Science.gov

Sample records for acute bilirubin encephalopathy

  1. Galactosaemia: an unusual cause of chronic bilirubin encephalopathy.

    PubMed

    Sahoo, Tanushree; Thukral, Anu; Agarwal, Ramesh; Sankar, Mari Jeeva

    2015-01-01

    Galactosaemia is a disorder of galactose metabolism in which raised levels of galactose and galactose-1-phosphate damage various organs. Although galactosaemia is a common metabolic liver disease in childhood, it is a rare cause of neonatal hyperbilirubinemia requiring intervention. We report an unusual case of neonatal galactosaemia that at presentation had features of acute bilirubin encephalopathy requiring exchange transfusion and at discharge had features of chronic bilirubin encephalopathy. This case report emphasises the need for timely suspicion and diagnosis of this disease for prevention of chronic morbidity. PMID:25618877

  2. Bilirubin Encephalopathy in a Domestic Shorthair Cat With Increased Osmotic Fragility and Cholangiohepatitis.

    PubMed

    Contreras, E T; Giger, U; Malmberg, J L; Quimby, J M; Schaffer, P A

    2016-05-01

    A 7-month-old female domestic shorthair cat was diagnosed with chronic regenerative hemolytic anemia characterized by increased osmotic fragility of unknown etiology. At 13 months of age, the cat was evaluated for acute collapse. The cat was icteric with severe hyperbilirubinemia but no hematocrit changes. Severe obtundation and lateral recumbency progressed to tetraparesis and loss of proprioception in all 4 limbs, and a cerebellar or brainstem lesion was suspected. Postmortem examination revealed suppurative cholangiohepatitis and acute neuronal necrosis in the nuclei of the brainstem and cerebellum, consistent with bilirubin encephalopathy. This is the first known occurrence of cholangiohepatitis and bilirubin encephalopathy in an adult cat with chronic hemolytic anemia. Although rare, bilirubin encephalopathy should be considered a possible sequela to hyperbilirubinemia in adult patients. It remains unknown whether increased osmotic fragility was related to the cholangiohepatopathy. PMID:26354310

  3. Magnetic Resonance Imaging of Bilirubin Encephalopathy: Current Limitations and Future Promise

    PubMed Central

    Wisnowski, Jessica L.; Panigrahy, Ashok; Painter, Michael J.; Watchko, Jon F.

    2014-01-01

    Infants with chronic bilirubin encephalopathy often demonstrate abnormal bilateral, symmetric, high-signal intensity on T2-weighted magnetic resonance imaging of the globus pallidus and subthalamic nucleus, consistent with the neuropathology of kernicterus. Early magnetic resonance imaging of at risk infants, while frequently showing increased T1-signal in these regions, may give false positive findings due to the presence of myelin in these structures. Advanced magnetic resonance imaging including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may shed new insights into the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy. PMID:25267277

  4. Acute, severe bilirubin encephalopathy in a newborn.

    PubMed

    Mollen, Thomas J; Scarfone, Richard; Harris, Mary Catherine

    2004-09-01

    In recent years, changes in health care practices including the early discharge of newborns have transformed the management of neonatal jaundice into an outpatient problem. At the same time, there has been a resurgence in the incidence of kernicterus. We report the case of a term male infant who presented to our emergency department at 4 days of age with severe jaundice and who subsequently died with autopsy findings of kernicterus. We review the infant's presentation and hospital course, diagnostic and therapeutic interventions, and autopsy findings. In the current era of increased frequency of breast-feeding, shortened hospital stays, and inconsistent follow-up after hospital discharge, emergency department physicians should be alerted to the rare but increasing occurrence of severe hyperbilirubinemia and kernicterus. PMID:15599261

  5. Uncommon cause of acute encephalopathy in liver cirrhosis.

    PubMed

    Dieuvil, Monique; Malaty, John

    2016-01-01

    A 49-year-old woman with a medical history of alcoholic cirrhosis status post-transjugular intrahepatic portosystemic shunt (post-TIPS) in 2012, and ongoing alcohol abuse, presented to the hospital, with haematuria. CT intravenous pyelogram (IVP) was normal except for 'a large intrahepatic cystic mass adjacent to the TIPS, causing intrahepatic biliary duct dilation'. The patient also presented with acute encephalopathy, jaundice, right upper quadrant abdominal pain and hyperbilirubinaemia (total bilirubin of 8.1 mg/dL with direct bilirubin of 3.0 mg/dL). She remained encephalopathic despite adequate treatment for alcohol withdrawal, hepatic encephalopathy and enterococcus urinary tract infection. MRI of the abdomen later confirmed presence of an obstructing biloma. The biloma, drained by CT-guided percutaneous drains, demonstrated an Escherichia coli and ESBL Klebsiella infection. The patient's encephalopathy completely resolved after treatment of the infected biloma. With adequate drainage, her hyperbilirubinaemia resolved to her post-TIPS baseline (total bilirubin of 3.7 mg/dL with direct bilirubin of 3.3 mg/dL). PMID:27194673

  6. [Imaging in acute toxic encephalopathy].

    PubMed

    Dietemann, J-L; Botelho, C; Nogueira, T; Vargas, M I; Audibert, C; Abu Eid, M; Bogorin, A; Bernardo, R; Jacques, C; Kremer, S; Zöllner, G

    2004-09-01

    Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...). PMID:15545943

  7. A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy.

    PubMed

    Riordan, Sean M; Bittel, Douglas C; Le Pichon, Jean-Baptiste; Gazzin, Silvia; Tiribelli, Claudio; Watchko, Jon F; Wennberg, Richard P; Shapiro, Steven M

    2016-01-01

    Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a "load" is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load (PGL) that affects the response to a specific insult has been previously reported as a PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system's response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP) causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin induced neurological disorders (BIND) such as kernicterus and could be the key to understanding ranges of outcome severity in

  8. A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy

    PubMed Central

    Riordan, Sean M.; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Gazzin, Silvia; Tiribelli, Claudio; Watchko, Jon F.; Wennberg, Richard P.; Shapiro, Steven M.

    2016-01-01

    Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60–80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a “load” is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load (PGL) that affects the response to a specific insult has been previously reported as a PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system's response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP) causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin induced neurological disorders (BIND) such as kernicterus and could be the key to understanding ranges of outcome severity

  9. Clinical assessment of bilirubin-induced neurotoxicity in premature infants.

    PubMed

    Amin, Sanjiv B

    2004-10-01

    The clinical assessment of bilirubin-induced neurotoxicity in premature infants remains difficult in the absence of a gestational age-specific total or free (unbound) bilirubin level that predicts bilirubin-induced neurotoxicity. Because the total serum bilirubin concentration is an unreliable predictor of bilirubin-induced neurotoxicity in premature infants, alternative mean for predicting bilirubin-induced neurotoxicity in jaundiced preterm newborns is needed. Over the last few years, we have witnessed substantial gain in our knowledge involving usefulness of bilirubin-binding variables (total bilirubin, free bilirubin, bilirubin:albumin molar ratio) for clinical assessment of bilirubin-induced neurotoxicity in preterm infants. The knowledge gained has provided impetus for more clinical studies that are geared toward confirming the usefulness of free bilirubin as a predictor of bilirubin-induced neurotoxicity and identifying the gestational age-specific free bilirubin level that may increase the risk of bilirubin-induced neurotoxicity in premature infants. The paper has attempted to provide an overview of bilirubin-induced auditory toxicity along with the existing clinical evidence in favor of free bilirubin assay and usefulness of auditory brainstem evoked response for evaluation of bilirubin-induced neurotoxicity in premature infants. In addition, the author has described findings that suggest an association of apnea, a clinical manifestation, with acute bilirubin encephalopathy in premature infants. PMID:15686265

  10. Determining Prevalence of Acute Bilirubin Encephalopathy in Developing Countries

    ClinicalTrials.gov

    2015-11-11

    Demonstrate BIND II Score of >=5, is Valid for Detecting Moderate to Severe ABE in Neonates <14 Days Old.; Demonstrate Community-BIND Instrument, a Modified BIND II, is a Valid and Reliable Tool for Detecting ABE.; Demonstrate That Community-BIND Can be Used for Acquiring Population-based Prevalence of ABE in the Community.

  11. Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

    PubMed

    Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi

    2016-05-01

    Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit. PMID:26818600

  12. Bilirubin-Induced Neurotoxicity in the Preterm Neonate.

    PubMed

    Watchko, Jon F

    2016-06-01

    Bilirubin-induced neurotoxicity in preterm neonates remains a clinical concern. Multiple cellular and molecular cascades likely underlie bilirubin-induced neuronal injury, including plasma membrane perturbations, excitotoxicity, neuroinflammation, oxidative stress, and cell cycle arrest. Preterm newborns are particularly vulnerable secondary to central nervous system immaturity and concurrent adverse clinical conditions that may potentiate bilirubin toxicity. Acute bilirubin encephalopathy in preterm neonates may be subtle and manifest primarily as recurrent symptomatic apneic events. Low-bilirubin kernicterus continues to be reported in preterm neonates, and although multifactorial in nature, is often associated with marked hypoalbuminemia. PMID:27235209

  13. Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

    PubMed Central

    O’Malley, Stephanie S.; Gueorguieva, Ralitza; Wu, Ran; Jatlow, Peter I.

    2015-01-01

    Background Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods 18 healthy individuals (8 cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL, in random order in 3 laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45 am prior to drinking, at 2 pm, and at 7:45 the next morning. Mixed effects regression models compared baseline and 24 hr. post-drinking bilirubin concentrations. Results Total serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24 hours in non-smokers (from Mean=0.38, SD=0.24 to Mean=0.51 SD=0.30, F(1, 32.2) =24.24, p<.0001) but not in smokers (from Mean=0.25, SD=0.12 to Mean=0.26, SD=0.15, F(1, 31.1) =0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. Conclusions Alcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies. PMID:25707709

  14. Acute necrotizing encephalopathy of childhood: report of a Spanish case.

    PubMed

    San Millan, Beatriz; Teijeira, Susana; Penin, Carmen; Garcia, Jose L; Navarro, Carmen

    2007-12-01

    Acute necrotizing encephalopathy of childhood is a rare disease with a broad clinical, radiologic, and biochemical spectrum. In the few postmortem studies published to date, the neuropathologic findings involved symmetric, necrotic brain lesions as the hallmark. Here we report on the clinical and neuropathologic findings of a Spanish child with the most severe form of the disease. PMID:18021928

  15. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    PubMed Central

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-01-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729

  16. Ceftriaxone-Induced Acute Encephalopathy in a Peritoneal Dialysis Patient

    PubMed Central

    Safadi, Sami; Mao, Michael; Dillon, John J.

    2014-01-01

    Encephalopathy is a rare side effect of third and fourth generation cephalosporins. Renal failure and preexisting neurological disease are notable risk factors. Recognition is important as discontinuing the offending agent usually resolves symptoms. We present a case of acute encephalopathy in a patient with end stage renal disease (ESRD) treated with peritoneal dialysis (PD) who received intravenous ceftriaxone for peritonitis. This case illustrates the potential severe neurologic effects of cephalosporins, which are recommended by international guidelines as first-line antimicrobial therapy for spontaneous bacterial peritonitis. PMID:25544915

  17. [Cytoprotective effects of bilirubin].

    PubMed

    Vítek, L

    2005-01-01

    Bilirubin, a major product of heme catabolism, belongs to compounds with pleiotropic biologic effects. For a long time bilirubin was considered as a metabolite dangerous for human health, neonatologists know well serious clinical complication of neonatal jaundice called bilirubin encephalopathy. Nevertheless, recent data has demonstrated that bilirubin exhibits potent antioxidant and even anti-inflammatory effects with substantial clinical impacts. The aim of the present study was to summarize present knowledge in this rapidly evolving field and suggest further possible clinical consequences. PMID:15981989

  18. Wernicke's Encephalopathy Mimicking Acute Onset Stroke Diagnosed by CT Perfusion

    PubMed Central

    Advani, Rajiv; Kurz, Kathinka D.; Kurz, Martin W.

    2014-01-01

    Background. Metabolic syndromes such as Wernicke's encephalopathy may present with a sudden neurological deficit, thus mimicking acute onset stroke. Due to current emphasis on rapid admission and treatment of acute stroke patients, there is a significant risk that these stroke mimics may end up being treated with thrombolysis. Rigorous clinical and radiological skills are necessary to correctly identify such metabolic stroke mimics, in order to avoid doing any harm to these patients due to the unnecessary use of thrombolysis. Patient. A 51-year-old Caucasian male was admitted to our hospital with suspicion of an acute stroke due to sudden onset dysarthria and unilateral facial nerve paresis. Clinical examination revealed confusion and dysconjugate gaze. Computed tomography (CT) including a CT perfusion (CTP) scan revealed bilateral thalamic hyperperfusion. The use of both clinical and radiological findings led to correctly diagnosing Wernicke's encephalopathy. Conclusion. The application of CTP as a standard diagnostic tool in acute stroke patients can improve the detection of stroke mimics caused by metabolic syndromes as shown in our case report. PMID:24716022

  19. Association between Serum Bilirubin and Acute Intraoperative Hyperglycemia Induced by Prolonged Intermittent Hepatic Inflow Occlusion in Living Liver Donors

    PubMed Central

    Han, Sangbin; Jin, Sang-Man; Ko, Justin Sangwook; Kim, Young Ri; Gwak, Mi Sook; Son, Hee Jeong; Joh, Jae-Won; Kim, Gaab Soo

    2016-01-01

    Background Intermittent hepatic inflow occlusion (IHIO) is associated with acute hyperglycemia during living donor hepatectomy when the ischemia is prolonged. Bilirubin is a potent antioxidant to play an important role for maintaining insulin sensitivity and preventing hyperglycemia. Thus, we aimed to test whether serum bilirubin level is associated with prolonged IHIO-induced intraoperative hyperglycemia. Methods Seventy-five living liver donors who underwent a prolonged IHIO with a >30 minute cumulative ischemia were included. The association between preoperative serum bilirubin concentrations and the risk of intraoperative hyperglycemia (blood glucose concentration >180 mg/dl) was analyzed using binary logistic regression with adjusting for potential confounders including age and steatosis. Results The number of donors who underwent 3, 4, 5, and 6 rounds of IHIO was 41, 22, 7, and 5, respectively. Twenty-nine (35%) donors developed intraoperative hyperglycemia. Total bilirubin concentration was inversely associated with hyperglycemia risk (odds ratio [OR] 0.033, 95% confidence interval [CI] 0.004–0.313, P = 0.003). There was an interaction between age and total bilirubin concentration: the effect of lower serum total bilirubin (≤0.7 mg/dl) on the development of hyperglycemia was greater in older donors (>40 years) than in younger donors (P = 0.0.028 versus P = 0.212). Both conjugated bilirubin (OR 0.001 95% CI 0.001–0.684) and unconjugated bilirubin (OR 0.011 95% CI 0.001–0.246) showed an independent association with hyperglycemia risk. Conclusions Lower preoperative serum bilirubin was associated with greater risk of prolonged IHIO-induced hyperglycemia during living donor hepatectomy particularly in older donors. Thus, more meticulous glycemic management is recommended when prolonged IHIO is necessary for surgical purposes in old living donors with lower serum bilirubin levels. PMID:27367602

  20. Posterior Reversible Encephalopathy Syndrome (PRES) After Acute Pancreatitis

    PubMed Central

    Murphy, Tara; Al-Sharief, Khalid; Sethi, Vineeta; Ranger, Gurpreet S.

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an unusual condition typified by acute visual impairment caused by sudden, marked parieto-occipital vasogenic edema. Thought to be inflammatory in origin, it has been described in patients undergoing chemotherapy, with autoimmune disease, and in some infections. We report a case of PRES that occurred one week after an episode of acute pancreatitis in an otherwise healthy 40-year-old female. There was progressive visual impairment over a 24-hour period with almost complete visual loss, with characteristic findings on magnetic resonance imaging. After treatment with steroids, the visual loss recovered. Clinicians should retain an index of suspicion of this rare condition in patients with visual impairment after acute pancreatitis. PMID:26759673

  1. Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus

    PubMed Central

    Tanaka, Tsukasa; Maruyama, Azusa; Nagase, Hiroaki

    2016-01-01

    Infection, whether viral or bacterial, can result in various forms of brain dysfunction (encephalopathy). Septic encephalopathy (SE) is caused by an excessive immune reaction to infection, with clinical features including disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is usually accompanied by viral infection in children and is characterized by biphasic seizures and impaired consciousness. The initial neurologic symptom of AESD is typically a febrile seizure that frequently lasts longer than 30 minutes. However, the possible forms this seizure takes are unclear. For example, it is unknown if nonconvulsive status epilepticus (NCSE) could be an early seizure symptomatic of AESD. In addition, thus far no cases of combined SE and AESD have been reported. Here, we describe the first reported case of SE with AESD that notably demonstrated NCSE as an early seizure. PMID:27051542

  2. Universal bilirubin screening for severe neonatal hyperbilirubinemia.

    PubMed

    Bhutani, V K; Vilms, R J; Hamerman-Johnson, L

    2010-10-01

    To reduce the incidence of severe neonatal hyperbilirubinemia affecting newborns with jaundice in the United States and to prevent kernicterus, there is a need to implement proven prevention strategies for severe neonatal hyperbilirubinemia as recommended in the 2004 American Academy of Pediatrics Guidelines for newborns >35 weeks gestational age. The purpose of universal predischarge bilirubin screening is to identify infants with bilirubin levels >75th percentile for age in hours and track those with rapid rates of bilirubin rise (>0.2 mg per 100 ml per h). Early identification has been reported to predict severe hyperbilirubinemia and allow for evidence-based targeted interventions. A systems approach is likely to reduce the preventable causes of acute bilirubin encephalopathy. To do so, highest priority should be given to (i) designating extreme hyperbilirubinemia (total serum bilirubin >427 μmol l(-1) or >25 mg per 100 ml) as a reportable condition by laboratories and health-care providers through public health mandates; (ii) implementation of Joint Commission's Sentinel Report for kernicterus; (iii) nursing outreach to communities for education of prospective parents; (iv) development of clinical pathways to monitor, evaluate and track infants with extreme hyperbilirubinemia; and (v) societal awareness. These efforts should be monitored by a state and national surveillance system in order to critically improve the timeliness and completeness of notifications and to allow evaluation and interventions at the policy and individual family level. PMID:20877410

  3. Bilirubin - urine

    MedlinePlus

    ... or gallbladder Considerations Bilirubin can break down in light. That is why babies with jaundice are sometimes placed under blue fluorescent lamps. Alternative Names Conjugated bilirubin - urine; Direct bilirubin - ...

  4. A case of recurrent acute encephalopathy with febrile convulsive status epilepticus with carnitine palmitoyltransferase II variation.

    PubMed

    Sakai, Eiko; Yamanaka, Gaku; Kawashima, Hisashi; Morishima, Yasuyuki; Ishida, Yu; Oana, Shingo; Miyajima, Tasuku; Shinohara, Mayu; Saitoh, Makiko; Mizuguchi, Masashi

    2013-08-01

    Acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is the most common type of acute encephalopathy in childhood in Japan, which develops with prolonged febrile convulsion, followed by mild unconsciousness. It is generally sporadic and nonrecurrent. In this report, a 1-year-old girl showed signs of AEFCSE triggered by respiratory syncytial virus infection. Two years later, she presented with AEFCSE triggered by influenza virus infection, resulting in severe neurologic sequelae. The patient had a thermolabile genotype of carnitine palmitoyltransferase II (CPT II) variations consisting of three single nucleotide polymorphisms in exons 4 [1055T > G/F352C and 1102G > A/V368I] and 5 [1939A > G/M647V]. The polymorphism has been identified as a genetic predisposition for acute encephalopathy. This report presents the first case of recurrent encephalopathy with CPT II variations that may partially associate with pathogenesis of recurrent AEFCSE. PMID:23450341

  5. A Child with Acute Encephalopathy Associated with Quadruple Viral Infection

    PubMed Central

    Nakata, Keiko; Kashiwagi, Mitsuru; Masuda, Midori; Shigehara, Seiji; Oba, Chizu; Murata, Shinya; Kase, Tetsuo; Komano, Jun A.

    2015-01-01

    Pediatric acute encephalopathy (AE) was sometimes attributed to virus infection. However, viral infection does not always result in AE. The risk factors for developing infantile AE upon virus infection remain to be determined. Here, we report an infant with AE co-infected with human herpesvirus-6 (HHV-6) and three picornaviruses, including coxsackievirus A6 (CVA6), Enterovirus D68 (EV-D68), and human parechovirus (HPeV). EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might be re-activated in the patient. It remained undetermined, which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection of four viruses should have evoked the cytokine storm, leading to the pathogenesis of AE. Conclusion: an infant case with active quadruple infection of potentially AE-causing viruses was seldom reported partly because systematic nucleic acid-based laboratory tests on picornaviruses were not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE. PMID:25883930

  6. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy

    PubMed Central

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah

    2016-01-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  7. Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy.

    PubMed

    Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Soon Sup; Lee, Ryung-Ah; Kim, Kwang Ho

    2016-03-01

    5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy. PMID:26942162

  8. Only a Touch of the Flu? The Simultaneous Manifestation of Acute Necrotizing Encephalopathy in Two Consanguineous Patients

    PubMed Central

    Bloch, C.; Suter, B.; Fischmann, A.; Gensicke, H.; Rüegg, S.; Weisser, M.

    2015-01-01

    This case report describes the simultaneous manifestation of acute necrotizing encephalopathy in 2 consanguineous patients after infection with influenza B based on the autosomal dominant missense mutation of the RANBP2-gene. Differential diagnosis of acute encephalopathy, clinical and radiological clues, and treatment strategies are outlined. PMID:26110162

  9. Bilirubin Test

    MedlinePlus

    ... test in conjunction with other laboratory tests ( alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase ) when someone shows signs ... Gilbert syndrome, due to low levels of the enzyme that produces conjugated bilirubin If conjugated (direct) bilirubin ...

  10. Posterior reversible encephalopathy syndrome following acute pancreatitis during chemotherapy for acute monocytic leukemia.

    PubMed

    Nishimoto, Mitsutaka; Koh, Hideo; Bingo, Masato; Yoshida, Masahiro; Nanno, Satoru; Hayashi, Yoshiki; Nakane, Takahiko; Nakamae, Hirohisa; Shimono, Taro; Hino, Masayuki

    2014-05-01

    We describe an 18-year-old man with acute leukemia who presented with posterior reversible encephalopathy syndrome (PRES) shortly after developing acute pancreatitis. On day 15 after the third consolidation course with high-dose cytarabine, treatment with broad-spectrum antibiotics was initiated for febrile neutropenia. On day 16, he developed septic shock, and subsequently, acute respiratory distress syndrome (ARDS). After adding vancomycin, micafungin and high-dose methylprednisolone (mPSL) to his treatment regimen, these manifestations subsided. On day 22, he received hemodialysis for drug-induced acute renal failure. On day 24, he developed acute pancreatitis possibly due to mPSL; the following day he had generalized seizures, and was intubated. Cerebrospinal fluid findings were normal. Brain MRI revealed hyperintense signals on FLAIR images and increased apparent diffusion coefficient values in the sub-cortical and deep white matter areas of the bilateral temporal and occipital lobes, indicative of vasogenic edema. Thus, we diagnosed PRES. Blood pressure, seizures and volume status were controlled, with MRI findings showing improvement by day 42. He was extubated on day 32 and discharged on day 49 without complications. Although little is known about PRES following acute pancreatitis, clinicians should be aware that this condition may develop. PMID:24881921

  11. EEG for Diagnosis and Prognosis of Acute Nonhypoxic Encephalopathy: History and Current Evidence.

    PubMed

    Sutter, Raoul; Kaplan, Peter W; Valença, Martina; De Marchis, Gian Marco

    2015-12-01

    The term encephalopathy encompasses a wide variety of complex syndromes caused by a large number of different toxic, metabolic, infectious, and degenerative derangements. Acute encephalopathy typically presents with a fluctuating course involving alteration of mental status or confusion and decreased (or rarely increased) motor activity. There usually are lethargy, cognitive impairment, altered memory and mental processing of information, and disturbed sleep-wake cycles. Encephalopathy mainly occurs in the elderly and is frequently encountered in intensive care units and postoperatively. Despite new diagnostic procedures and advances in intensive medical care, acute encephalopathy constitutes a significant cause of morbidity and mortality in hospitalized patients. EEG enables rapid bedside electrophysiological monitoring providing dynamic real-time information on neocortical brain activity and dysfunction. Hence, EEG complements clinical and neuroimaging assessments of encephalopathic patients. Progressive slowing of EEG background activity with increasing cerebral compromise, the emergence of episodic electrographic transients, seizures, and decreased EEG reactivity to external stimuli provide important diagnostic and prognostic information. The aim of this review was to provide a comprehensive overview of the current evidence for the diagnostic and prognostic value of EEG in adult intensive care unit patients with acute nonhypoxic encephalopathy. PMID:26629755

  12. Coagulopathy and encephalopathy in a dog with acute hepatic necrosis.

    PubMed

    Strombeck, D R; Krum, S; Rogers, Q

    1976-10-15

    Disseminated intravascular coagulation developed secondary to hepatic necrosis in a 5-year-old Saint Bernard. Although the coagulopathy responded to treatment with heparin, the dog died from the combined effects of gastric hemorrhage and encephalopathy, both of which are complications of hepatic necrosis. PMID:977448

  13. Clinical, Electroencephalographic, and Neuroradiological Outcome Predictors in Acute Nonhypoxic Encephalopathy: A Nine-Year Cohort Study.

    PubMed

    Sutter, Raoul; Kaplan, Peter W

    2016-01-01

    Marked impairment of consciousness, brain lesion on neuroimaging, and nonreactive electroencephalographic (EEG) background activity are established outcome predictors in patients with hypoxic encephalopathy. In this observational cohort study, we aimed to assess the predictive value of clinical, neuroimaging and EEG characteristics for outcome in different types of acute nonhypoxic encephalopathic patients. All adult intensive care unit patients from a tertiary academic medical care center with clinical and EEG evidence of acute nonhypoxic encephalopathy were included from 2004 to 2012. Clinical data, neuroimaging studies, EEG characteristics, and outcome were assessed. In-hospital death was the main outcome. Median age of 262 patients was 65 years (range 18-98 years). Mortality was 12.6%. In Poisson regression analyses, older age (P=.02), intracranial hemorrhage (P=.008), coma (P=.012), and nonreactive EEG background activity (P<.0001) were independently associated with death with nonreactive EEG being the strongest predictor (relative risk 3.74; 95% confidence interval 2.02-6.91). Subgroup analysis revealed no significant effect modification for the predictive value of nonreactive EEG by the presence or absence of coma and different types of acute brain lesions. In conclusion, this study identifies and quantifies the independent predictive value of older age, intracranial hemorrhage, coma, and nonreactive EEG for death, in patients with different types of acute nonhypoxic encephalopathy. These results add further credence to the limited body of evidence that EEG provides important prognostic information in different types of acute encephalopathy not related to hypoxic brain injury. Further studies are warranted to analyze the robustness of this predictor in larger subpopulations with specific etiologies of acute nonhypoxic encephalopathies. PMID:25828484

  14. Activated microglia in acute encephalopathy with biphasic seizures and late reduced diffusion.

    PubMed

    Fujita, Yuji; Takanashi, Jun-Ichi; Takei, Haruka; Ota, Setsuo; Fujii, Katsunori; Sakuma, Hiroshi; Hayashi, Masaharu

    2016-07-15

    Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. The exact pathogenesis of and the best therapeutic strategy for AESD are uncertain. We firstly performed a brain biopsy in a 2-year-old boy with AESD associated with RS viral infection, which revealed activated ameoboid microglia accumulation around degenerated neuron, and astrogliosis in the affected cortex. Glutamate released from activated microglia may play an important role in the pathogenesis of AESD, which is compatible with the previous report of magnetic resonance spectroscopy showing elevated glutamate. PMID:27288783

  15. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products. PMID:25510780

  16. Generalized chorea due to delayed encephalopathy after acute carbon monoxide intoxication

    PubMed Central

    Sung, Yueh-Feng; Chen, Ming-Hua; Peng, Giia-Sheun; Lee, Jiunn-Tay

    2015-01-01

    Movement disorder due to delayed encephalopathy after carbon monoxide (CO) intoxication is uncommon. Generalized chorea, presenting as an initial symptom of delayed encephalopathy, is extremely rare. We describe a 60-year-old woman, who had completely recovered from acute CO poisoning, developed mental and behavioral changes, urinary incontinence and generalized chorea 2 weeks thereafter. T2-weighted brain magnetic resonance imaging showed extensive hyperintensity of the bilateral periventricular and subcortical white matter and the globus pallidus. Brain single-photon emission computed tomography (SPECT) with technetium-99 ethylene cysteine dimer showed inhomogeneous perfusion in the cerebral cortex, with decreased uptake in bilateral frontal regions. Delayed encephalopathy after acute CO intoxication was diagnosed, and the symptoms gradually improved after hyperbaric oxygen therapy (HBOT). This case report demonstrates that generalized chorea may be one of the initial presenting symptoms of delayed encephalopathy after acute CO intoxication. We hypothesize that the generalized chorea in our patient may have been caused by the subcortical white matter lesions, which most likely interrupted the basal ganglia-thalamocortical circuits and that HBOT may be the treatment of choice for such patients. PMID:25745326

  17. Generalized chorea due to delayed encephalopathy after acute carbon monoxide intoxication.

    PubMed

    Sung, Yueh-Feng; Chen, Ming-Hua; Peng, Giia-Sheun; Lee, Jiunn-Tay

    2015-01-01

    Movement disorder due to delayed encephalopathy after carbon monoxide (CO) intoxication is uncommon. Generalized chorea, presenting as an initial symptom of delayed encephalopathy, is extremely rare. We describe a 60-year-old woman, who had completely recovered from acute CO poisoning, developed mental and behavioral changes, urinary incontinence and generalized chorea 2 weeks thereafter. T2-weighted brain magnetic resonance imaging showed extensive hyperintensity of the bilateral periventricular and subcortical white matter and the globus pallidus. Brain single-photon emission computed tomography (SPECT) with technetium-99 ethylene cysteine dimer showed inhomogeneous perfusion in the cerebral cortex, with decreased uptake in bilateral frontal regions. Delayed encephalopathy after acute CO intoxication was diagnosed, and the symptoms gradually improved after hyperbaric oxygen therapy (HBOT). This case report demonstrates that generalized chorea may be one of the initial presenting symptoms of delayed encephalopathy after acute CO intoxication. We hypothesize that the generalized chorea in our patient may have been caused by the subcortical white matter lesions, which most likely interrupted the basal ganglia-thalamocortical circuits and that HBOT may be the treatment of choice for such patients. PMID:25745326

  18. Acute lead encephalopathy in early infancy--clinical presentation and outcome.

    PubMed

    al Khayat, A; Menon, N S; Alidina, M R

    1997-03-01

    We studied 19 infants with a mean age of 3.8 months who presented with features consistent with acute lead encephalopathy following the use of traditional medicines. All presented with convulsions; CT scans of the brain on admission showed brain oedema in four, atrophy in four and normal findings in 11. Cerebrospinal fluid analysis in nine patients showed pleocytosis in six and a high protein content in eight. The median lead level in these 19 infants which encephalopathy was 3.6 mumol/l (74.5 micrograms/dl). Seven had a mean lead level of only 2.7 mumol/l (56.9 micrograms/dl) which is much below 70 micrograms/dl, the level usually proposed as the threshold for encephalopathy. Thirteen infants developed brain damage during follow-up; statistical analysis correlated the lead level at 2 months post chelation with an abnormal neurological outcome. Our findings indicate that in very young infants acute lead encephalopathy may occur at lead level lower than previously reported. PMID:9176576

  19. Identification of Viruses in Cases of Pediatric Acute Encephalitis and Encephalopathy Using Next-Generation Sequencing.

    PubMed

    Kawada, Jun-Ichi; Okuno, Yusuke; Torii, Yuka; Okada, Ryo; Hayano, Satoshi; Ando, Shotaro; Kamiya, Yasuko; Kojima, Seiji; Ito, Yoshinori

    2016-01-01

    Acute encephalitis/encephalopathy is a severe neurological syndrome that is occasionally associated with viral infection. Comprehensive virus detection assays are desirable because viral pathogens have not been identified in many cases. We evaluated the utility of next-generation sequencing (NGS) for detecting viruses in clinical samples of encephalitis/encephalopathy patients. We first determined the sensitivity and quantitative performance of NGS by comparing the NGS-determined number of sequences of human herpesvirus-6 (HHV-6) in clinical serum samples with the HHV-6 load measured using real-time PCR. HHV-6 was measured as it occasionally causes neurologic disorders in children. The sensitivity of NGS for detection of HHV-6 sequences was equivalent to that of real-time PCR, and the number of HHV-6 reads was significantly correlated with HHV-6 load. Next, we investigated the ability of NGS to detect viral sequences in 18 pediatric patients with acute encephalitis/encephalopathy of unknown etiology. A large number of Coxsackievirus A9 and mumps viral sequences were detected in the cerebrospinal fluid of 2 and 1 patients, respectively. In addition, Torque teno virus and Pepper mild mottle viral sequences were detected in the sera of one patient each. These data indicate that NGS is useful for detection of causative viruses in patients with pediatric encephalitis/encephalopathy. PMID:27625312

  20. Cortical gray matter lesions in acute encephalopathy with febrile convulsive status epilepticus.

    PubMed

    Sato, Atsushi; Mizuguchi, Masashi; Mimaki, Masakazu; Takahashi, Kan; Jimi, Hanako; Oka, Akira; Igarashi, Takashi

    2009-09-01

    In acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), subcortical white matter lesions on diffusion-weighted images are sometimes encountered on magnetic resonance imaging (MRI), such as in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). We report here a severe case of AEFCSE following respiratory syncytial virus infection, with emphasis on the cranial MRI findings. MRI in this patient showed widespread T2-hyperintensity along the cerebral cortical gray matter from day 3 to day 22. Lesions with reduced diffusion were noted on day 3 in the deep zone of gray matter of the left occipito-temporo-parietal cortex, but on day 7 they shifted to the subcortical white matter of both the cerebral hemispheres. These MRI findings provide radiologic evidence for damage to the cortical gray matter in AEFCSE. The serial change of diffusion-weighted images suggests that the cortical gray matter may be injured prior to the involvement of the subcortical white matter. PMID:18848752

  1. Bilirubin - blood

    MedlinePlus

    ... bilirubin is not processed normally by the liver ( Gilbert disease ) The following problems with gallbladder or bile ... Choledocholithiasis Cirrhosis Crigler-Najjar syndrome Dubin-Johnson syndrome Gilbert disease Glucose-6-phosphate dehydrogenase deficiency Hemoglobin Hemolytic ...

  2. Acute severe encephalopathy related to human herpesvirus-6 infection in a patient with carnitine palmitoyltransferase 2 deficiency carrying thermolabile variants.

    PubMed

    Kobayashi, Yoshiyuki; Ishikawa, Nobutsune; Tsumura, Miyuki; Fujii, Yuji; Okada, Satoshi; Shigematsu, Yosuke; Kobayashi, Masao

    2013-05-01

    We describe a male infant with carnitine palmitoyltransferase 2 (CPT2) deficiency who presented with acute encephalopathy related to human herpesvirus-6 (HHV-6) infection. He was hospitalized for pylexia and status epilepticus, diagnosed with acute encephalopathy, and treated with intensive supportive care including mechanical ventilation, support for hypothermia, and control of the intracranial pressure, that caused severe neurological sequelae. HHV-6 was detected in his cerebrospinal fluid, indicating HHV-6 related encephalopathy. In the acute phase, acylcarnitine analysis of blood suggested a defect of long chain fatty acid β-oxidation, and CPT2 deficiency was genetically confirmed. In addition, other gene alterations that have been previously reported as "thermolabile variants" were found. Some patients with the infantile form of CPT2 deficiency present with acute encephalopathy, but others do not develop encephalopathy. The correlation between phenotype and genotype has not been clarified. Our case may contribute to the elucidation of the genetic factor involved in acute encephalopathy in CPT2 deficiency. PMID:22854105

  3. Acute encephalitis and encephalopathy associated with human parvovirus B19 infection in children.

    PubMed

    Watanabe, Toru; Kawashima, Hideshi

    2015-11-01

    Reports of neurologic manifestations of human parvovirus B19 (B19) infection have been on the rise. Acute encephalitis and encephalopathy is the most common, accounting for 38.8% of total B19-associated neurological manifestations. To date, 34 children with B19 encephalitis and encephalopathy have been reported, which includes 21 encephalitis and 13 encephalopathy cases. Ten (29%) were immunocompromised and 17 (39%) had underlying diseases. Fever at the onset of disease and rash presented in 44.1% and 20.6% of patients, respectively. Neurological manifestations include alteration of consciousness occurred in all patients, seizures in 15 (44.1%) patients, and focal neurologic signs in 12 (35.3%) patients. Anemia and pleocytosis in cerebrospinal fluid (CSF) occurred in 56.3% and 48.1% of patients, respectively. Serum Anti-B19 IgM (82.6%) and CSF B19 DNA (90%) were positive in the majority of cases. Some patients were treated with intravenous immunoglobulins and/or steroids, although an accurate evaluation of the efficacy of these treatment modalities cannot be determined. Nineteen (57.6%) patients recovered completely, 11 (33.3%) patients had some neurological sequelae and 3 (8.8%) patients died. Although the precise pathogenesis underlying the development of B19 encephalitis and encephalopathy is unclear, direct B19 infection or NS1protein of B19 toxicity in the brain, and immune-mediated brain injuries have been proposed. PMID:26566485

  4. Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis

    PubMed Central

    Oguri, Masayoshi; Saito, Yoshiaki; Fukuda, Chisako; Kishi, Kazuko; Yokoyama, Atsushi; Lee, Sooyoung; Torisu, Hiroyuki; Toyoshima, Mitsuo; Sejima, Hitoshi; Kaji, Shunsaku; Hamano, Shin-ichiro; Okanishi, Toru; Tomita, Yutaka; Maegaki, Yoshihiro

    2016-01-01

    Background To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. Methods We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. Results Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. Conclusion Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD. PMID:27046946

  5. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers.

    PubMed

    DeKosky, Steven T; Blennow, Kaj; Ikonomovic, Milos D; Gandy, Sam

    2013-04-01

    Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE)--which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression--has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE. PMID:23558985

  6. Acute multiple focal neuropathies and delayed postanoxic encephalopathy after alcohol intoxication

    PubMed Central

    Wang, Wei-Che; Yang, Hsiu-Chun; Chen, Yao-Jen

    2015-01-01

    Acute-onset alcohol-associated neuropathy is only occasionally reported, and delayed postanoxic encephalopathy is rare. Here, we report a male who developed acute multiple focal neuropathies and later delayed postanoxic encephalopathy after alcohol intoxication. He had hypoxia and rhabdomyolysis, presenting with acute renal failure initially, and cardiopulmonary support, including mechanical ventilation, led to improvement of the patient at the acute stage. He suffered from bilateral hand numbness and mild weakness of the right lower limb thereafter. Nerve-conduction study revealed no pickup of compound muscle action potential or sensory nerve action potential in the bilateral ulnar nerve, but showed attenuated amplitude of compound muscle action potential in the right femoral nerve. Multiple focal neuropathies were suspected, and he received outpatient rehabilitation after being discharged. However, the patient developed gradual onset of weakness in four limbs and cognitive impairment 23 days after the hypoxia event. Brain computed tomography showed low attenuation over bilateral globus pallidus, and brain magnetic resonance imaging disclosed diffuse increased signal intensity on T2-weighted images and fluid-attenuated inversion recovery in bilateral white matter. He was admitted again under the impression of delayed postanoxic brain injury. Supportive treatment and active rehabilitation were given. He had gradual improvement in motor and functional status after rehabilitation. He could walk with festinating gait under supervision, and needed only minimal assistance in performing activities of daily living approximately 1 year later. PMID:26229472

  7. [A 6-year-old girl who exhibited residual reading disorder during the course of acute encephalopathy].

    PubMed

    Nagaharu, Sachiko; Inaba, Yuji; Motobayashi, Mitsuo; Misawa, Yuka; Fukuyama, Tetsuhiro; Higuchi, Tsukasa; Harada, Machiko

    2012-11-01

    We assessed a 6-year-old girl who developed status epilepticus and exhibited transient aphasia during the course of acute encephalopathy with late reduced diffusion, and who had a residual reading disorder in the recovery period. The aphasia appeared to be fluent aphasia and anomia, suggesting that the reading disorder during the recovery process was due to impairment of the phonological process. There were no biphasic seizures during the course of the patient's illness, but this case was acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) from the standpoint of the characteristic imaging findings. Lesions in the left parietal and temporal lobes were detected on MRI diffusion-weighted images and by SPECT and MRS, and they appeared to be the lesions responsible for the aphasia and residual reading disorder. This case appears to be important from the standpoint of assessing the pathophysiology and the treatment of coexisting illness observed in acute encephalopathy. PMID:23240531

  8. Acute Respiratory Distress Syndrome and Posterior Reversible Encephalopathy Syndrome following Rituximab Therapy.

    PubMed

    Wardrope, Katrina E; Manson, Lynn; Metcalfe, Wendy; Sullivan, Eoin D O

    2016-01-01

    The anti-CD20 monoclonal antibody rituximab is associated with rare but significant adverse events, notably posterior reversible encephalopathy syndrome (PRES) and acute respiratory distress syndrome (ARDS). We report a case of concomitant ARDS and PRES developing after rituximab therapy for treatment of cryoglobulinaemic vasculitis. There are 7 reported cases of PRES complicating rituximab use. PRES onset varied from immediate to 21 days after administration. All patients recovered completely, and rituximab was reintroduced in half of the cases. The occurrence of ARDS in association with rituximab is rarer. Only 3 confirmed cases exist, and ARDS may occur as a delayed reaction. PMID:27275457

  9. Acute Respiratory Distress Syndrome and Posterior Reversible Encephalopathy Syndrome following Rituximab Therapy

    PubMed Central

    Wardrope, Katrina E.; Manson, Lynn; Metcalfe, Wendy; Sullivan, Eoin D. O

    2016-01-01

    The anti-CD20 monoclonal antibody rituximab is associated with rare but significant adverse events, notably posterior reversible encephalopathy syndrome (PRES) and acute respiratory distress syndrome (ARDS). We report a case of concomitant ARDS and PRES developing after rituximab therapy for treatment of cryoglobulinaemic vasculitis. There are 7 reported cases of PRES complicating rituximab use. PRES onset varied from immediate to 21 days after administration. All patients recovered completely, and rituximab was reintroduced in half of the cases. The occurrence of ARDS in association with rituximab is rarer. Only 3 confirmed cases exist, and ARDS may occur as a delayed reaction.

  10. Posterior reversible encephalopathy syndrome in pediatric acute leukemia: Case series and literature review

    PubMed Central

    Appachu, M. Sandhya; Purohit, Samit; Lakshmaiah, K. C.; Kumari, B.S. Aruna; Appaji, L.

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state coupled with a unique radio imaging appearance. We describe this rare, mostly reversible condition in five cases undergoing similar treatment under preset protocol (MCP-841) for acute lymphoblastic leukemia (ALL) at our centre. Hypertension is a well-known adverse effect of high-dose corticosteroid therapy primarily mediated by its effects on the mineralocorticoid receptor especially in pediatric population and we hypothesize that this may be the etiology of PRES in two of these patients. PMID:25006290

  11. Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

    PubMed

    Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

    2015-11-15

    Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. PMID:26381705

  12. Periodic synchronous discharge occurred in an elderly with acute valacyclovir-associated encephalopathy.

    PubMed

    Nakatani, Mitsuyoshi; Tsukino, Mitsuhiro; Takahashi, Ryosuke; Ikeda, Akio

    2016-07-28

    An 81-year-old woman suffering from sarcoidosis, chronic renal failure caused by hypertention was treated by valacyclovir 500 mg/day, for the diagnosis of herpes zoster of her right back. Her consciousness gradually became worse, and 3 days after taking the drug, she was sent to the emergency department of the hospital. Her conscious level was E2V2M5 (Glasgow Coma Scale) and myoclonus especially in her lower extremities occurred. Head CT and MRI show no obvious, acute abnormal findings other than chronic ischemic lesions, while an electroencephalogram (EEG) shows periodic synchronous discharges (PSDs) and disorganized background activity. Based on these findings, she was diagnosed as valacyclovir-associated acute encephalopathy. After conservative therapy of maintenance hemodialysis, her consciousness gradually improved, and PSDs disappeared accordingly and background activity of EEG became improved. In this case report, we presented valacyclovir-associated neurotoxicity with PSDs in EEG as potentially a surrogate marker. We should be cautious to use valaciclovir which may cause drug-induced encephalopathy especially in elderly or patients with renal failure even though the dose was adjusted in advance. PMID:27356736

  13. Posterior reversible encephalopathy syndrome: an acute manifestation of systemic lupus erythematous.

    PubMed

    Chan, Dexter Yak Seng; Ong, Yin Sheng

    2013-09-01

    Stroke mimickers are common, and they represent a diagnostic dilemma for clinicians. Many, like posterior reversible encephalopathy syndrome (PRES), are easily reversible. The manifestation of PRES is characterised by headaches, convulsions, altered mental functioning and blindness. In most cases, computed tomography of the brain will show hypodense lesions in the parieto-occpitial lobe, which only further confounds the physician. Although this syndrome is uncommon, prompt and accurate recognition allows early treatment, which has been shown to produce favourable outcomes. Herein, we report the case of a 54-year-old woman, who presented with PRES, as an acute manifestation of systemic lupus erythematous (SLE) and lupus nephritis. The patient was initially thought to be experiencing an ischaemic stroke, but the diagnosis was later changed. On management of her underlying condition, her symptoms resolved. PRES should be recognised as an acute emergency manifestation of SLE. It should not be mistaken for an ischaemic stroke as inappropriate treatment could have adverse outcomes. PMID:24068069

  14. Pegylated Liposomal Doxorubicin-Induced Acute Transient Encephalopathy in a Patient with Breast Cancer: A Case Report

    PubMed Central

    Baker, Michelle; Markman, Maurie; Niu, Jiaxin

    2014-01-01

    Background Pegylated liposomal doxorubicin (PLD) has a unique pharmacokinetic profile and is widely used to treat a variety of malignancies, alone or in combination with other agents. Case Report A 57-year-old female patient with metastatic breast cancer developed dural metastases to the brain and underwent craniotomy and whole-brain radiation. She continued to receive chemotherapy with carboplatin without any serious complications. Four months later, there was evidence of progression leading to the institution of PLD. During the first course of PLD, there was evidence of acute encephalopathy which resolved after 18 h with discontinuation of this agent. Interestingly, she did well when she was rechallenged with conventional doxorubicin in the following cycles. Conclusion We hereby report, to the best of our knowledge, the first case of acute transient encephalopathy induced by PLD. We postulate that partial disruption of the blood-brain barrier may have been responsible for PLD-induced encephalopathy. PMID:24803900

  15. Acute confusional state caused by Hashimoto's encephalopathy in a patient with hypothyroidism: a case report

    PubMed Central

    Nookala, Vinod; Srivastava, Anupam; Qazizadeh, Salim; Fischman, Daniel

    2009-01-01

    Introduction Hashimoto's Encephalopathy is an unusual condition associated with Hashimoto's Thyroiditis. This immune-mediated, steroid-dependent entity was first described thirty years ago. In this case report, we discuss the importance of considering this diagnosis in the evaluation of confusion. Case presentation The patient is a 55-year-old African-American woman residing in United States, who was admitted to the hospital with a four-day history of mental status changes. Her past medical history was significant for type II Diabetes Mellitus, Hypertension, and Hypothyroidism. There was no reported seizure activity. The patient's vital signs were stable on admission. On examination, the patient was awake, alert, oriented to place and time. Her neurological examination revealed agraphia and dyslexia. Her speech showed lack of fluency and hesitation. Her complete blood count and electrolytes were within normal limits. The patient's brain CT scan did not reveal any significant findings. Her Magnetic Resonance Imaging only revealed mild chronic microangiopathy, which caused by “small vessel disease.” Her Electroencephalogram did not reveal any finding consistent with seizure activity. Cerebral spinal fluid analysis was likewise did not reveal a cause for this patient's acute onset of confusion. In contrast to the above negative finding, this patient's Thyroid stimulating hormone was discovered to be 15 UIU/ml. She was subsequently given 1000 mg of intravenous Methylprednisolone daily for 3 days. This three-day course of high-dose, intravenous steroids resulted complete resolution of the patient's symptoms. She was then discharged on an eleven-day course of oral prednisone 60 mg. Conclusion Hashimoto's Encephalopathy should be considered in the differential diagnosis of an acute confusional state since it is responsive to steroid therapy and represents a readily reversible cause acute mental status changes. Clues to this diagnosis include elevated antithyroid

  16. The Optimal Management of Acute Febrile Encephalopathy in the Aged Patient: A Systematic Review.

    PubMed

    Sheybani, Fereshte; Naderi, Hamid Reza; Sajjadi, Sareh

    2016-01-01

    The elderly comprise less than 13 percent of world population. Nonetheless, they represent nearly half of all hospitalized adults. Acute change in mental status from baseline is commonly seen among the elderly even when the main process does not involve the central nervous system. The term "geriatric syndrome" is used to capture those clinical conditions in older people that do not fit into discrete disease categories, including delirium, falls, frailty, dizziness, syncope, and urinary incontinence. Despite the growing number of elderly population, especially those who require hospitalization and the high burden of common infections accompanied by encephalopathy among them, there are several unresolved questions regarding the optimal management they deserve. The questions posed in this systematic review concern the need to rule out CNS infection in all elderly patients presented with fever and altered mental status in the routine management of febrile encephalopathy. In doing so, we sought to identify all potentially relevant articles using searches of web-based databases with no language restriction. Finally, we reviewed 93 research articles that were relevant to each part of our study. No prospective study was found to address how should AFE in the aged be optimally managed. PMID:26989409

  17. The Optimal Management of Acute Febrile Encephalopathy in the Aged Patient: A Systematic Review

    PubMed Central

    Sheybani, Fereshte; Naderi, HamidReza; Sajjadi, Sareh

    2016-01-01

    The elderly comprise less than 13 percent of world population. Nonetheless, they represent nearly half of all hospitalized adults. Acute change in mental status from baseline is commonly seen among the elderly even when the main process does not involve the central nervous system. The term “geriatric syndrome” is used to capture those clinical conditions in older people that do not fit into discrete disease categories, including delirium, falls, frailty, dizziness, syncope, and urinary incontinence. Despite the growing number of elderly population, especially those who require hospitalization and the high burden of common infections accompanied by encephalopathy among them, there are several unresolved questions regarding the optimal management they deserve. The questions posed in this systematic review concern the need to rule out CNS infection in all elderly patients presented with fever and altered mental status in the routine management of febrile encephalopathy. In doing so, we sought to identify all potentially relevant articles using searches of web-based databases with no language restriction. Finally, we reviewed 93 research articles that were relevant to each part of our study. No prospective study was found to address how should AFE in the aged be optimally managed. PMID:26989409

  18. Variable clinical course in acute necrotizing encephalopathy and identification of a novel RANBP2 mutation.

    PubMed

    Sell, Katharina; Storch, Katja; Hahn, Gabriele; Lee-Kirsch, Min Ae; Ramantani, Georgia; Jackson, Sandra; Neilson, Derek; von der Hagen, Maja; Hehr, Ute; Smitka, Martin

    2016-09-01

    Acute necrotizing encephalopathy (ANE) is a rare disease presenting with rapidly progressing encephalopathy. It usually occurs in otherwise healthy children after common viral infections. The hallmarks of ANE are the neuroradiological findings of multiple symmetric lesions in the thalami, midbrain, pons and brainstem. Most cases are sporadic and non recurrent. However, recurrent or familial forms of ANE due to mutations in RANBP2 gene have been reported. It has been suggested to give these cases the term ANE1. We report the clinical course in two male infants (P1, P2) with ANE1 and a variable clinical course and outcome. One patient is heterozygous for the most common RANBP2 missense mutation p.Thr585Met. In the other patient we observed a novel de novo missense mutation p.Trp681Cys in the RANBP2 gene causing recurrent ANE. Clinical and radiological features are presented and differential diagnoses are discussed. This report adds to the current knowledge of the phenotype in ANE, caused by mutations in RANBP2 gene. PMID:26923722

  19. The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.

    PubMed

    Yin, Xin-Lu; Liang, Min; Shi, Hai-Bo; Wang, Lu-Yang; Li, Chun-Yan; Yin, Shan-Kai

    2016-01-01

    Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity. PMID:26476400

  20. Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection.

    PubMed

    Zhang, Shuo; Feng, Juan; Shi, Yifang

    2016-01-01

    Infection with Epstein-Barr virus (EBV) is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical-radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions. PMID:26600186

  1. 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

  2. Acute intermittent porphyria leading to posterior reversible encephalopathy syndrome (PRES): a rare cause of abdominal pain and seizures.

    PubMed

    Dagens, Andrew; Gilhooley, Michael James

    2016-01-01

    Acute intermittent porphyria (AIP) is an inherited deficiency in the haem biosynthesis pathway. AIP is rare, affecting around 1 in 75 000 people. Acute attacks are characterised by abdominal pain associated with autonomic, neurological and psychiatric symptoms. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES). PRES is a clinicoradiological condition caused by the failure of the posterior circulation to autoregulate, resulting in cerebral oedema, headaches, nausea and seizures. This association is important because drugs used in the management of seizures may worsen an attack of AIP. This article describes a case of AIP and PRES in a young woman. PMID:27277587

  3. Predictive score for early diagnosis of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD).

    PubMed

    Tada, Hiroko; Takanashi, Jun-ichi; Okuno, Hideo; Kubota, Masaya; Yamagata, Takanori; Kawano, Gou; Shiihara, Takashi; Hamano, Shin-ichiro; Hirose, Shinichi; Hayashi, Takuya; Osaka, Hitoshi; Mizuguchi, Masashi

    2015-11-15

    Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) at onset manifests an early seizure (ES) usually lasting more than 30 min. Following ES, some patients exhibit almost clear consciousness with no neurological symptoms, and no MRI abnormality for a few days, which may lead to an initial misdiagnosis of prolonged febrile seizures (PFS). To allow an early diagnosis of AESD, we retrospectively analyzed clinical manifestations, laboratory data, and radiologic and EEG findings in patients with AESD (n=62) having ES of over 30 min, and ones with PFS (n=54), using logistic regression analyses. Multivariate logistic regression analysis revealed that an age below 1.5 years and a Glasgow Coma Scale score of 14 or less than 14 (Japan Coma Scale score of 1 or higher) were high risk factors of developing AESD. We proposed an AESD prediction score system consisting of consciousness level, age, duration of convulsions, enforcement of mechanical intubation, and aspartate aminotransferase, blood glucose and creatinine levels (full score: 9), the mean scores in AESD and PFS being 5.9 and 1.8, which were significantly different (p<0.001). We herein propose a scoring system for differentiating patients with AESD and PFS around the time of ES (score of 4 or more than 4 suggesting AESD), which may contribute to early therapeutic intervention and an improved neurologic outcome. PMID:26333951

  4. A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

    PubMed Central

    Gupta, Charu; Massaro, An N.

    2016-01-01

    Background Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. Methods To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). Results Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI–KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. Conclusions The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life. PMID:26857710

  5. [Recurrent posterior reversible encephalopathy due to vasospasm and cerebral hypoperfusionin in acute leukemia: a case report].

    PubMed

    Hiraide, Takuya; Matsubayashi, Tomoko; Ishigaki, Hidetoshi; Asahina, Miki; Sakaguchi, Kimiyoshi; Fukuda, Tokiko

    2015-11-01

    We report the case of a 4-year-old girl who presented with recurrent posterior reversible encephalopathy syndrome (PRES). She was diagnosed with B-precursor acute lymphocytic leukemia (ALL), and was administered remission-induction chemotherapy. On day 28 of the induction therapy, she experienced seizure and prolonged unconsciousness. Blood pressure was slightly elevated. MRI revealed cortical cytotoxic edema in the right temporal and occipital lobes. In the right occipital white matter the lesion with vasogenic edema also existed. Three days later, MRI showed vasogenic edema in subcortical white matter of the right temporal right occipital and bilateral occipital lobes. The lesions had receded with time. Since the seizure occurred, the chemotherapy had been discontinued. The episodes of seizure and prolonged consciousness recurred 22 days later. MRI revealed vasogenic edema in the right occipital lobe, and MR angiography demonstrated vessel irregularity and reduced branch visualization in the middle and posterior cerebral arteries. Arterial spin-labeling (ASL) showed hypoperfusion in both occipital lobes. It suggests that vasoconstriction and hypoperfusion could lead to recurrent PRES in this case. It is possible that ASL might be more sensitive than MRI in detecting the lesions of PRES. It should be noted that PRES might recur in leukemia. PMID:26717647

  6. Solvent encephalopathy.

    PubMed Central

    King, M D; Day, R E; Oliver, J S; Lush, M; Watson, J M

    1981-01-01

    Nineteen children aged 8-14 years were admitted over a six-year period with an acute encephalopathy due to toluene intoxication. Seven had a history of euphoria and hallucinations. The remainder presented with coma (4), ataxia (3), convulsions (3), and behaviour disturbance with diplopia (2), A history of glue sniffing was elicited in 14, but in the remainder toluene assay confirmed the diagnosis. Thirteen children recovered completely; five still had psychological impairment and personality change on discharge from hospital but were lost to follow-up, and one has a persistent cerebellar ataxia one year after the acute episode, despite absence of further exposure. Toluene inhalation is an important cause of encephalopathy in children and may lead to permanent neurological damage. Diagnosis is most important if further damage due to continued abuse is to be prevented, and toluene assay is a valuable aid to diagnosis. PMID:6790121

  7. Late-onset epilepsy in children with acute febrile encephalopathy with prolonged convulsions: A clinical and encephalographic study.

    PubMed

    Saito, Takashi; Saito, Yoshiaki; Sugai, Kenji; Nakagawa, Eiji; Komaki, Hirofumi; Okazaki, Tetsuya; Ishido, Yusaku; Kaneko, Yuu; Kaido, Takanobu; Takahashi, Akio; Ohtsuki, Taisuke; Sakuma, Hiroshi; Sasaki, Masayuki

    2013-06-01

    The aim of this study is to analyze the characteristics of epilepsies as the sequelae of acute febrile encephalopathy with prolonged convulsions during childhood. Sixteen patients (M:F=9:7) aged 2-13years (mean 6.1years) with history of febrile acute encephalopathy were retrospectively reviewed. These patients experienced febrile encephalopathy at the age of 11months to 4years, with 11 individuals presenting with findings of a biphasic clinical course (n=5), frontal predominant (n=8) lesions, and/or reduced diffusivity in the cerebral white matter on magnetic resonance imaging (MRI; n=3). The remaining 5 patients had unilateral lesions that manifested the phenotype of hemiconvulsion-hemiplegia-epilepsy syndrome (HHES). Epilepsy emerged with a latent period of 2months to 2years after the acute phase of febrile encephalopathy. Head nodding or spasm with subsequent motion arrest and brief tonic seizures were the main seizure phenotypes. Ictal records of epileptic seizures were available in 9 patients. Epileptiform discharges with a focal or uneven distribution appeared at the seizure onset and lasted less than 1s in all patients; these were followed by either generalized attenuation or fast activity in 8 patients with head nodding, spasm, or brief tonic seizures, and by localized fast activity in 1 patient with versive tonic seizures. Notably, the seizure onset area was often located outside the severe lesions on MRI, i.e., in the parietal areas in patients with frontal predominant lesions, and in the spared hemisphere of HHES. Although phenobarbital, zonisamide, carbamazepine, clobazam, clonazepam, and clorazepate were partially effective in some patients, daily seizures persisted in 11 patients. Callosotomy was performed in 2 patients, and beneficial effects were observed in both. These characteristics suggested a broad distribution of augmented excitability in these patients, resulting in the rapid propagation of epileptic activity in the initial phase of ictal

  8. [A case of paroxysmal sympathetic storm after acute disseminated encephalomyelitis and hypoxic encephalopathy responding to clonidine hydrochloride].

    PubMed

    Shimmura, Mitsunori; Kawamura, Nobutoshi; Tateishi, Takahisa; Shigeto, Hiroshi; Murai, Hiroyuki; Kira, Jun-Ichi

    2016-01-01

    We report the case of a 17-year-old woman with paroxysmal sympathetic storm (PSS), which was successfully treated with clonidine hydrochloride. The patient was hospitalized for acute disseminated encephalomyelitis in June 2006. Dysphagia led to severe aspiration pneumonia in September 2006, and she suffered cardiopulmonary arrest. She survived but had severe brain damage, with her brain MRI showing diffuse hypoxic encephalopathy. From October 2006, she had several episodes of profound tachypnea (> 60/min), tachycardia (160 to 170 beats/min), hypertension (> 140 mmHg), hyperthermia (39°C), and decerebrate posturing. During the attacks, the levels of catecholamines in the patient's blood and urine were markedly elevated. Accordingly, a diagnosis of PSS associated with hypoxic encephalopathy was made. Her PSS clearly improved after the administration of clonidine hydrochloride (900 μg/day). This case suggests that clonidine hydrochloride, an α2 blocker, may be one therapeutic option for PSS. PMID:26754594

  9. H1N1 triggered recurrent acute necrotizing encephalopathy in a family with a T653I mutation in the RANBP2 gene.

    PubMed

    Anand, Geetha; Visagan, Ravindran; Chandratre, Saleel; Segal, Shelley; Nemeth, Andrea H; Squier, Waney; Sheerin, Fintan; Neilson, Derek; Jayawant, Sandeep

    2015-03-01

    A 28-month-old infant presented with fever, vomiting and encephalopathy. Magnetic resonance imaging findings and family history confirmed a diagnosis of recurrent familial acute necrotizing encephalopathy (ANE1). We believe that this is the first description implicating the H1N1 viral strain as a trigger and the second report of a T653I mutation in the RANBP2 gene described in relation to ANE1. PMID:25170550

  10. Blood Test: Bilirubin

    MedlinePlus

    ... two forms in the body: indirect (unconjugated) and direct (conjugated). Indirect bilirubin, which doesn't dissolve in ... liver to be changed into the soluble form, direct bilirubin. Why It's Done Healthy newborns — especially those ...

  11. A novel autoantibody against ephrin type B receptor 2 in acute necrotizing encephalopathy

    PubMed Central

    2013-01-01

    Acute necrotizing encephalopathy (ANE) is characterized by symmetrical brain necrosis, suggested to be due to breakdown of the blood–brain barrier (BBB). We experienced a rare case of ANE complicated with systemic lupus erythematosus (SLE), and found that the patient’s serum (V10-5) had binding activity to human umbilical vein endothelial cells (HUVECs). By SARF (Serological identification system for Autoantigens using a Retroviral vector and Flow cytometry) method using V10-5 IgG, a clone bound to V10-5 IgG was isolated. This cell clone was integrated with cDNA identical to EphB2, which plays critical roles in neuronal cells and endothelial cells. HUVECs and human brain microvascular endothelial cells expressed EphB2 and the V10-5 IgG bound specifically to EphB2-transfected cells. Anti-EphB2 antibody was not detected in other SLE patients without ANE. In this report, we identified EphB2 as a novel autoantigen, and anti-EphB2 antibody may define a novel group of brain disorders. Anti-EphB2 antibody can interfere not only with endothelial cells including those of the BBB (acting as an anti-endothelial cell antibody), but also neuronal cells (acting as an anti-neuronal antibody) if the BBB has been breached. Future studies should determine the clinical prevalence and specificity of anti-EphB2 antibody, and the molecular mechanisms by which anti-EphB2 antibody mediates neuronal and vascular pathological lesions. PMID:24139226

  12. A novel autoantibody against ephrin type B receptor 2 in acute necrotizing encephalopathy.

    PubMed

    Shirai, Tsuyoshi; Fujii, Hiroshi; Ono, Masao; Watanabe, Ryu; Shirota, Yuko; Saito, Shinichiro; Ishii, Tomonori; Nose, Masato; Harigae, Hideo

    2013-01-01

    Acute necrotizing encephalopathy (ANE) is characterized by symmetrical brain necrosis, suggested to be due to breakdown of the blood-brain barrier (BBB). We experienced a rare case of ANE complicated with systemic lupus erythematosus (SLE), and found that the patient's serum (V10-5) had binding activity to human umbilical vein endothelial cells (HUVECs). By SARF (Serological identification system for Autoantigens using a Retroviral vector and Flow cytometry) method using V10-5 IgG, a clone bound to V10-5 IgG was isolated. This cell clone was integrated with cDNA identical to EphB2, which plays critical roles in neuronal cells and endothelial cells. HUVECs and human brain microvascular endothelial cells expressed EphB2 and the V10-5 IgG bound specifically to EphB2-transfected cells. Anti-EphB2 antibody was not detected in other SLE patients without ANE. In this report, we identified EphB2 as a novel autoantigen, and anti-EphB2 antibody may define a novel group of brain disorders. Anti-EphB2 antibody can interfere not only with endothelial cells including those of the BBB (acting as an anti-endothelial cell antibody), but also neuronal cells (acting as an anti-neuronal antibody) if the BBB has been breached. Future studies should determine the clinical prevalence and specificity of anti-EphB2 antibody, and the molecular mechanisms by which anti-EphB2 antibody mediates neuronal and vascular pathological lesions. PMID:24139226

  13. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy

    PubMed Central

    Cichoż-Lach, Halina; Michalak, Agata

    2013-01-01

    Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses. PMID:23326159

  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. Mechanisms of bilirubin toxicity: clinical implications.

    PubMed

    Hansen, Thor Willy Ruud

    2002-12-01

    The basic mechanism of kernicterus and bilirubin encephalopathy has not been unequivocally determined. Much knowledge has been gained about phenomena that contribute to bilirubin neurotoxicity, and this knowledge has implications for clinical practice. Conditions that impact on blood-brain barrier function, increase brain blood flow, or impact on bilirubin metabolism, including its transport in serum, should be avoided, if possible. Such conditions include drugs and drug stabilizers that compete with bilirubin binding to albumin, or that inhibit P-glycoprotein in the blood-brain barrier, prematurity/immaturity, and clinically significant illness in the infant that involves hemolysis, respiratory and metabolic acidosis, infection, asphyxia, hypoxia and (perhaps) hyperoxia, and hyperosmolality. If these conditions are not avoidable then there should be a more aggressive approach to the treatment of hyperbilirubinemia. The limits of tolerance for hyperbilirubinemia varies among neonates and there are no tools to determine with certainty when a particular infant is approaching the danger zone. Neurological symptoms in a jaundiced infant require extreme vigilance, and, in most cases, immediate intervention. PMID:12516745

  16. [Scapular and vertebral osteopathies during acute myoclonic bismuth encephalopathies. Apropos of 8 cases].

    PubMed

    Emile, J; De Bray, J M; Bernat, M; Morer, T; Allain, P

    1979-01-01

    Among 59 cases of bismuth encephalopathy, 8 patients were observed to have osteo-articular lesions of the shoulders and dorsal vertebral. These included osteonecrosis of the head of the humerus, which has been reported previously, uni- or bi-lateral fractures of the upper end of the humerus, and vertebral fractures. Severe and repeated myoclonic spasms appear to be capable of causing fractures; microscopic fractures in the spongy bone could explain the osteonecrotic images observed. PMID:434718

  17. Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction.

    PubMed

    Patel, Mahendra K; Patel, Tejas K; Tripathi, C B

    2012-01-01

    A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus (DPT) vaccine used for routine immunization. Postreaction computed tomography (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries. PMID:22368426

  18. Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction

    PubMed Central

    Patel, Mahendra K.; Patel, Tejas K.; Tripathi, C. B.

    2012-01-01

    A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus (DPT) vaccine used for routine immunization. Postreaction computed tomography (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries. PMID:22368426

  19. Inherited Disorders of Bilirubin Clearance

    PubMed Central

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  20. 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

  1. Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy.

    PubMed

    Freund, H; Dienstag, J; Lehrich, J; Yoshimura, N; Bradford, R R; Rosen, H; Atamian, S; Slemmer, E; Holroyde, J; Fischer, J E

    1982-08-01

    Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group

  2. MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke's Encephalopathy: A Review

    PubMed Central

    Manzo, Gaetana; De Gennaro, Angela; Cozzolino, Attilio; Serino, Antonietta; Fenza, Giacomo; Manto, Andrea

    2014-01-01

    Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. Apart from chronic alcoholism, the most common cause of WE, a lot of other conditions causing malnutrition and decreasing thiamine absorption such as gastrointestinal surgical procedures and hyperemesis gravidarum must be considered as predisposing factors. Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed, leading to persistent dysfunctions and, in some cases, to death. Nowadays, MR imaging of the brain, showing T2 and FLAIR hyperintensities in typical (thalami, mammillary bodies, tectal plate, and periaqueductal area) and atypical areas (cerebellum, cranial nerve nuclei, and cerebral cortex), is surely the most important and effective tool in the diagnostic assessment of WE. The aim of this paper is to propose a state of the art of the role of MR imaging in the early diagnosis of this complex disease. PMID:25050351

  3. Epidemiological analysis of a large enterohaemorrhagic Escherichia coli O111 outbreak in Japan associated with haemolytic uraemic syndrome and acute encephalopathy.

    PubMed

    Yahata, Y; Misaki, T; Ishida, Y; Nagira, M; Watahiki, M; Isobe, J; Terajima, J; Iyoda, S; Mitobe, J; Ohnishi, M; Sata, T; Taniguchi, K; Tada, Y; Okabe, N

    2015-10-01

    A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) O111 and O157 occurred in Japan in April 2011. We conducted an unmatched case-control study and trace-back investigation to determine the source of EHEC O111 infection and risk factors for severe complications. Pulsed-field gel electrophoresis was performed to help define cases. A total of 86 individuals met the case definition. Of these, 40% experienced haemolytic uraemic syndrome (HUS), 24% acute encephalopathy, and 6% died. Illness was significantly associated with eating the raw beef dish yukhoe (odds ratio 19·64, 95% confidence interval 7·03-54·83), the likely food vehicle. EHEC O111 and its closely related stx-negative variants were found in the beef. HUS occurred most frequently in individuals aged 5-9 years, and this age group was significantly associated with acute encephalopathy. The prevalence of HUS and acute encephalopathy was higher than in previous non-O157-related outbreaks, indicating a high risk of severe complications. PMID:25600435

  4. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, James W.

    1993-01-01

    A transcutaneous bilirubin detector comprising a source of light having spectral components absorbable and not absorbable by bilirubin, a handle assembly, electronic circuitry and a fiber optic bundle connecting the assembly to the light source and circuitry. Inside the assembly is a prism that receives the light from one end of the fiber optic bundle and directs it onto the skin and directs the reflected light back into the bundle. The other end of the bundle is trifucated, with one end going to the light source and the other two ends going to circuitry that determines how much light of each kind has been reflected. A relatively greater amount absorbed by the skin from the portion of the spectrum absorbable by bilirubin may indicate the presence of the illness. Preferably, two measurements are made, one on the kneecap and one on the forehead, and compared to determine the presence of bilirubin. To reduce the impact of light absorption by hemoglobin in the blood carried by the skin, pressure is applied with a plunger and spring in the handle assembly, the pressure limited by points of a button slidably carried in the assembly that are perceived by touch when the pressure applied is sufficient.

  5. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1991-03-04

    This invention consists of a transcutaneous bilirubin detector comprising a source of light having spectral components absorbable and not absorbable by bilirubin, a handle assembly, electronic circuitry and a fiber optic bundle connecting the assembly to the light source and circuitry. Inside the assembly is a prism that receives the light from one end of the fiber optic bundle and directs it onto the skin and directs the reflected light back into the bundle. The other end of the bundle is trifucated, with one end going to the light source and the other two ends going to circuitry that determines how much light of each kind has been reflected. A relatively greater amount absorbed by the skin from the portion of the spectrum absorbable by bilirubin may indicate the presence of the illness. Preferably, two measurements are made, one on the kneecap and one on the forehead, and compared to determine the presence of bilirubin. To reduce the impact of light absorption by hemoglobin in the blood carried by the skin, pressure is applied with a plunger and spring in the handle assembly, the pressure limited by points of a button slidably carried in the assembly that are perceived by touch when the pressure applied is sufficient.

  6. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1993-11-09

    A transcutaneous bilirubin detector is designed comprising a source of light having spectral components absorbable and not absorbable by bilirubin, a handle assembly, electronic circuitry and a fiber optic bundle connecting the assembly to the light source and circuitry. Inside the assembly is a prism that receives the light from one end of the fiber optic bundle and directs it onto the skin and directs the reflected light back into the bundle. The other end of the bundle is trifucated, with one end going to the light source and the other two ends going to circuitry that determines how much light of each kind has been reflected. A relatively greater amount absorbed by the skin from the portion of the spectrum absorbable by bilirubin may indicate the presence of the illness. Preferably, two measurements are made, one on the kneecap and one on the forehead, and compared to determine the presence of bilirubin. To reduce the impact of light absorption by hemoglobin in the blood carried by the skin, pressure is applied with a plunger and spring in the handle assembly, the pressure limited by points of a button slidably carried in the assembly that are perceived by touch when the pressure applied is sufficient. 6 figures.

  7. Bilirubin Nanoparticles as a Nanomedicine for Anti-inflammation Therapy.

    PubMed

    Lee, Yonghyun; Kim, Hyungjun; Kang, Sukmo; Lee, Jinju; Park, Jinho; Jon, Sangyong

    2016-06-20

    Despite the high potency of bilirubin as an endogenous anti-inflammatory compound, its clinical translation has been hampered because of its insolubility in water. Bilirubin-based nanoparticles that may overcome this critical issue are presented. A polyethylene glycol compound (PEG) was covalently attached to bilirubin, yielding PEGylated bilirubin (PEG-BR). The PEG-BR self-assembled into nanoscale particles with a size of approximately 110 nm, termed bilirubin nanoparticles (BRNPs). BRNPs are highly efficient hydrogen peroxide scavengers, thereby protecting cells from H2 O2 -induced cytotoxicity. In a murine model of ulcerative colitis, intravenous injection of BRNPs showed preferential accumulation of nanoparticles at the sites of inflammation and significantly inhibited the progression of acute inflammation in the colon. Taken together, BRNPs show potential for use as a therapeutic nanomedicine in various inflammatory diseases. PMID:27144463

  8. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  9. 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

  10. Bilirubin measurements in neonates

    NASA Astrophysics Data System (ADS)

    Newman, Gregory J.

    2000-04-01

    Infant Jaundice is a physiologic condition of elevated bilirubin in the tissue that affects nearly 60 percent of all term newborns and virtually 100 percent of premature infants. The high production of bilirubin in the newborn circulatory system and the inability of the immature liver to process and eliminate it case the condition. When the bilirubin levels rise, it starts to deposit in the baby's skin and in the brain. The deposits in the brain can cause neurologic impairment and death. The BiliCheck is a handheld, battery-powered device that measures the level of jaundice non-invasively using BioPhotonics at the point of care. The result is displayed on an LCD screen immediately, so physicians can now make treatment decision without waiting for results to return from the lab. The BiliCheck System has been marketed worldwide since April of 1998 and has received FDA clearance for use in the USA on pre-photo therapy infants in March of 1999.

  11. Alteration of serum bilirubin level in schizophrenia.

    PubMed

    Semnani, Yousef; Nazemi, Farzad; Azariyam, Aileen; Ardakani, Mohammad Javad Ehsani

    2010-11-01

    Abstract Objective. Alteration of serum bilirubin level in acute episodes of psychosis in patients with schizophrenia has been reported but the pattern of this alteration is controversial. Methods. Patients diagnosed as schizophrenia (162, group S) or bipolar disorder (155, group B) entered the study. The control group consisted of 95 patients admitted to cardiac care unit who had no personal or family history of major psychiatric disorders. Pre- and post-admission levels of bilirubin were measured and compared within and between the groups. Patients were examined to exclude all other causes of hyperbilirubinemia. Group S and B participants were also evaluated using positive and negative syndrome subscale (PANSS) both at admission and discharge. Results. The mean admission bilirubin levels of all the groups were in the normal range (significantly higher in group S than groups B and C) and were affected by the score of general psychopathology subscale rather than the scores of positive symptoms subscale. Conclusions. Although bilirubin decreased in all three groups at discharge, the rate of decrease was significantly higher in group S. The reason for this is not clear and needs further study. PMID:24917437

  12. Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma.

    PubMed

    Khoja, Leila; Maurice, Catherine; Chappell, MaryAnne; MacMillan, Leslie; Al-Habeeb, Ayman S; Al-Faraidy, Nada; Butler, Marcus O; Rogalla, Patrik; Mason, Warren; Joshua, Anthony M; Hogg, David

    2016-03-01

    Anti-PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown. Here, we report the case of a 51-year-old woman treated with pembrolizumab, as part of the Keynote-001 trial, as first-line treatment for metastatic disease. She experienced a complete response after 13.8 months of treatment with no adverse events. One month after the last drug infusion and 18 months from starting treatment, the patient presented with eosinophilic fasciitis. She then developed acute confusion and weakness, thought to be due to intracranial vasculitis. High-dose steroids were initiated with resolution of the fasciitis. Aspirin was commenced for presumed vasculitis with resolution of the neurologic symptoms. To our knowledge, there are no previous reports of eosinophilic fasciitis or cerebral vasculitis due to anti-PD-1 agents. This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab. PMID:26822024

  13. [Hashimoto's encephalopathy and autoantibodies].

    PubMed

    Yoneda, Makoto

    2013-04-01

    Encephalopathy occasionally occurs in association with thyroid disorders, but most of these are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism, called myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. Steroid treatment was successfully administered to these patients. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) are highly specific diagnostic biomarkers for HE. Further, we analyzed serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions throughout Japan and other countries. Approximately half of assessed HE patients carry anti-NAE antibodies. The age was widely distributed with 2 peaks (20-30 years and 50-70 years). Most HE patients were in euthyroid states, and all patients had anti-thyroid (TG) antibodies and anti-thyroid peroxidase (TPO) antibodies. Anti-TSH receptor (TSH-R) antibodies were observed in some cases. The common neuropsychiatry features are consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities on electroencephalography (EEG) and decreased cerebral blood flow on brain SPECT were common findings, whereas abnormal findings on brain magnetic resonance imaging (MRI) were rare. HE patients have various clinical phenotypes such as the acute encephalopathy form, the chronic psychiatric form, and other particular clinical forms, including limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-like form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on EEG. Taken together, these data suggest that the possibility of

  14. Bilirubin present in diverse angiosperms

    PubMed Central

    Pirone, Cary; Johnson, Jodie V.; Quirke, J. Martin E.; Priestap, Horacio A.; Lee, David

    2010-01-01

    Background and aims Bilirubin is an orange-yellow tetrapyrrole produced from the breakdown of heme by mammals and some other vertebrates. Plants, algae and cyanobacteria synthesize molecules similar to bilirubin, including the protein-bound bilins and phytochromobilin which harvest or sense light. Recently, we discovered bilirubin in the arils of Strelitzia nicolai, the White Bird of Paradise Tree, which was the first example of this molecule in a higher plant. Subsequently, we identified bilirubin in both the arils and the flowers of Strelitzia reginae, the Bird of Paradise Flower. In the arils of both species, bilirubin is present as the primary pigment, and thus functions to produce colour. Previously, no tetrapyrroles were known to generate display colour in plants. We were therefore interested in determining whether bilirubin is broadly distributed in the plant kingdom and whether it contributes to colour in other species. Methodology In this paper, we use HPLC/UV and HPLC/UV/electrospray ionization-tandem mass spectrometry (HPLC/UV/ESI-MS/MS) to search for bilirubin in 10 species across diverse angiosperm lineages. Principal results Bilirubin was present in eight species from the orders Zingiberales, Arecales and Myrtales, but only contributed to colour in species within the Strelitziaceae. Conclusions The wide distribution of bilirubin in angiosperms indicates the need to re-assess some metabolic details of an important and universal biosynthetic pathway in plants, and further explore its evolutionary history and function. Although colour production was limited to the Strelitziaceae in this study, further sampling may indicate otherwise. PMID:22476078

  15. 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

  16. 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

  17. The Biological Effects of Bilirubin Photoisomers.

    PubMed

    Jasprova, Jana; Dal Ben, Matteo; Vianello, Eleonora; Goncharova, Iryna; Urbanova, Marie; Vyroubalova, Karolina; Gazzin, Silvia; Tiribelli, Claudio; Sticha, Martin; Cerna, Marcela; Vitek, Libor

    2016-01-01

    Although phototherapy was introduced as early as 1950's, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells. PMID:26829016

  18. Posterior Reversible Encephalopathy Syndrome in ALL.

    PubMed

    Millichap, J Gordon

    2015-07-01

    Investigators from Soochow University, Suzhou, China, studied the possible pathogenetic mechanisms and treatment of posterior reversible encephalopathy syndrome (PRES) observed in 11 cases of pediatric acute lymphoblastic leukemia (ALL) after induction chemotherapy. PMID:26933594

  19. Bilirubin Binding Capacity in the Preterm Neonate.

    PubMed

    Amin, Sanjiv B

    2016-06-01

    Total serum/plasma bilirubin (TB), the biochemical measure currently used to evaluate and manage hyperbilirubinemia, is not a useful predictor of bilirubin-induced neurotoxicity in premature infants. Altered bilirubin-albumin binding in premature infants limits the usefulness of TB in premature infants. In this article, bilirubin-albumin binding, a modifying factor for bilirubin-induced neurotoxicity, in premature infants is reviewed. PMID:27235205

  20. Rifaximin in the treatment of hepatic encephalopathy

    PubMed Central

    Iadevaia, Maddalena Diana; Prete, Anna Del; Cesaro, Claudia; Gaeta, Laura; Zulli, Claudio; Loguercio, Carmelina

    2011-01-01

    Hepatic encephalopathy is a challenging complication in patients with advanced liver disease. It can be defined as a neuropsychiatric syndrome caused by portosystemic venous shunting, ranging from minimal to overt hepatic encephalopathy or coma. Its pathophysiology is still unclear, although increased levels of ammonia play a key role. Diagnosis of hepatic encephalopathy is currently based on specific tests evaluating the neuropsychiatric state of patients and their quality of life; the severity of hepatic encephalopathy is measured by the West Haven criteria. Treatment of hepatic encephalopathy consists of pharmacological and corrective measures, as well as nutritional interventions. Rifaximin received approval for the treatment of hepatic encephalopathy in 2010 because of its few side effects and pharmacological benefits. The aim of this work is to review the use and efficacy of rifaximin both in acute and long-term management of hepatic encephalopathy. Treatment of overt hepatic encephalopathy involves management of the acute episode as well as maintenance of remission in those patients who have previously experienced an episode, in order to improve their quality of life. The positive effect of rifaximin in reducing health care costs is also discussed. PMID:24367227

  1. Rifaximin in the treatment of hepatic encephalopathy.

    PubMed

    Iadevaia, Maddalena Diana; Prete, Anna Del; Cesaro, Claudia; Gaeta, Laura; Zulli, Claudio; Loguercio, Carmelina

    2011-01-01

    Hepatic encephalopathy is a challenging complication in patients with advanced liver disease. It can be defined as a neuropsychiatric syndrome caused by portosystemic venous shunting, ranging from minimal to overt hepatic encephalopathy or coma. Its pathophysiology is still unclear, although increased levels of ammonia play a key role. Diagnosis of hepatic encephalopathy is currently based on specific tests evaluating the neuropsychiatric state of patients and their quality of life; the severity of hepatic encephalopathy is measured by the West Haven criteria. Treatment of hepatic encephalopathy consists of pharmacological and corrective measures, as well as nutritional interventions. Rifaximin received approval for the treatment of hepatic encephalopathy in 2010 because of its few side effects and pharmacological benefits. The aim of this work is to review the use and efficacy of rifaximin both in acute and long-term management of hepatic encephalopathy. Treatment of overt hepatic encephalopathy involves management of the acute episode as well as maintenance of remission in those patients who have previously experienced an episode, in order to improve their quality of life. The positive effect of rifaximin in reducing health care costs is also discussed. PMID:24367227

  2. [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

  3. Photoacoustic microscopy of bilirubin in tissue phantoms

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Zhang, Chi; Yao, Da-Kang; Wang, Lihong V.

    2012-12-01

    Determining both bilirubin's concentration and its spatial distribution are important in disease diagnosis. Here, for the first time, we applied quantitative multiwavelength photoacoustic microscopy (PAM) to detect bilirubin concentration and distribution simultaneously. By measuring tissue-mimicking phantoms with different bilirubin concentrations, we showed that the root-mean-square error of prediction has reached 0.52 and 0.83 mg/dL for pure bilirubin and for blood-mixed bilirubin detection (with 100% oxygen saturation), respectively. We further demonstrated the capability of the PAM system to image bilirubin distribution both with and without blood. Finally, by underlaying bilirubin phantoms with mouse skins, we showed that bilirubin can be imaged with consistent accuracy down to >400 μm in depth. Our results show that PAM has potential for noninvasive bilirubin monitoring in vivo, as well as for further clinical applications.

  4. Non-Hyperammonemic valproate encephalopathy.

    PubMed

    Farooq, Omar; Zunga, Pervaiz M; Dar, Mohd I; Rather, Abdul Q; Rashid, Samia; Basu, Javid; Dar, Ishrat H; Ashraf, Mohd

    2014-04-01

    A 21-year-old male known case of primary hypothyroidism, Seizure disorder sequelae of an old trauma receiving sodium valproate, clobazam and phenobarbitone for control of Generalized tonic clonic seizures reported to neurology OPD with history of altered sensorium and gait unsteadiness for 1 week with history of hike in valproate dose 2 weeks before. On examination he was drowsy. Neurological examination was unremarkable except for gait unsteadiness and ataxia. Patient was admitted and evaluated for acute worsening. All (the) biochemical parameters including complete blood count, liver function tests, kidney function tests, routine urine examination, arterial blood gas analysis, blood and urine culture tests were normal. CSF analysis was also normal. Repeat MRI brain was also done which depicted all old changes with no fresh changes which will account for worsening of his sensorium. EEG was suggestive of diffuse encephalopathy. Thyroid function tests were also normal. Valproate encephalopathy was suspected and Valproate was empirically stopped and he was put on levetiracetam and phenytoin. His sensorium improved rapidly after stoppage of valproate with normalization of EEG. Serum valproate Levels were high with serum ammonia levels were in the normal range. We made the inference of nonhyperammoneamic valproate encephalopathy. This case highlights the existence of non-hyperammonemic valproate induced encephalopathy, suggesting mechanisms other than hyperammonemia responsible for this encephalopathy. PMID:25206067

  5. The Biological Effects of Bilirubin Photoisomers

    PubMed Central

    Jasprova, Jana; Dal Ben, Matteo; Vianello, Eleonora; Goncharova, Iryna; Urbanova, Marie; Vyroubalova, Karolina; Gazzin, Silvia; Tiribelli, Claudio; Sticha, Martin; Cerna, Marcela; Vitek, Libor

    2016-01-01

    Although phototherapy was introduced as early as 1950’s, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells. PMID:26829016

  6. Hashimoto's encephalopathy.

    PubMed

    Schiess, Nicoline; Pardo, Carlos A

    2008-10-01

    Hashimoto's encephalopathy (HE) is a controversial neurological disorder that comprises a heterogenous group of neurological symptoms that manifest in patients with high titers of antithyroid antibodies. Clinical manifestations of HE may include encephalopathic features such as seizures, behavioral and psychiatric manifestations, movement disorders, and coma. Although it has been linked to cases of Hashimoto's thyroiditis or thyroid dysfunction, the most common immunological feature of HE is the presence of high titers of antithyroglobulin or anti-TPO (antimicrosomal) antibodies. At present, it is unclear whether antithyroid antibodies represent an immune epiphenomenon in a subset of patients with encephalopathic processes or they are really associated with pathogenic mechanisms of the disorder. The significance of classifying encephalopathies under the term HE will be determined in the future once the relevance of the role of antithyroid antibodies is demonstrated or dismissed by more detailed experimental and immunopathological studies. The responsiveness of HE to steroids or other therapies such as plasmapheresis supports the hypothesis that this is a disorder that involves immune pathogenic mechanisms. Further controlled studies of the use of steroids, plasmapheresis, or immunosuppressant medications are needed in the future to prove the concept of the pathogenic role of antithyroid antibodies in HE. PMID:18990131

  7. [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

  8. Bilirubin Binding to PPARα Inhibits Lipid Accumulation.

    PubMed

    Stec, David E; John, Kezia; Trabbic, Christopher J; Luniwal, Amarjit; Hankins, Michael W; Baum, Justin; Hinds, Terry D

    2016-01-01

    Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin. PMID:27071062

  9. Bilirubin Binding to PPARα Inhibits Lipid Accumulation

    PubMed Central

    Stec, David E.; John, Kezia; Trabbic, Christopher J.; Luniwal, Amarjit; Hankins, Michael W.; Baum, Justin

    2016-01-01

    Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin. PMID:27071062

  10. Autoimmune encephalopathies

    PubMed Central

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2014-01-01

    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  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. Atypical Wernicke's syndrome sans encephalopathy with acute bilateral vision loss due to post-chiasmatic optic tract edema

    PubMed Central

    Desai, Soaham Dilip; Shah, Diva Sidharth

    2014-01-01

    A middle aged male presented with acute bilateral vision loss, 4 weeks after undergoing gastric bypass surgery for gastric carcinoma. He had normal sensorium, fundoscopy, normal pupillary reaction to light, but had mild opthalmoparesis and nystagmus with ataxia. Magnetic resonance imaging of the brain revealed post-chiasmatic optic tract edema along with other classical features of Wernicke's syndrome. Thiamine supplementation leads to complete resolution of clinical as well as imaging findings. In appropriate clinical settings, a high index of suspicion and early treatment are essential for managing Wernicke's syndrome even in patients with atypical clinical and imaging presentation. PMID:24753673

  13. Bilirubin and Its Carbohydrate Conjugates

    NASA Astrophysics Data System (ADS)

    Blanckaert, Norbert J. C.

    In mammals, the open tetrapyrrole bilirubin (structure 2, Fig. 1) is the principal degradation product of iron-protoporphyrin-IX (heme). The latter molecule is a tetrapyrrolic macrocycle and plays a critical role in aerobic metabolism by reversibly binding oxygen in hemoglobin and myoglobin, and by serving as the active site in oxidation reactions catalyzed by hemoprotein enzymes. Important cyclic tetrapyrroles in nature related to heme are chlorophylls, which contain magnesium and are derived from protoporphyrin-IX, and vitamin B12, a corrinoid derived from uroporphyrinogen-III.

  14. Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA.

    PubMed

    Xia, Zhen-Wei; Li, Chun-E; Jin, You-Xin; Shi, Yi; Xu, Li-Qing; Zhong, Wen-Wei; Li, Yun-Zhu; Yu, Shan-Chang; Zhang, Zi-Li

    2007-04-01

    Neonatal hyperbilirubinemia is a common clinical condition caused mainly by the increased production and decreased excretion of bilirubin. Current treatment is aimed at reducing the serum levels of bilirubin. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that generates bilirubin. In this study we intended to suppress HO-1 using the RNA interference technique. Small interfering RNA (siRNA)-A, -B, and -C were designed based on human HO-1 (hHO-1) mRNA sequences. siRNA was transfected into a human hepatic cell line (HL-7702). hHO-1 transcription and protein levels were then determined. In addition, the inhibitory effect of siRNA on hHO-1 was assessed in cells treated with hemin or transfected with an hHO-1 plasmid. siRNA-C showed the most potent suppressive effect on hHO-1. This inhibition is dose and time dependent. Compared with control, both hemin and hHO-1 plasmids up-regulated hHO-1 expression in HL-7702 cells. However, the up-regulation was significantly attenuated by siRNA-C. Furthermore, the decrease in hHO-1 activity was coincident with the suppression of its transcription. Finally, siRNA-C was shown to reduce hHO-1 enzymatic activity and bilirubin levels. Thus, this study provides a novel therapeutic rationale by blocking bilirubin formation via siRNA for preventing and treating neonatal hyperbilirubinemia and bilirubin encephalopathy at an early clinical stage. PMID:17392485

  15. The origins and kinetics of bilirubin in dogs with hepatobiliary and haemolytic diseases.

    PubMed

    Rothuizen, J; van den Brom, W E; Fevery, J

    1992-05-01

    In 35 dogs with spontaneous hepatobiliary liver disease the kinetics and the sources of bilirubin were quantified. The disorders were extrahepatic bile duct obstruction (n = 4), fulminant hepatitis (n = 2), (sub)acute hepatitis (n = 5), chronic active hepatitis (CAH) with cirrhosis (n = 6), hepatic lymphosarcoma (n = 5), centrizonal necrosis secondary to haemolytic anaemia (n = 6) and other (n = 2). The plasma disappearance of [3H]bilirubin was analyzed with a two-compartment model in all dogs. The ratio early labeled/late labeled bilirubin was determined by measuring the incorporation of [14C]glycine into erythrocyte haem and faecal stercobilin. By introducing this relation in the model analysis the bilirubin production rates from erythrocyte destruction (PE), ineffective erythropoiesis (PI) and hepatic haemoprotein (PL) could be quantified. Total bilirubin turnover was increased in both primary haemolytic disease and most cases of hepatobiliary disease. Erythrocyte survival was reduced in all cases but one. The bilirubin clearance was impaired to 30-50% of the normal value in most cases of hepatobiliary disease and also in primary haemolysis. In dogs with fulminant hepatitis, and cirrhosis with or without CAH, the clearance rates were reduced to values below 15% of normal. In these dogs both an impaired clearance and an increased production were important determinants of hyperbilirubinaemia. In other cases plasma bilirubin was primarily determined by increased production. These clearances and production rates were similar in haemolysis and in many cases of primary hepatobiliary disease. The hepatic haemoprotein turnover was quite variable in all subgroups, ranging from 1-74% of the total bilirubin turnover.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1506635

  16. Determination of bilirubin glucuronide and assay of glucuronyltransferase with bilirubin as acceptor

    PubMed Central

    Van Roy, F. P.; Heirwegh, K. P. M.

    1968-01-01

    1. Conjugated bilirubin is conveniently determined by coupling with the diazonium salt of ethyl anthranilate. 2. This method has been used in the development of assays for UDP-glucuronyltransferase (EC 2.4.1.17), with bilirubin as substrate, in rat liver homogenates, microsomal preparations and partly purified fractions. 3. Chromatographic analysis suggests that bilirubin monoglucuronide is the product of the enzyme systems studied. PMID:5660631

  17. Bovine Spongiform Encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...

  18. Hashimoto Encephalopathy or Neurosarcoidosis? A Case Report

    PubMed Central

    Sapkota, Biggya L.; Pitiyanuvath, Nataria

    2015-01-01

    Hashimoto encephalopathy (HE) is a rare autoimmune disease characterized by symptoms of acute or subacute encephalopathy associated with increased antithyroid antibody levels. Neurosarcoidosis is also a rare entity that occurs in less than 5% of patients with systemic sarcoidosis. Neurosarcoidosis usually presents with cranial neuropathies, myelopathy, or new-onset seizure. We report a case of a 49-year-old caucasian woman, previously healthy, who initially presented for a workup of a new-onset seizure. She had a gradually progressive course with neurocognitive decline and recurrent partial seizures refractory to conventional antiepileptic drugs. Her seizures responded well to a course of intravenous immunoglobulin. She was subsequently diagnosed with HE and pulmonary sarcoidosis based on serological and pathological studies. She improved neurologically once the seizures were controlled. Hashimoto encephalopathy is a rare condition that is potentially treatable and presents with various neuropsychiatric manifestations. It is a diagnosis of exclusion that requires a strong clinical suspicion and is often underrecognized. PMID:25829987

  19. Intermolecular interactions in the bilirubin-cholate-silica system

    NASA Astrophysics Data System (ADS)

    Vlasova, N. N.; Golovkova, L. P.; Severinovskaya, O. V.

    2007-06-01

    Bilirubin-cholate interactions in aqueous solutions were studied. The constants of binding of bilirubin with taurocholate dimers and taurodeoxycholate trimers were calculated. The adsorption of bilirubin and cholates on the surface of highly dispersed silica was studied. It was shown that taurine-conjugated cholates are poorly adsorbed from micellar solutions on the silica surface, the specific amount of bilirubin adsorbed decreases with increasing concentration of cholates in the solution, the affinity of free bilirubin for the silica surface is independent of the nature of the cholic acid, and that the affinity of cholate-bilirubin complexes for the silica surface is lower than the affinity of free bilirubin.

  20. 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

  1. 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

  2. Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity

    PubMed Central

    Maramattom, Boby Varkey; Raja, Rajat; Balagopal, Anuroop

    2016-01-01

    Urea cycle disorders (UCD) are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD) is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual.[1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain.

  3. Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity.

    PubMed

    Maramattom, Boby Varkey; Raja, Rajat; Balagopal, Anuroop

    2016-01-01

    Urea cycle disorders (UCD) are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD) is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual.[1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain. PMID:27570396

  4. PPARα: A Master Regulator of Bilirubin Homeostasis.

    PubMed

    Bigo, Cyril; Kaeding, Jenny; El Husseini, Diala; Rudkowska, Iwona; Verreault, Mélanie; Vohl, Marie Claude; Barbier, Olivier

    2014-01-01

    Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin synthesizing heme oxygenase- (HO-) 1 and biliverdin reductase (BVR) enzymes were determined. Human hepatocytes (HH) and HepG2 cells sustained similar treatments, except that the expression of the bilirubin conjugating UDP-glucuronosyltransferase (UGT) 1A1 enzyme and multidrug resistance-associated protein (MRP) 2 transporter was analyzed. In HUVECs, gemfibrozil, fenofibrate, and Wy14,643 upregulated HO-1 mRNA expression without affecting BVR. Wy14,643 and fenofibrate also caused HO-1 protein accumulation, while gemfibrozil and fenofibrate favored the secretion of bilirubin in cell media. Similar positive regulations were also observed with the 3 PPARα ligands in CASMCs where HO-1 mRNA and protein levels were increased. In HH and HepG2 cells, both UGT1A1 and MRP2 transcripts were also accumulating. These observations indicate that PPARα ligands activate bilirubin synthesis in vascular cells and metabolism in liver cells. The clinical implications of these regulatory events are discussed. PMID:25147562

  5. Initial photochemistry of bilirubin probed by femtosecond spectroscopy.

    PubMed

    Zietz, Burkhard; Gillbro, Tomas

    2007-10-18

    Bilirubin is a breakdown product from heme catabolism, and reduced excretion of bilirubin can lead to jaundice. Phototherapy is the most common treatment for neonatal jaundice, a condition frequently encountered in newborn infants. Knowledge of the photochemistry of bilirubin, which is dominated by (ultra)fast components, is necessary for the profound understanding of the processes in phototherapy. Here, we report results from femtosecond fluorescence upconversion measurements on bilirubin and half-bilirubin model compounds, as well as pump-probe absorption measurements on bilirubin. A fast component of ca. 120 fs in the multiexponential fluorescence decay, being only visible in the bilirubin molecule, is interpreted as exciton localization within the molecular halves. The slower components of several hundreds of femtoseconds and a few picoseconds, occurring in bilirubin and the half-bilirubin model, are interpreted as relaxation to a (twisted) intermediate, which decays further with ca. 15 ps to the ground state. PMID:17927274

  6. Antibiotic-associated encephalopathy.

    PubMed

    Bhattacharyya, Shamik; Darby, R Ryan; Raibagkar, Pooja; Gonzalez Castro, L Nicolas; Berkowitz, Aaron L

    2016-03-01

    Delirium is a common and costly complication of hospitalization. Although medications are a known cause of delirium, antibiotics are an underrecognized class of medications associated with delirium. In this article, we comprehensively review the clinical, radiologic, and electrophysiologic features of antibiotic-associated encephalopathy (AAE). AAE can be divided into 3 unique clinical phenotypes: encephalopathy commonly accompanied by seizures or myoclonus arising within days after antibiotic administration (caused by cephalosporins and penicillin); encephalopathy characterized by psychosis arising within days of antibiotic administration (caused by quinolones, macrolides, and procaine penicillin); and encephalopathy accompanied by cerebellar signs and MRI abnormalities emerging weeks after initiation of antibiotics (caused by metronidazole). We correlate these 3 clinical phenotypes with underlying pathophysiologic mechanisms of antibiotic neurotoxicity. Familiarity with these types of antibiotic toxicity can improve timely diagnosis of AAE and prompt antibiotic discontinuation, reducing the time patients spend in the delirious state. PMID:26888997

  7. Bilirubin Levels and Thrombus Burden in Patients With ST-Segment Elevation Myocardial Infarction.

    PubMed

    Hamur, Hikmet; Duman, Hakan; Bakirci, Eftal Murat; Kucuksu, Zafer; Demirelli, Selami; Kalkan, Kamuran; Degirmenci, Husnu

    2016-07-01

    We investigated whether serum bilirubin level (a marker of heme oxygenase activity) is a predictor of thrombus burden in patients with acute myocardial infarction. Patients (n = 229; male 72.9%; mean age 63 ± 13.4 years) who were admitted with ST-segment elevation myocardial infarction (STEMI) were enrolled. Patients were divided into 2 groups. Group 1 was defined as low thrombus burden and group 2 was defined as high thrombus burden. Patients with high thrombus burden had higher total bilirubin levels (14.4 [4.3-22.9] vs 7.7 [2.4-20.3] µmol/L, P ≤ .001), (0.84 [0.25-1.34] vs 0.45 [0.14-1.19] mg/dL P ≤ .001) and direct bilirubin levels (3.1 [2.1-8.4] vs 1.7 [0.5-6.5] µmol/L, P ≤ .001), (0.18 [0.03-0.49] vs 0.10 [0.03-0.38] mg/dL, P ≤ .001). At multivariate analysis, total bilirubin (odds ratio: 1.05, 95% confidence interval: 1.03-1.08, P ≤ .001) was the independent predictor of high thrombus burden. In conclusion, total bilirubin level is independently associated with high thrombus burden in patients with STEMI. PMID:26339042

  8. Can Excess Bilirubin Levels Cause Learning Difficulties?

    ERIC Educational Resources Information Center

    Pretorius, E.; Naude, H.; Becker, P. J.

    2002-01-01

    Examined learning problems in South African sample of 7- to 14-year-olds whose mothers reported excessively high infant bilirubin shortly after the child's birth. Found that this sample had lowered verbal ability with the majority also showing impaired short-term and long-term memory. Findings suggested that impaired formation of astrocytes…

  9. Intermediate dose 5-fluorouracil-induced encephalopathy.

    PubMed

    Kim, Yeon-A; Chung, Hyun Cheol; Choi, Hye Jin; Rha, Sun Young; Seong, Jin Sil; Jeung, Hei-Cheul

    2006-01-01

    As an acute neurotoxicity, high dose 5-fluorouracil (5-FU)-induced encephalopathy is well-known, but encephalopathy associated with lower dose is rarely reported. Here, we report a case of a male with anal cancer who was treated with 5-FU 1000 mg/m(2), continuous infusion for 5 days q4 weeks. At the second and the fourth cycles of chemotherapy, sudden confusion, cognitive dysfunction and disorientation occurred during 5-FU infusion. They were accompanied by hyperammonemia in the absence of focal neurological deficits or structural abnormalities. These symptoms completely disappeared and the serum ammonia level returned to normal after discontinuation of 5-FU and conservative care. In order to investigate a possible deficit of dihydropyrimidine dehydrogenase (DPD), we checked its mRNA level before and after treatment using real-time PCR. The patient's pre-treatment level was 80% compared with reference group, and it was elevated up to 187% of initial after 5-FU treatment, implying that that his encephalopathy may be 5-FU catabolite type rather than DPD deficiency. In conclusion, we report that encephalopathy can develop even with the dose of 5-FU lower than ever reported, and it should be considered as a differential diagnosis for proper management. PMID:16436463

  10. Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice

    PubMed Central

    Bortolussi, G; Codarin, E; Antoniali, G; Vascotto, C; Vodret, S; Arena, S; Cesaratto, L; Scaloni, A; Tell, G; Muro, A F

    2015-01-01

    Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration. PMID:25950469

  11. Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells.

    PubMed

    Ziberna, Lovro; Martelanc, Mitja; Franko, Mladen; Passamonti, Sabina

    2016-01-01

    Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9-1.5 pmol mg(-1) protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3-5 pmol mg(-1) protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in the range of reported values of free serum bilirubin (8.5-13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function. PMID:27381978

  12. Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells

    PubMed Central

    Ziberna, Lovro; Martelanc, Mitja; Franko, Mladen; Passamonti, Sabina

    2016-01-01

    Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9–1.5 pmol mg−1 protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3–5 pmol mg−1 protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in the range of reported values of free serum bilirubin (8.5–13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function. PMID:27381978

  13. Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders.

    PubMed

    Latt, N; Dore, G

    2014-09-01

    Wernicke encephalopathy is an acute, reversible neuropsychiatric emergency due to thiamine deficiency. Urgent and adequate thiamine replacement is necessary to avoid death or progression to Korsakoff syndrome with largely irreversible brain damage. Wernicke Korsakoff syndrome refers to a condition where features of Wernicke encephalopathy are mixed with those of Korsakoff syndrome. Although thiamine is the cornerstone of treatment of Wernicke encephalopathy, there are no universally accepted guidelines with regard to its optimal dose, mode of administration, frequency of administration or duration of treatment. Currently, different dose recommendations are being made. We present recommendations for the assessment and treatment of Wernicke encephalopathy based on literature review and our clinical experience. PMID:25201422

  14. Effects of N-Acetylcysteine on Cytokines in Non-Acetaminophen Acute Liver Failure: Potential Mechanism of Improvement in Transplant-Free Survival

    PubMed Central

    Stravitz, R. Todd; Sanyal, Arun J.; Reisch, Joan; Bajaj, Jasmohan S.; Mirshahi, Faridoddin; Cheng, Jianfeng; Lee, William M.

    2016-01-01

    Background N-Acetylcysteine (NAC) improves transplant-free survival in patients with non-acetaminophen acute liver failure (ALF) when administered in early stages of hepatic encephalopathy. The mechanisms of this benefit are unknown. Aim To determine whether NAC improves transplant-free survival in ALF by ameliorating the surge of pro-inflammatory cytokines. Methods Serum samples were obtained from 78 participants of the randomized, ALF Study Group NAC Trial with grade 1 or 2 hepatic encephalopathy on randomization. Concentrations of ten cytokines, chosen to represent a wide array of inflammatory responses, were determined by multiplex ELISA. Results In univariate analysis, predictors of transplant-free survival included NAC administration (P=0.012), admission bilirubin (P=0.003), INR (P=0.0002), grade 1 vs. grade 2 encephalopathy (P=0.006) and lower admission interleukin (IL)-17 concentrations (P=0.011). IL-17 levels were higher in patients with grade 2 vs. 1 encephalopathy on randomization (P=0.007) and in those who progressed to grade 3 or 4 encephalopathy over the following 7 days (P≤0.01). Stepwise multivariate logistic regression analysis identified only NAC administration and lower IL-17 concentrations as independent predictors of transplant-free survival. In patients with detectable IL-17 concentrations on admission, 78% of those who received NAC vs. 44% of those who received placebo had undetectable levels by day 3-5 (P=0.042), and the mean decrease in IL-17 concentrations between admission and late samples was significantly greater in patients who received NAC vs. placebo (P=0.045). Conclusions NAC may improve transplant-free survival in patients with non-acetaminophen ALF by ameliorating the production of IL-17, which is associated with progression of hepatic encephalopathy and poor outcome. PMID:23782487

  15. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases bilirubin formation but hampers quantitative hepatic conversion of biliverdin to bilirubin in rats with wild-type AH receptor.

    PubMed

    Niittynen, Marjo; Simanainen, Ulla; Pohjanvirta, Raimo; Sankari, Satu; Tuomisto, Jouni T

    2014-06-01

    In haem degradation, haem oxygenase-1 (HO-1) first cleaves haem to biliverdin, which is reduced to bilirubin by biliverdin IXα reductase (BVR-A). The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin in moderately TCDD-resistant line B (Kuopio) rats. Using line B and two TCDD-sensitive rat strains, the present study set out to probe the dose-response and biochemical mechanisms of this accumulation. At 28 days after exposure to 3-300 μg/kg TCDD in line B rats, already the lowest dose of TCDD tested, 3 μg/kg, affected serum bilirubin conjugates, and after doses ≥100 μg/kg, the liver content of bilirubin, biliverdin and their conjugates (collectively 'bile pigments') as well as HO-1 was elevated. BVR-A activity and serum bile acids were increased only by the doses of 100 and 300 μg/kg TCDD, respectively. Biliverdin conjugates correlated best with biliverdin suggesting it to be their immediate precursor. TCDD (100 μg/kg, 10 days) increased hepatic bilirubin and biliverdin levels also in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. Hepatic bilirubin and bile acids, but not biliverdin, were increased in feed-restricted L-E control rats. In TCDD-sensitive line C (Kuopio) rats, 10 μg/kg of TCDD increased the body-weight-normalized biliary excretion of bilirubin. Altogether, the results suggest that at acutely toxic doses, TCDD induces the formation of bilirubin in rats. However, concurrently, TCDD seems to hamper the quantitative conversion of biliverdin to bilirubin in line B and L-E rats' liver. Biliverdin conjugates are most likely formed as secondary products of biliverdin. PMID:24418412

  16. Nonalcoholic Wernicke's encephalopathy.

    PubMed

    Welsh, Amanda; Rogers, Peter; Clift, Fraser

    2016-07-01

    Wernicke's encephalopathy (WE) is a serious neurologic condition resulting from thiamine deficiency. The majority of cases involve alcoholism; however, nonalcohol-associated WE does occur and is under-recognized. We discuss a case of a 22-year-old man with a history of Crohn's disease who presented to our emergency department with multiple neurologic complaints related to WE. PMID:25985980

  17. [Bovine spongiform encephalopathy].

    PubMed

    Suárez Fernández, G

    2001-01-01

    An histórical and conceptual review is made about Bovine Spongiform Encephalopathy or mad cows disease and an epidemiological analysis as a present and future health problem. This analysis of BSE should not be negative, considering the truths that we know today. PMID:11783042

  18. A Case of Wernicke's Encephalopathy Following Fluorouracil-based Chemotherapy

    PubMed Central

    Cho, In Jeong; Chang, Hye Jung; Won, Hye Sung; Choi, Moon Young; Nam, Eun Mi; Mun, Yeung-Chul; Lee, Soon Nam; Seong, Chu-Myong

    2009-01-01

    The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy. PMID:19654964

  19. KCNQ2 encephalopathy

    PubMed Central

    Millichap, John J.; Park, Kristen L.; Tsuchida, Tammy; Ben-Zeev, Bruria; Carmant, Lionel; Flamini, Robert; Joshi, Nishtha; Levisohn, Paul M.; Marsh, Eric; Nangia, Srishti; Narayanan, Vinodh; Ortiz-Gonzalez, Xilma R.; Patterson, Marc C.; Pearl, Phillip L.; Porter, Brenda; Ramsey, Keri; McGinnis, Emily L.; Taglialatela, Maurizio; Tracy, Molly; Tran, Baouyen; Venkatesan, Charu; Weckhuysen, Sarah

    2016-01-01

    Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy. PMID:27602407

  20. A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy.

    PubMed

    Hashimoto, Joel G; Wiren, Kristine M; Wilhelm, Clare J

    2016-01-01

    Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model. PMID:27268733

  1. Hepatocyte cotransport of taurocholate and bilirubin glucuronides: Role of microtubules

    SciTech Connect

    Crawford, J.M.; Gollan, J.L. )

    1988-07-01

    Modulation of bile pigment excretion by bile salts has been attributed to modification of canalicular membrane transport or a physical interaction in bile. Based on the observation that a microtubule-dependent pathway is involved in the hepatocellular transport of bile salts, the authors investigated the possibility that bilirubin glucuronides are associated with bile salts during intracellular transport. Experiments were conducted in intact rats (basal) or after overnight biliary diversion and intravenous reinfusion of taurocholate (depleted/reinfused). All rats were pretreated with intravenous low-dose colchicine or its inactive isomer lumicolchicine. Biliary excretion of radiolabeled bilirubin glucuronides derived from tracer ({sup 14}C)bilirubin-({sup 3}H)bilirubin monoglucuronide (coinjected iv) was unchanged in basal rats but was consistently delayed in depleted/reinfused rats. This was accompanied by a significant shift toward bilirubin diglucuronide formation from both substrates. In basal Gunn rats, with deficient bilirubin glucuronidation, biliary excretion of intravenous ({sup 14}C)bilirubin monoglucuronide-({sup 3}H)bilirubin diglucuronide was unaffected by colchicine but was retarded in depleted/reinfused Gunn rats. Colchicine had no effect on the rate of bilirubin glucuronidation in vitro in rat liver microsomes. They conclude that a portion of the bilirubin glucuronides generated endogenously in hepatocytes or taken up directly from plasma may be cotransported with bile salts to the bile canalicular membrane via a microtubule-dependent mechanism.

  2. Preliminary development of a fiber optic sensor for measuring bilirubin.

    PubMed

    Babin, Steven M; Sova, Raymond M

    2014-01-01

    Preliminary development of a fiber optic bilirubin sensor is described, where an unclad sensing portion is used to provide evanescent wave interaction of the transmitted light with the chemical environment. By using a wavelength corresponding to a bilirubin absorption peak, the Beer-Lambert Law can be used to relate the concentration of bilirubin surrounding the sensing portion to the amount of absorbed light. Initial testing in vitro suggests that the sensor response is consistent with the results of bulk absorption measurements as well as the Beer-Lambert Law. In addition, it is found that conjugated and unconjugated bilirubin have different peak absorption wavelengths, so that two optical frequencies may potentially be used to measure both types of bilirubin. Future development of this device could provide a means of real-time, point-of-care monitoring of intravenous bilirubin in critical care neonates with hyperbilirubinemia. PMID:25057239

  3. Preliminary Development of a Fiber Optic Sensor for Measuring Bilirubin

    PubMed Central

    Babin, Steven M; Sova, Raymond M

    2014-01-01

    Preliminary development of a fiber optic bilirubin sensor is described, where an unclad sensing portion is used to provide evanescent wave interaction of the transmitted light with the chemical environment. By using a wavelength corresponding to a bilirubin absorption peak, the Beer–Lambert Law can be used to relate the concentration of bilirubin surrounding the sensing portion to the amount of absorbed light. Initial testing in vitro suggests that the sensor response is consistent with the results of bulk absorption measurements as well as the Beer–Lambert Law. In addition, it is found that conjugated and unconjugated bilirubin have different peak absorption wavelengths, so that two optical frequencies may potentially be used to measure both types of bilirubin. Future development of this device could provide a means of real-time, point-of-care monitoring of intravenous bilirubin in critical care neonates with hyperbilirubinemia. PMID:25057239

  4. [EEG manifestations in metabolic encephalopathy].

    PubMed

    Lin, Chou-Ching K

    2005-09-01

    Normal brain function depends on normal neuronal metabolism, which is closely related to systemic homeostasis of metabolites, such as glucose, electrolytes, amino acids and ammonia. "Metabolic encephalopathy" indicates diffuse brain dysfunction caused by various systemic derangements. Electroencephalogram (EEG) is widely used to evaluate metabolic encephalopathy since 1937, when Berger first observed slow brain activity induced by hypoglycemia. EEG is most useful in differentiating organic from psychiatric conditions, identifying epileptogenicity, and providing information about the degree of cortical or subcortical dysfunction. In metabolic encephalopathy, EEG evolution generally correlates well with the severity of encephalopathy. However, EEG has little specificity in differentiating etiologies in metabolic encephalopathy. For example, though triphasic waves are most frequently mentioned in hepatic encephalopathy, they can also be seen in uremic encephalopathy, or even in aged psychiatric patients treated with lithium. Spike-and-waves may appear in hyper- or hypo-glycemia, uremic encephalopathy, or vitamin deficiencies, etc. Common principles of EEG changes in metabolic encephalopathy are (1) varied degrees of slowing, (2) assorted mixtures of epileptic discharge, (3) high incidence of triphasic waves, and (4), as a rule, reversibility after treatment of underlying causes. There are some exceptions to the above descriptions in specific metabolic disorders and EEG manifestations are highly individualized. PMID:16252619

  5. Bilirubin UDP-glucuronyltransferase activity of wistar rat kidney.

    PubMed

    Foliot, A; Christoforov, B; Petite, J P; Etienne, J P; Housset, E; Dubois, M

    1975-08-01

    Wistar rat kidneys have been shown to possess a bilirubin glucuronyltransferase (BGT) activity capable of conjugating about 3/5 of the total pool of unconjugated bilirubin within 48 h of being grafted to Gunn rat hosts. Bilirubin conjugated by the kidney is taken up by the liver and excreted in the bile. Except when the bile duct is ligated, no conjugated bilirubin appears in the plasma or urine. Renal BGT activity is about 1/20th of the hepatic activity on a weight basis in Wistar rats. The Gunn rat's hyperbilirubinemia probably causes an induction of the renal enzyme since its activity doubles in 48 h. PMID:808968

  6. Bilirubin and its oxidation products damage brain white matter.

    PubMed

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-11-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  7. Bilirubin and its oxidation products damage brain white matter

    PubMed Central

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-01-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  8. Cerebral blood flow velocity increases during a single treatment with the molecular adsorbents recirculating system in patients with acute on chronic liver failure.

    PubMed

    Schmidt, L E; Svendsen, L B; Sørensen, V R; Hansen, B A; Larsen, F S

    2001-08-01

    The aim of this uncontrolled pilot study is to determine the effect of treatment with the molecular adsorbents recirculating system (MARS) on cerebral perfusion in patients with acute on chronic liver failure (AOCLF). In 8 patients (median age, 44 years; range, 35 to 52 years) admitted with AOCLF, a single 10-hour MARS treatment was performed. Hepatic encephalopathy (HE) was graded according to the Fogarty criteria. Changes in cerebral perfusion were determined by transcranial Doppler as mean flow velocity (V(mean)) in the middle cerebral artery. Arterial ammonia and bilirubin levels were monitored as a measure of the capability of the MARS to remove water-soluble and protein-bound toxins. During MARS treatment, HE grade improved in 3 patients and remained unchanged in 5 patients (P =.11). V(mean) increased from 42 cm/sec (range, 26 to 59 cm/sec) to 72 cm/sec (range, 52 to 106 cm/sec; P <.05), whereas arterial ammonia level decreased from 88 micromol/L (range, 45 to 117 micromol/L) to 71 micromol/L (range, 26 to 98 micromol/L; P <.05) and bilirubin level from 537 micromol/L (range, 324 to 877 micromol/L) to 351 micromol/L (range, 228 to 512 micromol/L; P <.05). In conclusion, cerebral perfusion is increased and levels of ammonia and bilirubin are reduced during MARS treatment in patients with AOCLF. PMID:11510016

  9. Enzymic oxidation of unconjugated bilirubin by rat liver.

    PubMed Central

    Cardenas-Vazquez, R; Yokosuka, O; Billing, B H

    1986-01-01

    The presence of the enzyme bilirubin oxidase, which degrades bilirubin in vitro, was demonstrated in the liver. Subcellular-fractionation experiments indicate that bilirubin oxidase is located in both the inner and outer membranes of the mitochondria. The mean rate of the reaction is 1.57 +/- 0.38 (S.D.) nmol of bilirubin degraded/min per mg of mitochondrial protein (munits/mg of protein). With respect to the overall breakdown of bilirubin, the enzyme has a Km' of 136 microM-bilirubin and a Vmax.' of 9.13 munits/mg of protein. Its activity is influenced by the ionic strength of the media and is inhibited by KCN, thiol reagents, NADH and albumin. The enzyme is aerobic, and between 1 and 1.5 mol of O2 are consumed per mol of bilirubin degraded. The products of the reaction include propentdyopents. The hepatic bilirubin oxidase activity of the jaundiced Gunn-rat liver is not significantly different from that of the Sprague-Dawley rat, and it is not induced by beta-naphthoflavone. PMID:3790083

  10. INDUCTION OF BILIRUBIN CLEARANCE BY THE CONSTITUTIVE ANDROSTANE RECEPTOR (CAR)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bilirubin clearance is one of the numerous important functions of the liver. Defects in this process result in jaundice, which is particularly common in neonates. Elevated bilirubin levels can be decreased by treatment with phenobarbital. Because the nuclear hormone receptor constitutive androstane ...

  11. Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy.

    PubMed

    Lucke-Wold, Brandon P; Turner, Ryan C; Logsdon, Aric F; Nguyen, Linda; Bailes, Julian E; Lee, John M; Robson, Matthew J; Omalu, Bennet I; Huber, Jason D; Rosen, Charles L

    2016-03-01

    OBJECT Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3β. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy. PMID

  12. Diets in Encephalopathy.

    PubMed

    Abdelsayed, George G

    2015-08-01

    As many as 80% of patients with end-stage liver disease and hepatic encephalopathy have significant protein-calorie malnutrition. Because of the severe hypercatabolic state of cirrhosis, the provision of liberal amounts of carbohydrate (at least 35 to 40 kcal/kg per day), and between 1.2 and 1.6 g/kg of protein is necessary. Protein restriction is not recommended. Branched-chain amino acid supplementation and vegetable protein are associated with improved outcomes. Dietary supplementation with vitamins, minerals (with the notable exception of zinc) and probiotics should be decided on a case-by-case basis. PMID:26195204

  13. Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

    PubMed Central

    Lang, Elisabeth; Gatidis, Sergios; Freise, Noemi F; Bock, Hans; Kubitz, Ralf; Lauermann, Christian; Orth, Hans Martin; Klindt, Caroline; Schuier, Maximilian; Keitel, Verena; Reich, Maria; Liu, Guilai; Schmidt, Sebastian; Xu, Haifeng C; Qadri, Syed M; Herebian, Diran; Pandyra, Aleksandra A; Mayatepek, Ertan; Gulbins, Erich; Lang, Florian; Häussinger, Dieter; Lang, Karl S; Föller, Michael; Lang, Philipp A

    2015-01-01

    Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284) PMID:25065608

  14. In Cellulo Mapping of Subcellular Localized Bilirubin.

    PubMed

    Park, Jong-Seok; Nam, Eunju; Lee, Hye-Kyeong; Lim, Mi Hee; Rhee, Hyun-Woo

    2016-08-19

    Bilirubin (BR) is a de novo synthesized metabolite of human cells. However, subcellular localization of BR in the different organelles of human cells has been largely unknown. Here, utilizing UnaG as a genetically encoded fluorescent BR sensor, we report the existence of relatively BR-enriched and BR-depleted microspaces in various cellular organelles of live cells. Our studies indicate that (i) the cytoplasmic facing membrane of the endoplasmic reticulum (ER) and the nucleus are relatively BR-enriched spaces and (ii) mitochondrial intermembrane space and the ER lumen are relatively BR-depleted spaces. Thus, we demonstrate a relationship between such asymmetrical BR distribution in the ER membrane and the BR metabolic pathway. Furthermore, our results suggest plausible BR-transport and BR-regulating machineries in other cellular compartments, including the nucleus and mitochondria. PMID:27232847

  15. Trans-Cutaneous Bilirubinometery versus Serum Bilirubin in Neonatal Jaundice.

    PubMed

    Mahram, Manoochehr; Oveisi, Sonia; Jaberi, Najmeh

    2015-12-01

    Hyperbilirubinemia is a common problem in neonates and causes serious complications. Thus, serial measurements of bilirubin should be done. This assessment is done through two methods of laboratory measurement in serum sample and transcutaneous bilirubinometer. This descriptive study compared transcutaneous bilirubin assessment and laboratory serum bilirubin. Bilirubin level was assessed among 256 neonates admitted to the Qods Children's Hospital in Qazvin- Iran, because of neonatal indirect jaundice, through two methods of transcutaneous bilirubinometery from two sites of forehead and sternum and laboratory measurement of bilirubin in serum. The cases were non-hemolytic icteric term neonates weighing 2500 gram or more and had not received phototherapy or other treatments. Neonates with hemolytic forms of jaundice, sepsis and suspicious to metabolic disorders were excluded. Assessments by means of KJ-8000 transcutaneous bilirubinometer from two sites of forehead and sternum and through laboratory measurement of serum bilirubin were registered and analyzed. The results of the current study showed that there was a correlation of 0.82 between serum bilirubin and transcutaneous forehead bilirubin assessment and for the used device sensitivity of 0.844; specificity of 0.842, Youden Index of 0.709 and Shortest of 0.042 for a cut-off of 12.4 in bilirubin of participants. Furthermore, Likelihood Ratio positive and negative (LR) were 5.665 and 0.164, respectively and diagnostic Odds Ratio (LR+/LR-) was 34.56. Transcutaneous bilirubinometery can be considered as a reliable tool to assess bilirubin for the screening of neonatal jaundice in term neonates. PMID:26749233

  16. Brain MRI findings in Wernicke encephalopathy.

    PubMed

    Wicklund, Meredith R; Knopman, David S

    2013-08-01

    A 71-year-old woman with myelofibrosis on chemotherapy experienced an acute illness with nausea, vomiting, and diarrhea. Two weeks later, she developed an acute confusional state characterized by disorientation and fluctuating alertness with normal speech and language. Her neurologic examination demonstrated an upper motor neuron pattern of right hemiparesis. She reported double vision though ophthalmoparesis was not appreciated. Her gait was normal. While hospitalized, she developed generalized tonic-clonic seizures. Brain MRI revealed a small area of restricted diffusion of the left precentral gyrus (figure). She was diagnosed with a stroke with secondary seizures; however, as the confusional state resolved, she developed profound retrograde and anterograde amnesia. Review of the brain MRI showed high T2 signal in the medial thalamus and contrast enhancement of the mamillary bodies; a diagnosis of Wernicke-Korsakoff syndrome was entertained and she was started on thiamine replacement. The encephalopathy and hemiparesis resolved though she remains severely amnestic. PMID:24195023

  17. A Rare Complication Developing After Hematopoietic Stem Cell Transplantation: Wernicke’s Encephalopathy

    PubMed Central

    Solmaz, Soner; Gereklioğlu, Çiğdem; Tan, Meliha; Demir, Şenay; Yeral, Mahmut; Korur, Aslı; Boğa, Can; Özdoğu, Hakan

    2015-01-01

    Thiamine is a water-soluble vitamin. Thiamine deficiency can present as a central nervous system disorder known as Wernicke’s encephalopathy, which classically manifests as confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy has rarely been reported following hematopoietic stem cell transplantation. Herein, we report Wernicke’s encephalopathy in a patient with acute myeloid leukemia who had been receiving prolonged total parenteral nutrition after haploidentical allogeneic hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case reported from Turkey in the literature. PMID:25912759

  18. Hepatic Encephalopathy: Early Diagnosis in Pediatric Patients With Cirrhosis

    PubMed Central

    DARA, Naghi; SAYYARI, Ali-Akbar; IMANZADEH, Farid

    2014-01-01

    Objective As acute liver failure (ALF) and chronic liver disease (cirrhosis) continue to increase in prevalence, we will see more cases of hepatic encephalopathy. Primary care physician are often the first to suspect it, since they are familiar with the patient’s usual physical and mental status. This serious complication typically occurs in patients with severe comorbidities and needs multidisciplinary evaluation and care. Hepatic encephalopathy should be considered in any patient with acute liver failure and cirrhosis who presents with neuropsychiatric manifestations, decrease level of consciousness (coma), change of personality, intellectual and behavioral deterioration, speech and motor dysfunction. Every cirrhotic patient may be at risk; potential precipitating factors should be addressed in regular clinic visits. The encephalopathy of liver disease may be prominent, or can be present in subtle forms, such as decline of school performance, emotional outbursts, or depression. “Subtle form” of hepatic encephalopathy may not be obvious on clinical examination, but can be detected by neurophysiologic and neuropsychiatric testing. PMID:24665321

  19. [Does bilirubin interfere with capillary electrophoresis of serum proteins?].

    PubMed

    Hellara, Ilhem; Fekih, Ons; Triki, Sonia; Elmay, Ahlem; Neffati, Fadoua; Najjar, Mohamed Fadhel

    2014-01-01

    Capillary electrophoresis of serum proteins is a fast, reliable and simple technique, but many interference exist. The objective of our work is to study the interference of bilirubin on this technique; 70 icteric sera were analysed on Capillarys ™ (Sebia). A second electrophoresis was performed on 40 samples after bilirubin photodegradation. The bilirubin and serum proteins were determinated respectively by Jendrassik and Grof and biuret methods on Konélab 20i ™ (Thermo Electron Corporation). We found abnormal spreading of the albumin fraction of the anode side wich constitute sometimes an isolated fraction in the traditional area of pre-albumin migration. This fraction varies from 2.0 ± 2.0% (0.0 to 7.3%) or 0.98 ± 1.53 g/L (0 to 5.3 g/L) and it seems to be related to the direct bilirubin since, following overloading sera with a solution of bilirubin, no further fraction was recovered. An average decrease of bilirubin after photodegradation of 58 ± 17% (26-89%) is followed by a decrease in the same order 64 ± 38% (10-100%) of the additional fraction. Acetate cellulose electrophoresis of the same samples showed no variation. The high bilirubin levels seem modify slightly the electrophoretic profile. However the impact of the interference on the interpretation of electrophoretic trace is negligible. PMID:24492101

  20. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

    PubMed

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Ludovico Rapaccini, Gian; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-04-01

    Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  1. A Case of Subacute Encephalopathy Developing After Treatment With Clofarabine and Methotrexate That Resolved With Corticosteroids.

    PubMed

    Tzachanis, Dimitrios; Haider, Mintallah; Papazisis, Georgios

    2016-01-01

    This is the case of a 24-year-old woman with relapsed acute undifferentiated leukemia who developed subacute encephalopathy with hemiparesis and dysarthria after treatment with high dose and intrathecal methotrexate, clofarabine, and cytarabine that resolved rapidly and completely after the administration of corticosteroids. We hypothesize that clofarabine might predispose to methotrexate-induced central nervous system toxicity by increasing endothelial permeability (capillary leak syndrome) and suggest that corticosteroids are effective in the treatment of this type of encephalopathy. PMID:24987945

  2. Treatment of epileptic encephalopathies.

    PubMed

    McTague, Amy; Cross, J Helen

    2013-03-01

    Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone. The epilepsy syndromes at high risk of this are a disparate group of conditions characterized by epileptic seizures that are difficult to treat and developmental delay. In this review, we discuss the ongoing debate regarding the significance of inter-ictal discharges and the impact of the seizures themselves on the cognitive delay or regression that is a common feature of these syndromes. The syndromes also differ in many ways and we provide a summary of the key features of the early-onset epileptic encephalopathies including Ohtahara and West syndromes in addition to later childhood-onset syndromes such as Lennox Gastaut and Doose syndromes. An understanding of the various severe epilepsy syndromes is vital to understanding the rationale for treatment. For example, the resolution of hypsarrhythmia in West syndrome is associated with an improvement in cognitive outcome and drives treatment choice, but the same cannot be applied to frequent inter-ictal discharges in Lennox Gastaut syndrome. We discuss the evidence base for treatment where it is available and describe current practice where it is not. For example, in West syndrome there is some evidence for preference of hormonal treatments over vigabatrin, although the choice and duration of hormonal treatment remains unclear. We describe the use of conventional and newer anti-epileptic medications in the various syndromes and discuss which medications should be avoided. Older possibly forgotten treatments such as sulthiame and potassium bromide also have a role in the severe epilepsies of childhood. We discuss hormonal treatment with particular focus on the treatment of West syndrome, continuous spike wave in slow wave sleep (CSWS)/electrical status epilepticus in slow wave

  3. [Prevention of hepatic encephalopathy].

    PubMed

    Morillas, Rosa M; Sala, Marga; Planas, Ramon

    2014-06-01

    Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis. PMID:24480288

  4. Hashimoto Encephalopathy in Case of Progressive Cognitive Impairment; a Case Report

    PubMed Central

    Tafakhori, Abbas; Siroos, Bahaadin; Ghabaii, Mojdeh; Harirchain, Mohammad Hossein; Tajdini, Masih; Garg, Sushil Kumar

    2014-01-01

    Hashimoto's encephalopathy (HE) is a rare condition characterized by atypical psychiatric and heterogeneous neurological manifestations such as acute cerebral ischemia, seizure, tremors, myoclonus, psychosis, depression, cognitive disorders, and fluctuating loss of consciousness. Here, a case of 28 year-old man was reported who referred to the emergency department (ED) with different acute neurologic disorders and final diagnose of HE. PMID:26495368

  5. Bilirubin Neurotoxicity in Preterm Infants: Risk and Prevention

    PubMed Central

    Bhutani, Vinod K.; Wong, Ronald J.

    2013-01-01

    Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% in babies <30, 31-32, and 33-34 wks gestational age, respectively. Phototherapy initiated at 24±12 hr effectively prevented hyperbilirubinemia in infants <2,000 g even in the presence of hemolysis. This approach (in 1985) reduced exchange transfusions from 23.9% to 4.8%. Now with 3 decades of experience in implementing effective phototherapy, the need for exchange transfusions has virtually been eliminated. However, bilirubin neurotoxicity continues to be associated with prematurity alone. The ability to better predict this risk, other than birthweight and gestation, has been elusive. Objective tests such as total bilirubin, unbound or free bilirubin, albumin levels, and albumin-bilirubin binding, together with observations of concurrent hemolysis, sepsis, and rapid rate of bilirubin rise have been considered, but their individual or combined predictive utility has yet to be refined. The disruptive effects of immaturity, concurrent neonatal disease, cholestasis, use of total parenteral nutrition or drugs that alter bilirubin-binding abilities augment the clinical risk of neurotoxicity. Current management options rely on the “fine-tuning” of each infant's exposure to beneficial antioxidants and avoidance of silent neurotoxic properties of bilirubin navigated within the safe spectrum of operational thresholds demarcated by experts. PMID:24049745

  6. Bilirubin as an endogenous modulator of neurotrophin redox signaling.

    PubMed

    Mancuso, Cesare; Capone, Caterina; Ranieri, Sofia Chiatamone; Fusco, Salvatore; Calabrese, Vittorio; Eboli, Maria Luisa; Preziosi, Paolo; Galeotti, Tommaso; Pani, Giovambattista

    2008-08-01

    Bilirubin is neurotoxic upon excess accumulation in the brain, but it also plays important physiological roles related to its antioxidant properties. Here we report that exposure of PC12 and primary rat cerebellar granule neurons to bilirubin (0.5-10 microM) drastically decreases nerve growth factor (NGF)/brain-derived neurotrophic factor signaling to Akt and extracellular signal-regulated kinases (ERKs), indicating a direct interference of the molecule with crucial prosurvival signaling pathways. This effect likely involves the scavenging capacity of bilirubin, the latter being able to inhibit, in PC12 cells, accumulation of intracellular reactive oxygen species and phosphorylation of Akt and ERKs in response to extracellular hydrogen peroxide. Interestingly, in the absence of exogenous growth factor, bilirubin elicited the phosphorylation of ERKs and of the cAMP responsive element binding (CREB) transcription factor, a signature of NGF-dependent survival signaling. These growth factor-like signaling effects were paralleled by the induction of the neuronal nitric oxide synthase (nNOS) and generation of nitric oxide (NO). Pharmacological dissection of the signaling cascade triggered by bilirubin revealed that phosphorylation of ERKs requires NO signaling through soluble guanylyl cyclase, and, further upstream, influx of extracellular calcium is necessary for nNOS induction and NO release, likely through calcium-dependent phosphorylation of CREB. Importantly, the cascade elicited by bilirubin through NO and ERK is cytoprotective, as revealed by exacerbated bilirubin toxicity in cultures treated by either NOS or MEK inhibitors. Taken together, these observations indicate an important action of bilirubin on redox signaling by neurotrophins, with either inhibitory or agonistic effects based on growth factor availability. PMID:18338802

  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. Hepatic Conversion of Bilirubin Monoglucuronide to Diglucuronide in Uridine Diphosphate-Glucuronyl Transferase-Deficient Man and Rat by Bilirubin Glucuronoside Glucuronosyltransferase

    PubMed Central

    Chowdhury, J. Roy; Jansen, P. L. M.; Fischberg, E. B.; Daniller, A.; Arias, I. M.

    1978-01-01

    The microsomal enzyme uridine diphosphate (UDP) glucuronate glucuronyltransferase (E.C. 2.4.1.17) catalyzes formation of bilirubin mono-glucuronide from bilirubin and UDPglucuronic acid. Bilirubin glucuronoside glucuronosyltransferase (E.C. 2.4.1.95), an enzyme concentrated in plasma membrane-enriched fractions of rat liver, converts bilirubin monoglucuronide to bilirubin diglucuronide. Bilirubin glucuronoside glucuronosyltransferase activity was studied in homogenates of liver biopsy specimens obtained from patients with the Crigler-Najjar syndrome (Type I) and in subcellular liver fractions of rats homozygous for UDP glucuronate glucuronyltransferase deficiency (Gunn strain). In patients with the Crigler-Najjar syndrome (Type I) and in Gunn rats, hepatic UDPglucuronate glucuronyltransferase activity was not measurable; however, bilirubin glucuronoside glucuronosyltransferase activity was similar to that in normal controls. The subcellular distribution of bilirubin glucuronoside glucuronosyltransferase activity in Gunn rat liver was similar to the distribution observed in normal Wistar rat liver. When bilirubin monoglucuronide was infused intravenously into Gunn rats, 29±5% of the conjugated bilirubin excreted in bile was bilirubin diglucuronide. After transplantation of normal Wistar rat kidney, which contained UDPglucuronate glucuronyltransferase activity, in Gunn rats, the serum bilirubin concentration decreased by 80% in 4 days. The major route of bilirubin removal was biliary excretion of conjugated bilirubin, approximately 70% of which was bilirubin diglucuronide. Although patients with the Crigler-Najjar syndrome (Type I) and Gunn rats lack UDP glucuronate glucuronyltransferase, their livers enzymatically convert bilirubin monoglucuronide to diglucuronide in vitro. Conversion in bilirubin monoglucuronide to diglucuronide was demonstrated in Gunn rats in vivo. PMID:96142

  9. Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy

    PubMed Central

    Gamal, Maha; Abdel Wahab, Zainab; Eshra, Mohamed; Rashed, Laila; Sharawy, Nivin

    2014-01-01

    Objective. Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone. Methods. 48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed. Results. ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema. Conclusion. Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes. PMID:24693424

  10. Need for early diagnosis of mental and mobility changes in Wernicke encephalopathy.

    PubMed

    Wijnia, Jan W; Oudman, Erik; Bresser, Esmay L; Gerridzen, Ineke J; van de Wiel, Albert; Beuman, Carla; Mulder, Cornelis L

    2014-12-01

    Korsakoff syndrome is a chronic form of amnesia resulting from thiamine deficiency. The syndrome can develop from unrecognized or undertreated Wernicke encephalopathy. The intra-individual course of Wernicke-Korsakoff syndrome has not been studied extensively, nor has the temporal progression of gait disturbances and other symptoms of Wernicke encephalopathy. Here we present the detailed history of a patient whose acute symptoms of Wernicke encephalopathy were far from stable. We follow his mobility changes and the shifts in his mental status from global confusion and impaired consciousness to more selective cognitive deficits. His Wernicke encephalopathy was missed and left untreated, being labeled as "probable" Korsakoff syndrome. Patients with a history of self-neglect and alcohol abuse, at risk of or suffering with Wernicke encephalopathy, should receive immediate and adequate vitamin replacement. Self-neglecting alcoholics who are bedridden may have severe illness and probably active Wernicke encephalopathy. In these patients, mobility changes, delirium, or impaired consciousness can be an expression of Wernicke encephalopathy, and should be treated to prevent further damage from the neurologic complications of thiamine deficiency. PMID:25539041

  11. The Severity of Cecal Ligature and Puncture-Induced Sepsis Correlates with the Degree of Encephalopathy, but the Sepsis Does Not Lead to Acute Activation of Spleen Lymphocytes in Mice.

    PubMed

    Jeremias, I C; Victorino, V J; Machado, J L; Barroso, W A; Ariga, S K; Lima, T M; Soriano, F G

    2016-07-01

    Septic encephalopathy represents the most frequently observed form of encephalopathy in intensive care units. Interactions between the immune and nervous systems have been observed in experimental sepsis. Therefore, the aim of the current study was to characterize the effect of different severities of sepsis on encephalopathy and the inflammatory profile of the spleen. We hypothesized that different grades of sepsis severity would lead to variations in encephalopathy and activation of spleen cells. We induced sepsis of different severities in Balb/c mice by cecal ligature and puncture (CLP). Six and 12 h after CLP induction, behavioral impairment was assessed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) test. The animals were then killed, and the plasma, spleen, and hippocampus were removed. Levels of the encephalopathy marker S100β were measured in plasma. Spleens were weighed and then a characterization of splenic lymphocytes was performed by flow cytometry (cytotoxic T lymphocyte, T helper lymphocytes, B lymphocytes, T regulatory cells, and Th17 cells). Cytokine levels in the spleen and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA), and cytokine levels in plasma were performed with MilliPlex® technology. Our results showed that behavioral impairment as measured by the SHIRPA test and elevation in plasma S100β levels were significant in moderate and severe CLP groups compared to those in the sham control group. Regarding immunological alterations, we were unable to observe changes in the weights of the spleen and the profile of lymphocytes 6 h after CLP. However, several cytokines, including IL-6, IL-10, and IL-1β, were increased in spleen and plasma. In conclusion, we observed variations in encephalopathy as measured by plasma S100β, which were mediated by the severity of sepsis; however, we did not observe a different activation of spleen cells 6 h post-CLP, despite evidence of

  12. Wernicke's encephalopathy in a child with high dose thiamine therapy

    PubMed Central

    Park, So Won; Yi, Yoon Young; Han, Jung Woo; Kim, Heung Dong; Lee, Joon Soo

    2014-01-01

    Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. It has been reported in individuals with alcohol dependence, hyperemesis gravidarum, and prolonged parenteral nutrition without vitamin supplementation. Here we present the case of a 13-year-old male patient with neuroblastoma and a history of poor oral intake and nausea for 3 months. After admission, he showed gait disturbances, nystagmus, and excessive dizziness; his mental state, however, indicated he was alert, which did not fit the classical triad of Wernicke's encephalopathy. A diagnosis of Wernicke's encephalopathy was made only after brain magnetic resonance imaging and serum thiamine level analyses were performed. The patient's symptoms remained after 5 days of treatment with 100-mg thiamine once daily; thus, we increased the dosage to 500 mg 3 times daily, 1,500 mg per day. His symptoms then improved after 20 days of replacement therapy. This case report describes a pediatric patient who was promptly diagnosed with Wernicke's encephalopathy, despite only 2 suspicious symptoms, and who completely recovered after high doses of thiamine were given intravenously. PMID:25550705

  13. The transmissible spongiform encephalopathies of livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein misfolding neurodegenerative diseases. TSEs have been described in several species including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, tr...

  14. [Posterior reversible encephalopathy syndrome].

    PubMed

    Fischer, M; Schmutzhard, E

    2016-06-01

    Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely. PMID:27272329

  15. Sepsis Associated Encephalopathy

    PubMed Central

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

    Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis. PMID:26556425

  16. Chronic traumatic encephalopathy.

    PubMed

    Yi, Juneyoung; Padalino, David J; Chin, Lawrence S; Montenegro, Philip; Cantu, Robert C

    2013-01-01

    Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research. PMID:23314081

  17. Sepsis-Associated Encephalopathy

    PubMed Central

    Cotena, Simona; Piazza, Ornella

    2012-01-01

    Summary Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct brain infection. Its pathogenesis is multifactorial. SAE generally occurs early during severe sepsis and precedes multiple-organ failure. The most common clinical feature of SAE is the consciousness alteration which ranges from mildly reduced awareness to unresponsiveness and coma. Diagnosis of SAE is primarily clinical and depends on the exclusion of other possible causes of brain deterioration. Electroencephalography (EEG) is almost sensitive, but it is not specific for SAE. Computed Tomography (CT) head scan generally is negative in case of SAE, while Magnetic Resonance Imaging (MRI) can show brain abnormalities in case of SAE, but they are not specific for this condition. Somatosensitive Evoked Potentials (SEPs) are sensitive markers of developing cerebral dysfunction in sepsis. Cerebrospinal fluid (CBF) analysis is generally normal, a part an inconstant elevation of proteins concentration. S100B and NSE have been proposed like biomarkers for diagnosis of SAE, but the existing data are controversial. SAE is reversible even if survivors of severe sepsis have often long lasting or irreversible cognitive and behavioral sequel; however the presence of SAE can have a negative influence on survival. A specific therapy of SAE does not exist and the outcome depends on a prompt and appropriate treatment of sepsis as whole. PMID:23905041

  18. [Mitochondrial neurogastrointestinal encephalopathy disease].

    PubMed

    Benureau, A; Meyer, P; Maillet, O; Leboucq, N; Legras, S; Jeziorski, E; Fournier-Favre, S; Jeandel, C; Gaignard, P; Slama, A; Rivier, F; Roubertie, A; Carneiro, M

    2014-12-01

    Mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) is a rare autosomal-recessive syndrome, resulting from mutations in the TYMP gene, located at 22q13. The mutation induces a thymidine phosphorylase (TP) deficit, which leads to a nucleotide pool imbalance and to instability of the mitochondrial DNA. The clinical picture regroups gastrointestinal dysmotility, cachexia, ptosis, ophthalmoplegia, peripheral neuropathy, and asymptomatic leukoencephalopathy. The prognosis is unfavorable. We present the case of a 14-year-old Caucasian female whose symptoms started in early childhood. The diagnosis was suspected after magnetic resonance imaging (MRI), performed given the atypical features of mental anorexia, which revealed white matter abnormalities. She presented chronic vomiting, postprandial abdominal pain, and problems gaining weight accompanied by cachexia. This diagnosis led to establishing proper care, in particular an enteral and parenteral nutrition program. There is no known specific effective treatment, but numerous studies are in progress. In this article, after reviewing the existing studies, we discuss the main diagnostic and therapeutic aspects of the disease. We argue for the necessity of performing a cerebral MRI given the atypical features of a patient with suspected mental anorexia (or when the clinical pattern of a patient with mental anorexia seems atypical), so that MNGIE can be ruled out. PMID:25282463

  19. Hyperammonemic Encephalopathy Caused by Carnitine Deficiency

    PubMed Central

    Zucker, Stephen D.

    2007-01-01

    Carnitine is an essential co-factor in fatty acid metabolism. Carnitine deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and encephalopathy. We present the case of a 35-year-old woman who developed acute mental status changes, asterixis, and diffuse muscle weakness. Her ammonia level was elevated at 276 μg/dL. Traditional ammonia-reducing therapies were initiated, but proved ineffective. Pharmacologic, microbial, and autoimmune causes for the hyperammonemia were excluded. The patient was severely malnourished and her carnitine level was found to be extremely low. After carnitine supplementation, ammonia levels normalized and the patient’s mental status returned to baseline. In the setting of refractory hyperammonemia, this case illustrates how careful investigation may reveal a treatable condition. PMID:18080167

  20. STEC:O111-HUS complicated by acute encephalopathy in a young girl was successfully treated with a set of hemodiafiltration, steroid pulse, and soluble thrombomodulin under plasma exchange

    PubMed Central

    Yada, Noritaka; Fujioka, Masayuki; Bennett, Charles L; Inoki, Kazuya; Miki, Toyokazu; Watanabe, Akihiko; Yoshida, Toshiko; Hayakawa, Masaki; Matsumoto, Masanori; Fujimura, Yoshihiro

    2015-01-01

    Key Clinical Message We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS. PMID:25914810

  1. Approach to Clinical Syndrome of Jaundice and Encephalopathy in Tropics

    PubMed Central

    Anand, Anil C.; Garg, Hitendra K.

    2015-01-01

    A large number of patients present with jaundice and encephalopathy in tropical country like India and acute liver failure is the usual cause. Clinical presentation like ALF is also a complication of many tropical infections, and these conditions may mimic ALF but may have subtle differences from ALF. Moreover, what hepatologists see as acute liver failure in tropics is different from what is commonly described in Western Textbooks. Paracetamol overdose, which is possibly the commonest cause of ALF in UK and USA, is hardly ever seen in India. Most common etiology here is viral hepatitis (hepatitis E > hepatitis B> hepatitis A). Apart from ALF, one may also come across subacute hepatic failure (SAHF) as well as acute-on-chronic liver failure (ACLF) due to viral hepatitis. Interestingly, a host of other conditions can mimic ALF because clinical presentation in these conditions can be dominated by jaundice and encephalopathy. Malarial hepatopathy is possibly the best-known condition out of these and is not an uncommon manifestation of severe malaria. A similar presentation can also be seen in other common infections in tropics such as dengue fever, typhoid fever, leptospirosis, scrub typhus, amoebic liver abscesses, tuberculosis and other bacterial and fungal infections with or without human immunodeficiency virus (HIV) related disease. In many of these conditions, liver failure may not be underlying pathophysiology. Some pregnancy related liver diseases could also present with jaundice and encephalopathy. This review summarizes the commonly seen presentations in tropical country like India, where jaundice and encephalopathy dominate the clinical picture. PMID:26041951

  2. Influence of hemoglobin on non-invasive optical bilirubin sensing

    NASA Astrophysics Data System (ADS)

    Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin

    2012-03-01

    Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.

  3. Diagnosis of minimal hepatic encephalopathy.

    PubMed

    Weissenborn, Karin

    2015-03-01

    Minimal hepatic encephalopathy (mHE) has significant impact upon a liver patient's daily living and health related quality of life. Therefore a majority of clinicians agree that mHE should be diagnosed and treated. The optimal means for diagnosing mHE, however, is controversial. This paper describes the currently most frequently used methods-EEG, critical flicker frequency, Continuous Reaction time Test, Inhibitory Control Test, computerized test batteries such as the Cognitive Drug Research test battery, the psychometric hepatic encephalopathy score (PHES) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)-and their pros and cons. PMID:26041959

  4. Hashimoto's Encephalopathy Presenting with Chorea.

    PubMed

    Sharan, Abhijeet; Sengupta, Sarbani; Mukhopadhyay, Sarmishtha; Ghosh, Bhaskar

    2015-09-01

    Hashimoto's encephalopathy (HE) is a steroid-responsive relapsing neuropsychiatric disorder associated with high titers of antithyroid antibody with or without thyroid dysfunction. We report a case of HE in a 78 year old female who developed sudden onset behavioral abnormalities associated with choreiform movement of extremities. All causes of vascular, infective, metabolic, autoimmune, paraneoplastic and toxic encephalopathy were excluded. Anti-thyroid peroxidase (anti-TPO) antibody was found to be raised with very high titre. A diagnosis of HE was made. Prompt treatment with high dose steroid led to dramatic improvement of symptoms including choreiform movement. PMID:27608878

  5. Fluorescent protein-based detection of unconjugated bilirubin in newborn serum

    PubMed Central

    Iwatani, Sota; Nakamura, Hajime; Kurokawa, Daisuke; Yamana, Keiji; Nishida, Kosuke; Fukushima, Sachiyo; Koda, Tsubasa; Nishimura, Noriyuki; Nishio, Hisahide; Iijima, Kazumoto; Miyawaki, Atsushi; Morioka, Ichiro

    2016-01-01

    Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin, and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum. PMID:27324682

  6. Fluorescent protein-based detection of unconjugated bilirubin in newborn serum.

    PubMed

    Iwatani, Sota; Nakamura, Hajime; Kurokawa, Daisuke; Yamana, Keiji; Nishida, Kosuke; Fukushima, Sachiyo; Koda, Tsubasa; Nishimura, Noriyuki; Nishio, Hisahide; Iijima, Kazumoto; Miyawaki, Atsushi; Morioka, Ichiro

    2016-01-01

    Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin, and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum. PMID:27324682

  7. Bilirubin oxidases in bioelectrochemistry: features and recent findings.

    PubMed

    Mano, Nicolas; Edembe, Lise

    2013-12-15

    Bilirubin oxidases, a sub class of the Multicopper oxidases family, were discovered in 1981 by Tanaka and Murao (Murao and Tanaka, 1981) and first used for the detection of bilirubin. Since 2001 and the pioneering work of Tsujimura, these BODs have attracted a lot of attention for the reduction of O2. Unlike laccases, these BODs are stable in physiological conditions (20mM phosphate buffer, pH 7.4, 0.14 M NaCl, 37 °C) and more than 120 papers have been published in the last 7 years. Here, we will first briefly describe some general features of BODs and then review the use of BODs for bilirubin biosensors and the recent achievements and progress toward the elaboration of efficient O2 reducing cathodes. PMID:23911663

  8. [Role of rifaximin in the treatment of hepatic encephalopathy].

    PubMed

    Sanchez-Delgado, Jordi; Miquel, Mireia

    2016-04-01

    Hepatic encephalopathy (HE) is a frequent and serious complication of liver cirrhosis. In addition to correction of the precipitating factors, the most commonly used treatments are non-absorbable disaccharides and rifaximin. Many of the recommendations are based on current clinical practice and there are few randomized controlled trials. Currently, rifaximin should be initiated during an episode of EH if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement. In recurrent EH, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode. Currently, standard treatment with rifaximin for minimal EH is not recommended. Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence. PMID:26545947

  9. Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy

    PubMed Central

    Rivera-Espinosa, Liliana; Floriano-Sánchez, Esaú; Pedraza-Chaverrí, José; Coballase-Urrutia, Elvia; Sampieri, Aristides; Ortega-Cuellar, Daniel; Cárdenas-Rodríguez, Noemí; Carmona-Aparicio, Liliana

    2013-01-01

    Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease. PMID:23921686

  10. Bilirubin-Induced Audiologic Injury in Preterm Infants.

    PubMed

    Olds, Cristen; Oghalai, John S

    2016-06-01

    Although hyperbilirubinemia is extremely common among neonates and is usually mild and transient, it sometimes leads to bilirubin-induced neurologic damage (BIND). The auditory pathway is highly sensitive to the effects of elevated total serum/plasma bilirubin (TB) levels, with damage manifesting clinically as auditory neuropathy spectrum disorder. Compared to full-term neonates, preterm neonates are more susceptible to BIND and suffer adverse effects at lower TB levels with worse long-term outcomes. Furthermore, although standardized guidelines for management of hyperbilirubinemia exist for term and late preterm neonates, similar guidelines for neonates less than 35 weeks gestational age are limited. PMID:27235210

  11. [Micelle-mediated extraction for concentrating conjugated bilirubin in urine].

    PubMed

    Matsudo, T; Saitoh, T; Matsubara, C

    2001-02-01

    An extraction method based on the phase separation of aqueous micellar solutions of n-octyl-beta-D-thioglucoside (OTG) was applied to the concentrating conjugated bilirubin in urine. The analyte in sample solutions could be efficiently concentrated into a small volume of surfactant-rich phase, while hydrophilic matrix components including urinary protein, ascorbic acid, and saccharide remained in the aqueous phase. The concentrated OTG negligibly affected the diazo reaction and the subsequent spectrophotometric detection. Conjugated bilirubin was successfully determined in the concentration range from 0.05 microgram/ml to 5 micrograms/ml with a 96-well microplate reader absorption spectrophotometer. PMID:11218735

  12. Neonatal jaundice: a critical review of the role and practice of bilirubin analysis.

    PubMed

    Kirk, Jean M

    2008-09-01

    Neonatal jaundice is common, and usually harmless, because of physiological jaundice or breast-feeding. In some neonates unconjugated bilirubin concentration, coupled with other risk factors, is sufficient to allow free bilirubin to cross the blood-brain barrier and cause kernicterus. Another subgroup of infants is jaundiced because of elevated conjugated bilirubin; a marker for a number of pathological conditions. Bilirubin measurement must identify those infants at risk. Transcutaneous bilirubin measurement is increasingly used in healthy infants, especially before early discharge or at home, to assess the need for laboratory bilirubin measurement. Transcutaneous measurements are not covered by laboratory quality assessment schemes. Guidelines on management of neonatal jaundice utilize age in hours and other risk factors to define bilirubin action thresholds, which may be as low as 100 micromol/L for sick premature infants, whereas early discharged babies may only present after bilirubin concentrations are extremely high. Hence, there is a requirement for accurate total bilirubin measurement from <100 to >500 micromol/L, with sufficient precision to assess the rate of bilirubin change with time. Babies presenting with late jaundice always require conjugated bilirubin measurement. It is of concern that many total and direct bilirubin automated kit methods suffer from haemolysis interference, while use of in-house methods or modification of commercial methods has virtually disappeared. External quality assessment has a vital role in providing data on different methods' performance, including accuracy, precision and susceptibility to interference. Laboratories should consider whether their adult bilirubin methods are suitable for neonates. PMID:18753416

  13. Posterior reversible encephalopathy syndrome (PRES) and hypomagnesemia: A frequent association?

    PubMed

    Chardain, A; Mesnage, V; Alamowitch, S; Bourdain, F; Crozier, S; Lenglet, T; Psimaras, D; Demeret, S; Graveleau, P; Hoang-Xuan, K; Levy, R

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a serious neurological condition encountered in various medical fields. Pathophysiological factor(s) common to PRES cases of apparently unrelated etiologies are yet to be found. Based on the hypothesis that hypomagnesemia might participate in the cascade leading to PRES, our study sought to verify whether hypomagnesemia is frequently associated with PRES regardless of etiology. From a retrospective study of a cohort of 57 patients presenting with PRES of different etiologies, presented here are the findings of 19 patients with available serum magnesium levels (SMLs) during PRES. In the acute phase of PRES, hypomagnesemia was present in all 19 patients in spite of differences in etiology (including immunosuppressive drugs, hypertensive encephalopathy, eclampsia, systemic lupus erythematosus, iatrogenic etiology and unknown). SMLs were within normal ranges prior to PRES and below normal ranges during the first 48h of PRES, with a significant decrease in SMLs during the acute phase. In this retrospective study, constant hypomagnesemia was observed during the acute phase of PRES regardless of its etiology. These results now require larger studies to assess the particular importance of acute hypomagnesemia in PRES and especially the possible need to treat PRES with magnesium sulfate. PMID:27371132

  14. Pharmacotherapy for hepatic encephalopathy.

    PubMed

    Phongsamran, Paula V; Kim, Jiwon W; Cupo Abbott, Jennifer; Rosenblatt, Angela

    2010-06-18

    Hepatic encephalopathy (HE) is a challenging clinical complication of liver dysfunction with a wide spectrum of neuropsychiatric abnormalities that range from mild disturbances in cognitive function and consciousness to coma and death. The pathogenesis of HE in cirrhosis is complex and multifactorial, but a key role is thought to be played by circulating gut-derived toxins of the nitrogenous compounds, most notably ammonia. Therapeutic treatment options for HE are currently limited and have appreciable risks and benefits associated with their use. Management of HE primarily involves avoidance of precipitating factors, limitation of dietary protein intake, and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and select antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. However, multiple adverse events have been associated with their use. In addition, recent literature has questioned the true efficacy of the disaccharides for this indication. Neomycin, metronidazole and vancomycin may be used as alternative treatments for patients intolerant or unresponsive to non-absorbable disaccharides. Antimicrobials reduce bacterial production of ammonia and other bacteria-derived toxins through suppression of intestinal flora. Neomycin has been reported to be as effective as lactulose, and similar efficacy has been reported with vancomycin and metronidazole for the management of HE. However, the adverse effects frequently associated with these antimicrobials limit their use as first-line pharmacological agents. Neomycin is the most commonly used antimicrobial for HE and, although poorly absorbed, systemic exposure to the drug in sufficient amounts causes hearing loss and renal toxicity. Long-term neomycin therapy requires annual auditory testing and continuous monitoring of renal function. Long-term use of metronidazole has been

  15. Nanofibrous polymeric beads from aramid fibers for efficient bilirubin removal.

    PubMed

    Peng, Zihang; Yang, Ye; Luo, Jiyue; Nie, Chuanxiong; Ma, Lang; Cheng, Chong; Zhao, Changsheng

    2016-08-16

    Polymer based hemoperfusion has been developed as an effective therapy to remove the extra bilirubin from patients. However, the currently applied materials suffer from either low removal efficiency or poor blood compatibility. In this study, we report the development of a new class of nanofibrous absorbent that exhibited high bilirubin removal efficiency and good blood compatibility. The Kevlar nanofiber was prepared by dissolving micron-sized Kevlar fiber in proper solvent, and the beads were prepared by dropping Kevlar nanofiber solutions into ethanol. Owing to the nanofiborous structure of the Kevlar nanofiber, the beads displayed porous structures and large specific areas, which would facilitate the adsorption of toxins. In the adsorption test, it was noticed that the beads possessed an adsorption capacity higher than 40 mg g(-1) towards bilirubin. In plasma mimetic solutions, the beads still showed high bilirubin removal efficiency. Furthermore, after incorporating with carbon nanotubes, the beads were found to have increased adsorption capacity for human degradation waste. Moreover, the beads showed excellent blood compatibility in terms of a low hemolysis ratio, prolonged clotting times, suppressed coagulant activation, limited platelet activation, and inhibited blood related inflammatory activation. Additionally, the beads showed good compatibility with endothelial cells. In general, the Kevlar nanofiber beads, which integrated with high adsorption capacity, good blood compatibility and low cytotoxicity, may have great potential for hemoperfusion and some other applications in biomedical fields. PMID:27481656

  16. Biphasic Effect of Rifampicin on Bilirubin- A Case Report.

    PubMed

    Gopi, Manigandan; Seshadri, Mandalam Subramanian

    2016-04-01

    Drug induced hepatitis is a major problem which a physician encounters in his clinical practice. In view of increasing incidence of tuberculosis in our country a large number of infected individuals are started on Antituberculous (ATT) drugs and rifampicin is invariably part of the regimen. One of the major adverse effects of ATT drugs is drug- induced hepatitis which is characterized by elevation of liver enzymes and bilirubin. Hepatotoxicity is usually idiosyncratic or dose-dependent. Rifampicin causes transient elevation of transaminases in 10-20 percent of individuals and this does not warrant dose adjustments of the drug. Rarely rifampicin can lead to severe hepatitis with hyperbilirubinaemia and marked elevations of SGOT and SGPT and in some patients this can be fatal. The exact mechanism of Rifampicin induced hepatotoxicity is not known but it is postulated to be due to idiosyncratic reaction to rifampicin metabolites which may be directly toxic or induce an immunologically mediated liver injury. Rarely rifampicin may cause hyperbilirubinaemia without enzyme elevation. Here we report a patient with bilateral pulmonary tuberculosis who developed transient severe indirect hyperbilirubinaemia on rifampicin. On review of relevant literature we find that rifampicin can have a biphasic effect on bilirubin, an initial increase in indirect bilirubin and later normalization of bilirubin. We have reported this case because of its rarity in clinical practice. PMID:27190870

  17. Biphasic Effect of Rifampicin on Bilirubin- A Case Report

    PubMed Central

    Seshadri, Mandalam Subramanian

    2016-01-01

    Drug induced hepatitis is a major problem which a physician encounters in his clinical practice. In view of increasing incidence of tuberculosis in our country a large number of infected individuals are started on Antituberculous (ATT) drugs and rifampicin is invariably part of the regimen. One of the major adverse effects of ATT drugs is drug- induced hepatitis which is characterized by elevation of liver enzymes and bilirubin. Hepatotoxicity is usually idiosyncratic or dose-dependent. Rifampicin causes transient elevation of transaminases in 10-20 percent of individuals and this does not warrant dose adjustments of the drug. Rarely rifampicin can lead to severe hepatitis with hyperbilirubinaemia and marked elevations of SGOT and SGPT and in some patients this can be fatal. The exact mechanism of Rifampicin induced hepatotoxicity is not known but it is postulated to be due to idiosyncratic reaction to rifampicin metabolites which may be directly toxic or induce an immunologically mediated liver injury. Rarely rifampicin may cause hyperbilirubinaemia without enzyme elevation. Here we report a patient with bilateral pulmonary tuberculosis who developed transient severe indirect hyperbilirubinaemia on rifampicin. On review of relevant literature we find that rifampicin can have a biphasic effect on bilirubin, an initial increase in indirect bilirubin and later normalization of bilirubin. We have reported this case because of its rarity in clinical practice. PMID:27190870

  18. Solar Irradiation of Bilirubin: An Experiment in Photochemical Oxidation

    ERIC Educational Resources Information Center

    Pillay A. E.; Salih, F. M.

    2006-01-01

    An experiment in photochemical oxidation, which deals with bilirubin, a well-known light-sensitive biological compound that is pedagogically ideal for photochemical experiments at tertiary institutes, is presented. The experiment would benefit students in chemistry who eventually branch out into the health sciences or biochemistry.

  19. Bilirubin chemistry and metabolism; harmful and protective aspects.

    PubMed

    Vítek, Libor; Ostrow, J Donald

    2009-01-01

    Unconjugated bilirubin (UCB), the principal mammalian bile pigment, is the end product of heme catabolism. Both belong to the superfamily of tetrapyrrolic compounds that serve multiple biological functions in animals and plants. Its six internal hydrogen bonds give UCB a unique structure responsible for its physico-chemical properties and biological effects. Like many weakly-polar, poorly-soluble compounds, UCB is transported in blood tightly bound to albumin, with less than 0.01% of total bilirubin circulating in an unbound form (free bilirubin, Bf). This fraction governs the diffusion of UCB into tissues, and therefore Bf is responsible for both its beneficial and toxic effects on cells. Although, UCB was long thought to be a non-functional waste product, recent studies have shown that the antioxidant effects of mildly elevated serum bilirubin levels, as well as activation of heme oxygenase, may protect against diseases associated with oxidative stress, such as atherosclerosis. By contrast, markedly elevated serum UCB levels may cause severe neurological damage, especially in neonates. The regulation of cellular UCB content, by its conjugation, oxidation, and export, are, therefore of paramount importance to cellular health. PMID:19754364

  20. The pharmacological features of bilirubin: the question of the century.

    PubMed

    Zahir, Farhana; Rabbani, Gulam; Khan, Rizwan Hasan; Rizvi, Shamim J; Jamal, Mohammad Sarwar; Abuzenadah, Adel M

    2015-09-01

    This review looks at the toxicity and metabolism of bilirubin in terms of its pharmacological potential. Its role has gained importance as more research has revealed the functional significance and interrelationship between the gasotransmitters nitric oxide and carbon monoxide. The biological actions of bilirubin have mostly been characterized in the high micromolar range where toxic effects occur. However, it could also prove to be an important cytoprotector for brain tissue, which is inherently less equipped for antioxidant defense. Plasma bilirubin levels negatively correlate to a number of disease states. Higher levels of bilirubin that are still within the normal range provide a protective effect to the body. The effects on various disorders could be tested using controlled pharmacological upregulation of the molecule with animal models. At nanomolar concentrations, considerable benefits have been obtained when the molecule was delivered pharmacologically under in vitro or in vivo test conditions, particularly in neurodegenerative disorders and after tissue or organ transplantation. The induction of heme oxygenase-1 (HMOX-1) via the activation of nuclear factor erythroid 2-related factor or the use of bile pigments in the harvesting of diseased tissue are novel applications, and like every new therapy, should be used with caution. HMOX-1 is tissue specific, and in exceptional states, such as schizophrenia and specific types of renal disorder, the same therapy may have disastrous effects. PMID:26208389

  1. Encephalopathy after persistent vomiting: Three cases of non-alcohol-related Wernicke's encephalopathy.

    PubMed

    Antel, K; Singh, N; Chisholm, B; Heckmann, J M

    2015-06-01

    Wernicke's encephalopathy (WE) is a medical emergency. Although WE is commonly viewed in the context of alcoholism, it can be caused by thiamine deficiency secondary to persistent vomiting. Non-alcohol-related WE may be more catastrophic in onset and less likely to present with the classic features than WE with alcoholism as a cause. We describe three cases of WE due to persistent vomiting without alcoholism in patients with hyperemesis gravidarum, drug-induced hyperlactataemia, and an acute gastrointestinal illness in an already malnourished individual. Our cases highlight the importance of recognising WE when undernutrition, which may be caused by gastrointestinal disease or surgery, or malignancy, is compounded by vomiting. Expert guidelines suggest that WE must be considered in the emergency room in any individual with disturbed consciousness of unknown cause. Treatment is with parenteral thiamine before glucose administration. PMID:26716155

  2. Distant Determination of Bilirubin Distribution in Skin by Multi-Spectral Imaging

    NASA Astrophysics Data System (ADS)

    Saknite, I.; Jakovels, D.; Spigulis, J.

    2011-01-01

    For mapping the bilirubin distribution in bruised skin the multi-spectral imaging technique was employed, which made it possible to observe temporal changes of the bilirubin content in skin photo-types II and III. The obtained results confirm the clinical potential of this technique for skin bilirubin diagnostics.

  3. Twenty-five years of progress in bilirubin metabolism (1952-77).

    PubMed Central

    Billing, B H

    1978-01-01

    This review deals with the development of our understanding of the chemistry of bilirubin and its glucuronide derivatives during the years 1952-1977. It examines the relation between haem metabolism and bilirubin formation and our present knowledge of hepatic transport of bilirubin. The heterogeneity of familial hyperbilirubinaemia is discussed. PMID:98394

  4. [Wernicke encephalopathy accompanying linitis plastica].

    PubMed

    Soós, Zsuzsanna; Salamon, Mónika; Oláh, Roland; Czégeni, Anna; Salamon, Ferenc; Folyovich, András; Winkler, Gábor

    2014-01-01

    Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke's disease. PMID:24379094

  5. [CLINICAL ASPECTS OF SEPTIC ENCEPHALOPATHY].

    PubMed

    Fesenko, O V; Sinopal'nikov, A I; Filatov, V V; Danishevsky, S V; Styrt, E A

    2016-01-01

    Septic encephalopathy is a form of general cerebral dysfunction caused by a systemic inflammatory reaction. Its investigation encounters enormous difficulties for the lack of reliable biological markers of neuronal lesions and methods for the evaluation of consciousness in severely ill patients. Hence, the importance of correct clinical interpretation of the character and magnitude of CNS activity. Examples are presented demonstrating the difficulty of interpreting disorders in CNS activity associated with evere community-acquired pneumonia. PMID:27172727

  6. Metabolic Causes of Epileptic Encephalopathy

    PubMed Central

    Pearl, Phillip L.

    2013-01-01

    Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria) and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies). Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category. PMID:23762547

  7. Isolated Posterior Fossa Involvement in Posterior Reversible Encephalopathy Syndrome

    PubMed Central

    Shimizu, Yukie; Tha, Khin Khin; Iguchi, Akihiro; Cho, Yuko; Yoshida, Atsushi; Fujima, Noriyuki; Tsukahara, Akiko; Shirato, Hiroki; Terae, Satoshi

    2013-01-01

    Summary Posterior reversible encephalopathy syndrome (PRES) is characterized by reversible vasogenic edema affecting the subcortical white matter of bilateral occipital and parietal lobes. We describe a case of isolated posterior fossa involvement of PRES which occurred during remission induction chemotherapy for T-cell acute lymphoblastic leukemia. Both the brainstem and cerebellum were extensively involved, but the supratentorial structures were completely spared. The follow-up magnetic resonance images revealed reversibility of most lesions. The knowledge of atypical radiological features of PRES is essential for prompt diagnosis. PMID:24199811

  8. Acute Liver Failure in Pregnancy: Causative and Prognostic Factors

    PubMed Central

    Sahai, Shweta; Kiran, Ravi

    2015-01-01

    Background/Aims: Acute liver failure (ALF) in pregnancy is often associated with a poor prognosis. In this single-center observational study we aim to study the incidence, causes, and factors affecting mortality in pregnant women with ALF. Patients and Methods: Sixty-eight pregnant women reporting with clinical features of liver dysfunction were enrolled as cases. Their clinical course was followed and laboratory studies were performed. The presence of ALF was defined as the appearance of encephalopathy. The results were compared with a control group of 16 nonpregnant women presenting with similar complaints. The cases were further subdivided into two groups of survivors and nonsurvivors and were compared to find out the factors that contribute to mortality. Results: ALF was seen in significantly more number of pregnant women than the controls (P = 0.0019). The mortality rate was also significantly higher (P = 0.0287). Hepatitis E virus (HEV) caused jaundice in a higher number of pregnant women (P < 0.001). It also caused ALF in majority (70.3%) of pregnant women, but HEV infection was comparable between the survivors and nonsurvivors (P = 0.0668), hence could not be correlated with mortality. Conclusions: Pregnant women appear to be more susceptible for HEV infection and development of ALF. The mortality of jaundiced pregnant women increased significantly with appearance of ALF, higher bilirubin, lower platelet count, higher international normalized ratio, and spontaneous delivery. PMID:25672236

  9. Posterior reversible encephalopathy syndrome is not associated with mutations in aquaporin-4.

    PubMed

    Matiello, Marcelo; Muralidharan, Rajanandini; Sun, David; Rabinstein, Alejandro A; Weinshenker, Brian G

    2015-08-01

    Posterior reversible encephalopathy syndrome (PRES) is characterized by acute reversible subcortical vasogenic edema that is typically bilateral and self-limiting. It preferentially affects posterior regions of the brain. Clinical manifestations include encephalopathy, seizures, headache, and cortical blindness. PRES may be precipitated by hypertensive crises such as eclampsia and by immunosuppressive agents. The pathophysiology of PRES is incompletely understood. Disordered cerebral autoregulation leading to protein and fluid extravasation is thought to be important.(1) Other theories implicate endothelial dysfunction or vasospasm.(2). PMID:27066556

  10. Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES).

    PubMed

    Raj, Shashi; Killinger, James; Overby, Philip

    2013-10-01

    Children with sickle cell disease have a very high risk of lifelong neurologic morbidity and mortality. Cerebrovascular accidents are a known complication in children with sickle cell disease. Posterior reversible encephalopathy syndrome is a constellation of acute neurologic findings increasingly recognized in pediatric critical care population with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial cell dysfunction. This report, for the first time, describes a young adult with sickle cell disease who developed posterior reversible encephalopathy syndrome following blood transfusion. PMID:22899796

  11. Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.

    PubMed

    Lee, Yonghyun; Lee, Soyoung; Lee, Dong Yun; Yu, Byeongjun; Miao, Wenjun; Jon, Sangyong

    2016-08-26

    Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers, their clinical translation has been limited. Ideally, materials used for the purpose should be biocompatible and nontoxic, provide "on-demand" drug release in response to internal or external stimuli, allow large-scale manufacturing, and exhibit intrinsic anticancer efficacy. We present multistimuli-responsive nanoparticles formed from bilirubin, a potent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity. Exposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS) or external laser light causes rapid disruption of the BRNP nanostructure as a result of a switch in bilirubin solubility, thereby releasing encapsulated drugs. In a xenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as a drug-delivery carrier as well as a companion medicine for effectively treating cancers. PMID:27485478

  12. Bilirubin oxidation products (BOXes): synthesis, stability and chemical characteristics

    PubMed Central

    Wurster, W. L.; Pyne-Geithman, G. J.; Peat, I. R.; Clark, J. F.

    2009-01-01

    Summary Bilirubin oxidation products (BOXes) have been a subject of interest in neurosurgery because they are purported to be involved in subarachnoid hemorrhage induced cerebral vasospasm. There is a growing body of information concerning their putative role in vasospasm; however, there is a dearth of information concerning the chemical and biochemical characteristics of BOXes. A clearer understanding of the synthesis, stability and characteristics of BOXes will be important for a better understanding of the role of BOXes post subarachnoid hemorrhage. We used hydrogen peroxide to oxidize bilirubin and produce BOXes. BOXes were extracted and analyzed using conventional methods such as HPLC and mass spectrometry. Characterization of the stability BOXes demonstrates that light can photodegrade BOXes with a t1/2 of up to 10 h depending upon conditions. Mixed isomers of BOXes have an apparent extinction coefficient of ε = 6985, and a λmax of 310 nm. BOXes are produced by the oxidation of bilirubin, yielding a mixture of isomers: 4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX A) and 3-methyl-5-oxo-4-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX B). The BOXes are photodegraded by ambient light and can be analyzed spectrophotometrically with their extinction coefficient as well as with HPLC or mass spectrometry. Their small molecular weight and photodegradation may have made them difficult to characterize in previous studies. PMID:18456996

  13. Autoimmune encephalopathy associated with thyroid autoantibodies as the cause of reversible cognitive impairment

    PubMed Central

    Maroz, Natallia; Bernhardt, Nechama; Chow, Robert Dobbin

    2012-01-01

    We herewith describe a patient with acute confusion, expressive aphasia and generalized seizures. A through workup excluded most causes of encephalopathy. He was, however, found to have TSH=18.6 MIU/ml, T3reverse=0.44nmol/L, T4=0.8ng/dl and Anti-Thyroid-Peroxidase AB titer >1000 IU/ml. Based on the above findings the patient was diagnosed with Hashimoto's encephalopathy and his mental status showed dramatic improvement (MMS 30/30) with high dose prednisone. Hashimoto's encephalopathy is rare disorder of presumed autoimmune origin characterized by cognitive decline, seizures, neuro-psychiatric symptoms, high titers of Anti-Thyroid-Peroxidase AB, and a positive response to steroids. PMID:23882359

  14. [FOLFIRINOX-induced hyperammonemic encephalopathy in a patient with pancreatic cancer].

    PubMed

    Yamada, Ikuhiro; Ozaka, Masato; Ishii, Hiroshi; Inoue, Dai; Matsuyama, Masato; Takano, Kouichi; Igarashi, Masahiro

    2014-11-01

    Hyperammonemic encephalopathy is a rare adverse event of chemotherapies based on high-dose 5-fluorouracil. We present a woman in her 70s with metastatic pancreatic adenocarcinoma who underwent FOLFIRINOX therapy. She developed acute onset disturbance of consciousness after completing the first 5-fluorouracil infusion cycle (2400 mg/m(2)/46h). We suspected hyperammonemic encephalopathy induced by 5-fluorouracil and administered branched-chain amino acids solutions and she recovered within a few hours of treatment. Brain computed tomography and magnetic resonance imaging revealed no abnormal findings. She subsequently received chemotherapy with gemcitabine and developed no further hyperammonemia. To the best of our knowledge, this is the first report of FOLFIRINOX-induced hyperammonemic encephalopathy in a patient with pancreatic cancer. PMID:25373377

  15. Palatal-Myoclonus as a Presentation of Hashimoto Encephalopathy: an interesting case report

    PubMed Central

    Shahidi, Gholam Ali; Rohani, Mohammad; Nabavi, Mohammad; Aghaei, Mahbubeh; Akhoundi, Fahimeh Haji

    2013-01-01

    Objective Hashimoto encephalopathy (HE) is known as a steroid- responsive encephalopathy associated with autoimmune thyroiditis or nonvascular inflammation-related autoimmune meningoencephalitis. The average age of onset of HE is approximately 50 years; and it is more common in women. The onset of HE may be acute or subacute. The course of most HE cases is relapsing and remitting, which is similar to that of vasculitis and stroke. Methods In this article, we present a previously healthy 32 years old;veterinarian male with palatal myoclonus, as a rare presentation of this disorder, and review the neurologic aspects of hashimoto encephalitis. Results The clinical presentation of HE is characterized by progressive cognitive decline tremor, transient aphasia, seizures, abnormal gait, sleep disorder and stroke-like episodes. Myoclonus, either generalized or multifocal, and tremor, often of the bilateral upper extremities, is the most frequently observed involuntary movements in HE. Conclusion The rapidly progressive cognitive dysfunction and encephalopathies observed. PMID:24454425

  16. Susceptibility of European red deer (Cervus elaphus elaphus) to alimentary challenge with bovine spongiform encephalopathy.

    PubMed

    Dagleish, Mark P; Martin, Stuart; Steele, Philip; Finlayson, Jeanie; Eaton, Samantha L; Sisó, Sílvia; Stewart, Paula; Fernández-Borges, Natalia; Hamilton, Scott; Pang, Yvonne; Chianini, Francesca; Reid, Hugh W; Goldmann, Wilfred; González, Lorenzo; Castilla, Joaquín; Jeffrey, Martin

    2015-01-01

    European red deer (Cervus elaphus elaphus) are susceptible to the agent of bovine spongiform encephalopathy, one of the transmissible spongiform encephalopathies, when challenged intracerebrally but their susceptibility to alimentary challenge, the presumed natural route of transmission, is unknown. To determine this, eighteen deer were challenged via stomach tube with a large dose of the bovine spongiform encephalopathy agent and clinical signs, gross and histological lesions, presence and distribution of abnormal prion protein and the attack rate recorded. Only a single animal developed clinical disease, and this was acute with both neurological and respiratory signs, at 1726 days post challenge although there was significant (27.6%) weight loss in the preceding 141 days. The clinically affected animal had histological lesions of vacuolation in the neuronal perikaryon and neuropil, typical of transmissible spongiform encephalopathies. Abnormal prion protein, the diagnostic marker of transmissible encephalopathies, was primarily restricted to the central and peripheral nervous systems although a very small amount was present in tingible body macrophages in the lymphoid patches of the caecum and colon. Serial protein misfolding cyclical amplification, an in vitro ultra-sensitive diagnostic technique, was positive for neurological tissue from the single clinically diseased deer. All other alimentary challenged deer failed to develop clinical disease and were negative for all other investigations. These findings show that transmission of bovine spongiform encephalopathy to European red deer via the alimentary route is possible but the transmission rate is low. Additionally, when deer carcases are subjected to the same regulations that ruminants in Europe with respect to the removal of specified offal from the human food chain, the zoonotic risk of bovine spongiform encephalopathy, the cause of variant Creutzfeldt-Jakob disease, from consumption of venison is probably

  17. The why and wherefore of hepatic encephalopathy.

    PubMed

    Grover, Vijay Pb; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary Me; Cook, Nicola A; Taylor-Robinson, Simon D

    2015-01-01

    Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that "those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief ". He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. PMID:26719720

  18. The why and wherefore of hepatic encephalopathy

    PubMed Central

    Grover, Vijay PB; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary ME; Cook, Nicola A; Taylor-Robinson, Simon D

    2015-01-01

    Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that “those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief ”. He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. PMID:26719720

  19. Bilirubin binding with liver cystatin induced structural and functional changes.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

    Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279 × 10(4) M(-1). The cystatin binding with

  20. [Wernicke encephalopathy and Korsakoff's psychosis: clinical-pathophysiological correlation, diagnostics and treatment].

    PubMed

    Sivolap, Iu P; Damulin, I V

    2013-01-01

    Wernicke's encephalopathy and Korsakoff's psychosis are severe unfavorable forms of alcoholic brain damage with poor prognosis. Thiamine deficiency represents a common cause of both diseases. In many cases, Korsakoff's psychosis develops in the outcome of Wernicke's encephalopathy, which, along with the general etiology, lets talk about a single disease - Wernicke-Korsakoff syndrome, acute (usually reversible) stage of which is Wernicke's encephalopathy and a chronic one (often irreversible) is Korsakoff psychosis. The dramatic paradox of Wernicke's encephalopathy is that in most cases it is difficult to detect, but early diagnosed cases are quite easy to cure. Unrecognized and therefore go untreated Wernicke's encephalopathy is a serious threat to the health and lives of patients, worsens the processes of brain aging and increases the risk of Alzheimer's disease in later life. The basic approach to the treatment of Wernicke-Korsakoff syndrome is long-term parenteral administration of thiamine, often in high doses. As an adjuvant means of therapy memantine is considered. PMID:23887463

  1. Antecedents of Neonatal Encephalopathy in the Vermont Oxford Network Encephalopathy Registry

    PubMed Central

    Bingham, Peter; Edwards, Erika M.; Horbar, Jeffrey D.; Kenny, Michael J.; Inder, Terrie; Pfister, Robert H.; Raju, Tonse; Soll, Roger F.

    2012-01-01

    BACKGROUND: Neonatal encephalopathy (NE) is a major predictor of death and long-term neurologic disability, but there are few studies of antecedents of NE. OBJECTIVES: To identify antecedents in a large registry of infants who had NE. METHODS: This was a maternal and infant record review of 4165 singleton neonates, gestational age of ≥36 weeks, meeting criteria for inclusion in the Vermont Oxford Network Neonatal Encephalopathy Registry. RESULTS: Clinically recognized seizures were the most prevalent condition (60%); 49% had a 5-minute Apgar score of ≤3 and 18% had a reduced level of consciousness. An abnormal maternal or fetal condition predated labor in 46%; maternal hypertension (16%) or small for gestational age (16%) were the most frequent risk factors. In 8%, birth defects were identified. The most prevalent birth complication was elevated maternal temperature in labor of ≥37.5°C in 27% of mothers with documented temperatures compared with 2% to 3.2% in controls in population-based studies. Clinical chorioamnionitis, prolonged membrane rupture, and maternal hypothyroidism exceeded rates in published controls. Acute asphyxial indicators were reported in 15% (in 35% if fetal bradycardia included) and inflammatory indicators in 24%. Almost one-half had neither asphyxial nor inflammatory indicators. Although most infants with NE were observably ill since the first minutes of life, only 54% of placentas were submitted for examination. CONCLUSIONS: Clinically recognized asphyxial birth events, indicators of intrauterine exposure to inflammation, fetal growth restriction, and birth defects were each observed in term infants with NE, but much of NE in this large registry remained unexplained. PMID:23071210

  2. Association of bilirubin and malondialdehyde levels with retinopathy in type 2 diabetes mellitus

    PubMed Central

    Dave, Apoorva; Kalra, Pramila; Gowda, B. H. Rakshitha; Krishnaswamy, Malavika

    2015-01-01

    Introduction: Bilirubin as an antioxidant and malondialdehyde (MDA) as an oxidant have been shown to be associated with various complications of type 2 diabetes mellitus (DM). Aims and Objectives: The aim was to measure the levels of serum bilirubin and MDA in type 2 DM patients with and without diabetic retinopathy (DR) and to correlate them with severity of DR. Materials and Methods: A total number of 120 subjects out of which 40 were controls without type 2 DM and the rest 80 were type 2 DM patients were included in the study. Of those 80 diabetics, 44 patients did not have DR and 36 patients had DR. Results: The total bilirubin, direct bilirubin, indirect bilirubin were higher in controls as compared to cases (P = 0.017, 0.033, 0.024). Serum MDA levels were found to be higher in diabetics as compared to controls (P = 0.00). The values of all the three parameters, that is, total bilirubin, direct bilirubin and indirect bilirubin were lower in patients with retinopathy as compared to those without retinopathic changes (P = 0.00, 0.020, and 0.007). Subjects were assigned to quartiles based on serum total bilirubin concentration. The prevalence of DR was significantly lower among persons with the highest bilirubin quartile compared to those with the lowest quartile. The severity of DR was inversely proportional to the total bilirubin levels (P = 0.001). The multiple logistic regression analysis showed total bilirubin to be associated with prevalence of DR (P = 0.035). Conclusions: The levels of total bilirubin were significantly lower in patients with DR and also in the late stages of retinopathy as compared to those without retinopathy and in controls but MDA levels did not show any association with DR. PMID:25932393

  3. Unconjugated Bilirubin and an Increased Proportion of Bilirubin Monoconjugates in the Bile of Patients with Gilbert's Syndrome and Crigler-Najjar Disease

    PubMed Central

    Fevery, Johan; Blanckaert, Norbert; Heirwegh, Karel P. M.; Préaux, Anne-Marie; Berthelot, Pierre

    1977-01-01

    Bilirubin pigments were studied in the bile of 20 normal adults, 25 patients with Gilbert's syndrome, 9 children with Crigler-Najjar disease, and 6 patients with hemolysis, to determine how a deficiency of hepatic bilirubin UDP-glucuronosyltransferase would affect the end products of bilirubin biotransformation. In the bile from patients with Gilbert's syndrome, a striking increase was found in the proportion of bilirubin monoconjugates (48.6±9.8% of total conjugates) relative to that in normal bile (27.2±7.8%). This increase was even more pronounced in children with Crigler-Najjar disease, in whom, even in the most severe cases, glucuronide could always be demonstrated in the bile. Furthermore, unconjugated bilirubin-IXα was unquestionably present in the bile of these children and amounted to 30-57% of their total bilirubin pigments (<1% in the controls). It was not possible to predict from the biliary bilirubin composition whether a child would respond to phenobarbital therapy or not. Bile composition was normal in patients with hemolysis, except when there was associated deficiency of hepatic glucuronosyltransferase. Therefore, the observed alterations were not a simple consequence of unconjugated hyperbilirubinemia. The present findings suggest that Crigler-Najjar disease represents a more pronounced expression than Gilbert's syndrome of a common biochemical defect. Hepatic bilirubin UDP-glucuronosyltransferase deficiency leads to decreased formation of diconjugates with an ensuing increase in the proportion of bilirubin monoconjugates in bile; in the most severe cases, an elevated content of biliary unconjugated bilirubin is also found. PMID:409736

  4. Comparison in different species of biliary bilirubin-IX alpha conjugates with the activities of hepatic and renal bilirubin-IX alpha-uridine diphosphate glycosyltransferases.

    PubMed Central

    Fevery, J; Van de Vijver, M; Michiels, R; Heirwegh, K P

    1977-01-01

    The bilrubin-IXalpha conjugates in bile and the activities of bilirubin-IX alpha--UDP-glycosyltransferases in liver and kidney were determined for ten species of mammals and for the chicken. 1. In the mammalian species, bilirubin-IX alpha glucuronide was the predominant bile pigment. Excretion of neutral glycosides was unimportant, except in the cat, the mouse, the rabbit and the dog, where glucose and xylose represented 12--41% of total conjugating groups bound to bilirubin-IX alpha. In chicken bile, glucoside and glucuronide conjugates were of equal importance. They probably represent only a small fraction of the total bile pigment. 2. The transferase activities in liver showed pronounced species variation. This was also apparent with regard to activation by digitonin, pH optimum and relative activities of transferases acting on either UDP-glucuronic acid or neutral UDP-sugars. 3. Man, the dog, the cat and the rat excrete bilirubin-IX alpha largely as diconjugated derivatives. In general, diconjugated bilirubin-IX alpha could also be synthesized in vitro with liver homogenate, bilirubin-IX alpha and UDP-sugar. In contrast, for the other species examined, bilirubin pigments consisted predominantly of monoconjugated bilirubin-IX alpha. Synthesis in vitro with UDP-glucuronic acid, UDP-glucose or UDP-xylose as the sugar donor led exclusively to the formation of monoconjugated bilirubin-IX alpha. 4. The transferase activities in the kidney were restricted to the cortex and were important only for the rat and the dog. No activity at all could be detected for several species, including man. 5. Comparison of the transferase activities in liver with reported values of the maximal rate of excretion in bile suggests a close linkage between conjugation and biliary secretion of bilirubin-IX alpha. PMID:407905

  5. Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin.

    PubMed

    Bacigalupo, A; Oneto, R; Bruno, B; Soracco, M; Lamparelli, T; Gualandi, F; Occhini, D; Raiola, A; Mordini, N; Berisso, G; Bregante, S; Dini, G; Lombardi, A; Lint, M V; Brand, R

    1999-09-01

    Transplant-related mortality (TRM) following allo- geneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin <0.9 and/or BUN <21) and 93 patients with score 2 (high risk) (bilirubin >/=0.9 and BUN >/=21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P < 0.01), after adjustment for year of transplant (P < 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be eligible for programs designed to intensify prophylaxis of post

  6. A Case of Chronic Wernicke's Encephalopathy: A Neuropsychological Study.

    PubMed

    Oudman, Erik; Van der Stigchel, Stefan; Postma, Albert; Wijnia, Jan W; Nijboer, Tanja C W

    2014-01-01

    A 54-year-old woman was referred to our Korsakoff Center because of extensive cognitive problems following acute Wernicke's encephalopathy (WE). She had a relatively short history of alcohol abuse and was found lying on the floor in her home by her son. After 5 days without treatment, she was diagnosed with WE in a general hospital. During the course of the disease, minimal change to the acute situation occurred, with chronic confusion, attention deficits, and incoherent behavior symptoms most notable unlike classical Korsakoff's syndrome. Neuropsychological assessment after 4 and 16 months after admission to the hospital revealed global cognitive decline, with striking impairments in attentional, executive, and memory functions. The present case study suggests that the state of confusion and the neuropsychological symptoms in WE can become chronic in case of very late treatment. We therefore recommend that confused alcoholics should receive appropriate parenteral thiamine according to the current clinical standards. PMID:24904442

  7. Current understanding and neurobiology of epileptic encephalopathies.

    PubMed

    Auvin, Stéphane; Cilio, Maria Roberta; Vezzani, Annamaria

    2016-08-01

    Epileptic encephalopathies are a group of diseases in which epileptic activity itself contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone. These impairments can worsen over time. This concept has been continually redefined since its introduction. A few syndromes are considered epileptic encephalopathies: early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, epilepsy of infancy with migrating focal seizures, West syndrome or infantile spasms, Dravet syndrome during infancy, Lennox-Gastaut syndrome, epileptic encephalopathy with continuous spikes-and-waves during sleep, and Landau-Kleffner syndrome during childhood. The inappropriate use of this term to refer to all severe epilepsy syndromes with intractable seizures and severe cognitive dysfunction has led to confusion regarding the concept of epileptic encephalopathy. Here, we review our current understanding of those epilepsy syndromes considered to be epileptic encephalopathies. Genetic studies have provided a better knowledge of neonatal and infantile epilepsy syndromes, while neuroimaging studies have shed light on the underlying causes of childhood-onset epileptic encephalopathies such as Lennox-Gastaut syndrome. Apart from infantile spasm models, we lack animal models to explain the neurobiological mechanisms at work in these conditions. Experimental studies suggest that neuroinflammation may be a common neurobiological pathway that contributes to seizure refractoriness and cognitive involvement in the developing brain. PMID:26992889

  8. Bilirubin release induced by tumor necrosis factor in combination with galactosamine is toxic to mice.

    PubMed

    Van Molle, W; Libert, C

    2003-08-01

    Application of tumor necrosis factor (TNF) in combination with galactosamine (GalN) in mice causes severe apoptosis of hepatocytes, resulting in complete destruction of the liver. Administration of high levels of unconjugated bilirubin and abnormally high production of unconjugated bilirubin have been reported to cause liver damage and are associated with several human pathologies. Serum alanine aminotransferase as well as total and direct bilirubin levels in mice were determined. Bilirubin levels are shown to significantly increase after a challenge with TNF/GalN in mice. Pretreatment with a heme oxygenase-1 inhibitor significantly prevents this release in bilirubin and offers significant protection against TNF/GalN-induced lethality. A correlation between the release of unconjugated bilirubin and the toxicity accompanied with this release is provided. PMID:12906872

  9. Paroxysmal Amnesia Attacks due to Hashimoto's Encephalopathy

    PubMed Central

    Nar Senol, Pelin; Bican Demir, Aylin; Bora, Ibrahim; Bakar, Mustafa

    2016-01-01

    Hashimoto's encephalopathy is a rare disease which is thought to be autoimmune and steroid responsive. The syndrome is characterized by cognitive impairment, encephalopathy, psychiatric symptoms, and seizures associated with increased level of anti-thyroid antibodies. The exact pathophysiology underlying cerebral involvement is still lesser known. Although symptoms suggest a nonlesional encephalopathy in most of the cases, sometimes the clinical appearance can be subtle and may not respond to immunosuppressants or immunomodulatory agents. Here we report a case who presented with drowsiness and amnestic complaints associated with paroxysmal electroencephalography (EEG) abnormalities which could be treated only with an antiepileptic drug. PMID:27034679

  10. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  11. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  12. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  13. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  14. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  15. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  16. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  17. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  18. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  19. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  20. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    PubMed

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-01-01

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

  1. Unconjugated bilirubin mediates heme oxygenase-1-induced vascular benefits in diabetic mice.

    PubMed

    Liu, Jian; Wang, Li; Tian, Xiao Yu; Liu, Limei; Wong, Wing Tak; Zhang, Yang; Han, Quan-Bin; Ho, Hing-Man; Wang, Nanping; Wong, Siu Ling; Chen, Zhen-Yu; Yu, Jun; Ng, Chi-Fai; Yao, Xiaoqiang; Huang, Yu

    2015-05-01

    Heme oxygenase-1 (HO-1) exerts vasoprotective effects. Such benefit in diabetic vasculopathy, however, remains unclear. We hypothesize that bilirubin mediates HO-1-induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for 2 weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and endothelial NO synthase (eNOS) phosphorylation in db/db mouse aortas, which were reversed by the HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin, and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by the Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. Hemin and bilirubin reversed high glucose-induced reductions in Akt and eNOS phosphorylation and NO production. The effect of hemin but not bilirubin was inhibited by biliverdin reductase silencing virus. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1-induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin, which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy. PMID:25475440

  2. Encephalopathy

    MedlinePlus

    ... pressure in the skull, prolonged exposure to toxic elements (including solvents, drugs, radiation, paints, industrial chemicals, and certain metals), chronic progressive trauma, poor nutrition, ...

  3. Treatment of Overt Hepatic Encephalopathy.

    PubMed

    Sussman, Norman L

    2015-08-01

    Hepatic encephalopathy (HE) is defined by an altered mental status in the setting of portosystemic shunting, with or without cirrhosis. The basis of HE is probably multi-factorial, but increased ammonia delivery to the brain is thought to play a pivotal role. Medical therapies have typically focused on reducing blood ammonia concentrations. These measures are moderately effective, but further improvements will require identification of new therapeutic targets. Two medications, lactulose and rifaximin, are currently approved for the treatment of HE in the USA - new compounds are available off-label, and are in clinical trials. The presence of HE is associated with a higher risk of death in cirrhotic patients. Liver transplantation typically cures HE, but HE does not increase the MELD score, and therefore does not contribute to the likelihood of liver transplantation. PMID:26195208

  4. Suicide and Chronic Traumatic Encephalopathy.

    PubMed

    Iverson, Grant L

    2016-01-01

    For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships. PMID:26449269

  5. Bovine Spongiform Encephalopathy: Atypical Pros and Cons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that affect several mammalian species including human beings. Four animal TSE agents have been reported: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink encephalopath...

  6. Neuroimaging in Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Krishnan, Pradeep; Shroff, Manohar

    2016-09-01

    Magnetic resonance (MR) imaging is emerging as one of the most important tools in identifying the etiology of neonatal encephalopathy as well as in predicting long-term outcomes. This makes it imperative to have a broader understanding of normal myelination of the neonatal brain on MR imaging and to be familiar with the spectrum of imaging features in ischemic and non-ischemic neonatal encephalopathy. Hypoxic ischemic injury (HIE) is one of the most common causes of neonatal encephalopathy and imaging appearances are influenced by factors such as the stage of maturation of the neonatal brain and severity as well as duration of ischemic insult. Other common causes of neonatal encephalopathy include infectious diseases, congenital disorders and inborn errors of metabolism. PMID:26909496

  7. Hepatic encephalopathy: An approach to its multiple pathophysiological features.

    PubMed

    Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

    2012-03-27

    Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in

  8. Hepatic encephalopathy: An approach to its multiple pathophysiological features

    PubMed Central

    Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

    2012-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in

  9. Purification, characterization and decolorization of bilirubin oxidase from Myrothecium verrucaria 3.2190

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myrothecium verrucaria 3.2190 is a nonligninolytic fungus that produces bilirubin oxidase. Both Myrothecium verrucaria and the extracellular bilirubin oxidase were tested for their ability to decolorize indigo carmine. The biosorption and biodegradation of the dye were detected during the process of...

  10. Protein-Support Interactions for Rationally Designed Bilirubin Oxidase Based Cathode: A Computational Study.

    PubMed

    Matanovic, Ivana; Babanova, Sofia; Chavez, Madelaine Seow; Atanassov, Plamen

    2016-04-21

    An example of biocathode based on bilirubin oxidase (BOx) was used to demonstrate how density functional theory can be combined with docking simulations in order to study the interface interactions between the enzyme and specifically designed electrode surface. The electrode surface was modified through the adsorption of bilirubin, the natural substrate for BOx, and the prepared electrode was electrochemically characterized using potentiostatic measurements. The experimentally determined current densities showed that the presence of bilirubin led to significant improvement of the cathode operation. On the basis of the computationally calculated binding energies of bilirubin to the graphene support and BOx and the analysis of the positioning of bilirubin relative to the support and T1 Cu atom of the enzyme, we hypothesize that the bilirubin serves as a geometric and electronic extension of the support. The computational results further confirm that the modification of the electrode surface with bilirubin provides an optimal orientation of BOx toward the support but also show that bilirubin facilitates the interfacial electron transfer by decreasing the distance between the electrode surface and the T1 Cu atom. PMID:27015361

  11. Reproducibility and intragastric variation of duodenogastric reflux using ambulatory gastric bilirubin monitoring.

    PubMed

    Manifold, D K; Anggiansah, A; Marshall, R E; Owen, W J

    2001-01-01

    Duodenogastric reflux has long been considered to be important in the pathogenesis of many gastric disorders that exhibit regional variation within the stomach. Ambulatory gastric bilirubin monitoring is a new technique and, although extensively validated, reproducibility and gastric regional variation have not been specifically addressed. Fourteen patients with symptoms of gastroesophageal reflux and 12 healthy subjects underwent 24-h ambulatory gastric bilirubin monitoring with the bilirubin sensor in the upper stomach. Gastric bilirubin monitoring with two simultaneous bilirubin probes, one in the upper stomach and the other in the antrum, was performed on a separate occasion. Gastric bilirubin exposure in the initial and repeat studies showed a good correlation (R = 0.60, P < 0.01). Gastric bilirubin exposure in the upper stomach and the antrum showed a high degree of correlation (R = 0.90, P < 0.01). In conclusion, reproducible results are obtained with ambulatory gastric bilirubin monitoring and duodenogastric reflux does not exhibit significant regional variation within the stomach. PMID:11270798

  12. Bilirubin content and 4-nitrophenol glucuronosyltransferase activity in Gunn rat liver.

    PubMed

    Celier, C; Foliot, A

    1984-04-01

    The purpose of this study was to determine whether the hepatic content of bilirubin could influence liver 4-nitrophenolglucuronosyltransferase (4-NP-GT) in the Gunn rat. In animals fed on a 45% lipid diet, compared with rats fed on a normal lipid diet (3%), the bilirubin content of the hepatic microsomal fraction decreased and the bilirubin/protein ratio was reduced. 4-NP-GT activities were comparable in both groups. Administration of clofibrate to Gunn rats greatly enhanced the bilirubin content of liver microsomal fraction. Since this treatment raised the microsomal protein content, the bilirubin/protein ratio was not modified. No significant change in 4-NP-GT was noted. After bilirubin perfusion in Gunn and Wistar rats, no change was observed in hepatic monooxygenase activities or in 4-NP-GT, although the bilirubin/protein ratio was dramatically increased in the microsomal fraction. From these results the low activity of liver 4-NP-GT in Gunn rats does not seem directly related to the hepatic content of bilirubin. PMID:6421531

  13. Measurement of serum bilirubin and its mono- and diconjugates: application to patients with hepatobiliary disease.

    PubMed Central

    Scharschmidt, B F; Blanckaert, N; Farina, F A; Kabra, P M; Stafford, B E; Weisiger, R A

    1982-01-01

    A technique has recently been described by Blanckaert and his colleagues that specifically and accurately quantifies unconjugated bilirubin, diconjugated bilirubin, and the C-8 and C-12 isomers of monoconjugated bilirubin. This technique has now been used to determine the distribution pattern of bilirubin and its ester conjugates in 91 sera from 65 patients with hepatobiliary disease, and the results were compared with two conventional diazo assays. Both diazo assays yielded values for total bilirubin concentration that were markedly and unpredictably higher than those obtained by the new technique, and the direct-reacting fraction by diazo assay showed little or no agreement with the fraction of total ester conjugates determined by the new method. Previous studies using the new method had shown that bilirubin conjugates are undetectable in sera from healthy adults or individuals with Gilbert's syndrome, but they were found in 89 of the 91 present patient sera. The fraction of total serum bilirubin represented by C-8 monoconjugates, C-12 monoconjugates, diconjugates, and total ester conjugates was higher in patients with biliary obstruction than in those with parenchymal liver disease, but extensive overlap between groups prevented determination of these conjugated species from being diagnostically useful. Overall, bilirubin ester conjugates in serum consisted of 30% C-8 monoconjugates, 37% C-12 monoconjugates, and 33% diconjugates, while urine contained predominantly diconjugates. PMID:7095558

  14. Relationship of Bilirubin Levels in Infancy to Later Intellectual Development. Interim Report No. 20.

    ERIC Educational Resources Information Center

    Rubin, Rosalyn A.; And Others

    The relationship of bilirubin (a red bile pigment that is sometimes found in the urine and occurs in the blood and tissues in jaundice) in infancy to later intellectual development was investigated in 241 infants with moderately elevated and high bilirubin levels. Ss were administered motor, psycholinguistic, and intelligence tests at age 8…

  15. Hepatocellular uptake of sulfobromophthalein and bilirubin is selectively inhibited by an antibody to the liver plasma membrane sulfobromophthalein/bilirubin binding protein.

    PubMed Central

    Stremmel, W; Berk, P D

    1986-01-01

    To clarify sulfobromophthalein (BSP) and bilirubin uptake mechanisms, isolated rat hepatocytes were incubated with [35S]BSP. The initial uptake velocity (V0), determined from the first, linear portion of the cumulative uptake curve, was saturable (Michaelis constant [Km] = 6.2 +/- 0.5 microM; Vmax = 638 +/- 33 pmol X min-1 per 10(5) hepatocytes), maximal at 37 degrees C and pH 7.4, and competitively inhibited by bilirubin, but not by taurocholate, cholate, or oleate. Preloading with unlabeled BSP led to trans-stimulation of V0. Sodium substitution or pretreatment of hepatocytes with ouabain or metabolic inhibitors had no effect on V0; trypsin reduced V0 by 39% (P less than 0.001). A rabbit antiserum to the rat liver plasma membrane (LPM)-BSP/bilirubin binding protein selectively reduced V0 of 5 microM [35S]BSP and [14C]bilirubin by 41 and 42%, respectively (P less than 0.01); uptakes of [3H]oleate, [3H]cholate and [3H]taurocholate were not affected. Hence, the LPM-BSP/bilirubin binding protein plays a role in the carrier-mediated uptake of BSP and bilirubin by hepatocytes. PMID:3745441

  16. Revalidation and rationale for high pKa values of unconjugated bilirubin

    PubMed Central

    Ostrow, J Donald; Mukerjee, Pasupati

    2007-01-01

    Background Our prior solvent partition analysis, published in 1992, yielded pKa values for unconjugated bilirubin of about 8.1 and 8.4, but these results have been challenged and studies by other methods have suggested pKa values below 5.0. Methods We repeated our published solvent partition studies, using 14C-unconjugated bilirubin highly purified by extraction of residual labeled impurities from CHCl3 into an aqueous buffer, pH 7.0. Partition ratios at six pH values from 5.0 to 9.0 were determined by radioassay and compared with our prior values obtained by diazo assay. Results At pH values ranging from 4.8 to 9.2, stable aqueous/chloroform 14C-partition ratios did not differ significantly from our published partition ratios based on diazo assay. Conclusion These results support the high pKa values of unconjugated bilirubin, above 8.0, derived from our earlier solvent partition study. In both studies, our measurements were based on the rapid analysis of clearly under-saturated solutions of highly-purified bilirubin over a wide pH range, using properly purified and preserved solvents. No previous direct estimate of the aqueous pKa values of unconjugated bilirubin meets all these preconditions. Three theoretical factors acting in combination, each related to the unique, extensive internal H-bonding of the -COOH groups, are proposed to support high pKa values of unconjugated bilirubin in water: a) donation of an H-bond from the -OH moiety of the -COOH group, which is broken on ionization; b) hindered solvation of the -COO- group after ionization; and c) restricted rotation of the -COO- and -COOH groups. Our findings and rationale rebut methodological and theoretical criticisms leveled against our prior work. High pKa values for unconjugated bilirubin dictate that: a) bilirubin diacid, which readily diffuses across membranes and can cause neurotoxicity, is the dominant unbound bilirubin species of unconjugated bilirubin in plasma at physiological pH; b) at the near

  17. Metabolism of bilirubin by human cytochrome P450 2A6

    SciTech Connect

    Abu-Bakar, A'edah; Arthur, Dionne M.; Wikman, Anna S.; Rahnasto, Minna; Juvonen, Risto O.; Vepsäläinen, Jouko; Raunio, Hannu; Ng, Jack C.; Lang, Matti A.

    2012-05-15

    The mouse cytochrome P450 (CYP) 2A5 has recently been shown to function as hepatic “Bilirubin Oxidase” (Abu-Bakar, A., et al., 2011. Toxicol. Appl. Pharmacol. 257, 14–22). To date, no information is available on human CYP isoforms involvement in bilirubin metabolism. In this paper we provide novel evidence for human CYP2A6 metabolising the tetrapyrrole bilirubin. Incubation of bilirubin with recombinant yeast microsomes expressing the CYP2A6 showed that bilirubin inhibited CYP2A6-dependent coumarin 7-hydroxylase activity to almost 100% with an estimated K{sub i} of 2.23 μM. Metabolite screening by a high-performance liquid chromatography/electrospray ionisation mass spectrometry indicated that CYP2A6 oxidised bilirubin to biliverdin and to three other smaller products with m/z values of 301, 315 and 333. Molecular docking analyses indicated that bilirubin and its positively charged intermediate interacted with key amino acid residues at the enzyme's active site. They were stabilised at the site in a conformation favouring biliverdin formation. By contrast, the end product, biliverdin was less fitting to the active site with the critical central methylene bridge distanced from the CYP2A6 haem iron facilitating its release. Furthermore, bilirubin treatment of HepG2 cells increased the CYP2A6 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A6 compared to cells treated only with CHX. Collectively, the observations indicate that the CYP2A6 may function as human “Bilirubin Oxidase” where bilirubin is potentially a substrate and a regulator of the enzyme. -- Highlights: ► Human CYP2A6 interacts with bilirubin with a high affinity. ► Bilirubin docking to the CYP2A6 active site is more stable than biliverdin docking. ► Recombinant CYP2A6 microsomes metabolised bilirubin to biliverdin. ► Bilirubin increased the hepatic CYP2

  18. Hepatic bilirubin UDP-glucuronyltransferase in patients with sickle cell anemia.

    PubMed

    Maddrey, W C; Cukier, J O; Maglalang, A C; Boitnott, J K; Odell, G B

    1978-02-01

    In sickle cell anemia the shortened survival of red blood cells presents the liver with an augmented load of bilirubin for hepatic clearance. To determine the effects of this excessive bilirubin load on the microsomal conjugating enzyme, hepatic bilirubin UDP-glucuronyltransferase, levels of this enzyme were measured in liver biopsies from patients with sickle cell anemia and several comparison groups. UDP-glucuronyltransferase activity in 14 patients with sickle cell anemia was 2-fold greater (P less than 0.005) than in 14 nonjaundiced comparison patients without liver disease. The elevated UDP-glucuronyltransferase activity in sickle cell anemia was similar to that found in 10 patients who chronically ingested drugs (barbiturates or estrogens) known to increase UDP-glucuronyltransferase activity. These observations suggest enhanced conjugation of bilirubin in patients with sickle cell anemia may result from substrate (bilirubin) induction of UDP-glycuronyltransferase. PMID:413760

  19. Metabolism of heme and bilirubin in rat and human small intestinal mucosa.

    PubMed Central

    Hartmann, F; Bissell, D M

    1982-01-01

    Formation of heme, bilirubin, and bilirubin conjugates has been examined in mucosal cells isolated from the rat upper small intestine. Intact, viable cells were prepared by enzymatic dissociation using a combined vascular and luminal perfusion and incubated with an isotopically labeled precursor, delta-amino-[2,3-3H]levulinic acid. Labeled heme and bile pigment were formed with kinetics similar to those exhibited by hepatocytes. Moreover, the newly formed bilirubin was converted rapidly to both mono- and diglucuronide conjugates. In addition, cell-free extracts of small intestinal mucosa from rats or humans exhibited a bilirubin-UDP-glucuronyl transferase activity that was qualitatively similar to that present in liver. The data suggest that the small intestinal mucosa normally contributes to bilirubin metabolism. PMID:6806320

  20. Comparison of transcutaneous and total serum bilirubin measurement in Turkish newborns.

    PubMed

    Şimşek, Fatih Mehmet; Narter, Fatma; Ergüven, Müferet

    2014-01-01

    Severe neonatal hyperbilirubinemia can be prevented by screening for neonatal jaundice. Transcutaneous bilirubin (TcB) measurement is a noninvasive method for screening neonates. The aim of this study was to examine the correlation between TcB measurement (using the JM-103 bilirubinometer) and total serum bilirubin (TSB) measurement. To our knowledge, this is the first study evaluating the usefulness of the JM-103 bilirubinometer in Turkish neonates. Two hundred and fifty healthy infants in our well-baby nurseries and follow-up clinic with a gestational age of ≥36 weeks who were ≤15 days old were enrolled in this study. TcB measurements were taken usinng the JM-103; almost simultaneously, TSB was checked using a spectrophotometric method. The mean±SD TSB level was 11.2±4.6 mg/dl (range, 0.9-27.0 mg/dl); 17.2% of cases had TSB>15 mg/dl. There was good correlation between transcutaneous bilirubin and total serum bilirubin measurements (Pearson's correlation coefficient 0.87 for TcB from the forehead, 0.88 for TcB from the sternum; p<0.001). The transcutaneous bilirubin measurement tended to underestimate the value with increasing discrepancy at higher TSB values. The mean difference between serum bilirubin and transcutaneous (from the sternum and forehead) bilirubin values was significantly lower in cases not requiring phototherapy than in those requiring phototherapy [2.6 mg/dl (sternum) vs 4.8 mg/dl, 2.9 mg/dl (forehead) vs. 5.2 mg/dl, respectively; p<0.001] Although the JM-103 bilirubinometer tends to underestimate serum bilirubin, especially in patients with high bilirubin levels, it is a suitable screening tool to identify jaundiced infants that require a serum bilirubin check and may reduce the need for TSB measurements. PMID:26388591

  1. Gut microbiota and hepatic encephalopathy.

    PubMed

    Dhiman, Radha K

    2013-06-01

    There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE. PMID:23463489

  2. Chronic Traumatic Encephalopathy: A Review

    PubMed Central

    Saulle, Michael; Greenwald, Brian D.

    2012-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is a long-term consequence of single or repetitive closed head injuries for which there is no treatment and no definitive pre-mortem diagnosis. It has been closely tied to athletes who participate in contact sports like boxing, American football, soccer, professional wrestling and hockey. Risk factors include head trauma, presence of ApoE3 or ApoE4 allele, military service, and old age. It is histologically identified by the presence of tau-immunoreactive NFTs and NTs with some cases having a TDP-43 proteinopathy or beta-amyloid plaques. It has an insidious clinical presentation that begins with cognitive and emotional disturbances and can progress to Parkinsonian symptoms. The exact mechanism for CTE has not been precisely defined however, research suggest it is due to an ongoing metabolic and immunologic cascade called immunoexcitiotoxicity. Prevention and education are currently the most compelling way to combat CTE and will be an emphasis of both physicians and athletes. Further research is needed to aid in pre-mortem diagnosis, therapies, and support for individuals and their families living with CTE. PMID:22567320

  3. Clinical Neurophysiology of Hepatic Encephalopathy

    PubMed Central

    Amodio, Piero; Montagnese, Sara

    2015-01-01

    Background/Objectives Hepatic encephalopathy (HE) has relevant impact on the quality of life of patients and their caregivers and causes relevant costs because of hospitalizations and work days lost. Its quantification is important to perform adequate clinical trials on this relevant complication of cirrhosis and portal-systemic shunting. Clinical neurophysiology, which detects functional alterations of the nervous system, has been applied to the study of HE for over 60 years. This review aims at summarizing and clarifying the role of neurophysiologic techniques in the study of HE. Methods A narrative review was performed aiming at interpreting the cited papers and the techniques on the basis of their physiological and pathophysiological meaning. Results The potential role of EEG, quantified EEG, evoked potentials—both exogenous, endogenous and motor—have been clarified to the reader that may be unfamiliar with neurophysiology. Conclusions The EEG, reflecting the oscillatory changes of neural network is the preferable tool to detect and monitor HE, with the exception of its most severe stage, when EEG flattens. SSEP and MEP have indication to detect and monitor transmission alterations that are likely related to myelin changes and microedema. PMID:26041960

  4. [Wernicke encephalopathy after subtotal gastrectomy for morbid obesity].

    PubMed

    Gabaudan, C; La-Folie, T; Sagui, E; Soulier, B; Dion, A-M; Richez, P; Brosset, C

    2008-05-01

    Wernicke's encephalopathy (WE) is one of the potential complications of obesity surgery. It is an acute neuropsychiatric syndrome resulting from thiamine deficiency often associated with repeated vomiting. The classic triad is frequently reported in these patients (optic neuropathy, ataxia and confusion), associated with uncommon features. Cerebral impairment affects the dorsal medial nucleus of the thalamus and the periaqueductal grey area, appearing on MRI, as hyperintense signals on T2, Flair and Diffusion weighted imaging. Early diagnosis and parenteral thiamine are required to decrease morbidity and mortality. We report a case of WE and Korsakoff's syndrome in a young obese patient after subtotal gastrectomy, who still has substantial sequelae. The contribution of MRI with diffusion-weighted imaging is illustrated. The interest of nutritional supervision in the first weeks and preventive thiamine supplementation in case of repeated vomiting are of particular importance in these risky situations. PMID:18555879

  5. [Research advances of posterior reversible encephalopathy syndrome in children].

    PubMed

    Liu, Jing; Qin, Jiong

    2016-08-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological entity affecting the posterior brain, i.e. occipital and parietal lobes. The syndrome are characterized by headaches, altered mental status, seizures, and visual disturbances. Although the pathogenesis remains unclear, endothelial dysfunction may be a key factor. The basic disease may play a crucial role in the incidence of PRES. In most cases, PRES resolves spontaneously and patients show both clinical and radiological improvements. In severe forms, PRES might cause substantial morbidity with sequel and even mortality, as a result of acute hemorrhage or massive posterior fossa edema causing obstructive hydrocephalus or brainstem compression. Early identification, active and appropriate treatment is very important. PMID:27530801

  6. Contemporary Understanding and Management of Overt and Covert Hepatic Encephalopathy

    PubMed Central

    NeSmith, Meghan; Ahn, Joseph

    2016-01-01

    Hepatic encephalopathy (HE) is a major complication of liver disease that leads to significant morbidity and mortality. Caring for hospitalized patients with HE is becoming more complex, and the economic burden of HE continues to rise. Defining and diagnosing HE, particularly covert HE (CHE), remain challenging. In this article, we review new tools and those currently under development for the diagnosis of CHE and the latest advances in the acute and long-term management of overt HE (OHE) and CHE. In particular, we review the latest data on the use of lactulose and rifaximin for treatment of OHE and summarize the data on adjunctive agents such as sodium benzoate and probiotics. PMID:27182210

  7. Prevention and treatment of hepatic encephalopathy: focusing on gut microbiota.

    PubMed

    Garcovich, Matteo; Zocco, Maria Assunta; Roccarina, Davide; Ponziani, Francesca Romana; Gasbarrini, Antonio

    2012-12-14

    The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation. PMID:23239905

  8. Contemporary Understanding and Management of Overt and Covert Hepatic Encephalopathy.

    PubMed

    NeSmith, Meghan; Ahn, Joseph; Flamm, Steven L

    2016-02-01

    Hepatic encephalopathy (HE) is a major complication of liver disease that leads to significant morbidity and mortality. Caring for hospitalized patients with HE is becoming more complex, and the economic burden of HE continues to rise. Defining and diagnosing HE, particularly covert HE (CHE), remain challenging. In this article, we review new tools and those currently under development for the diagnosis of CHE and the latest advances in the acute and long-term management of overt HE (OHE) and CHE. In particular, we review the latest data on the use of lactulose and rifaximin for treatment of OHE and summarize the data on adjunctive agents such as sodium benzoate and probiotics. PMID:27182210

  9. 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

  10. Multimodality magnetic resonance imaging in hepatic encephalopathy: An update

    PubMed Central

    Zhang, Xiao-Dong; Zhang, Long-Jiang; Wu, Sheng-Yong; Lu, Guang-Ming

    2014-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging (MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight of the increasingly important role of blood oxygen level dependent functional MRI. PMID:25170210

  11. Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

    PubMed

    Ogawa, Erika; Ishige, Mika; Takahashi, Yuno; Kodama, Hiroko; Fuchigami, Tatsuo; Takahashi, Shori

    2016-08-01

    A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF. PMID:27324861

  12. Rethinking the immune properties of bilirubin in viral hepatitis: from bench to bedside

    PubMed Central

    Corral-Jara, Karla F; Trujillo-Ochoa, Jorge L; Realpe, Mauricio; Panduro, Arturo; Roman, Sonia; Fierro, Nora A

    2015-01-01

    Communication between the immune system and metabolic components can be exemplified by the process of heme catabolism. The immunomodulatory functions of the enzymes, substrates and active products related to catabolism of the heme group have been extensively studied. Bilirubin (BR), the final breakdown product of heme, is primarily considered to be a toxic waste product but has recently been considered to be an immunomodulatory metabolite. Through mechanisms that include intracellular signaling and transcriptional control, BR affects those immune cell functions that regulate cell proliferation, differentiation and apoptosis. During the pathogenesis of viral hepatitis, the heme degradation pathway is disrupted, resulting in changes to normal BR concentrations. These alterations have been previously studied mainly as a consequence of the infection. However, little is known about the potential immunomodulatory role played by BR in the development of infectious hepatocellular diseases. Differences in BR levels in the context of viral hepatitis are likely to provide important insights into the metabolite-mediated mechanisms controlling the immune responses underlying both the long-term persistence of hepatitis C virus (HCV) infection and the resolution of hepatitis A virus (HAV) infection during the acute phase. In this review, the cross-talk between heme catabolism and immune function is described in detail. Special emphasis is given to discoveries that hold promise for identifying immunologic features of metabolic products in the resolution of viral diseases. PMID:26719800

  13. Wernicke's Encephalopathy Complicating Hyperemesis during Pregnancy

    PubMed Central

    Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha

    2016-01-01

    Wernicke's encephalopathy is caused by severe thiamine deficiency; it is mostly observed in alcoholic patients. We report the case of a 28-year-old woman, at 17 weeks of gestational age, with severe hyperemesis gravidarum. She presented with disturbance of consciousness, nystagmus, ophthalmoplegia, and ataxia. The resonance magnetic imagery showed bilaterally symmetrical hyperintensities of thalamus and periaqueductal area. The case was managed with very large doses of thiamine. The diagnosis of Wernicke's encephalopathy was confirmed later by a low thiamine serum level. The patient was discharged home on day 46 with mild ataxia and persistent nystagmus. Wernicke's encephalopathy is a rare complication of hyperemesis gravidarum. It should be diagnosed as early as possible to prevent long-term neurological sequela or death. Thiamine supplementation in pregnant women with prolonged vomiting should be initiated, especially before parenteral dextrose infusion. Early thiamine replacement will reduce maternal morbidity and fetal loss rate. PMID:26989522

  14. Clinical review of genetic epileptic encephalopathies

    PubMed Central

    Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.

    2012-01-01

    Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered. PMID:22342633

  15. Wernicke's Encephalopathy Complicating Hyperemesis during Pregnancy.

    PubMed

    Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha

    2016-01-01

    Wernicke's encephalopathy is caused by severe thiamine deficiency; it is mostly observed in alcoholic patients. We report the case of a 28-year-old woman, at 17 weeks of gestational age, with severe hyperemesis gravidarum. She presented with disturbance of consciousness, nystagmus, ophthalmoplegia, and ataxia. The resonance magnetic imagery showed bilaterally symmetrical hyperintensities of thalamus and periaqueductal area. The case was managed with very large doses of thiamine. The diagnosis of Wernicke's encephalopathy was confirmed later by a low thiamine serum level. The patient was discharged home on day 46 with mild ataxia and persistent nystagmus. Wernicke's encephalopathy is a rare complication of hyperemesis gravidarum. It should be diagnosed as early as possible to prevent long-term neurological sequela or death. Thiamine supplementation in pregnant women with prolonged vomiting should be initiated, especially before parenteral dextrose infusion. Early thiamine replacement will reduce maternal morbidity and fetal loss rate. PMID:26989522

  16. Pediatric Epileptic Encephalopathies: Pathophysiology and Animal Models.

    PubMed

    Shao, Li-Rong; Stafstrom, Carl E

    2016-05-01

    Epileptic encephalopathies are syndromes in which seizures or interictal epileptiform activity contribute to or exacerbate brain function, beyond that caused by the underlying pathology. These severe epilepsies begin early in life, are associated with poor lifelong outcome, and are resistant to most treatments. Therefore, they represent an immense challenge for families and the medical care system. Furthermore, the pathogenic mechanisms underlying the epileptic encephalopathies are poorly understood, hampering attempts to devise novel treatments. This article reviews animal models of the three classic epileptic encephalopathies-West syndrome (infantile spasms), Lennox-Gastaut syndrome, and continuous spike waves during sleep or Landau-Kleffner syndrome-with discussion of how animal models are revealing underlying pathophysiological mechanisms that might be amenable to targeted therapy. PMID:27544466

  17. Why the confusion in Hashimoto's encephalopathy?

    PubMed

    Jayasekera, Bodiabaduge A P; McShane, Michael Anthony; Roy, Prem; Anand, Geetha

    2011-01-01

    A 13-year-old girl presented with an afebrile seizure followed by prolonged confusion and visual hallucinations. Initial investigations in the form of blood tests, cerebrospinal fluid analysis and head imaging by CT, were normal. She represented with two further episodes within a period of 3 weeks. Further investigations considering infective, metabolic and some autoimmune causes of encephalopathy were negative. An MRI head scan was normal. Thyroid function testing disclosed primary hypothyroidism and elevated antithyroid antibodies. She responded well to glucocorticoid therapy for presumed Hashimoto's encephalopathy (HE). HE describes patients with various neurological manifestations with elevated titres of antithyroid antibodies. There are no clear criteria for diagnosis, with many cases labelled as HE. Responses to corticosteroid therapy are favourable. In patients with unexplained encephalopathy, HE should be considered given the favourable response to glucocorticoid therapy. PMID:22691944

  18. Experimental Interspecies Transmission Studies of the Transmissible Spongiform Encephalopathies to Cattle: Comparison to Bovine Spongiform Encephalopathy in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. Since the emergence of BSE and its pr...

  19. Concussion in Chronic Traumatic Encephalopathy

    PubMed Central

    Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.

    2015-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

  20. Concussion in Chronic Traumatic Encephalopathy.

    PubMed

    Stein, Thor D; Alvarez, Victor E; McKee, Ann C

    2015-10-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

  1. Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk

    SciTech Connect

    Alonso, E.M.; Whitington, P.F.; Whitington, S.H.; Rivard, W.A.; Given, G. )

    1991-03-01

    To test the hypothesis that enhanced intestinal absorption of bilirubin may contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed infants, we studied a cross-section of 36 healthy infants and mothers. Milk from mothers and serum from infants were collected at 16.3 +/- 2.4 days. Milk was studied for its effect on the absorption of bilirubin labeled with carbon 14 in rats and compared with buffer and iron-fortified infant formula (Similac With Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29 +/- 4.0% when it was administered into the duodenum with buffer, 4.67 +/- 2.4% with Similac formula, and 7.7 +/- 2.9% with human milk. Linear regression analysis, using the infant's serum nonconjugated bilirubin level as the dependent variable and the percentage of (14C)bilirubin absorbed by the rat with the corresponding mother's milk as the independent variable, revealed a significant correlation (r = 0.40; p = 0.016). Inspection of the data suggested that absorptive permissiveness correlated closely with infant serum bilirubin values greater than 24 mumol/L (1.4 mg/dl) (r = 0.55; p = 0.007), whereas in those with bilirubin values less than or equal to 24 mumol/L, there was no apparent correlation. Milk was also analyzed for beta-glucuronidase, nonesterified fatty acids, and the ability to inhibit glucuronosyltransferase activity of rat liver microsomes in vitro, none of which correlated with the infant's serum bilirubin. These data support the theory that enhanced intestinal absorption of bilirubin contributes to the jaundice associated with breast-feeding.

  2. Minimal Hepatic Encephalopathy Impairs Quality of Life

    PubMed Central

    Agrawal, Swastik; Umapathy, Sridharan; Dhiman, Radha K.

    2015-01-01

    Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life. PMID:26041957

  3. Minimal hepatic encephalopathy impairs quality of life.

    PubMed

    Agrawal, Swastik; Umapathy, Sridharan; Dhiman, Radha K

    2015-03-01

    Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life. PMID:26041957

  4. Bithalamic lesions of butane encephalopathy.

    PubMed

    Kile, Shawn J; Camilleri, Christopher C; Latchaw, Richard E; Tharp, Barry R

    2006-12-01

    Butane inhalation can cause serious medical complications and is particularly toxic to the nervous system. This is a report of an acutely encephalopathic youth with prominent abulia. MRI revealed severe bithalamic injury attributed to butane toxicity. Clinical issues, including particular radiologic findings, related to butane inhalation are reviewed. PMID:17138017

  5. Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barrè Syndrome.

    PubMed

    Rossi, Rosario; Saddi, Maria Valeria; Mela, Alessandro; Ticca, Anna

    2016-01-01

    We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barrè syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy. PMID:27403359

  6. Recurarization in a successfully managed case of posterior reversible encephalopathy syndrome (PRES) for emergency caesarean section.

    PubMed

    Parikh, Suchita; Tavri, Snehlata; Mohite, Shubha

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic syndrome of headache, visual changes, altered mental status and seizures with radiologic findings of posterior cerebral white matter edema. It is seen in hypertensive encephalopathy, renal failure, and autoimmune disorders or in patients on immunosuppressants. We report a case of 24-year-old primigravida who presented at term with sudden onset hypertension, neurological deficits, and an episode of the visual blackout. Magnetic resonance imaging showed features suggestive of PRES. She was posted for emergency lower segment cesarean section. General anesthesia was administered and blood pressure managed with antihypertensives. Postoperatively, she developed acute respiratory depression after prophylactic administration of injection magnesium sulfate. This case highlights that good clinical acumen along with early neuroimaging helps in prompt diagnosis, treatment and prevention of long-term neurological sequelae in PRES and the anesthetic implications of administering magnesium sulfate in the immediate post neuromuscular block reversal phase. PMID:27212776

  7. Recurarization in a successfully managed case of posterior reversible encephalopathy syndrome (PRES) for emergency caesarean section

    PubMed Central

    Parikh, Suchita; Tavri, Snehlata; Mohite, Shubha

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic syndrome of headache, visual changes, altered mental status and seizures with radiologic findings of posterior cerebral white matter edema. It is seen in hypertensive encephalopathy, renal failure, and autoimmune disorders or in patients on immunosuppressants. We report a case of 24-year-old primigravida who presented at term with sudden onset hypertension, neurological deficits, and an episode of the visual blackout. Magnetic resonance imaging showed features suggestive of PRES. She was posted for emergency lower segment cesarean section. General anesthesia was administered and blood pressure managed with antihypertensives. Postoperatively, she developed acute respiratory depression after prophylactic administration of injection magnesium sulfate. This case highlights that good clinical acumen along with early neuroimaging helps in prompt diagnosis, treatment and prevention of long-term neurological sequelae in PRES and the anesthetic implications of administering magnesium sulfate in the immediate post neuromuscular block reversal phase. PMID:27212776

  8. Posterior Reversible Encephalopathy Syndrome with Bilateral Independent Epileptic Foci Precipitated By Guillain-Barrè Syndrome

    PubMed Central

    Rossi, Rosario; Saddi, Maria Valeria; Mela, Alessandro; Ticca, Anna

    2016-01-01

    We report the case of a 56-year-old woman who developed status epilepticus (SE) related to independent occipital foci as clinical manifestation of posterior reversible encephalopathy syndrome (PRES) in the background of Guillain-Barrè syndrome (GBS). SE resulted from a series of focal seizures clinically characterized by left- and rightward deviations of the head and consequent oculoclonic movements. Electroencephalography recorded independent seizure activity in both occipital regions with alternate involvement of the two cerebral hemispheres. The epileptic foci corresponded topographically to parenchymal abnormalities of PRES in the occipital lobes. The manifestation of bilateral, independent occipital seizures with alternate deviations of the head and oculoclonic movements, previously not reported in patients with PRES, highlights the acute epileptogenicity of the cerebral lesions in this syndrome. Despite the variable clinical expression of seizures due to occipital damage in PRES, the development of independent seizure activity in both occipital lobes might represent a distinctive epileptic phenomenon of this encephalopathy. PMID:27403359

  9. Encephalopathy and fatty infiltration of the viscera (Reye-Johnson syndrome): a 17-year experience.

    PubMed

    Chaves-Carballo, E; Gomez, M R; Sharbrough, F W

    1975-04-01

    Reye-Johnson syndrome was found in 17 patients in a retrospective study of 235 children with acute encephalopathy seen at the Mayo Clinic in the period 1955 through 1971. Eight of the nine patients under 4 years of age developed the syndrome prior to 1968; eight children 10 to 15 years of age acquired the disorder from 1968 through 1971. Seven patients were admitted during the month of February. Prodromal symptoms preceded the encephalopathy in 13 patients. Eight patients had seizures. Progressive deterioration with brainstem signs led to death in 15 patients. Electroencephalographic findings correlated well with the clinical course and eventual outcome. However, no correlation was found between seizure activity and the electroencephalogram. Autopsy findings in 14 cases included cerebral edema, tonsillar herniation, hypoxic neuronal degeneration, and fatty inflitration of the liver and kidneys. PMID:1091786

  10. Total parenteral nutrition caused Wernicke’s encephalopathy accompanied by wet beriberi

    PubMed Central

    Long, Ling; Cai, Xiao-Dong; Bao, Jian; Wu, Ai-Min; Tian, Qing; Lu, Zheng-Qi

    2014-01-01

    Patient: Female, 17 Final Diagnosis: Wernicke’s encephalopathy Symptoms: Blurred vision • dizziness • nystygmus • tachycardia Medication: — Clinical Procedure: — Specialty: Neurology Objective: Mistake in diagnosis Background: Wernicke’s encephalopathy (WE) is an acute and life-threatening illness which is not only seen in alcoholics, but also in persons with poor nutrition lacking thiamine (vitamin B1). Case Report: Here, we presented a case of WE in a patient who received parenteral nutrition without complement of thiamine. Besides neuropsychiatric problems, she also manifested prominent cardiovascular abnormalities, which were consistent with wet beriberi. Conclusions: This case emphasizes the need for thiamine supplementation in prolonged total parenteral nutrition, and also highlights the awareness of WE in persons with parenteral nutrition lacking thiamine. More importantly, we call for attention to wet beriberi in such persons. PMID:24516692

  11. A Fatal Case of Wernicke's Encephalopathy after Sleeve Gastrectomy for Morbid Obesity

    PubMed Central

    Manatakis, Dimitrios K.; Georgopoulos, Nikolaos

    2014-01-01

    Wernicke's encephalopathy is an acute neuropsychiatric disorder, due to thiamine (vitamin B1) deficiency. It is traditionally described in chronic alcohol abusers; however obesity surgery is an emerging cause, as the number of bariatric procedures increases. A high index of clinical suspicion is required, since initial symptoms may be nonspecific and the classic triad of ophthalmoplegia, gait and stance disorders, and mental confusion is present only in one-third of patients. Laboratory tests can be within normal range and typical MRI brain lesions are found only in 50% of cases. Aggressive supplementation with intravenous thiamine should not be delayed until confirmation of diagnosis, as it may fully reverse symptoms, but almost half the patients will still display permanent neurological deficit. We present our experience with a fatal case of Wernicke's encephalopathy, following laparoscopic sleeve gastrectomy for morbid obesity. PMID:25276464

  12. Posterior reversible encephalopathy syndrome in a child with Henoch-Schönlein purpura

    PubMed Central

    Sivrioglu, Ali Kemal; Incedayi, Mehmet; Mutlu, Hakan; Meral, Cihan

    2013-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel vasculitis that affects the gastrointestinal and central nervous systems and the kidneys. The disease primarily affects children, but may occur in elderly children with allergic purpura and also in adults. Central nervous system involvement may be the first sign; however, it is rarely encountered. Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance and seizures. Its radiological signs can be observed in grey and white matter at the posterior region of the cerebral hemispheres. HSP should be considered in children with PRES in the presence of rash, joint and gastrointestinal symptoms. We reported a 5-year-old patient who developed acute renal failure and PRES by reason of HSP. PMID:23946524

  13. Bilirubin as a Determinant for Altered Neurogenesis, Neuritogenesis, and Synaptogenesis

    PubMed Central

    Fernandes, Adelaide; Falcão, Ana Sofia; Abranches, Elsa; Bekman, Evguenia; Henrique, Domingos; Lanier, Lorene M.; Brites, Dora

    2009-01-01

    Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life. PMID:19449315

  14. Neuropsychological functioning in Wernicke's encephalopathy

    PubMed Central

    Behura, Sushree Sangita; Swain, Sarada Prasanna

    2015-01-01

    Context: Wernicke's encephalopathy (WE) is caused by thiamine (Vitamin B1) deficiency and most commonly found in chronic alcoholism and malnutrition. Clinically, the key features are mental status disturbances (global confusion), oculomotor abnormalities, and gait disturbances (ataxia). Apart from these clinical features, we can find deficits in neuropsychological functioning in patients with WE, which is more prominent after the improvement in the physical conditions. Neuropsychological functioning includes both basic cognitive processes (i.e., attention-concentration) as well as higher order cognitive processes (i.e., memory, executive functioning, reasoning), which is much vital for the maintenance of quality of life of an individual. However, unfortunately, in most of the cases, neuropsychological functioning is ignored by the clinicians. Materials and Methods: In this study four case reports of WE have been presented. The patients were taken from the outdoor department of Mental Health Institute, S.C.B. Medical College, Cuttack, Odisha. Neuropsychological functioning was measured by administration of PGIBBD and Quality of Life was measured by WHO-QOL BREF Odia Version. Discussion: As described in the literature, among the three cardinal signs (global confusion, ataxia, and ocular sings), the first two were present in all cases, but nystagmus was present in only two cases. Memory dysfunction was so disabling that the persons were unable to maintain a good Quality of Life and occupational impairment was prominent. There are disturbances in recent, remote memory, immediate recall, delayed recall, and attention and concentration, ultimately creating both physical and mental disability. PGI-BBD findings also suggest the overall impairment in neuropsychological functioning other than memory, that is, executive functioning, visual acuity, and depth perception. Findings of WHO-QOL BREF suggest the impairment of four domains of QOL in all the cases, but the severity

  15. PRIONS AND THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

    EPA Science Inventory

    This book chapter is an invited, scholarly review of the mechanism(s) of TSEs for the 2nd edition of Metabolic Encephalopathies. Each chapter in the book assumes a professional knowledge of neuroscience and biochemistry, and the focus of the book is on the metabolic basis of dise...

  16. Epileptic encephalopathies: new genes and new pathways.

    PubMed

    Nieh, Sahar Esmaeeli; Sherr, Elliott H

    2014-10-01

    Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy, persistent severe electroencephalographic abnormalities, and cognitive dysfunction or decline. Next generation sequencing technologies have increased the speed of gene discovery tremendously. Whereas ion channel genes were long considered to be the only significant group of genes implicated in the genetic epilepsies, a growing number of non-ion-channel genes are now being identified. As a subgroup of the genetically mediated epilepsies, epileptic encephalopathies are complex and heterogeneous disorders, making diagnosis and treatment decisions difficult. Recent exome sequencing data suggest that mutations causing epileptic encephalopathies are often sporadic, typically resulting from de novo dominant mutations in a single autosomal gene, although inherited autosomal recessive and X-linked forms also exist. In this review we provide a summary of the key features of several early- and mid-childhood onset epileptic encephalopathies including Ohtahara syndrome, Dravet syndrome, Infantile spasms and Lennox Gastaut syndrome. We review the recent next generation sequencing findings that may impact treatment choices. We also describe the use of conventional and newer anti-epileptic and hormonal medications in the various syndromes based on their genetic profile. At a biological level, developments in cellular reprogramming and genome editing represent a new direction in modeling these pediatric epilepsies and could be used in the development of novel and repurposed therapies. PMID:25266964

  17. The transmissible spongiform encephalopathies of livestock.

    PubMed

    Greenlee, Justin J; Greenlee, M Heather West

    2015-01-01

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein-misfolding neurodegenerative diseases. TSEs have been described in several species, including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (called PrP(Sc)) in the central nervous system and other tissues, depending on the host species. Typically, TSEs are acquired through exposure to infectious material, but inherited and spontaneous TSEs also occur. All TSEs share pathologic features and infectious mechanisms but have distinct differences in transmission and epidemiology due to host factors and strain differences encoded within the structure of the misfolded prion protein. The possibility that BSE can be transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has brought attention to this family of diseases. This review is focused on the TSEs of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and goats. PMID:25991695

  18. [Myoclonic encephalopathy associated with proton pump inhibitors].

    PubMed

    Boulliat, J; Polard, E; Colin, F; Bentué-Ferrer, D; Allain, H

    2004-03-01

    Two men (66 and 73 Years) with a cardiovascular history were hospitalized for rapid onset encephalopathy associated with myoclonia and an extrapyramidal syndrome. On the basis of the French Pharmacovigilance system, this symptomatology has been attributed to the coadministration of a proton pump inhibitor, lansoprazole (15mg/day) with levodopa. Lansoprazole withdrawal led to a normalisation of the situation. PMID:15037850

  19. Solvation and crystal effects in bilirubin studied by NMR spectroscopy and density functional theory.

    PubMed

    Rohmer, Thierry; Matysik, Jörg; Mark, Franz

    2011-10-27

    The open-chain tetrapyrrole compound bilirubin was investigated in chloroform and dimethyl sulfoxide solutions by liquid-state NMR and as solid by (1)H, (13)C, and (15)N magic-angle spinning (MAS) solid-state NMR spectroscopy. Density functional theory (DFT) calculations were performed to interpret the data, using the B3LYP exchange-correlation functional to optimize geometries and to compute NMR chemical shieldings by the gauge-including atomic orbital method. The dependence of geometries and chemical shieldings on the size of the basis sets was investigated for the reference molecules tetramethylsilane, NH(3), and H(2)O, and for bilirubin as a monomer and in clusters consisting of up to six molecules. In order to assess the intrinsic errors of the B3LYP approximation in calculating NMR shieldings, complete basis set estimates were obtained for the nuclear shielding values of the reference molecules. The experimental liquid-state NMR data of bilirubin are well reproduced by a monomeric bilirubin molecule using the 6-311+G(2d,p) basis set for geometry optimization and for calculating chemical shieldings. To simulate the bilirubin crystal, a hexameric model was required. It was constructed from geometry-optimized monomers using information from the X-ray structure of bilirubin to fix the monomeric entities in space and refined by partial optimization. Combining experimental (1)H-(13)C and (1)H-(15)N NMR correlation spectroscopy and density functional theory, almost complete sets of (1)H, (13)C, and (15)N chemical shift assignments were obtained for both liquid and solid states. It is shown that monomeric bilirubin in chloroform solution is formed by 3-vinyl anti conformers, while bilirubin crystals are formed by 3-vinyl syn conformers. This conformational change leads to characteristic differences between the liquid- and solid-state NMR resonances. PMID:21846145

  20. Association of Serum Bilirubin with SYNTAX Score and Future Cardiovascular Events in Patients Undergoing Coronary Intervention

    PubMed Central

    Chang, Chun-Chin; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Huang, Shao-Sung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Background Bilirubin has emerged as an important endogenous antioxidant molecule, and increasing evidence shows that bilirubin may protect against atherosclerosis. The SYNTAX score has been developed to assess the severity and complexity of coronary artery disease. The aim of this study was to evaluate whether serum bilirubin levels are associated with SYNTAX scores and whether they could be used to predict future cardiovascular events in patients undergoing coronary intervention. Methods Serum bilirubin levels and other blood parameters in patients with at least 12-h fasting states were determined. The primary endpoint was any composite cardiovascular event within 1 year, including death, nonfatal myocardial infarction, and target-vessel revascularization. Results In total, 250 consecutive patients with stable coronary artery disease (mean age 70 ± 13) who had received coronary intervention were enrolled. All study subjects were divided into two groups: group 1 was defined as high SYNTAX score (> 22), and group 2 was defined as low SYNTAX score (≤ 22). Total bilirubin levels were significantly lower in the high SYNTAX score group than in the low SYNTAX score group (0.51 ± 0.22 vs. 0.72 ± 0.29 mg/dl, p < 0.001). By multivariate analysis, serum total bilirubin levels were identified as an independent predictor for high SYNTAX score (adjusted odds ratio: 0.28, 95% confidence interval 0.04-0.42; p = 0.004). Use of the Kaplan-Meier analysis demonstrated a significant difference in 1-year cardiovascular events between high (> 0.8 mg/dl), medium (> 0.5, ≤ 0.8 mg/dl), and low (≤ 0.5 mg/dl) bilirubin levels (log-rank test p = 0.011). Conclusions Serum bilirubin level is associated with SYNTAX score and predicts future cardiovascular events in patients undergoing coronary intervention. PMID:27471354

  1. Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study

    PubMed Central

    Abbasi, Ali; Deetman, Petronella E.; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O.B.; Hillege, Hans L.; van der Harst, Pim; Stolk, Ronald P.; Navis, Gerjan; Alizadeh, Behrooz Z.; Bakker, Stephan J.L.

    2014-01-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. T2D developed in a total of 210 (6.2%) participants during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P<1×10−122) and was also associated with T2D risk (OR 0.69 [95%CI, 0.54-0.90]; P=0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant. PMID:25368098

  2. Extended mathematical model for "in vivo" quantification of the interaction betweeen atazanavir and bilirubin.

    PubMed

    Lozano, Roberto; Domeque, Nieves; Apesteguia, Alberto-Fermín

    2014-02-01

    The objective of the present work was to conduct an "in vivo" analysis of the atazanavir-bilirubin interaction. We developed a new mathematical approach to PK/PDPK models for competitive interaction based on the Michaelis-Menten equation, which was applied to patients with polymorphisms in the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1). Atazanavir is known to induce concentration-dependent increases in bilirubin plasma levels. Thus, we employed our mathematical model to analyse rises in steady state atazanavir and bilirubin concentrations, ultimately plotting a nomogram for detection of suboptimal atazanavir exposure. Application of our model revealed that an absolute value or a steady state increase in bilirubin falling below 3.8Φ µmol/L (where Φ is a correction factor, =1 for UGT1A1 wild type and ≠1 for UGT1A1 variants) could be used to predict suboptimal atazanavir exposure and treatment failure. Thus, we have successfully established a new mathematical approach for pharmacodynamic-pharmacokinetic modelling of the interaction between atazanavir and bilirubin, as it relates to genetic variants of UGT1A1. Taken together, our findings indicate that bilirubin plasma levels represent a valuable marker of atazanavir exposure. PMID:24243081

  3. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

    PubMed Central

    Levitt, David G; Levitt, Michael D

    2014-01-01

    Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB) and unconjugated bilirubin (UB). While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis), and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert’s, Dubin–Johnson, Crigler–Najjar, Rotor syndromes). Novel aspects of this review include: 1) quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2) detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3) discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4) pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5) role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6) insights concerning the clinical interpretation of bilirubin measurements. PMID:25214800

  4. Surface-modified anodic aluminum oxide membrane with hydroxyethyl celluloses as a matrix for bilirubin removal.

    PubMed

    Xue, Maoqiang; Ling, Yisheng; Wu, Guisen; Liu, Xin; Ge, Dongtao; Shi, Wei

    2013-01-01

    Microporous anodic aluminum oxide (AAO) membranes were modified by 3-glycidoxypropyltrimethoxysilane to produce terminal epoxy groups. These were used to covalently link hydroxyethyl celluloses (HEC) to amplify reactive groups of AAO membrane. The hydroxyl groups of HEC-AAO composite membrane were further modified with 1,4-butanediol diglycidyl ether to link arginine as an affinity ligand. The contents of HEC and arginine of arginine-immobilized HEC-AAO membrane were 52.1 and 19.7mg/g membrane, respectively. As biomedical adsorbents, the arginine-immobilized HEC-AAO membranes were tested for bilirubin removal. The non-specific bilirubin adsorption on the unmodified HEC-AAO composite membranes was 0.8mg/g membrane. Higher bilirubin adsorption values, up to 52.6mg/g membrane, were obtained with the arginine-immobilized HEC-AAO membranes. Elution of bilirubin showed desorption ratio was up to 85% using 0.3M NaSCN solution as the desorption agent. Comparisons equilibrium and dynamic capacities showed that dynamic capacities were lower than the equilibrium capacities. In addition, the adsorption mechanism of bilirubin and the effects of temperature, initial concentration of bilirubin, albumin concentration and ionic strength on adsorption were also investigated. PMID:23290920

  5. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation.

    PubMed

    Aldridge, Dominic R; Tranah, Edward J; Shawcross, Debbie L

    2015-03-01

    The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. PMID:26041962

  6. Primary brain tumors and posterior reversible encephalopathy syndrome

    PubMed Central

    Kamiya-Matsuoka, Carlos; Cachia, David; Olar, Adriana; Armstrong, Terri S.; Gilbert, Mark R.

    2014-01-01

    Background Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly recognized occurrence in the oncology population. However, it is very uncommon in patients with primary brain tumors (PBTs). The aim of this study was to analyze the clinicoradiological features and report the clinical outcomes of PRES in PBT patients. Methods We identified 4 cases with PBT who developed PRES at MD Anderson Cancer Center (MDACC) between 2012 and 2014. Clinical and radiological data were abstracted from their records. In addition, we also solicited 8 cases from the literature. Results The median age at PRES onset was 19 years, male-to-female ratio was 1:1, and the syndrome occurred in patients with ependymoma (n = 4), glioblastoma (n = 3), diffuse intrinsic pontine glioma (DIPG; n = 3), juvenile pilocytic astrocytoma (n = 1), and atypical meningioma (n = 1). Two glioblastomas and 2 DIPG cases received bevacizumab and vandetanib before the onset of symptoms, respectively. The most common clinical presentation was seizures (n = 7). Three MDACC patients recovered completely in 3–4 weeks after the onset of symptoms. One patient died due to active cancer and several comorbidities including PRES. Conclusions Hypertension seems to be the most important coexisting risk factor for development of PRES; however, the potential effects of chemotherapeutic agents in the pathogenesis of PRES should also be examined. The clinicoradiological course of PRES in PBT patients did not vary from the classical descriptions of PRES found in other causes. PRES must be considered as part of the differential diagnosis in patients with PBTs presenting with seizures or acute encephalopathy. PMID:26034631

  7. Recurrent encephalopathy? No I'm a sleeping beauty!

    PubMed

    Iqbal, Mehtab; Prasad, Manish; Ritey, Christopher

    2014-01-01

    To describe the clinical presentation of 'Kleine-Levin (sleeping beauty) syndrome' in a child, who presented with recurrent episodes consistent with encephalopathy, associated with excessive sleepiness, cognitive and behavioural disturbance and hyper sexuality. 14 years old boy presented acutely with excessive tiredness, sleeping excessively, abnormal behaviour and hypersexuality following a viral throat infection. On examination he was sleepy but easily arousable. His GCS (15/15) and rest of the neurological examination including fundoscopy and other systemic examination was completely unremarkable. All his initial investigations including electrolytes, LFTs, CSF, virology screen and MRI brain scan were normal. Detailed autoimmune screening was also negative. EEG showed non-specific diffuse slowing consistent with encephalopathy. His excessive sleepiness gradually improved together with his altered behaviour in about two weeks after presentation. Hyper sexuality became more overt during this phase. All these symptoms completely disappeared three weeks after his presentation and he attended school as before. He was readmitted six weeks later with exactly similar presentation and again only positive result being diffuse non-specific slowing of EEG. His recovery was also similar and he was completely back to his normal self in three weeks time. His recurrent symptoms were consistent with 'Kleine-Levin syndrome (KLS)' or 'sleeping beauty syndrome'. KLS is a rare disorder which mainly affects adolescent males. Common symptoms include hypersomnia (100%), cognitive changes (96%), eating disturbances (80%), hypersexuality, compulsions, and depressed mood. The syndrome usually lasts for 8 years, with on an average seven episode of 10 days each recurring every 3.5 months. It is most frequently precipitated by infections and somnolence decreases using stimulants in nearly 40% of cases. PMID:24891916

  8. Recurrent encephalopathy? No I’m a sleeping beauty!

    PubMed Central

    Iqbal, Mehtab; Prasad, Manish; Ritey, Christopher

    2014-01-01

    To describe the clinical presentation of ‘Kleine-Levin (sleeping beauty) syndrome’ in a child, who presented with recurrent episodes consistent with encephalopathy, associated with excessive sleepiness, cognitive and behavioural disturbance and hyper sexuality. 14 years old boy presented acutely with excessive tiredness, sleeping excessively, abnormal behaviour and hypersexuality following a viral throat infection. On examination he was sleepy but easily arousable. His GCS (15/15) and rest of the neurological examination including fundoscopy and other systemic examination was completely unremarkable. All his initial investigations including electrolytes, LFTs, CSF, virology screen and MRI brain scan were normal. Detailed autoimmune screening was also negative. EEG showed non-specific diffuse slowing consistent with encephalopathy. His excessive sleepiness gradually improved together with his altered behaviour in about two weeks after presentation. Hyper sexuality became more overt during this phase. All these symptoms completely disappeared three weeks after his presentation and he attended school as before. He was readmitted six weeks later with exactly similar presentation and again only positive result being diffuse non-specific slowing of EEG. His recovery was also similar and he was completely back to his normal self in three weeks time. His recurrent symptoms were consistent with ‘Kleine-Levin syndrome (KLS)’ or ‘sleeping beauty syndrome’. KLS is a rare disorder which mainly affects adolescent males. Common symptoms include hypersomnia (100%), cognitive changes (96%), eating disturbances (80%), hypersexuality, compulsions, and depressed mood. The syndrome usually lasts for 8 years, with on an average seven episode of 10 days each recurring every 3.5 months. It is most frequently precipitated by infections and somnolence decreases using stimulants in nearly 40% of cases. PMID:24891916

  9. Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

    PubMed Central

    Aldridge, Dominic R.; Tranah, Edward J.; Shawcross, Debbie L.

    2015-01-01

    The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. PMID:26041962

  10. Food Safety: Bovine Spongiform Encephalopathy (Mad Cow Disease).

    PubMed

    Acheson, David W. K.

    2002-01-01

    Bovine spongiform encephalopathy is just one of a group of diseases known as transmissible spongiform encephalopathies. Only recently has it become recognized that transmissible spongiform encephalopathies are likely due to proteins known as prions. Although it has been recognized that transmissible spongiform encephalopathies may readily spread within species, the recent observations that bovine spongiform encephalopathy in cattle may have originated from another transmissible spongiform encephalopathy in sheep, known as scrapie, is cause for concern. Further, bovine spongiform encephalopathy has now been strongly linked with a universally fatal human neurologic disease known as new variant Creutzfeldt-Jakob disease. Currently the only approach to preventing bovine spongiform encephalopathy, and subsequent new variant Creutzfeldt-Jakob disease in humans, from ingestion of bovine spongiform encephalopathy-infected material is to avoid consumption of contaminated food. Little can be done to treat food that will destroy prions and leave a palatable product. At this stage we are continuing to learn about transmissible spongiform encephalopathies and their implications on human health. This is an ever-changing situation and has an unpredictable element in terms of the extent of the current outbreaks in England and other parts of Europe. PMID:11984426

  11. Advances in cirrhosis: Optimizing the management of hepatic encephalopathy.

    PubMed

    Liu, Andy; Perumpail, Ryan B; Kumari, Radhika; Younossi, Zobair M; Wong, Robert J; Ahmed, Aijaz

    2015-12-18

    Hepatic encephalopathy (HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE (CHE) and overt HE (OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis. PMID:26692331

  12. Posterior reversible encephalopathy syndrome in leukemic children: a sensitive issue.

    PubMed

    Kridis, Wala Ben; Mdhaffer, Moez; Hentati, Yosr; Kammoun, Fatma; Milad, Abir; Haddar, Sondes; Mahfoudh, Khaireddine Ben; Triki, Chahinez; Elloumi, Moez

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an acute central nervous system disorder characterized by reversible brain vasogenic edema. We report here a new case of a nine-year-old boy with B-cell acute lymphoblastic leukemia (B-ALL) who developed PRES secondary to induction chemotherapy including dexamethasone (dexamethasone®), vincristine (oncovin(®)), daunorubicin (adriblastine(®)) and intrathecal injection. Cerebral magnetic resonance imaging (MRI) showed high signal intensity on T2 at cortical and sub cortical region of parieto-frontal and parieto-occipital lobes. The patient was put under sodium valproate (depakine(®)) and we decided to continue dexamethasone (dexamethasone(®)) and daunorubicin (adriblastine(®)) injection. The MRI, after four weeks, was normal. So, we resumed vincristine (oncovin(®)) and we started L-asparaginase injections. Then, the outcome was favorable. The treatment of PRES is based on the withdrawal of the triggering factor to avoid the risk of irreversible lesions. But, due to the severity of leukemia the discontinuation of chemotherapy is difficult because of the risk of disease progression. PMID:24919742

  13. Advances in cirrhosis: Optimizing the management of hepatic encephalopathy

    PubMed Central

    Liu, Andy; Perumpail, Ryan B; Kumari, Radhika; Younossi, Zobair M; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Hepatic encephalopathy (HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE (CHE) and overt HE (OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis. PMID:26692331

  14. Heme Degradation by Heme Oxygenase Protects Mitochondria but Induces ER Stress via Formed Bilirubin

    PubMed Central

    Müllebner, Andrea; Moldzio, Rudolf; Redl, Heinz; Kozlov, Andrey V.; Duvigneau, J. Catharina

    2015-01-01

    Heme oxygenase (HO), in conjunction with biliverdin reductase, degrades heme to carbon monoxide, ferrous iron and bilirubin (BR); the latter is a potent antioxidant. The induced isoform HO-1 has evoked intense research interest, especially because it manifests anti-inflammatory and anti-apoptotic effects relieving acute cell stress. The mechanisms by which HO mediates the described effects are not completely clear. However, the degradation of heme, a strong pro-oxidant, and the generation of BR are considered to play key roles. The aim of this study was to determine the effects of BR on vital functions of hepatocytes focusing on mitochondria and the endoplasmic reticulum (ER). The affinity of BR to proteins is a known challenge for its exact quantification. We consider two major consequences of this affinity, namely possible analytical errors in the determination of HO activity, and biological effects of BR due to direct interaction with protein function. In order to overcome analytical bias we applied a polynomial correction accounting for the loss of BR due to its adsorption to proteins. To identify potential intracellular targets of BR we used an in vitro approach involving hepatocytes and isolated mitochondria. After verification that the hepatocytes possess HO activity at a similar level as liver tissue by using our improved post-extraction spectroscopic assay, we elucidated the effects of increased HO activity and the formed BR on mitochondrial function and the ER stress response. Our data show that BR may compromise cellular metabolism and proliferation via induction of ER stress. ER and mitochondria respond differently to elevated levels of BR and HO-activity. Mitochondria are susceptible to hemin, but active HO protects them against hemin-induced toxicity. BR at slightly elevated levels induces a stress response at the ER, resulting in a decreased proliferative and metabolic activity of hepatocytes. However, the proteins that are targeted by BR still have

  15. Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

    PubMed Central

    Kim, Kwi Suk; Moon, Aree; Kang, Hyoung Jin; Shin, Hee Young; Choi, Young Hee; Kim, Hyang Sook; Kim, Sang Geon

    2016-01-01

    AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy. METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group. PMID:27358786

  16. Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo*

    PubMed Central

    Cui, Jian; Zhao, Hailin; Yi, Bin; Zeng, Jing; Lu, Kaizhi

    2015-01-01

    Objective: To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine. Design: Prospective, randomized, controlled study. Setting: Research laboratory. Subjects: Sprague Dawley rats. Interventions: Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 μM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and flow cytometry. Sprague-Dawley rats were subjected to common bile duct ligation surgery to explore the protective effect of dexmedetomidine on hyperbilirubinemia-induced alveolar epithelial cell injury and respiratory failure in comparison with the Sham (subjected to the surgery procedure but without bile duct ligation) or dexmedetomidine control (only received intraperitoneal injection of dexmedetomidine). Measurements and Main Results: In vitro, dexmedetomidine reversed the collapse of mitochondrial membrane potential (Δψm), upregulation of cytochrome C, B cell leukemia 2 associated X protein, and cleaved-caspase 3 and 9 in A549 epithelial cells with bilirubin challenge. Furthermore, dexmedetomidine reversed the arrest of cell cycle and the downregulation of the transforming growth factorβ, phosphorylated mammalian target of rapamycin, and p42/44 mitogen-activated protein kinase induced by bilirubin. In vivo, pulmonary edema and inflammation were found after common bile duct ligation. Bilirubin and Paco2 were significantly increased, and oxygen (Pao2) was significantly decreased in the blood of common bile duct ligation rats from the postsurgery day 7 to day 21 when compared with those in the sham controls, respectively (p < 0.01). Daily intraperitoneal injection of dexmedetomidine significantly alleviated the lung edema and injury and prevented respiratory failure. Conclusion: Our data both in vitro and in vivo demonstrated that dexmedetomidine protected alveolar

  17. Serum total bilirubin levels and coronary heart disease--Causal association or epiphenomenon?

    PubMed

    Kunutsor, Setor K

    2015-12-01

    Observational epidemiological evidence supports a linear inverse and independent association between serum total bilirubin levels and coronary heart disease (CHD) risk, but whether this association is causal remains to be ascertained. A Mendelian randomization approach was employed to test whether serum total bilirubin is causally linked to CHD. The genetic variant rs6742078--well known to specifically modify levels of serum total bilirubin and accounting for up to 20% of the variance in circulating serum total bilirubin levels--was used as an instrumental variable. In pooled analysis of estimates reported from published genome-wide association studies, every copy of the T allele of rs6742078 was associated with 0.42 standard deviation (SD) higher levels of serum total bilirubin (95% confidence interval, 0.40 to 0.43). Based on combined data from the Coronary Artery Disease Genome wide Replication and Meta-analyses and the Coronary Artery Disease (C4D) Genetics Consortium involving a total of 36,763 CHD cases and 76,997 controls, the odds ratio for CHD per copy of the T allele was 1.01 (95% confidence interval, 0.99 to 1.04). The odds ratio of CHD for a 1 SD genetically elevated serum total bilirubin level was 1.03 (95% confidence interval, 0.98 to 1.09). The current findings casts doubt on a strong causal association of serum total bilirubin levels with CHD. The inverse associations demonstrated in observational studies may be driven by biases such as unmeasured confounding and/or reverse causation. However, further research in large-scale consortia is needed. PMID:26408227

  18. Development of a System Model for Non-Invasive Quantification of Bilirubin in Jaundice Patients

    NASA Astrophysics Data System (ADS)

    Alla, Suresh K.

    Neonatal jaundice is a medical condition which occurs in newborns as a result of an imbalance between the production and elimination of bilirubin. Excess bilirubin in the blood stream diffuses into the surrounding tissue leading to a yellowing of the skin. An optical system integrated with a signal processing system is used as a platform to noninvasively quantify bilirubin concentration through the measurement of diffuse skin reflectance. Initial studies have lead to the generation of a clinical analytical model for neonatal jaundice which generates spectral reflectance data for jaundiced skin with varying levels of bilirubin concentration in the tissue. The spectral database built using the clinical analytical model is then used as a test database to validate the signal processing system in real time. This evaluation forms the basis for understanding the translation of this research to human trials. The clinical analytical model and signal processing system have been successful validated on three spectral databases. First spectral database is constructed using a porcine model as a surrogate for neonatal skin tissue. Samples of pig skin were soaked in bilirubin solutions of varying concentrations to simulate jaundice skin conditions. The resulting skins samples were analyzed with our skin reflectance systems producing bilirubin concentration values that show a high correlation (R2 = 0.94) to concentration of the bilirubin solution that each porcine tissue sample is soaked in. The second spectral database is the spectral measurements collected on human volunteers to quantify the different chromophores and other physical properties of the tissue such a Hematocrit, Hemoglobin etc. The third spectral database is the spectral data collected at different time periods from the moment a bruise is induced.

  19. Disaccharides in the treatment of hepatic encephalopathy.

    PubMed

    Sharma, Praveen; Sharma, Barjesh Chander

    2013-06-01

    Management of hepatic encephalopathy (HE) primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as nonabsorbable disaccharides and antimicrobial agents like rifaximin. The nonabsorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and minimal hepatic encephalopathy (MHE). Lactulose significantly improves cognitive function and health-related quality of life in patients with MHE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Lactulose has also shown to be effective in primary and secondary prophylaxis of HE. Disaccharides were found to be comparable to rifaximin in recent systemic reviews in the treatment of HE however conclusion was based on inclusion of some poor quality trials. Combination therapy of disaccharides either with rifaximin, L-ornithine L-aspartate,probiotics for the treatment of HE needs further validation in large studies. PMID:23456517

  20. Head stereotypies in STXBP1 encephalopathy.

    PubMed

    Kim, Young Ok; Korff, Christian M; Villaluz, Mel Michel G; Suls, Arvid; Weckhuysen, Sarah; De Jonghe, Peter; Scheffer, Ingrid E

    2013-08-01

    STXBP1 encephalopathy is associated with a range of movement disorders. We observed head stereotypies in three patients. These comprised a slow (<1Hz), high-amplitude, horizontal, 'figure-of-eight' pattern, beginning at age 4-6 years and resulting in neck muscle hypertrophy, in two males; a faster (2-3Hz), side-to-side, 'no' movement, starting at the age of 9 years 6 months was observed in one female. Upper limb and truncal stereotypies and vocalization occurred intermittently with the head movements. The stereotypies increased with excitement but settled with concentration and sleep. Head and upper limb stereotypies are valuable clinical clues to the diagnosis of STXBP1 encephalopathy in patients with profound impairments. PMID:23763664

  1. Encephalopathy of infection and systemic inflammation.

    PubMed

    Young, G Bryan

    2013-10-01

    This review will discuss several intracranial infections and sepsis-associated encephalopathy. Intracranial infections and inflammation of interest to the neurologist and EEG technicians include viral and autoimmune encephalitides; bacterial, fungal, and other meningitides; cerebritis; and brain abscess and subdural empyema. Sepsis-associated encephalopathy refers to a diffuse brain dysfunction secondary to infection that is principally located outside of the central nervous system. It is much more common than all of the intracranial infections put together, at least for adults in Western society. It probably involves a number of mechanisms that are not mutually exclusive and likely vary from patient to patient. Morbidity and mortality are directly related to the severity of SAE. The earliest features of SAE are delirium and mild EEG slowing; it is crucial to recognize these early features and to search for and treat the underlying infection promptly to reduce mortality and morbidity. PMID:24084178

  2. Hashimoto's encephalopathy: A rare proteiform disorder.

    PubMed

    Montagna, Giacomo; Imperiali, Mauro; Agazzi, Pamela; D'Aurizio, Federica; Tozzoli, Renato; Feldt-Rasmussen, Ulla; Giovanella, Luca

    2016-05-01

    Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians. The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism, demonstrating an excellent response to high dose steroids is presented together with a systematic review of the literature. PMID:26849953

  3. Hyperammonemia-induced encephalopathy: A rare devastating complication of bariatric surgery

    PubMed Central

    Kromas, Michelle L; Mousa, Omar Y; John, Savio

    2015-01-01

    The clinical manifestations of hyperammonemia are usually easily identifiable to the clinician when associated with liver disease and lead to prompt diagnosis and treatment. However, hyperammonemia-induced encephalopathy is rare in adults in the absence of overt liver disease, thus diagnosis is often delayed or missed leading to potentially life threatening complications. Without proper treatment, such patients can decompensate rapidly with poor outcomes including seizures, coma, and death. Early assessment of plasma ammonia levels in patients with normal hepatic function and characteristic symptoms of encephalopathy can lead to early intervention while investigating the underlying etiology. We describe a patient who presented with a 2-year progression of waxing and waning acute mental status changes after a Roux-en-Y gastric bypass surgery. He was found to have elevated ammonia level as well as orotic aciduria; results consistent with a urea cycle disorder. After consulting neurology as well as toxicology, he ultimately improved after dietary protein restriction, sodium benzoate and lactulose therapy. While rare, clinicians should have a high index of suspicion for late onset urea cycle disorders in symptomatic patients presenting with encephalopathy secondary to hyperammonemia. PMID:25954483

  4. Wernicke's encephalopathy induced by hyperemesis gravidarum

    PubMed Central

    Palacios-Marqués, Ana; Delgado-García, Silvia; Martín-Bayón, Tina; Martínez-Escoriza, Juan Carlos

    2012-01-01

    Wernicke's encephalopathy (WE) is a reversible neurological emergency caused by thiamine deficiency. Prolonged vomiting in pregnancy results in thiamine depletion. The early recognition of its clinical signs and symptoms is essential to establish the suspected diagnosis and can be confirmed by MRI. Prompt administration of thiamine is important for preventing the occurrence of sequelae in the mother and for improving the fetal prognostic. We report a case of WE induced by hyperemesis gravidarum with a good maternal and fetal outcome. PMID:22684836

  5. Ciprofloxacin-associated posterior reversible encephalopathy

    PubMed Central

    Al Bu Ali, Waleed Hammad

    2013-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterised by numerous symptoms and of no specific aetiology. Headache, confusion, seizures, cortical visual disturbances or blindness are the key symptoms. As this syndrome is reversible and readily treated by interrupting or discontinuing the aetiology, it should sharply be acknowledged. Ciprofloxacin was associated with PRES in an adolescent male treated from chest infection. It was managed in a hospital intensive care unit and was observed until disappearance. PMID:23585504

  6. Transmissible Spongiform Encephalopathy and Meat Safety

    NASA Astrophysics Data System (ADS)

    Ward, Hester J. T.; Knight, Richard S. G.

    Prion diseases or transmissible spongiform encephalopathies (TSEs) comprise a wide-ranging group of neurodegenerative diseases found in animals and humans. They have diverse causes and geographical distributions, but have similar pathological features, transmissibility and, are ultimately, fatal. Central to all TSEs is the presence of an abnormal form of a normal host protein, namely the prion protein. Because of their potential transmissibility, these diseases have wide public health ramifications.

  7. [Drug therapy of patients with dyscirculatory encephalopathy].

    PubMed

    Macheret, Ie L; Khanenko, N V

    2002-01-01

    Results are submitted of treatment of discirculatory encephalopathy having developed against the background of arterial hypertension, with a combination of drugs aktovegin and captopril in 56 patients. The positive effect of the instituted monotherapy has been documented clinically, with correlation established with indices of additional methods of investigation. The secured results of treatment permit recommending actovegin and captopril for a wide use in practical medicine to treat patients in the above category. PMID:12145902

  8. Management of Hepatic Encephalopathy in the Hospital

    PubMed Central

    Leise, Michael D.; Poterucha, John J.; Kamath, Patrick S.; Kim, W. Ray

    2014-01-01

    Hepatic encephalopathy (HE) develops in about 50% of patients with cirrhosis and is one of the features of decompensated cirrhosis. The inpatient incidence of HE is approximately 23,000/year and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails two phases, induction and maintenance of remission. Most cases of significant hepatic encephalopathy are precipitated by infection, gastrointestinal bleeding, medications or other culprits. All patients should be evaluated for secondary triggers of HE and treatment should be initiated with a non-absorbable disaccharide (i.e. lactulose) in most cases. Rifaximin (off-label) can be added in patients not responding to lactulose. Neomycin is a less preferable alternative to rifaximin, due to its side effect profile. Other therapies including zinc, LOLA, and branch chain amino acids can be considered for patients not responding to a disaccharide and non-absorbable antibiotic. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe hepatic encephalopathy who do not respond to medical therapy. It is critically important that patients hospitalized with significant hepatic encephalopathy continue a maintenance medication(s) at the time of dismissal to prevent further episodes. Patients with a 1st time episode of HE can be placed on lactulose and careful instruction should be provided to patient and caregiver about titration of dose to achieve 3 bowel movements per day. Patients with recurrent HE episodes despite lactulose benefit from the addition of rifaximin which decreases the frequency of recurrent HE episodes and related hospitalizations. Lastly, patients and their families should be counselled about the risk of motor vehicle accidents which

  9. The Role of the Neurointensive Care Nursery for Neonatal Encephalopathy.

    PubMed

    Glass, Hannah C; Rowitch, David H

    2016-09-01

    Neonatal encephalopathy due to intrapartum events is estimated at 1 to 2 per 1000 live births in high-income countries. Outcomes have improved over the past decade due to implementation of therapeutic hypothermia, the only clinically available neuroprotective strategy for hypoxic-ischemic encephalopathy. Neonatal encephalopathy is the most common condition treated within a neonatal neurocritical care unit. Neonates with encephalopathy benefit from a neurocritical care approach due to prevention of secondary brain injury through attention to basic physiology, earlier recognition and treatment of neurologic complications, consistent management using guidelines and protocols, and use of optimized teams at dedicated referral centers. PMID:27524453

  10. Valproate-induced encephalopathy with predominant pancerebellar syndrome

    PubMed Central

    Verma, Rajesh; Kori, Prakash

    2012-01-01

    Valproate-induced hyperammonemic encephalopathy is a rare event clinically characterized by impaired sensorium, vomiting, headache, seizures and focal neurological deficits. The pathogenesis of this dreadful complication is not well understood, although hyperammonemia has been implicated in causation of encephalopathy. In this submission, we have highlighted a case of valproate-induced encephalopathy who presented mainly with bilateral cerebellar features and generalized slowing on electroencephalogram. High index of suspicion of valproate-induced hyperammonemic encephalopathy is required if diffuse ataxia is present as it is a potentially reversible clinical disorder. PMID:22345888

  11. Using saccades to diagnose covert hepatic encephalopathy.

    PubMed

    Cunniffe, Nicholas; Munby, Henry; Chan, Shona; Saatci, Defne; Edison, Eric; Carpenter, R H S; Massey, Dunecan

    2015-06-01

    Covert Hepatic Encephalopathy (CHE), previously known as Minimal Hepatic Encephalopathy, is a subtle cognitive defect found in 30-70 % of cirrhosis patients. It has been linked to poor quality of life, impaired fitness to drive, and increased mortality: treatment is possible. Despite its clinical significance, diagnosis relies on psychometric tests that have proved unsuitable for use in a clinical setting. We investigated whether measurement of saccadic latency distributions might be a viable alternative. We collected data on 35 cirrhosis patients at Addenbrooke's Hospital, Cambridge, with no evidence of clinically overt encephalopathy, and 36 age-matched healthy controls. Performance on standard psychometric tests was evaluated to determine those patients with CHE as defined by the World Congress of Gastroenterology. We then compared visually-evoked saccades between those with CHE and those without, as well as reviewing blood test results and correlating saccadic latencies with biochemical parameters and prognostic scores. Cirrhosis patients have significantly longer median saccadic latencies than healthy controls. Those with CHE had significantly prolonged saccadic latencies when compared with those without CHE. Analysis of a cirrhosis patient's saccades can diagnose CHE with a sensitivity of 75 % and a specificity of 75 %. We concluded that analysis of a cirrhosis patient's saccadic latency distributions is a fast and objective measure that can be used as a diagnostic tool for CHE. This improved early diagnosis could direct avoidance of high-risk activities such as driving, and better inform treatment strategies. PMID:25586511

  12. Blood Biomarkers for Evaluation of Perinatal Encephalopathy

    PubMed Central

    Graham, Ernest M.; Burd, Irina; Everett, Allen D.; Northington, Frances J.

    2016-01-01

    Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the “liquid brain biopsy.” A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment. PMID:27468268

  13. De novo mutations in epileptic encephalopathies.

    PubMed

    Allen, Andrew S; Berkovic, Samuel F; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E; Epstein, Michael P; Glauser, Tracy; Goldstein, David B; Han, Yujun; Heinzen, Erin L; Hitomi, Yuki; Howell, Katherine B; Johnson, Michael R; Kuzniecky, Ruben; Lowenstein, Daniel H; Lu, Yi-Fan; Madou, Maura R Z; Marson, Anthony G; Mefford, Heather C; Esmaeeli Nieh, Sahar; O'Brien, Terence J; Ottman, Ruth; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K; Scheffer, Ingrid E; Sherr, Elliott H; Yuskaitis, Christopher J; Abou-Khalil, Bassel; Alldredge, Brian K; Bautista, Jocelyn F; Berkovic, Samuel F; Boro, Alex; Cascino, Gregory D; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P; Fiol, Miguel; Fountain, Nathan B; French, Jacqueline; Friedman, Daniel; Geller, Eric B; Glauser, Tracy; Glynn, Simon; Haut, Sheryl R; Hayward, Jean; Helmers, Sandra L; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E; Knowlton, Robert C; Kossoff, Eric H; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H; McGuire, Shannon M; Motika, Paul V; Novotny, Edward J; Ottman, Ruth; Paolicchi, Juliann M; Parent, Jack M; Park, Kristen; Poduri, Annapurna; Scheffer, Ingrid E; Shellhaas, Renée A; Sherr, Elliott H; Shih, Jerry J; Singh, Rani; Sirven, Joseph; Smith, Michael C; Sullivan, Joseph; Lin Thio, Liu; Venkat, Anu; Vining, Eileen P G; Von Allmen, Gretchen K; Weisenberg, Judith L; Widdess-Walsh, Peter; Winawer, Melodie R

    2013-09-12

    Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders. PMID:23934111

  14. Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic encephalopathy.

    PubMed

    Nomoto, Koichi; Scurlock, Corey; Bronster, David

    2011-12-01

    An 85 year old man with a history of chronic renal insufficiency was admitted to the cardiothoracic intensive care unit after aortic valve replacement. His postoperative course was marked by acute oliguric renal failure for high blood urea nitrogen (BUN) and acute hyperactive delirium. At this time he also developed tremors with muscle twitching; he received no other form of sedatives. A neurology consult made the diagnosis of twitch-convulsive syndrome associated with uremic encephalopathy. While the patient was receiving the dexmedetomidine infusion, the signs of the twitch-convulsive syndrome, particularly the twitching and tremors, disappeared. Within 30 minutes of the end of the dexmedetomidine infusion, symptoms of the twitch-convulsive syndrome returned, manifesting as acute tremulousness. After several dialysis treatments, his BUN decreased and the dexmedetomidine was weaned, without return of the symptoms of twitch-convulsive syndrome. PMID:22137518

  15. Genetics Home Reference: acute necrotizing encephalopathy type 1

    MedlinePlus

    ... interacts with a protein complex known as the nuclear pore. The nuclear pore is a channel that allows transport of ... transport of proteins and other molecules through the nuclear pore and helps modify proteins coming into or ...

  16. Encephalopathy in Acute Leukaemia Associated with Methotrexate Therapy

    PubMed Central

    Kay, H. E. M.; Knapton, P. J.; O'Sullivan, J. P.; Wells, D. G.; Harris, Ruth F.; Innes, Elizabeth M.; Stuart, J.; Schwartz, F. C. M.; Thompson, Eileen N.

    1972-01-01

    Seven patients are described in whom dementia developed during treatment with methotrexate for meningeal leukaemia. The patients presented with confusion, tremor, ataxia, irritability, and somnolence. There were major epileptic fits in two cases and in one case there was progression to coma and death. Necropsy findings in the latter showed infarcted areas in the temporal and parietal lobes, with no evidence of active leukaemic disease or of viral encephalitis. The condition has not responded to radiotherapy and no positive evidence of viral encephalitis has been obtained. On the other hand, when treated with folinic and folic acid the deterioration has been arrested and there has been some improvement; thus the condition appears to be due to methotrexate. The occurrence of so many cases within the past year of a condition not previously described is probably attributable to the introduction of intensive cytotoxic therapy directed against meningeal leukaemia. ImagesFIG. 2.FIG. 3.FIG. 4FIG. 5 PMID:4504035

  17. Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

    2016-01-01

    Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. PMID:26679676

  18. The relationships between neonatal encephalopathy and cerebral palsy: a cohort study.

    PubMed

    Evans, K; Rigby, A S; Hamilton, P; Titchiner, N; Hall, D M

    2001-03-01

    There is a high risk of cerebral palsy (CP) following neonatal encephalopathy (NE) with fits, often attributed to intrapartum asphyxia. The evidence for the association is inconclusive and antepartum factors offer an alternative explanation. A cohort study was carried out to assess the evidence for and against hypoxic ischaemic injury as the cause of NE-associated CP in term infants. A total of 57 159 consecutive births were enrolled. There were 150 cases with NE, of whom 92 had at least one fit and 58 had no fits. The incidence of all NE was 2.62 per 1000 births and of NE with fits was 1.61 per 1000 births. Infants with NE were followed-up to identify those with cerebral palsy. There were 13 cases of four-limb cerebral palsy and three with hemiplegia among the survivors. In 12 of the 13 cases of four-limb CP, a combination of low Apgar scores, an early onset acute evolving encephalopathy, acidosis, renal dysfunction and the absence of antepartum factors suggested an acute intrapartum event as the immediate cause of the NE. An obstetric event likely to cause acute hypoxic injury was identified in four of the 12 cases. The clinical picture was similar in the four with and the eight without a specific obstetric event. The pathway leading to NE-associated CP remains unexplained, but intrapartum events appear to play a major role in most cases. PMID:12521875

  19. Physiological Antioxidative Network of the Bilirubin System in Aging and Age-Related Diseases

    PubMed Central

    Kim, Sung Young; Park, Sang Chul

    2012-01-01

    Oxidative stress is detrimental to life process and is particularly responsible for aging and age-related diseases. Thus, most organisms are well equipped with a spectrum of biological defense mechanisms against oxidative stress. The major efficient antioxidative mechanism is the glutathione system, operating a redox cycling mechanism for glutathione utilization, which consists of glutathione and its peroxidase and reductase. However, this system is mainly effective for hydrophilic oxidants, while lipophilic oxidants require another scavenging system. Since many age-related pathological conditions are related to lipid peroxidation, especially in association with the aging process, the physiological role of the scavenging system for lipophilic oxidants should be considered. In this regard, the biliverdin to bilirubin conversion pathway, via biliverdin reductase (BVR), is suggested to be another major protective mechanism that scavenges lipophilic oxidants because of the lipophilic nature of bilirubin. The efficiency of this bilirubin system might be potentiated by operation of the intertwined bicyclic systems of the suggested redox metabolic cycle of biliverdin and bilirubin and the interactive control cycle of BVR and heme oxygenase. In order to combat oxidative stress, both antioxidative systems against hydrophilic and lipophilic oxidants are required to work cooperatively. In this regard, the roles of the bilirubin system in aging and age-related diseases are reassessed in this review, and their interacting networks are evaluated. PMID:22457648

  20. Potential Cardiovascular Risk Protection of Bilirubin in End-Stage Renal Disease Patients under Hemodialysis

    PubMed Central

    do Sameiro-Faria, Maria; Kohlova, Michaela; Ribeiro, Sandra; Rocha-Pereira, Petronila; Teixeira, Laetitia; Nascimento, Henrique; Reis, Flávio; Miranda, Vasco; Bronze-da-Rocha, Elsa; Quintanilha, Alexandre; Belo, Luís; Costa, Elísio; Santos-Silva, Alice

    2014-01-01

    We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. The UGT1A1 genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 genotypes, respectively. Although no difference was found in UGT1A1 genotype distribution between the three tertiles of bilirubin, significant differences were found with increasing bilirubin levels, namely, a decrease in platelet, leukocyte, and lymphocyte counts, transferrin, oxidized low-density lipoprotein (ox-LDL), ox-LDL/low-density lipoprotein cholesterol ratio, apolipoprotein (Apo) A, Apo B, and interleukin-6 serum levels and a significant increased concentration of hemoglobin, hematocrit, erythrocyte count, iron, transferrin saturation, Apo A/Apo B ratio, adiponectin, and paraoxonase 1 serum levels. After adjustment for age these results remained significant. Our data suggest that higher bilirubin levels are associated with beneficial effects in HD patients, by improving lipid profile and reducing the inflammatory grade, which might contribute to increase in iron availability. These results suggest a potential cardiovascular risk protection of bilirubin in HD patients. PMID:25276769

  1. Pro-healing effects of bilirubin in open excision wound model in rats.

    PubMed

    Ahanger, Azad A; Leo, Marie D; Gopal, Anu; Kant, Vinay; Tandan, Surendra K; Kumar, Dinesh

    2016-06-01

    Bilirubin, a by-product of heme degradation, has an important role in cellular protection. Therefore, we speculated that bilirubin could be of potential therapeutic value in wound healing. To validate the hypothesis, we used a full-thickness cutaneous wound model in rats. Bilirubin (30 mg/kg) was administered intraperitoneally every day for 9 days. The surface area of the wound was measured on days 0, 2, 4, 7 and 10 after the creation of the wound. The granulation tissue was collected on day 10 post-wounding for analysing various parameters of wound healing. Bilirubin treatment accelerated wound contraction and increased hydroxyproline and glucosamine contents. mRNA expression of pro-inflammatory factors such as intercellular cell adhesion molecule-1 (ICAM-1) and tumour necrosis factor-α (TNF-α) were down-regulated and that of anti-inflammatory cytokine interleukin-10 (IL-10) was up-regulated. The findings suggest that bilirubin could be a new agent for enhancing cutaneous wound healing. PMID:24947136

  2. An amperometric bilirubin biosensor based on a conductive poly-terthiophene-Mn(II) complex.

    PubMed

    Rahman, Md Aminur; Lee, Kyung-Sun; Park, Deog-Su; Won, Mi-Sook; Shim, Yoon-Bo

    2008-01-18

    An amperometric bilirubin biosensor was fabricated by complexing the Mn(II) ion with a conducting polymer and the final biosensor surface was coated with a thin polyethyleneimine (PEI) film containing an enzyme, ascorbate oxidase (AsOx). The complexation between poly-5,2'-5',2''-terthiophene-3-carboxylic acid (PolyTTCA) and Mn(II) through the formation of Mn-O bond was confirmed by XPS. The PolyTTCA-Mn(II) complex was also characterized using cyclic voltammetry. The PolyTTCA-Mn(II)/PEI-AsOx biosensor specifically detect bilirubin through the mediated electron transfer by the Mn(II) ion. To optimize the experimental condition, various experimental parameters such as pH, temperature, and applied potential were examined. A linear calibration plot for bilirubin was obtained between 0.1 microM and 50 microM with the detection limit of 40+/-3.8 nM. Interferences from other biological compounds, especially ascorbate and dopamine were efficiently minimized by coating the biosensor surface with PEI-AsOx. The bilirubin sensor exhibited good stability and fast response time (<5s). The applicability of this bilirubin sensor was tested in a human serum sample. PMID:17964773

  3. A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

    PubMed Central

    Milton, Jacqueline N.; Sebastiani, Paola; Solovieff, Nadia; Hartley, Stephen W.; Bhatnagar, Pallav; Arking, Dan E.; Dworkis, Daniel A.; Casella, James F.; Barron-Casella, Emily; Bean, Christopher J.; Hooper, W. Craig; DeBaun, Michael R.; Garrett, Melanie E.; Soldano, Karen; Telen, Marilyn J.; Ashley-Koch, Allison; Gladwin, Mark T.; Baldwin, Clinton T.; Steinberg, Martin H.; Klings, Elizabeth S.

    2012-01-01

    Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities. PMID:22558097

  4. Early detection of hepatic encephalopathy by recording visual evoked potential (VEP).

    PubMed

    Zamir, Doron; Storch, Shimon; Kovach, Ivan; Storch, Rita; Zamir, Chen

    2002-01-01

    The visual evoked potential (VEP) record in response to a pattern stimulus is a non invasive and reliable method of detecting central and peripheral nerve system abnormalities. VEP recording have been used in animals with fulminant hepatic failure, and also in-patients with hepatic encephalopathy and acute severe hepatitis. Our aims were: a. to evaluate the potency of PVEP in assessing hepatic encephalopathy. b. to find the rate of pathologic PVEP in patients with advanced liver cirrhosis. VEP was recorded in 14 chronic liver cirrhotic patients (6 alcoholic, 6 HCV-related, 2 cryptogenic) and 14 controls. Patients with any neurologic abnormalities were excluded from the study. All patients were subjected to the Mental State Score (MSS) test, and venous blood ammonia was measured on the same day of VEP recording. In 10/14 (71%) patients some VEP recording abnormality was detected. In the cirrhotic patients, P100 latency was significantly longer (P < 0.05) than in controls. Low amplitude was observed in 8 patients compared to controls. Marked increase of N75 (3 patients) and marked increase of N145 (2 patients) were observed. Mean blood ammonia and MSS score were normal in all patients. No correlation was found between both MSS score and blood ammonia levels and the P100 delay. Five out of 10 patients with pathologic VEP developed hepatic encephalpathy during a follow-up of one year, compared to one out of 4 patients with no pathology on VEP recording. VEP recording may be a valuable tool in assessing patients with early hepatic encephalopathy and in predicting encephalopathy. PMID:12533959

  5. Wernicke's Encephalopathy: An Unusual Consequence of the Acquired Immune Deficiency Syndrome—Case Report and Literature Review

    PubMed Central

    Larsen, Timothy R.; Williams, Michael

    2013-01-01

    Introduction. Wernicke's encephalopathy is a well-described syndrome characterized by the classic triad of confusion, ataxia, and ophthalmoplegia. Wernicke's encephalopathy results from thiamine (vitamin B1) deficiency. Common causes include alcoholism and gastric disorders. Wernicke's has been described in patients with acquired immune deficiency syndrome (AIDS); however, given these patients' immunosuppressed state, the diagnosis of Wernicke's encephalopathy is not apparent. Case Presentation. A 31-year-old previously healthy male presented to the ER complaining of progressive dyspnea. Workup revealed HIV/AIDS and PCP pneumonia. He was treated and improved. On day 14 he became confused and developed nystagmus and ataxia. Considering his immunocompromised state, infectious and neoplastic etiologies topped the differential diagnosis. CT head was negative. Lumbar puncture was unremarkable. Brain MRI revealed increased T2 signal in the medial thalamus bilaterally. Intravenous thiamine was administered resulting in resolution of symptoms. Discussion. The classic triad of Wernicke's encephalopathy occurs in 10% of cases. When immunosuppressed patients develop acute neurologic symptoms infectious or neoplastic etiologies must be excluded. However, given the relative safety of thiamine supplementation, there should be a low threshold for initiating therapy in order to reverse the symptoms and prevent progression to Korsakoff dementia, which is permanent. PMID:23935638

  6. Wernicke's Encephalopathy: An Unusual Consequence of the Acquired Immune Deficiency Syndrome-Case Report and Literature Review.

    PubMed

    Larsen, Timothy R; Dragu, Dritan; Williams, Michael

    2013-01-01

    Introduction. Wernicke's encephalopathy is a well-described syndrome characterized by the classic triad of confusion, ataxia, and ophthalmoplegia. Wernicke's encephalopathy results from thiamine (vitamin B1) deficiency. Common causes include alcoholism and gastric disorders. Wernicke's has been described in patients with acquired immune deficiency syndrome (AIDS); however, given these patients' immunosuppressed state, the diagnosis of Wernicke's encephalopathy is not apparent. Case Presentation. A 31-year-old previously healthy male presented to the ER complaining of progressive dyspnea. Workup revealed HIV/AIDS and PCP pneumonia. He was treated and improved. On day 14 he became confused and developed nystagmus and ataxia. Considering his immunocompromised state, infectious and neoplastic etiologies topped the differential diagnosis. CT head was negative. Lumbar puncture was unremarkable. Brain MRI revealed increased T2 signal in the medial thalamus bilaterally. Intravenous thiamine was administered resulting in resolution of symptoms. Discussion. The classic triad of Wernicke's encephalopathy occurs in 10% of cases. When immunosuppressed patients develop acute neurologic symptoms infectious or neoplastic etiologies must be excluded. However, given the relative safety of thiamine supplementation, there should be a low threshold for initiating therapy in order to reverse the symptoms and prevent progression to Korsakoff dementia, which is permanent. PMID:23935638

  7. Neonatal bilirubin management as an implementation example of interdisciplinary continuum of care tools.

    PubMed

    Thornton, Sidney N; Thompson, Bryce S; Millar, Jean A; Eggert, Larry D; Wilcox, Adam B

    2007-01-01

    Management of newborn bilirubin spans the inpatient and outpatient continuum of care. Intermountain Healthcare has developed and implemented a web-based tool for managing bilirubin that follows newborn patients across care settings and providers with a consistent plan of care. The underlying model for the tool is derived from published guidelines. The model divides the time-sensitive data into risk zones and associates each zone with the appropriate order set for follow-up care. The tool integrates Intermountain's Help2 infrastructure for authoring terms, guidelines, and order sets, with alerts, results, and data entry within the context of the care model. Implementation of the bilirubin management tool is shown to improve communication, ease workflow, and improve guideline compliance. Lessons learned from the implementation include recommendations for handling point-of-care laboratory data and managing archival views, which are insightful to health networks managing longitudinal data. PMID:18693932

  8. Role of bilirubin overproduction in revealing Gilbert's syndrome: is dyserythropoiesis an important factor?

    PubMed Central

    Metreau, J M; Yvart, J; Dhumeaux, D; Berthelot, P

    1978-01-01

    Gilbert's syndrome was diagnosed in 37 patients with unconjugated hyperbilirubinaemia without overt haemolysis or structural liver abnormality, who had a marked reduction in hepatic bilirubin UDP-glucuronosyltransferase activity (B-GTA) (as compared with that of 23 normal subjects). No significant correlation existed in these patients between serum bilirubin level and the values of B-GTA, thus suggesting that factors other than a low B-GTA must influence the degree of hyperbilirubinaemia in Gilbert's syndrome. Studies of 51Cr erythrocyte survival and 59Fe kinetics in 10 unselected patients demonstrated slight haemolysis in eight, whereas mild ineffective erythropoiesis was suggested in all from a low 24-hour incorporation of radioactive iron into circulating red cells. This overproduction of bilirubin resulting from mild haemolysis and perhaps dyserythropoiesis might reflect only an extreme degree of the normal situation. It certainly contributes to the hyperbilirubinaemia of Gilbert's syndrome and may play a major role in the manifestation of this condition. PMID:101425

  9. Separation by thin-layer chromatography and structure elucidation of bilirubin conjugates isolated from dog bile.

    PubMed Central

    Heirwegh, K P; Fevery, J; Michiels, R; van Hees, G P; Compernolle, F

    1975-01-01

    1. A system for separation of bile pigments by t.l.c. and for their structure elucidation is presented. Separated bile pigments are characterized by t.l.c. of derived dipyrrolic azopigments. 2. At the tetrapyrrolic stage hydrolysis in strongly alkaline medium followed by t.l.c. demonstrates the presence of bilirubin-IIIalpha, -IXalpha and -XIIIalpha and allows assessment of their relative amounts. 3. Most structural information is derived from analysis of dipyrrolic azopigments. Such derivatives, obtained by treatment of separated bile pigments with diazotized ethyl anthranilate, were separated and purified by t.l.c. Micro methods showed (a) the nature of the dipyrrolic aglycone, (b) the nature of the bonds connecting aglycone to a conjugating group, (c) the ratio of vinyl/isovinyl isomers present in the aglycone and, (d) the nature of the conjugating groups (by suitable derivative formation and t.l.c. with reference to known compounds). 4. In bile of normal dogs at least 20 tetrapyrrolic, diazo-positive bile pigments could be recognized. Except for two pigments the tetrapyrrolic nucleus corresponded predominantly to bilirubin-IXalpha. All conjugated pigments had their conjugating groups connected in ester linkage to the tetrapyrrolic aglycone, Apart from bilirubin-IXalpha, monoconjugates and homogeneous and mixed diconjugates of bilirubin were demonstrated; conjugating groups of major importance were xylose, glucose and glucuronic acid. 5. Bilirubin isomer determination on native bile and isolated bile pigments, and dipyrrole-exchange assays with [14C8]bilirubin indicated (a) that the conjugates pre-exist in bile, and (b) that no significant dipyrrole exchange occurs during isolation of the pigments. PMID:1156357

  10. Sensitizing effect of Z,Z-bilirubin IXα and its photoproducts on enzymes in model solutions

    NASA Astrophysics Data System (ADS)

    Plavskii, V. Yu.; Mostovnikov, V. A.; Tret'yakova, A. I.; Mostovnikova, G. R.

    2008-05-01

    In model systems, we have studied side effects which may be induced by light during phototherapy of hyperbilirubinemia (jaundice) in newborn infants, with the aim of reducing the Z,Z-bilirubin IXα (Z,Z-BR IXα) level. We have shown that the sensitizing effect of Z,Z-BR IXα, localized at strong binding sites of the human serum albumin (HSA) macromolecule, is primarily directed at the amino acid residues of the carrier protein and does not involve the molecules of the enzyme (lactate dehydrogenase (LDH)) present in the buffer solution. The detected photodynamic damage to LDH is due to sensitization by bilirubin photoisomers, characterized by lower HSA association constants and located (in contrast to native Z,Z-BR IXα) on the surface of the HSA protein globule. Based on study of the spectral characteristics of the photoproducts of Z,Z-BR IXα and comparison of their accumulation kinetics in solution and the enzyme photo-inactivation kinetics, we concluded that the determining role in sensitized damage to LDH is played by lumirubin. The photosensitization effect depends on the wavelength of the radiation used for photoconversion of bilirubin. When (at the beginning of exposure) we make sure that identical numbers of photons are absorbed by the pigment in the different spectral ranges, the side effect is minimal for radiation corresponding to the long-wavelength edge of the bilirubin absorption band. We have shown that for a bilirubin/HSA concentration ratio >2 (when some of the pigment molecules are sorbed on the surface of the protein globule), the bilirubin can act as a photosensitizing agent for the enzyme present in solution. We discuss methods for reducing unfavorable side effects of light on the body of newborn infants during phototherapy of hyperbilirubinemia.

  11. [Rifaximin for hepatic encephalopathy in children. Case report].

    PubMed

    Malla, Ivone; Torres Cerino, Verónica; Villa, Andrés; Cheang, Yu; Giacove, Gisela; Pedreira, Alejandra; Silva, Marcelo

    2011-12-01

    Rifaximin is an antibiotic recently approved for the treatment of hepatic encephalopathy in adults. In children more than 12 year-old, it has been approved for travelers' diarrhea and it is also widely used in inflammatory bowel disease. We report, to our knowledge, the first case of a pediatric patient who received rifaximin for hepatic encephalopathy with good clinical outcome. PMID:22231877

  12. Typical and atypical cases of bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. It is the most likely cause of variant Creutzfeldt-Jakob disease (vCJD) in humans, but the origin of BSE has not been eluci...

  13. The Spectrum of Disease in Chronic Traumatic Encephalopathy

    ERIC Educational Resources Information Center

    McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

    2013-01-01

    Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…

  14. Evaluation of the zoonotic potential of transmissible mink encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis to the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques as...

  15. Comparison of Transmissible Mink Encephalopathy Isolates in Raccoons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Owing to its susceptibility to various transmissible spongiform encephalopathies (TSE) and relatively short incubation times, the raccoon (Procyon lotor) has been suggested as a model for TSE strain differentiation. Transmissible mink encephalopathy (TME) is a prion disease of undetermined origin in...

  16. A Novel Perspective on the Biology of Bilirubin in Health and Disease.

    PubMed

    Gazzin, Silvia; Vitek, Libor; Watchko, Jon; Shapiro, Steven M; Tiribelli, Claudio

    2016-09-01

    Unconjugated bilirubin (UCB) is known to be one of the most potent endogenous antioxidant substances. While hyperbilirubinemia has long been recognized as an ominous sign of liver dysfunction, recent data strongly indicate that mildly elevated bilirubin (BLB) levels can be protective against an array of diseases associated with increased oxidative stress. These clinical observations are supported by new discoveries relating to the role of BLB in immunosuppression and inhibition of protein phosphorylation, resulting in the modulation of intracellular signaling pathways in vascular biology and cancer, among others. Collectively, the evidence suggests that targeting BLB metabolism could be considered a potential therapeutic approach to ameliorate a variety of conditions. PMID:27515064

  17. Oxygen biosensor based on bilirubin oxidase immobilized on a nanostructured gold electrode.

    PubMed

    Pita, Marcos; Gutierrez-Sanchez, Cristina; Toscano, Miguel D; Shleev, Sergey; De Lacey, Antonio L

    2013-12-01

    Gold disk electrodes modified with gold nanoparticles have been used as a scaffold for the covalent immobilization of bilirubin oxidase. The nanostructured bioelectrodes were tested as mediator-less biosensors for oxygen in a buffer that mimics the content and the composition of human physiological fluids. Chronoamperometry measurements showed a detection limit towards oxygen of 6 ± 1 μM with a linear range of 6-300 μM, i.e. exceeding usual physiological ranges of oxygen in human tissues and fluids. The biosensor presented is the first ever-reported oxygen amperometric biosensor based on direct electron transfer of bilirubin oxidase. PMID:23973738

  18. Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo in mice

    PubMed Central

    Bortolussi, Giulia; Baj, Gabriele; Vodret, Simone; Viviani, Giulia; Bittolo, Tamara; Muro, Andrés F.

    2014-01-01

    Neonatal jaundice is caused by high levels of unconjugated bilirubin. It is usually a temporary condition caused by delayed induction of UGT1A1, which conjugates bilirubin in the liver. To reduce bilirubin levels, affected babies are exposed to phototherapy (PT), which converts toxic bilirubin into water-soluble photoisomers that are readily excreted out. However, in some cases uncontrolled hyperbilirubinemia leads to neurotoxicity. To study the mechanisms of bilirubin-induced neurological damage (BIND) in vivo, we generated a mouse model lacking the Ugt1a1 protein and, consequently, mutant mice developed jaundice as early as 36 hours after birth. The mutation was transferred into two genetic backgrounds (C57BL/6 and FVB/NJ). We exposed mutant mice to PT for different periods and analyzed the resulting phenotypes from the molecular, histological and behavioral points of view. Severity of BIND was associated with genetic background, with 50% survival of C57BL/6‑Ugt1−/− mutant mice at postnatal day 5 (P5), and of FVB/NJ-Ugt1−/− mice at P11. Life-long exposure to PT prevented cerebellar architecture alterations and rescued neuronal damage in FVB/NJ-Ugt1−/− but not in C57BL/6-Ugt1−/− mice. Survival of FVB/NJ-Ugt1−/− mice was directly related to the extent of PT treatment. PT treatment of FVB/NJ-Ugt1−/− mice from P0 to P8 did not prevent bilirubin-induced reduction in dendritic arborization and spine density of Purkinje cells. Moreover, PT treatment from P8 to P20 did not rescue BIND accumulated up to P8. However, PT treatment administered in the time-window P0–P15 was sufficient to obtain full rescue of cerebellar damage and motor impairment in FVB/NJ-Ugt1−/− mice. The possibility to modulate the severity of the phenotype by PT makes FVB/NJ-Ugt1−/− mice an excellent and versatile model to study bilirubin neurotoxicity, the role of modifier genes, alternative therapies and cerebellar development during high bilirubin conditions. PMID

  19. Regression approach to non-invasive determination of bilirubin in neonatal blood

    NASA Astrophysics Data System (ADS)

    Lysenko, S. A.; Kugeiko, M. M.

    2012-07-01

    A statistical ensemble of structural and biophysical parameters of neonatal skin was modeled based on experimental data. Diffuse scattering coefficients of the skin in the visible and infrared regions were calculated by applying a Monte-Carlo method to each realization of the ensemble. The potential accuracy of recovering the bilirubin concentration in dermis (which correlates closely with that in blood) was estimated from spatially resolved spectrometric measurements of diffuse scattering. The possibility to determine noninvasively the bilirubin concentration was shown by measurements of diffuse scattering at λ = 460, 500, and 660 nm at three source-detector separations under conditions of total variability of the skin biophysical parameters.

  20. Modeling Chronic Traumatic Encephalopathy: The Way Forward for Future Discovery

    PubMed Central

    Turner, Ryan C.; Lucke-Wold, Brandon P.; Logsdon, Aric F.; Robson, Matthew J.; Lee, John M.; Bailes, Julian E.; Dashnaw, Matthew L.; Huber, Jason D.; Petraglia, Anthony L.; Rosen, Charles L.

    2015-01-01

    Despite the extensive media coverage associated with the diagnosis of chronic traumatic encephalopathy (CTE), our fundamental understanding of the disease pathophysiology remains in its infancy. Only recently have scientific laboratories and personnel begun to explore CTE pathophysiology through the use of preclinical models of neurotrauma. Some studies have shown the ability to recapitulate some aspects of CTE in rodent models, through the use of various neuropathological, biochemical, and/or behavioral assays. Many questions related to CTE development, however, remain unanswered. These include the role of impact severity, the time interval between impacts, the age at which impacts occur, and the total number of impacts sustained. Other important variables such as the location of impacts, character of impacts, and effect of environment/lifestyle and genetics also warrant further study. In this work, we attempt to address some of these questions by exploring work previously completed using single- and repetitive-injury paradigms. Despite some models producing some deficits similar to CTE symptoms, it is clear that further studies are required to understand the development of neuropathological and neurobehavioral features consistent with CTE-like features in rodents. Specifically, acute and chronic studies are needed that characterize the development of tau-based pathology. PMID:26579067

  1. Modeling Chronic Traumatic Encephalopathy: The Way Forward for Future Discovery.

    PubMed

    Turner, Ryan C; Lucke-Wold, Brandon P; Logsdon, Aric F; Robson, Matthew J; Lee, John M; Bailes, Julian E; Dashnaw, Matthew L; Huber, Jason D; Petraglia, Anthony L; Rosen, Charles L

    2015-01-01

    Despite the extensive media coverage associated with the diagnosis of chronic traumatic encephalopathy (CTE), our fundamental understanding of the disease pathophysiology remains in its infancy. Only recently have scientific laboratories and personnel begun to explore CTE pathophysiology through the use of preclinical models of neurotrauma. Some studies have shown the ability to recapitulate some aspects of CTE in rodent models, through the use of various neuropathological, biochemical, and/or behavioral assays. Many questions related to CTE development, however, remain unanswered. These include the role of impact severity, the time interval between impacts, the age at which impacts occur, and the total number of impacts sustained. Other important variables such as the location of impacts, character of impacts, and effect of environment/lifestyle and genetics also warrant further study. In this work, we attempt to address some of these questions by exploring work previously completed using single- and repetitive-injury paradigms. Despite some models producing some deficits similar to CTE symptoms, it is clear that further studies are required to understand the development of neuropathological and neurobehavioral features consistent with CTE-like features in rodents. Specifically, acute and chronic studies are needed that characterize the development of tau-based pathology. PMID:26579067

  2. Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy.

    PubMed

    Cauli, Omar; Rodrigo, Regina; Llansola, Marta; Montoliu, Carmina; Monfort, Pilar; Piedrafita, Blanca; El Mlili, Nisrin; Boix, Jordi; Agustí, Ana; Felipo, Vicente

    2009-03-01

    Patients with hepatic encephalopathy (HE) may present different neurological alterations including impaired cognitive function and altered motor activity and coordination. HE may lead to coma and death. Many of these neurological alterations are the consequence of altered neurotransmission. Hyperammonemia is a main contributor to the alterations in neurotransmission and in neurological functions in HE. Both glutamatergic and GABAergic neurotransmission are altered in animal models of HE. We review some of these alterations, especially those alterations in glutamatergic neurotransmission responsible for some specific neurological alterations in hyperammonemia and HE: the role 1) of excessive NMDA receptors activation in death induced by acute hyperammonemia; 2) of impaired function of the glutamate-nitric oxide-cGMP pathway, associated to NMDA receptors, in cognitive impairment in chronic HE; 3) of increased extracellular glutamate and activation of metabotropic glutamate receptors in substantia nigra in hypokinesia in chronic HE. The therapeutic implications are discussed. We also review the alterations in the function of the neuronal circuits between basal ganglia-thalamus-cortex modulating motor activity and the role of sequential alterations in glutamatergic and GABAergic neurotransmission in these alterations. HE would be a consequence of altered neuronal communication due to alterations in general neurotransmission involving different neurotransmitter systems in different neurons. PMID:19085094

  3. Evaluation of rifaximin in management of hepatic encephalopathy.

    PubMed

    Wahib, Ali A; El-Deen Salem, M Negm; Ahmed, Mostafa A; El-Dessouky, Yasser M M; El-Tiby, Diaa M; El-Mola, Khaled; El-Sayed, Abeer M

    2014-12-01

    This study evaluated the efficacy of rifaximin versus lactulose in the treatment of hepatic encephalopathy (HE). The study population included 50 patients who were diagnosed to have signs of the first to third degree HE, according to the West Haven criteria and classified into two groups. GI: included 25 patients who had HE and were treated with lactulose syrup (laxolac) 90 ml daily divided into 3 doses for 7 days. GII: included 25 patients who had HE and were treated with rifaximin 1200 mg daily divided into 3 doses for 7 days. Patients in both groups also received other measures of treatment of HE as daily enema and protein restriction. Rifaximin significantly improved various subjective and measurable components of HE including mental status, behavior, asterixis, and serum ammonia concentration. In acute HE of grade 1 to grade 3, rifaximin may be a good alternative to non-absorbable disaccharides as it is broad spectrum, non-absorbable antibiotic with rapid action and little side effects. It is better tolerated, associated with less frequent and shorter hospitalization in comparison to lactulose. PMID:25643509

  4. Posterior reversible encephalopathy syndrome: another manifestation of CNS SLE?

    PubMed

    Ishimori, M L; Pressman, B D; Wallace, D J; Weisman, M H

    2007-01-01

    A variety of neuropsychiatric findings may complicate systemic lupus erythematosus (SLE) and pose diagnostic and therapeutic dilemmas. We describe the clinical and radiographic features of posterior reversible encephalopathy syndrome (PRES) and distinguish PRES from other conditions seen in SLE. Patient charts and magnetic resonance imaging (MRI) findings of four patients with SLE on immunosuppressive therapy with acute or subacute neurologic changes initially suggesting cerebritis or stroke were reviewed. The English language literature was reviewed using the Medline databases from 1996-2006 for other reports of PRES with SLE. Literature review yielded 26 other SLE cases reported with PRES. SLE patients with PRES were more commonly on immunosuppressive drugs, had episodes of relative hypertension, and had renal involvement. Characteristic findings are seen on MRI, which differentiate PRES from other CNS complications of SLE. Clinical and radiographic resolution of abnormalities within 1-4 weeks is typically seen. PRES has been increasingly recognized. Reversible changes are found on brain MRI accompanied by sometimes dramatic signs and symptoms. The therapeutic implications for separating PRES from stroke or cerebritis are important. We propose that PRES should be considered in the differential diagnosis in SLE patients with new-onset neurologic signs and symptoms. PMID:17664235

  5. A Case of Severe Ganciclovir-Induced Encephalopathy

    PubMed Central

    Sakamoto, Hikaru; Hirano, Makito; Nose, Kazuhiro; Ueno, Shuichi; Oki, Takashi; Sugimoto, Koichi; Nishioka, Tsukasa; Kusunoki, Susumu; Nakamura, Yusaku

    2013-01-01

    Background Ganciclovir, a drug against cytomegalovirus (CMV) infection, is generally well tolerated, but can cause neurotoxicity such as encephalopathy. Although ganciclovir-induced encephalopathy has been described in several reports, a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid were previously measured in only 3 patients with encephalopathy. Symptoms usually include confusion and disturbed consciousness, which mimic CMV encephalitis. Prompt and accurate diagnosis is thus sometimes difficult, and is derived solely from accumulated clinical information of definite cases, since ganciclovir concentrations, not routinely measured, become available after several days or a few weeks. Case Presentation Here, we summarize clinical information of all patients with definite ganciclovir-induced encephalopathy including our own patient, who had severe symptoms, with the highest reported trough concentration of ganciclovir in the blood, and underwent therapeutic dialysis with complete recovery. Conclusion Our summary of patients with definite encephalopathy could lead to prompt and accurate diagnoses. PMID:24403897

  6. The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies.

    PubMed

    Shbarou, Rolla; Mikati, Mohamad A

    2016-05-01

    Pediatric epileptic encephalopathies represent a clinically challenging and often devastating group of disorders that affect children at different stages of infancy and childhood. With the advances in genetic testing and neuroimaging, the etiologies of these epileptic syndromes are now better defined. The various encephalopathies that are reviewed in this article include the following: early infantile epileptic encephalopathy or Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome, severe myoclonic epilepsy in infancy (Dravet syndrome), Landau-Kleffner syndrome, Lennox-Gastaut syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep. Their clinical features, prognosis as well as underlying genetic etiologies are presented and updated. PMID:27544470

  7. Histopathological and imaging modifications in chronic ethanolic encephalopathy.

    PubMed

    Folescu, Roxana; Zamfir, Carmen Lăcrămioara; Sişu, Alina Maria; Motoc, Andrei Gheorghe Marius; Ilie, Adrian Cosmin; Moise, Marius

    2014-01-01

    Chronic abuse of alcohol triggers different types of brain damage. The Wernicke-Korsakoff syndrome gets together Wernicke's encephalopathy and Korsakoff's syndrome. Another type of encephalopathy associated with chronic ethanol consumption is represented by the Marchiafava-Bignami malady or syndrome, an extremely rare neurological disorder, which is characterized by a demielinization of corpus callosum, extending as far as a necrosis. Because the frequency of ethanolic encephalopathy is increased and plays a major role in the sudden death of ethanolic patients, we have studied the chronic ethanolic encephalopathy both in deceased and in living patients, presenting different pathologies related to the chronic ethanol consumption. The present study investigated the effects of chronic ethanolic encephalopathy on the central nervous system based both on the histopathological exam of the tissular samples and the imaging investigation, such as MRI and CT. PMID:25329105

  8. Three-dimensional brain metabolic imaging in patients with toxic encephalopathy

    SciTech Connect

    Callender, T.J.; Duhon, D.; Ristovv, M. ); Morrow, L. ); Subramanian, K. )

    1993-02-01

    Thirty-three workers, ages 24 to 63, developed clinical toxic encephalopathy after exposure to neurotoxins and were studied by SPECT brain scans. Five were exposed to pesticides, 13 were acutely exposed to mixtures of solvents, 8 were chronically exposed to mixtures of hazardous wastes that contained organic solvents, 2 were acutely exposed to phosgene and other toxins, and 5 had exposures to hydrogen sulfide. Twenty-nine had neuropsychological testing and all had a medical history and physical. Of the workers who had a clinical diagnosis of toxic encephalopathy, 31 (93.9%) had abnormal SPECT brain scans with the most frequent areas of abnormality being temporal lobes (67.7%), frontal lobes (61.3%), basal ganglia (45.2%), thalamus (29.0%), parietal lobes (12.9%), motorstrip (9.68%), cerebral hemisphere (6.45%), occipital lobes (3.23%), and caudate nucleus (3.23%). Twenty-three out of 29 (79.3%) neuropsychological evaluations were abnormal. Other modalities when performed included the following percentages of abnormals: NCV, 33.3%; CPT sensory nerve testing, 91.3%, vestibular function testing, 71.4%; olfactory testing, 89.2%; sleep EEG analysis, 85.7%; EEG, 8.33%; CT, 7.14%; and MRI brain scans, 28.6%. The complex of symptoms seen in toxic encephalopathy implies dysfunction involving several CNS regions. This series of patients adds to the previous experience of brain metabolic imaging and demonstrates that certain areas of the brain are typically affected despite differences in toxin structure, that these lesions can be globally defined by SPECT/PET brain scans, that these lesions correlate well with clinical and neuropsychological testing, and that such testing is a useful adjunct to previous methods. EEG and structural brain imaging such as CT and MRI are observed to have poor sensitivity in this type of patient. 32 refs., 5 tabs.

  9. Atypical presentation of human bocavirus: Severe respiratory tract infection complicated with encephalopathy.

    PubMed

    Akturk, Hacer; Sık, Guntulu; Salman, Nuran; Sutcu, Murat; Tatli, Burak; Ciblak, Meral Akcay; Erol, Oguz Bulent; Torun, Selda Hancerli; Citak, Agop; Somer, Ayper

    2015-11-01

    Human bocavirus (HBOV) has been reported as a worldwide distributed respiratory pathogen. It has also been associated with encephalitis recently by detection of the virus in cerebrospinal fluid (CSF) of patients presented with encephalitis. This retrospective study aimed to present clinical features of HBOV infections in children with respiratory symptoms and describe unexplained encephalopathy in a subgroup of these patients. Results of 1,143 pediatric nasal samples from mid-December 2013 to July 2014 were reviewed for detection of HBOV. A multiplex real time polymerase chain reaction assay was used for viral detection. Medical records of the patients were retrospectively analyzed. HBOV was detected in 30 patients (2.6%). Median age was 14 months (5-80). Clinical diagnoses were upper respiratory tract infection (n = 10), bronchopneumonia (n = 9), acute bronchiolitis (n = 5), pneumonia (n = 4), acute bronchitis (n = 1), and asthma execarbation (n = 1). Hospitalization was required in 16 (53.3%) patients and 10 (62.5%) of them admitted to pediatric intensive care unit (PICU). Noninvasive mechanical ventilation modalities was applied to four patients and mechanical ventilation to four patients. Intractable seizures developed in four patients while mechanically ventilated on the 2nd-3rd days of PICU admission. No specific reason for encephalopathy was found after a thorough investigation. No mortality was observed, but two patients were discharged with neurological sequela. HBOV may lead to respiratory infections in a wide spectrum of severity. This report indicates its potential to cause severe respiratory infections requiring PICU admission and highlights possible clinical association of HBOV and encephalopathy, which developed during severe respiratory infection. PMID:25966820

  10. Association between bilirubin and risk of Non-Alcoholic Fatty Liver Disease based on a prospective cohort study.

    PubMed

    Tian, Jianbo; Zhong, Rong; Liu, Cheng; Tang, Yuhan; Gong, Jing; Chang, Jiang; Lou, Jiao; Ke, Juntao; Li, Jiaoyuan; Zhang, Yi; Yang, Yang; Zhu, Ying; Gong, Yajie; Xu, Yanyan; Liu, Peiyi; Yu, Xiao; Xiao, Lin; Du, Min; Yang, Ling; Yuan, Jing; Wang, Youjie; Chen, Weihong; Wei, Sheng; Liang, Yuan; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Yao, Ping; Miao, Xiaoping

    2016-01-01

    The study aimed to assess the association between total, direct, and indirect bilirubin and nonalcoholic fatty live disease (NAFLD) risk given its high prevalence and serious clinical prognosis. Among 27,009 subjects who participated in a healthy screening program from the Dongfeng-Tongji cohort study in 2008, 8189 eligible subjects (aged 35-86 years; males, 43.95%) were ultimately enrolled. The incidence rates of NAFLD in 2013 were compared with respect to baseline bilirubin levels among subjects free of NAFLD, and the effect sizes were estimated by logistic regression analysis. During 5 years follow-up, we observed 1956 cases of newly developed NAFLD with the overall incidence of 23.88%. Direct bilirubin was presented to inversely associate with NAFLD risk. Compared with quartile 1 of direct bilirubin, the multivariable-adjusted ORs (95% CIs) for NAFLD of quartile 2 to 4 were 1.104 (0.867-1.187), 0.843 (0.719-0.989), and 0.768 (0.652-0.905), respectively, P for trend 0.002). Similarly, inverse effects of direct bilirubin on NAFLD incidence were also observed when stratified by sex and BMI. However, no significant associations were found between total, and indirect bilirubin and NAFLD risk. Direct bilirubin reduced NAFLD risk independent of possible confounders among middle-aged and elderly Chinese population, probably based on the endogenous antioxidation of bilirubin. PMID:27484402

  11. Association between bilirubin and risk of Non-Alcoholic Fatty Liver Disease based on a prospective cohort study

    PubMed Central

    Tian, Jianbo; Zhong, Rong; Liu, Cheng; Tang, Yuhan; Gong, Jing; Chang, Jiang; Lou, Jiao; Ke, Juntao; Li, Jiaoyuan; Zhang, Yi; Yang, Yang; Zhu, Ying; Gong, Yajie; Xu, Yanyan; Liu, Peiyi; Yu, Xiao; Xiao, Lin; Du, Min; Yang, Ling; Yuan, Jing; Wang, Youjie; Chen, Weihong; Wei, Sheng; Liang, Yuan; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Yao, Ping; Miao, Xiaoping

    2016-01-01

    The study aimed to assess the association between total, direct, and indirect bilirubin and nonalcoholic fatty live disease (NAFLD) risk given its high prevalence and serious clinical prognosis. Among 27,009 subjects who participated in a healthy screening program from the Dongfeng-Tongji cohort study in 2008, 8189 eligible subjects (aged 35–86 years; males, 43.95%) were ultimately enrolled. The incidence rates of NAFLD in 2013 were compared with respect to baseline bilirubin levels among subjects free of NAFLD, and the effect sizes were estimated by logistic regression analysis. During 5 years follow-up, we observed 1956 cases of newly developed NAFLD with the overall incidence of 23.88%. Direct bilirubin was presented to inversely associate with NAFLD risk. Compared with quartile 1 of direct bilirubin, the multivariable-adjusted ORs (95% CIs) for NAFLD of quartile 2 to 4 were 1.104 (0.867–1.187), 0.843 (0.719–0.989), and 0.768 (0.652–0.905), respectively, P for trend 0.002). Similarly, inverse effects of direct bilirubin on NAFLD incidence were also observed when stratified by sex and BMI. However, no significant associations were found between total, and indirect bilirubin and NAFLD risk. Direct bilirubin reduced NAFLD risk independent of possible confounders among middle-aged and elderly Chinese population, probably based on the endogenous antioxidation of bilirubin. PMID:27484402

  12. Hepatic Encephalopathy and Sleepiness: An Interesting Connection?

    PubMed Central

    Montagnese, Sara; Turco, Matteo; Amodio, Piero

    2015-01-01

    Sleep-wake abnormalities in patients with cirrhosis have been traditionally associated with hepatic encephalopathy (HE). In recent years, a certain amount of work has been devoted to the study of this relationship. This has lead to a modified picture, with weakening of the association between HE and poor night sleep, and the emergence of stronger links between HE and excessive daytime sleepiness. This brief review focuses on the evidence in favor of the interpretation of HE as a sleepiness syndrome, and on the diagnostic, therapeutic and social implications of such an interpretation. PMID:26041958

  13. Chronic Traumatic Encephalopathy and Movement Disorders: Update.

    PubMed

    Tarazi, Apameh; Tator, Charles H; Tartaglia, Maria Carmela

    2016-05-01

    Association of repetitive brain trauma with progressive neurological deterioration has been described since the 1920s. Punch drunk syndrome and dementia pugilistica (DP) were introduced first to explain symptoms in boxers, and more recently, chronic traumatic encephalopathy (CTE) has been used to describe a neurodegenerative disease in athletes and military personal with a history of multiple concussions. Although there are many similarities between DP and CTE, a number of key differences are apparent especially when comparing movement impairments. The aim of this review is to compare clinical and pathological aspects of DP and CTE with a focus on disorders of movement. PMID:27021775

  14. Post-dengue encephalopathy and Parkinsonism.

    PubMed

    Fong, Choong Yi; Hlaing, Chaw Su; Tay, Chee Geap; Ong, Lai Choo

    2014-10-01

    Parkinsonism as a neurologic manifestation of dengue infection is rare with only 1 reported case in an adult patient. We report a case of a 6-year-old child with self-limiting post-dengue encephalopathy and Parkinsonism. This is the first reported pediatric case of post-dengue Parkinsonism and expands the neurologic manifestations associated with dengue infection in children. Clinicians should consider the possibility of post-dengue Parkinsonism in children with a history of pyrexia from endemic areas of dengue. PMID:24776518

  15. Placental fetal thrombotic vasculopathy is associated with neonatal encephalopathy.

    PubMed

    McDonald, Denise G M; Kelehan, Peter; McMenamin, Joseph B; Gorman, Winifred A; Madden, David; Tobbia, Iqdam N; Mooney, Eoghan E

    2004-07-01

    Neonatal encephalopathy (NE) remains an important cause of morbidity and mortality in the term infant, and many cases have an antepartum, rather than an intrapartum, etiology. Chronic processes such as thrombosis result in changes in the placenta. We sought to determine whether histopathological examination of the placenta in cases of NE, focusing on these changes, could identify significant antenatal processes that are not recognized by clinical assessment alone. Infants born at term with NE were identified retrospectively over a 12-year period. Placental tissue from deliveries during the study period was available for reexamination. Controls were selected from a cohort of 1000 consecutive deliveries on which clinical and pathological data were collected as part of an earlier study. Bivariate and multivariate analyses of clinical and pathological factors for cases and controls were used to test for an independent association with NE. Clinical and placental data was collected on 93 cases of NE and 387 controls. The placental features of fetal thrombotic vasculopathy (FTV), funisitis (signifying a fetal response to infection), and accelerated villous maturation were independently associated with NE. Of the clinical factors studied, meconium-stained liquor and abnormal cardiotocograph were independently associated. There were no independently associated clinical antenatal factors. Placental features of infection, thrombosis, and disturbed uteroplacental flow are significant independent factors in the etiology of NE in this study. Acute and chronic features suggest that NE may result from acute stress in an already compromised infant. The absence of significant clinical antenatal factors supports the value of placental examination in the investigation of infants with NE. PMID:15257552

  16. Effect of sodium phenobarbital on bilirubin metabolism in an infant with congenital, nonhemolytic, unconjugated hyperbilirubinemia, and kernicterus

    PubMed Central

    Crigler, John F.; Gold, Norman I.

    1969-01-01

    Sodium phenobarbital and various hormones, compounds capable of hepatic enzyme induction, were given to an infant boy with congenital, nonhemolytic, unconjugated, hyperbilirubinemia and severe kernicterus for prolonged periods between the ages of 2 and 25 months to determine their effect on serum bilirubin concentrations. Phenobarbital, 5 mg/day orally, on two occasions decreased serum bilirubin concentrations approximately threefold over a period of 30 days. Withdrawal of phenobarbital after the first study resulted in a gradual (30 days) return of serum bilirubin to pretreatment levels. The lower serum bilirubin concentrations observed when phenobarbital therapy was reinstituted were maintained for 61 days on 2.5 mg/kg per day of the drug. Orally administered L-triiodothyronine, 0.05-0.1 mg/day for 71 days, intramuscular human growth hormone, 1 mg/day for 21 days, and testosterone propionate, 0.1 mg/day for 9 days, did not decrease serum bilirubin levels below lowest control values of 18 mg/100 ml. Bilirubin-3H was administered twice before and once with bilirubin-14C during phenobarbital therapy to study the kinetics of bilirubin metabolism. Results of the first and second control studies and of the bilirubin-3H and bilirubin-14C phenobarbital studies, respectively, were as follows: total body bilirubin pools, 200, 184, 73, and 72 mg; half-lives, 111, 84, 37, and 39 hr; and turnover, 30, 37, 33, and 31 mg/day. The data show that the approximate threefold decrease in serum bilirubin concentration and total body pool resulted from a comparable decrease in bilirubin half-life without a significant change in turnover. In vitro histological (electron microscopy) and enzymological studies of liver obtained by surgical biopsies before and during phenobaribtal administration showed that both the hepatocyte content of agranular endoplasmic reticulum (AER) and the ability of liver homogenate to conjugate p-nitrophenol were significantly increased during phenobarbital

  17. A neurologist's approach to delirium: diagnosis and management of toxic metabolic encephalopathies.

    PubMed

    Krishnan, Vaishnav; Leung, Lester Y; Caplan, Louis R

    2014-02-01

    Toxic metabolic encephalopathies (TMEs) present as an acute derangement in consciousness, cognition and behavior, and can be brought about by various triggers, including endocrine and metabolic disturbances, exogenous toxins, pain and infection. Also referred to as "delirium" or "acute confusional states," TMEs are characterized by (1) an altered level of consciousness and activity, (2) global changes in cognition with inattention, (3) a fluctuating course with disturbances in the sleep-wake cycle, and (4) asterixis and myoclonus. The pathophysiology of this syndrome is poorly understood. Imbalanced neurotransmitter signaling and pathologically heightened brain inflammatory cytokine signaling have been proposed as candidate mechanisms. Focal brain lesions can also occasionally mimic TMEs. A neurological examination is required to identify the presence of focal findings, which when present, identify a new focal lesion or the recrudescence of prior ischemic, inflammatory or neoplastic insults. Diagnostic testing must include a search for metabolic and infectious derangements. Offending medications should be withdrawn. Magnetic resonance imaging, cerebrospinal fluid analysis and electroencephalography should be considered in select clinical situations. In addition to being an unpleasant experience for the patient and family, this condition is associated with extended hospital stays, increased mortality and high costs. In individuals with diminished cognitive reserve, episodes of TME lead to an accelerated decline in cognitive functioning. Starting with an illustrative case, this paper provides a neurologist's approach to the diagnosis, differential diagnosis and management of toxic metabolic encephalopathies. PMID:24332366

  18. Bilirubin measured on a blood gas analyser: a suitable alternative for near-patient assessment of neonatal jaundice?

    PubMed

    Peake, M; Mazzachi, B; Fudge, A; Bais, R

    2001-09-01

    The reliability of a recently released total bilirubin assay for a blood gas analyser was assessed in two Australian hospital laboratories. The instrument computes total bilirubin concentration from multi-wavelength absorbance measurements of undiluted whole blood or plasma. Performance of the Radiometer ABL 735 blood gas analyser bilirubin method (software version 3.6) was compared with a proven Roche diazo method for Hitachi analysers, calibrated using primary standards prepared from NIST SRM 916a bilirubin. Acceptable bilirubin results were found over a wide concentration range for most neonatal samples of whole blood or plasma. For adult specimens, bilirubin results were approximately 10% lower on the blood gas analyser. Within-run imprecision (whole blood) was < 2.5%, between-day imprecision (synthetic controls) < 1.0%, and the bilirubin assay for both whole blood and plasma was linear to 1,000 micromol/L. Using sampling options from 35 microL to 195 microL, bilirubin results differed by less than 3%, with a 95 microL syringe option producing the highest results. We conclude that the Radiometer ABL 735 bilirubin assay is suitable for near-patient assessment of neonatal jaundice using whole blood, thus eliminating the need for sample centrifugation. Verification using laboratory methods can be used when required. A positive correction of approximately 10% is required for adult specimens to conform with Hitachi results (SRM 916a calibration), possibly due to the optical characteristics of the higher proportion of conjugated bilirubin and other substances present in most adult samples. PMID:11587132

  19. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins.

    PubMed

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    2014-05-21

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin. PMID:24589992

  20. Functionalized Magnetic Fe3O4-β-Cyclodextran Nanoparticles for Efficient Removal of Bilirubin.

    PubMed

    Han, Lulu; Chu, Simin; Wei, Houliang; Ren, Jun; Xu, Li; Jia, Lingyun

    2016-06-01

    Bilirubin (BR), as a lipophilic toxin, can binds and deposits in various tissues, especially the brain tissue, leading to hepatic coma and even death. Magnetic nanoparticles adsorbent modified by β-cyclodextran (Fe3O4-β-CD) was developed to remove the BR from the plasma. Fe3O4-β-CD nanoparticles was prepared through Schiff base reaction between the polyethylenimine (PEI)-modified Fe3O4 and aldehyde-functionalized β-CD, and characterized by Fourier transform infrared (FTIR) spectra, X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM) and dynamic light scattering (DLS). Under optimized conditions, the Fe3O4-β-CD adsorbent could adsorb 225.6 mg/g free BR in PBS and reach the adsorption equilibrium within 90 min mainly through hydrophobic interaction; Moreover, the adsorbent displayed better adsorption capability in a dialysis system for BSA-bound bilirubin, plasma bilirubin and total bile acid, and the removal rates of those were 66%, 31% and 41% respectively. Because of the advantages of fast separation and purification process, low preparation cost, good adsorption capability for plasma bilirubin, Fe3O4-β-CD may become an economical and promising absorbent of BR for clinical applications. PMID:27427594

  1. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  2. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  3. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  4. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  5. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  6. Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?

    PubMed

    Kundur, Avinash R; Singh, Indu; Bulmer, Andrew C

    2015-03-01

    Gilbert's syndrome (GS) is a relatively common condition, inducing a benign, non-hemolytic, unconjugated hyperbilirubinemia. Gilbert's Syndrome is associated with mutation in the Uridine Glucuronosyl Transferase 1A1 (UGT1A1) gene promoter, reducing UGT1A1 activity, which normally conjugates bilirubin allowing its elimination from the blood. Individuals with GS demonstrate mildly elevated plasma antioxidant capacity caused by elevated levels of unconjugated bilirubin (UCB), reduced thiols and glutathione. Interestingly, the development of, and risk of mortality from, cardiovascular disease is remarkably reduced in GS individuals. An explanation for this protection may be explained by bilirubin's ability to inhibit multiple processes that induce platelet hyper-reactivity and thrombosis, thus far under-appreciated in the literature. Reactive oxygen species are produced continuously via metabolic processes and have the potential to oxidatively modify proteins and lipids within cell membranes, which may encourage the development of thrombosis and CVDs. Oxidative stress induced platelet hyper-reactivity significantly increases the risk of thrombosis, which can potentially lead to tissue infarction. Here, we discuss the possible mechanisms by which increased antioxidant status might influence platelet function and link this to cardiovascular protection in GS. In summary, this is the first article to discuss the possible role of bilirubin as an anti-thrombotic agent, which inhibits platelet activation and potentially, organ infarction, which could contribute to the reduced mortality rate in mildly hyperbilirbinemic individuals. PMID:25576848

  7. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning - A Rare Complication.

    PubMed

    Kamarthi, Prabhakar; Subramani, Parimala; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-06-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  8. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning – A Rare Complication

    PubMed Central

    Kamarthi, Prabhakar; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-01-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  9. Management options for minimal hepatic encephalopathy.

    PubMed

    Bajaj, Jasmohan S

    2008-12-01

    Minimal hepatic encephalopathy (MHE) is a neurocognitive dysfunction that is present in the majority of patients with cirrhosis. MHE has a characteristic cognitive profile that cannot be diagnosed clinically. This cognitive dysfunction is independent of sleep dysfunction or problems with overall intelligence. MHE has a significant impact on quality of life, the ability to function in daily life and progression to overt hepatic encephalopathy. Driving ability can be impaired in MHE and this may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history, which is often ignored during routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of the care of patients with MHE. The preserved communication skills and lack of specific signs and insight make MHE difficult to diagnose. The predominant strategies for MHE diagnosis are psychometric or neurophysiological testing. These are usually limited by financial, normative or time constraints. Studies into inhibitory control, cognitive drug research and critical flicker frequency tests are encouraging. These tests do not require a psychologist for administration and interpretation. Lactulose and probiotics have been studied for their potential use as therapies for MHE, but these are not standard-of-care practices at this time. Therapy can improve the quality of life in MHE patients but the natural history, specific diagnostic strategies and treatment options are still being investigated. PMID:19090738

  10. Clinical presentation of chronic traumatic encephalopathy

    PubMed Central

    Daneshvar, Daniel H.; Baugh, Christine M.; Seichepine, Daniel R.; Montenigro, Philip H.; Riley, David O.; Fritts, Nathan G.; Stamm, Julie M.; Robbins, Clifford A.; McHale, Lisa; Simkin, Irene; Stein, Thor D.; Alvarez, Victor E.; Goldstein, Lee E.; Budson, Andrew E.; Kowall, Neil W.; Nowinski, Christopher J.; Cantu, Robert C.; McKee, Ann C.

    2013-01-01

    Objective: The goal of this study was to examine the clinical presentation of chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases. Methods: Thirty-six adult male subjects were selected from all cases of neuropathologically confirmed CTE at the Boston University Center for the Study of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no comorbid neurodegenerative or motor neuron disease, and had next-of-kin informants to provide retrospective reports of the subjects' histories and clinical presentations. These interviews were conducted blind to the subjects' neuropathologic findings. Results: A triad of cognitive, behavioral, and mood impairments was common overall, with cognitive deficits reported for almost all subjects. Three subjects were asymptomatic at the time of death. Consistent with earlier case reports of boxers, 2 relatively distinct clinical presentations emerged, with one group whose initial features developed at a younger age and involved behavioral and/or mood disturbance (n = 22), and another group whose initial presentation developed at an older age and involved cognitive impairment (n = 11). Conclusions: This suggests there are 2 major clinical presentations of CTE, one a behavior/mood variant and the other a cognitive variant. PMID:23966253

  11. Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange.

    PubMed

    Stenbøg, Poul; Busk, Troels; Larsen, Fin Stolze

    2013-06-01

    Severe liver injury result in development of hepatic encephalopathy (HE) and often also in brain edema that is a potentially fatal complication. HE and brain edema are correlated to the level and persistence of hyperammonemia and the presence of systemic inflammation. Treatment of HE and brain edema is based on restoring and keeping normal physiological variables including tonicity, blood gasses, lactate, temperature and vascular resistance by a wide variety of interventions. In addition liver support devices improve the stage of HE, cerebral metabolic rate for oxygen and glucose, and are used either as a bridge to liver transplantation or liver recovery in patients with fulminant hepatic failure and in patients with acute-on-chronic liver failure. This short review will mainly focus on the management and efficacy of doing plasma exchange on HE in patients with acute HE. PMID:23572273

  12. A Case of Chronic Wernicke’s Encephalopathy: A Neuropsychological Study

    PubMed Central

    Oudman, Erik; Van der Stigchel, Stefan; Postma, Albert; Wijnia, Jan W.; Nijboer, Tanja C. W.

    2014-01-01

    A 54-year-old woman was referred to our Korsakoff Center because of extensive cognitive problems following acute Wernicke’s encephalopathy (WE). She had a relatively short history of alcohol abuse and was found lying on the floor in her home by her son. After 5 days without treatment, she was diagnosed with WE in a general hospital. During the course of the disease, minimal change to the acute situation occurred, with chronic confusion, attention deficits, and incoherent behavior symptoms most notable unlike classical Korsakoff’s syndrome. Neuropsychological assessment after 4 and 16 months after admission to the hospital revealed global cognitive decline, with striking impairments in attentional, executive, and memory functions. The present case study suggests that the state of confusion and the neuropsychological symptoms in WE can become chronic in case of very late treatment. We therefore recommend that confused alcoholics should receive appropriate parenteral thiamine according to the current clinical standards. PMID:24904442

  13. [Diagnostic significance of electrocortical responses to rhythmic and solitary photic stimuli in patients with hepato-portal encephalopathy].

    PubMed

    Erokhina, L G; Ershov, Iu A; Puchinskaia, L M; Gubskiĭ, L V; Lisina, G I

    1976-01-01

    In order to clarify some diagnostical criteria of latent hepato-portal encephalopathy in 57 patients with intrahepatic forms of portal hypertension the authors studied the character of driving response in photorhythmical stimulation. In 9 patients the development of evoked potentials depending upon the significance of the stimula was studied as well. The studies confirmed the prognostical significance of a slowing down the mean frequency of rhythms in the EEG in relation to the development of acute encephalopathy and a certain tendency to the shift in the spectrum of driving responses to low frequency and a worsening of driving responses in slowing down the medium rhythm frequency of EEG. In patients with changed resting activity in the Background EEG there was a drop in the amplitude of late components of evoked potentials. PMID:952151

  14. [Clinical importance and diagnostic methods of minimal hepatic encephalopathy].

    PubMed

    Stawicka, Agnieszka; Zbrzeźniak, Justyna; Świderska, Aleksandra; Kilisińska, Natalia; Świderska, Magdalena; Jaroszewicz, Jerzy; Flisiak, Robert

    2016-02-01

    Minimal hepatic encephalopathy (MHE) encompasses a number of neuropsychological and neurophysiological disorders in patients suffering from liver cirrhosis, who do not display abnormalities during a medical interview or physical examination. A negative influence of MHE on the quality of life of patients suffering from liver cirrhosis was confirmed, which include retardation of ability of operating motor vehicles and disruption of multiple health-related areas, as well as functioning in the society. The data on frequency of traffic offences and accidents amongst patients diagnosed with MHE in comparison to patients diagnosed with liver cirrhosis without MHE, as well as healthy persons is alarming. Those patients are unaware of their disorder and retardation of their ability to operate vehicles, therefore it is of utmost importance to define this group. The term minimal hepatic encephalopathy (formerly "subclinical" encephalopathy) erroneously suggested the unnecessity of diagnostic and therapeutic procedures in patients with liver cirrhosis. Diagnosing MHE is an important predictive factor for occurrence of overt encephalopathy - more than 50% of patients with this diagnosis develop overt encephalopathy during a period of 30 months after. Early diagnosing MHE gives a chance to implement proper treatment which can be a prevention of overt encephalopathy. Due to continuing lack of clinical research there exist no commonly agreed-upon standards for definition, diagnostics, classification and treatment of hepatic encephalopathy. This article introduces the newest findings regarding the importance of MHE, scientific recommendations and provides detailed descriptions of the most valuable diagnostic methods. PMID:27000818

  15. Selective nonenzymatic bilirubin detection in blood samples using a Nafion/Mn-Cu sensor.

    PubMed

    Noh, Hui-Bog; Won, Mi-Sook; Shim, Yoon-Bo

    2014-11-15

    The specific detection of biological organics without the use of an enzyme is challenging, and it is crucial for analytical and clinical chemistry. We report specific nonenzymatic bilirubin detection through the catalytic oxidation of bilirubin molecule on the Nafion/Mn-Cu surface. The catalytic ability, true surface area, morphology, crystallinity, composition, and oxidation state of the sensor surface were assessed using voltammetry, coulometry, XPS, XRD, Brunauer-Emmett-Teller (BET), SEM, EDXS, and TOF-SIMS experiments. The results showed that the surface was composed of microporous Mn-Cu bimetallic crystal in flake shape with a large BET surface area (3.635 m(2)g(-1)), where the surface area and crystallinity mainly affected the sensor performance. Product analysis of the catalytic reaction on the sensor probe revealed a specific two-electron oxidation of dipyrromethane moiety to dipyrromethene in the bilirubin molecule. Experimental variables affecting the analysis of bilirubin were optimized in terms of probe composition, temperature, pH, and potential. At the optimized condition, the dynamic range was between 1.2 μM and 0.42 mM, which yielded the equation of ΔI (μA)=(1.03 ± 0.72)+(457.0 ± 4.03) [C] (mM) with 0.999 of correlation coefficient, and the detection limit was 25.0 ± 1.8 nM (n=5, k=3). The stability test, interference effects, and analysis of real clinical samples, human whole blood and certified serum samples were demonstrated to confirm the reliability of the proposed bilirubin sensor. PMID:24953842

  16. [Quantifying intestino-esophageal reflux with a fiberoptic bilirubin detection probe].

    PubMed

    Stein, H J; Kraemer, S J; Feussner, H; Siewert, J R

    1994-05-01

    Currently available methods to assess reflux of duodenal contents into the esophagus are cumbersome, unphysiologic, and inaccurate. The role of intestino-esophageal reflux has therefore been controversial. We assessed intestino-esophageal reflux using a new system which allows prolonged intraesophageal measurement of bilirubin, the major pigment of bile. Measurements were made with a newly developed fiber-optic sensor electrode connected to a portable data processing unit (BILITEC 2000, Synectics Medical Inc., Sweden). Light absorption was measured at the absorption peak of bilirubin and a reference point. Studies were performed in 9 subjects without esophagitis, 9 subjects with esophagitis and primary reflux disease and 7 subjects with erosive esophagitis after a total or subtotal gastrectomy. The fiberoptic electrode was placed 5 cm above the lower esophageal sphincter. In vitro studies showed linear correlations between absorbance measurements obtained with the BILITEC-unit and known bilirubin and bile acid concentrations, respectively (p < 0.01). Compared to both other groups, light absorption was markedly increased in the subjects who had esophagitis after a total or subtotal gastrectomy (p < 0.05) indicating severe biliary reflux. An increase in bilirubin absorption occurred particularly during the post-prandial and supine periodes (p < 0.01). A Roux-en-Y biliary diversion procedure completely abolished bile reflux in 2 of these patients. These data indicate that ambulatory 24-hour fiberoptic measurement of bilirubin in the esophagus is feasible and allows quantitation of intestino-esophageal reflux. Intestino-esophageal reflux occurs particularly during the postprandial period and the early morning hours in patients who had a previous subtotal or total gastrectomy. PMID:8073796

  17. The Role of Bilirubin in Diabetes, Metabolic Syndrome, and Cardiovascular Diseases

    PubMed Central

    Vítek, Libor

    2012-01-01

    Bilirubin belongs to a phylogenetically old superfamily of tetrapyrrolic compounds, which have multiple biological functions. Although for decades bilirubin was believed to be only a waste product of the heme catabolic pathway at best, and a potentially toxic compound at worst; recent data has convincingly demonstrated that mildly elevated serum bilirubin levels are strongly associated with a lower prevalence of oxidative stress-mediated diseases. Indeed, serum bilirubin has been consistently shown to be negatively correlated to cardiovascular diseases (CVD), as well as to CVD-related diseases and risk factors such as arterial hypertension, diabetes mellitus, metabolic syndrome, and obesity. In addition, the clinical data are strongly supported by evidence arising from both in vitro and in vivo experimental studies. This data not only shows the protective effects of bilirubin per se; but additionally, of other products of the heme catabolic pathway such as biliverdin and carbon monoxide, as well as its key enzymes (heme oxygenase and biliverdin reductase); thus, further underlining the biological impacts of this pathway. In this review, detailed information on the experimental and clinical evidence between the heme catabolic pathway and CVD, and those related diseases such as diabetes, metabolic syndrome, and obesity is provided. All of these pathological conditions represent an important threat to human civilization, being the major killers in developed countries, with a steadily increasing prevalence. Thus, it is extremely important to search for novel markers of these diseases, as well as for novel therapeutic modalities to reverse this unfavorable situation. The heme catabolic pathway seems to fulfill the criteria for both diagnostic purposes as well as for potential therapeutical interventions. PMID:22493581

  18. 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

  19. Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats

    PubMed Central

    Xu, Ping; Ling, Zhao-li; Zhang, Ji; Li, Ying; Shu, Nan; Zhong, Ze-yu; Chen, Yang; Di, Xin-yu; Wang, Zhong-jian; Liu, Li; Liu, Xiao-dong

    2016-01-01

    Aim: Liver failure is associated with dyshomeostasis of efflux transporters at the blood-brain barrier (BBB), which contributes to hepatic encephalopathy. In this study we examined whether breast cancer resistance protein (BCRP), a major efflux transporter at the BBB, was altered during liver failure in rats. Methods: Rats underwent bile duct ligation (BDL) surgery, and then were sacrificed after intravenous injection of prazosin on d3, d7 and d14. The brains and blood samples were collected. BCRP function at the BBB was assessed by the brain-to-plasma prazosin concentration ratio; Evans Blue extravasation in the brain tissues was used as an indicator of BBB integrity. The protein levels of BCRP in the brain tissues were detected. Human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) were tested in vitro. In addition, hyperbilirubinemia (HB) was induced in rats by intravenous injection of unconjugated bilirubin (UCB). Results: BDL rats exhibited progressive decline of liver function and HB from d3 to d14. In the brain tissues of BDL rats, both the function and protein levels of BCRP were progressively decreased, whereas the BBB integrity was intact. Furthermore, BDL rat serum significantly decreased BCRP function and protein levels in HCMEC/D3 cells. Among the abnormally altered components in BDL rat serum tested, UCB (10, 25 μmol/L) dose-dependently inhibit BCRP function and protein levels in HCMEC/D3 cells, whereas 3 bile acids (CDCA, UDCA and DCA) had no effect. Similar results were obtained in MDCK-BCRP cells and in the brains of HB rats. Correlation analysis revealed that UCB levels were negatively correlated with BCRP expression in the brain tissues of BDL rats and HB rats as well as in two types of cells tested in vitro. Conclusion: UCB elevation in BDL rats impairs the function and expression of BCRP at the BBB, thus contributing to hepatic encephalopathy. PMID:27180978

  20. The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat

    PubMed Central

    Chen, Xiao-Juan; Zhou, Hui-Qun; Ye, Hai-bo; Li, Chun-Yan; Zhang, Wei-Tian

    2016-01-01

    Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease. PMID:27611599

  1. The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat.

    PubMed

    Chen, Xiao-Juan; Zhou, Hui-Qun; Ye, Hai-Bo; Li, Chun-Yan; Zhang, Wei-Tian

    2016-01-01

    Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease. PMID:27611599

  2. Management of hepatic encephalopathy in the hospital.

    PubMed

    Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray

    2014-02-01

    Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes

  3. 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

  4. Role of brain cytochrome P450 mono-oxygenases in bilirubin oxidation-specific induction and activity.

    PubMed

    Gambaro, Sabrina E; Robert, Maria C; Tiribelli, Claudio; Gazzin, Silvia

    2016-02-01

    In the Crigler-Najjar type I syndrome, the genetic absence of efficient hepatic glucuronidation of unconjugated bilirubin (UCB) by the uridine 5'-diphospho-glucuronosyltransferase1A1 (UGT1A1) enzyme produces the rise of UCB level in blood. Its entry to central nervous system could generate toxicity and neurological damage, and even death. In the past years, a compensatory mechanism to liver glucuronidation has been indicated in the hepatic cytochromes P450 enzymes (Cyps) which are able to oxidize bilirubin. Cyps are expressed also in the central nervous system, the target of bilirubin toxicity, thus making them theoretically important to confer a protective activity toward bilirubin accumulation and neurotoxicity. We therefore investigated the functional induction (mRNA, EROD/MROD) and the ability to oxidize bilirubin of Cyp1A1, 1A2, and 2A3 in primary astrocytes cultures obtained from two rat brain region (cortex: Cx and cerebellum: Cll). We observed that Cyp1A1 was the Cyp isoform more easily induced by beta-naphtoflavone (βNF) in both Cx and Cll astrocytes, but oxidized bilirubin only after uncoupling by 3, 4,3',4'-tetrachlorobiphenyl (TCB). On the contrary, Cyp1A2 was the most active Cyp in bilirubin clearance without uncoupling, but its induction was confined only in Cx cells. Brain Cyp2A3 was not inducible. In conclusion, the exposure of astrocytes to βNF plus TCB significantly enhanced Cyp1A1 mediating bilirubin clearance, improving cell viability in both regions. These results may be a relevant groundwork for the manipulation of brain Cyps as a therapeutic approach in reducing bilirubin-induced neurological damage. PMID:25370011

  5. Inducible bilirubin oxidase: A novel function for the mouse cytochrome P450 2A5

    SciTech Connect

    Abu-Bakar, A'edah; Arthur, Dionne Maioha; Aganovic, Simona; Ng, Jack C.; Lang, Matti A.

    2011-11-15

    We have previously shown that bilirubin (BR), a breakdown product of haem, is a strong inhibitor and a high affinity substrate of the mouse cytochrome P450 2A5 (CYP2A5). The antioxidant BR, which is cytotoxic at high concentrations, is potentially useful in cellular protection against oxygen radicals if its intracellular levels can be strictly controlled. The mechanisms that regulate cellular BR levels are still obscure. In this paper we provide preliminary evidence for a novel function of CYP2A5 as hepatic 'BR oxidase'. A high-performance liquid chromatography/electrospray ionisation mass spectrometry screening showed that recombinant yeast microsomes expressing the CYP2A5 oxidise BR to biliverdin, as the main metabolite, and to three other smaller products with m/z values of 301, 315 and 333. The metabolic profile is significantly different from that of chemical oxidation of BR. In chemical oxidation the smaller products were the main metabolites. This suggests that the enzymatic reaction is selective, towards biliverdin production. Bilirubin treatment of primary hepatocytes increased the CYP2A5 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A5 compared to cells treated only with CHX. Collectively, the observations suggest that the CYP2A5 is potentially an inducible 'BR oxidase' where BR may accelerate its own metabolism through stabilization of the CYP2A5 protein. It is possible that this metabolic pathway is potentially part of the machinery controlling intracellular BR levels in transient oxidative stress situations, in which high amounts of BR are produced. -- Highlights: Black-Right-Pointing-Pointer CYP2A5 metabolizes bilirubin to biliverdin and dipyrroles. Black-Right-Pointing-Pointer Bilirubin increased the hepatic CYP2A5 protein and activity levels. Black-Right-Pointing-Pointer Bilirubin does not change the hepatic CYP2A5

  6. Wernicke's encephalopathy: expanding the diagnostic toolbox.

    PubMed

    Lough, Mary E

    2012-06-01

    Wernicke's encephalopathy (WE) is a life threatening neurological disorder that results from thiamine (Vitamin B1) deficiency. Clinical signs include mental status changes, ataxia, occulomotor changes and nutritional deficiency. The conundrum is that the clinical presentation is highly variable. WE clinical signs, brain imaging, and thiamine blood levels, are reviewed in 53 published case reports from 2001 to 2011; 81 % (43/53) were non-alcohol related. Korsakoff Syndrome or long-term cognitive neurological changes occurred in 28 % (15/53). Seven WE cases (13 %) had a normal magnetic resonance image (MRI). Four WE cases (8 %) had normal or high thiamine blood levels. Neither diagnostic tool can be relied upon exclusively to confirm a diagnosis of WE. PMID:22577001

  7. Does this patient have hypertensive encephalopathy?

    PubMed

    Christopoulou, Foteini; Rizos, Evangelos C; Kosta, Paraskevi; Argyropoulou, Maria I; Elisaf, Moses

    2016-05-01

    A 63-year-old man was admitted to our hospital for further investigation and management of brain metastases. The patient was initially presented with a 4-day history of confusion. On the day of admission, the patient was confused, agitated, disorientated in place and time, and had visual disturbances. His blood pressure was repeatedly recorded high, with levels of systolic blood pressure between 170-210 mm Hg. A brain magnetic resonance imaging showed areas of high signal on T2 and fluid-attenuated inversion recovery images, located bilaterally in the white matter of the occipital regions and unilateral in the left frontal lobe, suggestive of posterior reversible encephalopathy syndrome. Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome. PMID:26896240

  8. Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments

    PubMed Central

    Allen, Kimberly A.; Brandon, Debra H.

    2011-01-01

    Hypoxic ischemic encephalopathy (HIE) is a serious birth complication affecting full term infants: 40–60% of affected infants die by 2 years of age or have severe disabilities. The majority of the underlying pathologic events of HIE are a result of impaired cerebral blood flow and oxygen delivery to the brain with resulting primary and secondary energy failure. In the past, treatment options were limited to supportive medical therapy. Currently, several experimental treatments are being explored in neonates and animal models to ameliorate the effects of secondary energy failure. This review discusses the underlying pathophysiologic effects of a hypoxic-ischemic event and experimental treatment modalities being explored to manage infants with HIE. Further research is needed to better understand if the long-term impact of the experimental treatments and whether the combinations of experimental treatments can improve outcomes in infants with HIE. PMID:21927583

  9. Chronic Traumatic Encephalopathy: The Impact on Athletes.

    PubMed

    Galgano, Michael A; Cantu, Robert; Chin, Lawrence S

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE. PMID:27088064

  10. Optic nerve hypoplasia, encephalopathy, and neurodevelopmental handicap.

    PubMed Central

    Burke, J P; O'Keefe, M; Bowell, R

    1991-01-01

    Abnormalities of the central nervous system are frequently described in optic nerve hypoplasia. In a longitudinal study of 46 consecutive children (32 term, 14 preterm) with bilateral optic nerve hypoplasia 32 (69.5%) had associated neurodevelopmental handicap. Of these, 90% had structural central nervous system abnormalities on computed tomographic brain scans. Neurodevelopmental handicap occurred in 62.5% of the term and 86% of the preterm infants respectively. Term infants had a greater incidence of ventral developmental midline defects and proportionately fewer maternal and/or neonatal complications throughout pregnancy, while encephaloclastic lesions were commoner among the premature infants. An association of optic nerve hypoplasia with the twin transfusion syndrome and prenatal vascular encephalopathies is described. PMID:2021594

  11. Hepatic Encephalopathy: Pharmacological Therapies Targeting Ammonia.

    PubMed

    Rahimi, Robert S; Rockey, Don C

    2016-02-01

    Hepatic encephalopathy (HE) is a major complication in patients with decompensated cirrhosis, leading to higher readmission rates causing a profound burden of disease and considerable health care costs. Because ammonia is thought to play a crucial role in the pathogenesis of HE, therapies directed at reducing ammonia levels are now being aggressively developed. Ammonia scavengers such as AST-120 (spherical carbon adsorbent), glycerol phenylbutyrate, sodium phenylacetate or sodium benzoate, and ornithine phenylacetate have been used to improve HE symptoms. A new approach, bowel cleansing with polyethylene glycol 3350, appears to be a promising therapy, with a recent study demonstrating a more rapid improvement in overt HE (at 24 hours after treatment) than lactulose. Extracorporeal devices, although now used primarily in research settings, have also been utilized in patients with refractory HE, but are not approved for clinical management. PMID:26870932

  12. Leucine metabolism in patients with Hepatic Encephalopathy

    SciTech Connect

    McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

    1986-03-01

    A primed continuous infusion of (/sup 15/N, 1-/sup 13/C)leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet (0.6 g protein per kg ideal body weight (IBW)). An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO/sub 2/ enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy.

  13. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

    PubMed Central

    Dixon, Brandon J.; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  14. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Dixon, Brandon J; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  15. Is chronic traumatic encephalopathy a real disease?

    PubMed

    Randolph, Christopher

    2014-01-01

    Chronic traumatic encephalopathy (CTE) has received widespread media attention and is treated in the lay press as an established disease, characterized by suicidality and progressive dementia. The extant literature on CTE is reviewed here. There currently are no controlled epidemiological data to suggest that retired athletes are at increased risk for dementia or that they exhibit any type of unique neuropathology. There remain no established clinical or pathological criteria for diagnosing CTE. Despite claims that CTE occurs frequently in retired National Football League (NFL) players, recent studies of NFL retirees report that they have an all-cause mortality rate that is approximately half of the expected rate, and even lower suicide rates. In addition, recent clinical studies of samples of cognitively impaired NFL retirees have failed to identify any unique clinical syndrome. Until further controlled studies are completed, it appears to be premature to consider CTE a verifiable disease. PMID:24412888

  16. Pathogenesis, Diagnosis, and Treatment of Hepatic Encephalopathy

    PubMed Central

    Atluri, Dileep K; Prakash, Ravi; Mullen, Kevin D

    2011-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician. PMID:25755319

  17. Chronic Traumatic Encephalopathy: The Impact on Athletes

    PubMed Central

    Cantu, Robert; Chin, Lawrence S.

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE. PMID:27088064

  18. Interaction of bilirubin and indocyanine green with the binding and conjugation of sulfobromophthalein by rat liver cytosol proteins.

    PubMed

    Davis, D R; Yeary, R A

    1980-02-01

    The interaction of bilirubin and indocyanine green with sulfobromophthalein (BSP) binding and conjugation by rat liver cytosol proteins was studied. BSP bound to cytosol proteins X, ligandin and Z and the BSP-glutathione conjugate were isolated by sephadex gel chromatography. Neither bilirubin nor indocyanine green affected the binding of BSP to ligandin and Z protein. However, indocyanine green did significantly reduce BSP conjugation in both in vitro and in vivo experiments. Diethyl maleate significantly reduced liver glutathione levels and BSP conjugation. It is suggested that indocyanine gree competitively binds at the ligandin catalytic site whereas the primary binding site for bilirubin is probably a noncatalytic site. PMID:7367753

  19. Enhancements of the production of bilirubin and the expression of β-globin by carbon monoxide during erythroid differentiation.

    PubMed

    Mu, Anfeng; Li, Ming; Tanaka, Masakazu; Adachi, Yasushi; Tai, Tran Tien; Liem, Pham Hieu; Izawa, Shingo; Furuyama, Kazumichi; Taketani, Shigeru

    2016-05-01

    Heme is degraded by heme oxygenase to form iron, carbon monoxide (CO), and biliverdin. However, information about the catabolism of heme in erythroid cells is limited. In this study, we showed the production and export of bilirubin in murine erythroleukemia (MEL) cells. The production of bilirubin by MEL cells was enhanced when heme synthesis was induced. When mouse bone marrow cells were induced with erythropoietin to differentiate into erythroid cells, the synthesis of bilirubin increased. The expression of β-globin was enhanced by CO at the transcriptional level. These results indicate that constant production of CO from heme regulates erythropoiesis. PMID:27087140

  20. Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy.

    PubMed

    Kimer, Nina; Krag, Aleksander; Gluud, Lise L

    2014-01-01

    Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of ammonia by gut bacteria and, to some extent, other toxic derivatives from the gut. Clinical trials show that these effects improve episodes of hepatic encephalopathy. A large randomized trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy. Most patients were treated concurrently with lactulose. Trials have varied greatly in design, outcomes, and duration of treatment regimes. Although a number of retrospective studies have indicated that long-term treatment with rifaximin is safe and possibly beneficial, high quality trials are needed to further clarify efficacy and safety of long-term treatment with rifaximin and evaluate effects of combination therapy with lactulose and branched-chain amino acids for patients with liver cirrhosis and hepatic encephalopathy. PMID:24672227

  1. Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy

    PubMed Central

    Kimer, Nina; Krag, Aleksander; Gluud, Lise L

    2014-01-01

    Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of ammonia by gut bacteria and, to some extent, other toxic derivatives from the gut. Clinical trials show that these effects improve episodes of hepatic encephalopathy. A large randomized trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy. Most patients were treated concurrently with lactulose. Trials have varied greatly in design, outcomes, and duration of treatment regimes. Although a number of retrospective studies have indicated that long-term treatment with rifaximin is safe and possibly beneficial, high quality trials are needed to further clarify efficacy and safety of long-term treatment with rifaximin and evaluate effects of combination therapy with lactulose and branched-chain amino acids for patients with liver cirrhosis and hepatic encephalopathy. PMID:24672227

  2. Genetics Home Reference: MECP2-related severe neonatal encephalopathy

    MedlinePlus

    ... onset encephalopathy with microcephaly Patient Support and Advocacy Resources (2 links) Rare Disease Clinical Research Network: Rett Syndrome, MECP2 Duplication and Rett-Related Disorders Natural History Study RettSyndrome.org GeneReviews (1 link) MECP2- ...

  3. [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

  4. Posterior encephalopathy subsequent to cyclosporin A presenting as irreversible abulia.

    PubMed

    Nishie, Makoto; Kurahashi, Kozo; Ogawa, Masaya; Yoshida, Yasuji; Midorikawa, Hiroshi

    2003-08-01

    A case of cyclosporin A (Cys A)-induced posterior encephalopathy developed into persistent abulia despite rapid and marked improvement of abnormal T2- and FLAIR MRI hyperintense regions. Diffusion-weighted MRI signal intensity was also high at the onset. This change is atypical in Cys A-induced encephalopathy and was thought to predict poor recovery from the encephalopathy. Persistent abulia was probably due to marked hypoperfusion in the whole cortex including bilateral frontal lobes and basal ganglia as detected by SPECT. Apart from the breakdown of the blood-brain barrier, direct toxicity of Cys A to the brain may play a role in the pathogenesis of chronic, irreversible encephalopathy. PMID:12924507

  5. Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

    NASA Astrophysics Data System (ADS)

    Tsutsui, Toshiyuki; Kasuga, Fumiko

    Bovine spongiform encephalopathy (BSE) is a progressive neurological disease of cattle affecting the central nervous system and was first diagnosed in the United Kingdom (UK) in 1986 (Wells et al., 1987). This disease is one of the transmissible spongiform encephalopathy (TSE) which includes Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep. The causative agent of TSE is considered to be an abnormal form of prion protein. However, the details of its pathogenic mechanism have not been fully identified. Scrapie, which causes neurological symptoms in sheep and goats, has existed in the UK for 200 years (Hoinville, 1996) and spread across the rest of the world in the 1900s (Detwiler & Baylis, 2003). There has been no report so far that scrapie can be transmitted to humans. Initially, BSE was also considered as a disease affecting only animals. However, a variant type of Creutzfeldt-Jakob disease (vCJD) was first reported in the UK, and exposure to a BSE agent was suspected (Collinge, Sidle, Meads, Ironside, & Hill, 1996). vCJD is clinically and pathologically different from the sporadic type of CJD, and age at clinical onset of vCJD is younger than sporadic type (Will et al., 1996). Since the UK government announced the possible association between BSE and vCJD in 1996, BSE has become a huge public health concern all over the world. Of particular concern about vCJD, the fatal disease in younger age, distorted consumer confidence in beef safety, and as a result reduced beef consumption has been seen in many BSE-affected countries.

  6. Prion biology relevant to bovine spongiform encephalopathy.

    PubMed

    Novakofski, J; Brewer, M S; Mateus-Pinilla, N; Killefer, J; McCusker, R H

    2005-06-01

    Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE

  7. Temperature Profile and Outcomes of Neonates Undergoing Whole Body Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

    PubMed Central

    Shankaran, Seetha; Laptook, Abbot R.; McDonald, Scott A.; Higgins, Rosemary D.; Tyson, Jon E.; Ehrenkranz, Richard A.; Das, Abhik; Sant’Anna, Guilherme; Goldberg, Ronald N.; Bara, Rebecca; Walsh, Michele C.

    2011-01-01

    BACKGROUND Decreases below target temperature were noted among neonates undergoing cooling in the NICHD Neonatal Research Network Trial of whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. OBJECTIVE To examine the temperature profile and impact on outcome among ≥ 36 week gestation neonates randomized at ≤ 6 hours of age targeting esophageal temperature of 33.5°C for 72 hours. DESIGN/SETTING/PATIENTS Infants with intermittent temperatures recorded < 32.0°C during induction and maintenance of cooling were compared to all other cooled infants and relationship with outcome at 18 months was evaluated. RESULTS There were no differences in stage of encephalopathy, acidosis, or 10 minute Apgar scores between infants with temperatures < 32.0°C during induction (n=33) or maintenance (n=10) and all other infants who were cooled (n=58); however birth weight was lower and need for blood pressure support higher among infants with temperatures < 32.0 °C compared to all other cooled infants. No increase in acute adverse events were noted among infants with temperatures < 32.0 °C and hours spent < 32°C were not associated with the primary outcome of death or moderate/severe disability or the Bayley II Mental Developmental Index at 18 months. CONCLUSION Term infants with a lower birth weight are at risk for decreasing temperatures < 32.0°C while undergoing body cooling using a servo controlled system. This information suggests extra caution during the application of hypothermia as these lower birth weight infants are at risk for overcooling. Our findings may assist in planning additional trials of lower target temperature for neonatal hypoxic-ischemic encephalopathy. PMID:21499182

  8. Severe fever with thrombocytopenia syndrome with myocardial dysfunction and encephalopathy: A case report.

    PubMed

    Kawaguchi, Takeshi; Matsuda, Motohiro; Takajo, Ichiro; Kawano, Ayako; Kariya, Yumi; Kubo, Kazuyoshi; Miyauchi, Syunichi; Umekita, Kunihiko; Nagatomo, Yasuhiro; Yano, Takao; Yano, Kouji; Okayama, Akihiko

    2016-09-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Korea and Japan caused by a novel bunyavirus, SFTS virus (SFTSV). Although central nervous system manifestations are common in SFTS patients, the pathogenesis has not been elucidated; and there are few reports of myocardial dysfunction. Here we report an elderly Japanese patient with reversible myocardial dysfunction and encephalopathy. A previously healthy 65-year-old male engaged in forestry got a tick bite and developed fever and fatigue in 3 days. Three days after onset, he presented to a local hospital where the diagnosis of SFTS with hemophagocytotic syndrome was made. The blood test showed leukopenia and thrombocytopenia as well as elevated levels of alanine aminotransferase and aspartate aminotransferase. Marked hemophagocytosis was found on bone marrow smear. Peripheral blood was positive for SFTSV gene by reverse-transcription polymerase chain reaction. On day 7, the patient was transferred to our hospital. We observed disturbance of consciousness, Kernig sign and myoclonus to face and limbs. Decreased blood flow of whole cerebral cortex was detected by single photon emission computed tomography (SPECT). Chest X-ray revealed cardiomegaly and electrocardiography (ECG) showed abnormal T waves. These data suggested acute encephalopathy and myocardial dysfunction. We treated him with corticosteroid and blood transfusion, which resulted in the complete recovery of the above abnormal symptoms and laboratory data including the findings in SPECT and ECG in about a month. This case demonstrated transient myocardial dysfunction and encephalopathy can occur in addition to typical clinical manifestation of SFTS. PMID:26943978

  9. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy.

    PubMed

    Tapper, Elliot B; Jiang, Z Gordon; Patwardhan, Vilas R

    2015-05-01

    Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the

  10. Rifaximin therapy and hepatic encephalopathy: Pros and cons

    PubMed Central

    Zullo, Angelo; Hassan, Cesare; Ridola, Lorenzo; Lorenzetti, Roberto; Campo, Salvatore MA; Riggio, Oliviero

    2012-01-01

    Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides. PMID:22966484

  11. Rifaximin therapy and hepatic encephalopathy: Pros and cons.

    PubMed

    Zullo, Angelo; Hassan, Cesare; Ridola, Lorenzo; Lorenzetti, Roberto; Campo, Salvatore Ma; Riggio, Oliviero

    2012-08-01

    Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides. PMID:22966484

  12. Neurosteroids in hepatic encephalopathy: Novel insights and new therapeutic opportunities.

    PubMed

    Butterworth, Roger F

    2016-06-01

    Hepatic encephalopathy (HE) is a serious neuropsychiatric disorder resulting from liver failure. Symptoms of HE include mild cognitive impairment, stupor and coma. Morphological changes to neuroglia (both astrocytes and microglia) occur in HE consisting of cytotoxic brain edema (astrocyte swelling) in acute liver failure and Alzheimer type-2 astrocytosis in cirrhosis. Visual-evoked responses in animals with liver failure and HE manifest striking similarities to those in animals treated with agonists of the GABA-A receptor complex. Neurosteroids are synthesized in brain following activation of translocator protein (TSPO), a mitochondrial neuroglial cholesterol-transporter protein. TSPO sites are activated in both animal models of HE as well as in autopsied brain tissue from HE patients. Activation of TSPO sites results in increased cholesterol transport into the mitochondrion followed by stimulation of a metabolic pathway culminating in the synthesis of allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC), neurosteroids with potent positive allosteric modulatory action on the GABA-A receptor complex. Concentrations of ALLO and THDOC in brain tissue from mice with HE resulting from toxic liver injury are sufficient to induce sedation in animals of the same species and significant increases in concentrations of ALLO have been reported in autopsied brain tissue from cirrhotic patients with HE leading to the proposal that "increased GABAergic tone" in HE results from that increased brain concentrations of this neurosteroid. Agents with the potential to decrease neurosteroid synthesis and/or prevent their modulatory actions on the GABA-A receptor complex may provide novel approaches to the management and treatment of HE. Such agents include indomethacin, benzodiazepine receptor inverse agonists and a novel series of compounds known as GABA-A receptor-modulating steroid antagonists (GAMSA). PMID:26589093

  13. Persistence of Cognitive Impairment after Resolution of Overt Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S; Schubert, Christine M; Heuman, Douglas M; Wade, James B; Gibson, Douglas P; Topaz, Allyne; Saeian, Kia; Hafeezullah, Muhammad; Bell, Debulon E; Sterling, Richard K; Stravitz, R Todd; Luketic, Velimir; White, Melanie B; Sanyal, Arun J

    2010-01-01

    Background & Aims In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). Methods Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol [DS], block design [BD], and number connection [NCT-A&B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and 1st minus 2nd halves (ΔL1–2) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotics, with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE. Results In study A, (226 cirrhotic patients) 54 had experienced OHE, 120 had minimal HE and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotics were cognitively impaired, based on results from all tests. Learning of response inhibition (ΔL1–2 ≥1), was evident in patients with minimal HE and no minimal HE, but was lost after OHE. In study B (50 additional patients who developed ≥1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r=0.5, P=0.0001), DST (r=−0.39, P=0.002) and NCT-B (r=0.33, P=0.04). In the prospective study (59 cirrhotics without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs.18 after, P=0.0003) and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing. Conclusion In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning. PMID:20178797

  14. Developmental outcomes of newborn encephalopathy in the term infant.

    PubMed

    Badawi, N; Keogh, J M; Dixon, G; Kurinczuk, J J

    2001-06-01

    Newborn encephalopathy is a clinically defined condition of abnormal neurological behaviours in the newborn period. Though most cases have their origin in the preconceptional and antepartum period, newborn encephalopathy represents a crucial link between intrapartum events and permanent neurological problems in the child. The birth prevalence of newborn encephalopathy ranges from 1.8 to 7.7 per 1000 term live births according to the definition used and the population to which it is applied. Few studies have investigated the outcomes of newborn encephalopathy other than for cases solely attributed to intrapartum hypoxia. These adverse outcomes range from death to cerebral palsy, intellectual disability, and less severe neurological disabilities such as learning and behavioural problems. Outcomes following newborn encephalopathy may vary from country to country with 9.1% of affected babies dying in the newborn period in Western Australia and 10.1% manifesting cerebral palsy by the age of two. These compare to a case fatality of 30.5% in Kathmandu and a cerebral palsy rate of 14.5% by one year of age. The study by Robertson et al which followed children with hypoxic ischaemic encephalopathy found an incidence of impairment of 16% among survivors assessed at 8 years with 42% requiring school resource room help or special classes. This review emphasises the great need for comprehensive clinical and educational assessment as these infants approach school entry to enable appropriate educational provisions to be made. PMID:11450384

  15. Water-soluble adsorbent β-cyclodextrin-grafted polyethyleneimine for removing bilirubin from plasma.

    PubMed

    Wang, Zhi; Wei, Houliang; Jia, Lingyun; Xu, Li; Zou, Chunyi; Xie, Jian

    2012-10-01

    A water-soluble adsorbent was developed for removing bilirubin from the plasma of hyperbilirubinemia patient. The adsorbent was synthesized by grafting β-cyclodextrin (β-CD) to branched polyethyleneimine (PEI) matrix. The resulting β-CD-PEI polymer had an average molecular weight of 163.7 kD, and it contained 56.3 β-CD functional groups. In β-CD-PEI-spiked dialysis, 35.8% of plasma bilirubin was removed, which was higher than that removed by the same concentration of bovine serum albumin. β-CD-PEI also removed aromatic amino acids and bile acids. The results indicated that β-CD-PEI could be an effective adsorbent for blood purification application aiming at the removal of toxins. PMID:22836125

  16. Fully Oriented Bilirubin Oxidase on Porphyrin-Functionalized Carbon Nanotube Electrodes for Electrocatalytic Oxygen Reduction.

    PubMed

    Lalaoui, Noémie; Le Goff, Alan; Holzinger, Michael; Cosnier, Serge

    2015-11-16

    The efficient immobilization and orientation of bilirubin oxidase from Myrothecium verrucaria on multi-walled carbon nanotube electrodes by using π-stacked porphyrins as a direct electron-transfer promoter is reported. By comparing the use of different types of porphyrin, the rational effect of the porphyrin structure on both the immobilization and orientation of the enzyme is demonstrated. The best performances were obtained for protoporphyrin IX, which is the natural precursor of bilirubin. These electrodes exhibit full orientation of the enzyme, as confirmed by the observable non-catalytic redox system corresponding to the T1 copper center associated with pure Nernstian electrocatalytic behavior with high catalytic currents of almost 5 mA cm(-2) at neutral pH. PMID:26449635

  17. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice.

    PubMed

    Wagner, Martin; Halilbasic, Emina; Marschall, Hanns-Ulrich; Zollner, Gernot; Fickert, Peter; Langner, Cord; Zatloukal, Kurt; Denk, Helmut; Trauner, Michael

    2005-08-01

    Induction of hepatic phase I/II detoxification enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate involved enzymes and transporters, we aimed to induce adaptive alternative pathways with different CAR and PXR agonists in vivo. Mice were treated with the CAR agonists phenobarbital and 1,4-bis-[2-(3,5-dichlorpyridyloxy)]benzene, as well as the PXR agonists atorvastatin and pregnenolone-16alpha-carbonitrile. Hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Cyp3a11, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Ntcp, Oatp1,2,4, Bsep, Mrp2-4, Mdr2, Abcg5/8, Asbt) in the liver and kidney were analyzed via reverse-transcriptase polymerase chain reaction and Western blotting. Potential functional relevance was tested in common bile duct ligation (CBDL). CAR agonists induced Mrp2-4 and Oatp2; PXR agonists induced only Mrp3 and Oatp2. Both PXR and CAR agonists profoundly stimulated bile acid-hydroxylating/detoxifying enzymes Cyp3a11 and Cyp2b10. In addition, CAR agonists upregulated bile acid-sulfating Sult2a1 and bilirubin-glucuronidating Ugt1a1. These changes were accompanied by reduced serum levels of bilirubin and bile acids in healthy and CBDL mice and by increased levels of polyhydroxylated bile acids in serum and urine of cholestatic mice. Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other transporters and enzymes were moderately affected. In conclusion, administration of specific CAR or PXR ligands results in coordinated stimulation of major hepatic bile acid/bilirubin metabolizing and detoxifying enzymes and hepatic key alternative efflux systems, effects that are predicted to counteract cholestasis. PMID:15986414

  18. Direct Antioxidant Properties of Bilirubin and Biliverdin. Is there a Role for Biliverdin Reductase?

    PubMed Central

    Jansen, Thomas; Daiber, Andreas

    2012-01-01

    Reactive oxygen species (ROS) and signaling events are involved in the pathogenesis of endothelial dysfunction and represent a major contribution to vascular regulation. Molecular signaling is highly dependent on ROS. But depending on the amount of ROS production it might have toxic or protective effects. Despite a large number of negative outcomes in large clinical trials (e.g., HOPE, HOPE-TOO), antioxidant molecules and agents are important players to influence the critical balance between production and elimination of reactive oxygen and nitrogen species. However, chronic systemic antioxidant therapy lacks clinical efficacy, probably by interfering with important physiological redox signaling pathways. Therefore, it may be a much more promising attempt to induce intrinsic antioxidant pathways in order to increase the antioxidants not systemically but at the place of oxidative stress and complications. Among others, heme oxygenase (HO) has been shown to be important for attenuating the overall production of ROS in a broad range of disease states through its ability to degrade heme and to produce carbon monoxide and biliverdin/bilirubin. With the present review we would like to highlight the important antioxidant role of the HO system and especially discuss the contribution of the biliverdin, bilirubin, and biliverdin reductase (BVR) to these beneficial effects. The BVR was reported to confer an antioxidant redox amplification cycle by which low, physiological bilirubin concentrations confer potent antioxidant protection via recycling of biliverdin from oxidized bilirubin by the BVR, linking this sink for oxidants to the NADPH pool. To date the existence and role of this antioxidant redox cycle is still under debate and we present and discuss the pros and cons as well as our own findings on this topic. PMID:22438843

  19. Association between Serum Bilirubin and Estimated Glomerular Filtration Rate among Diabetic Patients

    PubMed Central

    Katoh, Takeaki; Kawamoto, Ryuichi; Kohara, Katsuhiko; Miki, Tetsuro

    2015-01-01

    The subjects comprised 230 men aged 77 ± 10 (range: 50–100) years and 279 women aged 81 ± 10 (50–101) years that visited the medical department. We examined the relationship between increased serum bilirubin and renal function evaluated by estimated glomerular filtration rate (eGFR) using CKD-EPI equations modified by a Japanese coefficient. Compared with the fourth quartile in serum bilirubin (1.01–1.97 mg/dL), the nonadjusted, age and gender-adjusted, and multivariate-adjusted odds ratios {95% confidence interval (CI)} of eGFR <60 mL/min/1.73 m2 for the first quartile in serum bilirubin (0.13–0.50 mg/dL) were 2.08 (1.25–3.44), 1.82 (1.07–3.09), and 1.53 (0.83–2.81), respectively. Moreover, compared with the fourth quartile, nonadjusted, age and gender-adjusted, and multivariate-adjusted odds ratios (95% CI) of eGFR <45 mL/min/1.73 m2 for the first quartile were 3.50 (1.95–6.23), 3.12 (1.72–5.65), and 3.53 (1.71–7.26), respectively. The data were further stratified by gender, age, medication (antihypertensive, antidyslipidemic, and antidiabetic agents), and prevalence of cardiovascular disease (CVD). The standardized coefficients for eGFR were significant in all the subgroups other than the prevalence of CVD, and there were significant interactions between the two groups regarding CVD. Our data demonstrated an independent positive association between serum bilirubin and eGFR among diabetic patients.

  20. Somatostatin inhibits the effect of secretin on bile flow and on hepatic bilirubin transport in the rat.

    PubMed Central

    Ricci, G L; Fevery, J

    1989-01-01

    Increasing amounts of porcine secretion (0.05 to 2.00 clinical units/h/100 g body wt) given to rats during a continuous infusion of bilirubin, increased bile flow and the apparent maximal biliary excretion of bilirubin ('Tm'). This increment was caused by an enhanced biliary output of bilirubin monoconjugates. The effect was dose dependent but maximal at a secretin infusion of 0.80 CU. Somatostatin 0.2 and 0.8 microgram/h/100 g body wt caused a dose related inhibition of the hepatic effects of secretin both on bile flow and on biliary output of bilirubin conjugates. As secretin elicits the release of somatostatin, a feed-back system could be envisaged whereby the somatostatin released stops the effects of secretin. PMID:2572517

  1. Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage.

    PubMed

    Ye, Hai-Bo; Shi, Hai-Bo; Wang, Jian; Ding, Da-Lian; Yu, Dong-Zhen; Chen, Zheng-Nong; Li, Chun-Yan; Zhang, Wei-Tian; Yin, Shan-Kai

    2012-11-01

    Bilirubin can cause temporary or permanent sensorineural deafness in newborn babies with hyperbilirubinemia. However, the underlying targets and physiological effects of bilirubin-induced damage in the peripheral auditory system are unclear. Using cochlear functional assays and electron microscopy imaging of the inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted in threshold elevation in both compound action potential (CAP) and auditory brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug administration. The threshold elevation was associated with delayed wave latencies and elongated interwave intervals in ABR and CAP. At 72 hr postinjection, these measures returned to control levels, except for the CAP amplitude. Cochlear microphonics remained unchanged during the experiment. Morphological abnormalities were consistent with the electrophysiological dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn, myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair cells at 8 hr posttreatment. Similar to the electrophysiological findings, morphological changes were mostly reversed 10 days after treatment, except for the ANF reduction in the basal turn. These results suggest that hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of SGNs and their fibers. Our observations indicate a potential connection between hyperbilirubinemia and auditory neuropathy. PMID:22847875

  2. Interference of Bilirubin in the Determination of Magnesium with Methyl Thymol Blue

    PubMed Central

    Maksinovic, Rada; Ketin, Sonja; Biocanin, Rade

    2015-01-01

    Introduction: Jaundice is a disease named for the yellow color of the skin. This color is the result of elevated levels of bilirubin in the blood serum. In Roma from Krusevac region in the last few years have seen the emergence of jaundice. Material and methods: In 80 of them (40 suffering and 40 from control group) were performed tests of numerous parameters in the laboratories of the Health Center in Krusevac. Magnesium was determined by spectrophotometry with methyl thymol blue, titanium yellow and blue xylidene. Bilirubin was determined by Jandrešek Grofov’s method. Results: The results were within the expectations, in addition to magnesium which was determined with methyl thymol blue. In all patients suffering from jaundice concentration of magnesium (0.67 ±0.14 mmol/l) statistically was significantly lower than tested of the control group (0.91± 0.059 mmol/). There is no theoretical data to reduce the concentration of magnesium in serum as a result of jaundice. That’s why we determined magnesium both in the control group and in sufferings with two methods as the titanium yellow, and xylidene blew. With these two methods we obtained results that were examined were within normal limits. Conclusion: This has led us to conclude that the determination of bilirubin interferes with magnesium methyl thymol blue. PMID:26244045

  3. The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin.

    PubMed

    Call, N B; Tisher, C C

    1975-02-01

    The role of high serum and tissue levels of unconjegated bilirubin in the pathogenesis of the impaired urinary concentrating ability was investigated in homozygous (jj) Gunn rats with the congenital absence of hepatic glucuronyl transferase. Continuous phototherapy with blue fluorescent lights at a wave length of 460 nm or oral cholestyramine feeding or both reduced serum levels of unconjugated hilirubin to levels consistently below 3.0 mg/100 ml for several weeks in both weanling and adult jj Gunn rats. The renal concentrating defect was already present in weanling jj Gunn rats by 21 days of age. In treated weanling jj animals, maximum concentrating ability and the concentration of urea and nonurea solutes in the papilla and medulla, determined after 24 h of fluid deprivation, were normal when compared to unaffected heterozygous (Jj) littermates. Solute-free water reabsorption which is reduced in jaundiced jj Gunn rats was restored to normal in treated weanling jj rats. The tissue concentration of unconjugated bilirubin was reduced throughout the papilla and inner and outer medulla in the treated jj rats in comparison with untreated jj littermates. The defect in urinary concentrating ability was only partially reversible and sometimes irreversible in adult jj rats, probably because of permanent renal parenchymal damage occurring secondary to massive crystalline deposits in the papilla and medulla. It is concluded that unconjugated bilirubin is directly involved in the pathogenesis of the concentrating defect in jaundiced jj Gunn rats. PMID:1127102

  4. Serum Bilirubin Is Inversely Associated with Increased Arterial Stiffness in Men with Pre-Hypertension but Not Normotension

    PubMed Central

    Huang, Yao-Hsien; Yang, Yi-Ching; Lu, Feng-Hwa; Sun, Zih-Jie; Wu, Jin-Shang; Chang, Chih-Jen

    2016-01-01

    Objective Serum bilirubin level has shown to be inversely associated with coronary atherosclerosis, and may serve as a protective biomarker of coronary artery disease. Serum bilirubin has also been shown to be negatively associated with brachial-ankle pulse wave velocity (baPWV) in men without a history of hypertension, and in men with hypertension. It is unknown whether such associations can be observed in the pre-hypertensive or normotensive population. This study thus aimed to investigate the relationship between serum bilirubin level and increased arterial stiffness in subjects with pre-hypertension and normotension for both genders. Methods A cross-sectional sample of 3,399 apparently healthy subjects undergoing a medical check-up at National Cheng Kung University Hospital was enrolled between October 2006 and August 2009, after excluding subjects with serum total bilirubin level greater than 20.52 μmol/L. Increased arterial stiffness was defined as baPWV of 1,400 cm/s or higher as the dichotomous variable and bilirubin as the continuous variable. Results Based on multiple linear regression analysis, serum bilirubin level was inversely associated with baPWV in non-hypertensive men (β = -0.066, p < 0.001) but not in non-hypertensive women. In addition, the inverse relationship between bilirubin level and baPWV was found statistically significant only in pre-hypertensive men (β = -0.110, p < 0.001). Multiple logistic regression analysis showed that serum bilirubin was inversely associated with increased arterial stiffness in men with pre-hypertension (odds ratio = 0.955, 95% confidence interval = 0.916–0.996, p < 0.05) but not normotension after adjustment for other confounding factors. However, the relationship between total bilirubin level and increased arterial stiffness did not reach statistical significance for female subjects with pre-hypertension and normotension. Conclusion Serum bilirubin is inversely associated with increased arterial stiffness in

  5. Wernicke's encephalopathy in a patient with gastric carcinoma: a diagnosis not to miss

    PubMed Central

    Udyavara Kudru, Chandrashekar; Kaniyoor Nagiri, Shivashankara; Rao, Sandeep

    2014-01-01

    We describe a case of a patient who presented with a 20-day history of vomiting, generalised weakness and loss of appetite and a 2-day history of altered sensorium. On examination, he was grossly emaciated and there were no palpable lymph nodes. Central nervous system examination revealed nystagmus with bilateral lateral recti palsy and abdominal examination showed mild hepatomegaly. MRI of the brain showed bilateral and symmetrical hypertense signal changes in T2-weighted and fluid-attenuated inversion recovery sequences with diffusion restriction in the paramedian ventromedial thalamus. These findings were compatible with Wernicke's encephalopathy. He was started on thiamine supplementation with which neurological signs improved. An ultrasound of the abdomen showed mild hepatomegaly with multiple hyperechoic lesions and wall thickening of the pyloric antrum. Upper gastroduodenoscopy showed ulcerative lesions involving the antrum, pylorus and duodenum. Biopsy revealed moderately differentiated adenocarcinoma. The patient underwent palliative gastrojejunostomy and was clinically better at discharge. It is important to consider Wernicke encephalopathy in patients with gastric cancer who have acute neurological symptoms. PMID:24654252

  6. Development of an experimental rat model of hyperammonemic encephalopathy and evaluation of the effects of rifaximin.

    PubMed

    Tamaoki, Satoru; Suzuki, Hiroyuki; Okada, Mami; Fukui, Norio; Isobe, Mitsui; Saito, Tomoyuki

    2016-05-15

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with hepatic dysfunction. However, the precise mechanism of HE is unclear. To elucidate the mechanism, we developed a new rat model of HE with coma using a combination of subcutaneous splenic transposition, partial hepatectomy and portal vein stenosis. In this model, blood ammonia levels increase in the postcaval vein over time and markedly increase in the cerebrospinal fluid (CSF). The distribution of ammonia in the various blood vessels in the HE model suggests that the origin of peripheral blood and CSF ammonia is the mesenteric veins that drain blood from the gastrointestinal tract. Behavioral analysis revealed decreased pain response, increased passivity, and decreased pinna and corneal reflexes, followed by the development of coma. The development of coma in this model was frequent and reproducible. Increased S100 calcium-binding protein B (S100B: a biomarker for brain injury) in venous blood, as well as damaged brain tissue, increased intracranial pressure and cerebral edema were observed in rats with coma. A very high correlation was observed between the blood ammonia concentration in the postcaval vein and the onset of coma. Rifaximin, a poorly absorbed antibiotic that targets gut flora, significantly improved symptoms of HE. Based on these results, our rat model appears to reflect the pathological state of HE associated with acute liver failure and may be a useful model for analysis of hyperammonemic encephalopathy. PMID:26980242

  7. Prognostic performance of clinical indices and model scorings for acute-on-chronic liver failure: A study of 164 patients

    PubMed Central

    ZHANG, QIANQIAN; GUO, XIAOLIN; ZHAO, SHIXING; PANG, XIAOLI; WANG, YANG; ZHANG, YUJIAO; CHI, BAORONG

    2016-01-01

    The present study aimed to analyze the prognostic factors of acute-on-chronic liver failure (ACLF), with the perspective of an improved selection of optimal therapeutic schemes. A retrospective analysis was used to study 164 patients with ACLF hospitalized between 2010 and 2014 in a single center. Patients were divided into favorable and unfavorable groups, according to the treatment outcomes. General characteristics and clinical manifestations were analyzed to determine whether they would affect the prognosis of the patients with ACLF, with a particular focus on the scoring systems Child-Pugh, model for end-stage liver disease (MELD), MELD with incorporation of sodium (MELD-Na), MELD and serum sodium ratio (MESO) and integrated MELD (iMELD). Hepatitis B virus infection was the predominant cause of ACLF, accounting for 88 cases (53.7%). Age, prothrombin time, thrombin time, international normalized ratio (INR), prothrombin activity, serum sodium, albumin, total bilirubin, serum creatinine, platelets, fasting blood sugar, infections, hepatic encephalopathy, hepatorenal syndrome (HRS), and electrolyte disorder were revealed to be associated with prognosis. Age, serum sodium, INR, HRS, and infection were independent prognostic risk factors, as determined by multivariate analysis. Child-Pugh, MELD, MELD-Na, MESO and iMELD scoring systems all demonstrated adequate predictive values, with MELD-Na as the most effective scoring system. In conclusion, age, hyponatremia, INR, HRS and bacterial or fungal infections were reported to be independent prognostic risk factors for ACLF. Among the various liver function scoring systems, MELD-Na was the most accurate in predicting the prognosis of ACLF. PMID:27073448

  8. Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

    PubMed Central

    Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

    2016-01-01

    AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

  9. Studies of the conformation of bilirubin and its dimethyl ester in dimethyl sulphoxide solutions by nuclear magnetic resonance.

    PubMed Central

    Kaplan, D; Navon, G

    1982-01-01

    The conformation of bilirubin and its dimethyl ester in dimethyl sulphoxide (DMSO) was investigated by n.m.r. spectroscopy. The chemical shifts of the pyrrole NH and Lactam protons of bilirubin and its dimethyl ester in DMSO indicate a strong interaction with the solvent. Inter-proton distances were calculated from nuclear Overhauser effects (NOE), selective and non-selective relaxation times (T1) and rotational correlation times taken from 13C relaxation times. The interproton distances indicate that the conformation of the skeleton of bilirubin and its dimethyl ester in DMSO is similar to that of bilirubin and mesobilirubin in the crystalline state and in chloroform solutions, except for a possible slight twist of the pyrrolenone rings about the methine bonds, which may be a consequence of solvation of the NH groups by DMSO. Unlike in chloroform solutions, no direct hydrogen-bonding occurs between the carboxylic acid and the lactam groups of bilirubin in DMSO, as shown by the absence of an NOE between these groups. The fast exchange of the pyrrole NH protons with 2H shows that no hydrogen-bonding occurs between these protons and the propionic residues, in line with their solvation by DMSO. From the above results, and from the slowness of the internal motion of the propionic residues of bilirubin and its dimethyl ester, it is concluded that these residues are tied to the skeleton via bound solvent molecules. PMID:6284124

  10. Serum bilirubin value predicts hospital admission in carbon monoxide-poisoned patients. Active player or simple bystander?

    PubMed Central

    Cervellin, Gianfranco; Comelli, Ivan; Buonocore, Ruggero; Picanza, Alessandra; Rastelli, Gianni; Lippi, Giuseppe

    2015-01-01

    OBJECTIVES: Although carbon monoxide poisoning is a major medical emergency, the armamentarium of recognized prognostic biomarkers displays unsatisfactory diagnostic performance for predicting cumulative endpoints. METHODS: We performed a retrospective and observational study to identify all patients admitted for carbon monoxide poisoning during a 2-year period. Complete demographical and clinical information, along with the laboratory data regarding arterial carboxyhemoglobin, hemoglobin, blood lactate and total serum bilirubin, was retrieved. RESULTS: The study population consisted of 38 poisoned patients (23 females and 15 males; mean age 39±21 years). Compared with discharged subjects, hospitalized patients displayed significantly higher values for blood lactate and total serum bilirubin, whereas arterial carboxyhemoglobin and hemoglobin did not differ. In a univariate analysis, hospitalization was significantly associated with blood lactate and total serum bilirubin, but not with age, sex, hemoglobin or carboxyhemoglobin. The diagnostic performance obtained after combining the blood lactate and total serum bilirubin results (area under the curve, 0.90; 95% CI, 0.81-0.99; p<0.001) was better than that obtained for either parameter alone. CONCLUSION: Although it remains unclear whether total serum bilirubin acts as an active player or a bystander, we conclude that the systematic assessment of bilirubin may, alongside lactate levels, provide useful information for clinical decision making regarding carbon monoxide poisoning. PMID:26375565

  11. Unilobar Versus Bilobar Biliary Drainage: Effect on Quality of Life and Bilirubin Level Reduction

    PubMed Central

    Gamanagatti, Shivanand; Singh, Tejbir; Sharma, Raju; Srivastava, Deep N; Dash, Nihar Ranjan; Garg, Pramod Kumar

    2016-01-01

    Background: Percutaneous biliary drainage is an accepted palliative treatment for malignant biliary obstruction. Purpose: To assess the effect on quality of life (QOL) and bilirubin level reduction in patients with inoperable malignant biliary obstruction treated by unilobar or bilobar percutaneous transhepatic biliary drainage (PTBD). Materials and Methods: Over a period of 2 years, 49 patients (age range, 22–75 years) of inoperable malignant biliary obstruction were treated by PTBD. Technical and clinical success rates, QOL, patency rates, survival rates, and complications were recorded. Clinical success rates, QOL, and bilirubin reduction were compared in patients treated with complete (n = 21) versus partial (n = 28) liver parenchyma drainage. QOL before and 1 month after biliary drainage were analyzed retrospectively between these two groups. Results: Biliary drainage was successful in all 49 patients, with an overall significant reduction of the postintervention bilirubin levels (P < 0.001) resulting in overall clinical success rate of 89.97%. Clinical success rates were similar in patients treated with whole-liver drainage versus partial-liver drainage. Mean serum bilirubin level before PTBD was 19.85 mg/dl and after the procedure at 1 month was 6.02 mg/dl. The mean baseline functional score was 39.35, symptom scale score was 59.55, and global health score was 27.45. At 1 month, mean functional score was 61.25, symptom scale score was 36.0 4, and global health score was 56.33, with overall significant improvement in QOL (<0.001). There was a statistically significant difference in the improvement of the QOL scores (P = 0.002), among patients who achieved clinical success, compared with those patients who did not achieve clinical success at 1 month. We did not find any significant difference in the QOL scores in patients according to the amount of liver drained (unilateral or bilateral drainage), the type of internalization used (ring biliary or stent

  12. Posterior reversible encephalopathy syndrome in a child with steroid-resistant nephrotic syndrome: a case report and review of literature.

    PubMed

    Zhang, Yu; Zhou, Jianhua; Chen, Yu

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare and serious syndrome of central nervous system that can develop in both adults and children. It is characterized by acute onset of headache, confusion, seizures or focal neurological deficits along with radiological findings of white matter abnormalities in the parietal and occipital lobes. In the past ten years, this syndrome has been described mainly in adults, rare in children. Here, we report a case of PRES presenting in a 12-year-old girl with steroid-resistant nephrotic syndrome. Her neurological symptom was rapidly recovered after control of hypertension without discontinuation of cyclosporine A. PMID:25120830

  13. Posterior reversible encephalopathy syndrome in a child with steroid-resistant nephrotic syndrome: a case report and review of literature

    PubMed Central

    Zhang, Yu; Zhou, Jianhua; Chen, Yu

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare and serious syndrome of central nervous system that can develop in both adults and children. It is characterized by acute onset of headache, confusion, seizures or focal neurological deficits along with radiological findings of white matter abnormalities in the parietal and occipital lobes. In the past ten years, this syndrome has been described mainly in adults, rare in children. Here, we report a case of PRES presenting in a 12-year-old girl with steroid-resistant nephrotic syndrome. Her neurological symptom was rapidly recovered after control of hypertension without discontinuation of cyclosporine A. PMID:25120830

  14. Biochemical basis of heterogeneity in acute presentations of propionic acidemia.

    PubMed

    Sindgikar, Seema Pavaman; Rao, Suchetha; Shenoy, Rathika D; Kamath, Nutan

    2013-01-01

    Propionic acidemia (PA), an uncommon organic acidemia has varied clinical and metabolic presentation causing difficulty and delay in the diagnosis. We report a case of PA in an infant who presented with failure to thrive, acute encephalopathy due to severe hyperammonemia without acidosis and fungal sepsis. The biochemical basis of severe hyperammonemia is discussed. PMID:24381430

  15. The Neuropathology of Chronic Traumatic Encephalopathy

    PubMed Central

    McKee, Ann C.; Stein, Thor D.; Kiernan, Patrick T.; Alvarez, Victor E.

    2015-01-01

    Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43 kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. PMID:25904048

  16. Posterior Reversible Encephalopathy Syndrome Complicating Traumatic Pancreatitis

    PubMed Central

    Sigurtà, Anna; Terzi, Valeria; Regna-Gladin, Caroline; Fumagalli, Roberto

    2016-01-01

    Abstract We are reporting a case of posterior reversible encephalopathy syndrome (PRES) developed in an unusual clinical scenario without the presence of the most described symptoms. PRES is a neurological and radiological syndrome described in many different clinical conditions. In children it has been mostly reported in association with hematological and renal disorders. Our patient was a 15 years old boy, admitted to our intensive care unit for pancreatitis after blunt abdominal trauma. During the stay in the intensive care unit, he underwent multiple abdominal surgical interventions for pancreatitis complications. He had a difficult management of analgesia and sedation, being often agitated with high arterial pressure, and he developed a bacterial peritonitis. After 29 days his neurological conditions abruptly worsened with neuroimaging findings consistent with PRES. His clinical conditions progressively improved after sedation and arterial pressure control. He was discharged at home with complete resolution of the neurological and imaging signs 2 months later. The pathophysiology of PRES is controversial and involves disordered autoregulation ascribable to hypertension and endothelial dysfunction. In this case both hypertension and endothelial activation, triggered by sepsis and pancreatitis, could represent the culprits of PRES onset. Even if there is no specific treatment for this condition, a diagnosis is mandatory to start antihypertensive and supportive treatment. We are therefore suggesting to consider PRES in the differential diagnosis of a neurological deterioration preceded by hypertension and/or septic state, even without other “typical” clinical features. PMID:27258506

  17. A critical review of chronic traumatic encephalopathy.

    PubMed

    Iverson, Grant L; Gardner, Andrew J; McCrory, Paul; Zafonte, Ross; Castellani, Rudy J

    2015-09-01

    Chronic traumatic encephalopathy (CTE) has been described in the literature as a neurodegenerative disease with: (i) localized neuronal and glial accumulations of phosphorylated tau (p-tau) involving perivascular areas of the cerebral cortex, sulcal depths, and with a preference for neurons within superficial cortical laminae; (ii) multifocal axonal varicosities and axonal loss involving deep cortex and subcortical white matter; (iii) relative absence of beta-amyloid deposits; (iv) TDP-43 immunoreactive inclusions and neurites; and (v) broad and diverse clinical features. Some of the pathological findings reported in the literature may be encountered with age and other neurodegenerative diseases. However, the focality of the p-tau cortical findings in particular, and the regional distribution, are believed to be unique to CTE. The described clinical features in recent cases are very similar to how depression manifests in middle-aged men and with frontotemporal dementia as the disease progresses. It has not been established that the described tau pathology, especially in small amounts, can cause complex changes in behavior such as depression, substance abuse, suicidality, personality changes, or cognitive impairment. Future studies will help determine the extent to which the neuropathology is causally related to the diverse clinical features. PMID:26183075

  18. Sodium Benzoate for Treatment of Hepatic Encephalopathy

    PubMed Central

    Misel, Michael L.; Patton, Heather; Mendler, Michel

    2013-01-01

    Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction. PMID:24711766

  19. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

    PubMed

    Gastaldi, Matteo; Thouin, Anaïs; Vincent, Angela

    2016-01-01

    Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies. PMID:26692392

  20. Chronic traumatic encephalopathy and other neurodegenerative proteinopathies.

    PubMed

    Tartaglia, Maria Carmela; Hazrati, Lili-Naz; Davis, Karen D; Green, Robin E A; Wennberg, Richard; Mikulis, David; Ezerins, Leo J; Keightley, Michelle; Tator, Charles

    2014-01-01

    "Chronic traumatic encephalopathy" (CTE) is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this "perspective" is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment. PMID:24550810

  1. A Case of 5-Fluorouracil Induced Encephalopathy

    PubMed Central

    Kwon, Kyung A; Kwon, Hyuk-Chan; Kim, Min Chan; Kim, Sung-Hyun; Oh, Sung Yong; Lee, Suee

    2010-01-01

    Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m2) for 5 days and cisplatin (60 mg/m2) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days. PMID:20622967

  2. Mycophenolate-Induced Posterior Reversible Encephalopathy Syndrome.

    PubMed

    Khajuria, Bhavik; Khajuria, Mansi; Agrawal, Yashwant

    2016-01-01

    A 29-year-old woman presented with diffuse anasarca and shortness of breath. Workup revealed a creatinine of 3.3 and a glomerular filtration rate of 17. The patient was also found to be pancytopenic with evidence of hemolytic anemia. A renal biopsy showed evidence of stage IV lupus nephritis with rapidly progressive glomerulonephritis. Her lupus was further classified as ANA negative and anti-dsDNA positive. Mycophenolate and triweekly hemodialysis were started along with a steroid burst of methylprednisolone 1 g for 3 days followed by prednisone 60 mg daily. Four days after discharge, the patient represented with a witnessed 3-minute seizure involving bowel incontinence, altered mental status, and tongue biting. She was given 2 mg intravenous lorazepam and loaded with 1000 mg levetiracetam for seizure prophylaxis. Magnetic resonance imaging of the head revealed bilateral posterior hemispheric subcortical edema, and the diagnosis of posterior reversible encephalopathy syndrome was made. Mycophenolate was immediately discontinued and replaced with cyclophosphamide. Strict blood pressure control below 140/90 mm Hg was maintained initially with intravenous nicardipine drip and then transitioned to oral nifedipine, clonidine, losartan, and minoxidil. A repeat head magnetic resonance imaging 8 days later showed resolved subcortical edema consistent with the patient's improved mental status. No permanent neurologic sequelae were recorded as a result of this hospital episode. PMID:25933141

  3. The spectrum of disease in chronic traumatic encephalopathy

    PubMed Central

    McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

    2013-01-01

    Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I–IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I–III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy

  4. Posterior reversible encephalopathy syndrome with PLEDs-plus due to mesalamine

    PubMed Central

    Cherian, Ajith; Soumya, C. V.; Iype, Thomas; Mathew, Mini; Sandeep, P.; Thadam, Jessline K.; Chithra, P.

    2014-01-01

    A 32-year-old lady developed status epilepticus and acute visual loss while on mesalamine for Crohn's disease. Her clinical course and magnetic resonance imaging (MRI) were suggestive of posterior reversible encephalopathy syndrome (PRES). She had periodic lateralized epileptiform discharges plus (PLEDs-plus) on electroencephalogram (EEG), which responded to sodium valproate. Her vision improved from counting fingers at one-meter distance to 6/12. Though different cytotoxic drugs have been implicated as causative agents, this is the first case report of mesalamine-induced PRES. This case highlights the need for aggressive treatment of PLEDs-plus with EEG monitoring using a broad-spectrum antiepileptic drug like valproate, which has contributed to the rapid reversibility of vision in PRES subjects, and the need for a thorough drug history for etiological clues. PMID:24741259

  5. Iatrogenic Coagulopathy and the Development of Posterior Reversible Encephalopathy Syndrome after L-asparaginase Chemotherapy.

    PubMed

    Rota, Eugenia; Vallisa, Daniele; Morelli, Nicola; Scagnelli, Paola

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome mostly related to hypertension, eclampsia, renal failure, or to chemotherapy and/or immunosuppressive drugs. Although the PRES pathophysiology is multifactorial, hypertension and endothelial dysfunction are hypothesized to be the pivotal factors. Here we report a case of PRES in an adult patient after chemotherapy (Escherichia coli L-asparaginase [L-ASP], daunorubicin, vincristine, and intrathecal methotrexate) for acute lymphoblastic leukemia. The development of the PRES was strictly associated with an iatrogenic coagulopathy induced by L-ASP, which inhibits the biosynthesis of hepatic coagulation factors. The nadir of platelet count, antithrombin III (ATIII) and fibrinogen curve was coincident with the onset of the PRES neurological picture; subsequently, the normalization of the ATIII and fibrinogen levels seemed to parallel the good clinical evolution. This case seems to provide new insights into the PRES pathophysiological mechanisms. PMID:27014503

  6. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients.

    PubMed

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-08-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image. PMID:27322924

  7. Iatrogenic Coagulopathy and the Development of Posterior Reversible Encephalopathy Syndrome after L-asparaginase Chemotherapy

    PubMed Central

    Rota, Eugenia; Vallisa, Daniele; Morelli, Nicola; Scagnelli, Paola

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome mostly related to hypertension, eclampsia, renal failure, or to chemotherapy and/or immunosuppressive drugs. Although the PRES pathophysiology is multifactorial, hypertension and endothelial dysfunction are hypothesized to be the pivotal factors. Here we report a case of PRES in an adult patient after chemotherapy (Escherichia coli L-asparaginase [L-ASP], daunorubicin, vincristine, and intrathecal methotrexate) for acute lymphoblastic leukemia. The development of the PRES was strictly associated with an iatrogenic coagulopathy induced by L-ASP, which inhibits the biosynthesis of hepatic coagulation factors. The nadir of platelet count, antithrombin III (ATIII) and fibrinogen curve was coincident with the onset of the PRES neurological picture; subsequently, the normalization of the ATIII and fibrinogen levels seemed to parallel the good clinical evolution. This case seems to provide new insights into the PRES pathophysiological mechanisms. PMID:27014503

  8. A treatable metabolic cause of encephalopathy: cobalamin C deficiency in an 8-year-old male.

    PubMed

    Krueger, Jena M; Piantino, Juan; Smith, Craig M; Angle, Brad; Venkatesan, Charu; Wainwright, Mark S

    2015-01-01

    Neurologic regression in a previously healthy child may be caused by metabolic or neurodegenerative disorders, many of which have no definitive treatment. We report a case of a previously healthy 8-year-old boy who presented with a month-long history of waxing and waning encephalopathy and acute regression, followed by seizures. Evaluation for a metabolic disorder revealed methylmalonic acidemia and hyperhomocysteinemia of the cobalamin C type due to a single, presumed homozygous pathogenic c.394 C>T mutation in the MMACHC gene. With the appropriate diet restrictions and vitamin replacement, he improved significantly and returned to his premorbid level of behavior. This case illustrates an unusual presentation of a treatable metabolic disorder and highlights the need to consider cobalamin defects in the differential diagnosis of healthy children with neurologic regression. PMID:25511120

  9. Changing face of hepatic encephalopathy: Role of inflammation and oxidative stress

    PubMed Central

    Seyan, Amit S; Hughes, Robin D; Shawcross, Debbie L

    2010-01-01

    The face of hepatic encephalopathy (HE) is changing. This review explores how this neurocognitive disorder, which is associated with both acute and chronic liver injury, has grown to become a dynamic syndrome that spans a spectrum of neuropsychological impairment, from normal performance to coma. The central role of ammonia in the pathogenesis of HE remains incontrovertible. However, over the past 10 years, the HE community has begun to characterise the key roles of inflammation, infection, and oxidative/nitrosative stress in modulating the pathophysiological effects of ammonia on the astrocyte. This review explores the current thoughts and evidence base in this area and discusses the potential role of existing and novel therapies that might abrogate the oxidative and nitrosative stresses inflicted on the brain in patients with, or at risk of developing, HE. PMID:20632436

  10. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients.

    PubMed

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-08-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image. PMID:27483175

  11. Wernicke’s encephalopathy following Roux en Y gastric bypass surgery

    PubMed Central

    Zafar, Azra

    2015-01-01

    Wernicke’s encephalopathy (WE) is a serious neurological disorder characterized by a classical triad of acute mental confusion, ataxia, and opthalmoplegia due to thiamine deficiency. It was initially described in chronic alcoholics; however, any condition resulting in poor nutritional status places the patient at risk of WE. Bariatric surgery is now considered as an emergent cause of WE. The number of bariatric surgery is increasing for morbid obesity. We present a case of a 40-year-old male who presented with confusion and difficulty in maintaining the balance while walking 3 months after Roux en Y gastric bypass surgery. Diagnosis of WE was made on clinical ground and confirmed by magnetic resonance imaging of the brain, which showed bilateral hyperintense signals in paramedian thalami. Parenteral thiamine replacement was started, and patient showed complete recovery. PMID:26620994

  12. Neuromyelitis Optica in Pregnancy Complicated by Posterior Reversible Encephalopathy Syndrome, Eclampsia and Fetal Death

    PubMed Central

    Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

    2015-01-01

    Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable. PMID:25584107

  13. Hyponatremic encephalopathy after excessive water ingestion prior to pelvic ultrasound: neuroimaging findings.

    PubMed

    Yalcin-Cakmakli, Gul; Karli Oguz, Kader; Shorbagi, Ali; Funda Bas, Demet; Ergan-Arsava, Begum; Kunt, Mahir; Topcuoglu, Mehmet Akif

    2010-01-01

    We report two patients with acute hyponatremic encephalopathy which developed after massive water ingestion for pelvic ultrasound and emphasize the findings of magnetic resonance (MR) imaging including diffusion-weighted imaging (DWI). Both subjects had completely recovered within 24 hours following fluid restriction and salt replacement. MR imaging revealed cortical sulcal narrowing, restricted diffusion and sulcal T2 hyperintensity along with diffuse pial enhancement suggesting diffuse cerebral cortical cytotoxic edema and blood-brain barrier breakdown. In addition to the first illustration of multimodality MR imaging features of water-intoxication, these two cases also highlight the need for standardized practice on the quantity of water intake recommended to distend the bladder for pelvic ultrasound, especially in patients at risk for serum inappropriate ADH syndrome-related hyponatremia. PMID:20720364

  14. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients

    PubMed Central

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image.

  15. Diagnosis of acute cholecystitis using hepatobiliary scan with technetium-99m PIPIDA

    SciTech Connect

    Bennett, M.T.; Sheldon, M.I.; dos Remedios, L.V.; Weber, P.M.

    1981-09-01

    Sixty patients were evaluated for acute abdominal pain using technetium-99m PIPIDA hepatobiliary imaging. The sensitivity of the test was 90.6 percent in all patients and the accuracy was 93.3 percent. In the evaluation of acutely ill patients with right upper quadrant pain, fever, nausea and vomiting, hepatobiliary imaging with PIPIDA is the preferred test for diagnosing acute cholecystitis. If the test is positive, disease of the gallbladder and probably acute cholecystitis are present. Early operation can proceed if desirable. If the test is negative and the bilirubin level is less than 5.0 mg/dl, acute cholecystitis is not present. In such cases conservative treatment is appropriate, and follow-up tests should be performed to evaluate the possibility of chronic cholecystitis. When the bilirubin level exceeds 5.0 mg/dl, the test is often indeterminate.

  16. Diffusion restriction in ethylmalonic encephalopathy - An imaging evidence of the pathophysiology of the disease.

    PubMed

    Bhat, Maya Dattatraya; Prasad, Chandrajit; Tiwari, Sarbesh; Chandra, Sadanandavalli Retnaswami; Christopher, Rita

    2016-09-01

    Ethylmalonic encephalopathy is an inborn error of metabolism characterized by encephalopathy, petechiae chronic diarrhea and acrocyanosis. Imaging findings include patchy signal changes in the basal ganglia, periaqueductal region, subcortical white matter and cerebellum. We describe the novel finding of diffusion restriction in brain lesions, in a proven case of ethylmalonic encephalopathy. PMID:26992475

  17. Electroencephalogram of Age-Dependent Epileptic Encephalopathies in Infancy and Early Childhood

    PubMed Central

    Wong-Kisiel, Lily C.; Nickels, Katherine

    2013-01-01

    Epileptic encephalopathy syndromes are disorders in which the epileptiform abnormalities are thought to contribute to a progressive cerebral dysfunction. Characteristic electroencephalogram findings have an important diagnostic value in classification of epileptic encephalopathy syndromes. In this paper, we focus on electroencephalogram findings of childhood epileptic encephalopathy syndromes and provide sample illustrations. PMID:24024028

  18. 70 FR 18251 - Bovine Spongiform Encephalopathy; Minimal-Risk Regions and Importation of Commodities; Finding of...

    Code of Federal Regulations, 2014 CFR

    2005-04-08

    ... Agriculture Animal and Plant Health Inspection Service 9 CFR Part 93, et al. Bovine Spongiform Encephalopathy... Implementing Procedures (7 CFR part 372). Bovine Spongiform Encephalopathy; Minimal-Risk Regions and... pointed to the four confirmed cases of bovine spongiform encephalopathy (BSE) in cows of Canadian...

  19. Posterior reversible encephalopathy syndrome with neurological sequelae - a case report.

    PubMed

    Nesteruk, Marta; Kurdyła, Anna; Nesteruk, Tomasz; Dorobek, Małgorzata

    2016-04-01

    Posterior reversible encephalopathy syndrome (PRES) is a set of neurological symptoms including impaired consciousness, cognitive disorders, seizures, blurred vision, dizziness and headache. The symptoms are closely related to the location of pathological changes in the brain; bilateral occipitto-parietal region is most often affected. Both focal neurological symptoms and encephalopathy are usually transient. We present the case of 64-year-old woman with PRES. She suffered from many internal diseases and was admitted to the hospital due to impaired consciousness, speech disorders, balance disorders. Significant neurological deterioration was observed within several days from the onset. Differential diagnosis included stroke and viral neuroinfection (cytosis 23 cells /ul, protein level of 93 mg/dl); magnetic resonance examination revealed lesions typical for posterior reversible encephalopathy.After 6 weeks of hospitalization patient condition improved, but did not restore to the premorbid state. The patient was discharged with generalized cognitive impairment. PMID:27137827

  20. Fundamental immunological problems associated with "transmissible spongiform encephalopathies".

    PubMed

    Ebringer, Alan; Rashid, Taha; Wilson, Clyde

    2015-02-01

    "Bovine spongiform encephalopathy", "scrapie", as well as Creutzfeldt-Jakob disease and kuru belong to a group of related neurological conditions termed "transmissible spongiform encephalopathies". These diseases are based on the LD50 measurement whereby saline brain homogenates are injected into experimental animals and when 50% of them develop symptoms, this is considered as transmission of the disease, but the gold standard for diagnosis is autopsy examination. However, an untenable assumption is being made in that saline brain homogenates do not cause tissue damage but it is known since the time of Pasteur, that they give rise to "post-rabies vaccination allergic encephalomyelitis". This is the fundamental flaw in the diagnosis of these diseases. A way forward, however, is to examine infectious agents, such as Acinetobacter which show molecular mimicry with myelin and elevated levels of antibodies to this microbe are found in multiple sclerosis patients and animals affected by "bovine spongiform encephalopathy". PMID:25573495

  1. Colectomy for Porto-Systemic Encephalopathy: Is it Still Topical?

    PubMed

    Ennaifer, Rym; Hayfa, Romdhane; Hefaiedh, Rania; Marsaoui, Lobna; Hadj, Najet Bel; Khalfallah, Tahar

    2013-01-25

    Hepatic encephalopathy (HE) is a common long term complication of porto-systemic shunt. We report herein the case of a 59-year-old man with Child-Pugh A cirrhosis treated successfully 9 years earlier with distal splenorenal shunt for uncontrolled variceal bleeding. In the last year, he developed a severe and persistent hepatic encephalopathy secondary to the shunt, which was resistant to medical therapy. As liver transplantation was not available and obliteration of the shunt was hazardous, we performed subtotal colectomy in order to reduce ammonia production. This therapeutic option proved successful, as the grade of encephalopathy decreased and the patient improved. Our experience indicates that colonic exclusion should be considered as an option in the management of HE refractory to medical treatment in highly selected patients when liver transplantation is not available or even as a bridge given the long waiting time on lists. PMID:24765497

  2. Covert and Overt Hepatic Encephalopathy: Diagnosis and Management.

    PubMed

    Patidar, Kavish R; Bajaj, Jasmohan S

    2015-11-01

    Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into 2 broad categories based on severity: covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE). CHE has a significant impact on a patient's quality of life, driving performance, and recently has been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, early diagnosis and management are imperative. In addition, focus also should be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of nonabsorbable disaccharides, antibiotics (ie, rifaximin), and, potentially, probiotics. Other therapies currently under further investigation include L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion. PMID:26164219

  3. Useful Tests for Hepatic Encephalopathy in Clinical Practice

    PubMed Central

    Nabi, Eiman; Bajaj, Jasmohan S

    2014-01-01

    Hepatic encephalopathy (HE) is a serious complication of liver disease and portosystemic shunting that represents a continuum of neuropsychiatric changes and altered consciousness. It is classified as overt hepatic encephalopathy (OHE) when clinically apparent or as covert hepatic encephalopathy (CHE) in its mildest form. Progression of CHE to OHE and its impact of quality of life make its early diagnosis imperative. Several diagnostic techniques ranging from simple clinical scales to sophisticated computerized tests exist yet diagnosis remains a challenge due to the time, cost and personnel involved. Psychometric tests appear promising due to their high sensitivity and low cost but results are variable depending on age and education. The pros and cons of current diagnostic methods for overt and covert HE are reviewed along with strategy to CHE testing. PMID:24357348

  4. Utility of bilirubins and bile acids as endogenous biomarkers for the inhibition of hepatic transporters.

    PubMed

    Watanabe, Tomoko; Miyake, Manami; Shimizu, Toshinobu; Kamezawa, Miho; Masutomi, Naoya; Shimura, Takesada; Ohashi, Rikiya

    2015-04-01

    It is useful to identify endogenous substrates for the evaluation of drug-drug interactions via transporters. In this study, we investigated the utility of bilirubins, substrates of OATPs and MRP2, and bile acids and substrates of NTCP and BSEP, as biomarkers for the inhibition of transporters. In rats administered 20 and 80 mg/kg rifampicin, the plasma levels of bilirubin glucuronides were elevated, gradually decreased, and almost returned to the baseline level at 24 hours after administration without an elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This result indicates the transient inhibition of rOatps and/or rMrp2. Although the correlation between free plasma concentrations and IC50 values of rOatps depended on the substrates used in the in vitro studies, the inhibition of rOatps by rifampicin was confirmed in the in vivo study using valsartan as a substrate of rOatps. In rats administered 10 and 30 mg/kg cyclosporin A, the plasma levels of bile acids were elevated and persisted for up to 24 hours after administration without an elevation of ALT and AST. This result indicates the continuous inhibition of rNtcp and/or rBsep, although there were differences between the free plasma or liver concentrations and IC50 values of rNtcp or rBsep, respectively. This study suggests that the monitoring of bilirubins and bile acids in plasma is useful in evaluating the inhibitory potential of their corresponding transporters. PMID:25581390

  5. 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

  6. Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress

    SciTech Connect

    Muhsain, Siti Nur Fadzilah; Lang, Matti A.; Abu-Bakar, A'edah

    2015-01-01

    The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200 mg pyrazole/kg/day for 3 days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection. - Highlights: • Pyrazole induces oxidative stress in the mouse liver. • Pyrazole-induced oxidative stress induces mitochondrial targeting of key bilirubin regulatory enzymes, HMOX1

  7. Gut microbiota: its role in hepatic encephalopathy.

    PubMed

    Rai, Rahul; Saraswat, Vivek A; Dhiman, Radha K

    2015-03-01

    Ammonia, a key factor in the pathogenesis of hepatic encephalopathy (HE), is predominantly derived from urea breakdown by urease producing large intestinal bacteria and from small intestine and kidneys, where the enzyme glutaminases releases ammonia from circulating glutamine. Non-culture techniques like pyrosequencing of bacterial 16S ribosomal ribonucleic acid are used to characterize fecal microbiota. Fecal microbiota in patients with cirrhosis have been shown to alter with increasing Child-Turcotte-Pugh (CTP) and Model for End stage Liver Disease (MELD) scores, and with development of covert or overt HE. Cirrhosis dysbiosis ratio (CDR), the ratio of autochthonous/good bacteria (e.g. Lachnospiraceae, Ruminococcaceae and Clostridiales) to non-autochthonous/pathogenic bacteria (e.g. Enterobacteriaceae and Streptococcaceae), is significantly higher in controls and patients with compensated cirrhosis than patients with decompensated cirrhosis. Although their stool microbiota do not differ, sigmoid colonic mucosal microbiota in liver cirrhosis patients with and without HE, are different. Linkage of pathogenic colonic mucosal bacteria with poor cognition and inflammation suggests that important processes at the mucosal interface, such as bacterial translocation and immune dysfunction, are involved in the pathogenesis of HE. Fecal microbiome composition does not change significantly when HE is treated with lactulose or when HE recurs after lactulose withdrawal. Despite improving cognition and endotoxemia as well as shifting positive correlation of pathogenic bacteria with metabolites, linked to ammonia, aromatic amino acids and oxidative stress, to a negative correlation, rifaximin changes gut microbiome composition only modestly. These observations suggest that the beneficial effects of lactulose and rifaximin could be associated with a change in microbial metabolic function as well as an improvement in dysbiosis. PMID:26041954

  8. Progressive cerebral vascular degeneration with mitochondrial encephalopathy.

    PubMed

    Longo, Nicola; Schrijver, Iris; Vogel, Hannes; Pique, Lynn M; Cowan, Tina M; Pasquali, Marzia; Steinberg, Gary K; Hedlund, Gary L; Ernst, Sharon L; Gallagher, Renata C; Enns, Gregory M

    2008-02-01

    MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a maternally inherited disorder characterized by recurrent cerebral infarctions that do not conform to discreet vascular territories. Here we report on a patient who presented at 7 years of age with loss of consciousness and severe metabolic acidosis following vomiting and dehydration. She developed progressive sensorineural hearing loss, myopathy, ptosis, short stature, and mild developmental delays after normal early development. Biochemical testing identified metabolites characteristic of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (hexanoylglycine and suberylglycine), but also severe lactic acidemia (10-25 mM) and, in urine, excess of lactic acid, intermediates of the citric cycle, and marked ketonuria, suggesting mitochondrial dysfunction. She progressed rapidly to develop temporary cortical blindness. Brain imaging indicated generalized atrophy, more marked on the left side, in addition to white matter alterations consistent with a mitochondrial disorder. Magnetic resonance angiography indicated occlusion of the left cerebral artery with development of collateral circulation (Moyamoya syndrome). This process worsened over time to involve the other side of the brain. A muscle biopsy indicated the presence of numerous ragged red fibers. Molecular testing confirmed compound heterozygosity for the common mutation in the MCAD gene (985A>G) and a second pathogenic mutation (233T>C). MtDNA testing indicated that the muscle was almost homoplasmic for the 3243A>T mutation in tRNALeu, with a lower mutant load (about 50% heteroplasmy) in blood and skin fibroblasts. These results indicate that mitochondrial disorders may be associated with severe vascular disease resulting in Moyamoya syndrome. The contribution of the concomitant MCAD deficiency to the development of the phenotype in this case is unclear. PMID:18203188

  9. [Posterior reversible encephalopathy syndrome after neurosurgery: A literature review].

    PubMed

    Durán Paz, S; Moreno Casanova, I; Benatar-Haserfaty, J

    2015-12-01

    Posterior reversible encephalopathy syndrome is a clinical-radiological characterized by decreased level of consciousness, seizures, and visual disturbances, as well as radiologically ras brain edema, predominantly in parieto-occipital white matter regions. There are many situations that can trigger the disorder, including the administration of immunosuppressants, chemotherapy agents, hypertensive disorders, and sepsis. The case is described of a patient diagnosed with stage IV prostate adenocarcinoma, receiving chemotherapy, andundergoing a posterior reversible encephalopathy syndrome after surgery for resection of brain metastasis. PMID:25866131

  10. Treatment of chronic hepatic encephalopathy with levodopa 1

    PubMed Central

    Lunzer, Michael; James, I. M.; Weinman, J.; Sherlock, Sheila

    1974-01-01

    Three of six patients with chronic hepatic encephalopathy treated with levodopa showed a significant improvement. One patient was probably improved whilst the remaining two patients failed to show any benefit. Serial electroencephalography did not demonstrate significant changes. Treatment with levodopa was associated with an improvement in `speed-based' tasks as assessed by computerized psychometry. A significant rise in cerebral oxygen consumption was found during levodopa therapy. Gastrointestinal side effects were dose limiting. It is concluded that a therapeutic trial of levodopa in patients with chronic hepatic encephalopathy is indicated when the response to conventional therapy has been poor. PMID:4430473

  11. Toxic encephalopathy due to colchicine--Gloriosa superba poisoning.

    PubMed

    Gooneratne, Inuka Kishara; Weeratunga, Praveen; Caldera, Manjula; Gamage, Ranjanie

    2014-10-01

    Gloriosa superba, a flowering plant widespread in South and Southeast Asia, is implicated in many cases of self-poisoning. Colchicine is concentrated in the seeds and tubers and this mediates its toxicity. We describe a 28-year-old woman who developed delayed encephalopathy after eating G superba tubers. MR scan of brain showed bilateral symmetrical T2 basal ganglia hyperintensities in the caudate and lentiform nuclei. The delay in onset of encephalopathy is attributable to a direct-effect colchicine, probably mediated through its effect on microtubular transport. PMID:24591648

  12. Cefepime-induced encephalopathy with normal renal function

    PubMed Central

    Meillier, Andrew; Rahimian, David

    2016-01-01

    Cefepime is a fourth-generation cephalosporin that is frequently used in a wide array of infections. Since approval for use, concerns have been raised due to adverse effects including seizures, encephalopathy and myoclonus especially if renal dysfunction is present. Despite having appropriate renal dose adjustments, cases have been found with adverse neurological effects. On this occasion, we present a case of a patient with normal renal function that had demonstrated cefepime-induced encephalopathy with full resolution of symptoms following discontinuation of the medication. PMID:27274853

  13. Neonatal Encephalopathy: Update on Therapeutic Hypothermia and Other Novel Therapeutics.

    PubMed

    McAdams, Ryan M; Juul, Sandra E

    2016-09-01

    Neonatal encephalopathy (NE) is a major cause of neonatal mortality and morbidity. Therapeutic hypothermia (TH) is standard treatment for newborns at 36 weeks of gestation or greater with intrapartum hypoxia-related NE. Term and late preterm infants with moderate to severe encephalopathy show improved survival and neurodevelopmental outcomes at 18 months of age after TH. TH can increase survival without increasing major disability, rates of an IQ less than 70, or cerebral palsy. Neonates with severe NE remain at risk of death or severe neurodevelopmental impairment. This review discusses the evidence supporting TH for term or near term neonates with NE. PMID:27524449

  14. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions.

    PubMed

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-07-15

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

  15. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

    PubMed Central

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-01-01

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

  16. Differential regional responsiveness of astroglia in mild hepatic encephalopathy: An Immunohistochemical approach in bile duct ligated rat.

    PubMed

    Hiba, Omar El; Elgot, Abdeljalil; Ahboucha, Samir; Gamrani, Halima

    2016-05-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. However, the pathomechanisms of the disease remains obscure. Neuropathological studies have demonstrated a primary gliopathy in humans as well as in animal models of chronic and acute liver failure. Here, we have investigated in an animal model of mild HE: the bile duct ligated rat (BDL) at the cirrhotic stage (4 weeks after surgery), the expression of the key marker of mature astrocytes; the glial fibrillary acidic protein (GFAP) in different brain areas such as: Substantia nigra pars compacta (SNc), Ventral tegmental area (VTA), hippocampus, dorsal striatum and brain cortex by means of immunohistochemistry. The immunohistochemical study showed, in BDL compared to the operated controls (shams), a diminished astrocyte reactivity corresponding to a loss of GFAP expression within SNc, VTA, hippocampus and dorsal striatum (p<0.05),whereas in the brain cortex astrocytes appeared strongly immunoreactive with increased GFAP expression (p<0.05) as compared to shams. Our finding demonstrated differential astroglial responses which depend to the specificity of the area investigated and its particular neuronal neighboring environment, and could have possible outcomes on the diverse neuronal functions especially those observed during the different episodes of hepatic encephalopathy. PMID:26995310

  17. [Acute blood pressure elevations].

    PubMed

    Chamontin, B; Amar, J; Chollet, F; Rouge, P; Bonetti-d'Esteve, L; Guittard, J; Salvador, M

    2000-11-01

    Blood pressure (BP) elevations may correspond to different clinical situations. Hypertensives emergencies are situations that require immediate reduction in BP because of acute or rapidly progressing target organ damage: accelerated malignant hypertension, hypertensive encephalopathy, acute myocardial infarction, acute aortic dissection, acute left ventricular failure, and eclampsia. Hypertensive urgencies are those with marked elevated BP in which it is desirable to reduce BP progressively within few hours, such as severe hypertension, progressive target organ damage, perioperative hypertension. Cerebrovascular accidents have to be individualized. In most patients in the immediate post-stroke period, BP should not be lowered. Caution is advised in lowering BP in these patients because excessive falls may precipitate cerebral ischemia. In situations without symptoms or progressive target organ it is necessary to exclude proximate causes of elevated BP such as pain and elevated BP alone rarely requires antihypertensive treatment. Among parenteral antihypertensive (AH) drugs labetalol, nicardipine, urapidil, and nitroprussiate are generally used, and the choice of AH drug depends on the clinical situation. It is not required to normalize BP immediately but to reduce mean BP no more than 25%, then toward 160/100 mmHg as recommended by JNC VI, in order to avoid an impairment of renal, cerebral or coronary ischemia. Oral long-acting dihydropyridines are often subsequently administrated, except in myocardial ischemia. Therapeutic attitudes vary considerably according to the clinical situation: abstention, immediate decrease or progressive decrease in BP have to be decided. PMID:11190294

  18. Impact of Rhesus disease on the global problem of bilirubin-induced neurologic dysfunction.

    PubMed

    Zipursky, Alvin; Bhutani, Vinod K

    2015-02-01

    Clinical experience with Rhesus (Rh) disease and its post-icteric sequelae is limited among high-income countries because of nearly over four decades of effective prevention care. We hypothesized that Rh disease is prevalent in other regions of the world because it is likely that protection is limited or non-existent. Following a worldwide study, it has been concluded that Rh hemolytic disease is a significant public health problem resulting in stillbirths and neonatal deaths, and is a major cause of severe hyperbilirubinemia with its sequelae, kernicterus and bilirubin-induced neurologic dysfunction. Knowing that effective Rh-disease prophylaxis depends on maternal blood-type screening, healthcare afforded to the high-risk mothers needs to be free of bottlenecks and coupled with unfettered access to effective Rh-immunoglobulin. Future studies that match the universal identification of Rh-negative status of women and targeted use of immunoprophylaxis to prevent childhood bilirubin neurotoxicity are within reach, based on vast prior experiences. PMID:25582277

  19. Method for Estimating Bilirubin Isomerization Efficiency in Phototherapy to Treat Neonatal Jaundice

    NASA Astrophysics Data System (ADS)

    Lisenko, S. A.; Kugeiko, M. M.

    2014-11-01

    We propose a method for quantitative assessment of the efficacy of phototherapy to treat neonatal jaundice using the diffuse reflectance spectrum for the newborn's skin, based on the analytical dependence of the measured spectrum on the structural and morphological parameters of the skin, affecting the optical conditions in the medium, and an algorithm for rapid calculation of the bilirubin photoisomerization rate in the skin tissues as a function of the structural and morphological parameters of the skin and the wavelength of the exciting radiation. From the results of a numerical simulation of the process of radiation transport in the skin, we assess the stability of our method to variations in the scattering properties of the skin and the concentrations of its optically active chromophores (melanin, oxyhemoglobin, deoxyhemoglobin). We show that in order to achieve the maximum efficacy of phototherapy, we should use light from the range 484-496 nm. In this case, the intensity of the exciting radiation should be selected individually for each newborn according to the bilirubin photoisomerization rate characteristic for it.

  20. Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation

    PubMed Central

    NaveenKumar, Somanathapura K.; Thushara, Ram M.; Sundaram, Mahalingam S.; Hemshekhar, Mahadevappa; Paul, Manoj; Thirunavukkarasu, Chinnasamy; Basappa; Nagaraju, Ganesh; Raghavan, Sathees C.; Girish, Kesturu S.; Kemparaju, Kempaiah; Rangappa, Kanchugarakoppal S.

    2015-01-01

    Thrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro, and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation. PMID:26459859