestations was four weeks. The prodromal symptoms were weakness, anorexia, and vomiting, then in a few weeks occurred a jaundice and an hepatic encephalopathy leading to death. Among laboratory findings disturbance of liver tests and particularly depressed levels of clotting factors were observed. The histologic study of the liver showed an extended centrolobular necrosis associated with fatty change and fibrosis. The mechanism of this hepatic failure remains unknown. The seriousness of this complication necessitates to respect any contraindications. PMID:7583902

  5. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  6. What Is Heart Failure?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Heart Failure? Heart failure is a condition in which the heart can' ... force. Some people have both problems. The term "heart failure" doesn't mean that your heart has stopped ...

  7. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial

    PubMed Central

    2011-01-01

    Background Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. Methods A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. Trial Registration ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN2887836 PMID:21645332

  8. The role of pre-ischaemic application of the nitric oxide donor spermine/nitric oxide complex in enhancing flap survival in a rat model.

    PubMed

    Küntscher, M V; Juran, S; Menke, H; Gebhard, M M; Erdmann, D; Germann, G

    2002-07-01

    Spermine/nitric oxide complex (Sper/NO) is a new nitric oxide (NO) donor with a long half-life providing controlled biological release of NO in vivo. The purpose of this study was to determine whether flap survival could be improved by pre-ischaemic or post-ischaemic intravenous administration of Sper/NO. We divided 37 male Wistar rats into four experimental groups. An extended epigastric adipocutaneous flap was raised in each animal. The mean area of flap necrosis was assessed for all groups on the fifth postoperative day, using planimetry software. The average area of flap necrosis was mean +/- s.d. = 68.2%+/-18.1% in the control group, and 29.7% +/- 13.3% in the non-ischaemic controls. The group with pre-ischaemic application of Sper/NO demonstrated an average flap necrosis of mean+/-s.d. = 11.2%+/-5.9%, whereas this increased to 59.2%+/-14.4% in the group receiving Sper/NO 5 min prior to reperfusion. The group with pre-ischaemic application of Sper/NO showed a significantly lower area of flap necrosis than either of the control groups or the group receiving Sper/NO just prior to reperfusion (P < 0.05). The group receiving Sper/NO just prior to reperfusion demonstrated a significantly higher mean area of flap necrosis than the non-ischaemic controls (P < 0.05), but did not differ significantly from the control group. Our data show that pharmacological preconditioning and enhancement of flap survival can be achieved by intravenous administration of Sper/NO. The application of Sper/NO at the end of the ischaemia period or in the early reperfusion period provides no protection against ischaemia-reperfusion injury. PMID:12372374

  9. Heart failure - medicines

    MedlinePlus

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  10. Hepatitis (For Parents)

    MedlinePlus

    ... people at risk for contracting hepatitis. But frequent hand washing and good hygiene practices can reduce this risk. All kids in ... to prevent viral hepatitis you should: Follow good hygiene and avoid crowded, ... their hands thoroughly after using the toilet and before eating. ...

  11. Hepatitis and activity

    PubMed Central

    Krikler, Dennis M.

    1971-01-01

    The effects of physical activity during an attack of infectious hepatitis are discussed. There is no evidence that activity during convalescence produces any ill-effects. On the other hand, strenuous physical activity in the acute stage may be dangerous, possibly because hepatic blood-flow is reduced. PMID:5560143

  12. Hepatitis E Virus Superinfection and Clinical Progression in Hepatitis B Patients

    PubMed Central

    Hoan, Nghiem Xuan; Tong, Hoang Van; Hecht, Nicole; Sy, Bui Tien; Marcinek, Patrick; Meyer, Christian G.; Song, Le Huu; Toan, Nguyen Linh; Kurreck, Jens; Kremsner, Peter G.; Bock, C-Thomas; Velavan, Thirumalaisamy P.

    2015-01-01

    Hepatitis E virus (HEV) infection may cause acute hepatitis and lead to hepatic failure in developing and developed countries. We studied HEV seroprevalences in patients with hepatitis B virus (HBV) infection to understand the consequences of HEV superinfection in a Vietnamese population. This cross-sectional study was conducted from 2012 to 2013 and included 1318 Vietnamese patients with HBV-related liver diseases and 340 healthy controls. The case group included patients with acute (n = 26) and chronic hepatitis B (n = 744), liver cirrhosis (n = 160), hepatocellular carcinoma (n = 166) and patients with both liver cirrhosis and hepatocellular carcinoma (n = 222). Anti-HEV IgG and IgM antibodies were assessed in patients and controls by ELISA. HEV-RNA was identified by PCR assays and sequencing. Seroprevalences of anti-HEV IgG among hepatitis B patients and controls were 45% and 31%, respectively (adjusted P = 0.034). Anti-HEV IgM seroprevalences were 11.6% and 4.7% in patients and controls, respectively (adjusted P = 0.005). Seroprevalences were higher among the elder individuals. When stratifying for patient groups, those with liver cirrhosis had the highest anti-HEV IgG (52%) and anti-HEV IgM (19%) seroprevalences. Hepatitis B patients with current HEV infection had abnormal liver function tests compared to patients with past or without HEV infection. One HEV isolate was retrieved from a patient with both liver cirrhosis and hepatocellular carcinoma and identified as HEV genotype 3. This study indicates high prevalences of HEV infection in Vietnamese HBV patients and among healthy individuals and shows that HEV superinfection may influence the outcome and progression of HBV-related liver disease. PMID:26844288

  13. Hepatitis B virus infection in immigrant populations

    PubMed Central

    Coppola, Nicola; Alessio, Loredana; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Zampino, Rosa; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention. PMID:26730274

  14. Major hepatic resection. A 25-year experience.

    PubMed Central

    Thompson, H H; Tompkins, R K; Longmire, W P

    1983-01-01

    Major hepatic resections were performed on 138 patients for a variety of conditions. There was one intraoperative death. Including this patient, there were 15 deaths within 30 days of the operation (operative mortality 10.9%). Important postoperative complications were intra-abdominal sepsis (17%), biliary leak (11%), hepatic failure (8%), and hemorrhage (6%). The results of 30 resections for the benign lesions, liver cell adenoma, focal nodular hyperplasia, hemangioma, and cystadenoma showed no operative mortality and low morbidity. Of 26 patients with hepatocellular carcinoma, seven died within a month of operation. The cumulative survival of the 26 at five years was 38%, and of the 19 who survived the procedure, 51%. Poor survival followed resections for cholangiocarcinoma and "mixed tumors." The five-year cumulative survival of 22 patients who had colorectal metastases excised was 31%. Apart from a patient with carcinoid, prolonged survival was rare after resection of other secondaries and after en bloc resections for tumors directly invading the liver. Hepatic resection was of value in the management of some patients with hepatic trauma, Caroli's disease, liver cysts, and intrahepatic stones. PMID:6299217

  15. [Beta-blocking drugs indicated in patients with heart failure].

    PubMed

    Voors, A A; van Gilst, W H; van Veldhuisen, D J

    2003-12-13

    Until recently, beta-blocking drugs were considered to be contraindicated in patients with chronic heart failure. However, several well-conducted randomised clinical trials have now proven otherwise. Yet, it was still not clear whether nonselective alpha-, beta 1- and beta 2-receptor blockade with carvedilol would be superior to selective beta 1-receptor blockade with metoprolol. One of the studies ('Carvedilol or metoprolol European trial' (COMET)) demonstrated a statistically significant 17% reduction of all-cause mortality with carvedilol. Although striking, the results may have been influenced by differences in blood pressure and heart rate, as well as the short-acting formula of metoprolol that was used. Furthermore, the 'Carvedilol hibernation reversible ischaemia trial; marker of success' (CHRISTMAS) study demonstrated myocardial hibernation in the majority of ischaemic heart-failure patients, and showed beneficial effects on left-ventricle function with carvedilol in both hibernated and non-hibernated patients. Despite this and the rest of the overwhelming evidence, at present only a minority of eligible chronic heart-failure patients are treated with beta-blockers. PMID:14708208

  16. [Update chronic viral hepatitis].

    PubMed

    Ziegenhagen, D J

    2016-03-01

    More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade. PMID:27111951

  17. Hepatitis E in Transplantation.

    PubMed

    Marion, Olivier; Abravanel, Florence; Lhomme, Sebastien; Izopet, Jacques; Kamar, Nassim

    2016-03-01

    Hepatitis E virus (HEV) has a worldwide distribution and is known to cause acute and fulminant hepatitis. However, over the last few years, it has been shown to also cause chronic hepatitis and cirrhosis in immunosuppressed patients, especially solid-organ-transplant patients. In immunocompetent and immunosuppressed patients, HEV is also associated with extra-hepatic manifestations, such as neurological symptoms and kidney injury. Unfortunately, a diagnostic assay for HEV infection is still not available in all countries. Reduction of immunosuppression is the first-line therapeutic option for organ-transplant patients with chronic hepatitis. In addition, ribavirin is highly efficient at treating chronic HEV infection. In this comprehensive review, we summarize the current knowledge regarding HEV diagnosis, its natural history, clinical manifestations, and treatments in patients with a solid-organ transplant. PMID:26838163

  18. Current issues in the management of paediatric viral hepatitis.

    PubMed

    Yeung, Latifa T F; Roberts, Eve A

    2010-01-01

    Viral hepatitis poses important problems for children. In preschoolers, hepatitis A virus (HAV) infection frequently causes acute liver failure. Vaccinating toddlers against HAV in countries with high endemicity is expected to decrease mortality. HAV vaccine demonstrates efficacy (comparable to immunoglobulin) as post-exposure prophylaxis. A recently developed vaccine against hepatitis E virus (HEV) may benefit fetal health, because pregnant women are most prone to acute liver failure as a result of HEV. Hepatitis B vaccine continues to demonstrate value and versatility for preventing serious liver disease. With chronic infection, undetectable levels of serum HBV DNA complement e-seroconversion as the preferred outcome measure; suppressed viral load correlates with long-term complications better than HBeAg status. Among Taiwanese children, low pretreatment HBV DNA (<2 x 10(8) copies/ml) strongly predicted response to interferon-alpha. Future paediatric studies must incorporate HBV DNA levels. The rationale for routine treatment of immunotolerant hepatitis B during childhood remains uncertain. Any treatment of chronic hepatitis B in childhood requires consideration of the risks and benefits. Childhood hepatitis C virus (HCV) infection results mainly from mother-to-infant transmission. Babies of HCV-infected women should be tested for serum HCV RNA at 1 month of age. If negative, confirmatory anti-HCV antibody testing may be performed between 12 and 15 months of age. Children with chronic hepatitis C may develop progressive fibrosis/cirrhosis, particularly in the setting of obesity and insulin resistance. Treatment of children chronically infected with genotype 2 or 3 is highly successful: combination therapy of pegylated interferon-alpha and ribavirin is well tolerated and superior to pegylated interferon-alpha alone. PMID:19840256

  19. Case of pneumatosis intestinalis and hepatic portal venous gas following a laparoscopic right hemicolectomy.

    PubMed

    Castren, Edit Elisa; Hakeem, Abdul R; Mahmood, Nabil S; Aryal, Kamal

    2016-01-01

    Hepatic portal venous gas (HPVG) in most cases signifies either mechanical migration of air into the portal system due to bowel ischaemia (pneumatosis intestinalis) or portal sepsis due to gas-forming organisms. Successful management of portal sepsis involves early identification of the condition, intensive resuscitation, broad-spectrum antibiotics and a laparotomy for possible bowel ischaemia. In this report, we discuss the case of a patient with pneumatosis intestinalis and HPVG after an elective laparoscopic right hemicolectomy. After an initial slow recovery, on postoperative day seven, the patient had profuse diarrhoea and confusion, and was hyponatraemic. A CT scan revealed pneumatosis intestinalis and HPVG. A laparotomy showed no obvious cause for HPVG and there was no ischaemic bowel. She was managed with intensive care, hyperbaric oxygen therapy, broad-spectrum antibiotics and total-parenteral nutrition. She has made a good recovery. This case highlights the presenting features, differential diagnoses, and management of pneumatosis intestinalis and HPVG. PMID:27001599

  20. Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation.

    PubMed

    Vargas, Hugo E; Laskus, Tomasz; Radkowski, Marek; Wilkinson, Jeff; Balan, Vijay; Douglas, David D; Harrison, M Edwyn; Mulligan, David C; Olden, Kevin; Adair, Debra; Rakela, Jorge

    2002-11-01

    Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated. PMID:12424714

  1. Down‐regulation of cardiac lineage protein (CLP‐1) expression in CLP‐1 +/− mice affords cardioprotection against ischaemic stress

    PubMed Central

    Mascareno, Eduardo; Manukyan, Irena; Das, Dipak K.

    2008-01-01

    Abstract In order to understand the transcriptional mechanism that underlies cell protection to stress, we evaluated the role of CLP‐1, a known inhibitor of the transcription elongation complex (pTEFb), in CLP‐1 +/− mice hearts. Using the isolated heart model, we observed that the CLP‐1+/− hearts, when subjected to ischaemic stress and evaluated by haemodynamic measurements, exhibit significant cardioprotection. CLP‐1 remains associated with the pTEFb complex in the heterozygous hearts, where as it is released in the wild‐type hearts suggesting the involvement of pTEFb regulation in cell protection. There was a decrease in Cdk7 and Cdk9 kinase activity and consequently in phosphorylation of serine‐5 and serine‐2 of Pol II CTD in CLP‐1 +/− hearts. However, the levels of mitochondrial proteins, PGC‐1α and HIF‐1α, which enhance mitochondrial activity and are implicated in cell survival, were increased in CLP‐1+/− hearts subjected to ischaemic stress compared to that in wild‐type CLP‐1+/+ hearts treated identically. There was also an increase in the expression of pyruvate dehydrogenase kinase (PDK‐1), which facilitates cell adaptation to hypoxic stress. Taken together, our data suggest that regulation of the CLP‐1 levels is critical to cellular adaptation of the survival program that protects cardiomyocytes against stress due collectively to a decrease in RNA Pol II phosphorylation but an increase in expression of target proteins that regulate mitochondrial function and metabolic adaptation to stress. PMID:18624753

  2. Visual function in term infants with hypoxic-ischaemic insults: correlation with neurodevelopment at 2 years of age

    PubMed Central

    Mercuri, E.; Haataja, L.; Guzzetta, A.; Anker, S.; Cowan, F.; Rutherford, M.; Andrew, R.; Braddick, O.; Cioni, G.; Dubowitz, L.; Atkinson, J.

    1999-01-01

    AIMS—To determine if there is any association between the findings of visual assessment performed at the age of 5 months and neurodevelopmental outcome at the age of 2 years in children who have sustained hypoxic-ischaemic insults.
METHODS—Twenty nine term infants with hypoxic-ischaemic encephalopathy and/or brain lesions on neonatal magnetic resonance imaging (MRI) were prospectively evaluated. At 5 months of age all the infants had their visual function assessed using the Atkinson Battery of Child Development for Examining Functional Vision, which includes the assessments of optokinetic nystagmus (OKN), acuity, visual fields, fixation shift and phase and orientation reversal visual evoked potentials. At 2 years of age the children had a structured neurological evaluation and a Griffiths developmental assessment.
RESULTS—There was good correlation between the extent of the early detected visual impairment and both neuromotor and global development. Children with more than three out of five abnormal visual tests at 5 months of age tended to have abnormal neurological examination results and abnormal developmental quotients. Children with three or fewer abnormalities tended to have developmental quotients in the normal range; the level of their performance, however, was still related to the number of visual tests passed.
CONCLUSIONS—Individual visual tests can provide important prognostic information. While abnormal OKN and acuity were always associated with abnormal outcome, normal results on visual evoked potentials and fixation shift tended to be associated with normal outcome.

 PMID:10325784

  3. Use of dialysis in the treatment of renal failure in liver disease

    PubMed Central

    Parsons, Victor; Wilkinson, S. P.; Weston, M. J.

    1975-01-01

    Early and thorough peritoneal and haemodialysis has a part to play in the management of selected patients with hepato-renal failure. Patients with advanced irreversible hepatic damage due to cirrhosis, however, may have their prognosis shortened by dialysis, but there are many problems in these techniques in patients with multiple organ failure which still require investigation and solution. PMID:1234334

  4. The effect of cangrelor and access site on ischaemic and bleeding events: insights from CHAMPION PHOENIX

    PubMed Central

    Gutierrez, J. Antonio; Harrington, Robert A.; Blankenship, James C.; Stone, Gregg W.; Steg, Ph. Gabriel; Gibson, C. Michael; Hamm, Christian W.; Price, Matthew J.; Généreux, Philippe; Prats, Jayne; Deliargyris, Efthymios N.; Mahaffey, Kenneth W.; White, Harvey D.; Bhatt, Deepak L.

    2016-01-01

    Aims To assess whether the use of the femoral or radial approach for percutaneous coronary intervention (PCI) interacted with the efficacy and safety of cangrelor, an intravenous P2Y12 inhibitor, in CHAMPION PHOENIX. Methods and results A total of 11 145 patients were randomly assigned in a double-dummy, double-blind manner either to a cangrelor bolus and 2-h infusion or to clopidogrel at the time of PCI. The primary endpoint, a composite of death, myocardial infarction, ischaemia-driven revascularization, or stent thrombosis, and the primary safety endpoint, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) defined severe bleeding, were evaluated at 48 h. Of the patients undergoing PCI and receiving study drug treatment, a total of 8064 (74%) and 2855 (26%) patients underwent femoral or radial PCI, respectively. Among the femoral cohort, the primary endpoint rate was 4.8% with cangrelor vs. 6.0% with clopidogrel (odds ratio, OR [95% confidence interval, CI] = 0.79 [0.65–0.96]); among the radial cohort, the primary endpoint was 4.4% with cangrelor vs. 5.7% with clopidogrel (OR [95% CI] = 0.76 [0.54–1.06]), P-interaction 0.83. The rate of GUSTO severe bleeding in the femoral cohort was 0.2% with cangrelor vs. 0.1% with clopidogrel (OR [95% CI] = 1.73 [0.51–5.93]). Among the radial cohort, the rate of GUSTO severe bleeding was 0.1% with cangrelor vs. 0.1% with clopidogrel (OR [95% CI] = 1.02 [0.14–7.28]), P-interaction 0.65. The evaluation of safety endpoints with the more sensitive ACUITY-defined bleeding found major bleeding in the femoral cohort to be 5.2% with cangrelor vs. 3.1% with clopidogrel (OR [95% CI] = 1.69 [1.35–2.12]); among the radial cohort the rate of ACUITY major bleeding was 1.5% with cangrelor vs. 0.7% with clopidogrel (OR [95% CI] = 2.17 [1.02–4.62], P-interaction 0.54). Conclusion In CHAMPION PHOENIX, cangrelor reduced ischaemic events with no significant increase in GUSTO-defined severe bleeding. The absolute rates

  5. Back seat driving: hindlimb corticospinal neurons assume forelimb control following ischaemic stroke.

    PubMed

    Starkey, Michelle Louise; Bleul, Christiane; Zörner, Björn; Lindau, Nicolas Thomas; Mueggler, Thomas; Rudin, Markus; Schwab, Martin Ernst

    2012-11-01

    Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex 'take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur. The exact mechanisms underlying functional recovery after small- to medium-sized strokes remain undetermined but are of utmost importance for understanding the human situation and for designing effective treatments and rehabilitation strategies. In the present study, we selectively destroyed large parts of the forelimb motor and premotor cortex of adult rats with an ischaemic injury. A behavioural test requiring highly skilled, cortically controlled forelimb movements showed that some animals recovered well from this lesion whereas others did not. To investigate the reasons behind these differences, we used anterograde and retrograde tracing techniques and intracortical microstimulation. Retrograde tracing from the cervical spinal cord showed a correlation between the number of cervically projecting corticospinal neurons present in the hindlimb sensory-motor cortex and good behavioural recovery. Anterograde tracing from the hindlimb sensory-motor cortex also showed a positive correlation between the degree of functional recovery and the sprouting of neurons from this region into the cervical spinal cord. Finally, intracortical microstimulation confirmed the positive correlation between rewiring of the hindlimb sensory-motor cortex and the degree of forelimb motor recovery. In conclusion, these experiments suggest that following stroke to the

  6. Severe Hepatic Necrosis Associated with Methyldopa

    PubMed Central

    Cameron, Ian A.; Achord, James L.; Bartee, Harry

    1981-01-01

    Family physicians should carefully follow their patients receiving methyldopa for liver toxicity. Methyldopa is commonly used in treating hypertension and its hepatotoxic potential is frequently overlooked. This point is illustrated in the following case report involving a 45-year-old black female. The patient had been receiving oral methyldopa for 7.5 months prior to hospitalization for control of severe hypertension. Methyldopa was discontinued on her second hospital day when her liver tests were found to be abnormal. She developed progressive liver failure and lapsed into hepatic coma. Subsequently, her liver biopsy showed severe hepatic necrosis. She slowly improved with medical management. Her liver tests returned to normal; she resumed work and at 14 months follow up her liver biopsy showed no evidence of chronic active liver disease. Monitoring for methyldopa toxicity as outlined in this article could have prevented this costly and near lethal side effect. ImagesFig. 1Fig. 2 PMID:21289717

  7. Hepatitis C virus. A review.

    PubMed Central

    Tang, E.

    1991-01-01

    Hepatitis C virus has been shown to be responsible for most cases of posttransfusion hepatitis, as well as for sporadic non-A, non-B viral hepatitis. Hepatitis C virus has also been implicated in the development of primary hepatocellular carcinoma, autoimmune hepatitis, and fulminant viral hepatitis. Although the role of the parenteral transmission of hepatitis C virus is well established, its route of transmission in cases of sporadic infection remains unclear. Sexual transmission is suspected but not confirmed. Recent work regarding treatment has shown interferon alfa to be effective, but the discontinuation of therapy is associated with a 50% relapse rate. PMID:1656611

  8. Advanced Heart Failure

    MedlinePlus

    ... High Blood Pressure Tools & Resources Stroke More Advanced Heart Failure Updated:Oct 8,2015 When heart failure (HF) ... content was last reviewed on 04/06/2015. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  9. Acute-on-chronic and Decompensated Chronic Liver Failure: Definitions, Epidemiology, and Prognostication.

    PubMed

    Olson, Jody C

    2016-07-01

    Chronic liver disease is the fifth leading cause of death worldwide and represents a major burden for the health care community. Cirrhosis is a progressive disease resulting in end-stage liver failure, which in the absence of liver transplantation is fatal. Acute-on-chronic liver failure carries high short-term mortality but is potentially reversible. Viral hepatitis, alcohol, and nonalcoholic fatty liver disease remain the principal causes of liver disease. Though treatments exist for hepatitis B and C, they remain unavailable to many with these diseases. This article reviews the epidemiology of advanced liver disease and the concept of acute-on-chronic liver failure. PMID:27339672

  10. Acute Hepatic Necrosis Caused by Salmonella enterica Serotype I 4,5,12:−:1,2 in a Dog

    PubMed Central

    Meiring, Thelma; Grant, Andrew J.; Watson, Penny J.

    2015-01-01

    Acute hepatic necrosis was diagnosed in a dog. Gram staining and fluorescence in situ hybridization identified Salmonella enterica in the liver, subsequently confirmed as S. enterica serotype I 4,5,12:−:1,2. This is the first report of acute hepatic necrosis with liver failure caused by Salmonella in a dog. PMID:26292301

  11. Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E

    MedlinePlus

    ... Hepatitis: What you should know from A to E Past Issues / Spring 2009 Table of Contents For ... condition is called chronic hepatitis. Hepatitis A and E do not cause chronic hepatitis. Hepatitis viruses B, ...

  12. Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy: the case for repeat application as a novel therapy for lower extremity ulceration.

    PubMed

    Epps, J A; Smart, N A

    2016-01-01

    An emerging treatment modality for reducing damage caused by ischaemia-reperfusion injury is ischaemic conditioning. This technique induces short periods of ischaemia that have been found to protect against a more significant ischaemic insult. Remote ischaemic conditioning (RIC) can be administered more conveniently and safely, by inflation of a pneumatic blood pressure cuff to a suprasystolic pressure on a limb. Protection is then transferred to a remote organ via humoral and neural pathways. The diabetic state is particularly vulnerable to ischaemia-reperfusion injury, and ischaemia is a significant cause of many diabetic complications, including the diabetic foot. Despite this, studies utilising ischaemic conditioning and RIC in type 2 diabetes have often been disappointing. A newer strategy, repeat RIC, involves the repeated application of short periods of limb ischaemia over days or weeks. It has been demonstrated that this improves endothelial function, skin microcirculation, and modulates the systemic inflammatory response. Repeat RIC was recently shown to be beneficial for healing in lower extremity diabetic ulcers. This article summarises the mechanisms of RIC, and the impact that type 2 diabetes may have upon these, with the role of neural mechanisms in the context of diabetic neuropathy a focus. Repeat RIC may show more promise than RIC in type 2 diabetes, and its potential mechanisms and applications will also be explored. Considering the high costs, rates of chronicity and serious complications resulting from diabetic lower extremity ulceration, repeat RIC has the potential to be an effective novel advanced therapy for this condition. PMID:27613524

  13. Motor Testing at 1 Year Improves the Prediction of Motor and Mental Outcome at 2 Years after Perinatal Hypoxic-Ischaemic Encephalopathy

    ERIC Educational Resources Information Center

    van Schie, Petra Em; Becher, Jules G.; Dallmeijer, Annet J.; Barkhof, Frederik; van Weissenbruch, Mirjam M.; Vermeulen, R. Jeroen

    2010-01-01

    Aim: To investigate the predictive value of motor testing at 1 year for motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy (HIE) in term neonates. Method: Motor and mental outcome at 2 years was assessed with the Bayley Scales of Infant Development, 2nd edition (BSID-II) in 32 surviving children (20 males, 12…

  14. Viral hepatitis and hepatitis B antigen: recent advances

    PubMed Central

    Krugman, Saul

    1974-01-01

    Recent advances in hepatitis research have shed new light on the etiology, pathogenesis, epidemiology and prevention of type B hepatitis infection. The so-called ‘Dane’ particle is probably the complete hepatitis B virion; its outer coat is the hepatitis B (Australia) antigen (HB Ag) and its inner core is an immunologically distinct particle. Subtypes of HB Ag (a, d, y, w and r) are useful indices for epidemiological surveys. Concepts of epidemiology have changed: type B hepatitis is transmissible by contact as well as by inoculation. The presence of HB Ag in blood is indicative of the presence of hepatitis B virus. Tests to detect antigen and use of voluntary blood donors have played a major role in the decreased incidence of post transfusion hepatitis. A special hepatitis B gammaglobulin preparation and a heat-inactivated hepatitis B vaccine have proved to be effective in preliminary studies. PMID:4219230

  15. Acute hepatitis C in an HIV-infected patient: a case report and review of literature.

    PubMed

    Driver, Todd H; Terrault, Norah; Saxena, Varun

    2013-05-01

    With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease. PMID:23151989

  16. Fatal fulminant hepatitis caused by infection with subgenotype A1 hepatitis B virus with C1766T/T1768A core promoter mutations.

    PubMed

    Hoshino, Takashi; Takagi, Hitoshi; Suzuki, Yuhei; Naganuma, Atsushi; Sato, Ken; Kakizaki, Satoru; Nishizawa, Tsutomu; Okamoto, Hiroaki; Yamada, Masanobu

    2016-06-01

    Adults initially infected with the hepatitis B virus develop various types of hepatitis ranging from asymptomatic to fulminant, and the clinical course of infection is influenced by a variety of host and viral factors. The viral risk factors associated with fulminant hepatitis reportedly include subgenotype B1, negative HBe antigen, and mutations in the precore and core promoter regions. Here, we present a case of fatal fulminant hepatitis caused by infection with subgenotype A1 hepatitis B virus with C1766T/T1768A double mutations in the core promoter region. A 53-year-old man was hospitalized with acute hepatitis B. Immediately after admission, entecavir was administered. However, his condition deteriorated, developing into fulminant hepatitis 2 days later. Artificial extracorporeal liver support therapy with plasma exchange (PE) and hemodiafiltration (HDF) were started. At one time point, the severity of hepatic encephalopathy decreased from grade II to grade 0, and the prothrombin time also improved, increasing from 11 to 73 %. However, the total bilirubin levels remained at or above 20 mg/dL and blood creatinine levels gradually increased. HDF was restarted, and therapies such as bilirubin adsorption and PE were administered. However, neither hepatic nor renal failure was alleviated, and the patient died 78 days after admission. PMID:27165167

  17. Drug-induced hepatitis

    MedlinePlus

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  18. Hepatitis C and sex.

    PubMed

    Page, Emma E; Nelson, Mark

    2016-04-01

    An outbreak of acute hepatitis C among HIV-positive men who have sex with men (MSM) in the last decade has been shown to be sexually transmitted. Initially recreational drug use, in particular drug injection, was not prevalent among those becoming infected with hepatitis C. However more recently chemsex (the use of drugs to enhance sexual experience) and its associated drugs, which are not uncommonly injected, have become more frequently reported among those diagnosed with hepatitis C. It is hoped that the widespread -introduction of direct-acting antivirals and upscaling of numbers treated may have a positive impact on this epidemic. However their introduction may negatively impact on the perceived risk of acquiring hepatitis C and in conjunction with the introduction of HIV transmission prevention strategies may result in increased transmissions and spread to the HIV-negative MSM population. PMID:27037392

  19. Hepatitis C - children

    MedlinePlus

    ... chap 358. Jhaveri R. Hepatitis C virus. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ, eds. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 7th ed. Philadelphia, ...

  20. Hepatitis Risk Assessment

    MedlinePlus

    ... About the Division of Viral Hepatitis Contact Us File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...