Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder

PubMed Central

Wu, Xiujuan; Wu, Wei; Pan, Wei; Wu, Limin; Liu, Kangding; Zhang, Hong-Liang

2015-01-01

Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease. PMID:25873770

[Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat].

PubMed

Song, Min-ning; Song, Yu-na; Chen, Fu; Luo, Mei-lan

2007-01-01

To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(P<0.05 or P<0.01). The clinical manifestations, liver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26) micromol/L, both P<0.01], while the value of NA decreased in the group of CLF encephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,P<0.05]. The levels of 5-HT are elevated in the groups of ALF encephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.

Short and long-term outcomes in children with suspected acute encephalopathy.

PubMed

Nishiyama, Masahiro; Nagase, Hiroaki; Tanaka, Tsukasa; Fujita, Kyoko; Kusumoto, Mayumi; Kajihara, Shinsuke; Yamaguchi, Yoshimichi; Maruyama, Azusa; Takeda, Hiroki; Uetani, Yoshiyuki; Tomioka, Kazumi; Toyoshima, Daisaku; Taniguchi-Ikeda, Mariko; Morioka, Ichiro; Takada, Satoshi; Iijima, Kazumoto

2016-09-01

The time-dependent changes that occur in children after acute encephalopathy are not clearly understood. Therefore, we assessed changes in brain function after suspected acute encephalopathy over time. We created a database of children admitted to the pediatric intensive care unit at Kobe Children's Hospital because of convulsions or impaired consciousness with fever between 2002 and 2013. Clinical courses and outcomes were reviewed and patients who met the following criteria were included in the study: (1) 6months to 15years of age, (2) no neurological abnormality before onset, (3) treated for suspected acute encephalopathy, and (4) followed after 1 (0-2) month and 12 (10-17) months of onset. Outcomes were assessed using the Pediatric Cerebral Performance Category (PCPC) scale, with a score of 1 representing normal performance; 2, mild disability; 3, moderate disability; 4, severe disability; 5, vegetative state; and 6, brain death. A total of 78 children (32 male) with a median (range) age at onset of 20 (6-172) months were enrolled. Fifty-one cases scored 1 on the PCPC, 13 scored 2, three scored 3, five scored 4, one scored 5, and five cases scored 6 at discharge. Whereas seven of the 13 cases that scored a 2 on the PCPC recovered normal brain function after 12months, none of the nine cases that scored a 3-5 on the PCPC recovered normal function. Our findings suggest moderate to severe disability caused by acute encephalopathy had lasting consequences on brain function, whereas mild disability might result in improved function. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Deep cerebral venous thrombosis mimicking influenza-associated acute necrotizing encephalopathy: a case report.

PubMed

Taniguchi, Daisuke; Nakajima, Sho; Hayashida, Arisa; Kuroki, Takuma; Eguchi, Hiroto; Machida, Yutaka; Hattori, Nobutaka; Miwa, Hideto

2017-09-26

Acute necrotizing encephalopathy is one of the most devastating neurological complications of influenza virus infection. Acute necrotizing encephalopathy preferentially affects the thalamus bilaterally, as does deep cerebral venous thrombosis, which can lead to misdiagnosis. A 52-year-old Japanese woman infected with seasonal influenza B virus presented to the emergency care unit in our hospital with progressive alteration of her level of consciousness. Bilateral thalamic lesions were demonstrated by magnetic resonance imaging, leading to a tentative diagnosis of acute necrotizing encephalopathy. However, she had deep cerebral venous thrombosis, and the presence of diminished signal and enlargement of deep cerebral veins on T2*-weighted imaging contributed to a revised diagnosis of deep cerebral venous thrombosis. Anticoagulant therapy was initiated, leading to her gradual recovery, with recanalization of the deep venous system and straight sinus. To the best of our knowledge, these results represent the first report of deep cerebral venous thrombosis associated with influenza infection. It is clinically important to recognize that deep cerebral venous thrombosis, although rare, might be one of the neurological complications of influenza infection. In the presence of bilateral thalamic lesions in patients with influenza infection, deep cerebral venous thrombosis should be considered in addition to acute necrotizing encephalopathy. Delays in diagnosis and commencement of anticoagulant therapy can lead to unfavorable outcomes.

Prognostic factors for acute encephalopathy with bright tree appearance.

PubMed

Azuma, Junji; Nabatame, Shin; Nakano, Sayaka; Iwatani, Yoshiko; Kitai, Yukihiro; Tominaga, Koji; Kagitani-Shimono, Kuriko; Okinaga, Takeshi; Yamamoto, Takehisa; Nagai, Toshisaburo; Ozono, Keiichi

2015-02-01

To determine the prognostic factors for encephalopathy with bright tree appearance (BTA) in the acute phase through retrospective case evaluation. We recruited 10 children with encephalopathy who presented with BTA and classified them into 2 groups. Six patients with evident regression and severe psychomotor developmental delay after encephalopathy were included in the severe group, while the remaining 4 patients with mild mental retardation were included in the mild group. We retrospectively analyzed their clinical symptoms, laboratory data, and magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings. Patients in the severe group developed subsequent complications such as epilepsy and severe motor impairment. Univariate analysis revealed that higher maximum lactate dehydrogenase (LDH) levels (p=0.055) were a weak predictor of poor outcome. Maximum creatinine levels were significantly higher (p<0.05) and minimal platelet counts were significantly lower (p<0.05) in the severe group than in the mild group. Acute renal failure was not observed in any patient throughout the study. MRS of the BTA lesion during the BTA period showed elevated lactate levels in 5 children in the severe group and 1 child in the mild group. MRI performed during the chronic phase revealed severe brain atrophy in all patients in the severe group. Higher creatinine and LDH levels and lower platelet counts in the acute phase correlated with poor prognosis. Increased lactate levels in the BTA lesion during the BTA period on MRS may predict severe physical and mental disability. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A new infectious encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX).

PubMed

Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Yasukawa, Kumi; Takanashi, Jun-Ichi

2017-09-15

Acute infectious encephalopathy is often observed in children in East Asia including Japan. More than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanisms in those with unclassified encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among seven patients with acute encephalopathy admitted to our hospital from June 2016 to May 2017, three were classified into acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). The other four showed consciousness disturbance lasting more than three days with no parenchymal lesion visible on MRI, which led to a diagnosis of unclassified encephalopathy. MR spectroscopy in these four patients, however, revealed an increase of glutamine with a normal N-acetyl aspartate level on days 5 to 8, which had normalized by follow-up studies on days 11 to 16. The four patients clinically recovered completely. Among 27 patients with encephalopathy, including the present seven patients, admitted to our hospital from January 2015 to March 2017, seven (26%) were classified into this type, which we propose is a new encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX). MEEX is the second most common subtype, following AESD (30%). This study suggests that excitotoxicity may be a common underlying pathomechanism of acute infectious encephalopathy, and prompt astrocytic neuroprotection from excitotoxicity may prevent progression of MEEX into AESD. Copyright © 2017 Elsevier B.V. All rights reserved.

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

2016-01-05

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. Copyright © 2015. Published by Elsevier Ireland Ltd.

A case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Hazama, Kyoko; Shiihara, Takashi; Tsukagoshi, Hiroyuki; Hasegawa, Shunji; Dowa, Yuri; Watanabe, Mio

2017-10-01

Mumps is a common childhood viral disease characterized by fever and swelling of the parotid gland. The prognosis is generally good, although some complications, such as encephalitis (0.1%), exist. Acute encephalopathy with biphasic seizures and late reduced diffusion is the most common type of acute encephalopathy. However, this type of encephalopathy has not been reported in association with mumps infection. A previously healthy 3-year-old Japanese boy had a brief convulsion after fever for 3days, and then had conscious disturbance and parotitis. After several days, he had a second brief convulsion and was admitted. Increased serum amylase levels and presence of anti-mumps immunoglobulin M antibody confirmed mumps parotitis. The patient had another brief seizure later the day of admission. He did not have status or cluster seizures, although the biphasic nature of his seizures, conscious disturbance between the seizures, no pleocytosis in cerebrospinal fluid, and brain magnetic resonance images were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion. In Japan, the mumps vaccine is not administered as a part of routine immunizations. It thus has low coverage (30-40%), and as a result, mumps infections are still common. However, this is the first case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion. This case may be representative of only a minority of patients with mumps-associated central nervous system involvement. Nevertheless, this diagnostic possibility may be considered. In order to prevent mumps-related complications, routine mumps vaccination might be warranted. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Acute hyperammonemic encephalopathy after fluoropyrimidine-based chemotherapy: A case series and review of the literature.

PubMed

Mitani, Seiichiro; Kadowaki, Shigenori; Komori, Azusa; Sugiyama, Keiji; Narita, Yukiya; Taniguchi, Hiroya; Ura, Takashi; Ando, Masashi; Sato, Yozo; Yamaura, Hidekazu; Inaba, Yoshitaka; Ishihara, Makoto; Tanaka, Tsutomu; Tajika, Masahiro; Muro, Kei

2017-06-01

Acute hyperammonemic encephalopathy induced by fluoropyrimidines (FPs) is a rare complication. Its pathophysiology remains unclear, especially given the currently used regimens, including intermediate-doses of 5-fluorouracil (5-FU) or oral FP agents. We aimed to characterize the clinical manifestations in cancer patients who developed hyperammonemic encephalopathy after receiving FP-based chemotherapy.We retrospectively reviewed 1786 patients with gastrointestinal or primary-unknown cancer who received FP-based regimens between 2007 and 2012. Eleven patients (0.6%) developed acute hyperammonemic encephalopathy. The incidence according to the administered anticancer drugs were as follows: 5-FU (8 of 1176, 0.7%), S-1 (1 of 679, 0.1%), capecitabine (2 of 225, 0.9%), and tegafur-uracil (UFT) (0 of 39, 0%). Ten patients (90.9%) had at least 1 aggravating factor, including infection, dehydration, constipation, renal dysfunction, and muscle loss. All the 10 patients met the definition of sarcopenia. Median time to the onset of hyperammonemic encephalopathy in the cycle was 3 days (range: 2-21). Three patients (27.3%) developed encephalopathy during the first cycle of the regimen and the remaining 8 patients during the second or more cycles. Seven patients (63.6%) had received at least 1 other FP-containing regimen before without episodes of encephalopathy.All patients recovered soon after immediate discontinuation of chemotherapy and supportive therapies, such as hydration, infusion of branched-chain amino acids, and oral lactulose intake, with a median time to recovery of 2 days (range: <1-7). Four patients (36.4%) received FP-based regimens after improvement of symptoms; 3 patients were successfully managed with dose reduction, and 1 patient, who had developed encephalopathy due to S-1 monotherapy, received modified FOLFOX-6 therapy without encephalopathy later.FP-associated acute hyperammonemic encephalopathy is extremely rare, but a possible event at any time and even

Impact of dynamic changes of elevated bilirubin on survival in patients on veno-arterial extracorporeal life support for acute circulatory failure.

PubMed

Freundt, Miriam; Lunz, Dirk; Philipp, Alois; Panholzer, Bernd; Lubnow, Matthias; Friedrich, Christine; Rupprecht, Leopold; Hirt, Stephan; Haneya, Assad

2017-01-01

Veno-arterial extracorporeal life support (ECLS) is an established method to stabilize acute circulatory failure. Parameters and data on when to ideally wean circulatory support are limited. Bilirubin is a marker of end-organ damage. Therefore, the purpose of this large study was to evaluate the impact of dynamic changes of elevated bilirubin levels on survival in patients on ECLS. We reviewed 502 consecutive cases of ECLS from 2007 to 2015. Bilirubin levels were recorded before implantation and until six days after explantation. Dynamic bilirubin changes, and hemodynamic and laboratory outcome parameters were compared in survivors and nonsurvivors. Reason for ECLS implantation was cardiac arrest with ongoing resuscitation in 230 (45.8%), low cardiac output in 174 (34.7%) and inability to wean off cardiopulmonary bypass in 98 (19.5%) patients. 307 (61.2%) patients were weaned off ECLS, however, 206 (41.0%) survived. Mean duration of ECLS was 3 (2-6) days, and survivors received significantly longer ECLS (5 vs 3 days, p < 0.001). Survivors had significantly lower baseline bilirubin levels (p = 0.003). Bilirubin started to rise from day 2 in all patients. In survivors, bilirubin levels had trended down on the day of ECLS explantation and stayed at an acceptable level. However, in weaned patients who did not survive and patients who died on ECLS bilirubin levels continued to rise during the recorded period. ECLS support improves survival in patients with acute circulatory failure. Down trending bilirubin levels on veno-arterial ECLS indicate improved chances of successful weaning and survival in hemodynamically stable patients.

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

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.

PubMed

Cichoż-Lach, Halina; Michalak, Agata

2013-01-07

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

Modulation of bilirubin neurotoxicity by the Abcb1 transporter in the Ugt1-/- lethal mouse model of neonatal hyperbilirubinemia.

PubMed

Bockor, Luka; Bortolussi, Giulia; Vodret, Simone; Iaconcig, Alessandra; Jašprová, Jana; Zelenka, Jaroslav; Vitek, Libor; Tiribelli, Claudio; Muro, Andrés F

2017-01-01

Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma. However, their role in reducing the risk of developing neurological damage and death during neonatal development is still unknown.To this end, we mated Abcb1a/b-/- and Abcc1-/- strains with Ugt1-/- mice, which develop severe neonatal hyperbilirubinemia. While about 60% of Ugt1-/- mice survived after temporary phototherapy, all Abcb1a/b-/-/Ugt1-/- mice died before postnatal day 21, showing higher cerebellar levels of unconjugated bilirubin. Interestingly, Abcc1 role appeared to be less important.In the cerebellum of Ugt1-/- mice, hyperbilirubinemia induced the expression of Car and Pxr nuclear receptors, known regulators of genes involved in the genotoxic response.We demonstrated a critical role of Abcb1 in protecting the cerebellum from bilirubin toxicity during neonatal development, the most clinically relevant phase for human babies, providing further understanding of the mechanisms regulating bilirubin neurotoxicity in vivo. Pharmacological treatments aimed to increase Abcb1 and Abcc1 expression, could represent a therapeutic option to reduce the risk of bilirubin neurotoxicity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinically mild infantile encephalopathy associated with excitotoxicity.

PubMed

Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Honda, Takafumi; Yasukawa, Kumi; Takanashi, Jun-Ichi

2017-02-15

Acute infectious encephalopathy is very frequently observed in children in East Asia including Japan. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype in Japan; however, more than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanism in those with unclassified acute encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among 20 patients with acute encephalopathy admitted to our hospital during January 2015 to May 2016, 12 could not be classified into specific syndromes. MR spectroscopy was performed in 8 of these 12 patients with unclassified encephalopathy. MR spectroscopy showed an increase of glutamine with a normal N-acetyl aspartate level on days 3 to 8 in three of the 8 patients, which had normalized by follow-up studies. The three patients clinically recovered completely. This study suggests that excitotoxicity may be the underlying pathomechanism in some patients with unclassified mild encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

Spectral Electroencephalogram Analysis for the Evaluation of Encephalopathy Grade in Children With Acute Liver Failure.

PubMed

Press, Craig A; Morgan, Lindsey; Mills, Michele; Stack, Cynthia V; Goldstein, Joshua L; Alonso, Estella M; Wainwright, Mark S

2017-01-01

Spectral electroencephalogram analysis is a method for automated analysis of electroencephalogram patterns, which can be performed at the bedside. We sought to determine the utility of spectral electroencephalogram for grading hepatic encephalopathy in children with acute liver failure. Retrospective cohort study. Tertiary care pediatric hospital. Patients between 0 and 18 years old who presented with acute liver failure and were admitted to the PICU. None. Electroencephalograms were analyzed by spectral analysis including total power, relative δ, relative θ, relative α, relative β, θ-to-Δ ratio, and α-to-Δ ratio. Normal values and ranges were first derived using normal electroencephalograms from 70 children of 0-18 years old. Age had a significant effect on each variable measured (p < 0.03). Electroencephalograms from 33 patients with acute liver failure were available for spectral analysis. The median age was 4.3 years, 14 of 33 were male, and the majority had an indeterminate etiology of acute liver failure. Neuroimaging was performed in 26 cases and was normal in 20 cases (77%). The majority (64%) survived, and 82% had a good outcome with a score of 1-3 on the Pediatric Glasgow Outcome Scale-Extended at the time of discharge. Hepatic encephalopathy grade correlated with the qualitative visual electroencephalogram scores assigned by blinded neurophysiologists (rs = 0.493; p < 0.006). Spectral electroencephalogram characteristics varied significantly with the qualitative electroencephalogram classification (p < 0.05). Spectral electroencephalogram variables including relative Δ, relative θ, relative α, θ-to-Δ ratio, and α-to-Δ ratio all significantly varied with the qualitative electroencephalogram (p < 0.025). Moderate to severe hepatic encephalopathy was correlated with a total power of less than or equal to 50% of normal for children 0-3 years old, and with a relative θ of less than or equal to 50% normal for children more than 3 years old (p

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.

Single-Photon Emission Computed Tomography Is an Ambiguous Imaging Method on Initial Diagnosis for Acute Encephalopathy.

PubMed

Yamanaka, Gaku; Morishita, Nastumi; Oana, Shingo; Takeshita, Mika; Morichi, Shinichiro; Ishida, Yu; Kashiwagi, Yasuyo; Kawashima, Hisashi

2016-01-01

The distinction between acute encephalopathy (AE) and convulsive disorders with pyrexia may be problematic. We analyzed the clinical and laboratory features in 127 children who were admitted for suspected AE. They were categorized into (1) definite acute encephalopathy group (DAEG; n = 17, abnormal findings on electroencephalography [EEG], magnetic resonance imaging, or single-photon emission computed tomography [SPECT] with prolonged impaired consciousness), (2) probable acute encephalopathy group (PAEG; n = 21, abnormal findings without prolonged impaired consciousness), and (3) nonacute encephalopathy group (NAEG; n = 89). Cerebrospinal fluid interleukin-6 (CSF IL-6), and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase levels were significantly higher in DAEG compared with NAEG but not PAEG. No significant differences were observed between DAEG and PAEG except for serum creatinine levels. In PAEG, an area of hypoperfusion was observed on SPECT images of nine patients with normal CSF IL-6 levels. AE was suspected in two PAEG patients who exhibited high CSF IL-6 levels and abnormal EEG findings without abnormal SPECT findings. All seven patients with severe neurological sequelae were categorized to DAEG. CSF IL-6 and serum AST, ALT, and creatine kinase levels may be valid predictors of typical AE; prolonged impaired consciousness is an important sign of AE. However, SPECT may not be suitable for initial diagnosis of AE. Georg Thieme Verlag KG Stuttgart · New York.

Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis.

PubMed

Weiss, Nicolas; Rosselli, Matteo; Mouri, Sarah; Galanaud, Damien; Puybasset, Louis; Agarwal, Banwari; Thabut, Dominique; Jalan, Rajiv

2017-04-01

Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p < 0.0001). Cirrhotic patients with ACLF have decreased CSF-SG as compared to cirrhotic patients without ACLF (-0.2 %, p = 0.0030) that remained higher than in healthy controls. The presence of hepatic encephalopathy did not modify CSF-SG (-0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain damage resembling acute necrotizing encephalopathy as a specific manifestation of haemophagocytic lymphohistiocytosis - induced by hypersensitivity.

PubMed

Dai, Dongling; Wen, Feiqiu; Liu, Sixi; Zhou, Shaoming

2016-08-31

Both haemophagocytic lymphohistiocytosis and acute necrotizing encephalopathy are life-threatening condition. It presents major diagnostic difficulties, since it may have a diversity in clinical picture and with many conditions leading to the same clinical presentation. So it is key important to understand the disorders. We report a pediatric case of haemophagocytic lymphohistiocytosis with specific presentation which predominantly featured as acute necrotizing encephalopathy of childhood. We discuss the diagnosis and differential diagnosis, and speculate the etiology of haemophagocytic lymphohistiocytosis is due to hypersensitivity. Haemophagocytic lymphohistiocytosis and brain damage in this case may be induced by hypersensitivity, which have good clinical outcome if diagnosed and treated early.

Familial acute necrotizing encephalopathy without RANBP2 mutation: Poor outcome.

PubMed

Nishimura, Naoko; Higuchi, Yoshihisa; Kimura, Nobusuke; Nozaki, Fumihito; Kumada, Tomohiro; Hoshino, Ai; Saitoh, Makiko; Mizuguchi, Masashi

2016-11-01

Most childhood cases of acute necrotizing encephalopathy (ANE) involve neither family history nor recurrence. ANE occasionally occurs, however, as a familial disorder or recurs in Caucasian patients. A mutation of RAN-binding protein 2 (RANBP2) has been discovered in more than one half of familial or recurrent ANE patients. In contrast, there has been no report of this mutation in East Asia. Here, we report the first sibling cases of typical ANE in Japan, with poor outcome. DNA analysis of genes associated with ANE or other encephalopathies, including RANBP2 and carnitine palmitoyl transferase II (CPT2), indicated neither mutations nor disease-related polymorphisms. On literature review, recurrent or familial ANE without the RANBP2 mutation has a more severe outcome and greater predilection for male sex than that with the RANBP2 mutation. This suggests that there are unknown gene mutations linked to ANE. © 2016 Japan Pediatric Society.

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

Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009--associated encephalopathy in children.

PubMed

Ishida, Yu; Kawashima, Hisashi; Morichi, Shinichiro; Yamanaka, Gaku; Okumura, Akihisa; Nakagawa, Satoshi; Morishima, Tsuneo

2015-02-01

Pandemic influenza A (H1N1) 2009 has been shown to be associated more with neurological complications than the seasonal influenza virus. In this study, we focused on the clinical usefulness of magnetic resonance imaging (MRI) in the acute phase of influenza A (H1N1) 2009-associated encephalopathy. A questionnaire was distributed to pediatric and general hospitals in Japan that treat children with encephalopathy. We conducted a questionnaire-based study involving the collection of information regarding 207 patients with encephalopathy. Brain MRI was performed in 97 of these 207 patients in the age group of 9 months to 15 years (mean, 7.5 years) within 48 hours after the development of encephalopathy symptoms. Sixty-six patients (68%) showed normal imaging. Diffuse brain edema was visible in five patients and an abnormal signal in the deep gray matter in two patients which is consistent with acute necrotizing encephalopathy. Abnormal signals of the splenial lesion, subcortical white matter (bright tree appearance), and cortical area were observed in 15, 1, and 8 patients, respectively. From our findings based on the questionnaire results, we suggest that MRI is useful for determining fatal cases of pandemic influenza A (H1N1) 2009 infection when performed in the acute phase. However, MRI is not useful in predicting the development of sequelae. Georg Thieme Verlag KG Stuttgart · New York.

[Acute encephalopathy due to late-onset maple syrup urine disease in a school boy].

PubMed

Qu, Su-Qing; Yang, Li-Cai; Luan, Zuo; Du, Kan; Yang, Hui

2012-03-01

Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.

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.

Gemifloxacin-associated neurotoxicity presenting as encephalopathy.

PubMed

Barrett, Matthew J; Login, Ivan S

2009-04-01

To report a case of acute encephalopathy associated with ingestion of gemifloxacin, a fluoroquinolone. A 67-year-old woman presented to the emergency department with an acute alteration in mental status. Twenty-four hours earlier she had taken one 320-mg tablet of her husband's gemifloxacin prescription to treat symptoms of a mild upper respiratory infection. During her initial evaluation at our institution, the woman was dysphasic, unable to follow commands, and agitated, suggesting encephalopathy. A thorough diagnostic investigation did not reveal any structural, metabolic, or infectious etiology. Her mental status returned to normal within 2 days without any definitive treatment. Fluoroquinolone-associated neurotoxicity may manifest as encephalopathy, seizures, confusion, or toxic psychosis. To date, none of these adverse effects, specifically encephalopathy, has been reported with gemifloxacin. An objective causality assessment revealed that encephalopathy was probably associated with gemifloxacin use. Seizures, either convulsive or nonconvulsive, may have contributed to our patient's presentation, but she denied seizures prior to this event and did not suffer a seizure in the 18 months following her discharge. However, her second electroencephalograph revealed an underlying predisposition to seizures, which gemifloxacin may have unmasked. This report illustrates that severe central nervous system adverse effects associated with some fluoroquinolones may also occur with gemifloxacin. Gemifloxacin and other fluoroquinolones should be considered in the etiologic evaluation of patients with acute encephalopathy.

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.

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

PubMed

Watanabe, Toru; Kawashima, Hideshi

2015-11-08

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.

IL-1 or TNF receptor gene deletion delays onset of encephalopathy and attenuates brain edema in experimental acute liver failure.

PubMed

Bémeur, Chantal; Qu, Hong; Desjardins, Paul; Butterworth, Roger F

2010-01-01

Previous reports suggested that brain-derived proinflammatory cytokines are involved in the pathogenesis of hepatic encephalopathy (HE) and brain edema in acute liver failure (ALF). To further address this issue, expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were measured in the brains of mice with acute liver failure resulting from exposure to azoxymethane. In addition, time to severe encephalopathy (coma) was assessed in mice lacking genes coding for interferon-gamma, the tumor necrosis factor receptor-1 or the interleukin-1 type 1 receptor. Interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma expression were quantified using RT-PCR. Significant increases in interleukin-1beta and tumor necrosis factor-alpha mRNA were observed in the frontal cortex of azoxymethane-treated wild-type mice at coma stages of encephalopathy. Interferon-gamma, however, could not be detected in the brains of these animals. Onset of severe encephalopathy (coma) and brain edema in ALF mice were significantly delayed in interleukin-1 type 1 receptor or tumor necrosis factor receptor-1 knockout mice. Deletion of the interferon-gamma gene, on the other hand, had no significative effect on the neurological status or brain water content of acute liver failure mice. These results demonstrate that toxic liver injury resulting from exposure to azoxymethane is associated with selective induction of proinflammatory cytokines in the brain and that deletion of tumor necrosis factor receptor-1 or interlukin-1 type 1 receptor delays the onset of coma and brain edema in this model of acute liver failure. These findings further support a role for selective brain-derived cytokines in the pathogenesis of the cerebral complications in acute liver failure and suggest that anti-inflammatory strategies could be beneficial in their prevention. Copyright 2009 Elsevier Ltd. All rights reserved.

Acute encephalopathy in a 2-year-old pot-bellied pig following accidental intoxication with clonazepam.

PubMed

Setlakwe, Emilie L; Johnson, Amy L

2017-05-01

To describe a case of successful management of clonazepam toxicity causing encephalopathy in a pot-bellied pig. A 2-year-old female pot-bellied pig weighing 13.5 kg was presented for evaluation of clinical signs of acute encephalopathy. Based on the animal's history and clinical signs, a tentative diagnosis of benzodiazepine (BZP) intoxication was made. The results of a urinary drug screening test designed to detect illicit substances in human urine indicated benzodiazepine exposure. Gas chromatography and mass spectrometry analysis later confirmed clonazepam (urinary concentration 496 ng/mL) as the intoxicating substance. The pig responded favorably to treatment which included administration of flumazenil, decontamination with enteral activated charcoal, and intravenous isotonic crystalloid administration. The pig had a rapid improvement in mentation 10 minutes following IV flumazenil administration and was considered mentally appropriate following 24 hours of hospitalization. The pig was discharged from the hospital after 48 hours of care, and was reported to be doing well 6 months later. Intoxication with prescription benzodiazepines can occur in companion animals and result in clinical signs of acute encephalopathy. Urinary drug screening tests designed for human use may provide rapid results to indicate drug intoxication and guide therapeutic intervention in veterinary species. Administration of flumazenil resulted in a rapid improvement in mentation following clonazepam intoxication in a pot-bellied pig. © Veterinary Emergency and Critical Care Society 2017.

A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

PubMed

Baek, Hyun Seok; Lee, Se-Jin

2015-01-01

Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. Copyright © 2015 Elsevier Inc. All rights reserved.

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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Blood Test: Bilirubin

MedlinePlus

... Videos for Educators Search English Español Blood Test: Bilirubin KidsHealth / For Parents / Blood Test: Bilirubin What's in ... liver or kidneys) is working. What Is a Bilirubin Test? A bilirubin test measures how much bilirubin ...

Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

2015-08-01

The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF).

PubMed

Cordoba, Juan; Ventura-Cots, Meritxell; Simón-Talero, Macarena; Amorós, Àlex; Pavesi, Marco; Vilstrup, Hendrik; Angeli, Paolo; Domenicali, Marco; Ginés, Pere; Bernardi, Mauro; Arroyo, Vicente

2014-02-01

In spite of the high incidence of hepatic encephalopathy (HE) in cirrhosis, there are few observational studies. We performed an analysis to define the characteristics of HE and associated features using the database of the Canonic Study. Clinical, laboratory and survival data of 1348 consecutive cirrhotic patients admitted with an acute decompensation were compared according to the presence (n=406) or absence of HE and of acute-on-chronic liver failure (ACLF) (n=301). HE development was independently associated with previous HE episodes; survival probabilities worsen in relation to the presence and grade of HE. There were marked differences between HE associated (n=174) and not associated (n=286) to ACLF. HE not associated with ACLF occurred in older cirrhotics, inactive drinkers, without severe liver failure or systemic inflammatory reaction and in relation to diuretic use. In contrast, HE associated with ACLF occurred in younger cirrhotics, more frequently alcoholics, with severe liver failure and systemic inflammatory reaction, and in relation to bacterial infections, active alcoholism and/or dilutional hyponatremia. Prognosis was relatively preserved in the first and extremely poor in the second group. Independent risk factors of mortality in patients with HE were age, bilirubin, INR, creatinine, sodium, and HE grade. In cirrhosis, previous HE identifies a subgroup of patients that is especially vulnerable for developing new episodes of HE. The course of HE appears to be different according to the presence of ACLF. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Auditory neuropathy spectrum disorder in late preterm and term infants with severe jaundice.

PubMed

Saluja, Satish; Agarwal, Asha; Kler, Neelam; Amin, Sanjiv

2010-11-01

To evaluate if severe jaundice is associated with acute auditory neuropathy spectrum disorder in otherwise healthy late preterm and term neonates. In a prospective observational study, all neonates who were admitted with severe jaundice at which exchange transfusion may be indicated as per American Academy of Pediatrics guidelines had comprehensive auditory evaluation performed before discharge to home. Neonates with infection, perinatal asphyxia, chromosomal disorders, cranio-facial malformations, or family history of childhood hearing loss were excluded. Comprehensive auditory evaluations (tympanometry, oto-acoustic emission tests, and auditory brainstem evoked responses) were performed by an audiologist unaware of the severity of jaundice. Total serum bilirubin and serum albumin were measured at the institutional chemistry laboratory using the Diazo and Bromocresol purple method, respectively. A total of 13 neonates with total serum bilirubin concentration at which exchange transfusion is indicated as per American Academy of Pediatrics were admitted to the Neonatal Intensive Care Unit over 3 month period. Six out of 13 neonates (46%) had audiological findings of acute auditory neuropathy spectrum disorder. There was no significant difference in gestational age, birth weight, hemolysis, serum albumin concentration, peak total serum bilirubin concentrations, and peak bilirubin:albumin molar ratio between six neonates who developed acute auditory neuropathy and seven neonates who had normal audiological findings. Only two out of six infants with auditory neuropathy spectrum disorder had clinical signs and symptoms of acute bilirubin encephalopathy. Our findings strongly suggest that auditory neuropathy spectrum disorder is a common manifestation of acute bilirubin-induced neurotoxicity in late preterm and term infants with severe jaundice. Our findings also suggest that comprehensive auditory evaluations should be routinely performed in neonates with severe

Piezoelectric detection of bilirubin based on bilirubin-imprinted titania film electrode.

PubMed

Yang, Zhengpeng; Yan, Jinlong; Zhang, Chunjing

2012-02-01

A novel quartz crystal microbalance (QCM) sensor with a high selectivity and sensitivity has been developed for bilirubin determination, based on the modification of bilirubin-imprinted titania film onto a quartz crystal by molecular imprinting and surface sol-gel techniques. The performance of the developed bilirubin biosensor was evaluated and the results indicated that a sensitive bilirubin biosensor could be fabricated. The obtained bilirubin biosensor presents high-selectivity monitoring of bilirubin, better reproducibility, shorter response time (30 min), wider linear range (0.1-50 μM), and lower detection limit (0.05 μM). The analytical application of the bilirubin biosensor confirms the feasibility of bilirubin determination in serum sample. Copyright © 2011 Elsevier Inc. All rights reserved.

Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.

PubMed

Heemann, Uwe; Treichel, Ulrich; Loock, Jan; Philipp, Thomas; Gerken, Guido; Malago, Massimo; Klammt, Sebastian; Loehr, Matthias; Liebe, Stephan; Mitzner, Steffen; Schmidt, Reinhardt; Stange, Jan

2002-10-01

Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.

Newborn Jaundice Technologies: Unbound Bilirubin and Bilirubin Binding Capacity In Neonates

PubMed Central

Amin, Sanjiv B.; Lamola, Angelo A.

2011-01-01

Neonatal jaundice (hyperbilirubinemia), extremely common in neonates, can be associated with neurotoxicity. A safe level of bilirubin has not been defined in either premature or term infants. Emerging evidence suggest that the level of unbound (or “free”) bilirubin has a better sensitivity and specificity than total serum bilirubin for bilirubin-induced neurotoxicity. Although recent studies suggest the usefulness of free bilirubin measurements in managing high-risk neonates including premature infants, there currently exists no widely available method to assay the serum free bilirubin concentration. To keep pace with the growing demand, in addition to reevaluation of old methods, several promising new methods are being developed for sensitive, accurate, and rapid measurement of free bilirubin and bilirubin binding capacity. These innovative methods need to be validated before adopting for clinical use. We provide an overview of some promising methods for free bilirubin and binding capacity measurements with the goal to enhance research in this area of active interest and apparent need. PMID:21641486

Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

PubMed

Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

2015-07-01

Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with hemophagocytic syndrome.

PubMed

Tadokoro, Rieko; Okumura, Akihisa; Nakazawa, Tomoyuki; Hara, Satoshi; Yamakawa, Yoko; Kamata, Ayako; Kinoshita, Keiji; Obinata, Kaoru; Shimizu, Toshiaki

2010-06-01

We reported a girl with HHV-6 infection associated with both acute encephalopathy with biphasic seizures and late reduced diffusion, and hemophagocytic syndrome. She had a prolonged convulsion after a one-day history of febrile illness. Cerebrospinal fluid or brain CT showed no abnormalities on admission and her consciousness was recovered on the next day. However, a prolonged seizure and deterioration of consciousness appeared on the sixth day of illness. Diffusion-weighted images revealed marked reduction of water diffusion in the bilateral frontal areas. HHV-6 infection was virologically proven by polymerase chain reaction. She was treated with gamma-globulin, steroid pulse therapy, and brain hypothermia. In addition, decrease in white blood cells and platelet counts, and elevation of liver enzymes and ferritin were noted on the fourth day of illness. Hemophagocytic macrophages were revealed by bone marrow aspiration on the sixth day. Her hematological and blood chemistry abnormalities recovered gradually after steroid pulse therapy. An elevation of interleukin-6, -8, and -10, and tumor necrosis factor in the serum and that of interleukin-4, -6, and-8 in the cerebrospinal fluid were observed at the onset of a late seizure. These facts suggested that hypercytokinemia will be related to the pathogenesis of acute encephalopathy of our patient. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Recent advances in hepatic encephalopathy

PubMed Central

DeMorrow, Sharon

2017-01-01

Hepatic encephalopathy describes the array of neurological alterations that occur during acute liver failure or chronic liver injury. While key players in the pathogenesis of hepatic encephalopathy, such as increases in brain ammonia, alterations in neurosteroid levels, and neuroinflammation, have been identified, there is still a paucity in our knowledge of the precise pathogenic mechanism. This review gives a brief overview of our understanding of the pathogenesis of hepatic encephalopathy and then summarizes the significant recent advances made in clinical and basic research contributing to our understanding, diagnosis, and possible treatment of hepatic encephalopathy. A literature search using the PubMed database was conducted in May 2017 using “hepatic encephalopathy” as a keyword, and selected manuscripts were limited to those research articles published since May 2014. While the authors acknowledge that many significant advances have been made in the understanding of hepatic encephalopathy prior to May 2014, we have limited the scope of this review to the previous three years only. PMID:29026534

Predictors for delayed encephalopathy following acute carbon monoxide poisoning

PubMed Central

2014-01-01

Background In Japan, many carbon monoxide (CO) poisoning cases are transported to emergency settings, making treatment and prognostic assessment an urgent task. However, there is currently no reliable means to predict whether “delayed neuropsychiatric sequelae (DNS)” will develop after acute CO poisoning. This study is intended to find out risk factors for the development of DNS and to characterize the clinical course following the development of DNS in acute CO poisoning cases. Methods This is a retrospective cohort study of 79 consecutive patients treated at a single institution for CO poisoning. This study included 79 cases of acute CO poisoning admitted to our emergency department after attempted suicide, who were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not. The two groups were compared and analyzed in terms of clinical symptoms, laboratory findings, etc. Results Predictors for the development of DNS following acute CO poisoning included: serious consciousness disturbance at emergency admission; head CT findings indicating hypoxic encephalopathy; hematology findings including high creatine kinase, creatine kinase-MB and lactate dehydrogenase levels; and low Global Assessment Scale scores. The clinical course of the DNS-developing cases was characterized by prolonged hospital stay and a larger number of hyperbaric oxygen (HBO) therapy sessions. Conclusion In patients with the characteristics identified in this study, administration of HBO therapy should be proactively considered after informing their family, at initial stage, of the risk of developing DNS, and at least 5 weeks’ follow-up to watch for the development of DNS is considered necessary. PMID:24484081

Predictors for delayed encephalopathy following acute carbon monoxide poisoning.

PubMed

Kudo, Kaoru; Otsuka, Kotaro; Yagi, Junko; Sanjo, Katsumi; Koizumi, Noritaka; Koeda, Atsuhiko; Umetsu, Miki Yokota; Yoshioka, Yasuhito; Mizugai, Ayumi; Mita, Toshinari; Shiga, Yu; Koizumi, Fumito; Nakamura, Hikaru; Sakai, Akio

2014-01-31

In Japan, many carbon monoxide (CO) poisoning cases are transported to emergency settings, making treatment and prognostic assessment an urgent task. However, there is currently no reliable means to predict whether "delayed neuropsychiatric sequelae (DNS)" will develop after acute CO poisoning. This study is intended to find out risk factors for the development of DNS and to characterize the clinical course following the development of DNS in acute CO poisoning cases. This is a retrospective cohort study of 79 consecutive patients treated at a single institution for CO poisoning. This study included 79 cases of acute CO poisoning admitted to our emergency department after attempted suicide, who were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not. The two groups were compared and analyzed in terms of clinical symptoms, laboratory findings, etc. Predictors for the development of DNS following acute CO poisoning included: serious consciousness disturbance at emergency admission; head CT findings indicating hypoxic encephalopathy; hematology findings including high creatine kinase, creatine kinase-MB and lactate dehydrogenase levels; and low Global Assessment Scale scores. The clinical course of the DNS-developing cases was characterized by prolonged hospital stay and a larger number of hyperbaric oxygen (HBO) therapy sessions. In patients with the characteristics identified in this study, administration of HBO therapy should be proactively considered after informing their family, at initial stage, of the risk of developing DNS, and at least 5 weeks' follow-up to watch for the development of DNS is considered necessary.

Relationship between transcutaneous bilirubin and circulating unbound bilirubin in jaundiced neonates.

PubMed

Letamendia-Richard, Emmanuelle; Ammar, Rafik Ben; Tridente, Ascanio; De Luca, Daniele

2016-12-01

Transcutaneous bilirubin (TcB) consists of the skin-deposited bilirubin. Free bilirubin represents the protein-unbound bilirubin (UB) that is able to pass into the tissues. We aimed to describe the relationship UB-TcB and study the passage of UB into the skin. We prospectively enrolled 194 neonates and we measured TcB, UB, serum bilirubin and albumin. Multiple sites TcB measurement was performed, bilirubin-albumin equilibrium constant and plasma bilirubin avidity (PBA) were calculated. TcB has a similar correlation with UB and TSB. There is a quadratic relationship between UB and TcB (R 2 =0.48; p<0.001), remaining significant (β for UB 2 =-0.8; p<0.001. β for UB=1.1; p<0.001) after adjustment for gestational age, birth weight, postnatal age and albumin (Adj-R 2 =0.72). UB contributes to the skin bilirubin deposition, as there are significant correlations between albumin and TcB (r=-0.202; p=0.01) and between PBA and ΔTcB (r=0.323; p=0.017). TcB assay does not seem to directly replace UB measurement. However, TcB and UB are linked by a quadratic relationship: UB contributes to the skin bilirubin deposition but it is not the only bilirubin species measured by transcutaneous bilirubinometry. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

PubMed

Krige, Jake E J; Kotze, Urda K; Distiller, Greg; Shaw, John M; Bornman, Philippus C

2009-10-01

Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.

PubMed

Tzoulis, Charalampos; Neckelmann, Gesche; Mørk, Sverre J; Engelsen, Bernt E; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A

2010-05-01

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging. We compared radiological, electrophysiological and pathological findings where available to study potential mechanisms underlying the episodes of exacerbation and acute cerebral lesions. We studied a total of 112 magnetic resonance tomographies and 11 computed tomographies in 32 patients with polymerase gamma-encephalopathy, including multiple serial examinations performed during both the chronic and acute phases of the disease and, in several cases, magnetic resonance spectroscopy and serial diffusion weighted studies. Data from imaging, electroencephalography and post-mortem examination were compared in order to study the underlying disease process. Our findings show that magnetic resonance imaging in polymerase gamma-related encephalopathies has high sensitivity and can identify patterns that are specific for individual syndromes. One form of chronic polymerase gamma-encephalopathy, that is associated with the c.1399G > A and c.2243G > C mutations, is characterized by progressive cerebral and cerebellar atrophy and focal lesions of the thalamus, deep cerebellar structures and medulla oblongata. Acute encephalopathies, both infantile and later onset, show similar pictures with cortical stroke-like lesions occurring during episodes of exacerbation. These lesions can occur both

Influenza-associated Encephalitis/Encephalopathy Identified by the Australian Childhood Encephalitis Study 2013-2015.

PubMed

Britton, Philip N; Dale, Russell C; Blyth, Christopher C; Macartney, Kristine; Crawford, Nigel W; Marshall, Helen; Clark, Julia E; Elliott, Elizabeth J; Webster, Richard I; Cheng, Allen C; Booy, Robert; Jones, Cheryl A

2017-11-01

Influenza-associated encephalitis/encephalopathy (IAE) is an important cause of acute encephalitis syndrome in children. IAE includes a series of clinicoradiologic syndromes or acute encephalopathy syndromes that have been infrequently reported outside East Asia. We aimed to describe cases of IAE identified by the Australian Childhood Encephalitis study. Children ≤ 14 years of age with suspected encephalitis were prospectively identified in 5 hospitals in Australia. Demographic, clinical, laboratory, imaging, and outcome at discharge data were reviewed by an expert panel and cases were categorized by using predetermined case definitions. We extracted cases associated with laboratory identification of influenza virus for this analysis; among these cases, specific IAE syndromes were identified where clinical and radiologic features were consistent with descriptions in the published literature. We identified 13 cases of IAE during 3 southern hemisphere influenza seasons at 5 tertiary children's hospitals in Australia; 8 children with specific acute encephalopathy syndromes including: acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late diffusion restriction, mild encephalopathy with reversible splenial lesion, and hemiconvulsion-hemiplegia syndrome. Use of influenza-specific antiviral therapy and prior influenza vaccination were infrequent. In contrast, death or significant neurologic morbidity occurred in 7 of the 13 children (54%). The conditions comprising IAE are heterogeneous with varied clinical features, magnetic resonance imaging changes, and outcomes. Overall, outcome of IAE is poor emphasizing the need for optimized prevention, early recognition, and empiric management.

Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict Overall Survival in High-Risk Patients Undergoing Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma.

PubMed

Hansmann, Jan; Evers, Maximilian J; Bui, James T; Lokken, R Peter; Lipnik, Andrew J; Gaba, Ron C; Ray, Charles E

2017-09-01

To evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades in predicting overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma (HCC). This single-center retrospective study included 180 high-risk patients (142 men, 59 y ± 9) between April 2007 and January 2015. Patients were considered high-risk based on laboratory abnormalities before the procedure (bilirubin > 2.0 mg/dL, albumin < 3.5 mg/dL, platelet count < 60,000/mL, creatinine > 1.2 mg/dL); presence of ascites, encephalopathy, portal vein thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End-Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values were used to determine ALBI and PALBI grades. Overall survival was stratified by ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index was used to determine discriminatory ability and survival prediction accuracy. Median survival for 79 ALBI grade 2 patients and 101 ALBI grade 3 patients was 20.3 and 10.7 months, respectively (P < .0001). Median survival for 30 PALBI grade 2 and 144 PALBI grade 3 patients was 20.3 and 12.9 months, respectively (P = .0667). Substratification yielded distinct ALBI grade survival curves for CPC B (P = .0022, C-index 0.892), BCLC A (P = .0308, C-index 0.887), and BCLC C (P = .0287, C-index 0.839). PALBI grade demonstrated distinct survival curves for BCLC A (P = 0.0229, C-index 0.869). CPC yielded distinct survival curves for the entire cohort (P = .0019) but not when substratified by BCLC stage (all P > .05). ALBI and PALBI grades are accurate survival metrics in high-risk patients undergoing conventional transarterial chemoembolization for HCC. Use of these scores allows for more refined survival stratification within CPC and BCLC stage. Copyright © 2017 SIR. Published by Elsevier Inc. All

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

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

PubMed

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

2015-05-07

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.

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

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

PubMed

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

Comparison of Transcutaneous Bilirubin Measurement With Total Serum Bilirubin Levels in Preterm Neonates Receiving Phototherapy.

PubMed

Pendse, Amruta; Jasani, Bonny; Nanavati, Ruchi; Kabra, Nandkishor

2017-08-15

To compare transcutaneous bilirubin with total serum bilirubin in preterm neonates after initiation of phototherapy. Jaundice was assessed in 30 preterm neonates with transcutaneous bilirubin and total serum bilirubin before initiation of phototherapy and at 12 hr after initiation of phototherapy. A photo-occlusive patch was applied over the sternum. Transcutaneous bilirubin has a good correlation with total serum bilirubin after initiation of phototherapy. (r=0.918, P<0.001). Transcutaneous bilirubin at 28-32 weeks of gestation (r = 0.97) was better correlated with total serum bilirubin than those at 32-37 weeks (r =0.88). The correlation was better for neonates <72 hours old (r = 0.96) than those >72 hours of age (r = 0.82). Transcutaneous bilirubin correlates significantly with total serum bilirubin at the patched sternal site after initiation of phototherapy in preterm neonates.

Bilirubin and atherosclerotic diseases.

PubMed

Vítek, L

2017-04-05

Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincingly suggest that mildly elevated bilirubin concentrations are associated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with these results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of coronary heart as well as peripheral vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonstrated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations.

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

[Sub-acute encephalopathy that responds to steroids without any evidence of autoimmune thyroid disease: a case of non-vasculitic autoimmune meningoencephalitis].

PubMed

López-Ariztegui, N; Lobato-Casado, P; Muñoz-Escudero, F; Polo-Martín, M; Montes-Gonzalo, M C; Alvarez-Tejerina, A

To report a case of sub-acute encephalopathy with all the extension study negative and with response to steroid therapy. The study involves a 22-year-old female with no relevant past history who presented symptoms of sub-acute encephalopathy consisting in behavioural disorders, generalised seizures and bradypsychia, which gradually progressed to a state of low-level consciousness. While she was in hospital all kinds of diagnostic tests were conducted, the results of which were either normal or negative; the electroencephalogram was repeatedly abnormal and detection of protein 14-3-3 in cerebrospinal fluid was positive. Empirical corticoid therapy was begun with clinical and electrophysiological improvements and the patient recovered completely without any sequelae. With no evidence of autoimmune thyroid disease, although non-specific autoimmunity was present, the patient was diagnosed as having non-vasculitic autoimmune meningoencephalitis.

Acute encephalopathy due to angel's trumpet intoxication: A case report and literature review.

PubMed

Takeshima, Shinichi; Neshige, Shuichiro; Hara, Naoyuki; Kubo, Tomoshi; Himeno, Takahiro; Kuriyama, Masaru

2017-05-27

We report two cases (a married couple) of intoxication due to angel's trumpet ingestion. Case 1: A 71-year-old woman was found lying unconscious on the sofa at home and was brought to our hospital by ambulance. She showed mydriatic anisocoria, and an intracerebral lesion was suspected. However, the brain magnetic resonance imaging showed no abnormal lesion and acute encephalopathy of unknown cause was diagnosed. Case 2: A 68-year-old man (husband of the patient of Case 1) showed alteration of consciousness with agitation and was admitted to our hospital on the next day. He also had slight mydriasis. As his manifestations were similar to those of his wife, we studied their medical history again. We found that they mistook the roots of angel's trumpet for burdock and cooked and ate them. This intoxication causes characteristic encephalopathy with altered consciousness and mydriasis. In the case of anisocoria or mild mydriasis, the diagnosis is difficult sometimes. The intoxication occurred within a family; this was a clue to the correct diagnosis. Severe cases exhibit pyramidal signs and symptoms or convulsion, and deaths have been reported. Angel's trumpet intoxication is an important neurological emergency.

D-lactic acidosis mediated neuronal encephalopathy in acute lymphoblastic leukemia patient: an under diagnosis.

PubMed

Mendu, Damodara Rao; Fleisher, Martin; McCash, Samuel I; Pessin, Melissa S; Ramanathan, Lakshmi V

2015-02-20

D-lactic acidosis, also referred as D-lactate encephalopathy, has been reported in patients with short bowl syndrome (SBS). The neurologic symptoms include altered mental status, slurred speech, and ataxia. Onset of neurological symptoms is accompanied by metabolic acidosis and high anion gap. We present here a case of D-lactic acidosis in a patient with acute lymphoblastic leukemia (ALL) who developed severe neurological symptoms and metabolic acidosis due to vancomycin-resistant enterococci (VRE) infection, and elevated D-lactic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

Measurement of plasma unbound unconjugated bilirubin.

PubMed

Ahlfors, C E

2000-03-15

A method is described for measuring the unconjugated fraction of the unbound bilirubin concentration in plasma by combining the peroxidase method for determining unbound bilirubin with a diazo method for measuring conjugated and unconjugated bilirubin. The accuracy of the unbound bilirubin determination is improved by decreasing sample dilution, eliminating interference by conjugated bilirubin, monitoring changes in bilirubin concentration using diazo derivatives, and correcting for rate-limiting dissociation of bilirubin from albumin. The unbound unconjugated bilirubin concentration by the combined method in plasma from 20 jaundiced newborns was significantly greater than and poorly correlated with the unbound bilirubin determined by the existing peroxidase method (r = 0.7), possibly due to differences in sample dilution between the methods. The unbound unconjugated bilirubin was an unpredictable fraction of the unbound bilirubin in plasma samples from patients with similar total bilirubin concentrations but varying levels of conjugated bilirubin. A bilirubin-binding competitor was readily detected at a sample dilution typically used for the combined test but not at the dilution used for the existing peroxidase method. The combined method is ideally suited to measuring unbound unconjugated bilirubin in jaundiced human newborns or animal models of kernicterus. Copyright 2000 Academic Press.

Unconjugated Bilirubin Inhibits Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Protease

PubMed Central

Lu, Rui-Nan; Yang, Shangbin; Wu, Haifeng M.; Zheng, X. Long

2015-01-01

Summary Background Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood. Objectives The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13. Methods Fluorogenic, SELDI-TOF mass spectrometric assay, and Western blotting analyses were employed to address this question. Results Unconjugated bilirubin inhibits the cleavage of F485-rVWF73-H, D633-rVWF73-H, and GST-rVWF71-11K by ADAMTS13 in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of ~13 μM, ~70 μM, and ~17 μM, respectively. Unconjugated bilirubin also dose-dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633-rVWF73-H and multimeric VWF, but not F485-rVWF73-H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia is lower prior to than after treatment with bilirubin oxidase. Conclusions unconjugated bilirubin directly inhibits ADAMTS13’s ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has an adverse effect in vivo remains to be determined in our future study. PMID:25782102

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

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. 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. 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. Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.

The Evolving Landscape of Neurotoxicity by Unconjugated Bilirubin: Role of Glial Cells and Inflammation

PubMed Central

Brites, Dora

2012-01-01

Unconjugated hyperbilirubinemia is a common condition in the first week of postnatal life. Although generally harmless, some neonates may develop very high levels of unconjugated bilirubin (UCB), which may surpass the protective mechanisms of the brain in preventing UCB accumulation. In this case, both short-term and long-term neurodevelopmental disabilities, such as acute and chronic UCB encephalopathy, known as kernicterus, or more subtle alterations defined as bilirubin-induced neurological dysfunction (BIND) may be produced. There is a tremendous variability in babies’ vulnerability toward UCB for reasons not yet explained, but preterm birth, sepsis, hypoxia, and hemolytic disease are comprised as risk factors. Therefore, UCB levels and neurological abnormalities are not strictly correlated. Even nowadays, the mechanisms of UCB neurotoxicity are still unclear, as are specific biomarkers, and little is known about lasting sequelae attributable to hyperbilirubinemia. On autopsy, UCB was shown to be within neurons, neuronal processes, and microglia, and to produce loss of neurons, demyelination, and gliosis. In isolated cell cultures, UCB was shown to impair neuronal arborization and to induce the release of pro-inflammatory cytokines from microglia and astrocytes. However, cell dependent sensitivity to UCB toxicity and the role of each nerve cell type remains not fully understood. This review provides a comprehensive insight into cell susceptibilities and molecular targets of UCB in neurons, astrocytes, and oligodendrocytes, and on phenotypic and functional responses of microglia to UCB. Interplay among glia elements and cross-talk with neurons, with a special emphasis in the UCB-induced immunostimulation, and the role of sepsis in BIND pathogenesis are highlighted. New and interesting data on the anti-inflammatory and antioxidant activities of different pharmacological agents are also presented, as novel and promising additional therapeutic approaches to BIND

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

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

PubMed Central

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

2015-01-01

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

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. Copyright © 2015 the American Physiological Society.

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

Human T-cell lymphotropic virus (HTLV)-associated encephalopathy: an under-recognised cause of acute encephalitis? Case series and literature review.

PubMed

Crawshaw, Ania A; Dhasmana, Divya; Jones, Brynmor; Gabriel, Carolyn M; Sturman, Steve; Davies, Nicholas W S; Taylor, Graham P

2018-04-01

Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) is well described. Clinical features are predominantly consistent with cord pathology, though imaging and autopsy studies also demonstrate brain inflammation. In general, this is subclinical; however, six cases have previously been reported of encephalopathy in HTLV-1-infected patients, without alternative identified aetiology. We describe three further cases of encephalitis in the UK HAM cohort (n = 142), whereas the annual incidence of acute encephalitis in the general population is 0.07-12.6 per 100,000. Clinical features included reduced consciousness, fever/hypothermia, headaches, seizures, and focal neurology. Investigation showed: raised CSF protein; pleocytosis; raised CSF:peripheral blood mononuclear cell HTLV-1 proviral load ratio; and MRI either normal or showing white matter changes in brain and cord. Four of the six previous case reports of encephalopathy in HTLV-infected patients also had HAM. Histopathology, reported in three, showed perivascular predominantly CD8+ lymphocytic infiltrates in the brain. One had cerebral demyelination, and all had cord demyelination. We have reviewed the existing six cases in the literature, together with our three new cases. In all seven with HAM, the spastic paraparesis deteriorated sub-acutely preceding encephalitis. Eight of the nine were female, and four of the seven treated with steroids improved. We propose that HTLV-associated encephalopathy may be part of the spectrum of HTLV-1-induced central nervous system disease.

Clinical characteristics of hypertensive encephalopathy in pediatric patients

PubMed Central

Ahn, Chang Hoon; Han, Seung-A; Kong, Young Hwa

2017-01-01

Purpose The aim of this study was to assess the clinical characteristics of hypertensive encephalopathy according to the underlying etiologies in children. Methods We retrospectively evaluated 33 pediatric patients who were diagnosed as having hypertensive encephalopathy in Chonbuk National University Children's Hospital. Among the patients, 18 were excluded because of incomplete data or because brain magnetic resonance imaging (MRI) was not performed. Finally, 17 patients were enrolled and divided into a renal-origin hypertension group and a non-renal-origin hypertension group according to the underlying cause. We compared the clinical features and brain MRI findings between the 2 groups. Results The renal group included renal artery stenosis (4), acute poststreptococcal glomerulonephritis (2), lupus nephritis (2), and acute renal failure (1); the nonrenal group included essential hypertension (4), pheochromocytoma (2), thyrotoxicosis (1), and acute promyelocytic leukemia (1). The mean systolic blood pressure of the renal group (172.5±36.9 mmHg) was higher than that of the nonrenal group (137.1±11.1 mmHg, P<0.05). Seizure was the most common neurologic symptom, especially in the renal group (P<0.05). Posterior reversible encephalopathy syndrome (PRES), which is the most typical finding of hypertensive encephalopathy, was found predominantly in the renal group as compared with the nonrenal group (66.6% vs. 12.5%, P<0.05). Conclusion We conclude that the patients with renal-origin hypertension had a more severe clinical course than those with non-renal-origin hypertension. Furthermore, the renal-origin group was highly associated with PRES on brain MRI. PMID:29042869

[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

Bilirubin present in diverse angiosperms.

PubMed

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

2010-01-01

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. 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. Bilirubin was present in eight species from the orders Zingiberales, Arecales and Myrtales, but only contributed to colour in species within the Strelitziaceae. 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.

Bilirubin metabolism in the fetus

PubMed Central

Bernstein, Ralph B.; Novy, Miles J.; Piasecki, George J.; Lester, Roger; Jackson, Benjamin T.

1969-01-01

Bilirubin metabolism was studied in dog and monkey fetuses. Bilirubin-3H was administered to fetal animals in utero by prolonged intravenous infusion. Fetal plasma disappearance, hepatic uptake, biliary excretion, and placental transfer of bilirubin-3H were measured. Bilirubin metabolism and excretion in the fetus was much less efficient than in the adult. Fetal plasma levels of tritium were elevated for prolonged periods, and the combined rate of placental and fetal hepatic excretion was lower than normal values for adult hepatic excretion. Species differences were noted. Hepatic conjugation and excretion appeared to be the primary mechanism of fetal metabolism in the dog. In contrast, the amounts of conjugated bilirubin-3H excreted in fetal monkey bile were negligible. Small amounts of 3H-labeled bilirubin derivatives were excreted in fetal bile, but 10 times as much of the administered material was transferred intact across the placenta and excreted by the maternal liver. The relationship of this functional difference to known anatomic and biochemical species differences is discussed. Preliminary observations on alternate routes of fetal bilirubin metabolism were obtained. Images PMID:4980771

Bilirubin photoisomers in rhesus monkey serum.

PubMed

Okada, Hitoshi; Itoh, Susumu; Nii, Kohichiroh; Sugino, Masashiro; Fuke, Noriko; Koyano, Kosuke; Yasuda, Saneyuki; Kusaka, Takashi

2018-05-23

As rhesus monkeys exhibit physiological jaundice during the neonatal period, we used rhesus monkey serum to examine changes in bilirubin photoisomers. Bilirubin-rhesus monkey serum solution was irradiated with blue light-emitting diode, and changes in the absorbance and bilirubin fraction were compared with those in bilirubin- human serum albumin (HSA) and bilirubin-rat albumin solutions. The λ max decreased with light irradiation. The mean production rate of cyclobilirubin IXα was 1.98, 199 and 0.76 × 10 -2 /min in rhesus monkey serum, HSA and rat albumin, respectively. There was no significant difference between rhesus monkey serum and HSA. The (ZE)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.33, 0.45, and 0.10, respectively, differing significantly among the groups. The (EZ)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.020, 0.010, and 0.062, respectively, with no significant difference between rhesus monkey serum and HSA. The production rate of (EZ)-cyclobilirubin XIIIα(= (ZE)-cyclobilirubin XIIIα) was 0.73, 1.60, and 0.51 × 10 -2 /min, respectively, with differing significantly among the groups. The (EZ)-bilirubin IIIα/(ZZ)-bilirubin IIIα ratio was significantly different among the groups at 0.20, 0.38, and 0.15, respectively. This is the first report demonstrating the photoisomerization of bilirubin in rhesus monkey serum and the animal with the same cyclobilirubin production rate as HSA.Rhesus monkeys may be used as an animal model for neonatal hyperbilirubinemia in humans to evaluate the efficacy of phototherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Management of Hepatic Encephalopathy

PubMed Central

Wright, G.; Chattree, A.; Jalan, R.

2011-01-01

Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease. PMID:21994873

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

Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and possible significance

PubMed Central

2014-01-01

Background Small changes of bilirubin and liver enzymes are often detected during the acute phase of stroke, but their origin and significance are still poorly understood. Methods On days 0, 3, 7, and 14 after admission, 180 patients with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT, γGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count. On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day 3 cerebral infarct volume (IV) was calculated from CT scan slices. Results During the first week GOT, GPT, γGT (P < 0.001) and CRP (P = 0.03) increased with subsequent plateau, while significant decrements (P < 0.001) concerned unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase, direct bilirubin and common bile duct diameter remained stable. IV correlated with CRP, leukocytes, GOT, γGT (r > 0.3, P < 0.001 for all) and direct bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT remained independently associated with IV (P < =0.001). The correlation of IV with GOT increased progressively from admission to day 14. GOT independently correlated with GPT which, in turn, correlated with γGT. γGT was also highly correlated with leukocytes. Unconjugated bilirubin correlated with haemoglobin, which was inversely correlated with CRP. Conclusions The changes of bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which are both related to IV: 1) inflammation, with consequent increment of CRP, leukocytes and γGT, and decrease of haemoglobin and unconjugated bilirubin and 2) an unknown signal, independent from inflammation, leading to increasing GOT and GPT levels. PMID:24903748

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.

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.

Hemolytic-uremic syndrome with acute encephalopathy in a pregnant woman infected with epidemic enterohemorrhagic Escherichia coli: characteristic brain images and cytokine profiles.

PubMed

Ito, M; Shiozaki, A; Shimizu, M; Saito, S

2015-05-01

A food-poisoning outbreak due to enterohemorrhagic Escherichia coli (EHEC) occurred in Toyama, Japan. The case of a 26-year-old pregnant woman with hemolytic-uremic syndrome who developed acute encephalopathy due to EHEC infection after eating raw meat is presented herein. On day 2 following admission, a cesarean section was performed because of a non-reassuring fetal status. Fecal bacterial culture confirmed an O111/O157 superinfection. Intensive care therapies including continuous hemodiafiltration and plasma exchange were performed. After the operation, the patient developed encephalopathy for which steroid pulse therapy was added. Her condition improved gradually and she was discharged 55 days after delivery. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

PubMed

Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

2014-07-01

Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

Bilirubin Binding Capacity in the Preterm Neonate

PubMed Central

Amin, Sanjiv B

2016-01-01

SYNOPSIS 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

Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

PubMed

Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

2015-02-01

Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Two cases of traumatic head injury mimicking acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Nishiyama, Masahiro; Fujita, Kyoko; Maruyama, Azusa; Nagase, Hiroaki

2014-11-01

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) presents a distinct clinical course of biphasic seizures and impaired consciousness. These symptoms are followed by reduced diffusion in the subcortical white matter on magnetic resonance imaging that is typically observed between 3 and 9 days after illness onset. Here, we report two cases of traumatic head injury with clinical and radiological features similar to those for AESD. The similarities between our cases and AESD may be useful in understanding the pathogenesis of AESD. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Photoacoustic microscopy of bilirubin in tissue phantoms

PubMed Central

Zhou, Yong; Zhang, Chi; Yao, Da-Kang

2012-01-01

Abstract. 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. PMID:23235894

Quantitative imaging of bilirubin by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

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

2013-03-01

Noninvasive detection of both bilirubin concentration and its distribution is important for disease diagnosis. Here we implemented photoacoustic microscopy (PAM) to detect bilirubin distribution. We first demonstrate that our PAM system can measure the absorption spectra of bilirubin and blood. We also image bilirubin distributions in tissuemimicking samples, both without and with blood mixed. Our results show that PAM has the potential to quantitatively image bilirubin in vivo for clinical applications.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

PubMed

Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

2017-08-01

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27-5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

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

Encephalopathy Associated with Influenza B in a Healthy Young Man.

PubMed

Shimamoto, Masaki; Okada, Satoshi; Terashima, Takeshi

2017-01-01

A 19-year-old man presented with a fever, convulsions, and loss of consciousness at our hospital. The patient had a Glasgow Coma Scale score of 12. Influenza B virus infection was diagnosed using the rapid test kit, and an eight-fold increase in the serum levels of anti-influenza B virus antibody was confirmed using the complement fixation test. Brain magnetic resonance imaging showed multifocal high-signal lesions, and an electroencephalogram showed diffuse slowing of the background activity, indicating acute encephalopathy. After treatment with peramivir and methylprednisolone for 3 days, the patient was discharged without any neurological impairment. This was a case of influenza B infection associated with acute encephalopathy in a healthy young man.

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

A case of recurrent encephalopathy with SCN2A missense mutation.

PubMed

Fukasawa, Tatsuya; Kubota, Tetsuo; Negoro, Tamiko; Saitoh, Makiko; Mizuguchi, Masashi; Ihara, Yukiko; Ishii, Atsushi; Hirose, Shinichi

2015-06-01

Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na(+) channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

Serum Procalcitonin in Patients with Acute Liver Failure

PubMed Central

Sugihara, Takaaki; Koda, Masahiko; Okamoto, Toshiaki; Miyoshi, Kenichi; Matono, Tomomitsu; Oyama, Kenji; Hosho, Keiko; Okano, Jun-ichi; Isomoto, Hajime

2017-01-01

Background Procalcitonin (PCT) is a known diagnostic marker of bacterial infection. There are no previous reports of PCT concerning acute liver failure (ALF). We evaluated the clinical value of serum PCT levels in patients with ALF. Methods Forty-four patients with acute hepatitis (19 men and 25 women; median age, 40 years; range, 20–79 years) were retrospectively enrolled from January 2001 and June 2015. PCT levels were measured by saved serum samples obtained within 3 days after admission. ALF was defined as prothrombin time (PT) < 40% regardless of hepatic encephalopathy. Results Serum PCT levels were significantly higher in the patients with ALF (n = 16) than in those with non-ALF (n = 28) [0.25 (0.13–2.66) ng/mL vs. 0.165 (0.03–1.08), P = 0.00967]. Creatinine, total bilirubin, and direct bilirubin were positively correlated, and PT was negatively correlated with PCT. Receiver operating characteristic curve analysis showed an area under the curve of 0.74 for detecting ALF. With a PCT cut-off value of 0.5 ng/mL, the presence of ALF could be demonstrated with low sensitivity (37.5%) and high specificity (96.5%) with high positive (85.7%) and negative (72.9%) predictive value. Multivariate analysis showed that PCT was an independent factor associated with the presence of ALF. The cumulative survival rate was also significantly lower in patients with PCT ≥ 0.5 ng/mL (P = 0.0314), but it was not an independent prognostic factor. Conclusion Serum PCT level was significantly higher in patients with ALF. PMID:28331420

Serum and cerebrospinal fluid levels of visinin-like protein-1 in acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Takahara, Midori; Kajimoto, Madoka; Momonaka, Hiroshi; Oka, Momoko; Isumi, Hiroshi; Emi, Sakie; Hayashi, Megumi; Ichiyama, Takashi

2014-08-01

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has recently been recognized as an encephalopathy subtype. Typical clinical symptoms of AESD are biphasic seizures, and MRI findings show reduced subcortical diffusion during clustering seizures with unconsciousness after the acute phase. Visinin-like protein-1 (VILIP-1) is a recently discovered protein that is abundant in the central nervous system, and some reports have shown that VILIP-1 may be a prognostic biomarker of conditions such as Alzheimer's disease, stroke, and brain injury. However, there have been no reports regarding serum and cerebrospinal fluid (CSF) levels of VILIP-1 in patients with AESD. We measured the serum and CSF levels of VILIP-1 in patients with AESD, and compared the levels to those in patients with prolonged febrile seizures (FS). Both serum and CSF levels of VILIP-1 were significantly higher in patients with AESD than in patients with prolonged FS. Serum and CSF VILIP-1 levels were normal on day 1 of AESD. Our results suggest that both serum and CSF levels of VILIP-1 may be one of predictive markers of AESD. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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.

[Ammonia as a cause for hepatic encephalopathy].

PubMed

Naimushin, Alexey; Livneh, Avi

2010-02-01

In a patient with cirrhosis of the liver, associated with hepatitis B virus, who was admitted for confusion and acute elevation of liver enzymes, a diagnosis of hepatic encephalopathy was made. A serum ammonia level of 54 (normal less than 33) microgram/liter, supported the diagnosis, but puzzled the medical staff regarding the possibility that ammonia may directly induce the confusion. While it is widely accepted that the ammonia level is a marker that usually parallels the amount of toxins and metabolites that bypasses the liver, its role in causing brain dysfunction is debated. However, since ammonia may directly hinder the metabolism of neuro-transmitters, and drugs and treatments specifically aimed at reducing ammonia levels may minimize the time interval for recovery from the acute brain insult, it is assumed that ammonia by itself had a role in bringing about the encephalopathy manifestations in our patients and other patients with cirrhosis of the liver.

Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

PubMed

Hughes, Adrienne; Brown, Alisha; Valento, Matthew

2016-09-01

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.

Serum Bilirubin and Disease Progression in Mild COPD

PubMed Central

Apperley, Scott; Park, Hye Yun; Holmes, Daniel T.; Wise, Robert A.; Connett, John E.

2015-01-01

BACKGROUND: COPD is a chronic inflammatory disorder associated with oxidative stress. Serum bilirubin has potent antioxidant actions, and higher concentrations have been shown to protect against oxidative stress. The relation between serum bilirubin and COPD progression is unknown. METHODS: Serum bilirubin was measured in 4,680 smokers aged 35 to 60 years old with mild to moderate airflow limitation. The relationship of serum bilirubin to postbronchodilator FEV1 and rate of FEV1 decline over 3 to 9 years was determined using regression modeling. Total and disease-specific mortality were also ascertained. RESULTS: Serum bilirubin was positively related to FEV1 (P < .001). Serum bilirubin was also negatively related to the annual decline in FEV1 when adjusted for baseline demographics, pack-years smoked, and baseline measures of lung function (P = .01). Additionally, serum bilirubin was negatively associated with risk of death from coronary heart disease (P = .03); however, the relationships between bilirubin and other mortality end points were not statistically significant (P > .05). CONCLUSIONS: Bilirubin is inversely related to COPD disease severity and progression. Higher serum bilirubin concentration was associated with a higher FEV1 and less annual decline in FEV1. Bilirubin was also associated with less coronary heart disease mortality. These data support the hypothesis that bilirubin has a protective effect on COPD disease progression, possibly through its antioxidant actions. Bilirubin may prove useful as an easily accessible and readily available blood-based COPD biomarker. PMID:25539285

[Acute encephalopathy caused by cyanogenic fungi in 2004, and magic mushroom regulation in Japan].

PubMed

Gonmori, Kunio; Yokoyama, Kazumasa

2009-03-01

Two topics, related to mushroom poisoning of recent interest in Japan, have been presented. In autumn 2004, 59 cases of acute encephalopathy were reported across 9 prefectures in Japan (24 from Akita Prefecture with 8 deaths; age 48-93, average 70; female 14, male 10). Of 24 cases, 20 had kidney dysfunction. Four poisoned subjects showed no kidney trouble. Of the 24 poisoning cases, 23 people ate Pleurocybella porrigens, and one ate Grifola frondosa. The latter subject (female, late 40's) was receiving dialysis for more than 35 years. In August, she felt dizziness, headache and tinnitus. She visited hospital and asked to stay there. In the hospital she ate 5g of stewed G. frondosa and 10g of the same fungus boiled with chicken and taro on different days. Fourteen to 18 days after the eatings, she developed cramps and lost consciousness, and fell into a coma. Her cramp and coma continued for about 10 days almost until her death. Her symptoms caused by G. frondosa were similar to those observed for the above 23 cases of P. porrigens ingestion. Therefore, we concluded that encephalopathy experienced in Akita Prefecture caused by was the cyanogenic fungi such as P. porrigens , G. frondosa, Pleurotus eringii etc. Although the amounts of mushrooms eaten by poisoned subjects were not so clear, we estimated that the amounts of hydrogen cyanide (HCN) taken into human bodies exceeded the detoxication limit of HCN, resulting in HCN poisoning. However, it has not been proved that the encephalopathy is directly or indirectly caused by the HCN poisoning. Many typhoons came across Japan and landed 10 times in 2004, and mushroom size was larger than usual one, and HCN contents in fruit-bodies seemed to be increased especially in the late-stage of their growth. Thirteen species of magic mushrooms were prohibited by the law from 2002 in Japan. They include Copelandia (Panaeolus) cyanescens, Panaeolus papilionaceus, Panaeolus sphinctrinus, Panaeolus subbalteatus, Psilocybe argentipes

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline

PubMed Central

2014-01-01

Background Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Methods Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Results Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. Conclusions These findings suggest that CCL2 is elevated systemically following acute liver injury

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

PubMed

McMillin, Matthew; Frampton, Gabriel; Thompson, Michelle; Galindo, Cheryl; Standeford, Holly; Whittington, Eric; Alpini, Gianfranco; DeMorrow, Sharon

2014-07-10

Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the

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

Wernicke’s encephalopathy associated with liver abscess.

PubMed

Verma, Rajesh; Garg, Vipul

2017-07-31

Wernicke's encephalopathy is a rare neurological disorder caused by thiamine deficiency, characterised by ocular motor dysfunction, ataxia and impairment in consciousness. It predominantly affects brain regions with a high metabolic rate such as mammillary bodies, medial thalamic nuclei, the tectal region and the cerebellum. Although chronic alcoholism is the most common cause of Wernicke's encephalopathy, various other conditions not related to alcohol consumption such as bariatric surgery, acute pancreatitis, hyperemesis gravidarum, prolonged fasting and gastrointestinal surgery have been implicated in its aetiology. We report the case of a patient who underwent surgery for liver abscess and subsequently developed Wernicke's encephalopathy; he showed a positive response to thiamine supplementation. This is the first report describing liver abscess as the cause of Wernicke's encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

Relationships between serum bilirubins and production and conjugation of bilirubin. Studies in Gilbert's syndrome, Crigler-Najjar disease, hemolytic disorders, and rat models.

PubMed

Muraca, M; Fevery, J; Blanckaert, N

1987-02-01

The pattern of serum bilirubins was determined in serum of humans and rats with unconjugated hyperbilirubinemia due to increased pigment load or defective hepatic conjugation. Bilirubin ester conjugates were present in all serum samples tested and were identified as bilirubin 1-O-acyl glucuronides. In Gilbert's syndrome, the concentration of total conjugates was comparable to the values in healthy control subjects. Because the concentration of unconjugated pigment was increased, the fraction of conjugated relative to total bilirubins was markedly decreased. Sera from patients with Crigler-Najjar disease differed from those with Gilbert's syndrome by the higher unconjugated bilirubin levels and the undetectability of diconjugated bilirubins. A striking finding was that in hemolytic disease, the concentration of both monoconjugates and diconjugates was enhanced in parallel with the increase of unconjugated pigment. Therefore, the fraction of conjugated relative to total bilirubins remained within the normal range. As in Gilbert's syndrome, heterozygote R/APfd-j/+ rats with impaired hepatic bilirubin conjugation exhibit an increased unconjugated bilirubin level in serum, whereas the concentration of total conjugates was comparable to the values in normal rats. In serum of normal rats loaded intraperitoneally with unconjugated bilirubin, both unconjugated and mono- and diconjugated bilirubins were increased in parallel so that the ratio of unconjugated to esterified pigment remained unaffected. Decreased hepatic conjugation or increased bilirubin load was associated with a lower percentage of diconjugates relative to total conjugates both in human and rat serum. The present results are consistent with a compartmental model in which there is bidirectional transfer across the sinusoidal membrane for unconjugated bilirubin as well as for the bilirubin glucuronides. Because typical patterns of serum bilirubins are found in Gilbert's syndrome and patients with hemolytic

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: new observations with potential therapy.

PubMed

Brusilow, Saul W; Cooper, Arthur J L

2011-11-01

Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure, is a contributing factor: the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Case report. Johns Hopkins Hospital. A 22-yr-old woman who, 36 hrs before admission, ingested 15 g acetaminophen was admitted to the Johns Hopkins Hospital. She was treated with N-acetylcysteine. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hrs after ingestion when she became confused, irritable, and agitated. She was intubated, ventilated, and placed on lactulose. Shortly thereafter, she was noncommunicative, unresponsive to painful stimuli, and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure was made. She improved very slowly until 180 hrs after ingestion when she moved all extremities. She woke up shortly thereafter. Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in acute liver failure, the patient's plasma ammonia peaked when she exhibited no obvious neurologic deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurologic status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high but began to normalize several hours after plasma ammonia had returned to normal. The patient only started to recover as her plasma glutamine began

Effectiveness and safety of noninvasive positive-pressure ventilation for severe hypercapnic encephalopathy due to acute exacerbation of chronic obstructive pulmonary disease: a prospective case-control study.

PubMed

Zhu, Guang-fa; Zhang, Wei; Zong, Hua; Xu, Qiu-fen; Liang, Ying

2007-12-20

Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years. Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) < 10 served as group A and 21 with GCS = 10 as group B. Compared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102 +/- 27) mmHg vs (74 +/- 17) mmHg, P < 0.01), lower levels of GCS (7.5 +/- 1.9 vs 12.2 +/- 1.8, P < 0.01), arterial pH value (7.18 +/- 0.06 vs 7.28 +/- 0.07, P < 0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168 +/- 39 vs 189 +/- 33, P < 0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A, which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P > 0.05), but group A needed an average of 7 cm H2O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P < 0.05 or P < 0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.

PubMed

Radha Krishna, Yellapu; Saraswat, Vivek Anand; Das, Khaunish; Himanshu, Goel; Yachha, Surender Kumar; Aggarwal, Rakesh; Choudhuri, Gour

2009-03-01

Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto-systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver-operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score. ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3+/-18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4+/-1.6 and mean MELD score was 28.6+/-9.06. Three-month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in

[Portal vein thrombosis associated with hepatic encephalopathy].

PubMed

Iwatani, Nao; Inatomi, Yuichiro; Yonehara, Toshiro; Fujioka, Shodo; Hashimoto, Yoichiro; Hirano, Teruyuki; Uchino, Makoto

2005-03-01

A 54-year-old man who had been administered chlormadinone acetate 3 months after prostatectomy for prostate cancer, acutely developed disorientation and memory disturbance. Six days later, he experienced high grade fever and epigastralgia. He was suspected to have hepatic encephalopathy, because the Fischer ratio was low although serum ammonia level remained normal. Further examinations including abdominal echography and CT scan disclosed a thrombus extending from the portal vein to the superior mesenteric vein together with abnormal collateral vessels originating from the portal vein. He was successfully treated with warfarin potassium, urokinase and heparin sodium. It was suggested that the patient developed hepatic encephalopathy due to portal-systemic circulation shunting secondary to portal vein thrombosis.

Traumatic head injury mimicking acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Inoue, Hirofumi; Hasegawa, Shunji; Kajimoto, Madoka; Matsushige, Takeshi; Ichiyama, Takashi

2014-10-01

Many studies have reported acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with viral infection at onset, but few studies have reported AESD without infection. We report the case of a 9-month-old boy who had a clinical course mimicking AESD after a traffic accident. The traffic accident caused a mild subdural hematoma without neurological abnormalities on admission. The boy became unconscious on the second day, and he was diagnosed with non-convulsive status epilepticus on the third day. Diffusion-weighted imaging showed reduced water diffusion in the subcortical white matter. On laboratory analysis interleukin (IL)-6 was elevated in the cerebrospinal fluid (CSF), but not in the serum. He had severe neurological sequelae with mental retardation, spastic tetraplegia, and epilepsy. We suggest that brain damage mimicking AESD was caused by the traffic accident and the prolonged seizure during infancy. © 2014 Japan Pediatric Society.

Bronchiolitis-associated encephalopathy in critically-ill infants: an underestimated complication?

PubMed

Antonucci, Roberto; Chiappe, Stefano; Porcella, Annalisa; Rosatelli, Daniela; Fanos, Vassilios

2010-05-01

To investigate the bronchiolitis-associated encephalopathy in critically ill infants. The records of infants with severe bronchiolitis admitted to our intensive care unit between 1991 and 2003 were reviewed. Subjects with underlying neurological disorders were excluded. Encephalopathy was defined as occurrence of seizures or at least two nonconvulsive neurologic manifestations. A semistructured telephone interview investigated long-term neurodevelopmental outcome. Twenty-one infants (11 newborns) were enrolled. All patients required oxygen supplementation and 14 required mechanical ventilation. Encephalopathy occurred in 10 infants, six of whom developed seizures. Encephalopathic infants frequently (six of nine) showed transient EEG abnormalities, and occasionally (one of nine) cranial ultrasound abnormalities. A positive respiratory syncytial virus test was found in five of nine encephalopathic infants. One encephalopathic patient died, while 20 infants clinically normalised before discharge and showed a good neurodevelopmental outcome. Acute encephalopathy was frequently observed in our patients with severe bronchiolitis. Long-term prognosis of encephalopathic infants was good.

Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

PubMed

Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

2016-10-01

Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

Functionalized SBA-15 materials for bilirubin adsorption

NASA Astrophysics Data System (ADS)

Tang, Tao; Zhao, Yanling; Xu, Yao; Wu, Dong; Xu, Jun; Deng, Feng

2011-05-01

To investigate the driving force for bilirubin adsorption on mesoporous materials, a comparative study was carried out between pure siliceous SBA-15 and three functionalized SBA-15 mesoporous materials: CH 3-SBA-15 (MS), NH 2-SBA-15 (AS), and CH 3/NH 2-SBA-15 (AMS) that were synthesized by one-pot method. The obtained materials exhibited large surface areas (553-810 m 2/g) and pore size (6.6-7.1 nm) demonstrated by XRD and N 2-ad/desorption analysis. The SEM images showed that the materials had similar fiberlike morphology. The functionalization extent was calculated according to 29Si MAS NMR spectra and it was close to the designed value (10%). The synthesized mesoporous materials were used as bilirubin adsorbents and showed higher bilirubin adsorption capacities than the commercial active carbon. The adsorption capacities of amine functionalized samples AMS and AS were larger than those of pure siliceous SBA-15 and MS, indicating that electrostatic interaction was the dominant driving force for bilirubin adsorption on mesoporous materials. Increasing the ionic strength of bilirubin solution by adding NaCl would decrease the bilirubin adsorption capacity of mesoporous material, which further demonstrated that the electrostatic interaction was the dominant driving force for bilirubin adsorption. In addition, the hydrophobic interaction provided by methyl groups could promote the bilirubin adsorption.

Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.

PubMed

Peng, You-Fan; Deng, Yi-Bin

2017-06-01

- Bilirubin has strong anti-inflammatory and antioxidative stress action. Progression of inflammation involving arteries is a crucial activator in pathogenesis of Takayasu arteritis (TA). - To investigate the relationship between serum bilirubin and TA. - Our study involved 115 consecutive TA patients. Patients with active-phase disease were followed and received prednisone therapy. - Lower concentrations of serum bilirubin were detected in TA patients compared with healthy subjects (0.6 ± 0.31 versus 0.7 ± 0.22 mg/dL, P = .02). Serum bilirubin concentrations in active TA patients were lower than those in inactive patients (0.5 ± 0.20 versus 0.8 ± 0.32 mg/dL, P < .001). In all patients with TA, serum bilirubin correlated positively with total protein (r = 0.193, P = .04) and negatively with C-reactive protein and erythrocyte sedimentation rate (r = -0.213, P = .03, and r = -0.532, P < .001, respectively). Multiple logistic regression analysis showed that each decrease of 1 mg/dL in serum bilirubin was associated with a 1.10 times increase in the odds for TA compared with the controls (odds ratio = 0.913, 95% CI, 0.856-0.974; P = .006). Serum bilirubin was correlated with erythrocyte sedimentation rate (β = -0.170, P < .001) in multiple linear regression analysis. The area under the curve for serum bilirubin in predicting active TA patients was 0.802. Serum bilirubin levels were found to be significantly increased after prednisone treatment (0.5 ± 0.20 versus 0.7 ± 0.15 mg/dL, P = .002). - Lower serum bilirubin levels are associated with TA, and serum bilirubin may be influenced by prednisone therapy in active TA patients. Serum bilirubin levels in TA patients correlate negatively with erythrocyte sedimentation rate.

Mortality associated with bilirubin levels in insurance applicants.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2009-01-01

Determine the relationship between bilirubin levels with and without other liver function test (LFT) elevations and relative mortality in life insurance applicants. By use of the Social Security Death Master File mortality was determined in 1,905,664 insurance applicants for whom blood samples were submitted to the Clinical Reference Laboratory. There were 50,174 deaths observed in this study population. Results were stratified by 3 age/sex groups: females, age <60; males, age <60; and all, age 60+. The median follow-up was 12 years. Relative mortality increased as bilirubin decreased below bilirubin levels seen for the middle 50% of the population. The known association of smoking with lower bilirubin values explained only part of the additional elevated risk at low bilirubin levels. In the absence of other LFT elevations, relative mortality remained unchanged as bilirubin increased beyond levels seen for the middle 50% of the population. When a bilirubin elevation was combined with other LFT elevations, mortality further increased only at the highest elevations of other LFTs, seen only in <2.5% of applicants. Isolated elevations of bilirubin in this healthy screening population were not associated with excess mortality but values below the midpoint were. Other investigations have suggested a cardiovascular cause may underlie the excess mortality associated with low bilirubin. In association with other LFT elevations, bilirubin elevation further increases the mortality risk only at the highest elevations of other LFTs.

Association Of Serum Total Bilirubin Level With Diabetic Retinopathy In Type 2 Diabetes Mellitus.

PubMed

Ghaffar, Tahir; Marwat, Zahid Irfan; Ullah, Fahim; Khan, Salman; Hassan Aamir, Aziz Ul

2016-01-01

Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time.

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.

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.

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.

Increased toll-like receptor 4 in cerebral endothelial cells contributes to the astrocyte swelling and brain edema in acute hepatic encephalopathy.

PubMed

Jayakumar, Arumugam R; Tong, Xiao Y; Curtis, Kevin M; Ruiz-Cordero, Roberto; Abreu, Maria T; Norenberg, Michael D

2014-03-01

Astrocyte swelling and the subsequent increase in intracranial pressure and brain herniation are major clinical consequences in patients with acute hepatic encephalopathy. We recently reported that conditioned media from brain endothelial cells (ECs) exposed to ammonia, a mixture of cytokines (CKs) or lipopolysaccharide (LPS), when added to astrocytes caused cell swelling. In this study, we investigated the possibility that ammonia and inflammatory agents activate the toll-like receptor 4 (TLR4) in ECs, resulting in the release of factors that ultimately cause astrocyte swelling. We found a significant increase in TLR4 protein expression when ECs were exposed to ammonia, CKs or LPS alone, while exposure of ECs to a combination of these agents potentiate such effects. In addition, astrocytes exposed to conditioned media from TLR4-silenced ECs that were treated with ammonia, CKs or LPS, resulted in a significant reduction in astrocyte swelling. TLR4 protein up-regulation was also detected in rat brain ECs after treatment with the liver toxin thioacetamide, and that thioacetamide-treated TLR4 knock-out mice exhibited a reduction in brain edema. These studies strongly suggest that ECs significantly contribute to the astrocyte swelling/brain edema in acute hepatic encephalopathy, likely as a consequence of increased TLR4 protein expression by blood-borne noxious agents. © 2013 International Society for Neurochemistry.

Does bilirubin protect against developing diabetes mellitus?

PubMed

Breimer, Lars H; Mikhailidis, Dimitri P

2016-01-01

After 25 years of evaluating bilirubin as a possible protective agent in neonatal and cardiovascular disease, interest has moved on to a exploring a possible protective role in diabetes mellitus (DM). This review finds conflicting prospective data for a protective relationship though there are retrospective, case-controlled data, that can only show association, which is not causality. Only prospective studies can show causality. Also, it would appear that the underlying biochemical assumptions do not readily translate from the animal to the human setting. Given that many factors impact on circulating bilirubin levels, it is not surprising that a clear-cut answer is not available; the jury is still out. Any relationship between DM and bilirubin might relate to intermediates in bilirubin metabolism, including relationships involving the genes for the enzymes participating in those steps. Nevertheless, the pursuit of bilirubin in disease causation is opening new avenues for research and if it is established that serum bilirubin can predict risks, much will have been achieved. The answer may have to come from molecular genetic analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Bilirubin - urine

MedlinePlus

... Direct bilirubin - urine Images Male urinary system References Berk PD, Korenblat KM. Approach to the patient with ... Review Date 5/21/2017 Updated by: Laura J. Martin, MD, MPH, ABIM Board Certified in Internal ...

Bilirubin Blood Test: MedlinePlus Lab Test Information

MedlinePlus

... https://medlineplus.gov/labtests/bilirubinbloodtest.html Bilirubin Blood Test To use the sharing features on this page, please enable JavaScript. What is a Bilirubin Blood Test? A bilirubin blood test measures the levels of ...

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

PubMed

Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Serum bilirubin and the risk of rheumatoid arthritis.

PubMed

Juping, Du; Yuan, Yuan; Shiyong, Chen; Jun, Li; Xiuxiu, Zhou; Haijian, Ying; Jianfeng, Shi; Bo, Shen

2017-11-01

Oxidative stress and immune imbalance play an important role in the pathogenesis of rheumatoid arthritis (RA). Bilirubin is a powerful antioxidant and also regarded as immunomodulator. Increased evidence shows that bilirubin should be a protective factor for autoimmune disease. However, the relationship between bilirubin and RA remain unclear. We analyzed serum bilirubin levels and other laboratory and clinical data in 130 RA patients (35 patients without any complications), 81 osteoarthritis (OA) patients and 96 healthy controls. Binary logistic regression adjusted by age and gender revealed that the levels of serum total, indirect bilirubin were significantly lower in RA patients, when compared with healthy controls (P=.015, OR=0.767, 95% CI=0.619-0.951; P=.010, OR=0.664, 95% CI=0.487-0.906, respectively) or OA patients (P=.000, OR=0.763, 95% CI=0.661-0.882; P=.000, OR=0.656, 95% CI=0.532-0.808, respectively). A reduced trend of levels of bilirubin has been detected along with increased disease activity, despite with no significance (P>.05). Spearman rank test further demonstrated that IgG and ESR were negative associated with total, indirect bilirubin, and albumin, prealbumin, APOA, HDL-C were positively associated with bilirubin. In conclusion, the levels of serum bilirubins were decreased in RA, and decreased levels could be associated with IgG, albumin and inflammatory marker ESR. © 2017 Wiley Periodicals, Inc.

Animal pigment bilirubin discovered in plants.

PubMed

Pirone, Cary; Quirke, J Martin E; Priestap, Horacio A; Lee, David W

2009-03-04

The bile pigment bilirubin-IXalpha is the degradative product of heme, distributed among mammals and some other vertebrates. It can be recognized as the pigment responsible for the yellow color of jaundice and healing bruises. In this paper we present the first example of the isolation of bilirubin in plants. The compound was isolated from the brilliant orange-colored arils of Strelitzia nicolai, the white bird of paradise tree, and characterized by HPLC-ESMS, UV-visible, (1)H NMR, and (13)C NMR spectroscopy, as well as comparison with an authentic standard. This discovery indicates that plant cyclic tetrapyrroles may undergo degradation by a previously unknown pathway. Preliminary analyses of related plants, including S. reginae, the bird of paradise, also revealed bilirubin in the arils and flowers, indicating that the occurrence of bilirubin is not limited to a single species or tissue type.

Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

PubMed

Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

2015-10-01

The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

Supramolecular Complexes Formed in Systems Bile Salt-Bilirubin-Silica

NASA Astrophysics Data System (ADS)

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

The formation of supramolecular complexes between bilirubin and primary micelles of bile salts has been studied. The association constants of bile salts and binding of bilirubin with these associates have been determined. The adsorption of bilirubin and bile salts from individual and mixed aqueous solutions onto hydrophobic silica surfaces has been investigated. The interaction of bilirubin with primary bile salt micelles and the strong retention in mixed micelles, which are supramolecular complexes, result in the adsorption of bilirubin in free state only.

The Bilirubin Binding Panel: A Henderson-Hasselbalch Approach to Neonatal Hyperbilirubinemia.

PubMed

Ahlfors, Charles E

2016-10-01

Poor plasma bilirubin binding increases the risk of bilirubin neurotoxicity in newborns with hyperbilirubinemia. New laboratory tests may soon make it possible to obtain a complete bilirubin binding panel when evaluating these babies. The 3 measured components of the panel are the plasma total bilirubin concentration (B Total ), which is currently used to guide clinical care; the bilirubin binding capacity (BBC); and the concentration of non-albumin bound or free bilirubin (B Free ). The fourth component is the bilirubin-albumin equilibrium dissociation constant, K D , which is calculated from B Total , BBC, and B Free The bilirubin binding panel is comparable to the panel of components used in the Henderson-Hasselbalch approach to acid-base assessment. Bilirubin binding population parameters (not prospective studies to determine whether the new bilirubin binding panel components are better predictors of bilirubin neurotoxicity than B Total ) are needed to expedite the clinical use of bilirubin binding. At any B Total , the B Free and the relative risk of bilirubin neurotoxicity increase as the K D /BBC ratio increases (ie, bilirubin binding worsens). Comparing the K D /BBC ratio of newborns with B Total of concern with that typical for the population helps determine whether the risk of bilirubin neurotoxicity varies significantly from the inherent risk at that B Total Furthermore, the bilirubin binding panel individualizes care because it helps to determine how aggressive intervention should be at any B Total , irrespective of whether it is above or below established B Total guidelines. The bilirubin binding panel may reduce anxiety, costs, unnecessary treatment, and the likelihood of undetected bilirubin neurotoxicity. Copyright © 2016 by the American Academy of Pediatrics.

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.

Facility-based constraints to exchange transfusions for neonatal hyperbilirubinemia in resource-limited settings

PubMed Central

Mabogunje, Cecilia A; Olaifa, Sarah M; Olusanya, Bolajoko O

2016-01-01

Several clinical guidelines for the management of infants with severe neonatal hyperbilirubinemia recommend immediate exchange transfusion (ET) when the risk or presence of acute bilirubin encephalopathy is established in order to prevent chronic bilirubin encephalopathy or kernicterus. However, the literature is sparse concerning the interval between the time the decision for ET is made and the actual initiation of ET, especially in low- and middle-income countries (LMICs) with significant resource constraints but high rates of ET. This paper explores the various stages and potential delays during this interval in complying with the requirement for immediate ET for the affected infants, based on the available evidence from LMICs. The vital role of intensive phototherapy, efficient laboratory and logistical support, and clinical expertise for ET are highlighted. The challenges in securing informed parental consent, especially on religious grounds, and meeting the financial burden of this emergency procedure to facilitate timely ET are examined. Secondary delays arising from post-treatment bilirubin rebound with intensive phototherapy or ET are also discussed. These potential delays can compromise the effectiveness of ET and should provide additional impetus to curtail avoidable ET in LMICs. PMID:27170928

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

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

Seeing more clearly through the fog of encephalopathy.

PubMed

Kaplan, Peter W; Sutter, Raoul

2013-10-01

Patients with acute confusional states (often referred to as encephalopathy or delirium) pose diagnostic and management challenges for treating physicians. Encephalopathy is associated with a high morbidity and mortality rate, and the diagnosis rests on clinical grounds but may also be supported by the finding of electroencephalographic (EEG) evidence for diffuse cerebral dysfunction. The myriad cerebral transmitter and metabolic disruptions are generated by systemic organ system failures, principal among which are those of the liver, kidneys, lungs, heart, and endocrine system, along with the effects of exogenous toxins and medications. In most cases, several of these organ failures together contribute to the confusional state, frequently in the context of a diffuse cerebral atrophy that affects the aging brain. This special issue of the Journal of Clinical Neurophysiology is dedicated to exploring the electrophysiology of these conditions. It reviews the pathophysiology, psychiatric manifestations, clinical and imaging correlations of the many causes and types of encephalopathy. A literature review of the EEG abnormalities in the various types of encephalopathy provides an overview that ranges from paraneoplastic causes, through organ system failures, postcardiorespiratory arrest, to postoperative delirium. The issue is supplemented by tables of relevant clinical correlations, graphs, Venn diagrams, and the use of mathematical modeling used to explain how defects in the neuronal interplay might generate the EEG patterns seen in encephalopathy. We hope that this assembly will act as a springboard for further discussion and investigation into the EEG underpinnings, clinical correlations, diagnosis. and prognostication of these common and morbid disturbances of brain function.

Bilirubin and Stroke Risk Using a Mendelian Randomization Design.

PubMed

Lee, Sun Ju; Jee, Yon Ho; Jung, Keum Ji; Hong, Seri; Shin, Eun Soon; Jee, Sun Ha

2017-05-01

Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. The 14 single-nucleotide polymorphisms (SNPs) (<10 -7 ) including rs6742078 of uridine diphosphoglucuronyl-transferase were selected from genome-wide association study of bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke. © 2017 American Heart Association, Inc.

A microscopic evaluation of collagen-bilirubin interactions: in vitro surface phenomenon.

PubMed

Usharani, N; Jayakumar, G C; Rao, J R; Chandrasekaran, B; Nair, B U

2014-02-01

This study is carried out to understand the morphology variations of collagen I matrices influenced by bilirubin. The characteristics of bilirubin interaction with collagen ascertained using various techniques like XRD, CLSM, fluorescence, SEM and AFM. These techniques are used to understand the distribution, expression and colocalization patterns of collagen-bilirubin complexes. The present investigation mimic the in vivo mechanisms created during the disorder condition like jaundice. Fluorescence technique elucidates the crucial role played by bilirubin deposition and interaction during collagen organization. Influence of bilirubin during collagen fibrillogenesis and banding patterns are clearly visualize using SEM. As a result, collagen-bilirubin complex provides different reconstructed patterns because of the influence of bilirubin concentration. Selectivity, specificity and spatial organization of collagen-bilirubin are determined through AFM imaging. Consequently, it is observed that the morphology and quantity of the bilirubin binding to collagen varied by the concentrations and the adsorption rate in protein solutions. Microscopic studies of collagen-bilirubin interaction confirms that bilirubin influence the fibrillogenesis and alter the rate of collagen organization depending on the bilirubin concentration. This knowledge helps to develop a novel drug to inhibit the interface point of interaction between collagen and bilirubin. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Chronic traumatic encephalopathy.

PubMed

Omalu, Bennet

2014-01-01

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative syndrome, which is caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. CTE presents clinically as a composite syndrome of mood disorders and behavioral and cognitive impairment, with or without sensorimotor impairment. Symptoms of CTE may begin with persistent symptoms of acute traumatic brain injury (TBI) following a documented episode of brain trauma or after a latent period that may range from days to weeks to months and years, up to 40 years following a documented episode of brain trauma or cessation of repetitive TBI. Posttraumatic encephalopathy is distinct from CTE, can be comorbid with CTE, and is a clinicopathologic syndrome induced by focal and/or diffuse, gross and/or microscopic destruction of brain tissue following brain trauma. The brain of a CTE sufferer may appear grossly unremarkable, but shows microscopic evidence of primary and secondary proteinopathies. The primary proteinopathy of CTE is tauopathy, while secondary proteinopathies may include, but are not limited to, amyloidopathy and TDP proteinopathy. Reported prevalence rates of CTE in cohorts exposed to TBI ranges from 3 to 80% across age groups. © 2014 S. Karger AG, Basel.

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.

Treatment of Acute Hepatic Encephalopathy: Comparing the Effects of Adding Rifaximin to Lactulose on Patient Outcomes.

PubMed

Courson, Alesa; Jones, G Morgan; Twilla, Jennifer D

2016-06-01

Rifaximin is approved for the reduction of hepatic encephalopathy (HE) recurrence in patients with chronic liver disease (CLD); however, few studies have evaluated the benefit of adding rifaximin to lactulose for treatment of acute HE. The aim of this study was to determine the impact of combination therapy with lactulose and rifaximin on hospital length of stay (LOS) and readmission rates. A retrospective study of patients admitted to an adult hospital within the Methodist LeBonheur Healthcare (MLH) System in Memphis, Tennessee, between 2007 and 2012 was conducted. Patients were identified via International Classification of Diseases, Ninth Revision (ICD-9) coding for liver cirrhosis. Of the 173 patients included, 87 (50%) received lactulose monotherapy and 62 (36%) combination therapy, while 24 (14%) underwent therapy escalation. Median LOS was 6 days in monotherapy group and 8 days in combination group (P = .9). At 180 days, patients receiving combination therapy had fewer readmissions for HE than those receiving monotherapy (2.4% vs 16.2%, P = .02). Addition of rifaximin to lactulose for treatment of acute HE did not reduce hospital LOS; however, it did result in lower readmission rates for HE at 180 days. © The Author(s) 2015.

Hepato- and neuro-protective influences of biopropolis on thioacetamide-induced acute hepatic encephalopathy in rats.

PubMed

Mostafa, Rasha E; Salama, Abeer A A; Abdel-Rahman, Rehab F; Ogaly, Hanan A

2017-05-01

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato- and neuro-protective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into 5 groups: Group 1 (normal control) received only saline and paraffin oil. Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4, and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of HE were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato- and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, biopropolis, at a dose of 200 mg/kg per day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.

Hepatic Encephalopathy

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A decision-making tool for exchange transfusions in infants with severe hyperbilirubinemia in resource-limited settings.

PubMed

Olusanya, B O; Iskander, I F; Slusher, T M; Wennberg, R P

2016-05-01

Late presentation and ineffective phototherapy account for excessive rates of avoidable exchange transfusions (ETs) in many low- and middle-income countries. Several system-based constraints sometimes limit the ability to provide timely ETs for all infants at risk of kernicterus, thus necessitating a treatment triage to optimize available resources. This article proposes a practical priority-setting model for term and near-term infants requiring ET after the first 48 h of life. The proposed model combines plasma/serum bilirubin estimation, clinical signs of acute bilirubin encephalopathy and neurotoxicity risk factors for predicting the risk of kernicterus based on available evidence in the literature.

Influence of assessment site in measuring transcutaneous bilirubin

PubMed Central

da Conceição, Cristiane Maria; Dornaus, Maria Fernanda Pellegrino da Silva; Portella, Maria Aparecida; Deutsch, Alice D'Agostini; Rebello, Celso Moura

2014-01-01

ABSTRACT Objective: To investigate the influence of the site of measurement of transcutaneous bilirubin (forehead or sternum) in reproducibility of results as compared to plasma bilirubin. Methods: A cohort study including 58 term newborns with no hemolytic disease. Transcutaneous measurements were performed on the forehead (halfway between the headline and the glabella, from the left toward the right side, making consecutive determinations, one-centimeter apart) and the sternum (five measurements, from the suprasternal notch to the xiphoid process with consecutive determinations, one-centimeter apart) using Bilicheck® (SpectRx Inc, Norcross, Georgia, USA). The correlation and agreement between both methods and plasma bilirubin were calculated. Results: There was a strong linear correlation between both determinations of serum bilirubin at the forehead and sternum (r=0.704; p<0.01 and r=0.653; p<0.01, respectively). There was correspondence of the mean values of transcutaneous bilirubin measured on the sternum (9.9±2.2mg/dL) compared to plasma levels (10.2±1.7mg/dL), but both differ from the values measured on the forehead (8.6±2.0mg/dL), p<0.05. Conclusion: In newborn term infants with no hemolytic disease, measuring of transcutaneous bilirubin on the sternum had higher accuracy as compared to serum bilirubin measurement on the forehead. PMID:24728239

Veno-Occlusive Disease of the Liver in the Absence of Elevation in Bilirubin in Pediatric Patients after Hematopoietic Stem Cell Transplantation

PubMed Central

Myers, Kasiani C.; Dandoy, Christopher; El-Bietar, Javier; Davies, Stella M.; Jodele, Sonata

2016-01-01

Veno-occlusive disease (VOD) of the liver is a well-described and significant complication of hematopoietic stem cell transplantation (HSCT), with limited successful therapeutic options in severe cases. Prompt diagnosis and initiation of treatment is crucial to restrict the extent of disease. However, a subset of patients may not meet all current diagnostic criteria at presentation, and waiting for these to be met may delay therapy. We retrospectively reviewed 794 HSCT patients treated at our institution between 2003 and 2013, identifying 17 (2.1%) who developed VOD. Of these, 5 (29%) were noted to have an absence of elevated bilirubin at the time of VOD diagnosis and reversal of portal venous flow on ultrasound. Median total and conjugated bilirubin at VOD diagnosis were 1.0 and 0.2 mg/dL, respectively. All 5 patients were subsequently diagnosed with multiorgan failure associated with VOD, including 1 with encephalopathy. Four were treated with intravenous high-dose methylprednisolone (500 mg/m2 per dose every 12 hours for 6 doses). One patient received defibrotide therapy in addition to steroids and another supportive care alone. VOD resolved in 4 of 5 patients, with median time to resolution of VOD, defined as recovery of all organ function and normalization of bilirubin and portal venous flow, of 8 days. Two patients died later from progressive primary disease and chronic graft-versus-host disease, respectively. We conclude that a high index of suspicion for VOD should be maintained in patients despite lack of bilirubin elevation in the presence of other diagnostic criteria such as hepatomegaly, abdominal pain, ascites, or weight gain. Early ultrasound evaluation in these patients may lead to more timely diagnosis and therapeutic interventions. PMID:25300869

The biliverdin-bilirubin antioxidant cycle of cellular protection: Missing a wheel?

PubMed

McDonagh, Antony F

2010-09-01

Bilirubin reportedly protects cultured cells from the toxicity of a 10,000-fold molar excess of H(2)O(2). A bilirubin-biliverdin cycling mechanism has been proposed to explain this remarkable effect whereby bilirubin reacts with oxyradicals specifically generating biliverdin, which is then reduced back to bilirubin by NADPH/biliverdin reductase. Chemical evidence for this mechanism was formation of biliverdin during incubation of bilirubin-albumin with 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) in vitro and the assumption that biliverdin was formed by the reaction of peroxyl radicals with bilirubin. This paper describes spectroscopic studies on the reaction of bilirubin with AAPH in the presence and absence of human serum albumin. Reactions were run in air and also under oxygen-depleted and oxygen-saturated solutions, the former to inhibit peroxyl radical formation, the latter to augment it. The results confirm that degradation of bilirubin, rather than dehydrogenation to biliverdin, predominates in the reaction of bilirubin with peroxyl radicals generated by AAPH thermolysis. They also suggest that biliverdin produced in the presence of albumin is not formed by the reaction of bilirubin with alkyl peroxyl radicals, as previously assumed. The observations undermine the plausibility of the bilirubin-biliverdin recycling mechanism proposed to explain the reported hyperprotective effect of bilirubin on mammalian cells exposed to excess H(2)O(2). Copyright 2010 Elsevier Inc. All rights reserved.

The effect of hemoperfusion on patients with toxic encephalopathy induced by silkworm chrysalis ingestion.

PubMed

Hu, Haixia; Wang, Xu; Lv, Jiaqi; Sun, Jing; Xing, Jihong; Liu, Xiaoliang

2016-08-01

This study aims to determine therapeutic effect of hemoperfusion on patients with acute toxic encephalopathy induced by silkworm chrysalis ingestion. Three patients who developed toxic encephalopathy after chrysalis ingestion were analysed. Two patients lost their consciousness, while two patients had typical extrapyramidal tremor symptoms. Further neurological examination revealed various degrees of muscle strength impairment in these patients. All of them received treatments of omeprazole (40 mg/day), furosemide (one dose of 20 mg), vitamin C (2.0 g/day), calcium gluconate (2.0 g/day) and rehydration with glucose and sodium chloride (1500 ml/day). In addition, they received hemoperfusion treatment for 1.5 h. All patients recovered well after hemoperfusion. Two patients with loss of consciousness significantly recovered at 45 min and 65 min after hemoperfusion, respectively. All tremor symptoms were completely resolved in these patients at 30 min, 50 min, and 70 min following treatment, respectively. After the hemoperfusion treatment, encephalopathy symptoms of two patients had completely disappeared. All patients were followed up for one month and did not report any abnormalities. Our study indicates that hemoperfusion could be a useful and efficient treatment strategy for patients with acute encephalopathy after silkworm chrysalis ingestion. Larger clinical trials with longer follow-up are warranted to confirm the clinical benefit of hemoperfusion. © The Author(s) 2015.

Brain-derived neurotrophic factor and interleukin-6 levels in the serum and cerebrospinal fluid of children with viral infection-induced encephalopathy.

PubMed

Morichi, Shinichiro; Yamanaka, Gaku; Ishida, Yu; Oana, Shingo; Kashiwagi, Yasuyo; Kawashima, Hisashi

2014-11-01

We investigated changes in the brain-derived neurotrophic factor (BDNF) and interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS) infections, particularly viral infection-induced encephalopathy. Over a 5-year study period, 24 children hospitalized with encephalopathy were grouped based on their acute encephalopathy type (the excitotoxicity, cytokine storm, and metabolic error types). Children without CNS infections served as controls. In serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased in all encephalopathy groups, and significant increases were noted in the influenza-associated and cytokine storm encephalopathy groups. Children with sequelae showed higher BDNF and IL-6 levels than those without sequelae. In pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a prognostic index of CNS infections, particularly for the diagnosis of encephalopathy and differentiation of encephalopathy types.

Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group.

PubMed

Ng, Vicky L; Li, Ruosha; Loomes, Kathleen M; Leonis, Mike A; Rudnick, David A; Belle, Steven H; Squires, Robert H

2016-09-01

Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P < 0.001). Mortality 21 days after enrollment was highest in participants enrolled with severe HE (grades III or IV) or demonstrating HE progression. Four percent of participants without recorded clinical HE in the 7 days after enrollment, however, died within 21 days. Improved assessment of neurological injury and pediatric acute liver failure prognostication schema are needed.

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

 Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy.

PubMed

Moretti, Rita; Gazzin, Silvia; Crocè, Lory Saveria; Baso, Beatrice; Masutti, Flora; Bedogni, Giorgio; Tiribelli, Claudio

2016-01-01

 Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients.

Refeeding encephalopathy in a patient with severe hypophosphataemia and hyperammonaemia.

PubMed

Becker, S; Dam, G; Hvas, C L

2015-02-01

The refeeding syndrome is a potentially fatal condition that affects multiple organ systems. It is the consequence of fluid and electrolyte shifts that may occur in a malnourished patient following the introduction of nutrition therapy. The most prominent characteristic is hypophosphataemia. Although hyperammonaemia is usually seen in decompensated liver cirrhosis or acute liver failure, it may occur in other settings. We report a clinical case of prolonged and severe encephalopathy accompanied by hypophosphataemia and hyperammonaemia in a 59-year-old woman with no preexisting liver disease, urea cycle defects or portosystemic shunting. We suggest that these biochemical abnormalities were caused by uncontrolled refeeding and that the clinical picture was consistent with refeeding encephalopathy.

Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias.

PubMed

Lichter-Konecki, Uta; Nadkarni, Vinay; Moudgil, Asha; Cook, Noah; Poeschl, Johannes; Meyer, Michael T; Dimmock, David; Baumgart, Stephen

2013-08-01

Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child. Animal experiments and small clinical trials in hepatic encephalopathy caused by acute liver failure suggest that therapeutic hypothermia provides neuroprotection in hyperammonemia associated encephalopathy. We report results of an ongoing pilot study that assesses if whole body cooling during rescue treatment of neonates with acute hyperammonemia and encephalopathy is feasible and can be conducted safely. Adjunct whole body therapeutic hypothermia was conducted in addition to standard treatment in acutely encephalopathic, hyperammonemic neonates with UCDs and OAs requiring dialysis. Therapeutic hypothermia was initiated using cooling blankets as preparations for dialysis were underway. Similar to standard therapeutic hypothermia treatment for neonatal hypoxic ischemic encephalopathy, patients were maintained at 33.5°C±1°C for 72h, they were then slowly rewarmed by 0.5°C every 3h over 18h. In addition data of age-matched historic controls were collected for comparison. Seven patients were cooled using the pilot study protocol and data of seven historic controls were reviewed. All seven patients survived the initial rescue and cooling treatment, 6 patients were discharged home 2-4weeks after hospitalization, five of them feeding orally. The main complication observed in a majority of patients was hypotension. Adjunct therapeutic hypothermia for neonates with UCDs and OAs receiving standard treatment was

Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure.

PubMed

Lal, Bikrant B; Alam, Seema; Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev

2018-01-11

There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury. A total of 84 children with acute-on-chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute-on-chronic liver failure. The median duration from acute-on-chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation. Acute kidney injury developed in 22.6% of children with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with staphylococcal toxic shock syndrome caused by burns.

PubMed

Yokochi, Takaoki; Sakanishi, Shinpei; Ishidou, Yuuki; Kawano, Go; Matsuishi, Toyojiro; Akita, Yukihiro; Obu, Keizo

2016-10-01

We report a case of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with toxic shock syndrome caused by burns. A one-year-old girl was admitted to our hospital for treatment of severe burns. On day 3, she exhibited a fever, generalized rash and multiple organ failure. She was diagnosed with toxic shock syndrome after burns. She had seizures with fever twice on the same day, followed by secondary seizures on day 8 and transient deterioration of the gross motor functions involved in sitting alone and rolling over. On day 9, MRI diffusion-weighted images showed bright tree appearance (BTA). We conclude that she developed AESD. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Association of abnormal plasma bilirubin with aggressive HCC phenotype

PubMed Central

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

2014-01-01

Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods 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 AFP levels, tumor size, presence of PVT and tumor multifocality. Results 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 for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had 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

Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Ichimiya, Yuko; Kaku, Noriyuki; Sakai, Yasunari; Yamashita, Fumiya; Matsuoka, Wakato; Muraoka, Mamoru; Akamine, Satoshi; Mizuguchi, Soichi; Torio, Michiko; Motomura, Yoshitomo; Hirata, Yuichiro; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Takada, Hidetoshi; Maehara, Yoshihiko; Ohga, Shouichi

2017-08-01

Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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.

De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy.

PubMed

Belal, Hazrat; Nakashima, Mitsuko; Matsumoto, Hiroshi; Yokochi, Kenji; Taniguchi-Ikeda, Mariko; Aoto, Kazushi; Amin, Mohammed Badrul; Maruyama, Azusa; Nagase, Hiroaki; Mizuguchi, Takeshi; Miyatake, Satoko; Miyake, Noriko; Iijima, Kazumoto; Nonoyama, Shigeaki; Matsumoto, Naomichi; Saitsu, Hirotomo

2018-05-16

By whole exome sequencing, we identified three de novo RHOBTB2 variants in three patients with epileptic encephalopathies (EEs). Interestingly, all three patients showed acute encephalopathy (febrile status epilepticus), with magnetic resonance imaging revealing hemisphere swelling or reduced diffusion in various brain regions. RHOBTB2 encodes Rho-related BTB domain-containing protein 2, an atypical Rho GTPase that is a substrate-specific adaptor or itself is a substrate for the Cullin-3 (CUL3)-based ubiquitin/proteasome complex. Transient expression experiments in Neuro-2a cells revealed that mutant RHOBTB2 was more abundant than wild-type RHOBTB2. Co-expression of CUL3 with RHOBTB2 decreased the level of wild-type RHOBTB2 but not the level of any of the three mutants, indicating impaired CUL3 complex-dependent degradation of the three mutants. These data indicate that RHOBTB2 variants are a rare genetic cause of EEs, in which acute encephalopathy might be a characteristic feature, and that precise regulation of RHOBTB2 levels is essential for normal brain function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Is serum bilirubin associated with the severity of Guillain-Barré syndrome?

PubMed

Li, Xiaohong; Li, Wenchao; Shi, Xiang; Mo, Lijun; Luo, Yuzhen; Qin, Liuqun; Yang, Zheng; Mo, Wuning

2018-07-01

Our aim was to assess the correlation between serum bilirubin levels and Guillain-Barré syndrome (GBS). One hundred and one newly diagnosed patients with Guillain-Barré syndrome and 111 healthy age- and sex-matched individuals in the First Affiliated Hospital of Guangxi Medical University (Guangxi, China) from June 2012 to May 2017 were included in this study. Clinical characteristics and laboratory parameters of Guillain-Barré syndrome patients and healthy controls were retrospectively analysed. Serum bilirubin levels in Guillain-Barré syndrome patients were significantly lower as compared with those in healthy controls (p < 0.001); besides, log C-reactive protein and erythrocyte sedimentation rate were significantly higher. We found that there was a negative correlation between GBS disability scale scores and total bilirubin, direct bilirubin, indirect bilirubin (r = -0.541, P < 0.001; r = -0.403, P < 0.001; r = -0.526, P < 0.001), respectively. Among patients with GBS, serum total bilirubin, direct bilirubin, and indirect bilirubin levels were independently associated with Guillain-Barré syndrome disability scale scores in multiple linear regression analysis, respectively. We observed that serum bilirubin levels were lower in patients with Guillain-Barré syndrome, and suggested total bilirubin, direct bilirubin, and indirect bilirubin were independently and inversely associated with Guillain-Barré syndrome severity.

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

[Star fruit (Averrhoa carambola) toxic encephalopathy].

PubMed

Signaté, A; Olindo, S; Chausson, N; Cassinoto, C; Edimo Nana, M; Saint Vil, M; Cabre, P; Smadja, D

2009-03-01

Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.

Bilirubin in Urine: MedlinePlus Lab Test Information

MedlinePlus

... Information → Bilirubin in Urine URL of this page: https://medlineplus.gov/labtests/bilirubininurine.html Bilirubin in Urine ... 2017 Mar 23]; [about 3 screens]. Available from: https://www.liverfoundation.org/for-patients/about-the-liver/ ...

Reduced total serum bilirubin levels are associated with ulcerative colitis.

PubMed

Schieffer, Kathleen M; Bruffy, Shannon M; Rauscher, Richard; Koltun, Walter A; Yochum, Gregory S; Gallagher, Carla J

2017-01-01

Chronic inflammation associated with inflammatory bowel disease (IBD) results in increased oxidative stress that damages the colonic microenvironment. Low levels of serum bilirubin, an endogenous antioxidant, have been associated with increased risk for Crohn's disease (CD). Therefore, the aim of this study was to examine whether total serum bilirubin levels are associated with ulcerative colitis (UC). We identified a retrospective case-control population (n = 6,649) from a single tertiary care center, Penn State Hershey Medical Center (PSU) and a validation cohort (n = 1,996) from Virginia Commonwealth University Medical Center (VCU). Cases were age- and sex-matched to controls (PSU: CD n = 254, UC n = 187; VCU: CD n = 233, UC n = 124). Total serum bilirubin levels were obtained from de-identified medical records and segregated into quartiles. Logistic regression analysis was performed on each quartile of total serum bilirubin compared to the last quartile (highest bilirubin levels) to determine the association of total serum bilirubin with UC. Similar to CD patients, UC patients demonstrated reduced levels of total serum bilirubin compared to controls at PSU and VCU. The lowest quartile of total serum bilirubin was independently associated with UC for the PSU (OR: 1.98 [95% CI: 1.09-3.63]) and VCU cohorts (OR: 6.07 [95% CI: 3.01-12.75]). Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. Therapeutics that reduce oxidative stress may be beneficial for these patients.

Reduced total serum bilirubin levels are associated with ulcerative colitis

PubMed Central

Schieffer, Kathleen M.; Bruffy, Shannon M.; Rauscher, Richard; Koltun, Walter A.; Gallagher, Carla J.

2017-01-01

Chronic inflammation associated with inflammatory bowel disease (IBD) results in increased oxidative stress that damages the colonic microenvironment. Low levels of serum bilirubin, an endogenous antioxidant, have been associated with increased risk for Crohn’s disease (CD). Therefore, the aim of this study was to examine whether total serum bilirubin levels are associated with ulcerative colitis (UC). We identified a retrospective case-control population (n = 6,649) from a single tertiary care center, Penn State Hershey Medical Center (PSU) and a validation cohort (n = 1,996) from Virginia Commonwealth University Medical Center (VCU). Cases were age- and sex-matched to controls (PSU: CD n = 254, UC n = 187; VCU: CD n = 233, UC n = 124). Total serum bilirubin levels were obtained from de-identified medical records and segregated into quartiles. Logistic regression analysis was performed on each quartile of total serum bilirubin compared to the last quartile (highest bilirubin levels) to determine the association of total serum bilirubin with UC. Similar to CD patients, UC patients demonstrated reduced levels of total serum bilirubin compared to controls at PSU and VCU. The lowest quartile of total serum bilirubin was independently associated with UC for the PSU (OR: 1.98 [95% CI: 1.09–3.63]) and VCU cohorts (OR: 6.07 [95% CI: 3.01–12.75]). Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. Therapeutics that reduce oxidative stress may be beneficial for these patients. PMID:28594959

Metabolism of bilirubin by human cytochrome P450 2A6

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

Abu-Bakar, A'edah, E-mail: a.abubakar@uq.edu.au; Arthur, Dionne M.; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide

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 biliverdinmore » 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

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.

Lipopolysaccharide precipitates hepatic encephalopathy and increases blood-brain barrier permeability in mice with acute liver failure.

PubMed

Chastre, Anne; Bélanger, Mireille; Nguyen, Bich N; Butterworth, Roger F

2014-03-01

Acute liver failure (ALF) is frequently complicated by infection leading to precipitation of central nervous system complications such as hepatic encephalopathy (HE) and increased mortality. There is evidence to suggest that when infection occurs in ALF patients, the resulting pro-inflammatory mechanisms may be amplified that could, in turn, have a major impact on blood-brain barrier (BBB) function. The aim of this study was to investigate the role of endotoxemia on the progression of encephalopathy in relation to BBB permeability during ALF. Adult male C57-BL6 mice with ALF resulting from azoxymethane-induced toxic liver injury were administered trace amounts of the endotoxin component lipopolysaccharide (LPS). Effects on the magnitude of the systemic inflammatory response, liver pathology and BBB integrity were measured as a function of progression of HE, defined as time to loss of corneal reflex (coma). Lipopolysaccharide caused additional two- to seven-fold (P < 0.001) increases in circulating pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), worsening liver pathology and associated increases of circulating transaminases as well as increased hyperammonaemia consistent with a further loss of viable hepatocytes. LPS treatment of ALF mice led to a rapid precipitation of hepatic coma and the BBB became permeable to the 25-kDa protein immunoglobulin G (IgG). This extravasation of IgG was accompanied by ignificant up-regulation of matrix metalloproteinase-9 (MMP-9), an endopeptidase known to modulate opening of the BBB in a wide range of neurological disorders. These findings represent the first direct evidence of inflammation-related BBB permeability changes in ALF. © 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.

Fluorescence sensor for the quantification of unbound bilirubin concentrations.

PubMed

Huber, Andrew H; Zhu, Baolong; Kwan, Thomas; Kampf, J Patrick; Hegyi, Thomas; Kleinfeld, Alan M

2012-05-01

Hyperbilirubinemia in jaundiced neonates is routinely assessed by use of total serum bilirubin. However, the unbound or free form (B(f)), not total bilirubin, crosses the blood-brain barrier and can be neurotoxic. Although the peroxidase-mediated oxidation of bilirubin can be used to measure plasma concentrations of B(f), this measurement is relatively complex and the assay is not routinely used. We describe a fluorescence sensor for quantifying B(f) in plasma. Our method uses a mutated fatty acid binding protein labeled with the fluorescent molecule acrylodan (BL22P1B11), whose fluorescence is quenched upon binding bilirubin. Another configuration (BL22P1B11-Rh) was developed that uses BL22P1B11 together with the fluorophore rhodamine B, which responds by a change in the ratio of its fluorescence. The "B(f) probes" were calibrated with aqueous solutions of bilirubin and yielded similar bilirubin dissociation constants [K(d) = 16 (1.5) nmol/L]. We used the probes to determine B(f) concentrations in equilibrium with human serum albumin (HSA) and in human plasma samples supplemented with bilirubin. We obtained equivalent B(f) values in both systems, and the B(f) probe results were in agreement with the peroxidase assay. B(f) measurements revealed that bilirubin-HSA binding was well described by 2 sites with K(d) values of 15.4 (1) nmol/L and 748 (14) nmol/L. We measured B(f) concentrations in the range expected in jaundiced neonates with a mean CV of approximately 3%. The BL22P1B11-Rh probe provides accurate plasma sample B(f) concentrations with a single measurement, in 1 min with either a handheld B(f) meter or a laboratory fluorometer.

Percutaneous biliary drainage effectively lowers serum bilirubin to permit chemotherapy treatment.

PubMed

Levy, Jennifer L; Sudheendra, Deepak; Dagli, Mandeep; Mondschein, Jeffrey I; Stavropoulos, S William; Shlansky-Goldberg, Richard D; Trerotola, Scott O; Teitelbaum, Ursina; Mick, Rosemarie; Soulen, Michael C

2016-02-01

For digestive tract cancers, the bilirubin threshold for administration of systemic chemotherapy can be 5 or 2 mg/dL (85.5 or 34.2 μmol/L) depending upon the regimen. We examined the ability of percutaneous biliary drainage (PBD) in patients with malignant biliary obstruction to achieve these clinically relevant endpoints. 106 consecutive patients with malignant biliary obstruction and a baseline serum bilirubin >2 mg/dL underwent PBD. Time to achieve a bilirubin of 5 mg/dL (85.5 μmol/L), 2 mg/dL (34.2 μmol/L), and survival was estimated by Kaplan-Meier analysis. Potential technical and clinical prognostic factors were subjected to univariate and multivariate analysis. Categorical variables were analyzed by the log rank test. Hazard ratios were calculated for continuous variables. Median survival was 100 days (range 1-3771 days). Among 88 patients with a pre-drainage bilirubin >5 mg/dL, 62% achieved a serum bilirubin ≤5 mg/dL within 30 days and 84% within 60 days, median 21 days. Among 106 patients with a pre-drainage bilirubin >2 mg/dL, 37% achieved a serum bilirubin ≤2 mg/dL by 30 days and 70% within 60 days, median 43 days. None of the technical or clinical factors evaluated, including pre-drainage bilirubin, were significant predictors of time to achieve a bilirubin ≤2 mg/dL (p = 0.51). Size and type of biliary device were the only technical variables found to affect time to bilirubin of 5 mg/dL (p = 0.016). PBD of malignant obstruction achieves clinically relevant reduction in serum bilirubin in the majority of patients within 1-2 months, irrespective of the pre-drainage serum bilirubin, sufficient to allow administration of systemic chemotherapy. However, the decision to undergo this procedure for this indication alone must be considered in the context of patients' prognosis and treatment goals.

Manifestations and characteristics of congenital adrenal hyperplasia-associated encephalopathy.

PubMed

Abe, Yuichi; Sakai, Tetsuro; Okumura, Akihisa; Akaboshi, Shinjiro; Fukuda, Mitsumasa; Haginoya, Kazuhiro; Hamano, Shin-Ichiro; Hirano, Kouichi; Kikuchi, Kenjiro; Kubota, Masaya; Lee, Sooyoung; Maegaki, Yoshihiro; Sanefuji, Masafumi; Shimozato, Sachiko; Suzuki, Motomasa; Suzuki, Yasuhiro; Takahashi, Mitsugi; Watanabe, Kenji; Mizuguchi, Masashi; Yamanouchi, Hideo

2016-08-01

This study aimed to clarify the characteristics of acute encephalopathic episodes in patients with congenital adrenal hyperplasia (CAH), which we termed "CAH-associated encephalopathy (CAHE)." This retrospective study was conducted using a questionnaire as a nationwide survey of patients with CAH with acute encephalopathy and related episodes. Fifteen patients were recruited on the bases of clinical data that supported a diagnosis of CAHE. Fourteen patients displayed seizures at onset, and 12 patients exhibited refractory seizures. Deep coma lasting >24h was noted in 12 patients. Neuroimaging studies revealed some heterogeneous features. Diffuse or focal edematous lesions in the cerebrum, which produce high signal intensity on diffusion-weighted magnetic resonance imaging or low density on computer tomography, were found in the acute period in all 15 patients. In the chronic period, 14 patients survived, 11 of whom had some degree of neurological sequelae. Moreover, various degrees of cerebral shrinkage were observed in 11 of 14 surviving patients. Surprisingly, there were no abnormal neuroimaging findings in the basal ganglia, brainstem, and cerebellum in any patient. Our results indicated that patients with CAH have a risk of developing CAHE, and thus, they should be followed closely because not only status epilepticus or deep coma but also minor symptoms, such as fever and nausea, may lead to CAHE. Because CAHE may feature some heterogeneous encephalopathic episodes, further validation is needed to clarify its etiology. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[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. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Comparative evaluation of neonatal bilirubin using Radiometer whole blood co-oximetry and plasma bilirubin methods from Roche Diagnostics and Ortho Clinical Diagnostics.

PubMed

Lano, Ian Marie; Lyon, Andrew W; Wang, Li; Ruskin, Rob; Lyon, Martha E

2018-03-01

Clinically significant variation has been reported within and between plasma and whole blood total bilirubin methods used to identify neonates for whom clinical intervention for hyperbilirubinemia may be required. To evaluate total bilirubin measurements between the Radiometer whole blood co-oximeter and plasma bilirubin methods from Roche Diagnostics and Ortho Clinical Diagnostics using neonatal specimens. Total bilirubin levels were analyzed by whole blood co-oximetry (Radiometer® ABL90). Specimens were centrifuged and plasma analyzed for total bilirubin with a diazo method (Roche Cobas® C-601) and a reflectance spectrophotometric BuBc dry film method (Ortho Clinical Diagnostics VITROS® 350). Results were evaluated by regression, Bland-Altman comparisons and t-tests. The patient correlation study yielded the following regression equations in μmol/L: a) Radiometer=1.03 Roche - 3.5μmol/L b) Radiometer=0.98 Ortho - 5.7μmol/L c) Roche=0.97 Ortho - 2.4μmol/L. The mean bias over the range of total bilirubin levels examined was -1.0μmol/L for the Radiometer versus the Roche (p≤0.305); -4.4μmol/L for the Radiometer versus Ortho (p≤0.005) and -4.4μmol/L for the Roche versus Ortho (p≤0.002). Whole blood total bilirubin measurement using the Radiometer ABL90 blood gas analyzer provides accurate and precise results compared to the Roche plasma diazo method. Compared to the reflectance spectrophotometric method, results are precise and had a small but statistically significant bias of -4.4μmol/L. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Thyroid hormones and the hepatic handling of bilirubin. I. Effects of hypothyroidism and hyperthyroidism on the hepatic transport of bilirubin mono- and diconjugates in the Wistar rat.

PubMed

Van Steenbergen, W; Fevery, J; De Vos, R; Leyten, R; Heirwegh, K P; De Groote, J

1989-02-01

The effects of thyroidectomy and of thyroid hormone administration on the hepatic transport of endogenous bilirubin were investigated in the Wistar R/APfd rat. Hypothyroidism resulted in an enhanced hepatic bilirubin UDP-glucuronosyltransferase activity and in a decreased p-nitrophenol transferase activity. It caused a cholestatic condition with a 50% decrease in bile flow and bile salt excretion, and an increased proportion of conjugated bilirubin in serum. The biliary output of unconjugated and monoconjugated bilirubins decreased in parallel by about 65%, whereas the excretion rate of the diconjugate dropped by only 47%, resulting in an increased di- to monoconjugate ratio in bile. Hyperthyroidism was characterized by a decreased bilirubin and an increased p-nitrophenol transferase activity, and by an augmented bilirubin output in bile. The output of unconjugated and monoconjugated bilirubins increased in parallel by about 50 or 100%, whereas the excretion of the diconjugate increased by only 20 to 50%, depending on the dose of thyroxine administered; this resulted in a decreased di- to monoconjugate ratio in bile. A linear positive relationship was found between bilirubin UDP-glucuronosyltransferase activity and the ratio of bilirubin di- to monoconjugates present in bile or formed by in vitro incubation of liver homogenates at low concentration of bilirubin (10 to 15 microM), indicating that bile pigment composition is mainly determined by the conjugation activity in the liver. The inverse relationship observed between hepatic beta-glucuronidase activity and the ratio of di- to monoconjugates in bile warrants further investigation to analyze whether this enzyme activity also plays a possible role in the changes in bile pigment composition in hypo- and hyperthyroid rats.

Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literature.

PubMed

Yanagiha, Kumi; Ishii, Kazuhiro; Tamaoka, Akira

2017-02-01

Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

Bilirubin Inhibits Neointima Formation and Vascular Smooth Muscle Cell Proliferation and Migration

PubMed Central

Peyton, Kelly J.; Shebib, Ahmad R.; Azam, Mohammad A.; Liu, Xiao-ming; Tulis, David A.; Durante, William

2012-01-01

Bilirubin is a heme metabolite generated by the concerted action of the enzymes heme oxygenase and biliverdin reductase. Although long considered a toxic byproduct of heme catabolism, recent preclinical, and clinical studies indicate the bilirubin exerts beneficial effects in the circulation. In the present study, we determined whether local administration of bilirubin attenuates neointima formation following injury of rat carotid arteries. In addition, the ability of bilirubin to regulate the proliferation and migration of human arterial smooth muscle cells (SMCs) was investigated. Local perivascular administration of bilirubin immediately following balloon injury of rat carotid arteries significantly attenuated neointima formation. Bilirubin-mediated inhibition of neointimal thickening was associated with a significant decrease in ERK activity and cyclin D1 and A protein expression, and an increase in p21 and p53 protein expression in injured blood vessels. Treatment of human aortic SMCs with bilirubin inhibited proliferation and migration in a concentration-dependent manner without affecting cell viability. In addition, bilirubin resulted in a concentration-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and this was paralleled by a decrease in the fraction of cells in the S and G2M phases of the cell cycle. Finally, bilirubin had no effect on mitochondrial function and ATP content of vascular SMCs. In conclusion, these studies demonstrate that bilirubin inhibits neointima formation after arterial injury and this is associated with alterations in the expression of cell cycle regulatory proteins. Furthermore, bilirubin blocks proliferation and migration of human arterial SMCs and arrests SMCs in the G0/G1 phase of the cell cycle. Bilirubin represents an attractive therapeutic agent in treating occlusive vascular disease. PMID:22470341

Hepatic encephalopathy in a liver transplant recipient with stable liver function.

PubMed

Arab, Juan Pablo; Meneses, Luis; Pérez, Rosa M; Arrese, Marco; Benítez, Carlos

2013-04-01

Postshunt hepatic encephalopathy after liver transplantation (LT) is an infrequent condition and is commonly associated with portal occlusion or stenosis and the presence of a patent portosystemic shunt. Portal vein stenosis (PVS) or thrombosis (PVT) are uncommon complications after LT. The overall frequency of both complications is reported to be less than 3%. When PVS or PVT develop early after LT, the occlusion of the portal vein can have catastrophic consequences to the graft including acute liver failure and graft loss. Late PVT/PVS are asymptomatic in approximately 50% of the cases and mainly diagnosed by a routine ultrasound. Symptomatic postshunt hepatic encephalopathy (HE) is a very infrequent condition after LT that has been scarcely reported in the literature. We present here the case of a liver recipient with normal graft function who presented with hepatic encephalopathy 3 months after LT with stable liver function but a severe portal stenosis and the presence of a spontaneous portosystemic shunt whose successful endovascular treatment was followed by the complete resolution of the HE.

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.

Encephalopathy after bladder irrigation with alum: case report and literature review.

PubMed

Phelps, K R; Naylor, K; Brien, T P; Wilbur, H; Haqqie, S S

1999-09-01

A 70-year-old man with advanced obstructive nephropathy began to hemorrhage from the bladder after decompression with a Foley catheter. Manifestations of encephalopathy appeared after continuous irrigation with 1% alum for 2 days and were associated with elevated serum aluminum concentrations. Repeated treatments with deferoxamine and hemodialysis accomplished some aluminum removal, but the patient succumbed to bronchopneumonia. Brain aluminum content was not excessive at autopsy. A literature review suggests that intact renal function is essential to rapid disposal of a parenteral aluminum load and indicates that most reported instances of encephalopathy after alum irrigation have occurred in patients with compromised renal function. We conclude that alum should not be employed as a bladder irrigant in patients with acute or chronic renal failure.

Periodic Paralysis and Encephalopathy as Initial Manifestations of Graves' Disease: Case Report and Review of the Literature.

PubMed

Tsironis, Theocharis; Tychalas, Athanasios; Kiourtidis, Dimitrios; Kountouras, Jannis; Xiromerisiou, Georgia; Rudolf, Jobst; Deretzi, Georgia

2017-07-01

Thyrotoxic periodic paralysis (TPP) is an uncommon complication of Graves' disease, characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. Graves' encephalopathy is an extremely rare form of encephalopathy associated with autoimmune thyroid disease (EAATD), characterized by neuropsychiatric symptoms, increased antithyroid antibodies and cerebrospinal fluid protein concentration, nonspecific electroencephalogram abnormalities, and cortico-responsiveness. Coexistence of both these complications in the same patient has not been reported before. We herein present a 48-year-old white male patient with TPP and encephalopathy as initial presentations of Graves' disease. Flaccid tetraparesis was reversed a few hours after potassium level correction and the patient did not suffer any relapse with the successful pharmaceutical management of the thyroid function. One month later, the patient presented with dizziness and behavioral symptoms, such as inappropriate laughter and anger. Brain magnetic resonance imaging revealed meningeal enhancement and cerebrospinal fluid analysis showed a mild protein increase, with a blood-brain barrier disruption. With the suspicion of EAATD, the patient was treated with high doses of corticosteroids and improved dramatically. To our knowledge this is the first reported coexistence of potentially treatable TPP and EAATD as initial neurological manifestations of Graves' disease, thereby underscoring the necessity of suspicion of possible underlying Graves' disease in patients with acute paralysis and encephalopathy of unclear origin.

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

PubMed Central

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

BiliChek transcutaneous bilirubin meter overestimates serum bilirubin as measured by the Doumas reference method.

PubMed

Karon, Brad S; Wickremasinghe, Andrea C; Lo, Stanley F; Saenger, Amy K; Cook, Walter J

2010-08-01

To determine the relationship between BiliChek TcB (Respironics, Marietta GA) and Doumas reference serum or plasma total bilirubin (TSB). Pooled samples with values assigned by the Doumas reference method were used to establish the relationship between a local laboratory and reference Doumas TSB. We then established the relationship between TcB and TSB in the 3 months before and after reassignment of calibrator setpoints undertaken to match the local laboratory to Doumas reference bilirubin values. Before calibrator setpoint reassignment TSB as measured in our laboratory overestimated Doumas reference bilirubin. After calibrator adjustment laboratory TSB was within 1.7-6.8 micromol/L (0.1-0.4 mg/dL) of Doumas reference values. Mean bias between BiliChek TcB and TSB was 42.8+/-22.2 micromol/L (2.5+/-1.3mg/dL) (n=94) before and 49.6+/-22.2 micromol/L (2.9+/-1.3mg/dL) (n=115) after calibration adjustment. BiliChek TcB significantly overestimates TSB as measured by the Doumas reference method. 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Limitations and opportunities of whole blood bilirubin measurements by GEM premier 4000®.

PubMed

Wang, Li; Albert, Arianne Y K; Jung, Benjamin; Hadad, Keyvan; Lyon, Martha E; Basso, Melanie

2017-03-29

Neonatal hyperbilirubinemia has traditionally been screened by either total serum bilirubin or transcutaneous bilirubin. Whole blood bilirubin (TwB) by the GEM Premier 4000® blood gas analyzer (GEM) is a relatively new technology and it provides fast bilirubin results with a small sample volume and can measure co-oximetry and other analytes. Our clinical study was to evaluate the reliability of TwB measured by the GEM and identify analytical and clinical factors that may contribute to possible bias. 440 consecutive healthy newborn samples that had plasma bilirubin ordered for neonatal hyperbilirubinemia screening were included. TwB was first measured using the GEM, after which the remainder of the blood was spun and plasma neonatal bilirubin was measured using the VITROS 5600® (VITROS). 62 samples (14%) were excluded from analysis due to failure in obtaining GEM results. Passing-Bablok regression suggested that the GEM results were negatively biased at low concentrations of bilirubin and positively biased at higher concentrations relative to the VITROS results (y = 1.43x-61.13). Bland-Altman plots showed an overall negative bias of the GEM bilirubin with a wide range of differences compared to VITROS. Both hemoglobin concentration and hemolysis affected the accuracy of the GEM results. Clinically, male infants had higher mean bilirubin levels, and infants delivered by caesarean section had lower hemoglobin levels. When comparing the number of results below the 40th percentile and above the 95th percentile cut-offs in the Bhutani nomogram which would trigger discharge or treatment, GEM bilirubin exhibited poor sensitivity and poor specificity in contrast to VITROS bilirubin. An imperfect correlation was observed between whole blood bilirubin measured on the GEM4000® and plasma bilirubin on the VITROS 5600®. The contributors to the observed differences between the two instruments were specimen hemolysis and the accuracy of hemoglobin measurements, the latter

Does bilirubin prevent hepatic steatosis through activation of the PPARα nuclear receptor?

PubMed

Hinds, Terry D; Adeosun, Samuel O; Alamodi, Abdulhadi A; Stec, David E

2016-10-01

Several large population studies have demonstrated a negative correlation between serum bilirubin levels and the development of obesity, hepatic steatosis, and cardiovascular disease. Despite the strong correlative data demonstrating the protective role of bilirubin, the mechanism by which bilirubin can protect against these pathologies remains unknown. Bilirubin has long been known as a powerful antioxidant and also has anti-inflammatory actions, each of which may contribute to the protection afforded by increased levels. We have recently described a novel function of bilirubin as a ligand for the peroxisome proliferator-activated receptor-alpha (PPARα), which we show specifically binds to the nuclear receptor. Bilirubin may function as a selective PPAR modulator (SPPARM) to control lipid accumulation and blood glucose. However, it is not known to what degree bilirubin activation of PPARα is responsible for the protection afforded to reduce hepatic steatosis. We hypothesize that bilirubin, acting as a novel SPPARM, increases hepatic fatty acid metabolism through a PPARα-dependent mechanism which reduces hepatic lipid accumulation and protects against hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Copyright © 2016 Elsevier Ltd. All rights reserved.

A bioartificial liver to treat severe acute liver failure.

PubMed Central

Rozga, J; Podesta, L; LePage, E; Morsiani, E; Moscioni, A D; Hoffman, A; Sher, L; Villamil, F; Woolf, G; McGrath, M

1994-01-01

OBJECTIVE: To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. METHODS: Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. RESULTS: All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. CONCLUSIONS: This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients. Images Figure 2. Figure 3. PMID:8185403

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.

Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury.

PubMed

Kim, Jin Yong; Lee, Dong Yun; Kang, Sukmo; Miao, Wenjun; Kim, Hyungjun; Lee, Yonghyun; Jon, Sangyong

2017-07-01

Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress. BRNPs exerted potent antioxidant and anti-apoptotic activity in primary hepatocytes exposed to hydrogen peroxide, a precursor of reactive oxygen species (ROS). In a model of hepatic IRI in mice, BRNP preconditioning exerted profound protective effects against hepatocellular injury by reducing oxidative stress, pro-inflammatory cytokine production, and recruitment of neutrophils. They also preferentially accumulated in IRI-induced inflammatory lesions. Collectively, our findings indicate that BRNP preconditioning provides a simple and safe approach that can be easily monitored in the blood like endogenous bilirubin, and could be a promising strategy to protect against IRI in a clinical setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

The kinetics of oxidation of bilirubin and ascorbic acid in solution

NASA Astrophysics Data System (ADS)

Solomonov, A. V.; Rumyantsev, E. V.; Kochergin, B. A.; Antina, E. V.

2012-07-01

The results of a comparative study of the oxidation of bilirubin, ascorbic acid, and their mixture in aqueous solutions under the action of air oxygen and hydrogen peroxide are presented. The observed and true rate constants for the oxidation reactions were determined. It was shown that the oxidation of tetrapyrrole pigment occurred under these conditions bypassing the stage of biliverdin formation to monopyrrole products. Simultaneous oxidation of bilirubin and ascorbic acid was shown to be accompanied by the inhibition of ascorbic acid oxidation by bilirubin, whereas ascorbic acid itself activated the oxidation of bilirubin.

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

Utilization of Reflex Testing for Direct Bilirubin in the Early Recognition of Biliary Atresia.

PubMed

Lam, Leo; Musaad, Samarina; Kyle, Campbell; Mouat, Stephen

2017-05-01

Delayed diagnosis of biliary atresia is an important cause of pediatric end-stage liver failure and liver transplantation. We sought to determine whether direct bilirubin is underutilized by retrospectively reviewing patients with biliary atresia. Further, we aimed to determine the role of reflex testing for direct bilirubin in patients suspected for jaundice. The time intervals between total bilirubin and direct bilirubin measurements were retrospectively reviewed in patients with biliary atresia. We also audited the results of two major laboratories that had implemented reflex testing for direct bilirubin. We evaluated the clinical impact and cost of reflex testing in infants with increased direct bilirubin (>1.5 mg/dL; >25 μmol/L). In patients with known biliary atresia, an isolated total bilirubin measurement preceded direct bilirubin measurement in 46% (40/87) of patients; with a median delay of 19 days (interquartile range 3-44 days). In the community setting, direct bilirubin had a higher clinical specificity for biliary atresia than in the hospital setting. Reporting direct bilirubin results in 1591 infants younger than 2 weeks of age in the community was associated with three admissions to the hospital, one of whom was diagnosed with biliary atresia. The cost for the two laboratories for direct-bilirubin testing was estimated at US$3200 (NZ$4600) for each newly diagnosed case of biliary atresia. We identified underutilization of direct bilirubin as a cause of delay in the recognition of biliary atresia and show that reflex testing for direct bilirubin in jaundiced infants is a cost-effective solution. © 2017 American Association for Clinical Chemistry.

Unbound bilirubin measurements by a novel probe in preterm infants.

PubMed

Hegyi, Thomas; Kleinfeld, Alan; Huber, Andrew; Weinberger, Barry; Memon, Naureen; Shih, Weichung; Carayannopoulos, Mary; Oh, William

2018-03-12

Hyperbilirubinemia occurs in over 80% of newborns and severe bilirubin toxicity can lead to neurological dysfunction and death, especially in preterm infants. Currently, the risk of bilirubin toxicity is assessed by measuring the levels of total serum bilirubin (TSB), which are used to direct treatments including immunoglobulin administration, phototherapy, and exchange transfusion. However, free, unbound bilirubin levels (Bf) predict the risk of bilirubin neurotoxicity more accurately than TSB. To examine Bf levels in preterm infants and determine the frequency with which they exceed reported neurotoxic thresholds. One hundred thirty preterm infants (BW 500-2000 g; GA 23-34 weeks) were enrolled and Bf levels measured during the first week of life by the fluorescent Bf sensor BL22P1B11-Rh. TSB and plasma albumin were measured by standard techniques. Bilirubin-albumin dissociation constants (K d ) were calculated based on Bf and plasma albumin. Five hundred eighty samples were measured during the first week of life, with an overall mean Bf of 13.6 ± 9.0 nM. A substantial number of measurements exceeded potential toxic thresholds levels as reported in the literature. The correlation between Bf and TSB was statistically significant (r 2 0.17), but this weak relationship was lost at high Bf levels. Infants <28-week gestations had more hearing screening failures than infants ≥28-week gestation. Unbound (free) bilirubin values are extremely variable during the first week of life in preterm infants. A significant proportion of these values exceeded reported neurotoxic thresholds.

Enzymatic Removal of Bilirubin from Blood: A Potential Treatment for Neonatal Jaundice

NASA Astrophysics Data System (ADS)

Lavin, Arthur; Sung, Cynthia; Klibanov, Alexander M.; Langer, Robert

1985-11-01

Current treatments for severe jaundice can result in major complications. Neonatal jaundice is caused by excessive accumulation of bilirubin in the blood. A small blood filter containing immobilized bilirubin oxidase was developed to reduce serum bilirubin concentrations. When human or rat blood was passed through the enzyme filter, more than 90 percent of the bilirubin was degraded in a single pass. This procedure may have important applications in the clinical treatment of neonatal jaundice.

Neuroinflammation in hepatic encephalopathy: mechanistic aspects.

PubMed

Jayakumar, Arumugam R; Rama Rao, Kakulavarapu V; Norenberg, Michael D

2015-03-01

Hepatic encephalopathy (HE) is a major neurological complication of severe liver disease that presents in acute and chronic forms. While elevated brain ammonia level is known to be a major etiological factor in this disorder, recent studies have shown a significant role of neuroinflammation in the pathogenesis of both acute and chronic HE. This review summarizes the involvement of ammonia in the activation of microglia, as well as the means by which ammonia triggers inflammatory responses in these cells. Additionally, the role of ammonia in stimulating inflammatory events in brain endothelial cells (ECs), likely through the activation of the toll-like receptor-4 and the associated production of cytokines, as well as the stimulation of various inflammatory factors in ECs and in astrocytes, are discussed. This review also summarizes the inflammatory mechanisms by which activation of ECs and microglia impact on astrocytes leading to their dysfunction, ultimately contributing to astrocyte swelling/brain edema in acute HE. The role of microglial activation and its contribution to the progression of neurobehavioral abnormalities in chronic HE are also briefly presented. We posit that a better understanding of the inflammatory events associated with acute and chronic HE will uncover novel therapeutic targets useful in the treatment of patients afflicted with HE.

NEW INSIGHTS INTO THE PRESENCE OF BILIRUBIN IN A PLANT SPECIES STRELITZIA NICOLAI (STRELITZIACEAE).

PubMed

Dwarka, Depika; Thaver, Veneesha; Naidu, Mickey; Baijnath, Himansu

2017-01-01

The fortuitous discovery of an animal pigment bilirubin found in the plant Strelitzia nicolai has opened an enormous number of questions regarding bilirubin's formation and its ultimate function in the human body. A methodical review of bilirubin in humans and animals was carried out, information was gathered using published scientific journals, books and conference proceedings. Articles based on case studies of elevated levels of bilirubin were analysed thoroughly. Even though for numerous years bilirubin was assumed to be merely a desecrate product of the heme catabolic pathway by greatest, and a likely lethal compound at worst; statistics from the last few decades clearly shows that placidly high serum bilirubin levels are robustly related to have abundant beneficial effects on the human body. This study reveals new insights into the presence of the only animal pigment found in Strelitzia nicolai arils, the potential advantages of bilirubin found in a plant and its therapeutic value indications. This review hopes to resuscitate researchers' credence regarding bilirubin as a toxic compound.

Unconjugated free bilirubin in preterm infants.

PubMed

van der Schoor, Lori W E; Dijk, Peter H; Verkade, Henkjan J; Kamsma, Anna C J; Schreuder, Andrea B; Groen, Henk; Hulzebos, Christian V

Hyperbilirubinemia guidelines are based on total serum bilirubin (TSB), in combination with either gestational age (GA) or birth weight (BW), postnatal age and specific risk factors. However, TSB is a poor predictor of bilirubin-induced neurotoxicity (BIND). Free unconjugated bilirubin (UCBfree) and the UCBfree/TSB ratio are more directly related to BIND, but data on their postnatal courses are unknown. To characterize the postnatal courses of UCBfree and UCBfree/TSB ratio, and assess their relationships with clinical characteristics. 72 preterm infants≤32weeks GA, admitted to the University Medical Center Groningen, The Netherlands. During the first postnatal week, bilirubin plasma parameters were analyzed and their relationship with clinical parameters was analyzed. Postnatal changes were analyzed using Generalized Estimating Equations. Data are expressed as medians [ranges]. Less than 10% of the cohort (GA: 29 [26-31] weeks; BW: 1165 [600-1975] g) showed hyperbilirubinemic risk factors. We observed a large variation in UCBfree (27 [1-197] nmol/L), that could partly be explained by postnatal age and gender, but not by other risk factors. Maximal UCBfree levels of 50 [13-197] nmol/L occurred at day 4 and were higher in males. In contrast to TSB, UCBfree/TSB ratios (0.19 [0.01-1.04]) were higher in infants with low GA/BW. UCBfree levels vary considerably in preterm infants, despite a low incidence of hyperbilirubinemic risk factors and similar TSB-based phototherapy treatment. UCBfree could not be predicted by GA or BW, but UCBfree/TSB ratios are highest in the smallest preterms, while they have the lowest TSB levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Laser Transcutaneous Bilirubin Meter: A New Device For Bilirubin Monitoring In Neonatal Jaundice

NASA Astrophysics Data System (ADS)

Hamza, Mostafa; Hamza, Mohammad

1988-06-01

Neonates with jaundice require monitoring of serum bilirubin which should be repeated at frequent intervals. However, taking blood samples from neonates is not always an easy job, plus being an invasive and traumatising procedure with the additional risk of blood loss. In this paper the authors present the theory and design of a new noninvasive device for transcutaneous bilirubinometry, using a differential absorption laser system. The new technique depends upon illuminating the skin of the neonate with radiation from a two wave-length oscillation laser. The choice of the wavelengths follows the principles of optical bilirubinometry. For obtaining more accurate measurements, different pairs of two wave-lengths are incorporated in the design. The presence of hemoglobin is corrected for by appropriate selection of the laser wavelengths. The new design was tested for accuracy and precision using an argon ion laser. Correlation study between serum bilirubin determination by laser transcutaneous bilirubinometry and by American optical bilirubinometer was highly significant.

Acute liver failure in Cuban children.

PubMed

Silverio, César E; Smithen-Romany, Chleo Y; Hondal, Norma I; Díaz, Hetzel O; Castellanos, Marlen I; Sosa, Oramis

2015-01-01

Acute liver failure is rare in pediatric patients and is one of the most challenging medical emergencies due to its prognostic and therapeutic implications. The best scientific evidence worldwide comes from multicenter studies in developed countries. In Cuba, there are no prior studies of this disorder in children. Describe the main clinical features of Cuban children treated at a national referral center for acute liver failure, as defined by recognized diagnostic criteria for pediatric patients. A case series study was conducted comprising patients diagnosed with acute liver failure treated from 2005 to 2011 in the hepatology and liver transplant service at Havana's William Soler University Children's Hospital. Variables were age group, etiology of acute liver failure, grade of hepatic encephalopathy, blood chemistry variables, and clinical outcome (whether or not spontaneous recovery of liver function occurred). Associations between variables were assessed using contingency tables, and case fatality was calculated, as well as relative risk with its 95% confidence interval. The Mann-Whitney U test was used to compare means of laboratory test results. Median age of the 31 patients studied (14 boys and 17 girls) was 24 months (range 1-180). Time between symptom onset and diagnosis of acute liver failure was 25.1 days (SD 16.8). Infection was the most common etiology, present in 61.3% of cases (19/31); nonhepatotropic viruses, especially cytomegalovirus, predominated in infants. Spontaneous recovery occurred in 15 patients (48.4%), 3 (9.7%) received transplants, and 13 died, for a case fatality of 41.9%. Outcome was not associated with etiology (p = 0.106), but was statistically associated with degree of hepatic encephalopathy (p <0.01): 77.8% of patients (7/9) with grades III-IV encephalopathy died, for a relative risk of 4.0 (95% CI 1.15-13.8), versus 11.1% (1/9) with grade II or less encephalopathy. Cholesterol levels were significantly lower in patients who

Elevated serum bilirubin levels are inversely associated with coronary artery atherosclerosis.

PubMed

Kang, Seung Joo; Kim, Donghee; Park, Hyo Eun; Chung, Goh Eun; Choi, Seung Ho; Choi, Su-Yeon; Lee, Whal; Kim, Joo Sung; Cho, Sang-Heon

2013-10-01

Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT). A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis. The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48-0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49-0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56-0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53-0.84) were inversely associated with the bilirubin grade in a dose-dependent manner. The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome.

PubMed

Lee, You-Bin; Lee, Seung-Eun; Jun, Ji Eun; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Kim, Jae Hyeon

2016-01-01

Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults. We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS. During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094-2.785) in men and 2.156 (95% CI 1.738-2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229-1.326) in men and 1.366 (95% CI 1.288-1.447) in women. Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development

Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome

PubMed Central

Lee, You-Bin; Lee, Seung-Eun; Jun, Ji Eun; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Kim, Jae Hyeon

2016-01-01

Aim Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults. Methods We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS. Results During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094–2.785) in men and 2.156 (95% CI 1.738–2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229–1.326) in men and 1.366 (95% CI 1.288–1.447) in women. Conclusions Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might

Association between bilirubin and mode of death in severe systolic heart failure.

PubMed

Wu, Audrey H; Levy, Wayne C; Welch, Kathleen B; Neuberg, Gerald W; O'Connor, Christopher M; Carson, Peter E; Miller, Alan B; Ghali, Jalal K

2013-04-15

The bilirubin level has been associated with worse outcomes, but it has not been studied as a predictor for the mode of death in patients with systolic heart failure. The Prospective Randomized Amlodipine Evaluation Study (PRAISE) cohort (including New York Heart Association class IIIB-IV patients with left ventricular ejection fraction <30%, n = 1,135) was analyzed, divided by bilirubin level: ≤0.6 mg/dl, group 1; >0.6 to 1.2 mg/dl, group 2; and >1.2 mg/dl, group 3. Multivariate Cox proportional hazards models were used to determine the association of bilirubin with the risk of sudden or pump failure death. Total bilirubin was entered as a base 2 log-transformed variable (log2 bilirubin), indicating doubling of the bilirubin level corresponding to each increase in variable value. The higher bilirubin groups had a lower ejection fraction (range 19% to 21%), sodium (range 138 to 139 mmol/L), and systolic blood pressure (range 111 to 120 mm Hg), a greater heart rate (range 79 to 81 beats/min), and greater diuretic dosages (range 86 to 110 furosemide-equivalent total daily dose in mg). The overall survival rates declined with increasing bilirubin (24.3, 31.3, and 44.3 deaths per 100 person-years, respectively, for groups 1, 2, and 3). Although a positive relation was seen between log2 bilirubin and both pump failure risk and sudden death risk, the relation in multivariate modeling was significant only for pump failure mortality (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82, p = 0.0004), not for sudden death mortality (hazard ratio 1.21, 95% confidence interval 0.98 to 1.49, p = 0.08). In conclusion, an increasing bilirubin level was significantly associated with the risk of pump failure death but not for sudden death in patients with severe systolic heart failure. Copyright © 2013 Elsevier Inc. All rights reserved.

Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema.

PubMed

Wei, Jingjing; Zhao, Hui; Fan, Guoquan; Li, Jianqiang

2015-09-18

Cigarette smoking is a significant risk factor for emphysema, which is characterized by airway inflammation and oxidative damage. To assess the capacity of bilirubin to protect against smoke-induced emphysema. Smoking status and bilirubin levels were recorded in 58 patients with chronic obstructive pulmonary diseases (COPD) and 71 non-COPD participants. The impact of smoking on serum bilirubin levels and exogenous bilirubin (20 mg/kg/day) on pulmonary injury was assessed in a rat model of smoking-induced emphysema. At sacrifice lung histology, airway leukocyte accumulation and cytokine and chemokine levels in serum, bronchoalveolar lavage fluid (BALF) and lung were analyzed. Oxidative lipid damage and anti-oxidative components was assessed by measuring malondialdehyde, superoxide dismutase (SOD) activity and glutathione. Total serum bilirubin levels were lower in smokers with or without COPD than non-smoking patients without COPD (P < 0.05). Indirect serum bilirubin levels were lower in COPD patients than patients without COPD (P < 0.05). In rats, cigarette smoke reduced serum total and indirect bilirubin levels. Administration of bilirubin reduced mean linear intercept and mean alveoli area, increased mean alveoli number, reduced macrophage, neutrophil and TNF-α content of BALF, and increased BALF and serum IL-10 level, but lowered local and systemic CCL2, CXCL2, CXCL8 and IL-17 levels. Bilirubin suppressed the smoke-induced systemic and regional oxidative lipid damage associated with increased SOD activity. Bilirubin attenuated smoking-induced pulmonary injury by suppressing inflammatory cell recruitment and pro-inflammatory cytokine secretion, increasing anti-inflammatory cytokine levels, and anti-oxidant SOD activity in a rat model of smoke-induced emphysema. Copyright © 2015. Published by Elsevier Inc.

Serum Bilirubin and Their Association With C-Reactive Protein in Patients With Migraine.

PubMed

Peng, You-Fan; Xie, Li-Qiu; Xiang, Yang; Xu, Gui-Dan

2016-11-01

Increased levels of C-reactive protein (CRP) have been considered as a marker in assessing neurogenic inflammation of migraine patients. An inverse relationship between serum bilirubin and CRP has been observed in various diseases. Therefore, we analyzed serum bilirubin levels in migraine patients, and investigated the relationship between serum bilirubin and CRP in migraineurs. A total of 86 newly diagnosed migraine patients were consecutively recruited to this study. Significantly lower median serum total bilirubin, conjugated bilirubin (CB) and unconjugated bilirubin were found in patients with migraine than healthy controls, and the levels of CRP were significantly higher in migraine patients than healthy controls. A negative correlation between CRP and CB was observed in patients with migraine (r = -0.255, P = 0.018). In a multiple linear regression model, the concentrations of CRP remained negatively correlated with CB. Our study demonstrates that serum bilirubin concentrations are decreased in migraineurs, and CB levels were found to be positively correlated with CRP in migraine patents. However, larger cross-sectional and prospective studies are needed to establish whether serum bilirubin may be a useful biomarker for assessing neurogenic inflammation in migraine patients and eventually guiding the therapy. © 2016 Wiley Periodicals, Inc.

Posterior reversible encephalopathy syndrome (PRES) after granulocyte-colony stimulating factor (G-CSF) therapy: a report of 2 cases.

PubMed

Stübgen, Joerg-Patrick

2012-10-15

Two patients with recurrent lymphoma developed an acute, transient encephalopathy following administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF), filgrastim, in anticipation of leukapheresis for hematopoietic stem cell transplantation. Head magnetic resonance imaging showed evidence of blood-brain barrier (BBB) breakdown, compatible with posterior reversible encephalopathy syndrome (PRES). The proposed pathogenesis of PRES was rhG-CSF-induced neutrophil mobilization and activation with the release of inflammatory mediators, resulting in transient alteration of barrier permeability and capillary leakage. Copyright © 2012 Elsevier B.V. All rights reserved.

Bilirubin-a potential marker of drug exposure in atazanavir-based antiretroviral therapy.

PubMed

Rekić, Dinko; Clewe, Oskar; Röshammar, Daniel; Flamholc, Leo; Sönnerborg, Anders; Ormaasen, Vidar; Gisslén, Magnus; Abelö, Angela; Ashton, Michael

2011-12-01

The objective of this work was to examine the atazanavir-bilirubin relationship using a population-based approach and to assess the possible application of bilirubin as a readily available marker of atazanavir exposure. A model of atazanavir exposure and its concentration-dependent effect on bilirubin levels was developed based on 200 atazanavir and 361 bilirubin samples from 82 patients receiving atazanavir in the NORTHIV trial. The pharmacokinetics was adequately described by a one-compartment model with first-order absorption and lag-time. The maximum inhibition of bilirubin elimination rate constant (I(max)) was estimated at 91% (95% CI, 87-94) and the atazanavir concentration resulting in half of I(max) (IC50) was 0.30 μmol/L (95% CI, 0.24-0.37). At an atazanavir/ritonavir dose of 300/100 mg given once daily, the bilirubin half-life was on average increased from 1.6 to 8.1 h. A nomogram, which can be used to indicate suboptimal atazanavir exposure and non-adherence, was constructed based on model simulations.

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.

Involuntary movements and coma as the prognostic marker for acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Lee, Sooyoung; Sanefuji, Masafumi; Torio, Michiko; Kaku, Noriyuki; Ichimiya, Yuko; Mizuguchi, Soichi; Baba, Haruhisa; Sakai, Yasunari; Ishizaki, Yoshito; Torisu, Hiroyuki; Kira, Ryutaro; Hara, Toshiro; Ohga, Shouichi

2016-11-15

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) occurs in children associated with infection. It is characterized by a prolonged febrile seizure in the first phase, and a cluster of seizures, deterioration of consciousness and the white matter lesions with reduced diffusion in the second phase. The patients often have severe neurological sequelae, but the prognostic indicators remain unknown. The present study aimed to clarify the characteristics of AESD patients who subsequently exhibited severe neurological sequelae. We retrospectively analyzed the clinical and laboratory findings along with the brain imaging in patients who had severe (n=8) and non-severe neurodevelopmental outcomes (n=12). Severe group more frequently showed coma (p=0.014) or involuntary movements including dystonia and oral dyskinesia (p=0.018) before the second phase than non-severe group. Severe group exhibited higher levels of serum alanine aminotransferase than non-severe group (p=0.001). Quantitatively assessed MRI in the second phase revealed that severe group had more extensive lesions than non-severe group, in the anterior (p=0.015) and posterior parts (p=0.011) of the cerebrum and basal ganglia (p=0.020). Early appearing involuntary movements or coma might account for the extension of acute brain lesions and the poor neurological outcomes in AESD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute Liver Failure in Children: The First 348 Patients in The Pediatric Acute Liver Failure Study Group

PubMed Central

Squires, Robert H.; Shneider, Benjamin L.; Bucuvalas, John; Alonso, Estella; Sokol, Ronald J.; Narkewicz, Michael R.; Dhawan, Anil; Rosenthal, Philip; Rodriguez-Baez, Norberto; Murray, Karen F.; Horslen, Simon; Martin, Martin G.; Lopez, M. James; Soriano, Humberto; McGuire, Brendan M.; Jonas, Maureen M.; Yazigi, Nada; Shepherd, Ross W.; Schwarz, Kathleen; Lobritto, Steven; Thomas, Daniel W.; Lavine, Joel E.; Karpen, Saul; Ng, Vicky; Kelly, Deirdre; Simonds, Nancy; Hynan, Linda S.

2008-01-01

Objectives To determine short-term outcome for children with acute liver failure (ALF) as it relates to etiology, clinical status, patient demographics and to determine prognostic factors. Study design A prospective, multi-center case study collecting demographic, clinical, laboratory and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and INR remained ≥ 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures three weeks after study entry were death, death after transplant, alive with native liver, alive with transplanted organ. Results The etiology of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-APAP drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never developed clinical encephalopathy. Conclusions Etiologies of ALF in children differ from adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation. PMID:16737880

IN VITRO CHEMO-PREVENTATIVE ACTIVITY OF STRELITZIA NICOLAI ARIL EXTRACT CONTAINING BILIRUBIN.

PubMed

Dwarka, Depika; Thaver, Veneesha; Naidu, Mickey; Koorbanally, Neil A; Baijnath, And Himansu

2017-01-01

The discovery of the only animal pigment, bilirubin, in the plant Strelitzia nicolai has triggered a vast number of questions regarding bilirubin's formation and its role in the human body. Recent studies have confirmed that bilirubin at certain levels have many medical benefits. Various case studies have revealed that bilirubin is a potent antioxidant. Cervical cancer is one of South Africa's largest womens' health crises. It is estimated that it affects one out of 41 South African women and kills approximately 8 women in the country every day. Thus, the aim of this study was to investigate if the aril extract of Strelitzia nicolai (Regel and Körn.) containing bilirubin possesses anti-cancer activity and to determine its effect on the induction of apoptosis. The DPPH activity was firstly used to determine the antioxidant effect of the extract. Thereafter, the cytotoxic effect was tested using the XTT assay. Apoptosis was confirmed and quantified using the Annexin V-PE kit and the morphology was studied using acridine orange and ethidium bromide. The aril extract decreased cell viability by 52% and induced apoptosis in HeLa cells; as shown by the Annexin V-PE Apoptosis detection kit and morphological studies with acridine orange/ethidium bromide staining. The activity of the extract as a potent antioxidant was immensely enhanced as compared to the bilirubin standard. These results suggest that S. nicolai aril extract containing bilirubin works synergistically as opposed to bilirubin on its own. Furthermore, this extract might be a good candidate for the therapeutic intervention of cervical cancer.

Contributory factors and potentially avoidable neonatal encephalopathy associated with perinatal asphyxia.

PubMed

Sadler, Lynn C; Farquhar, Cynthia M; Masson, Vicki L; Battin, Malcolm R

2016-06-01

The recently published monograph, Neonatal encephalopathy and neurologic outcome, from the American College of Obstetricians and Gynecologists calls for a root cause analysis to identify components of care that contributed to cases of neonatal encephalopathy to design better practices, surveillance mechanisms, and systems. All cases of infants born in New Zealand with moderate and severe neonatal encephalopathy were reported to the New Zealand Perinatal and Maternal Mortality Review Committee from 2010. A national clinical review of these individual cases has not previously been undertaken. The objective of the study was to undertake a multidisciplinary structured review of all cases of neonatal encephalopathy that arose following the onset of labor in the absence of acute peripartum events in 2010-2011 to determine the frequency of contributory factors, the proportion of potentially avoidable morbidity and mortality and to identify themes for quality improvement. National identification of, and collection of clinical records on, cases of moderate or severe neonatal encephalopathy occurring after the onset of labor in the absence of an acute peripartum event, excluding those with normal gases and Apgar scores at 1 minute, among all cases of moderate and severe neonatal encephalopathy at term in New Zealand in 2010-2011 was undertaken. Cases were included if they had abnormal gases as defined by any of pH of ≤ 7.2, base excess of ≤ -10, or lactate of ≥ 6 or if there were no cord gases, an Apgar score at 1 minute of ≤ 7. A clinical case review was undertaken by a multidisciplinary team using a structured tool to record contributory factors (organization and/or management, personnel, and barriers to access and/or engagement with care), potentially avoidable morbidity and mortality and to identify themes to guide quality improvement. Eighty-three babies fulfilled the inclusion criteria for the review, 56 moderate (67%) and 27 severe (33%), 21 (25%) of whom were

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

USDA-ARS?s Scientific Manuscript database

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...

Elevated thyroid peroxidase antibodies with encephalopathy in MELAS syndrome.

PubMed

Chan, Derrick W S; Lim, C C Tchoyoson; Tay, Stacey K H; Choong, Chew-Thye; Phuah, Huan Kee

2007-06-01

Both the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) and Hashimoto's encephalopathy can present with nonspecific encephalopathy. Hashimoto's encephalopathy is an association of steroid-responsive encephalopathy with elevated thyroid peroxidase antibodies. Steroid-responsive encephalopathy, however, is not characteristic of the MELAS syndrome, which typically presents with stroke-like episodes and lactic acidosis in cerebrospinal fluid and blood. Here, a patient is described with goiter, recurrent encephalopathy and elevated thyroid peroxidase antibodies who apparently responded to steroid therapy; however, magnetic resonance imaging was atypical for Hashimoto's encephalopathy, and she was diagnosed with MELAS syndrome. This syndrome can present with apparent steroid-responsive encephalopathy and elevated thyroid peroxidase antibodies, mimicking Hashimoto's encephalopathy, and should be suspected if lactic acidosis is present and typical features are detected on magnetic resonance imaging.

[Icterus of the newborn caused by indirect bilirubin--recent progress].

PubMed

Hervei, Sarolta

2004-06-13

Recently a big shift has taken place in the judgment and treatment of jaundice in newborn, caused by increased unconjugated bilirubin level. New techniques evolved for assessing the prognosis of developing jaundice. An important major discovery is the antioxidant effect of bilirubin. We have a broader range of knowledge concerning the mechanism of bilirubin toxicity and for judging the chance of developing kernicterus. The prevention techniques do not stop at prohibiting anti-D immunisation but go on to preventing hydrops foetalis, the life-threatening form of haemolytic disease. There are data about the complications of phototherapy and EPO treatment for prolonged anaemia.

Bilirubin Modulates Acetylcholine Receptors In Rat Superior Cervical Ganglionic Neurons In a Bidirectional Manner

PubMed Central

Zhang, Chengmi; Wang, Zhenmeng; Dong, Jing; Pan, Ruirui; Qiu, Haibo; Zhang, Jinmin; Zhang, Peng; Zheng, Jijian; Yu, Weifeng

2014-01-01

Autonomic dysfunction as a partial contributing factor to cardiovascular instability in jaundiced patients is often associated with increased serum bilirubin levels. Whether increased serum bilirubin levels could directly inhibit sympathetic ganglion transmission by blocking neuronal nicotinic acetylcholine receptors (nAChRs) remains to be elucidated. Conventional patch-clamp recordings were used to study the effect of bilirubin on nAChRs currents from enzymatically dissociated rat superior cervical ganglia (SCG) neurons. The results showed that low concnetrations (0.5 and 2 μM) of bilirubin enhanced the peak ACh-evoked currents, while high concentrations (3 to 5.5 µM) of bilirubin suppressed the currents with an IC50 of 4 ± 0.5 μM. In addition, bilirubin decreased the extent of desensitization of nAChRs in a concentration-dependent manner. This inhibitory effect of bilirubin on nAChRs channel currents was non-competitive and voltage independent. Bilirubin partly improved the inhibitory effect of forskolin on ACh-induced currents without affecting the action of H-89. These data suggest that the dual effects of enhancement and suppression of bilirubin on nAChR function may be ascribed to the action mechanism of positive allosteric modulation and direct blockade. Thus, suppression of sympathetic ganglionic transmission through postganglionic nAChRs inhibition may partially contribute to the adverse cardiovascular effects in jaundiced patients. PMID:25503810

Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro.

PubMed

Tang, Yinhe; Zhang, Qiyu; Zhu, Yefan; Chen, Gang; Yu, Fuxiang

2017-04-01

Hepatic stellate cell (HSC) activation serves a key role in liver fibrosis, and is associated with chronic liver diseases. Bilirubin, a product of heme degradation, has been demonstrated to have antioxidant properties. The present study investigated the effects of physiological concentrations of bilirubin on rat HSC activation. Rat HSCs were isolated and cultured for several generations to induce activation. The activated HSCs were subsequently treated with 0, 1, 10 or 20 mg/l bilirubin and assayed for parameters of cell activation. As the bilirubin concentration increased, HSCs demonstrated reduced production of reactive oxygen species, reduced protein expression levels of α‑smooth muscle actin, a decreased mRNA expression ratio of tissue inhibitor of matrix metalloproteinase‑1/matrix metalloproteinase‑2, decreased proliferation and increased apoptosis. In conclusion, elevated bilirubin levels, within its physiological concentration range, appeared to inhibit HSC activation. These findings suggested a potential role for bilirubin in the treatment of fibrosis that requires further investigation.

Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

PubMed

Park, Sehoon; Kim, Do Hyoung; Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

2017-01-01

Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

Predictors of poor outcomes in patients with wild mushroom-induced acute liver injury.

PubMed

Kim, Taerim; Lee, Danbi; Lee, Jae Ho; Lee, Yoon-Seon; Oh, Bum Jin; Lim, Kyoung Soo; Kim, Won Young

2017-02-21

To identify early predictive markers of poor outcomes in patients with acute liver injury from wild mushroom intoxication. This observational, retrospective record review involved adults aged ≥ 18 years admitted to emergency department with mushroom intoxication from January 2005 to December 2015. The diagnosis of mushroom intoxication was based on the following: (1) a positive history of recent wild mushroom intake (either raw or cooked); (2) the onset of gastrointestinal symptoms, such as watery diarrhea, vomiting, and/or abdominal pain, after ingestion; and (3) the exclusion of other possible causes of acute liver injury. Acute liver injury was defined by a > 5-fold elevation of liver enzymes or moderate coagulopathy [international normalized ratio (INR) > 2.0]. Clinical and laboratory findings were compared in survivors and non-survivors. Of 93 patients with mushroom intoxication, 23, 11 men (47.8%) and 12 women (52.2%), of median age 61 years, developed acute liver injury. The overall in-hospital mortality rate was 43.5% (10/23). Among the laboratory variables, mean serum alkaline phosphatase (73.38 ± 10.89 mg/dL vs 180.40 ± 65.39 mg/dL, P < 0.01), total bilirubin (2.312 ± 1.16 mg/dL vs 7.16 ± 2.94 mg/dL, P < 0.01) concentrations and indirect/direct bilirubin (2.45 ± 1.39 mg/dL vs 0.99 ± 0.45 mg/dL, P < 0.01) ratio as well as prothrombin time (1.88 ± 0.83 mg/dL vs 10.43 ± 4.81 mg/dL, P < 0.01), and activated partial thromboplastin time (aPTT; 32.48 ± 7.64 s vs 72.58 ± 41.29 s, P = 0.01), were significantly higher in non-survivors than in survivors. Logistic regression analysis showed that total bilirubin concentration (OR = 3.58, 95%CI: 1.25-10.22), indirect/direct bilirubin ratio (OR = 0.14, 95%CI: 0.02-0.94) and aPTT (OR = 1.30, 95%CI: 1.04-1.63) were significantly associated with mortality. All patients with total bilirubin > 5 mg/dL or aPTT > 50 s on day 3 died. Monitoring of bilirubin concentrations and aPTT may help in predicting clinical

Posterior reversible encephalopathy syndrome in chronic alcoholism with acute psychiatric symptoms.

PubMed

Kimura, Ryo; Yanagida, Makoto; Kugo, Aki; Taguchi, Satoki; Matsunaga, Hidenori

2010-01-01

To highlight the association between posterior reversible encephalopathy syndrome (PRES) and chronic alcoholism. We present a case report, a review of the literature and a discussion. We report on the case of a 51-year-old man with chronic alcoholism, who suddenly developed visual disturbance and confusion. Magnetic resonance imaging (MRI) on admission demonstrated abnormal findings. However, clinical symptoms and imaging promptly improved, indicating the diagnosis of PRES. PRES should be considered when making a diagnosis for disturbed consciousness in alcoholic patients. Copyright 2010 Elsevier Inc. All rights reserved.

Bilirubin levels and phototherapy use before and after neonatal red blood cell transfusions.

PubMed

Carroll, Patrick D; Christensen, Robert D; Baer, Vickie L; Sheffield, Mark J; Gerday, Erick; Ilstrup, Sarah J

2016-11-01

Our previous retrospective study suggested that red blood cell (RBC) transfusion of preterm neonates can be associated with an increase in bilirubin, but this has not been tested prospectively. We studied neonates before and after RBC transfusions, recording serial bilirubin levels and whether they qualified for phototherapy. Because lysed RBCs release plasma-free hemoglobin (Hb), a precursor to bilirubin, we also measured plasma free Hb and bilirubin from the donor blood. We studied 50 transfusions given to 39 neonates. Gestation ages of transfused neonates, at birth, were 26 (24-29) weeks (median [interquartile range]); birthweights were 750 (620-1070) g. The study transfusion was given on Day of Life 9.9 (3.4-19.2). In 20% (10/50) phototherapy was being administered at the beginning of and during the transfusion. In these patients neither the 4- to 6- nor the 24- to 36-hour-posttransfusion bilirubin levels were significantly higher than before transfusion. However, in 30% of the others (12/40) phototherapy was started (or restarted) after the transfusion and 15% had a posttransfusion bilirubin increase of at least 2.5 mg/dL. These neonates received donor blood with a higher plasma-free Hb (p < 0.05). Neonates commonly qualify for phototherapy after transfusion. A minority (15% in this series) have a posttransfusion bilirubin increase of at least 2.5 mg/dL. We speculate that neonates qualifying for a RBC transfusion, who are judged to be at high risk for bilirubin-induced neurotoxicity, might benefit from checking their serum bilirubin level after the transfusion and providing donor blood with low plasma-free Hb levels. © 2016 AABB.

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: New observations with potential therapy

PubMed Central

Brusilow, Saul W; Cooper, Arthur J.L.

2011-01-01

Objective Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure (ALF), is a contributing factor – the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Design Case report. Setting Johns Hopkins Hospital. Patient A 22-year old white female who, 36 hours prior to admission, ingested 15 grams of acetaminophen was admitted to the Johns Hopkins Hospital. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hours after ingestion when she became confused, irritable and agitated. Interventions She was intubated, ventilated and placed on lactulose. Shortly thereafter she was non-communicative, unresponsive to painful stimuli and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure (ICP) was made. She improved very slowly until 180 hours after ingestion when she moved all extremities. She woke up shortly thereafter. Measurements and main results Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in ALF the patient’s plasma ammonia peaked when she exhibited no obvious neurological deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurological status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high, but began to normalize several hours after plasma ammonia had returned to normal. The

Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by modulating function of signal transducer and activator of transcription factors

PubMed Central

Castro-García, Flor P; Corral-Jara, Karla F; Escobedo-Melendez, Griselda; Sandoval-Hernandez, Monserrat A; Rosenstein, Yvonne; Roman, Sonia; Panduro, Arturo; Fierro, Nora A

2014-01-01

Hepatitis A virus (HAV) infection is the major cause of acute liver failure in paediatric patients. The clinical spectrum of infection is variable, and liver injury is determined by altered hepatic enzyme function and bilirubin concentration. We recently reported differences in cytokine profiles between distinct HAV-induced clinical courses, and bilirubin has been recognized as a potential immune-modulator. However, how bilirubin may affect cytokine profiles underlying the variability in the course of infection has not been determined. Herein, we used a transcription factor (TF) binding site identification approach to retrospectively analyse cytokine expression in HAV-infected children and to predict the entire set of TFs associated with the expression of specific cytokine profiles. The results suggested that modulation of the activity of signal transducers and activators of transcription proteins (STATs) may play a central role during HAV infection. This led us to compare the degree of STAT phosphorylation in peripheral blood lymphoid cells (PBLCs) from paediatric patients with distinct levels of conjugated bilirubin (CB). Low CB levels in sera were associated with increased STAT-1 and STAT-5 phosphorylation. A positive correlation was observed between the serum interleukin-6 (IL-6) content and CB values, whereas higher levels of CB correlated with reduced serum IL-8 values and with a reduction in the proportion of PBLCs positive for STAT-5 phosphorylation. When CB was used to stimulate patients’ PBLCs in vitro, the levels of IL-6 and tumour necrosis factor-α were increased. The data showed that bilirubin plays a role in STAT function and affects cytokine profile expression during HAV infection. PMID:24943111

Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by modulating function of signal transducer and activator of transcription factors.

PubMed

Castro-García, Flor P; Corral-Jara, Karla F; Escobedo-Melendez, Griselda; Sandoval-Hernandez, Monserrat A; Rosenstein, Yvonne; Roman, Sonia; Panduro, Arturo; Fierro, Nora A

2014-12-01

Hepatitis A virus (HAV) infection is the major cause of acute liver failure in paediatric patients. The clinical spectrum of infection is variable, and liver injury is determined by altered hepatic enzyme function and bilirubin concentration. We recently reported differences in cytokine profiles between distinct HAV-induced clinical courses, and bilirubin has been recognized as a potential immune-modulator. However, how bilirubin may affect cytokine profiles underlying the variability in the course of infection has not been determined. Herein, we used a transcription factor (TF) binding site identification approach to retrospectively analyse cytokine expression in HAV-infected children and to predict the entire set of TFs associated with the expression of specific cytokine profiles. The results suggested that modulation of the activity of signal transducers and activators of transcription proteins (STATs) may play a central role during HAV infection. This led us to compare the degree of STAT phosphorylation in peripheral blood lymphoid cells (PBLCs) from paediatric patients with distinct levels of conjugated bilirubin (CB). Low CB levels in sera were associated with increased STAT-1 and STAT-5 phosphorylation. A positive correlation was observed between the serum interleukin-6 (IL-6) content and CB values, whereas higher levels of CB correlated with reduced serum IL-8 values and with a reduction in the proportion of PBLCs positive for STAT-5 phosphorylation. When CB was used to stimulate patients' PBLCs in vitro, the levels of IL-6 and tumour necrosis factor-α were increased. The data showed that bilirubin plays a role in STAT function and affects cytokine profile expression during HAV infection. © 2014 John Wiley & Sons Ltd.

Acute aluminum encephalopathy in a dialysis center caused by a cement mortar water distribution pipe.

PubMed

Berend, K; van der Voet, G; Boer, W H

2001-02-01

In Curaçao, distilled seawater from the water plant was used without further purification for hemodialysis for several decades. A new distribution pipe supplying water to a dialysis center on the island was installed in May 1996. To protect it from corrosion, this pipe was lined on the inside with a cement mortar. Because of the aggressiveness of the distilled water, calcium and aluminum (Al) leached from the cement mortar into the water used to prepare dialysate. This caused a possible hard water syndrome and definite acute Al intoxication. We reviewed clinical details and outcome at follow-up, and arranged laboratory and toxicological studies of serum and hemodialysis water. Of the 27 patients who had a similar exposure ( approximately 60 hours) to the contaminated dialysate, 10 died from acute Al encephalopathy, whereas 17 patients had no or only minor symptoms and survived. The nonsurvivors were older (64 +/- 3 years vs. 52 +/- 2 years, P < 0.01) and had a lower body weight (57.5 +/- 5.9 kg vs. 86.5 +/- 4.1 kg, P < 0.01) and lower serum albumin concentrations (33 +/- 1 vs. 36 +/- 1 g/L, P < 0.01). Anuria tended to be more common in the nonsurvivors (8 out of 10 vs. 8 out of 17, P> 0.05). Serum Al concentrations, available in seven nonsurvivors, were significantly higher than in the survivors (808 +/- 127 vs. 255 +/- 25 microg/L, P < 0.01). The water distribution pipe was lined with a cement mortar that was probably inappropriate for transporting drinking water. Water distribution facilities as well as the dialysis community should be aware of the possibility of Al leaching from cemented water distribution pipes. Similar Al loads appear to induce a more severe intoxication in malnourished, older patients with smaller Al distribution volumes and anuria.

Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis

PubMed Central

Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

2017-01-01

Background Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. Methods We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. Results As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8–1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19–0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). Conclusions Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression. PMID:28225832

NEW INSIGHTS INTO THE PRESENCE OF BILIRUBIN IN A PLANT SPECIES STRELITZIA NICOLAI (STRELITZIACEAE)

PubMed Central

Dwarka, Depika; Thaver, Veneesha; Naidu, Mickey; Baijnath, Himansu

2017-01-01

Background: The fortuitous discovery of an animal pigment bilirubin found in the plant Strelitzia nicolai has opened an enormous number of questions regarding bilirubin’s formation and its ultimate function in the human body. Materials and Methods: A methodical review of bilirubin in humans and animals was carried out, information was gathered using published scientific journals, books and conference proceedings. Articles based on case studies of elevated levels of bilirubin were analysed thoroughly. Results: Even though for numerous years bilirubin was assumed to be merely a desecrate product of the heme catabolic pathway by greatest, and a likely lethal compound at worst; statistics from the last few decades clearly shows that placidly high serum bilirubin levels are robustly related to have abundant beneficial effects on the human body. Conclusion: This study reveals new insights into the presence of the only animal pigment found in Strelitzia nicolai arils, the potential advantages of bilirubin found in a plant and its therapeutic value indications. This review hopes to resuscitate researchers’ credence regarding bilirubin as a toxic compound. PMID:28573242

Studies on the interference by haemoglobin in the determination of bilirubin.

PubMed

van der Woerd-de Lange, J A; Guder, W G; Schleicher, E; Paetzke, I; Schleithoff, M; Wieland, O H

1983-07-01

Haemoglobin interference in the determination of bilirubin was compared in 7 different methods using the Jendrassik-Grof procedure, the Jendrassik-Grof-Nosslin modification, and the more recent procedures using nitrophenyldiazonium, 2,5-dichlorophenyldiazonium, 2,4-dichloraniline, and a direct reading method. To a variable degree, haemoglobin decreased the apparent absorption of the reaction product in all procedures. The extent of this decrease depended on the reagent used, the wavelength, incubation time, bilirubin concentration and the type of blank used. In an attempt to elucidate the mechanism of interference, haemoglobin was found to destroy the bilirubin diazo-compound whereas haemoglobin was ineffective. Likewise, storage of haemolytic samples for several days led to a disappearance of haemoglobin. H2O2, which had no effect in the absence of haemoglobin, potentiated the action of haemoglobin on diazobilirubin coupling. From our observations it can be concluded that haemoglobin disturbs the diazo-bilirubin reaction by a dual mechanism. H2O2, formed from oxyhaemoglobin by autoxidation, destroys the diazo bilirubin colour. In accordance with this explanation, potassium iodide stabilized the diazo compound against the peroxidative effect of oxyhaemoglobin; stabilization was not effective with superoxide dismutase, mannitol or ascorbate.

Possible roles of bilirubin and breast milk in protection against retinopathy of prematurity.

PubMed

Kao, Joanna S; Dawson, Jeffrey D; Murray, Jeffrey C; Dagle, John M; Berends, Susan K; Gillen, Susan B; Bell, Edward F

2011-03-01

To explore the association of serum bilirubin level and breast milk feeding with retinopathy of prematurity (ROP) in preterm infants. We conducted a case-control study to examine the independent and combined effects of serum bilirubin and breast milk feeding on ROP risk in infants <32 weeks gestation or with birth weight <1500 g. Cases (66 infants with ROP) were matched with controls (66 infants without ROP) based on factors known to affect ROP risk. When analysed using the paired t-test, the peak bilirubin levels were lower in ROP cases than in controls (mean 7.2 vs. 7.9 mg/dL; p = 0.045). Using conditional logistic regression, we found a negative association between highest serum bilirubin level and risk of ROP (OR = 0.82 per 1-mg/dL change in bilirubin; p = 0.06). There was no significant association between breast milk feeding and risk of ROP. Bilirubin may help to protect preterm infants against ROP. © 2010 The Author(s)/Acta Paediatrica © 2010 Foundation Acta Paediatrica.

Total antioxidant capacity in children with acute appendicitis.

PubMed

Kaya, M; Boleken, M E; Kanmaz, T; Erel, O; Yucesan, S

2006-02-01

This study aimed to investigate antioxidant capacity by using a novel automated method in children with acute appendicitis. Blood samples were obtained from consecutive patients with acute appendicitis (appendicitis group, n = 12) and acute abdominal pain due to non surgical disease (non-appendicitis group, n = 11), and from patients with inguinal hernia (healthy group, n = 12) as the control group. At admission, total antioxidant capacity (TAC) levels of plasma were evaluated in all patients by a method recently developed by Erel. Four other major individual plasma antioxidant components, the levels of total protein, albumin, uric acid and bilirubin, were also evaluated. Total antioxidant capacity in patients with acute appendicitis was statistically compared with the two other groups. While the TAC level in the appendicitis group was significantly greater than in the non-appendicitis group, no significant difference was found in healthy groups (p < 0.05, p > 0.05, 1.94 +/- 0.38, 1.40 +/- 0.36, and 1.99 +/- 0.35 respectively). Individual components of total antioxidant capacity, i.e. total protein, albumin, uric acid and bilirubin concentrations, were also higher in the patients with acute appendicitis than those of the other two control groups. Our data show that children with acute appendicitis do not have deficient blood plasma antioxidant capacity. These results provide evidence that acute appendicitis results in more induction of antioxidative response than non-surgical diseases.

Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy.

PubMed

Tanaka, Shigeru; Ninomiya, Toshiharu; Masutani, Kosuke; Nagata, Masaharu; Tsuchimoto, Akihiro; Tsuruya, Kazuhiko; Kitazono, Takanari

2015-12-01

Serum bilirubin has been recognized as a novel endogenous antioxidant. The aim of our study was to evaluate the impact of serum bilirubin on kidney prognosis in IgA nephropathy (IgAN). We followed retrospectively 694 patients with IgAN diagnosed by renal biopsy between 1982 and 2010. The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazard model. Predictive performance between models with or without serum bilirubin was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Seventy-seven patients developed ESRD during the median 4.9 years of follow-up. Estimated glomerular filtration rate, proteinuria and histological severity were inversely related to bilirubin levels. In multivariate analysis, serum bilirubin was an independent risk factor for ESRD (hazard ratio for every 0.1 mg/dL decrease in serum bilirubin, 1.18; 95 % CI, 1.04-1.33). The incidence rate of ESRD decreased linearly with the increases in bilirubin levels (P for trend <0.01). When bilirubin was incorporated into a model with conventional ESRD risk factors, the NRI and IDI were 0.281 (P = 0.02) and 0.019 (P = 0.01), respectively. We demonstrated that lower bilirubin levels were significantly associated with higher risk of ESRD in IgAN. In addition, bilirubin provided incremental predictive value in the risk assessment for progression of IgAN beyond that provided by standard risk factors.

Transition from upbeat to downbeat nystagmus observed in a patient with Wernicke's encephalopathy.

PubMed

Suzuki, Yasuo; Matsuda, Taisuke; Washio, Noriaki; Ohtsuka, Kenji

2005-01-01

We report an unusual case of Wernicke's encephalopathy presenting with transient upbeat nystagmus that changed to a persistent downbeat nystagmus. A 27-year-old man presented with upbeat nystagmus. Three months earlier, he had been diagnosed with Wernicke's encephalopathy after fasting for a month. This diagnosis was supported by his symptoms (ataxia, a confused state). Clinical recovery followed thiamine therapy. His upbeat nystagmus had linear slow phases with average amplitude and frequency (+/-SD) during fixation straight ahead of 2.8 +/- 0.7 degrees and 4.6 +/- 2.2 Hz, respectively. Two months later, the primary position upbeat nystagmus had diminished and downbeat nystagmus (0.9 +/- 0.5 degrees and 3.2 +/- 0.7 Hz on average) for a 20 degrees downward gaze had developed. Then, 8 months later, he showed only downbeat nystagmus, which obeyed Alexander's law. His primary position downbeat nystagmus was completely suppressed by clonazepam, a gamma-aminobutyric acid (GABA) agonist. Owing to an underlying central vestibular imbalance, even after the recovery of acute neurological symptoms, Wernicke's encephalopathy can be complicated by persistent downbeat nystagmus, which can be treated by a GABA agonist.

Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers

PubMed Central

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

2014-01-01

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

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.

Constituents of Bile, Bilirubin and TUDCA, Protect Against Oxidative Stress-Induced Retinal Degeneration

PubMed Central

Oveson, Brian C.; Iwase, Takeshi; Hackett, Sean F.; Lee, Sun Young; Usui, Shinichi; Sedlak, Thomas W.; Snyder, Solomon H.; Campochiaro, Peter A.; Sung, Jennifer U.

2014-01-01

Two constituents of bile, bilirubin and tauroursodeoxycholic acid (TUDCA), have antioxidant activity. However, bilirubin can also cause damage to some neurons and glial cells, particularly immature neurons. In this study, we tested the effects of bilirubin and TUDCA in two models in which oxidative stress contributes to photoreceptor cell death, prolonged light exposure and rd10+/+ mice. In albino BALB/c mice, intraperitoneal (IP) injection of 5 mg/kg of bilirubin or 500 mg/kg of TUDCA prior to exposure to 5,000 lux of white light for 8 hours significantly reduced loss of rod and cone function assessed by electroretinograms (ERGs). Both treatments also reduced light-induced accumulation of superoxide radicals in the outer retina, rod cell death assessed by outer nuclear layer (ONL) thickness, and disruption of cone inner and outer segments. In rd10+/+ mice, IP injections of 5 or 50 mg/kg of bilirubin or 500 mg/kg of TUDCA every 3 days starting at postnatal day (P) 6, caused significant preservation of cone cell number and cone function at P50. Rods were not protected at P50, but both bilirubin and TUDCA provided modest preservation of ONL thickness and rod function at P30. These data suggest that correlation of serum bilirubin levels with rate of vision loss in patients with retinitis pigmentosa (RP) could provide a useful strategy to test the hypothesis that cones die from oxidative damage in patients with RP. If proof-of-concept is established, manipulation of bilirubin levels and administration of TUDCA could be tested in interventional trials. PMID:21054389

Genetics Home Reference: early infantile epileptic encephalopathy 1

MedlinePlus

... infantile epileptic encephalopathy 1 Early infantile epileptic encephalopathy 1 Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Early infantile epileptic encephalopathy 1 (EIEE1) is ...

Visual inspection versus spectrophotometry in detecting bilirubin in cerebrospinal fluid

PubMed Central

Linn, F; Voorbij, H; Rinkel, G; Algra, A; van Gijn, J

2005-01-01

Methods: Clinicians and students assessed CSF specimens with seven degrees of extinction between 0.00 and 0.09 at 450–460 nm as "yellow," "doubtful," or "colourless" after random presentation under standard conditions. The assessments were compared with spectrophotometry, with 0.05 being taken as the cut off level for the presence of bilirubin. Results were compared between the two groups and explored by means of receiver operating characteristic (ROC) curves. Results: All 51 clinicians and 50 of 51 students scored the tubes with extinction of 0.06 or higher as "yellow" or "doubtful." Tubes without any bilirubin were scored as "yellow" by three of the students only. The ROC curves confirmed that the diagnostic properties of the visual inspection versus spectrophotometry were slightly better for the clinicians than for the students. Conclusions: If CSF is considered colourless, the extinction of bilirubin is too low to be compatible with a diagnosis of recent subarachnoid haemorrhage. If CSF is not considered colourless, spectrophotometry should be carried out to determine the level of extinction of bilirubin. PMID:16170095

Clinical Characteristics of Transplant-associated Encephalopathy in Children.

PubMed

Lee, Yun Jeong; Yum, Mi Sun; Kim, Eun Hee; Kim, Min Jee; Kim, Kyung Mo; Im, Ho Joon; Kim, Young Hwue; Park, Young Seo; Ko, Tae Sung

2017-03-01

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0-491 days), 10 days after HT (1-296 days), 49.5 days after HSCT (9-1,405 days), and 39 days after LT (1-1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.

Clinical Characteristics of Transplant-associated Encephalopathy in Children

PubMed Central

2017-01-01

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0–491 days), 10 days after HT (1–296 days), 49.5 days after HSCT (9–1,405 days), and 39 days after LT (1–1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation. PMID:28145649

Bilirubin glucuronidation revisited: proper assay conditions to estimate enzyme kinetics with recombinant UGT1A1.

PubMed

Zhou, Jin; Tracy, Timothy S; Remmel, Rory P

2010-11-01

Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1-catalyzed bilirubin glucuronidation in vitro has become common practice. However, the instability of bilirubin and its glucuronides presents substantial technical challenges to conduct in vitro bilirubin glucuronidation assays. Furthermore, because bilirubin can be diglucuronidated through a sequential reaction, establishment of initial rate conditions can be problematic. To address these issues, a robust high-performance liquid chromatography assay to measure both bilirubin mono- and diglucuronide conjugates was developed, and the incubation conditions for bilirubin glucuronidation by human embryonic kidney 293-expressed UGT1A1 were carefully characterized. Our results indicated that bilirubin glucuronidation should be assessed at very low protein concentrations (0.05 mg/ml protein) and over a short incubation time (5 min) to assure initial rate conditions. Under these conditions, bilirubin total glucuronide formation exhibited a hyperbolic (Michaelis-Menten) kinetic profile with a K(m) of ∼0.2 μM. In addition, under these initial rate conditions, the relative proportions between the total monoglucuronide and the diglucuronide product were constant across the range of bilirubin concentration evaluated (0.05-2 μM), with the monoglucuronide being the predominant species (∼70%). In conclusion, establishment of appropriate incubation conditions (i.e., very low protein concentrations and short incubation times) is necessary to properly characterize the kinetics of bilirubin glucuronidation in a recombinant UGT1A1 system.

The correlation of serum bilirubin levels with disease activity in patients with rheumatoid arthritis.

PubMed

Peng, You-Fan; Wang, Jun-Li; Pan, Guo-Gang

2017-06-01

We investigated the relationship between serum bilirubin and disease activity in patients with rheumatoid arthritis (RA). We included a total of 173 consecutive RA patients without steroid treatment and 346 healthy subjects; the disease activity score in 28 joints (DAS28) was used to assess disease activity in patients with RA. Serum bilirubin concentrations were significantly lower in RA patients than in controls. Serum bilirubin was found to be negatively correlated with C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in patients with RA. There was a negative correlation between the serum bilirubin and DAS28 score (r=-0.331, P<0.001). Serum bilirubin was independently associated with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression analysis. Serum bilirubin concentrations are lower in patients with RA compared to controls and correlate with disease activity in patients with RA. Copyright © 2017. Published by Elsevier B.V.

Relationship between red blood cell distribution width, bilirubin, and clinical characteristics of patients with gastric cancer.

PubMed

Wei, T-T; Wang, L-L; Yin, J-R; Liu, Y-T; Qin, B-D; Li, J-Y; Yin, X; Zhou, L; Zhong, R-Q

2017-10-01

Red blood cell distribution width (RDW) and bilirubin have been proved to be prognostic factors for various types of cancer. However, their prognostic value in patients with gastric cancer (GC) remains largely unknown. To verify whether RDW and bilirubin are prognostic factors for patients with GC, we performed a cross-sectional study to analyze the relationship between RDW, bilirubin, and the clinical characteristics of patients with GC. Medical records of all newly diagnosed and pathologically proved patients with GC admitted to Changzheng Hospital between January 2016 and July 2016 were retrospectively reviewed. The relationship between RDW, bilirubin, and the clinical characteristics of patients with GC was analyzed. A total of 144 patients with GC were enrolled. Patients with GC had significantly higher RDW than healthy controls, even after adjusting for hemoglobin, while total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were significantly decreased. Furthermore, RDW and bilirubin were significantly correlated with tumor stage, as well as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Our study indicated that RDW and bilirubin could be potential prognostic factors for patients of GC. © 2017 John Wiley & Sons Ltd.

Validation of the peak bilirubin criterion for outcome after partial hepatectomy.

PubMed

van Mierlo, Kim M C; Lodewick, Toine M; Dhar, Dipok K; van Woerden, Victor; Kurstjens, Ralph; Schaap, Frank G; van Dam, Ronald M; Vyas, Soumil; Malagó, Massimo; Dejong, Cornelis H C; Olde Damink, Steven W M

2016-10-01

Postoperative liver failure (PLF) is a dreaded complication after partial hepatectomy. The peak bilirubin criterion (>7.0 mg/dL or ≥120 μmol/L) is used to define PLF. This study aimed to validate the peak bilirubin criterion as postoperative risk indicator for 90-day liver-related mortality. Characteristics of 956 consecutive patients who underwent partial hepatectomy at the Maastricht University Medical Centre or Royal Free London between 2005 and 2012 were analyzed by uni- and multivariable analyses with odds ratios (OR) and 95% confidence intervals (95%CI). Thirty-five patients (3.7%) met the postoperative peak bilirubin criterion at median day 19 with a median bilirubin level of 183 [121-588] μmol/L. Sensitivity and specificity for liver-related mortality after major hepatectomy were 41.2% and 94.6%, respectively. The positive predictive value was 22.6%. Predictors of liver-related mortality were the peak bilirubin criterion (p < 0.001, OR = 15.9 [95%CI 5.2-48.7]), moderate-severe steatosis and fibrosis (p = 0.013, OR = 8.5 [95%CI 1.6-46.6]), ASA 3-4 (p = 0.047, OR = 3.0 [95%CI 1.0-8.8]) and age (p = 0.044, OR = 1.1 [95%CI 1.0-1.1]). The peak bilirubin criterion has a low sensitivity and positive predictive value for 90-day liver-related mortality after major hepatectomy. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features

Higher direct bilirubin levels during mid-pregnancy are associated with lower risk of gestational diabetes mellitus.

PubMed

Liu, Chaoqun; Zhong, Chunrong; Zhou, Xuezhen; Chen, Renjuan; Wu, Jiangyue; Wang, Weiye; Li, Xiating; Ding, Huisi; Guo, Yanfang; Gao, Qin; Hu, Xingwen; Xiong, Guoping; Yang, Xuefeng; Hao, Liping; Xiao, Mei; Yang, Nianhong

2017-01-01

Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.

Serum bilirubin levels are inversely associated with PAI-1 and fibrinogen in Korean subjects.

PubMed

Cho, Hyun Sun; Lee, Sung Won; Kim, Eun Sook; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun

2016-01-01

Oxidative stress may contribute to atherosclerosis and increased activation of the coagulation pathway. Bilirubin may reduce activation of the hemostatic system to inhibit oxidative stress, which would explain its cardioprotective properties shown in many epidemiological studies. This study investigated the association of serum bilirubin with fibrinogen and plasminogen activator inhibitor-1 (PAI-1), respectively. A cross-sectional analysis was performed on 968 subjects (mean age, 56.0 ± 11.2 years; 61.1% men) undergoing a general health checkup. Serum biochemistry was analyzed including bilirubin subtypes, insulin resistance (using homeostasis model of assessment [HOMA]), C-reactive protein (CRP), fibrinogen, and PAI-1. Compared with subjects with a total bilirubin (TB) concentration of <10.0 μmol/L, those with a TB concentration of >17.1 μmol/L had a smaller waist circumference, a lower triglyceride level, a lower prevalence of metabolic syndrome, and decreased HOMA-IR and CRP levels. Correlation analysis revealed linear relationships of fibrinogen with TB and direct bilirubin (DB), whereas PAI-1 was correlated with DB. After adjustment for confounding factors, bilirubin levels were inversely associated with fibrinogen and PAI-1 levels, respectively. Multivariate regression models showed a negative linear relationship between all types of bilirubin and fibrinogen, whereas there was a significant linear relationship between PAI-1 and DB. High bilirubin concentrations were independently associated with low levels of fibrinogen and PAI-1, respectively. The association between TB and PAI-1 was confined to the highest TB concentration category whereas DB showed a linear association with PAI-1. Bilirubin may protect against the development of atherothrombosis by reducing the hemostatic response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

IN VITRO CHEMO-PREVENTATIVE ACTIVITY OF STRELITZIA NICOLAI ARIL EXTRACT CONTAINING BILIRUBIN

PubMed Central

Dwarka, Depika; Thaver, Veneesha; Naidu, Mickey; Koorbanally, Neil A; Baijnath, and Himansu

2017-01-01

Background: The discovery of the only animal pigment, bilirubin, in the plant Strelitzia nicolai has triggered a vast number of questions regarding bilirubin’s formation and its role in the human body. Recent studies have confirmed that bilirubin at certain levels have many medical benefits. Various case studies have revealed that bilirubin is a potent antioxidant. Cervical cancer is one of South Africa’s largest womens’ health crises. It is estimated that it affects one out of 41 South African women and kills approximately 8 women in the country every day. Thus, the aim of this study was to investigate if the aril extract of Strelitzia nicolai (Regel and Körn.) containing bilirubin possesses anti-cancer activity and to determine its effect on the induction of apoptosis. Materials and methods: The DPPH activity was firstly used to determine the antioxidant effect of the extract. Thereafter, the cytotoxic effect was tested using the XTT assay. Apoptosis was confirmed and quantified using the Annexin V-PE kit and the morphology was studied using acridine orange and ethidium bromide. Results: The aril extract decreased cell viability by 52% and induced apoptosis in HeLa cells; as shown by the Annexin V-PE Apoptosis detection kit and morphological studies with acridine orange/ethidium bromide staining. Conclusion: The activity of the extract as a potent antioxidant was immensely enhanced as compared to the bilirubin standard. These results suggest that S. nicolai aril extract containing bilirubin works synergistically as opposed to bilirubin on its own. Furthermore, this extract might be a good candidate for the therapeutic intervention of cervical cancer. PMID:28480426

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetics Home Reference: STXBP1 encephalopathy with epilepsy

MedlinePlus

... Conditions STXBP1 encephalopathy with epilepsy STXBP1 encephalopathy with epilepsy Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description STXBP1 encephalopathy with epilepsy is a condition characterized by recurrent seizures (epilepsy), ...

Highly Sensitive and Selective Sensing of Free Bilirubin Using Metal-Organic Frameworks-Based Energy Transfer Process.

PubMed

Du, Yaran; Li, Xiqian; Lv, Xueju; Jia, Qiong

2017-09-13

Free bilirubin, a key biomarker for jaundice, was detected with a newly designed fluorescent postsynthetically modified metal organic framework (MOF) (UIO-66-PSM) sensor. UiO-66-PSM was prepared based on the aldimine condensation reaction of UiO-66-NH 2 with 2,3,4-trihydroxybenzaldehyde. The fluorescence of UIO-66-PSM could be effectively quenched by free bilirubin via a fluorescent resonant energy transfer process, thus achieving its recognition of free bilirubin. It was the first attempt to design a MOF-based fluorescent probe for sensing free bilirubin. The probe exhibited fast response time, low detection limit, wide linear range, and high selectivity toward free bilirubin. The sensing system enabled the monitor of free bilirubin in real human serum. Hence, the reported free bilirubin sensing platform has potential applications for clinical diagnosis of jaundice.

Constitutive androstane receptor activation promotes bilirubin clearance in a murine model of alcoholic liver disease.

PubMed

Wang, Xiuyan; Zheng, Liyu; Wu, Jinming; Tang, Binbin; Zhang, Mengqin; Zhu, Debin; Lin, Xianfan

2017-06-01

Increased plasma levels of bilirubin have been reported in rat models and patients with alcoholic liver disease (ALD). The constitutive androstane receptor (CAR) is a known xenobiotic receptor, which induces the detoxification and transport of bilirubin. In the present study, the bilirubin transport regulatory mechanisms, and the role of CAR activation in hepatic and extrahepatic bilirubin clearance were investigated in a murine model of ALD. The mice were fed a Lieber-DeCarli ethanol diet or an isocaloric control diet for 4 weeks, followed by the administration of CAR agonists, 1,4-bis-[2‑(3,5-dichlorpyridyloxy)]benzene (TCPOBOP) and phenobarbital (PB), and their vehicles to examine the effect of the pharmacological activation of CAR on serum levels of bilirubin and on the bilirubin clearance pathway in ALD by serological survey, western blotting and reverse transcription‑quantitative polymerase chain reaction. The results showed that chronic ethanol ingestion impaired the nuclear translocation of CAR, which was accompanied by elevated serum levels of bilirubin, suppression of the expression of hepatic and renal organic anion transporting polypeptide (OATP) 1A1 and hepatic multidrug resistance‑associated protein 2 (MRP2), and induction of the expression of UDP-glucuronosyltransferase (UGT) 1A1. The activation of CAR by TCPOBOP and PB resulted in downregulation of the serum levels of bilirubin followed by selective upregulation of the expression levels of OATP1A1, OATP1A4, UGT1A1 and MRP2 in ALD. These results revealed the bilirubin transport regulatory mechanisms and highlighted the importance of CAR in modulating the bilirubin clearance pathway in the ALD mouse model.

Adult-onset of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presenting as acute meningoencephalitis: a case report.

PubMed

Hsu, Yu-Chuan; Yang, Fu-Chi; Perng, Cherng-Lih; Tso, An-Chen; Wong, Lee-Jun C; Hsu, Chang-Hung

2012-09-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Epileptic seizures are common features of both MELAS and meningoencephalitis and are typically treated with anticonvulsants. To provide the reader with a better understanding of MELAS and the adverse effects of valproic acid. A 47-year-old man with a history of diabetes, hearing loss, sinusitis, and otitis media was brought to our emergency department due to acute onset of fever, headache, generalized seizure, and agitation. Because acute meningoencephalitis was suspected, the patient was treated with antibiotics on an empirical basis. The seizure activity was aggravated by valproic acid and abated after its discontinuation. MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. Detailed history-taking and systematic review help emergency physicians differentiate MELAS from meningoencephalitis in patients with the common presentation of epileptic seizures. Use of valproic acid to treat epilepsy in patients suspected of having mitochondrial disease should be avoided. Underlying mitochondrial disease should be suspected if seizure activity worsens with valproic acid therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Bilirubin induces a calcium-dependent inhibition of multifunctional Ca2+/calmodulin-dependent kinase II activity in vitro.

PubMed

Churn, S B; DeLorenzo, R J; Shapiro, S M

1995-12-01

Excessive bilirubin levels in newborn infants result in long-term neurologic deficits that remain after bilirubin levels return to normal. Much of the observed neurologic deficits can be attributed to bilirubin-induced, delayed neuronal cell death. Inhibition of calcium/calmodulin-dependent kinase II (CaM kinase II) activity that precedes cell death is observed in conditions such as seizure activity, stroke, and glutamate excitotoxicity. Because neonatal bilirubin exposure results in neuronal loss in developing brain systems, we tested whether bilirubin exposure would induce an immediate inhibition of CaM activity, in vitro. P-81 filtration assay of basal and calcium-stimulated kinase activity was performed under standard kinase assay conditions. Bilirubin and/or albumin was added to the reaction vessels to determine the effect of these agents on kinase activity. Bilirubin exposure resulted in a concentration-dependent inhibition of CaM kinase II activity (IC50 = 16.78 microM). At concentrations above 50 microM, bilirubin exposure resulted in a 71 +/- 8% (mean +/- SD) inhibition of kinase activity (p < 0.001, t test, n = 10). Bilirubin exposure did not result in kinase inhibition if excessive bilirubin was removed by albumin binding before stimulation of kinase activity (106.9 +/- 9.6% control activity, n = 5). However, removal of bilirubin by binding with albumin after calcium addition did not restore kinase activity. (36.1 +/- 3.8% control activity, n = 5). Thus, once inhibition was observed, the activity could not be restored by addition of albumin. The data suggest that bilirubin exposure resulted in a calcium-dependent inhibition of CaM kinase II activity that, once induced, was not reversible by removing bilirubin by the addition of albumin. Because inhibition of CaM kinase II activity has been correlated with delayed neuronal cell death in many neuropathologic conditions, bilirubin-induced inhibition of this enzyme may be a cellular mechanism by which

Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment?

PubMed

Mcintyre, Sarah; Badawi, Nadia; Blair, Eve; Nelson, Karin B

2015-04-01

Neonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates. © The Authors. Journal compilation © 2015 Mac Keith Press.

Encephalopathy and liver transplantation.

PubMed

Chavarria, Laia; Cordoba, Juan

2013-06-01

Liver transplantation (LT) candidates experience frequently episodic or persistent hepatic encephalopathy. In addition, these patients can exhibit neurological comorbidities that contribute to cognitive impairment in the pre-transplant period. Assessment of the respective contribution of hepatic encephalopathy or comorbidities in the cognitive manifestations is critical to estimate the neurological benefits of restoring liver function. Magnetic resonance imaging and spectroscopy are useful to assess the impact of liver failure or comorbidities. This assessment is critical to decide liver transplant in difficult cases. In the early postoperative period, LT is commonly complicated by a confusional syndrome. The possible role of persisting hepatic encephalopathy in its development has not been clearly established. The origin is usually considered multifactorial and relates to complications following LT, such as infections, rejection, primary liver dysfunction, immunosuppressors, etc.… The diagnosis and treatment is based in the recognition of comorbidities and optimal care of metabolic disturbances. Several studies have demonstrated recovery of cognitive function after LT in patients that have exhibited hepatic encephalopathy. However, some deficits may persist specifically among patients with persistent HE. Other factors present before LT that contribute to a worse neuropsychological outcome after LT are diabetes mellitus and alcohol consumption. Long-term after LT, cognitive function may worsen in relation to vascular risk factors.

The Turkish Neonatal Jaundice Online Registry: A national root cause analysis

PubMed Central

Erdeve, Omer; Olukman, Ozgur; Ulubas, Dilek; Buyukkale, Gokhan; Narter, Fatma; Tunc, Gaffari; Atasay, Begum; Gultekin, Nazli Dilay; Arsan, Saadet; Koc, Esin

2018-01-01

Background Neonatal jaundice (NNJ) is common, but few root cause analyses based on national quality registries have been performed. An online registry was established to estimate the incidence of NNJ in Turkey and to facilitate a root cause analysis of NNJ and its complications. Methods A multicenter prospective study was conducted on otherwise healthy newborns born at ≥35 weeks of gestation and hospitalized for only NNJ in 50 collaborator neonatal intensive care units across Turkey over a 1-year period. Patients were analyzed for their demographic and clinical characteristics, treatment options, and complications. Results Of the 5,620 patients enrolled, 361 (6.4%) had a bilirubin level ≥25 mg/dL on admission and 13 (0.23%) developed acute bilirubin encephalopathy. The leading cause of hospital admission was hemolytic jaundice, followed by dehydration related to a lack of proper feeding. Although all infants received phototherapy, 302 infants (5.4%) received intravenous immunoglobulin in addition to phototherapy and 132 (2.3%) required exchange transfusion. The infants who received exchange transfusion were more likely to experience hemolytic causes (60.6% vs. 28.1%) and a longer duration of phototherapy (58.5 ± 31.7 vs. 29.4 ± 18.8 h) compared to infants who were not transfused (p < 0.001). The incidence of short-term complications among discharged patients during follow-up was 8.5%; rehospitalization was the most frequent (58%), followed by jaundice for more than 2 weeks (39%), neurological abnormality (0.35%), and hearing loss (0.2%). Conclusions Severe NNJ and bilirubin encephalopathy are still problems in Turkey. Means of identifying at-risk newborns before discharge during routine postnatal care, such as bilirubin monitoring, blood group analysis, and lactation consultations, would reduce the frequency of short- and long-term complications of severe NNJ. PMID:29474382

Altered Sleep Spindles in Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

PubMed

Yoshiike, Takuya; Nishida, Masaki; Yagishita, Kazuyoshi; Nariai, Tadashi; Ishii, Kenji; Nishikawa, Toru

2016-06-15

Delayed encephalopathy (DE) affects not only the cerebral white matter and globus pallidus but also the cortex and thalamus. However, it remains unknown whether these brain lesions alter sleep along with clinical manifestations of DE. A 46-year-old man with DE underwent repetitive hyperbaric oxygen therapy. The patient was evaluated by not only neuropsychological and neuroimaging testing but polysomnography over the clinical course. Neurological symptoms improved markedly; however, profound frontal cognitive deficits continued. The polysomnography revealed prolonged absence and delayed recovery of sleep spindles across recordings. Alterations in spindle oscillations in DE could provide further insight into sleep regulatory networks. © 2016 American Academy of Sleep Medicine.

Point Spectroscopy System for Noncontact and Noninvasive Prediction of Transcutaneous Bilirubin Concentration

NASA Astrophysics Data System (ADS)

Ong, P. E.; K. C Huong, Audrey

2017-08-01

This paper presents the use of a point spectroscopy system to determine one’s transcutaneous bilirubin level using Modified Lambert Beer model and the developed fitting routine. This technique required a priori knowledge of extinction coefficient of bilirubin and hemoglobin components in the wavelength range of 440-500 nm for the prediction of the required parameter value. This work was conducted on different skin sites of six healthy Asians namely on the thenar region of the palm of their hand, back of the hand, posterior and anterior forearm. The obtained results revealed the lowest mean transcutaneous bilirubin concentration of 0.44±0.3 g/l predicted for palm site while the highest bilirubin level of 0.98±0.2 g/l was estimated for posterior forearm. These values were also compared with that presented in the literature. This study found considerably good consistency in the value predicted for different subjects especially at the thenar region of the palm. This work concluded that the proposed system and technique may be suitably served as an alternative means to noncontact and noninvasive measurement of one’s transcutaneous bilirubin level at palm site.

Metronidazole-induced encephalopathy in a patient with liver cirrhosis.

PubMed

Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul; Cho, Eun-Young

2011-06-01

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

PubMed Central

Heikel, T. A. J.; Lathe, G. H.

1970-01-01

1. The effect of oestrogens and progestogens and their 17α-ethinyl derivatives on bile flow, maximum rate of bilirubin secretion, serum and liver bilirubin has been studied. 2. Both 17α-ethinyl substituted oestrogens and progestogens greatly reduced the basal bile flow. The parent compounds, oestradiol-17β and 19-nortestosterone had little or no effect. 3. A much larger dose of progestogens (40 mg/kg) than oestrogens (5 mg/kg) was needed. 4. Between 12 and 48 h were required for 17α-ethinyloestradiol to produce the effect. 5. Bilirubin maximum secretion rate (Tm) was little affected, the only significant reduction being produced by the 3-methyl ether of 17α-ethinyloestradiol (mestranol). 6. Rises in serum conjugated bilirubin following infusion of bilirubin were produced by 17α-ethinyloestradiol and mestranol but not by the progestogens. PMID:5441412

Amine-functionalized PVA-co-PE nanofibrous membrane as affinity membrane with high adsorption capacity for bilirubin.

PubMed

Wang, Wenwen; Zhang, Hao; Zhang, Zhifeng; Luo, Mengying; Wang, Yuedan; Liu, Qiongzhen; Chen, Yuanli; Li, Mufang; Wang, Dong

2017-02-01

In this study, poly(vinyl alcohol-co-ethylene) (PVA-co-PE) nanofibrous membrane was activated by sodium hydroxide and cyanuric chloride, and then the activated membranes were functionalized by 1,3-propanediamine, hexamethylenediamine and diethylenetriamine to be affinity membranes for bilirubin removal, respectively. The chemical structures and morphologies of membranes were investigated by SEM, FTIR and XPS. And the adsorption ability of different amine-functionalized nanofibrous membranes for bilirubin was characterized. Furthermore, the effects of temperature, initial concentration of bilirubin, NaCl concentration and BSA concentration on the adsorption capacity for bilirubin of diethylenetriamine-functionalized nanofibrous membrane were studied. Results indicated that the adsorption capacity for bilirubin of diethylenetriamine-functionalized nanofibrous membrane could reach 85mg/g membrane when the initial bilirubin concentration was 200mg/L while the adsorption capacity could be increased to 110mg/g membrane if the initial bilirubin concentration was more than 400mg/L. The dynamic adsorption of diethylenetriamine-functionalized nanofibrous membrane showed that the ligands of amine groups on the membrane surface could be used as far as possible by recirculating the plasma with certain flow rates. Therefore, the diethylenetriamine-functionalized PVA-co-PE nanofibrous membrane possessed high adsorption capacity for bilirubin and it can be candidate as affinity membrane for bilirubin removal. Copyright © 2016. Published by Elsevier B.V.

Noninvasive versus conventional ventilation to treat hypercapnic encephalopathy in chronic obstructive pulmonary disease.

PubMed

Scala, Raffaele; Nava, Stefano; Conti, Giorgio; Antonelli, Massimo; Naldi, Mario; Archinucci, Ivano; Coniglio, Giovanni; Hill, Nicholas S

2007-12-01

We recently reported a high success rate using noninvasive positive pressure ventilation (NPPV) to treat COPD exacerbations with hypercapnic encephalopathy. This study compared the hospital outcomes of NPPV vs. conventional mechanical ventilation (CMV) in COPD exacerbations with moderate to severe hypercapnic encephalopathy, defined by a Kelly score of 3 or higher. A 3-year prospective matched case-control study in a respiratory semi-intensive care unit (RSICU) and intensive care unit (ICU). From 103 consecutive patients the study included 20 undergoing NPPV and 20 CMV, matched for age, simplified acute physiology score II, and baseline arterial blood gases. ABG significantly improved in both groups after 2 h. The rate of complications was lower in the NPPV group than in the CMV group due to fewer cases of nosocomial pneumonia and sepsis. In-hospital mortality, 1-year mortality, and tracheostomy rates were similar in the two groups. Fewer patients remained on ventilation after 30 days in NPPV group. The NPPV group showed a shorter duration of ventilation. In COPD exacerbations with moderate to severe hypercapnic encephalopathy, the use of NPPV performed by an experienced team compared to CMV leads to similar short and long-term survivals with a reduced nosocomial infection rate and duration of ventilation.

The transmissible spongiform encephalopathies of livestock

USDA-ARS?s Scientific Manuscript database

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...

[Haemolysis and turbidity influence on three analysis methods of quantitative determination of total and conjugated bilirubin on ADVIA 1650].

PubMed

Gobert De Paepe, E; Munteanu, G; Schischmanoff, P O; Porquet, D

2008-01-01

Plasma bilirubin testing is crucial to prevent the occurrence of neonatal kernicterus. Haemolysis may occur during sampling and interfere with bilirubin determination. Moreover, lipidic infusions may induce plasma lipemia and also interfere with bilirubin measurement. We evaluated the interference of haemolysis and lipemia with three methods of total and direct bilirubin measurement adaptated on an Advia 1650 analyser (Siemens Medical Solutions Diagnostics) : Synermed (Sofibel), Bilirubin 2 (Siemens) and Bilirubin Auto FS (Diasys). The measurement of total bilirubin was little affected by haemolysis with all three methods. The Bilirubin 2 (Siemens) method was the less sensitive to haemolysis even at low bilirubin levels. The measurement of conjugated bilirubin was significantly altered by low heamoglobin concentrations for Bilirubin Auto FS(R) (30 microM or 0,192 g/100 mL haemoglobin) and for Synermed (60 microM or 0,484 g/100 mL haemoglobin). In marked contrast, we found no haemoglobin interference with the Direct Bilirubin 2 reagent which complied with the method validation criteria from the French Society for Biological Chemistry. The lipemia up to 2 g/L of Ivelip did not affect neither the measurement of total bilirubin for all three methods nor the measurement of conjugated bilirubin with the Diasys and Siemens reagents. However, we observed a strong interference starting at 0,5 g/L of Ivelip with the Synermed reagent. Our data suggest that both Siemens and Diasys methods allow to measure accurately total and conjugated bilirubin in hemolytic and lipemic samples, nevertheless, the Siemens methodology is less affected by these interferences.

Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme

PubMed Central

John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

2017-01-01

Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome. PMID:28127211

Hepatic Encephalopathy

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... People ALF Near You Events ALF Blogs Financial Information Policies Advocacy Patient Advisory Council Media Center Careers ... and abdomen (ascites) or hepatic encephalopathy. For more information about cirrhosis of the liver and symptoms, call ...

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

USDA-ARS?s Scientific Manuscript database

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...

Clinical system model for monitoring the physiological status of jaundice by extracting bilirubin components from skin diffuse reflectance spectra

NASA Astrophysics Data System (ADS)

Kumar, Alla S.; Clark, Joseph; Beyette, Fred R., Jr.

2009-02-01

Neonatal jaundice is a medical condition which occurs in newborns as a result of an imbalance between the production and elimination of bilirubin. The excess bilirubin in the blood stream diffuses into the surrounding tissue leading to a yellowing of the skin. As the bilirubin levels rise in the blood stream, there is a continuous exchange between the extra vascular bilirubin and bilirubin in the blood stream. Exposure to phototherapy alters the concentration of bilirubin in the vascular and extra vascular regions by causing bilirubin in the skin layers to be broken down. Thus, the relative concentration of extra vascular bilirubin is reduced leading to a diffusion of bilirubin out of the vascular region. Diffuse reflectance spectra from human skin contains physiological and structural information of the skin and nearby tissue. A diffuse reflectance spectrum must be captured before and after blanching in order to isolate the intravascular and extra vascular bilirubin. A new mathematical model is proposed with extra vascular bilirubin concentration taken into consideration along with other optical parameters in defining the diffuse reflectance spectrum from human skin. A nonlinear optimization algorithm has been adopted to extract the optical properties (including bilirubin concentration) from the skin reflectance spectrum. The new system model and nonlinear algorithm have been combined to enable extraction of Bilirubin concentrations within an average error of 10%.

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

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.

Serum bilirubin concentration is associated with eGFR and urinary albumin excretion in patients with type 1 diabetes mellitus.

PubMed

Nishimura, Takeshi; Tanaka, Masami; Sekioka, Risa; Itoh, Hiroshi

2015-01-01

Although relationships of serum bilirubin concentration with estimated glomerular filtration rate (eGFR) and urinary albumin excretion (UAE) in patients with type 2 diabetes have been reported, whether such relationships exist in patients with type 1 diabetes is unknown. A total of 123 patients with type 1 diabetes were investigated in this cross-sectional study. The relationship between bilirubin (total and indirect) concentrations and log(UAE) as well as eGFR was examined by Pearson's correlation analyses. Multivariate regression analyses were used to assess the association of bilirubin (total and indirect) with eGFR as well as log(UAE). A positive correlation was found between serum bilirubin concentration and eGFR; total bilirubin (r=0.223, p=0.013), indirect bilirubin (r=0.244, p=0.007). A negative correlation was found between serum bilirubin concentration and log(UAE); total bilirubin (r=-0.258, p=0.005), indirect bilirubin (r=-0.271, p=0.003). Multivariate regression analyses showed that indirect bilirubin concentration was an independent determinant of eGFR and log(UAE). Bilirubin concentration is associated with both eGFR and log(UAE) in patients with type 1 diabetes. Bilirubin might have a protective role in the progression of type 1 diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

Higher hydrocortisone dose increases bilirubin in hypopituitary patients- results from an RCT.

PubMed

Werumeus Buning, Jorien; Kootstra-Ros, Jenny E; Brummelman, Pauline; van den Berg, Gerrit; van der Klauw, Melanie; Wolffenbuttel, Bruce H R; van Beek, André P; Dullaart, Robin P F

2016-05-01

Bilirubin has anti-oxidative and anti-inflammatory properties, which may explain its proposed protective effects on the development of cardiometabolic disorders. Glucocorticoids affect heme oxygenase regulation in vitro, which plays a key role in bilirubin production. Effects of variations in glucocorticoid exposure on circulating bilirubin levels in humans are unknown. Here we tested whether a higher hydrocortisone replacement dose affects circulating bilirubin in hypopituitary patients. A randomized double-blind cross-over study (ClinicalTrials.gov, number NCT01546992) was performed in 47 patients with secondary adrenal failure [10-week exposure to a higher hydrocortisone dose (0·4-0·6 mg/kg body weight) vs. 10 weeks of a lower hydrocortisone dose (0·2-0·3 mg/kg body weight)]. Plasma total bilirubin was increased by 10% from 7 to 8 μM in response to the higher hydrocortisone dose (P = 0·033). This effect was inversely related to age (P = 0·042), but was unaffected by sex, obesity and (replacement for) other hormonal insufficiencies. The higher hydrocortisone dose also resulted in lower alkaline phosphatase (P = 0·006) and aspartate aminotransferase activities (P = 0·001). Bilirubin is modestly increased in response to higher glucocorticoid exposure in humans, in conjunction with lower alkaline phosphatase and aspartate aminotransferase activities, which are supposed to represent biomarkers of a pro-inflammatory state and enhanced liver fat accumulation. © 2016 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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. © The Author(s) 2014.

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants.

PubMed

Amin, Sanjiv B; Wang, Hongyue

2018-01-01

To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day. For the 166 infants studied, peak UB significantly correlated with concomitant Ka (r = -0.44, P = .001) but not with concomitant TSB or BAMR after adjusting for GA. On multiple regression analyses, there was a significant association of concomitant Ka (-0.06, 95% CI -0.08 to -0.04, P = .0001), but not concomitant TSB or BAMR with peak UB after controlling for GA, birth weight, race, and sex. GA group was a significant effect modifier for the association between Ka and peak UB (0.03, 95% CI 0.02-0.04, P < .001). Interaction analyses showed the association between concomitant Ka and peak UB was significant for the 24-30 weeks GA group infants, but not for the 30 1/7 -33 weeks GA group infants. Peak UB was primarily associated with a decrease in binding affinity in infants ≤30 weeks GA. Interventions aimed at improving binding affinity may be important in decreasing the risk of bilirubin-induced neurotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Wernicke encephalopathy in a patient with liver failure

PubMed Central

Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

2016-01-01

Abstract Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice. A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1. To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians’ awareness of its possible onset. PMID:27399058

Minimal hepatic encephalopathy in patients with cirrhosis by measuring liver stiffness and hepatic venous pressure gradient.

PubMed

Sharma, Praveen; Kumar, Ashish

2012-01-01

Transient elastography (TE) of liver and hepatic venous pressure gradient (HVPG) allows accurate prediction of cirrhosis and its complications in patients with chronic liver disease. There is no study on prediction of minimal hepatic encephalopathy (MHE) using TE and HVPG in patients with cirrhosis. Consecutive cirrhotic patients who never had an episode of hepatic encephalopathy (HE) were enrolled. All patients were assessed by psychometry (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), critical flicker frequency test (CFF), TE by FibroScan and HVPG. MHE was diagnosed if there were two or more abnormal psychometry tests (± 2 SD controls). 150 patients with cirrhosis who underwent HVPG were screened; 91 patients (61%, age 44.0 ± 11.4 years, M:F:75:16, Child's A:B:C 18:54:19) met the inclusion criteria. Fifty three (58%) patients had MHE (Child A (7/18, 39%), Child B (32/54, 59%) and Child C (14/19, 74%)). There was no significant difference between alanine aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin level in patients with MHE versus non MHE. Patients with MHE had significantly lower CFF than non MHE patients (38.4 ± 3.0 vs. 40.2 ± 2.2 Hz, P = 0.002). TE and HVPG in patients with MHE did not significantly differ from patients with no MHE (30.9 ± 17.2 vs. 29.8 ± 18.2 KPas, P = 0.78; and 13.6 ± 2.7 vs. 13.6 ± 3.2 mmHg, P = 0.90, respectively).There was significant correlation of TE with Child's score (0.25, P = 0.01), MELD (0.40, P = 0.001) and HVPG (0.72, P = 0.001) while no correlation with psychometric tests, CFF and MHE. TE by FibroScan and HVPG cannot predict minimal hepatic encephalopathy in patients with cirrhosis.

Hypertensive brain stem encephalopathy.

PubMed

Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

2015-01-01

A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal.

The effect of steroids and nucleotides on solubilized bilirubin uridine diphosphate glucuronyltransferase

PubMed Central

Adlard, B. P. F.; Lathe, G. H.

1970-01-01

1. It was confirmed that bilirubin glucuronyltransferase can be obtained in solubilized form from rat liver microsomes. 2. Michaelis–Menten kinetics were not followed by the enzyme with bilirubin as substrate when the bilirubin/albumin ratio was varied. High concentrations of bilirubin were inhibitory. 3. The Km for UDP-glucuronic acid at the optimum bilirubin concentration was 0.46mm. 4. Low concentrations of Ca2+ were inhibitory in the absence of Mg2+ but stimulatory in its presence; the converse applied for EDTA. 5. UDP-N-acetylglucosamine and UDP-glucose enhanced conjugation by untreated, but not by solubilized microsomes. 6. The apparent 9.5-fold increase in activity after solubilization was probably due to the absence of UDP-glucuronic acid pyrophosphatase activity in the solubilized preparation. 7. The activation of solubilized enzyme activity by ATP was considered to be a result of chelation of inhibitory metal ions. 8. The solubilized enzyme activity was inhibited by UMP and UDP. The effect of UMP was not competitive with respect to UDP-glucuronic acid. 9. A number of steroids inhibited the solubilized enzyme activity. The competitive effects of stilboestrol, oestrone sulphate and 3β-hydroxyandrost-5-en-17-one, with respect to UDP-glucuronic acid, may be explained on an allosteric basis. PMID:4251180

Three-dimensionally porous graphene: A high-performance adsorbent for removal of albumin-bonded bilirubin.

PubMed

Ma, Chun Fang; Gao, Qiang; Xia, Kai Sheng; Huang, Zhi Yuan; Han, Bo; Zhou, Cheng Gang

2017-01-01

The development of bilirubin adsorbents with high adsorption efficiencies towards albumin-bonded bilirubin is still a considerable challenge. In this work, a three-dimensionally porous graphene (3D-pGR) has been fabricated through a simple carbon dioxide (CO 2 ) activation of thermally exfoliated graphite oxide (EGO). Intriguingly, the resultant 3D-pGR material showed hierarchically micro-meso-macroporous structure, high specific surface area of up to 843m 2 g -1 , and large pore volume as high as 2.71cm 3 g -1 . Besides, the large planar π-configuration structure of 3D-pGR made it possible to compete effectively with albumin for bilirubin binding. Taking advantages of these fantastic characteristics, the 3D-pGR was demonstrated to be extraordinarily efficient for bilirubin removal from a bovine serum albumin (BSA)-rich solution. Under optimized conditions, the maximum adsorption capacity of 3D-pGR for BSA-bonded bilirubin was up to 126.1mgg -1 , which is not only significantly higher than the adsorption capacities of currently available adsorbents towards albumin-bonded bilirubin, but also superior to those of many reported adsorbents towards free bilirubin. In addition, the hemolysis assay of 3D-pGR indicated that this material had negligible hemolysis effect. Findings from this study may open up important new possibilities for removal of protein-bonded toxins. Copyright © 2016 Elsevier B.V. All rights reserved.

Serum bilirubin levels are positively associated with glycemic variability in women with type 2 diabetes.

PubMed

Kim, Lee Kyung; Roh, Eun; Kim, Min Joo; Kim, Min Kyeong; Park, Kyeong Seon; Kwak, Soo Heon; Cho, Young Min; Park, Kyong Soo; Jang, Hak Chul; Jung, Hye Seung

2016-11-01

Glycemic variability is known to induce oxidative stress. We investigated the relationships between glycemic variability and serum bilirubin levels, an endogenous anti-oxidant, in patients with diabetes. A cross-sectional study was carried out with 77 patients with type 2 diabetes who had been recruited to two clinical studies from 2008 to 2014. There were no participants with diseases of the pancreas, liver, biliary tract and chronic renal insufficiency. Glycemic variation was calculated by a continuous glucose monitoring system, and correlation analyses were carried out to evaluate their association with bilirubin levels. Multiple linear regression was carried out to identify independent factors influencing bilirubin levels and glycemic variation. Among the participants, 42.3% were men. The mean (standard deviation) age was 61.5 years (10.4 years), body mass index was 24.2 kg/m 2 (2.8 kg/m 2 ), diabetes duration was 17.7 years (9.5 years), hemoglobin A 1c was 60.7 mmol/mol (7.1 mmol/mol; 7.7 [0.7]%) and bilirubin was 11.8 μmol/L (4.10 μmol/L). Serum bilirubin levels were not different according to age, body mass index and hemoglobin A 1c . However, the mean amplitude of glucose excursion was positively associated with bilirubin levels in women (r = 0.588, P < 0.001). After adjustment with duration of diabetes, serum albumin, liver enzymes, and mean glucose, the correlation between bilirubin and mean amplitude of glucose excursion remained significant (r = 0.566, P < 0.001). Multiple linear regression analyses showed that bilirubin was an independent determinant for the mean amplitude of glucose excursion in women. 1,5-Anhydroglucitol was also associated with bilirubin levels in women. Bilirubin level within the physiological range might be an independent predictor for glycemic variability in women with type 2 diabetes. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons

The imaging spectrum of posterior reversible encephalopathy syndrome: A pictorial review.

PubMed

Brady, Emily; Parikh, Neal S; Navi, Babak B; Gupta, Ajay; Schweitzer, Andrew D

Posterior reversible encephalopathy syndrome (PRES) is characterized by the acute onset of neurologic symptoms (headache, altered mental status, visual changes, seizures) with accompanying vasogenic edema on brain imaging. Risk factors for PRES include infection, uremia, malignancy, autoimmune disorders, the peripartum state and hypertension. PRES is classically described as being posterior (i.e. parieto-occipital) but radiologic variants are increasingly recognized. This pictorial review demonstrates the heterogeneity of the different radiologic presentations of PRES in reference to lesion distribution, hemorrhage, diffusion restriction, contrast enhancement, and other associated findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Updated Etiology and Significance of Elevated Bilirubin During Pregnancy: Changes Parallel Shift in Demographics and Vaccination Status.

PubMed

Duraiswamy, Sangeethapriya; Sheffield, Jeanne S; Mcintire, Donald; Leveno, Kenneth; Mayo, Marlyn J

2017-02-01

The most common cause of jaundice during pregnancy in the United States (US) is still attributed to viral hepatitis, despite the dramatic drop in incidence of viral hepatitis in the US. We hypothesized that viral hepatitis is no longer a frequent etiology of jaundice among the pregnant population in the US and sought to identify the contemporary causes of elevated bilirubin during pregnancy as well as to quantify the associated risk to the mother and fetus. Clinical data from all pregnant women who delivered an infant between 2005 and 2011 at a single hospital in Dallas, Texas, were ascertained using prospectively collected computerized databases. Women with elevated total bilirubin (>1.2 mg/dl) were analyzed to determine the cause of hyperbilirubinemia and maternal and fetal outcomes. Out of a total of 80,857 consecutive deliveries, there were 397 (0.5 %) pregnancies with hyperbilirubinemia. The most common etiology was gallstones (98/397 = 25 %), followed by preeclampsia/eclampsia/HELLP (94/397 = 24 %) and intrahepatic cholestasis of pregnancy (53/397 = 13 %). Adverse infant outcomes, including stillbirths, fetal malformations, neonatal deaths, and small for gestational age births, were more common in the women with hyperbilirubinemia during pregnancy, but there were no maternal deaths. Acute viral hepatitis is no longer a common cause of jaundice in pregnant women in the US. In the current era, gallstones and preeclampsia-related disorders are the most common causes of jaundice in pregnant women. Disorders that cause elevated maternal bilirubin during pregnancy are associated with increased risk for the fetus.

Clinical characteristics of acute hepatitis A complicated by acute kidney injury.

PubMed

Yu, Jung Hwan; Kim, Ja Kyung; Park, Jun Yong; Paik, Yong Han; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Lee, Kwan Sik

2012-02-01

The incidence of acute viral hepatitis A (AHA) in Korea is increasing rapidly. Additionally, we are encountering more cases with acute kidney injury (AKI), which was once regarded as a rare complication of AHA. Thus, we investigated recent aspects of the incidence and clinical characteristics of AHA complicated by AKI. Patients diagnosed with AHA at 2 referral hospitals in Seoul during the period January 2006 to December 2009 were enrolled. Of 1025 patients, 71 (6.9%) had AKI. The incidence of AKI was 3.1% in 2006, 6.0% in 2007, 8.9% in 2008, and 6.9% in 2009. Patients with AKI were predominantly male, heavy alcohol drinkers, and smokers, and also had a higher rate of underlying hypertension than patients without AKI. At admission, patients with AKI had significantly higher white blood cell counts, prolonged prothrombin times, and elevated liver enzymes, including total and direct bilirubin, gamma-glutamyltransferase, and C-reactive protein. Additionally, patients with AKI had a higher peak total bilirubin level and lower initial serum albumin level than patients without AKI. Although most patients with AHA complicated by AKI recover with conservative treatment, we should pay particular attention to patients who have risk factors for AKI.

Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette Transporter A1 Protein Expression.

PubMed

Wang, Dongdong; Tosevska, Anela; Heiß, Elke H; Ladurner, Angela; Mölzer, Christine; Wallner, Marlies; Bulmer, Andrew; Wagner, Karl-Heinz; Dirsch, Verena M; Atanasov, Atanas G

2017-04-28

Mild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low-density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals. Cholesterol efflux from THP-1 macrophages was assessed using plasma obtained from normo- and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3-17.1 μmol/L) exogenously added to plasma- or apolipoprotein A1-supplemented media also decreased macrophage cholesterol efflux in a concentration- and time-dependent manner. We also showed reduced protein expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apolipoprotein A1-mediated cholesterol efflux, in THP-1 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the ABCA1 protein in THP-1 macrophages. Cholesterol efflux from THP-1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of bilirubin's role in cardiovascular disease. © 2017 The Authors. Published on

[Value of early-stage cerebral oxygen utilization coefficient in predicting delayed encephalopathy after acute carbon monoxide poisoning].

PubMed

Liu, Q; Li, W; Li, N; Xiao, Q M; He, J Q; Wang, W Z; Qi, H N; Wang, P

2017-05-20

Objective: To investigate the dynamic change in cerebral oxygen utilization coefficient (O(2)UCc) in the early stage of acute severe carbon monoxide poisoning (ASCMP) and its value in predicting delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) . Methods: A prospective observational study was conducted for patients with ASCMP who were admitted to our hospital from November 2013 to March 2016, and their baseline features and physiological parameters were recorded. Observation ended at two months after acute poisoning; according to the presence or absence of DEACMP, the patients were divided into DEACMP group with 21 patients and non-DEACMP group with 64 patients. The change in O(2)UCc was monitored on admission and at 6, 24, 48, and 72 hours. Spearman correlation was used to investigate the correlation between O(2)UCc and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of O(2)UCc in predicting DEACMP. Results: Both groups had a significant increase in O(2)UCc on admission, and the DEACMP group had a significantly greater increase than the non-DEACMP group (52.57%±9.30% vs 41.46±%6.37%, P <0.05) . Then both groups tended to have a reduction in O(2)UCc, and the DEACMP group had a significantly higher O(2)UCc than the non-DEACMP group at 6, 24, and 48 hours (47.40%±7.92%, 39.38%±8.01%, and 32.29%±6.31% vs 34.51%±7.89%, 28.79%±5.4%, and 27.72%±5.46%, P <0.05) . On admission and at 6, 24, and 48 hours, O2UCc was positively correlated with APACHE II score ( r =0.304, 0.398, 0.426, and 0.300, P =0.005, 0.000, 0.000, and 0.005) . The ROC curve showed that O(2)UCc had a value in predicting DEACMP on admission and at 6, 24, and 48 hours, and 6-hour O2UCc had the highest predictive value with an area under the ROC curve of 0.870 (95% confidence interval 0.794-0.947, P <0.05) . Conclusion: The dynamic change in O(2)UCc has a reference value in

Chronic traumatic encephalopathy: The unknown disease.

PubMed

Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F

2017-04-01

Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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

PubMed

Gupta, Charu; Massaro, An N; Ray, Patricio E

2016-07-01

Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. 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). 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. The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life.

Ursodeoxycholic Acid Improves Bilirubin but Not Albumin in Primary Biliary Cirrhosis: Further Evidence for Nonefficacy

PubMed Central

Tsochatzis, Emmanuel A.; Feudjo, Maurille; Rigamonti, Cristina; Vlachogiannakos, Jiannis; Carpenter, James R.; Burroughs, Andrew K.

2013-01-01

Background/Aim. In randomised controlled trials (RCTs) of ursodeoxycholic acid (UDCA), although serum bilirubin is frequently reduced, its effect on disease progression and mortality is unclear. As serum albumin is an established independent prognostic marker, one might expect less deterioration of serum albumin values in a UDCA-treated group. We therefore modelled the typical evolution of serum bilirubin and albumin levels over time in UDCA-untreated patients and compared it with the observed levels in UDCA RCTs. Methods. Multilevel modelling was used to relate the evolution of serum albumin to serum bilirubin and time since patient referral. For each considered RCT, the derived model was used to predict the relationship between final mean serum albumin and bilirubin concentration, adjusted for mean serum albumin at referral and followup duration. Results. Five RCTs were eligible in terms of available data, of which two had long followup. In all trials, serum albumin did not significantly differ between UDCA- and placebo-treated patients, despite the UDCA effect on serum bilirubin. Therefore, there is no evidence over time for changes or maintenance of albumin levels for UDCA-treated patients above the levels predicted for placebo-treated patients. Conclusions. Our findings suggest that UDCA does not alter serum albumin in a way that is consistent with its effect on serum bilirubin. Therefore, reductions in serum bilirubin of UDCA-treated PBC do not parallel another validated and independent prognostic marker, further questioning the validity of serum bilirubin reduction with UDCA as a surrogate therapeutic marker. PMID:23984317

The utility of inpatient rebound bilirubin levels in infants readmitted after birth hospitalization for hyperbilirubinemia.

PubMed

Berkwitt, Adam; Osborn, Rachel; Grossman, Matthew

2015-02-01

There are few data evaluating the role of inpatient rebound bilirubin levels in the management of infants readmitted after their birth hospitalization for indirect hyperbilirubinemia. The goal of the present study was to evaluate the clinical utility of inpatient rebound bilirubin levels within this patient population. A retrospective cohort study was conducted of 226 infants readmitted after their birth hospitalization for indirect hyperbilirubinemia. Data from 130 infants with rebound bilirubin levels drawn at a mean of 6.1±2.4 hours after discontinuation of phototherapy were compared with data from 96 infants without rebound bilirubin levels. The primary outcome was readmission to the hospital, and secondary outcomes included length of stay and discharge time. A subgroup analysis compared characteristics of children who required repeat phototherapy versus those who did not. Overall, 5 of 130 patients from the rebound group were readmitted compared with 4 of 96 patients from the no-rebound group (P=.98). Length of stay was significantly longer for patients with rebound bilirubin levels (27.7 vs 23.2 hours; P=.001). Patients with bilirubin levels lowered to ≤14 mg/dL were less likely to receive repeat phototherapy than those with levels>14 mg/dL (2 of 129 vs 12 of 97; P=.001). Early inpatient rebound bilirubin levels do not successfully predict which patients will require hospital readmission for repeat phototherapy. Children with bilirubin levels lowered to ≤14 mg/dL with phototherapy are unlikely to receive repeat phototherapy. Copyright © 2015 by the American Academy of Pediatrics.

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. © 2013, The American College of Clinical Pharmacology.

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.

Relationship between serum bilirubin concentrations and diabetic nephropathy in Shanghai Han's patients with type 1 diabetes mellitus.

PubMed

Li, Xu; Zhang, Lei; Chen, Haibing; Guo, Kaifeng; Yu, Haoyong; Zhou, Jian; Li, Ming; Li, Qing; Li, Lianxi; Yin, Jun; Liu, Fang; Bao, Yuqian; Han, Junfeng; Jia, Weiping

2017-03-31

Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20-0.60; Q2, 0.60-0.80; Q3, 0.80-1.00; Q4, 1.00-1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. The median bilirubin level was 0.56 (interquartile: 0.43-0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58-0.89 mg/dL], P < 0.001). Spearman's correlational analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P < 0.05) and multiple stepwise regression analysis showed bilirubin concentrations were independently associated with 24 h urinary microalbumin. In logistic regression analysis, bilirubin concentrations were significantly inversely associated with nephropathy. In addition, in stratified analysis, from the first to the fourth quartile group, increased bilirubin concentrations were associated with decreased prevalence of DN from 21.90% to 2.00%. High bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.

Transcutaneous Bilirubin Nomogram for Healthy Term and Late Preterm Neonates in First 96 Hours of Life.

PubMed

Thakkar, Pareshkumar; Chavda, Hardas; Doshi, Vikas

2017-05-15

To develop nomogram of Transcutaneous Bilirubin among healthy term and late-preterm neonates during first 96 hours of age. Longitudinal observational study. Neonatal unit of a tertiary care Hospital of Central Gujarat, India. 1075 healthy term and late preterm neonates (≥35weeks). Six-hourly transcutaneous bilirubin was obtained from birth to 96 hour of life using Drager JM 103 Transcutaneous Bilirubinometer. Main outcome measures: Nomogram of Transcutaneous Bilirubin with percentile values was obtained, rate of rise of bilirubin was calculated and predictive ability of normative data was analyzed for subsequent need of phototherapy. The age-specific percentile curves and nomogram were developed from the transcutaneous bilirubin readings of 1,010 neonates. Rate of rise in first 12 hour was 0.2 mg/dL and was 0.17 mg/dL in 12 to 24 hour of life which decreased on second day of life. Neonates who required phototherapy had consistently higher readings of transcutaneous bilirubin and also higher rate of rise in first 48 hrs. Neonates whose transcutaneous bilirubin is above the 50th percentile should be monitored for the development of significant hyperbilirubinemia.

Conformational analysis and circular dichroism of bilirubin, the yellow pigment of jaundice

NASA Astrophysics Data System (ADS)

Lightner, David A.; Person, Richard; Peterson, Blake; Puzicha, Gisbert; Pu, Yu-Ming; Bojadziev, Stefan

1991-06-01

Conformational analysis of (4Z, 15Z)-bilirubin-IX(alpha) by molecular mechanics computations reveals a global energy minimum folded conformation. Powerful added stabilization is achieved through intramolecular hydrogen bonding. Theoretical treatment of bilirubin as a molecular exciton predicts an intense bisignate circular dichroism spectrum for the folded conformation: (Delta) (epsilon) is congruent to 270 L (DOT) mole-1 (DOT) cm-1 for the $OM450 nm electronic transition(s). Synthesis of bilirubin analogs with propionic acid groups methylated at the (alpha) or (beta) position introduces an allosteric effect that allows for an optical resolution of the pigments, with enantiomers exhibiting the theoretically predicted circular dichroism.

Hypoglycaemia and hypoxic-ischaemic encephalopathy.

PubMed

Boardman, James P; Hawdon, Jane M

2015-04-01

The transition from fetal to neonatal life requires metabolic adaptation to ensure that energy supply to vital organs and systems is maintained after separation from the placental circulation. Under normal conditions, this is achieved through the mobilization and use of alternative cerebral fuels (fatty acids, ketone bodies, and lactate) when blood glucose concentration falls. Severe hypoxia-ischaemia is associated with impaired metabolic adaptation, and animal and human data suggest that levels of hypoglycaemia that are tolerated under normal conditions can be harmful in association with hypoxia-ischaemia. The optimal target blood glucose level for ensuring adequate energy provision in hypoxic-ischaemic encephalopathy (HIE) remains unknown. However, recent data support guidance to maintain a blood glucose concentration of 2.5 mmol/L or more in neonates with signs of acute neurological dysfunction, which includes those with HIE, and this is higher than the accepted threshold of 2 mmol/L in infants without signs of neurological dysfunction or hyperinsulinism. © The Authors. Journal compilation © 2015 Mac Keith Press.

Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: a community-based study.

PubMed

Zhong, P; Sun, D M; Wu, D H; Li, T M; Liu, X Y; Liu, H Y

2017-01-26

We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (P<0.001). Serum total bilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (P<0.005). Logistic regression showed that serum total bilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863-0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.

Probiotics for people with hepatic encephalopathy.

PubMed

Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C

2017-02-23

Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration

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.

Higher Bilirubin Levels of Healthy Living Liver Donors Are Associated With Lower Posttransplant Hepatocellular Carcinoma Recurrence.

PubMed

Han, Sangbin; Yang, Ju Dong; Sinn, Dong Hyun; Ko, Justin Sangwook; Kim, Jong Man; Shin, Jun Chul; Son, Hee Jeong; Gwak, Mi Sook; Joh, Jae-Won; Kim, Gaab Soo

2016-09-01

Serum bilirubin level, which may reflect the host defense against increased oxidative stress, is inversely associated with the risk of cancer development. In liver transplantation, the intrinsic bilirubin metabolism of donor liver is subsequently translated into recipient. Thus, we hypothesized that liver transplantation conducted with living donors with higher serum bilirubin reduces hepatocellular carcinoma (HCC) recurrence. Two hundred fifty recipients who underwent liver transplantation for treating HCC within the Milan criteria were included in the study. The association between donor preoperative total bilirubin concentration and the risk of HCC recurrence was analyzed using the Fine and Gray regression model with posttransplant death as a competing risk event with adjustment for tumor biology including α-fetoprotein, histological differentiation, and microvascular invasion. All donors were confirmed to have no underlying hepatobiliary diseases or hematological disorders. Donor preoperative total bilirubin concentration was 0.7 mg/dL in median and ranged from 0.2 to 2.7 mg/dL. Thirty-five (14.0%) recipients developed HCC recurrence. Multivariable analysis demonstrated that donor preoperative total bilirubin concentration was inversely associated with the recurrence risk (hazard ratio, 0.22; 95% confidence interval, 0.07-0.72; P = 0.013). The highest (≥1.0 mg/dL) versus lowest (≤0.6 mg/dL) tertile of donor preoperative total bilirubin showed a significant reduction of the recurrence risk (hazard ratio, 0.28; 95% confidence interval, 0.11-0.70; P = 0.006). Hepatocellular carcinoma recurrence risk decreases in relation to the increase in total serum bilirubin level of healthy living donors without underlying hepatobiliary or hematological disorders. Further validation of bilirubin as a potent anticancer substance against HCC is warranted.

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

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

Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response.

PubMed

Adin, Christopher A; VanGundy, Zachary C; Papenfuss, Tracey L; Xu, Feng; Ghanem, Mostafa; Lakey, Jonathan; Hadley, Gregg A

2017-01-24

Bilirubin has been recognized as a powerful cytoprotectant when used at physiologic doses and was recently shown to have immunomodulatory effects in islet allograft transplantation, conveying donor-specific tolerance in a murine model. We hypothesized that bilirubin, an antioxidant, acts to suppress the innate immune response to islet allografts through two mechanisms: 1) by suppressing graft release of damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and 2) by producing a tolerogenic phenotype in antigen-presenting cells. Bilirubin was administered intraperitoneally before pancreatic procurement or was added to culture media after islet isolation in AJ mice. Islets were exposed to transplant-associated nutrient deprivation and hypoxia. Bilirubin significantly decreased islet cell death after isolation and hypoxic stress. Bilirubin supplementation of islet media also decreased the release of DAMPs (HMGB1), inflammatory cytokines (IL-1β and IL-6), and chemokines (MCP-1). Cytoprotection was mediated by the antioxidant effects of bilirubin. Treatment of macrophages with bilirubin induced a regulatory phenotype, with increased expression of PD-L1. Coculture of these macrophages with splenocytes led to expansion of Foxp3+ Tregs. In conclusion, exogenous bilirubin supplementation showed cytoprotective and antioxidant effects in a relevant model of islet isolation and hypoxic stress. Suppression of DAMP release, alterations in cytokine profiles, and tolerogenic effects on macrophages suggest that the use of this natural antioxidant may provide a method of preconditioning to improve outcomes after allograft transplantation.

Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response

PubMed Central

Adin, Christopher A.; Vangundy, Zachary C.; Papenfuss, Tracey L.; Xu, Feng; Ghanem, Mostafa; Lakey, Jonathan; Hadley, Gregg A.

2017-01-01

Bilirubin has been recognized as a powerful cytoprotectant when used at physiologic doses and was recently shown to have immunomodulatory effects in islet allograft transplantation, conveying donor-specific tolerance in a murine model. We hypothesized that bilirubin, an antioxidant, acts to suppress the innate immune response to islet allografts through two mechanisms: 1) by suppressing graft release of damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and 2) by producing a tolerogenic phenotype in antigen-presenting cells. Bilirubin was administered intraperitoneally before pancreatic procurement or was added to culture media after islet isolation in AJ mice. Islets were exposed to transplant-associated nutrient deprivation and hypoxia. Bilirubin significantly decreased islet cell death after isolation and hypoxic stress. Bilirubin supplementation of islet media also decreased the release of DAMPs (HMGB1), inflammatory cytokines (IL-1β and IL-6), and chemokines (MCP-1). Cytoprotection was mediated by the antioxidant effects of bilirubin. Treatment of macrophages with bilirubin induced a regulatory phenotype, with increased expression of PD-L1. Coculture of these macrophages with splenocytes led to expansion of Foxp3+ Tregs. In conclusion, exogenous bilirubin supplementation showed cytoprotective and antioxidant effects in a relevant model of islet isolation and hypoxic stress. Suppression of DAMP release, alterations in cytokine profiles, and tolerogenic effects on macrophages suggest that the use of this natural antioxidant may provide a method of preconditioning to improve outcomes after allograft transplantation. PMID:27393133

Gasoline sniffing and lead encephalopathy.

PubMed Central

Ross, C. A.

1982-01-01

Gasoline sniffing is endemic in northern Manitoba and perhaps throughout much of northern Canada. Its most serious complication is lead encephalopathy, which can be fatal. Most of the toxic effects are thought to be due to tetraethyl lead and its metabolites. The specific treatment is chelation therapy, for which a protocol has been developed at the Health Sciences Centre, Winnipeg. Lead encephalopathy, however, is a manifestation of social, cultural and psychologic malaise. PMID:7139470

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.

The epileptic encephalopathy jungle - from Dr West to the concepts of aetiology-related and developmental encephalopathies.

PubMed

Kalser, Judith; Cross, J Helen

2018-04-01

We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy. The concept of 'epileptic encephalopathy' has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence. It defines a process of neurological impairment caused by the epileptic activity itself and, therefore, potentially reversible with successful treatment, although to a variable extent. Epileptic activity interfering with neurogenesis, synaptogenesis, and normal network organization as well as triggering neuroinflammation are among the possible pathophysiological mechanisms leading to the neurological compromise. This differs from the newly introduced concept of 'developmental encephalopathy' which applies to where the epilepsy and developmental delay are both because of the underlying aetiology and aggressive antiepileptic treatment may not be helpful. The understanding and use of correct terminology is crucial in clinical practice enabling appropriate expectations of antiepileptic treatment. Further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets.

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

2016-08-03

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.

Evaluation of BiliCare™ transcutaneous bilirubin device in Japanese newborns.

PubMed

Yamana, Keiji; Morioka, Ichiro; Kurokawa, Daisuke; Fukushima, Sachiyo; Nishida, Kosuke; Ohyama, Shohei; Nishimura, Noriyuki; Nozu, Kandai; Taniguchi-Ikeda, Mariko; Nagase, Hiroaki; Fujioka, Kazumichi; Iwatani, Sota; Nakamura, Hajime; Iijima, Kazumoto

2017-10-01

Non-invasive transcutaneous bilirubin (TcB) monitoring has been widely used to screen for hyperbilirubinemia. TcB measured using the recently developed BiliCare™ system, however, has not been fully evaluated. One hundred and seven TcB measurements were obtained from 82 Japanese newborns ≥35 weeks' gestational age within 2 weeks after birth. Measurements were taken at the scaphoid fossa, conchal cavity, and lobe of the ear using BiliCare. BiliCare TcB were compared with total serum bilirubin (TB) and TcB obtained using another bilirubinometer (JM-105™). Transcutaneous bilirubin measured at all three sites significantly correlated with TB (r = 0.91, 0.93, and 0.93 at the scaphoid fossa, conchal cavity, and lobe, respectively). The mean differences were 0.1, -0.3, and 3.6 at the scaphoid fossa, conchal cavity, and lobe, respectively. BiliCare TcB at the scaphoid fossa significantly correlated with that using the JM-105 (r = 0.91). The mean difference was 0.0. BiliCare, however, produced a significantly higher and lower TcB than the JM-105 for TB <7 and ≥15 mg/dL, respectively. Transcutaneous bilirubin measurements taken at the scaphoid fossa or conchal cavity using BiliCare were more reliable than those at the earlobe. BiliCare TcB differed from those of the JM-105, for TB <7 or ≥15 mg/dL. © 2017 Japan Pediatric Society.

Moderate unconjugated hyperbilirubinemia causes a transient but delayed suppression of amplitude-integrated electroencephalographic activity in preterm infants.

PubMed

Ter Horst, Hendrik J; Bos, Arend F; Duijvendijk, Jildou; Hulzebos, Christian V

2012-01-01

Unconjugated hyperbilirubinemia occurs frequently in preterm infants and may result in bilirubin encephalopathy. Amplitude-integrated electroencephalography (aEEG) is used to evaluate brain function in newborns. To investigate the influence of total serum bilirubin (TSB) on the aEEG amplitude of preterm infants and to evaluate aEEG as a noninvasive method to identify acute bilirubin encephalopathy. We performed a prospective observational study of 34 infants with a gestational age (GA) of 26-31 6/7 weeks. Infants had aEEG recordings on the 1st-5th, 8th and 15th day after birth. Infants with asphyxia, intraventricular hemorrhage >grade I or circulatory insufficiency were excluded. aEEG was evaluated by calculating the mean 5th, 50th and 95th centiles of the aEEG amplitudes. TSB peaked on the 4th day after birth. There was no synchronous relationship between TSB and aEEG amplitudes. The 5th, 50th, and 95th aEEG amplitude centiles on the 8th day correlated negatively with the TSB peak value (r = -0.37, p = 0.048; r = -0.60, p = 0.001; r = -0.44, p = 0.017, respectively), irrespective of GA. The 5th and 50th aEEG amplitude centiles increased with increasing GA (r = 0.45, p < 0.001, and r = 0.26, p < 0.001, respectively) and postnatal age (r = 0.25, p < 0.001, and r = 0.16, p = 0.023, respectively). TSB had no direct effect on aEEG amplitudes in preterm infants. There is, however, a delayed effect on electrocerebral activity in the 2nd week after birth. Copyright © 2012 S. Karger AG, Basel.

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. Copyright © 2012 Elsevier B.V. All rights reserved.

Serum bilirubin: a simple routine surrogate marker of the progression of chronic kidney disease.

PubMed

Moolchandani, K; Priyadarssini, M; Rajappa, M; Parameswaran, S; Revathy, G

2016-10-01

Studies suggest that Chronic Kidney Disease (CKD) is a global burden health associated with significant comorbid conditions. Few biochemical parameters have gained significance in predicting the disease progression. The present work aimed to study the association of the simple biochemical parameter of serum bilirubin level with the estimated glomerular filtration rate (eGFR), and to assess their association with the co-morbid conditions in CKD. We recruited 188 patients with CKD who attended a Nephrology out-patient department. eGFR values were calculated based on the serum creatinine levels using CKD-EPI formula. Various biochemical parameters including glucose, creatinine, uric acid, total and direct bilirubin were assayed in all study subjects. Study subjects were categorized into subgroups based on their eGFR values and their diabetic status and the parameters were compared among the different subgroups. We observed a significantly decreased serum bilirubin levels (p < 0.001) in patients with lower eGFR values, compared to those with higher eGFR levels. There was a significant positive correlation between the eGFR levels and the total bilirubin levels (r = 0.92). We also observed a significant positive correlation between the eGFR levels and the direct bilirubin levels (r = 0.76). On multivariate linear regression analysis, we found that total and direct bilirubin independently predict eGFR, after adjusting for potential confounders (p < 0.001). Our results suggest that there is significant hypobilirubinemia in CKD, especially with increasing severity and co-existing diabetes mellitus. This finding has importance in the clinical setting, as assay of simple routine biochemical parameters such as serum bilirubin may help in predicting the early progression of CKD and more so in diabetic CKD.

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction.

PubMed

Wang, Wei-Wei; Zhang, Yu; Huang, Xiao-Bing; You, Nan; Zheng, Lu; Li, Jing

2017-10-14

To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl 4 )-induced acute hepatic dysfunction. A rat model of HE was established with CCl 4 . Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined. FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice

PubMed Central

Amin, Sanjiv B; Wang, Hongyue; Laroia, Nirupama; Orlando, Mark

2016-01-01

Objective To evaluate if unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥ 20 mg/dL or TSB that met exchange transfusion criteria). Study design Infants ≥ 34 weeks gestational age with severe jaundice during the first two weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80 decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Results Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (odds ratio 4.6, 95% CI: 1.6-13.5, p = 0.002). On comparing receiver operating characteristic curves, the area under the curve (AUC) for unbound bilirubin (0.92) was significantly greater (p = 0.04) compared with the AUC for TSB (0.50) or BAMR (0.62). Conclusions Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice. PMID:26952116

Brain proton magnetic resonance spectroscopy for hepatic encephalopathy

NASA Astrophysics Data System (ADS)

Ong, Chin-Sing; McConnell, James R.; Chu, Wei-Kom

1993-08-01

Liver failure can induce gradations of encephalopathy from mild to stupor to deep coma. The objective of this study is to investigate and quantify the variation of biochemical compounds in the brain in patients with liver failure and encephalopathy, through the use of water- suppressed, localized in-vivo Proton Magnetic Resonance Spectroscopy (HMRS). The spectral parameters of the compounds quantitated are: N-Acetyl Aspartate (NAA) to Creatine (Cr) ratio, Choline (Cho) to Creatine ratio, Inositol (Ins) to Creatine ratio and Glutamine-Glutamate Amino Acid (AA) to Creatine ratio. The study group consisted of twelve patients with proven advanced chronic liver failure and symptoms of encephalopathy. Comparison has been done with results obtained from five normal subjects without any evidence of encephalopathy or liver diseases.

Surgical Treatment of Pediatric Epileptic Encephalopathies

PubMed Central

Fridley, J.; Reddy, G.; Curry, D.; Agadi, S.

2013-01-01

Pediatric epileptiform encephalopathies are a group of neurologically devastating disorders related to uncontrolled ictal and interictal epileptic activity, with a poor prognosis. Despite the number of pharmacological options for treatment of epilepsy, many of these patients are drug resistant. For these patients with uncontrolled epilepsy, motor and/or neuropsychological deterioration is common. To prevent these secondary consequences, surgery is often considered as either a curative or a palliative option. Magnetic resonance imaging to look for epileptic lesions that may be surgically treated is an essential part of the workup for these patients. Many surgical procedures for the treatment of epileptiform encephalopathies have been reported in the literature. In this paper the evidence for these procedures for the treatment of pediatric epileptiform encephalopathies is reviewed. PMID:24288601

The impact of the UGT1A1*60 allele on bilirubin serum concentrations.

PubMed

Pasternak, Amy L; Crews, Kristine R; Caudle, Kelly E; Smith, Colton; Pei, Deqing; Cheng, Cheng; Broeckel, Ulrich; Gaur, Aditya H; Hankins, Jane; Relling, Mary V; Haidar, Cyrine E

2017-01-01

Identify the functional status of the uridine-diphosphate glucuronyl transferase 1A1 (UGT1A1) -3279T>G (*60) variant. Retrospective review of clinically obtained serum bilirubin concentrations in pediatric patients to evaluate the association of the UGT1A1 -3279T>G (*60) variant with bilirubin concentrations and assessed linkage disequilibrium of the UGT1A1 -3279T>G (*60) and A(TA)7TAA (*28) variants. Total bilirubin concentration did not differ between patients who had a UGT1A1*1/*1 diplotype and patients homozygous for the UGT1A1 -3279T>G (*60/*60) variant. Total bilirubin concentration was lower in patients homozygous for the UGT1A1 -3279T>G (*60/*60) variant than in patients homozygous for the UGT1A1 A(TA)7TAA (*28/*28) variant (p < 0.01). The -3279T>G (*60) and A(TA)7TAA (*28) variants were in strong incomplete linkage disequilibrium in both black and white patients. The presence of the UGT1A1 -3279T>G (*60) variant is not associated with increased bilirubin concentrations.

Electroencephalography and Brain MRI Patterns in Encephalopathy.

PubMed

Wabulya, Angela; Lesser, Ronald P; Llinas, Rafael; Kaplan, Peter W

2016-04-01

Using electroencephalography (EEG) and histology in patients with diffuse encephalopathy, Gloor et al reported that paroxysmal synchronous discharges (PSDs) on EEG required combined cortical gray (CG) and "subcortical" gray (SCG) matter pathology, while polymorphic delta activity (PDA) occurred in patients with white matter pathology. In patients with encephalopathy, we compared EEG findings and magnetic resonance imaging (MRI) to determine if MRI reflected similar pathological EEG correlations. Retrospective case control study of 52 cases with EEG evidence of encephalopathy and 50 controls without evidence of encephalopathy. Review of clinical, EEG and MRI data acquired within 4 days of each other. The most common EEG finding in encephalopathy was background slowing, in 96.1%. We found PSDs in 0% of cases with the combination of CG and SCG abnormalities. Although 13.5% (n=7) had PSDs on EEG; 3 of these had CG and 4 had SCG abnormalities. A total of 73.1% (38/52) had white matter abnormalities-of these 28.9% (11/38) had PDA. PSDs were found with either CG or "SCG" MRI abnormalities and did not require a combination of the two. In agreement with Gloor et al, PDA occurred with white matter MRI abnormalities in the absence of gray matter abnormalities. © EEG and Clinical Neuroscience Society (ECNS) 2015.

Computational chemical analysis of unconjugated bilirubin anions and insights into pKa values clarification

NASA Astrophysics Data System (ADS)

Vega-Hissi, Esteban G.; Estrada, Mario R.; Lavecchia, Martín J.; Pis Diez, Reinaldo

2013-01-01

The pKa, the negative logarithm of the acid dissociation equilibrium constant, of the carboxylic acid groups of unconjugated bilirubin in water is a discussed issue because there are quite different experimental values reported. Using quantum mechanical calculations we have studied the conformational behavior of unconjugated bilirubin species (in gas phase and in solution modeled implicitly and explicitly) to provide evidence that may clarify pKa values because of its pathophysiological relevance. Our results show that rotation of carboxylate group, which is not restricted, settles it in a suitable place to establish stronger interactions that stabilizes the monoanion and the dianion to be properly solvated, demonstrating that the rationalization used to justify the high pKa values of unconjugated bilirubin is inappropriate. Furthermore, low unconjugated bilirubin (UCB) pKa values were estimated from a linear regression analysis.

Bilirubin nomogram for prediction of significant hyperbilirubinemia in north Indian neonates.

PubMed

Pathak, Umesh; Chawla, Deepak; Kaur, Saranjit; Jain, Suksham

2013-04-01

(i) To construct hour-specific serum total bilirubin (STB) nomogram in neonates born at =35 weeks of gestation; (ii)To evaluate efficacy of pre-discharge bilirubin measurement in predicting hyperbilirubinemia needing treatment. Diagnostic test performance in a prospective cohort study. Teaching hospital in Northern India. Healthy neonates with gestation =35 weeks or birth weight =2000 g. Serum total bilirubin was measured in all enrolled neonates at 24 ± 6, 72-96 and 96-144 h of postnatal age and when indicated clinically. Neonates were followed up during hospital stay and after discharge till completion of 7th postnatal day. Key outcome was significant hyperbilirubinemia (SHB) defined as need of phototherapy based on modified American Academy of Pediatrics (AAP) guidelines. In neonates born at 38 or more weeks of gestation middle line and in neonates born at 37 or less completed weeks of gestation, lower line of phototherapy thresholds were used to initiate phototherapy. For construction of nomogram, STB values were clubbed in six-hour epochs (age ± 3 hours) for postnatal age up to 48 h and twelve-hour epochs (age ± 6 hours) for age beyond 48 h. Predictive ability of the nomogram was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio, by plotting receiver-operating characteristics (ROC) curve and calculating c-statistic. 997 neonates (birth weight: 2627 ± 536 g, gestation: 37.8 ± 1.5 weeks) were enrolled, of which 931 completed followup. Among enrolled neonates 344 (34.5%) were low birth weight. Rate of exclusive breastfeeding during hospital stay was more than 80%. Bilirubin nomogram was constructed using 40th, 75th and 95th percentile values of hour-specific bilirubin. Pre-discharge STB of =95th percentile was assigned to be in high-risk zone, between 75th and 94th centile in upper-intermediate risk zone, between 40th and 74th centile in lower-intermediate risk zone and below 40th

Continuous de novo biosynthesis of haem and its rapid turnover to bilirubin are necessary for cytoprotection against cell damage

PubMed Central

Takeda, Taka-aki; Mu, Anfeng; Tai, Tran Tien; Kitajima, Sakihito; Taketani, Shigeru

2015-01-01

It is well known that haem serves as the prosthetic group of various haemoproteins that function in oxygen transport, respiratory chain, and drug metabolism. However, much less is known about the functions of the catabolites of haem in mammalian cells. Haem is enzymatically degraded to iron, carbon monoxide (CO), and biliverdin, which is then converted to bilirubin. Owing to difficulties in measuring bilirubin, however, the generation and transport of this end product remain unclear despite its clinical importance. Here, we used UnaG, the recently identified bilirubin-binding fluorescent protein, to analyse bilirubin production in a variety of human cell lines. We detected a significant amount of bilirubin with many non-blood cell types, which was sensitive to inhibitors of haem metabolism. These results suggest that there is a basal level of haem synthesis and its conversion into bilirubin. Remarkably, substantial changes were observed in the bilirubin generation when cells were exposed to stress insults. Since the stress-induced cell damage was exacerbated by the pharmacological blockade of haem metabolism but was ameliorated by the addition of biliverdin and bilirubin, it is likely that the de novo synthesis of haem and subsequent conversion to bilirubin play indispensable cytoprotective roles against cell damage. PMID:25990790

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

Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins

NASA Astrophysics Data System (ADS)

Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

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.

Malnutrition-induced Wernicke's encephalopathy following a water-only fasting diet.

PubMed

Hutcheon, Deborah A

2015-02-01

Wernicke's encephalopathy is a critical condition of neurological dysfunction resulting from a deficiency in thiamine. Chronic alcoholism is recognized as the most common cause of Wernicke's encephalopathy, but other causes, including fasting/starvation and malnutrition, have been documented within the scientific literature. These causes may not be readily recognized by healthcare professionals and may lead to Wernicke's encephalopathy being overlooked as a diagnosis when a nonalcoholic patient presents with classic signs and symptoms of the disorder. A narrative review of thiamine and its relationship to the development, diagnosis, and treatment of Wernicke's encephalopathy is presented based on a review of evidence-based guidelines and published research. To heighten awareness of the development of Wernicke's encephalopathy in fasted/starved and malnourished patients and to contribute to the scientific body of knowledge for the identification and management of Wernicke's encephalopathy in these patients, the clinical course and treatment of an adult woman who developed Wernicke's encephalopathy following a 40-day water-only fasting diet is outlined. Clinical suspicion was required to identify the patient's condition and initiate immediate intervention through parenteral thiamine administration. Oral thiamine supplementation of 100 to 800 mg per day for 6 months was required to aid recovery. The patient's clinical course and response to treatment illustrate the necessity for clinical awareness and suspicion of Wernicke's encephalopathy among healthcare professionals, timely and adequate parenteral thiamine administration, and oral thiamine supplementation at therapeutic doses to correct the nutrient deficiency, halt the progression of Wernicke's encephalopathy, and promote recovery. © 2014 American Society for Parenteral and Enteral Nutrition.

PEGylated bilirubin nanoparticle as an anti-oxidative and anti-inflammatory demulcent in pancreatic islet xenotransplantation.

PubMed

Kim, Min Jun; Lee, Yonghyun; Jon, Sangyong; Lee, Dong Yun

2017-07-01

Transplanted islets suffer hypoxic stress, which leads to nonspecific inflammation. This is the major cause of islet graft failure during the early stage of intrahepatic islet transplantation. Although bilirubin has shown potent anti-oxidative and anti-inflammatory functions, its clinical applications have been limited due to its insolubility and short half-life. To overcome this problem, novel amphiphilic bilirubin nanoparticles are designed. Hydrophilic poly(ethylene glycol) (PEG) is conjugated to the hydrophobic bilirubin molecule. Then, the PEG-bilirubin conjugates form nanoparticles via self-assembly, i.e., so-called to BRNPs. BRNPs can protect islet cells not only from chemically induced oxidative stress by scavenging reactive oxygen species molecules, but also from activated macrophages by suppressing cytokine release. Importantly, in vivo experiments demonstrate that BRNP treatment can dramatically and significantly prolong islet graft survival compared to bilirubin treatment. In addition, immunohistochemical analysis shows BRNPs have potent anti-oxidative and anti-inflammatory capabilities. Collectively, novel BRNPs can be a new potent remedy for successful islet transplantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Blue emitting copper nanoclusters as colorimetric and fluorescent probe for the selective detection of bilirubin

NASA Astrophysics Data System (ADS)

R. S., Aparna; J. S., Anjali Devi; John, Nebu; Abha, K.; S. S., Syamchand; George, Sony

2018-06-01

Hurdles to develop point of care diagnostic methods restrict the translation of progress in the health care sector from bench side to bedside. In this article a simple, cost effective fluorescent as well as colorimetric nanosensor was developed for the early and easy detection of hyperbilirubinemia. A stable, water soluble bovine serum albumin stabilised copper nanocluster (BSA CuNC) was used as the fluorescent probe which exhibited strong blue emission (404 nm) upon 330 nm excitation. The fluorescence of the BSA CuNC can be effectively quenched by the addition of bilirubin by the formation of copper-bilirubin complex. Meanwhile the copper-bilirubin complex resulted in an observable colour change from pale violet to green facilitating colorimetric detection. The prepared sensor displayed good selectivity and sensitivity over other co-existing molecules, and can be used for quantifying bilirubin with a detection limit down to 257 fM. Additionally, the as-prepared probe was coated on a paper strip to develop a portable paper strip sensor of bilirubin. Moreover, the method was successfully applied in real sample analysis and obtained promising result.

Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease

MedlinePlus

... the CDC Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease Note: Javascript is disabled or is not ... spongiform encephalopathy) is a progressive neurological disorder of cattle that results from infection by an unusual transmissible ...

Qualifying and quantifying minimal hepatic encephalopathy.

PubMed

Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A; Jackson, Clive D; Kircheis, Gerald; Lauridsen, Mette M; Montagnese, Sara; Schiff, Sami; Weissenborn, Karin

2016-12-01

Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is no gold standard for the diagnosis of this syndrome. As these patients have, by definition, no recognizable clinical features of brain dysfunction, the primary prerequisite for the diagnosis is careful exclusion of clinical symptoms and signs. A large number of psychometric tests/test systems have been evaluated in this patient group. Of these the best known and validated is the Portal Systemic Hepatic Encephalopathy Score (PHES) derived from a test battery of five paper and pencil tests; normative reference data are available in several countries. The electroencephalogram (EEG) has been used to diagnose hepatic encephalopathy since the 1950s but, once popular, the technology is not as accessible now as it once was. The performance characteristics of the EEG are critically dependent on the type of analysis undertaken; spectral analysis has better performance characteristics than visual analysis; evolving analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test together with one of the validated alternative techniques or the EEG. Minimal hepatic encephalopathy has a detrimental effect on the well-being of patients and their care

Neurological and cognitive impairment associated with leaded gasoline encephalopathy.

PubMed

Cairney, Sheree; Maruff, Paul; Burns, Chris B; Currie, Jon; Currie, Bart J

2004-02-07

A toxic encephalopathy (or 'lead encephalopathy') may arise from leaded gasoline abuse that is characterised by tremor, hallucinations, nystagmus, ataxia, seizures and death. This syndrome requires emergency and intensive hospital treatment. We compared neurological and cognitive function between chronic gasoline abusers with (n=15) and without (n=15) a history of leaded gasoline encephalopathy, and with controls who had never abused gasoline (n=15). Both groups of chronic gasoline abusers had abused gasoline for the same length of time and compared to controls, showed equivalently elevated blood lead levels and cognitive abnormalities in the areas of visuo-spatial attention, recognition memory and paired associate learning. However, where gasoline abusers with no history of leaded gasoline encephalopathy showed only mild movement abnormalities, gasoline abusers with a history of leaded gasoline encephalopathy showed severe neurological impairment that manifest as higher rates of gait ataxia, abnormal rapid finger tapping, finger to nose movements, dysdiadochokinesia and heel to knee movements, increased deep tendon reflexes and presence of a palmomental reflex. While neurological and cognitive functions are disrupted by chronic gasoline abuse, leaded gasoline encephalopathy is associated with additional and long-lasting damage to cortical and cerebellar functions.

The myth of maternal transmission of spongiform encephalopathy.

PubMed Central

Ridley, R. M.; Baker, H. F.

1995-01-01

It has long been accepted that the pattern of occurrence of scrapie--the form of spongiform encephalopathy associated with sheep--is determined mainly by maternal transmission, and this view has had a profound influence on policy decisions in the control of bovine spongiform encephalopathy and on public concern over the risk to human health form this disease. The occurrence of maternal transmission is, however, not predicted by modern knowledge of the aetiology of spongiform encephalopathy, and even though claims of maternal transmission have been reiterated frequently in the literature, re-examination of the source data reveals that these data are extremely scanty, unreplicated, and probably subject to ascertainment bias. The probability of maternal transmission of spongiform encephalopathy in any species should be viewed with the greatest scepticism. Images p1073-a PMID:7580668

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. Copyright © 2015

Studies on the genetic linkage of bilirubin and androsterone UDP-glucuronyltransferases by cross-breeding of two mutant rat strains.

PubMed Central

Nagai, F; Homma, H; Tanase, H; Matsui, M

1988-01-01

Gunn rats, which have defects in bilirubin and 4-nitrophenol UDP-glucuronyltransferases (GT), were crossed with LA Wistar rats with a defect in androsterone GT. The F1 hybrids showed normal GT activities towards androsterone, bilirubin and 4-nitrophenol, demonstrating that Gunn and LA ('low activity') Wistar rats inherit a homozygous dominant trait for androsterone GT and bilirubin GT respectively. The F2 progeny showed four different combinations of bilirubin and androsterone GT activities: defects in both GT activities, a single defect in bilirubin GT activity, a single defect in androsterone GT activity and two normal GT activities. They were segregated in the approximate ratio of 1:3:3:9, which is compatible with Mendel's Principle of Independent Assortment. These results provide evidence that androsterone GT and bilirubin GT are located on different chromosomes. In the F2 generation, defective bilirubin and 4-nitrophenol GT activities were not segregated, indicating that these two mutant genes are closely linked on the same chromosome. PMID:3138978

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice.

PubMed

Amin, Sanjiv B; Wang, Hongyue; Laroia, Nirupama; Orlando, Mark

2016-06-01

This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

Protein-encapsulated bilirubin: paving the way to a useful probe for singlet oxygen.

PubMed

Pimenta, Frederico M; Jensen, Jan K; Etzerodt, Michael; Ogilby, Peter R

2015-04-01

When dissolved in a bulk solvent, bilirubin efficiently removes singlet molecular oxygen, O2(a(1)Δg), through a combination of chemical reactions and by promoting the O2(a(1)Δg)→O2(X(3)Σg(-)) nonradiative transition to populate the ground state of oxygen. To elucidate how such processes can be exploited in the development of a biologically useful fluorescent probe for O2(a(1)Δg), pertinent photophysical and photochemical parameters of bilirubin encapsulated in a protein were determined. The motivation for studying a protein-encapsulated system reflects the ultimate desire to (a) use genetic engineering to localize the probe at a specific location in a living cell, and (b) provide a controlled environment around the chromophore/fluorophore. Surprisingly, explicit values of oxygen- and O2(a(1)Δg)-dependent parameters that characterize the behavior of a given chromophore/fluorophore encased in a protein are not generally available. To the end of quantifying the effects of such an encasing protein, a recently discovered bilirubin-binding protein isolated from a Japanese eel was used. The data show that this system indeed preferentially responds to O2(a(1)Δg) and not to the superoxide ion. However, this protein not only shields bilirubin such that the rate constants for interaction with O2(a(1)Δg) decrease relative to what is observed in a bulk solvent, but the fraction of the total O2(a(1)Δg)-bilirubin interaction that results in a chemical reaction between O2(a(1)Δg) and bilirubin also decreases appreciably. The rate constants thus obtained provide a useful starting point for the general design and development of reactive protein-encased fluorescent probes for O2(a(1)Δg).

Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy

DTIC Science & Technology

2015-10-01

available, work will commence. Tau, genetics , susceptibility, MAPT, chronic traumatic encephalopathy, Alzheimer disease U U U U 1 USAMRMC Table of...AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...Include area code) October 2015 Annual Report 30 Sep 2014 - 29 Sep 2015 Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy John

Photodamage of the cells in culture sensitized with bilirubin

NASA Astrophysics Data System (ADS)

Kozlenkova, O. A.; Plavskaya, L. G.; Mikulich, A. V.; Leusenko, I. A.; Tretyakova, A. I.; Plavskii, V. Yu

2016-08-01

It has been shown that exposure to radiation of LED sources of light with an emission band maximum at about 465 and 520 nm having substantially identical damaging effects on animal cells in culture, that are in a logarithmic growth phase and preincubated with pigment. Photobiological effect is caused by photodynamic processes involving singlet oxygen generated by triplet excited sensitizer. Mono-exponential type dependence of cell survival on the energy dose indicates that it is bilirubin that acts as a sensitizer but not its photoproducts. The inclusion of bilirubin in the cells, where it is primarily localized in the mitochondria cells, it is accompanied by multiple amplification photochemical stability compared to pigment molecules bound with albumin

Reversible dementia with psychosis: Hashimoto's encephalopathy.

PubMed

Mocellin, Ramon; Lubman, Dan I; Lloyd, John; Tomlinson, E Bruce; Velakoulis, Dennis

2006-12-01

A case of presumed Hashimoto's encephalopathy (HE) is presented. The presentation included memory loss, delusions, functional decline and culminated in a generalized seizure. Anti-thyroid antibodies were detected and symptoms resolved with prednisolone. Patients with HE may present with prominent neuropsychiatric symptoms, attract psychiatric diagnoses and present to psychiatric services. Primarily a diagnosis of exclusion, HE should be considered in cases of encephalopathy in which standard investigations are negative.

The spectrum of disease in chronic traumatic encephalopathy.

PubMed

McKee, Ann C; Stern, Robert A; Nowinski, Christopher J; Stein, Thor D; Alvarez, Victor E; Daneshvar, Daniel H; Lee, Hyo-Soon; Wojtowicz, Sydney M; Hall, Garth; 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 was

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

Influence of photoisomers in bilirubin determinations on Kodak Ektachem and Hitachi analysers in neonatal specimens study of the contribution of structural and configurational isomers.

PubMed

Gulian, J M; Dalmasso, C; Millet, V; Unal, D; Charrel, M

1995-08-01

We compared data obtained with the Kodak Ektachem and Hitachi 717 Analysers and HPLC from 83 neonates under phototherapy. Total bilirubin values determined with the Kodak and Hitachi are in good agreement, but we observed a large discrepancy in the results for conjugated (Kodak) and direct (Hitachi) bilirubin. HPLC revealed that all the samples contained configurational isomers, while only 7.7% and 30.8% contained conjugated bilirubin and structural isomers, respectively. We developed a device for the specific and quantitative production of configurational or structural isomers, by irradiation with blue or green light. In vitro, total bilirubin values are coherent for the routine analysers in the presence of configurational or structural isomers. With configurational isomers, unconjugated bilirubin (Kodak) is lower than total bilirubin (Kodak), and conjugated bilirubin (Kodak) is always equal to zero, so the apparatus gives a false positive response for delta bilirubin. In contrast, the direct bilirubin (Hitachi) is constant. Furthermore, in the presence of structural isomers, unconjugated bilirubin (Kodak) is unexpectedly higher than total bilirubin (Kodak), conjugated bilirubin (Kodak) is proportional to the quantity of these isomers, and direct bilirubin (Hitachi) is constant. The contribution of photoisomers in bilirubin measurements is discussed.

Albumin-bilirubin score for predicting the in-hospital mortality of acute upper gastrointestinal bleeding in liver cirrhosis: A retrospective study.

PubMed

Zou, Deli; Qi, Xingshun; Zhu, Cuihong; Ning, Zheng; Hou, Feifei; Zhao, Jiancheng; Peng, Ying; Li, Jing; Deng, Han; Guo, Xiaozhong

2016-03-01

The albumin-bilirubin (ALBI) score is a new model for assessing the severity of liver dysfunction. In the present study, we aimed to retrospectively compare the performance of ALBI with Child-Pugh and the model for end-stage liver disease (MELD) scores for predicting the in-hospital mortality of acute gastrointestinal bleeding (AUGIB) in liver cirrhosis. All cirrhotic patients with AUGIB were eligible, provided they had the data needed to determine the ALBI score. Areas under the receiving-operator characteristics curve (AUC) are reported. Overall, 631 patients were included. In all the included patients, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.808, 0.785 (p=0.5831), and 0.787 (p=0.7033), respectively. In patients with only hepatitis B virus-related liver cirrhosis, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.865, 0.836 (p=0.6064), and 0.818 (p=0.6399), respectively. In patients with only alcohol-related liver cirrhosis, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.869, 0.860 (p=0.9003), and 0.801 (p=0.5548), respectively. In patients treated with endoscopic therapy for AUGIB, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.873, 0.884 (p=0.7898), and 0.834 (p=0.5531), respectively. The prognostic performance of the ALBI score was comparable with that of the Child-Pugh and MELD scores for predicting the in-hospital mortality of AUGIB in liver cirrhosis.

[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. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Steroid-Responsive Recurrent Encephalopathy Associated with Subacute Thyroiditis

PubMed Central

Chung, Yun Jae; Ahn, Jihyun; Ha, Sam-Yeol; Youn, Young Chul

2008-01-01

Background Steroid-responsive encephalopathy associated with subacute thyroiditis has, to our knowledge, not been reported previously. Case Report A 49-year-old woman was found collapsed and brought to our institution with decreased mentality, dysarthria, and gait disturbance. Brain magnetic resonance imaging and angiography were normal but blood tests revealed thyroid-autoantibody-negative thyrotoxicosis. Results of a 99mtechnetium-pertechnetate scan were compatible with the thyrotoxic phase of subacute thyroiditis. 14-3-3 proteins were detected in cerebrospinal fluid. Her mental status began to improve from the day following steroid administration. Recurrent encephalopathy was found 2 months after the initial admission, which was also effectively treated with steroid. Conclusions We speculate that steroid-responsive recurrent encephalopathy associated with subacute thyroiditis is a subtype of Hashimoto's encephalopathy, and consider that steroid treatment should not be delayed in suspected patients. PMID:19513293

Relationship Between the Serum Total Bilirubin and Inflammation in Patients With Psoriasis Vulgaris.

PubMed

Zhou, Zhen-Xing; Chen, Jian-Kui; Hong, Yan-Ying; Zhou, Ru; Zhou, Dong-Mei; Sun, Li-Yun; Qin, Wen-Li; Wang, Tian-Cheng

2016-09-01

Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response. © 2016 Wiley Periodicals, Inc.

Prevalence of and Factors Associated With Minimal Hepatic Encephalopathy in Patients With Cirrhosis of Liver.

PubMed

Bale, Abhijith; Pai, C Ganesh; Shetty, Shiran; Balaraju, Girisha; Shetty, Anurag

2018-06-01

Minimal hepatic encephalopathy (MHE), though highly prevalent, is a frequently underdiagnosed complication of cirrhosis of the liver. Because lack of time is reported as the major reason for non-testing, identifying patients at high risk of MHE would help in targeting them for screening. We aimed to determine the factors associated with MHE to help identify patient subgroups with a higher risk of MHE for targeted screening. Patients with cirrhosis of liver presenting between April 2015 and November 2016 were included. Those with a Psychometric Hepatic Encephalopathy Score (PHES) of ≤-5 points on psychometric testing were diagnosed to have MHE. Various demographic, clinical and laboratory parameters were included in a univariate and later multiple logistic regression models. Of the 180 (male = 166, 92.2%) patients included 94 (52.2%) had MHE. Though serum albumin, serum total bilirubin, serum aspartate aminotransferase, international normalized ration, Child-Turcotte-Pugh and Model-For-End-Stage-Liver-Disease scores were significant on univariate analysis, only CTP score was found to be significantly associated with MHE ( P  = 0.002) on multivariate analysis. A higher CTP class was associated with a higher risk of the presence of MHE. The Odds ratio for having MHE was higher with CTP classes of B ( P  ≤ 0.001) and C ( P  ≤ 0.001) compared to class A. MHE is a common complication in patients with cirrhosis of liver and higher CTP scores independently predict the presence of MHE. Patients with CTP class B and C have a higher risk of suffering from MHE than CTP class A. Screening of patients in CTP class B and C is likely to increase the MHE detection rates while saving time, although select CTP class A patients may also need screening in view of public safety or poor quality of life.

The Frequency and Severity of Magnetic Resonance Imaging Abnormalities in Infants with Mild Neonatal Encephalopathy.

PubMed

Walsh, Brian H; Neil, Jeffrey; Morey, JoAnn; Yang, Edward; Silvera, Michelle V; Inder, Terrie E; Ortinau, Cynthia

2017-08-01

To assess and contrast the incidence and severity of abnormalities on cerebral magnetic resonance imaging (MRI) between infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia. This retrospective cohort studied infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia at a single tertiary neonatal intensive care unit between 2013 and 2015. Two neuroradiologists masked to the clinical condition evaluated brain MRIs for cerebral injury after therapeutic hypothermia using the Barkovich classification system. Additional abnormalities not included in this classification system were also noted. The rate, pattern, and severity of abnormalities/injury were compared across the grades of neonatal encephalopathy. Eighty-nine infants received therapeutic hypothermia and met study criteria, 48 with mild neonatal encephalopathy, 35 with moderate neonatal encephalopathy, and 6 with severe neonatal encephalopathy. Forty-eight infants (54%) had an abnormality on MRI. There was no difference in the rate of overall MRI abnormalities by grade of neonatal encephalopathy (mild neonatal encephalopathy 54%, moderate neonatal encephalopathy 54%, and severe neonatal encephalopathy 50%; P= .89). Basal ganglia/thalamic injury was more common in those with severe neonatal encephalopathy (mild neonatal encephalopathy 4%, moderate neonatal encephalopathy 9%, severe neonatal encephalopathy 34%; P = .03). In contrast, watershed injury did not differ between neonatal encephalopathy grades (mild neonatal encephalopathy 36%, moderate neonatal encephalopathy 32%, severe neonatal encephalopathy 50%; P = .3). Mild neonatal encephalopathy is commonly associated with MRI abnormalities after therapeutic hypothermia. The grade of neonatal encephalopathy during the first hours of life may not discriminate adequately between infants with and without cerebral injury noted on MRI after therapeutic hypothermia

Hemolytic Uremic Syndrome-associated Encephalopathy Successfully Treated with Corticosteroids.

PubMed

Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira

2017-11-01

The encephalopathy that occurs in association with hemolytic uremic syndrome (HUS), which is caused by enterohemorrhagic Escherichia coli (E. coli), has a high mortality rate and patients sometimes present sequelae. We herein describe the case of a 20-year-old woman who developed encephalopathy during the convalescent stage of HUS caused by E.coli O26. Hyperintense lesions were detected in the pons, basal ganglia, and cortex on diffusion-weighted brain MRI. From the onset of HUS encephalopathy, we treated the patient with methylprednisolone (mPSL) pulse therapy alone. Her condition improved, and she did not present sequelae. Our study shows that corticosteroids appear to be effective for the treatment of some patients with HUS encephalopathy.

The Relationship between Serum Bilirubin and Elevated Fibrotic Indices among HBV Carriers: A Cross-Sectional Study of a Chinese Population.

PubMed

Du, Min; Zhang, Shanshan; Xiao, Lin; Xu, Yanyan; Liu, Peiyi; Tang, Yuhan; Wei, Sheng; Xing, Mingyou; Miao, Xiaoping; Yao, Ping

2016-12-09

The study probed the association between bilirubin and hepatitis B virus (HBV) infection and progression. A cross-sectional analysis of 28,500 middle aged and elderly Chinese participants was performed to analyze the differences of bilirubin in terms of hepatitis B surface antigen (HBsAg) positive or negative and the correlation between bilirubin and severity of hepatic fibrosis estimated by non-invasive indices. Bilirubin was significantly higher in the HBsAg (+) group than the HBsAg (-) group. Higher bilirubin levels were consistently associated with elevated liver fibrosis indices among HBsAg carriers. Compared with quartile 1 of total bilirubin (TBil), the multivariable-adjusted ORs (95% CIs) for elevated fibrosis indices of quartile 4 were 2.24 (95% CIs, 1.57-3.21) estimated by fibrosis 4 score (FIB-4) and 2.22 (95% CIs, 1.60-3.08) estimated by aspartate transaminase to platelet ratio index (APRI). In addition, direct bilirubin (DBil) had a stronger association with elevated liver fibrosis indices than did indirect bilirubin (IBil). Furthermore, the relationship between DBil and elevated fibrosis indices was more robust among participants who were female, overweight or had central fat distribution. These findings suggested that bilirubin levels, especially DBil, were independently associated with an increased risk of increased fibrosis indices.

Dengue-Associated Posterior Reversible Encephalopathy Syndrome, Vietnam

PubMed Central

Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Nghia, Ho Dang Trung; Phuong, Tran My; Duc, Du Trong; Chau, Nguyen Van Vinh; Wills, Bridget; Lim, Choie Cheio Tchoyoson; Thwaites, Guy; Simmons, Cameron Paul

2018-01-01

Dengue can cause neurologic complications in addition to the more common manifestations of plasma leakage and coagulopathy. Posterior reversible encephalopathy syndrome has rarely been described in dengue, although the pathophysiology of endothelial dysfunction likely underlies both. We describe a case of dengue-associated posterior reversible encephalopathy syndrome and discuss diagnosis and management. PMID:29350156

Can Patients Who Develop Cerebral Death in Fulminant Liver Failure Despite Liver Transplantation Be Previously Forseen?

PubMed

Sarici, K B; Karakas, S; Otan, E; Ince, V; Koc, C; Koc, S; Bayraktar, H; Aydin, C; Kayaalp, C; Gungor, S; Kablan, Y; Yilmaz, S

2017-04-01

The outcome of medical treatment is worse in fulminant liver failure (FLF) developing on acute or chronic ground. Recently, liver transplantations with the use of living and cadaveric donors have been performed in these diseases and good results obtained. In this study, we aimed to present the factors affecting the recovery of cerebral functions after liver transplantation in hepatic encephalopathy (HE) developing in FLF, to identify irreversible patient groups and to prevent unnecessary liver transplantation. In Inonu University's Liver Transplant Institute, 69 patients who made an emergency notice to the National Coordination Center for liver transplantation owing to FLF from January 2012 to December 2015 were included in the study. Patients were divided into 2 groups. Group 1 consisted of 52 patients who underwent liver transplantation and recovered normal brain function, and group 2 had 17 patients who underwent liver transplantation and did not recover normal brain function and had cerebral death. All patients were evaluated before surgery for clinical encephalopathy stage, light reflex, and convulsions. Groups were compared and assessed according to age (>40, 10-40 and <10 years), body mass index, etiologic factor, preoperative laboratory values, transplantation type, mortality, and encephalopathy level. Multivariate analysis was done for specific parameters. Prothrombin time (PT), international normalized ratio (INR), and total bilirubin values were significantly different between the groups. There was no significant difference between the groups regarding ammonia and lactate levels. There was a statistically significant difference between the groups regarding sodium and potassium levels from serum electrolytes. However, the averages of both groups were within normal limits. pH and total bilirubin levels were meaningful for multivariate analysis. HE reversibility, mortality, and morbidity are important in patients with HE who undergo liver

Comparison of Transmissible Mink Encephalopathy Isolates in Raccoons

USDA-ARS?s Scientific Manuscript database

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...

Antioxidant status of bilirubin and uric acid in patients diagnosed with Plasmodium falciparum malaria in Douala.

PubMed

Bertrand, Kouam Eric; Mathieu, Ndomou; Inocent, Gouado; Honore, Fotso Kuate

2008-06-15

Oxidative stress and changes in antioxidant status have been implicated in the pathogenesis of malaria. To assess the antioxidant level ofbilirubin and uric acid associated with falciparum malaria infection, 60 untreated patients (30 men and 30 women) in Douala, Cameroon were screened for the study. Sixty five healthy individuals (29 men and 36 women) were used as controls. Total and conjugated bilirubin were calculated using Jendrassik-Grof method while uric acid was determined using Barham-Trinder method. It was observed that total and conjugated bilirubins were significantly (p < 0.001) higher in malaria patients (10.722 +/- 4.043 and 3.627 +/- 1.571 mg L(-1), respectively) when compared to control (6.830 +/- 2.436 and 1.777 +/- 0.729 mg L(-1)) and these bilirubin levels increased significantly with parasite count (p < 0.050). There was also significant increased (p = 0.021) of uric acid in malaria patients (56.262 +/- 13.963 mg L(-1)) compared to controls (49.838 +/- 15.419 mg L(-1)). No significant differences based on sex were observed on uric acid, parasite count, total and conjugated bilirubins in malaria patients. Positive correlations were obtained between parasite count and total bilirubin (r = 0.320, p < 0.050), conjugated bilirubin (r = 0.477, p < 0.001), uric acid (r = 0.060, p > 0.050) and between total and conjugated bilirubin (r = 0.729, p < 0.001). From this study, it has been hypothesized that the augmentation of plasma level ofbilirubin and uric acid could provide more protection against oxidative stress induced by malaria.

Parental infant jaundice colour card design successfully validated by comparing it with total serum bilirubin.

PubMed

Xue, Guo-Chang; Ren, Ming-Xing; Shen, Lin-Na; Zhang, Li-Wen

2016-12-01

We designed a jaundice colour card that could be used by the parents of neonates and validated it by comparing it with total serum bilirubin levels. There were 106 term Chinese neonates in the study. The majority weighed between 2500 g and 3499 g (63%) and had a gestational age of 37-40 weeks (77%). The jaundice colour card and photometric determination were used to screen for neonatal jaundice and compared with serum bilirubin. The bilirubin levels were measured by mothers using the jaundice colour card, and 67% of the measurements were taken at 11-20 days (range 3-30). The measurements at the infant's forehead, cheek and sternum showed strong correlations with total serum bilirubin. The mean differences between the total serum bilirubin and the jaundice colour card measurements from the forehead, cheek and sternum were 1.9 mg/dL, 0.3 mg/dL and 1.5 mg/dL, respectively. When total serum bilirubin >13 mg/dL was used as the cut-off point, the areas under the receiver operating characteristics curves were 0.934 for the forehead, 0.985 for the cheek and 0.966 for the sternum. We established the validity of the jaundice colour card as a parental measurement tool for jaundice in Chinese neonates, and the cheek was the best measurement site. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

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

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…

Rare and unusual ... or are they? Less commonly diagnosed encephalopathies associated with systemic disease.

PubMed

Weathers, Allison L; Lewis, Steven L

2009-04-01

Encephalopathy due to hepatic or renal failure, electrolyte disturbances, or the administration of benzodiazepines and narcotics is commonly encountered, well reviewed in the literature, and, therefore, not usually missed. This article focuses on encephalopathies that were previously well described but may be overlooked by modern clinicians, as well as those that are still taught in the classroom but seldom thought of in practice. Due to the presumed relative rarity of these cases and emphasis on the well-memorized "classic" clinical presentations, these often treatable, and perhaps not so rare, encephalopathies due to systemic medical illness may go undiagnosed and untreated. Pancreatic encephalopathy, Wernicke's encephalopathy, and pellagra encephalopathy are reviewed in detail; cefepime and ifosfamide encephalopathies are discussed as examples of specific medication-induced encephalopathies. Septic encephalopathy, central pontine myelinolysis, and fat embolism syndrome are briefly reviewed. The encephalopathies reviewed have the potential for devastating neurological consequences if recognition and, therefore, treatment are delayed. Clinical improvement for many of these syndromes depends on prompt intervention. This article highlights some representative examples of less-commonly diagnosed metabolic and toxic encephalopathies.

Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy.

PubMed

Elwir, Saleh; Hal, Hassan; Veith, Joshua; Schreibman, Ian; Kadry, Zakiyah; Riley, Thomas

2016-08-01

Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient's clinical profile. A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P < 0.05) were analysed by a multivariate logistic regression model. A total of 117 patients met the inclusion criteria and were divided into a hepatic encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy.

PubMed

Eckman, Elizabeth A; Pacheco-Quinto, Javier; Herdt, Aimee R; Halperin, John J

2018-01-11

Lyme encephalopathy, characterized by non-specific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to CNS infection. Identical symptoms occur in innumerable other inflammatory states and may reflect the effect of systemic immune mediators on the CNS. Multiplex immunoassays were used to characterize the inflammatory profile in serum and CSF from Lyme and non-Lyme patients with a range of symptoms to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. CSF CXCL13 was elevated dramatically in confirmed neuroborreliosis (n=8) and to a lesser extent in possible neuroborreliosis (n=11) and other neuroinflammatory conditions (n=44). Patients with Lyme (n=63) or non-Lyme (n=8) encephalopathy had normal CSF findings, but had elevated serum levels of IL-7, TSLP, IL-17A, IL-17F, and MIP-1α/CCL3. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody (ITAb) production. However, CXCL13 does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory ITAb, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or following appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors. These markers are also elevated in non-Lyme disease patients experiencing similar symptoms. Our results support that in the absence of CSF abnormalities, neurobehavioral symptoms are associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Contrast-induced encephalopathy following cardiac catheterization.

PubMed

Spina, Roberto; Simon, Neil; Markus, Romesh; Muller, David Wm; Kathir, Krishna

2017-08-01

To describe the epidemiology, pathophysiology, clinical presentation, and management of contrast-induced encephalopathy (CIE) following cardiac catheterization. CIE is an acute, reversible neurological disturbance directly attributable to the intra-arterial administration of iodinated contrast medium. The PubMed database was searched and all cases in the literature were retrieved and reviewed. 52 reports of CIE following cardiac catheterization were found. Encephalopathy, motor and sensory disturbances, vision disturbance, opthalmoplegia, aphasia, and seizures have been reported. Transient cortical blindness is the most commonly reported neurological syndrome, occurring in approximately 50% of cases. The putative mechanism involves disruption of the blood brain barrier and direct neuronal injury. Contrast-induced transient vasoconstriction has also been implicated. Symptoms typically appear within minutes to hours of contrast administration and resolve entirely within 24-48 hr. Risk factors may include hypertension, diabetes mellitus, renal impairment, the administration of large volumes of iodinated contrast, percutaneous coronary intervention or selective angiography of internal mammary grafts, and previous adverse reaction to iodinated contrast. Characteristic findings on cerebral imaging include cortical and sub-cortical contrast enhancement on computed tomography (CT). Imaging findings in CIE may mimic subarachnoid hemorrhage or cerebral ischemia; the Hounsfield scale on CT and the apparent diffusion coefficient on magnetic resonance imaging (MRI) are useful imaging tools in distinguishing these entities. In some cases, brain imaging is normal. Prognosis is excellent with supportive management alone. CIE tends to recur, although re-challenge with iodinated contrast without adverse effects has been documented. CIE is an important clinical entity to consider in the differential diagnosis of stroke following cardiac catheterization. Given that prognosis is

Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats

NASA Astrophysics Data System (ADS)

Kuznietsova, H. M.; Lynchak, O. V.; Dziubenko, N. V.; Osetskyi, V. L.; Ogloblya, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Ritter, U.; Scharff, P.

2018-03-01

Sclerosing cholangitis is the liver disease of uncertain etiology, extremely unfavorable prognosis and lack of effective medication therapy. Therefore, the effect of water-soluble biocompatible C60 fullerenes (C60FAS) on the liver functional state on rat acute-cholangitis model was aimed to be discovered. Acute cholangitis was simulated by single α-naphthyl isothiocyanate (ANIT, 100 mg/kg) per os administration; C60FAS (0.5 mg/kg) was administered either per os or intraperitoneally in 24 and 48 h after ANIT ingestion, and in 72 h the animals were sacrificed. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), the total and direct bilirubin, creatinine and urea in the blood serum were determined, and the liver morphological state was assessed. In animals experienced ANIT-induced acute cholangitis, the total and direct bilirubin, creatinine, ALT, AST, ALP and LDH 1.5-4-fold increase were observed, indicating cytolysis of hepatocytes, cholestasis, and renal dysfunction. The features of periductal fibrosis, biliary epithelium atrophy, and portal-portal linking septa formation were detected, confirming the sclerosing cholangitis development. C60FAS promoted to the normalization of direct and total bilirubin levels, the ALT activity and diminution of fibrotic features. In addition, C60FAS intraperitoneal administration also normalized the ALP activity, indicating the attenuation of disease symptoms. However, the AST activity and creatinine level remained unchanged, and the LDH activity even increased, manifesting the partial persistence of cholestasis and renal dysfunction. Thus, the therapeutic application of C60FAS promotes a partial protection of liver against cholangitis.

Combined application of dexamethasone and hyperbaric oxygen therapy yields better efficacy for patients with delayed encephalopathy after acute carbon monoxide poisoning.

PubMed

Xiang, Wenping; Xue, Hui; Wang, Baojun; Li, Yuechun; Zhang, Jun; Jiang, Changchun; Liang, Furu; Pang, Jiangxia; Yu, Lehua

2017-01-01

Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) commonly occurs after recovering from acute CO poisoning. This study was performed to assess the efficacy of the combined application of dexamethasone and hyperbaric oxygen (HBO) therapy in patients with DEACMP. A total of 120 patients with DEACMP were recruited and randomly assigned into the experimental group (receiving dexamethasone 5 mg/day or 10 mg/day plus HBO therapy) and control group (HBO therapy as monotherapy). Meanwhile, the conventional treatments were provided for all the patients. We used the Mini-Mental State Examination (MMSE) scale to assess the cognitive function, the National Institutes of Health Stroke Scale (NIHSS) to assess the neurological function and the remission rate (RR) to assess the clinical efficacy. Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) was also measured. After 4 weeks of treatment, compared to the control group, the experimental group had a significantly higher remission rate ( P =0.032), a significantly higher average MMSE score ( P =0.037) and a significantly lower average NIHSS score ( P =0.002). Meanwhile, there was a trend toward better improvement with dexamethasone 10 mg/day, and the level of MBP in the CSF of patients was significantly lower in the experimental group than in the control group ( P <0.0001). The addition of dexamethasone did not significantly increase the incidence of adverse events. These results indicate that the combined application of dexamethasone and HBO therapy could yield better efficacy for patients with DEACMP and should be viewed as a potential new therapy.

Bovine spongiform encephalopathy: "mad cow disease".

PubMed

1996-07-01

Bovine spongiform encephalopathy (BSE), also known as "mad cow disease," is a fatal brain disease of cattle first recognized in the United Kingdom. In humans, the most common transmissible spongiform encephalopathy is Creutzfeldt-Jacob Disease (CJD). Although no cases of CJD have been directly linked to beef consumption, an advisory committee has reported that 10 recent cases of a CJD variant may be associated with BSE. This announcement has alarmed consumers well beyond the borders of the United Kingdom.

Evaluation of bilirubin interference and accuracy of six creatinine assays compared with isotope dilution-liquid chromatography mass spectrometry.

PubMed

Nah, Hyunjin; Lee, Sang-Guk; Lee, Kyeong-Seob; Won, Jae-Hee; Kim, Hyun Ok; Kim, Jeong-Ho

2016-02-01

The aim of this study was to estimate bilirubin interference and accuracy of six routine methods for measuring creatinine compared with isotope dilution-liquid chromatography mass spectrometry (ID-LC/MS). A total of 40 clinical serum samples from 31 patients with serum total bilirubin concentration >68.4μmol/L were collected. Serum creatinine was measured using two enzymatic reagents and four Jaffe reagents as well as ID-LC/MS. Correlations between bilirubin concentration and percent difference in creatinine compared with ID-LC/MS were analyzed to investigate bilirubin interference. Bias estimations between the six reagents and ID-LC/MS were performed. Recovery tests using National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 967a were also performed. Both the enzymatic methods showed no bilirubin interference. However, three of the four Jaffe methods demonstrated significant bilirubin concentration-dependent interference in samples with creatinine levels <53μmol/L, and two of them showed significant bilirubin interference in samples with creatinine levels ranging from 53.0 to 97.2μmol/L. Comparison of these methods with ID-LC/MS using patients' samples with elevated bilirubin revealed that the tested methods failed to achieve the bias goal at especially low levels of creatinine. In addition, recovery test using NIST SRM 967a showed that bias in one Jaffe method and two enzymatic methods did not achieve the bias goal at either low or high level of creatinine, indicating they had calibration bias. One enzymatic method failed to achieve all the bias goals in both comparison experiment and recovery test. It is important to understand that both bilirubin interference and calibration traceability to ID-LC/MS should be considered to improve the accuracy of creatinine measurement. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Hyperbilirubinaemia a predictive factor for complicated acute appendicitis: a study in a tertiary care hospital.

PubMed

Jamaluddin, Muhammad; Hussain, Syed Mohammad Abbas; Ahmad, Humaid

2013-11-01

To study the role of hyperbilirubinaemia as a predictive factor for appendiceal perforation in acute appendicitis. The prospective, descriptive study was conducted at the Abbasi Shaheed Hospital and the Karachi Medical and Dental College, Karachi, from January 2010 to June 2012. It comprised all patients coming to the surgical outpatient department and emergency department with pain in the right iliac fossa with duration less than seven days. They were clinically assessed for signs and symptoms of acute appendicitis and relevant tests were conducted. Patients were diagnosed as a case of acute appendicitis on the basis of clinical and ultrasound findings, and were prepared for appendicectomy. Per-operative findings were recorded and specimens were sent for histopathology to confirm the diagnosis. SPSS version 10 was used to analyse the data. Of the 71 patients, 37 (52.10%) were male and 34 (47.90%) were female. The age range was 3-57 years, and most of the patients (n = 33; 46.5%) were between 11 and 20 years. Besides, 63 (89%) patients had pain in the right iliac fossa of less than four-days duration, while 8 (11%) had pain of longer duration.Total leukocyte count was found to be elevated in 33 (46.5%) patients, while total serum bilirubin was elevated in 41 (57.70%). Ultrasound of abdomen showed 9 (12.70%) patients having normal appearance of appendix and 59 (83.30%) had inflamed appendix. Four (5.60%) patients had no signs of inflammation on naked eye appearance per operatively. Histopathology of appendix showed 10 (14.10%) patients had non-inflammatory appendix. Patients with signs and symptoms of acute appendicitis and a raised total serum bilirubin level indicated a complication of acute appendicitis requiring an early intervention to prevent peritonitis and septicaemia. A raised serum bilirubin level is a good indicator of complicated acute appendicitis, and should be included in the assessment of patients with suspected complicated acute appendicitis.

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

Early Recognition of Chronic Traumatic Encephalopathy through FDDNP PET Imaging

DTIC Science & Technology

2014-10-01

Encephalopathy through FDDNP PET Imaging PRINCIPAL INVESTIGATOR: Charles Bernick, MD, MPH...Traumatic Encephalopathy through FDDNP PET Imaging 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0486 5c. PROGRAM ELEMENT NUMBER 6... Encephalopathy . This project will examine whether FDDNP PET imaging correlates with, and/or can predict, decline in cognitive function in those exposed to

Simultaneous estimation of transcutaneous bilirubin, hemoglobin, and melanin based on diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Abdul, Wares MD.; Ohtsu, Mizuki; Nakano, Kazuya; Haneishi, Hideaki

2018-02-01

We propose a method to estimate transcutaneous bilirubin, hemoglobin, and melanin based on the diffuse reflectance spectroscopy. In the proposed method, the Monte Carlo simulation-based multiple regression analysis for an absorbance spectrum in the visible wavelength region (460-590 nm) is used to specify the concentrations of bilirubin (Cbil), oxygenated hemoglobin (Coh), deoxygenated hemoglobin (Cdh), and melanin (Cm). Using the absorbance spectrum calculated from the measured diffuse reflectance spectrum as a response variable and the extinction coefficients of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Total hemoglobin concentration (Cth) and tissue oxygen saturation (StO2) are simply calculated from the oxygenated hemoglobin and deoxygenated hemoglobin. In vivo animal experiments with bile duct ligation in rats demonstrated that the estimated Cbil is increased after ligation of bile duct and reaches to around 20 mg/dl at 72 h after the onset of the ligation, which corresponds to the reference value of Cbil measured by a commercially available transcutaneous bilirubin meter. We also performed in vivo experiments with rats while varying the fraction of inspired oxygen (FiO2). Coh and Cdh decreased and increased, respectively, as FiO2 decreased. Consequently, StO2 was dramatically decreased. The results in this study indicate potential of the method for simultaneous evaluation of multiple chromophores in skin tissue.

Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma.

PubMed

Kim, Dong Eon; Lee, Yonghyun; Kim, MinGyo; Lee, Soyoung; Jon, Sangyong; Lee, Seung-Hyo

2017-09-01

Although asthma, a chronic inflammatory airway disease, is relatively well-managed by inhaled corticosteroids, the side effects associated with the long-term use of these agents precipitate the need for alternative therapeutic options based on differing modes of action. Bilirubin, a potent endogenous antioxidant, and anti-inflammatory molecule have been shown to ameliorate asthmatic symptoms; however, its clinical translation has been limited owing to its water insolubility and associated potential toxicity. Here we report the first application of bilirubin-based nanoparticles (BRNPs) as a nanomedicine for the treatment of allergic lung inflammatory disease. BRNPs were prepared directly from self-assembly of PEGylated bilirubin in aqueous solution and had a hydrodynamic diameter of ∼100 nm. Because allergen-specific type 2 T-helper (Th2) cells play a key role in the pathogenesis and progression of allergic asthma, the effects of BRNPs on Th2 immune responses were investigated both in vivo and in vitro. BRNPs after intravenous injection (i.v.) showed much higher serum concentration and a longer circulation time of bilirubin than the intraperitoneal injection (i.p.) of BRNPs or unconjugated bilirubin (UCB). The anti-asthmatic effects of BRNPs were assessed in a mouse model of allergen-induced asthma. Compared with UCB, treatment with BRNPs suppressed the symptoms of experimental allergic asthma and dramatically ameliorated Th2-related allergic lung inflammation. Consistent with these results, BRNPs caused a reduction of Th2 cell populations and the expression of related cytokines by antibody-stimulated CD4 + T cells in vitro. Therefore, our results establish BRNPs as an important immunomodulatory agent that may be useful as a therapeutic for allergic lung inflammatory disease and other immune-mediated disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Topiramate increases the risk of valproic acid-induced encephalopathy.

PubMed

Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

2013-01-01

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Analysis of urobilinogen and urine bilirubin for intra-abdominal injury in blunt trauma patients.

PubMed

Gorchynski, Julie; Dean, Kevin; Anderson, Craig L

2009-05-01

To determine the point prevalence of urine bilirubin, urine hemoglobin and urobilinogen in blunt trauma patients, and to evaluate its utility as a screening tool for intra-abdominal injury. Data analysis of 986 consecutive trauma patients of which 698 were adult blunt trauma patients. Five-hundred sixteen subjects had a urinalysis and a CT scan of the abdomen/pelvis or exploratory laparotomy. We reviewed initial urinalysis results from trauma patients in the emergency department (ED) for the presence of urine hemoglobin, uroblinogen and urine bilirubin. Computed tomography (CT) scan results and operative reports were reviewed from the trauma registry for evidence of liver laceration, spleen laceration, bowel or mesenteric injuries. There were 73 injuries and 57/516 patients (11%) with intra-abdominal injury. Urinalysis was positive for urobilinogen in 28/516 (5.4%) patients, urine bilirubin in 15/516 (2.9%) patients and urine hemoglobin in 313/516 (61%) patients. Nineteen/forty-seven (4%) subjects had liver lacerations, 28/56 (5%) splenic lacerations, and 15/5 (3%) bowel or mesenteric injury. Comparing the proportion of patients that had urobilinogen detected in the group with and without intra-abdominal injury, 8/28 (29%) subjects with urobilinogen, 5/15 (33%) subjects with bilirubin and 47/313 (15%) subjects with urine hemoglobin were found to have liver lacerations, spleen lacerations, or bowel/mesenteric injuries. Preexisting liver or biliary conditions were not statistically associated with elevation of urine bilirubin, urine hemoglobin or urobilinogen on initial urinalysis after blunt abdominal trauma. Point prevalence for urobilinogen, urine bilirubin and urine hemoglobin are 5.43% (28/516), 2.91% (15/516) and 60.7% (313/516) respectively. The utility of the initial routine urinalysis in the ED for adult blunt abdominal trauma patients should not be used as a screening tool for the evaluation of intra-abdominal injury.

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…

CADASIL: Migraine, Encephalopathy, Stroke and Their Inter-Relationships.

PubMed

Tan, Rhea Yan Ying; Markus, Hugh Stephen

2016-01-01

Migraine is common in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) but its treatment responses are not well described, and its relationship to stroke risk unknown. Encephalopathy is a less common presentation; it has been suggested it is related to migraine. We characterised migraine patterns and treatment responses in CADASIL, and examined associations between migraine and both stroke risk and encephalopathy. 300 symptomatic CADASIL patients were prospectively recruited from a national referral clinic over a nineteen year period, from 1996 to 2015. Data was collected using a standardised questionnaire. Migraine was classified according to the International Classification of Headache Disorders, 3rd edition (beta version). A cross-sectional analysis was carried out on the data collected. Migraine was present in 226 (75.3%), and the presenting feature in 203 (67.7%). It was usually accompanied by aura (89.8%). Patients showed variable responses to a variety of drugs for migraine. Of 24 given triptans, 45.5% had consistent or partial responses. None had complications following triptans. Thirty-three (11.0%) patients experienced encephalopathy lasting on average 8.1 ± 3.4 days. Patients with migraine with aura had higher odds of encephalopathy (OR = 5.4; 95%CI 1.6-28.4; p = 0.002). Patients with confusional aura had higher odds of encephalopathy than those with other aura types (OR = 2.5, 95%CI = 1.0-5.8, p = 0.04). There was also no increase in risk of encephalopathy with sex or age at onset of migraine. Migraineurs had a lower stroke risk than non-migraineurs (HR = 0.46, 95%CI 0.3-0.6, p = 2.1x10-6). Migraine with aura is a prominent feature of CADASIL. Treatment responses are similar to those seen in the general migraine population and no complications were observed with triptans. Migraine with aura was associated with increased risk of encephalopathy suggesting they may share pathophysiological mechanisms

Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated Encephalomyelitis From Multiple Sclerosis at First Demyelination.

PubMed

Aung, Wint Yan; Massoumzadeh, Parinaz; Najmi, Safa; Salter, Amber; Heaps, Jodi; Benzinger, Tammie L S; Mar, Soe

2018-01-01

There are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disability. Therefore, we intend to explore neuroimaging biomarkers that can reliably distinguish between the two diagnoses. We reviewed prospectively collected clinical, standard MRI and diffusion tensor imaging data from 12 pediatric patients who presented with acute demyelination with and without encephalopathy. Patients were followed for an average of 6.5 years to determine the accuracy of final diagnosis. Final diagnosis was determined using 2013 International Pediatric MS Study Group criteria. Control subjects consisted of four age-matched healthy individuals for each patient. The study population consisted of six patients with central nervous system demyelination with encephalopathy with a presumed diagnosis of acute disseminated encephalomyelitis and six without encephalopathy with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome at high risk for multiple sclerosis. During follow-up, two patients with initial diagnosis of acute disseminated encephalomyelitis were later diagnosed with multiple sclerosis. Diffusion tensor imaging region of interest analysis of baseline scans showed differences between final diagnosis of multiple sclerosis and acute disseminated encephalomyelitis patients, whereby low fractional anisotropy and high radial diffusivity occurred in multiple sclerosis patients compared with acute disseminated encephalomyelitis patients and the age-matched controls. Fractional anisotropy and radial diffusivity measures may have the potential to serve as biomarkers for distinguishing acute disseminated encephalomyelitis from multiple sclerosis at the onset. Copyright © 2017 Elsevier Inc. All

Genetics Home Reference: familial encephalopathy with neuroserpin inclusion bodies

MedlinePlus

... Home Health Conditions FENIB Familial encephalopathy with neuroserpin inclusion bodies Printable PDF Open All Close All Enable ... expand/collapse boxes. Description Familial encephalopathy with neuroserpin inclusion bodies ( FENIB ) is a disorder that causes progressive ...

Relationship between clock and star drawing and the degree of hepatic encephalopathy.

PubMed

Edwin, Natasha; Peter, John Victor; John, George; Eapen, C E; Graham, Petra L

2011-09-01

PURPOSE OF THE STUDY Current hepatic encephalopathy grading tools are limited because of complexity or subjectivity. The degree of constructional apraxia could serve as a simple, objective and reproducible tool to grade encephalopathy. STUDY DESIGN In this cross-sectional study of patients with chronic liver disease, the degree of constructional apraxia was judged by their ability to copy a star and clock face and compared with conventional encephalopathy grading by the West Haven Criteria (WHC) and the Porto Systemic Encephalopathy Index (PSEI). Three blinded observers independently graded the figures. Sensitivity, specificity and positive predictive value (PPV) of clock and star scores (score 0 implying no encephalopathy and >0 hepatic encephalopathy) were assessed against conventional scoring systems (WHC grade >0 or PSEI ≥0.33 indicating encephalopathy). Mosaic and box plots were generated to assess if the degree of constructional apraxia correlated with the severity of encephalopathy. RESULTS 71 patients were studied between October 2008 and July 2009; 11 (15.4%) had WHC grade 0, 32 (45%) grade 1, and 28 (39.4%) grades 2 and 3 encephalopathy. The sensitivity, specificity and PPV of the clock drawing for the diagnosis of encephalopathy was 85%, 80%, and 96%, respectively, and 77%, 70%, and 94%, respectively, for the star drawing. Box plots and intervals on mean PSEI showed an increasing relationship between clock/star scores and PSEI. There was substantial agreement between WHC and clock (weighted κ 0.61) and star scores (weighted κ 0.71). Inter-observer reliability was at least 0.70 for star and at least 0.79 for the clock score. CONCLUSION Clock and star drawing may serve as reproducible, inexpensive bedside tools for diagnosing and grading the severity of hepatic encephalopathy.

Conical intersection in a bilirubin model A possible pathway for phototherapy of neonatal jaundice

NASA Astrophysics Data System (ADS)

Zietz, Burkhard; Blomgren, Fredrik

2006-03-01

Phototherapy of neonatal jaundice involves Z- E-isomerisation around an exocyclic double bond in bilirubin. Our results of a CASSCF study on dipyrrinone, a bilirubin model, show a conical intersection between the ground and first excited singlet states associated with the Z- E-isomerisation. The conical intersection, located ca. 50 kJ/mol below the Franck-Condon-point, together with the S 1 minimum, ca. 50 kJ/mol below the conical intersection, are able to explain the available time-resolved spectroscopic data (the very short lifetime of the initially excited state and transient 'dark state' intermediate) as well as bilirubin's very low fluorescence quantum yield and the medium-efficient photoisomerisation reaction.

External validation of the bilirubin-atazanavir nomogram for assessment of atazanavir plasma exposure in HIV-1-infected patients.

PubMed

Rekić, Dinko; Röshammar, Daniel; Bergstrand, Martin; Tarning, Joel; Calcagno, Andrea; D'Avolio, Antonio; Ormaasen, Vidar; Vigan, Marie; Barrail-Tran, Aurélie; Ashton, Michael; Gisslén, Magnus; Äbelö, Angela

2013-04-01

Atazanavir increases plasma bilirubin levels in a concentration-dependent manner. Due to less costly and readily available assays, bilirubin has been proposed as a marker of atazanavir exposure. In this work, a previously developed nomogram for detection of suboptimal atazanavir exposure is validated against external patient populations. The bilirubin nomogram was validated against 311 matching bilirubin and atazanavir samples from 166 HIV-1-infected Norwegian, French, and Italian patients on a ritonavir-boosted regimen. In addition, the nomogram was evaluated in 56 Italian patients on an unboosted regimen. The predictive properties of the nomogram were validated against observed atazanavir plasma concentrations. The use of the nomogram to detect non-adherence was also investigated by simulation. The bilirubin nomogram predicted suboptimal exposure in the patient populations on a ritonavir-boosted regimen with a negative predictive value of 97% (95% CI 95-100). The bilirubin nomogram and monitoring of atazanavir concentrations had similar predictive properties for detecting non-adherence based on simulations. Although both methods performed adequately during a period of non-adherence, they had lower predictive power to detect past non-adherence episodes. Using the bilirubin nomogram for detection of suboptimal atazanavir exposure in patients on a ritonavir-boosted regimen is a rapid and cost-effective alternative to routine measurements of the actual atazanavir exposure in plasma. Its application may be useful in clinical settings if atazanavir concentrations are not available.

Significance of change in serum bilirubin in predicting left ventricular reverse remodeling and outcomes in heart failure patients with cardiac resynchronization therapy.

PubMed

Hosoda, Junya; Ishikawa, Toshiyuki; Matsumoto, Katsumi; Iguchi, Kohei; Matsushita, Hirooki; Ogino, Yutaka; Taguchi, Yuka; Sugano, Teruyasu; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi

2017-11-01

Research on the correlation of serum bilirubin level with cardiac function as well as outcomes in heart failure patients with cardiac resynchronization therapy (CRT) has not yet been reported. The aim of this study was to analyze the relationship between change in serum bilirubin level and left ventricular reverse remodeling, and also to clarify the impact of bilirubin change on clinical outcomes in CRT patients. We evaluated 105 consecutive patients who underwent CRT. Patients who had no serum total-bilirubin data at both baseline and 3-9 months' follow-up or had died less than 3 months after CRT implantation were excluded. Accordingly, a total of 69 patients were included in the present analysis. The patients were divided into two groups: decreased bilirubin group (serum total-bilirubin level at follow-up≤that at baseline; n=48) and increased bilirubin group (serum total-bilirubin level at follow-up>that at baseline; n=21). Mean follow-up period was 39.3 months. In the decreased bilirubin group, mean left ventricular end-systolic diameter decreased from 54.5mm to 50.2mm (p=0.001) and mean left ventricular ejection fraction increased significantly from 29.8% to 37.0% (p=0.001). In the increased bilirubin group, there was no significant change in echocardiographic parameters from baseline to follow-up. In Kaplan-Meyer analysis, cardiac mortality combined with heart failure hospitalization in the increased bilirubin group was significantly higher than that in the decreased bilirubin group (log-rank p=0.018). Multivariate Cox regression analysis revealed that increased bilirubin was an independent predictor of cardiac mortality combined with heart failure hospitalization (OR=2.66, p=0.023). The change in serum bilirubin is useful for assessment of left ventricular reverse remodeling and prediction of outcomes in heart failure patients with CRT. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Refractory Causes of Kernicterus in Developed Countries: Can We Eradicate G6PD Deficiency Triggered and Low-Bilirubin Kernicterus?

PubMed

Watchko, Jon F

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency triggered and low-bilirubin kernicterus persist despite current prevention strategies. Review efforts to eradicate bilirubin induced brain injury in these two conditions including novel approaches to risk assessment and hyperbilirubinemia evaluation. In the case of G6PD deficiency, a heightened awareness of populations at risk and an expanded kernicterus prevention strategy focused on intensified parental engagement, education and counselling on neonatal jaundice is needed. In the case of low-bilirubin kernicterus, a renewed focus on identifying infants with hypoalbuminemia and implementation of hyperbilirubinemia treatment thresholds based on the bilirubin/albumin ratio is needed. Bilirubin binding panels when commercially available will prove valuable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency.

PubMed

Serrano, Mercedes; Rebollo, Mónica; Depienne, Christel; Rastetter, Agnès; Fernández-Álvarez, Emilio; Muchart, Jordi; Martorell, Loreto; Artuch, Rafael; Obeso, José A; Pérez-Dueñas, Belén

2012-09-01

Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive basal ganglia disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Two Spanish siblings with a biotin-responsive basal ganglia disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. The clinical features resolved rapidly after thiamine administration. Despite the rarity of thiamine transporter-2 deficiency, it should be suspected in patients with acute dystonia and basal ganglia injury, as thiamine can halt disease evolution and prevent further episodes. © 2012 Movement Disorder Society. Copyright © 2012 Movement Disorder Society.

Early discontinuation of antiseizure medications in neonates with hypoxic-ischemic encephalopathy.

PubMed

Fitzgerald, Mark P; Kessler, Sudha Kilaru; Abend, Nicholas S

2017-06-01

Neonates with hypoxic-ischemic encephalopathy (HIE) managed with therapeutic hypothermia (TH) often experience acute symptomatic seizures, prompting treatment with antiseizure medications (ASMs). Because the risk of seizure occurrence after hospital discharge is unknown, the optimal ASM treatment duration is unclear. We aimed to determine the risk of seizure occurrence after hospital discharge and the impact of ASM treatment duration on this outcome. We performed a single-center, retrospective study of consecutive neonates with HIE managed with TH who received ASMs for acute symptomatic seizures from June 2010 through December 2014. Neonates were monitored with continuous electroencephalography (EEG) during TH. Follow-up data were available for 59 (82%) of 72 neonates who survived to discharge, with a median follow-up period of 19 months (interquartile range [IQR] 11-25). Acute symptomatic seizures occurred in 35 neonates (59%), including electrographic seizures in 21 neonates (36%). ASMs were continued upon discharge in 17 (49%) of 35 neonates. Seizures occurred in follow-up in four neonates (11%). No patient for whom ASMs were discontinued prior to discharge experienced seizures during the follow-up period. Among neonates with HIE, seizures after hospital discharge were rare in those with acute symptomatic seizures and did not occur in neonates without acute symptomatic seizures. ASM discontinuation prior to discharge did not increase the risk of seizures during the follow-up period, suggesting that ASMs may be discontinued in many neonates prior to discharge. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

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…

Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution for Treatment of Overt Hepatic Encephalopathy

PubMed Central

Rahimi, Robert S.; Singal, Amit G.; Cuthbert, Jennifer A.; Rockey, Don C.

2017-01-01

IMPORTANCE Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. OBJECTIVE To compare polyethylene glycol 3350–electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. DESIGN, SETTING, AND PARTICIPANTS The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. INTERVENTIONS Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. MAIN OUTCOMES AND MEASURES The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. RESULTS A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely

Wernicke encephalopathy in a patient with liver failure: Clinical case report.

PubMed

Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

2016-07-01

Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice.A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1.To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians' awareness of its possible onset.

Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat.

PubMed

Bakrania, B; Du Toit, E F; Ashton, K J; Wagner, K-H; Headrick, J P; Bulmer, A C

2017-08-01

Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content. No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin in vivo. Ex vivo analysis of baseline function revealed reduced left ventricular pressure development (LVDP) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post-ischaemic recoveries of LVDP (76 ± 22% vs. 29 ± 17% Control, P < 0.01) and coronary flow (96 ± 9% vs. 86 ± 16% Control, P < 0.01) were improved in Gunn hearts, accompanied by reduced infarct area (21 ± 5% vs. 47 ± 15% Control, P < 0.01), and ventricular malondialdehyde and protein carbonyl content. Expression of myocardial nitric oxide-regulating genes including Nos1 and Noa1 were not significantly different. These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resistance. In addition, bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

21 CFR 862.1110 - Bilirubin (total or direct) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test... or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and...

Serum Bilirubin Concentration is Associated with Left Ventricular Remodeling in Patients with Type 2 Diabetes Mellitus: A Cohort Study.

PubMed

Inoue, Tomoaki; Sonoda, Noriyuki; Hiramatsu, Shinsuke; Kimura, Shinichiro; Ogawa, Yoshihiro; Inoguchi, Toyoshi

2018-02-01

Previous studies have shown that serum bilirubin concentration is inversely associated with the risk of cardiovascular disease. The relationship between serum bilirubin concentration and left ventricular geometry, however, has not been investigated in patients with diabetes mellitus. In this cohort study, 158 asymptomatic patients with type 2 diabetes mellitus without overt heart disease were enrolled. Left ventricular structure and function were assessed using echocardiography. Serum bilirubin concentration, glycemic control, lipid profile, and other clinical characteristics were evaluated, and their association with left ventricular geometry was determined. Patients with New York Heart Association Functional Classification greater than I, left ventricular ejection fraction less than 50%, history of coronary artery disease, severe valvulopathy, chronic atrial fibrillation, or creatinine clearance less than 30 ml/min, and those receiving insulin treatment, were excluded. Univariate analyses showed that relative wall thickness (RWT) was significantly correlated with diastolic blood pressure (P = 0.003), HbA1c (P = 0.024), total cholesterol (P = 0.043), urinary albumin (P = 0.023), and serum bilirubin concentration (P = 0.009). There was no association between left ventricular mass index and serum bilirubin concentration. Multivariate linear regression analysis showed that log RWT was positively correlated with diastolic blood pressure (P = 0.010) and that log RWT was inversely correlated with log bilirubin (P = 0.003). In addition, the patients with bilirubin less than 0.8 mg/dl had a higher prevalence of concentric left ventricular remodeling compared with those with bilirubin 0.8 mg/dl or more. Our study shows that the serum bilirubin concentration may be associated with the progression of concentric left ventricular remodeling in patients with type 2 diabetes mellitus.

Bilirubin Level is Associated with Left Ventricular Hypertrophy Independent of Blood Pressure in Previously Untreated Hypertensive Patients

PubMed Central

Ayaz, Teslime; Kocaman, Sinan Altan; Durakoğlugil, Tuğba; Erdoğan, Turan; Şahin, Osman Zikrullah; Şahin, Serap Baydur; Çiçek, Yüksel; Şatiroğlu, Ömer

2014-01-01

Background and Objectives Left ventricular hypertrophy (LVH), a sign of subclinical cardiovascular disease, is an important predictor of cardiovascular morbidity and mortality. The aim of our study was to determine the association of left ventricular mass (LVM) with possible causative anthropometric and biochemical parameters as well as carotid intima-media thickness (CIMT) and brachial flow-mediated dilation (FMD) as surrogates of atherosclerosis and endothelial dysfunction, respectively, in previously untreated hypertensive patients. Subjects and Methods Our study included 114 consecutive previously untreated hypertensive patients who underwent echocardiography and ultrasonography to evaluate their vascular status and function via brachial artery CIMT and FMD. Results Among all study parameters, age, systolic blood pressure (BP), diastolic BP, pulse pressure, plasma glucose, uric acid, total bilirubin, direct bilirubin, hemoglobin, and CIMT were positively correlated with the LVM index. Multiple logistic regression analysis revealed that office systolic BP, age, male gender, and total bilirubin were independent predictors of LVH. Conclusion Bilirubin seems to be related to LVM and LVH. The positive association of bilirubin with these parameters is novel and requires further research. PMID:25278987

77 FR 29914 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... Spongiform Encephalopathy; Importation of Bovines and Bovine Products AGENCY: Animal and Plant Health... derived from bovines with regard to bovine spongiform encephalopathy. This action will allow interested... importation of live bovines and products derived from bovines with regard to bovine spongiform encephalopathy...

Electrochemical Sensor for Bilirubin Detection Using Screen Printed Electrodes Functionalized with Carbon Nanotubes and Graphene.

PubMed

Thangamuthu, Madasamy; Gabriel, Willimann Eric; Santschi, Christian; Martin, Olivier J F

2018-03-07

Practice oriented point-of-care diagnostics require easy-to-handle, miniaturized, and low-cost analytical tools. In a novel approach, screen printed carbon electrodes (SPEs), which were functionalized with nanomaterials, are employed for selective measurements of bilirubin, which is an important biomarker for jaundice. Multi-walled carbon nanotubes (MWCNT) and graphene separately deposited on SPEs provide the core of an electrochemical sensor for bilirubin. The electrocatalytic activity towards bilirubin oxidation (bilirubin to biliverdin) was observed at +0.25 V. In addition, a further peak corresponding to the electrochemical conversion of biliverdin into purpurin appeared at +0.48 V. When compared to MWCNT, the graphene type shows a 3-fold lower detection limit (0.3 ± 0.022 nM and 0.1 ± 0.018 nM, respectively), moreover, the graphene type exhibits a larger linear range (0.1-600 µM) than MWCNT (0.5-500 µM) with a two-fold better sensitivity, i.e., 30 nA µM -1 cm -2 , and 15 nA µM -1 cm -2 , respectively. The viability is validated through measurements of bilirubin in blood serum samples and the selectivity is ensured by inhibiting common interfering biological substrates using an ionic nafion membrane. The presented approach enables the design and implementation of low cost and miniaturized electrochemical sensors.

Genetics Home Reference: SCN8A-related epilepsy with encephalopathy

MedlinePlus

... epilepsy with encephalopathy . This condition is estimated to account for 1 percent of all cases of epilepsy with encephalopathy. Related Information What information about a genetic condition can statistics ...

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients.

PubMed

Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

2016-02-28

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. 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. 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. Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

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

Antioxidant status of serum bilirubin and uric acid in patients with polymyositis and dermatomyositis.

PubMed

Chen, Zhibo; Su, Zhongqian; Pang, Wanhui; Huang, Yuanyuan; Lin, Jie; Ding, Zhangna; Wu, Senmin; Xu, Shunyao; Quan, Weiwei; Zheng, Juzeng; Chen, Huale; Li, Zhengzheng; Li, Xiang; Li, Jia; Weng, Yiyun; Zhang, Xu

2017-07-01

Oxidative stress and variations in antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Polymyositis and dermatomyositis (PM/DM) are autoimmune diseases with inflammatory cells infiltrating into skeletal muscles, and the antioxidant status is still controversial. The aim of our study was to investigate the correlation between PM/DM and the antioxidant status of serum bilirubin (Tbil, Dbil and Ibil) and uric acid (UA). We measured serum concentrations of bilirubin (Tbil, Dbil and Ibil) and uric acid in 384 individuals, including 110 PM/DM patients and 274 healthy controls. We found that PM/DM patients had significantly lower serum concentrations of bilirubin (Tbil and Ibil) and uric acid than healthy controls, whether male or female. Also, after separately adjusting the covariances of age and gender, Tbil, Dbil, Ibil and UA were all relevant factors for PM/DM. Moreover, there were no significant differences in serum antioxidant molecule levels between PM and DM subgroups. Our study demonstrated the low serum levels of bilirubin and uric acid in patients with PM/DM. This suggested low antioxidant status in PM/DM patients with excessive oxidative stress.

Evaluation of the zoonotic potential of transmissible mink encephalopathy

USDA-ARS?s Scientific Manuscript database

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...

Acute esophageal necrosis and liver pathology, a rare combination

PubMed Central

Khan, Amir Maqbul; Hundal, Rangit; Ramaswamy, Vijaya; Korsten, Mark; Dhuper, Sunil

2004-01-01

Acute esophageal necrosis (AEN) or “black esophagus” is a clinical condition found at endoscopy. It is a rare entity the exact etiology of which remains unknown. We describe a case of ‘black esophagus’, first of its kind, in the setting of liver cirrhosis and hepatic encephalopathy. PMID:15285044

[Hypertensive crisis and posterior reversible encephalopathy syndrome (PRES)].

PubMed

Eberhardt, Olaf

2018-05-01

The urgency and intensity of therapeutic response to a hypertensive crisis are governed by the presence or absence of acute end-organ damage, which define hypertensive emergency and hypertensive urgency, respectively. In case of hypertensive urgency a slow and moderate lowering of blood pressure by oral antihypertensive agents seems adequate, while the approach to hypertensive emergency has to be tailored to the specific type of organ failure. Optimal blood pressure management in the context of neurovascular emergencies is made difficult by contradictory data from observational and interventional studies. It might prove advantageous to individualize treatment according to characteristics such as the location of persistent vessel occlusion or the presence of collaterals. Reversible posterior encephalopathy may present with atypical features that might make diagnosis difficult. Clevidipine might be a welcome supplement to current intravenous antihypertensive agents in neurological disease. Georg Thieme Verlag KG Stuttgart · New York.

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.

Determination of lactic acid level in systemic liquids in children with progressive encephalopathies.

PubMed

Marszał, Elzbieta; Wojaczyńska-Stanek, Katarzyna; Pietruszewski, Jerzy; Emich-Widera, Ewa; Bielińska-Bujniewicz, Eugenia

2002-03-01

This article reports the results of research into the activities of lactic acid concentrations in the body fluids of children with progressive encephalopathies (PE) in comparison to patients with non-progressive encephalopathies (NPE) and those with non-progressive encephalopathies with concomitant epilepsy (NPEE). The study was designed to determine whether there is difference between the serum and CSF lactic acid concentrations in children with progressive encephalopathies (PE), static (non-progressive) encephalopathies (NPE) and non progressive encephalopathies with concomitant epilepsy (NPEE), and whether the clinical status correlates with the concentration of these biochemical markers in children with PE. The assessment involved 138 children of both sexes, whose age ranged between 8 months and 15 years, diagnosed and treated in the Neurology Department at the Pediatric Clinic of the Silesian Medical Academy in Katowice between 1995 and 1997. Lactate concentrations were determined in serum and cerebro-spinal fluid and analyzed statistically. The findings showed higher serum and CSF concentrations in children with PE than in patients who manifested non-progressive forms of encephalopathy. The degree of clinical symptom aggravation in PE children was likewise analyzed and compared to the values of lactate concentrations in body fluids; however, no correlation was found between these parameters. Children with progressive encephalopathies present higher lactate concentrations in serum and cerebrospinal fluid than patients with static (non-progressive) encephalopathy.

Analysis of wavelength-dependent photoisomerization quantum yields in bilirubins by fitting two exciton absorption bands

NASA Astrophysics Data System (ADS)

Mazzoni, M.; Agati, G.; Troup, G. J.; Pratesi, R.

2003-09-01

The absorption spectra of bilirubins were deconvoluted by two Gaussian curves of equal width representing the exciton bands of the non-degenerate molecular system. The two bands were used to study the wavelength dependence of the (4Z, 15Z) rightarrow (4Z, 15E) configurational photoisomerization quantum yield of the bichromophoric bilirubin-IXalpha (BR-IX), the intrinsically asymmetric bile pigment associated with jaundice and the symmetrically substituted bilirubins (bilirubin-IIIalpha and mesobilirubin-XIIIalpha), when they are irradiated in aqueous solution bound to human serum albumin (HSA). The same study was performed for BR-IX in ammoniacal methanol solution (NH4OH/MeOH). The quantum yields of the configurational photoprocesses were fitted with a combination function of the two Gaussian bands normalized to the total absorption, using the proportionality coefficients and a scaling factor as parameters. The decrease of the (4Z, 15Z) rightarrow (4Z, 15E) quantum yield with increasing wavelength, which occurs for wavelengths longer than the most probable Franck-Condon transition of the molecule, did not result in a unique function of the exciton absorptions. In particular we found two ranges corresponding to different exciton interactions with different proportionality coefficients and scaling factors. The wavelength-dependent photoisomerization of bilirubins was described as an abrupt change in quantum yield as soon as the resulting excitation was strongly localized in each chromophore. The change was correlated to a variation of the interaction between the two chromophores when the short-wavelength exciton absorption became vanishingly small. With the help of the circular dichroism (CD) spectrum of BR-IX in HSA, a small band was resolved in the bilirubin absorption spectrum, delivering part of the energy required for the (4Z, 15Z) rightarrow (4Z, 15E) photoisomerization of the molecule.

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.

Neuropathology of italian cats in feline spongiform encephalopathy surveillance.

PubMed

Iulini, B; Cantile, C; Mandara, M T; Maurella, C; Loria, G R; Castagnaro, M; Salvadori, C; Porcario, C; Corona, C; Perazzini, A Z; Maroni, A; Caramelli, M; Casalone, C

2008-09-01

Feline spongiform encephalopathy (FSE) is a transmissible spongiform encephalopathy associated with the consumption of feedstuffs contaminated with tissue from bovine spongiform encephalopathy-affected cattle and characterized by the accumulation in the central nervous system of an abnormal isoform of the prion protein (PrP(sc)). Clinically, it presents as a progressive fatal neurologic syndrome that is not easily distinguished from other feline neurologic conditions. Most cases of FSE have been reported in England, where it was first detected in 1990, but a few cases have been reported from other European countries. To identify possible cases of FSE in Italy, the Italian Ministry of Health funded a 2-year surveillance project during which the brains from 110 domestic cats with neurologic signs were evaluated histologically for spongiform encephalopathy and immunohistochemically to detect PrP(sc). Although no cases of FSE were found, the study proved useful in monitoring the Italian cat population for other neurologic diseases: neoplasia (21.8%), toxic-metabolic encephalopathy (18.2%), granulomatous encephalitis (15.5%), suppurative encephalitis (4.6%), trauma (3.6%), circulatory disorders (3.6%), degeneration (2.7%), nonsuppurative encephalitis (2.7%), and neuromuscular diseases (1.8%). No histologic lesions were found in 20% of the brains, and samples from 5.5% of the cats were rejected as unsuitable.

Molecular adsorbent recirculating system (MARS) in acute liver injury and graft dysfunction: Results from a case-control study.

PubMed

Gerth, Hans U; Pohlen, Michele; Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Wilms, Christian; Hüsing-Kabar, Anna; Görlich, Dennis; Kabar, Iyad; Schmidt, Hartmut H J

2017-01-01

The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3-5 sessions). Independent of the underlying etiology, MARS improved the patients' bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0-15.3); SMT 3.3% (95% CI: 0-9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0-44.7), SMT 11.1% (95% CI: 0-31.7), p = 0.478). Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of

Molecular adsorbent recirculating system dialysis in patients with acute liver failure who are assessed for liver transplantation.

PubMed

Camus, Christophe; Lavoué, Sylvain; Gacouin, Arnaud; Le Tulzo, Yves; Lorho, Richard; Boudjéma, Karim; Jacquelinet, Christian; Thomas, Rémi

2006-11-01

To assess the usefulness of dialysis with the molecular adsorbent recirculating system (MARS) in patients with acute liver failure who fulfil criteria for liver transplantation. Observational cohort study. ICU at a liver transplantation centre. Twenty-two patients (23 episodes) received MARS dialysis. They were either listed for LT (n=14), delayed (n=1), or not listed (contra-indication, n=7). A total of 56 MARS treatments (median per patient 2; mean duration 7.6+/-2.6h) were performed on haemodialysis. Clinical and biological variables were assessed before and 24[Symbol: see text]h after MARS therapy. The rate of recovery of liver function without transplantation was compared with an expected rate and survival was analysed. Following MARS dialysis, we observed an improvement in the grade of hepatic encephalopathy (P=0.02) and the Glasgow coma score (P=0.02), a decrease in conjugated bilirubin (P=0.05) and INR (P=0.006), and an increase in prothrombin index (P=0.005). Overall, liver function improved in seven patients (32%): four listed patients in whom transplantation could be avoided and three patients among those not listed due to contra-indications. The transplant-free recovery rate in listed patients was 29% (vs. expected 9%, P=0.036). Listed patients (n=14) had a higher 30-day survival rate [86% (12/14) vs 38% (3/8), P=0.05] and a higher long-term survival rate (P=0.02). A statistically significant improvement of liver function was observed after MARS therapy. Transplant-free recovery was more frequent than expected. The apparent benefit of MARS dialysis to treat acute liver failure needs to be confirmed by a controlled study.

Serial brain MRI and ultrasound findings: relation to gestational age, bilirubin level, neonatal neurologic status and neurodevelopmental outcome in infants at risk of kernicterus.

PubMed

Gkoltsiou, Konstantina; Tzoufi, Meropi; Counsell, Serena; Rutherford, Mary; Cowan, Frances

2008-12-01

To describe cranial ultrasound (cUS) and magnetic resonance imaging (MRI) findings in neonates at risk of kernicterus, in relation to gestational age (GA), total serum bilirubin (TSB), age at imaging and neurodevelopmental outcome. Neonates with peak TSB > 400 micromol/L and/or signs of bilirubin encephalopathy. Review of neonatal data, cUS, preterm, term and later MRI scans and neurodevelopmental outcome. 11 infants were studied, two < 31, four 34-36 and five 37-40 weeks GA. TSB levels: 235-583 micromol/L (preterms); 423-720 micromol/L (terms). Neonatal neurological examination was abnormal in 8/10. cUS showed increased basal ganglia (BG) in 4/9 infants and white matter (WM) echogenicity, lenticulostriate vasculopathy (LSV) and caudothalamic hyperechogencity/cysts (GLCs) in 5/9 infants. MRI showed abnormal signal intensity (SI) in the globus pallidum (GP) in 1/2 preterm, 8/9 term and 9/11 later scans. Abnormal WM SI occurred in 2 preterm, 7 term and 10/11 later scans. Seven infants developed athetoid/dystonic cerebral palsy (CP) and 6 hearing loss (HL). Adverse outcome was associated with abnormal BG on cUS (3/4 CP, 4/4 HL), with high SI in GP (7/9 CP, 6/9 HL) on late T2-weighted MRI (all GA) and on T1/T2-weighted term MRI, mainly in term-born infants. WM abnormalities, GLCs and LSV did not correlate with outcome. Severe CP occurred with relatively low TSB levels in preterms but only at high levels in full-terms; HL was difficult to predict. Early scans did not reliably predict motor deficits whilst all children with CP had abnormal central grey matter on later scans. Abnormal WM was seen early suggesting primary involvement rather than change secondary to grey matter damage. Why characteristic central grey matter MRI features of kernicterus are not seen early remains unexplained.

Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by Bilirubin at the Blood-CSF and Blood-Brain Barriers in the Gunn Rat

PubMed Central

Gazzin, Silvia; Berengeno, Andrea Lorena; Strazielle, Nathalie; Fazzari, Francesco; Raseni, Alan; Ostrow, J. Donald; Wennberg, Richard; Ghersi-Egea, Jean-François; Tiribelli, Claudio

2011-01-01

Accumulation of unconjugated bilirubin (UCB) in the brain causes bilirubin encephalopathy. Pgp (ABCb1) and Mrp1 (ABCc1), highly expressed in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj) Gunn rats compared to heterozygous, not jaundiced (Jj) littermates at different developmental stages (2, 9, 17 and 60 days after birth). BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16–27% of adult values), despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17–P60, respectively); Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60–70% of the adult values) in both jj and Jj at P2, but was markedly (50%) down-regulated in jj pups starting at P9, particularly in the 4th ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity. PMID:21297965

Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by bilirubin at the blood-CSF and blood-brain barriers in the Gunn rat.

PubMed

Gazzin, Silvia; Berengeno, Andrea Lorena; Strazielle, Nathalie; Fazzari, Francesco; Raseni, Alan; Ostrow, J Donald; Wennberg, Richard; Ghersi-Egea, Jean-François; Tiribelli, Claudio

2011-01-31

Accumulation of unconjugated bilirubin (UCB) in the brain causes bilirubin encephalopathy. Pgp (ABCb1) and Mrp1 (ABCc1), highly expressed in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj) Gunn rats compared to heterozygous, not jaundiced (Jj) littermates at different developmental stages (2, 9, 17 and 60 days after birth). BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16-27% of adult values), despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17-P60, respectively); Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60-70% of the adult values) in both jj and Jj at P2, but was markedly (50%) down-regulated in jj pups starting at P9, particularly in the 4(th) ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity.

An update of clinical management of acute intermittent porphyria

PubMed Central

Pischik, Elena; Kauppinen, Raili

2015-01-01

Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP

Effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion in humans.

PubMed

Lam, W F; Masclee, A A; Muller, E S; Souverijn, J H; Lamers, C B

1998-08-01

This study was undertaken to investigate the effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion. Seven healthy subjects participated in two experiments performed in random order during normoglycemia and hyperglycemic clamping at 15 mM. Duodenal outputs of bilirubin, trypsin, amylase, and bicarbonate were measured by aspiration with a recovery marker under basal conditions for 60 min and during continuous infusion of bombesin (1 ng/kg x min) for 60 min. Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were determined at regular intervals. Compared to normoglycemia, during hyperglycemia basal outputs of bilirubin (17 +/- 3 vs. 0.9 +/- 0.4 micromol/60 min), trypsin (24 +/- 4 vs. 4 +/- 1 U/60 min), amylase (12 +/- 1 vs. 3 +/- 1 kU/60 min), and bicarbonate (2.9 +/- 0.5 vs. 1.2 +/- 0.2 mmol/60 min) were significantly p < 0.05) reduced. Bombesin significantly (p < 0.05) increased pancreaticobiliary output during both normo- and hyperglycemia. During hyperglycemia bombesin-stimulated 60-min outputs of bilirubin, trypsin, amylase, and bicarbonate were not significantly different compared to those during normoglycemia. Basal and bombesin-stimulated plasma PP concentrations were significantly (p < 0.05) reduced during hyperglycemia, but plasma CCK levels were not significantly different. It is concluded that acute hyperglycemia reduces basal but does not affect bombesin-induced pancreaticobiliary secretion.

Neonatal encephalopathy and socioeconomic status: population-based case-control study.

PubMed

Blume, Heidi K; Loch, Christian M; Li, Christopher I

2007-07-01

To investigate the association between maternal socioeconomic status and the risk of encephalopathy in full-term newborns. Population-based case-control study. Washington State births from 1994 through 2002 recorded in the linked Washington State Birth Registry and Comprehensive Hospital Abstract Reporting System. Cases (n = 1060) were singleton full-term newborns with Comprehensive Hospital Abstract Reporting System International Classification of Diseases, Ninth Revision diagnoses of seizures, birth asphyxia, central nervous system dysfunction, or cerebral irritability. Control cases (n = 5330) were singleton full-term newborns selected from the same database. Main Exposures Socioeconomic status was defined by median income of the census tract of the mother's residence, number of years of maternal educational achievement, or maternal insurance status. Odds ratios estimating the risk of encephalopathy associated with disadvantaged socioeconomic status were calculated in 3 separate analyses using multivariate adjusted logistic regression. Newborns of mothers living in neighborhoods in which residents have a low median income were at increased risk of encephalopathy compared with newborns in neighborhoods in which residents have a median income more than 3 times the poverty level (adjusted odds ratio, 1.9; 95% confidence interval, 1.5-2.3). There was also a trend for increasing risk of encephalopathy associated with decreasing neighborhood income (P<.001). Newborns of mothers with less than 12 years of educational achievement had a higher risk of encephalopathy compared with newborns of mothers with more than 16 years of educational achievement (adjusted odds ratio, 1.7; 95% confidence interval, 1.3-2.3). Newborns of mothers receiving public insurance also had a higher risk of encephalopathy compared with newborns of mothers who have commercial insurance (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7). Disadvantaged socioeconomic status was

Bilirubin exposure is associated with neonatal sepsis in the eight days preceding symptoms: a retrospective study.

PubMed

Raimondi, Francesco; Borrelli, Angela Carla; Ferrara, Teresa; Giannattasio, Antonietta; Capasso, Letizia

2017-09-01

To compare levels of bilirubin (using the area under the curve, AUC) in preterm infants before the onset of sepsis with healthy matched-controls. Preterm infants born between January 2011 and December 2015 with late-onset sepsis were enrolled in our retrospective study and were matched with healthy controls (sex, birth weight and gestational age). Levels of bilirubin were registered in the eight days preceding the onset of sepsis and the AUC was calculated for both groups. Eighty-eight neonates (44 cases) were studied. GA and BW did not differ between cases and controls. In cases, we found a higher value of AUC (30.7 versus 22.5; p = 0.021). In our retrospective cohort, we found that the levels of bilirubin and the AUC in the first eight days before the onset of sepsis in preterm infants were significantly higher than the healthy controls. These data suggest that the prolonged exposition to high levels of bilirubin could increase the infection susceptibility in preterm infants.

Bilirubin Increases Insulin Sensitivity in Leptin-Receptor Deficient and Diet-Induced Obese Mice Through Suppression of ER Stress and Chronic Inflammation

PubMed Central

Dong, Huansheng; Huang, Hu; Yun, Xinxu; Kim, Do-sung; Yue, Yinan; Wu, Hongju; Sutter, Alton; Chavin, Kenneth D.; Otterbein, Leo E.; Adams, David B.; Kim, Young-Bum

2014-01-01

Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties. PMID

Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight.

PubMed