Glover, D R; Littler, W A
An evaluation of factors which may influence survival and mode of death was conducted over a three year period in a consecutive series of 50 patients with severe chronic ischaemic cardiac failure for more than three months. At the initial assessment all patients were already receiving intensive medical treatment. During follow up four patients successfully underwent cardiac surgery and medical treatment was modified in most patients, with four patients receiving antiarrhythmic drugs. Twenty six patients died: 17 suddenly within one hour of onset of symptoms and nine of progressive cardiac failure. The mortality by one year was 26% and by two years it was 62%. Comparison of those who survived with those who died within one year of follow up showed that a very low left ventricular ejection fraction, severe ventricular arrhythmias, the presence of gallop rhythm, and New York Heart Association class IV were the variables that predicted mortality. By two years left ventricular ejection fraction, ventricular arrhythmias, and pulmonary capillary wedge pressure were the variables that were significantly different in survivors and patients who died. No differences were found in any of the recorded variables between those who died suddenly and those who did not. Thus in patients with chronic ischaemic cardiac failure determination of the left ventricular ejection fraction and the severity of ventricular arrhythmia on the ambulatory electrocardiogram are the best ways to predict prognosis. The presence of gallop rhythm and New York Heart Association class IV status predict early death. PMID:3814447
Kodali, Sudha; McGuire, Brendan M
Hepatic encephalopathy (HE) is associated with cerebral edema (CE), increased intracranial pressure (ICP), and subsequent neurologic complications; it is the most important cause of morbidity and mortality in fulminant hepatic failure. The goal of therapy should be early diagnosis and treatment of HE with measures to reduce CE. A combination of clinical examination and diagnostic modalities can aid in prompt diagnosis. ICP monitoring and transcranial Doppler help diagnose and monitor response to treatment. Transfer to a transplant center and intensive care unit admission with airway management and reduction of CE with hypertonic saline, mannitol, hypothermia, and sedation are recommended as a bridge to liver transplantation.
Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram; Gautier, Aude; Sharratt, Peter; Fuller, Barry; Hodgson, Humphrey
Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell
Paschoal Jr, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson
Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545
Kramer, Ludwig; Bauer, Edith; Schenk, Peter; Steininger, Rudolf; Vigl, Marion; Mallek, Reinhold
Ecstasy-induced fulminant hepatic failure is associated with high mortality. If complicated by cerebral oedema, orthotopic liver transplantation is the only established treatment. We report a case of combined ecstasy/cocaine-induced fulminant hepatic failure presenting with severe rhabdomyolysis, myocardial infarction and multiorgan failure. Transplantation was declined by the transplant surgeons because of a history of intravenous drug abuse. As excessive hyperammonaemia (318 mumol/l) and refractory transtentorial herniation developed, treatment with a new liver detoxification device combining high-flux haemodialysis and adsorption (FPSA-Prometheus) was initiated. Within a few hours of treatment, ammonia levels normalised. Cerebral oedema was greatly reduced by day 4 and hepatic function gradually recovered. Following neurologic rehabilitation for ischaemic sequelae of herniation, the patient was discharged from hospital with only minimal deficits. In conclusion, efficient extracorporeal detoxification may be an option for reversal of hyperammonaemia and refractory cerebral oedema in ecstasy/cocaine-induced acute liver failure.
Cheng, Yanping; Aboodi, Michael S.; Wechsler, Andrew S.; Kaluza, Greg L.; Granada, Juan F.; Van Bladel, Kevin; Annest, Lon S.; Yi, Geng-Hua
OBJECTIVES Surgical ventricular reconstruction has been used to treat ischaemic cardiomyopathy with large akinetic or dyskinetic areas. However, application of this approach requires a sternotomy, cardiopulmonary bypass and a left ventriculotomy. This study assessed the feasibility and efficacy of minimally invasive, off-pump, epicardial catheter-based ventricular reconstruction (ECVR) in an anteroapical aneurysm ovine model. METHODS Left ventricular (LV) anteroapical myocardial infarction was induced percutaneously by coil embolization of the left anterior descending coronary artery. Eight weeks after infarction, via mini left thoracotomy and without cardiopulmonary bypass, ECVR was performed in six sheep. The scar was excluded by placing anchor pairs on the LV epicardial anterior wall and the right ventricular side of the interventricular septum under fluoroscopic guidance. LV performance was evaluated before, immediately after device implantation and after 6 weeks by echocardiography. Terminal histopathology was performed. RESULTS ECVR was completed expeditiously in all animals without complications. Parameters obtained 6 weeks after device implantation were compared with baseline (pre-device). End-systolic volume was decreased by 38% (25.6 ± 6.1 ml vs baseline 41.2 ± 7.2 ml, P = 0.02) with preservation of stroke volume. Ejection fraction was significantly increased by 13% (48.5 ± 7% vs baseline 35.8 ± 7%, P = 0.02). The circumferential strain in the anterior septum (−7.67 ± 5.12% vs baseline −0.96 ± 2.22%, P = 0.03) and anterior wall (−9.01 ± 3.51% vs baseline −4.15 ± 1.36%, P = 0.01) were significantly improved. The longitudinal strain in apex was reversed (−3.08 ± 1.53% vs baseline 3.09 ± 3.39%, P = 0.01). Histopathology showed full endocardial healing over the anchors with appreciable reduction of the chronic infarct in the LV. CONCLUSIONS ECVR without cardiopulmonary bypass is a less invasive alternative to current standard therapies
Franco, D; Durandy, Y; Deporte, A; Bismuth, H
Emergency fibroscopy revealed bleeding lesions in 84 cirrhotic patients. In patients with moderate or no hepatic failure, the commonest actively bleeding sources were oesophagogastric varices and acute mucosal ulcers associated with the ingestion of anti-inflammatory drugs. In patients with severe hepatic failure, acute mucosal ulcers unrelated to drugs predominated and there was evidence that these were stress-induced erosions.
Søreide, E; Harboe, S; Søndenaa, K
A young trauma patient developed severe adult respiratory distress syndrome (ARDS), right heart failure, hepatic congestion and an extreme hepatomegaly but no hepatic failure. The patient needed 100% oxygen during ventilatory support for 80 days and was weaned from the ventilator after more than 100 days. The hepatomegaly gradually disappeared. Four months after the injury, the anatomical shape of the lungs, heart and liver were normalized. This case illustrates that severe ARDS may cause right heart failure and extreme hepatomegaly due to venous congestion in the liver and spleen, but without hepatic failure.
Ring-Larsen, H; Palazzo, U
Forty patients with terminal cirrhosis and 40 patients with fulminant hepatic failure-all consecutively admitted-were studied with regard to incidence, types, and prognosis of complicating renal insufficiency. Renal failure was considered present when the serum creatinine was greater than 0.20 mmol/l. Of the patients with cirrhosis 26 (65%) developed renal failure. In 15 the type was functional, in three due to acute tubular necrosis, and in eight indeterminable. Of the patients with fulminant hepatic failure 22 (55%) had renal insufficiency; of these 13 had functional renal failure, five acute tubular necrosis, and in four the type was indeterminable. In both categories of patients, renal failure was equally frequent among patients with or without gastrointestinal bleeding and with or without ascites or diuretic therapy. The biochemical tests of liver function were similar in patients with or without renal failure in both categories. The mean renal blood flow in seven unselected patients with fulminant hepatic failure was reduced in the same order as previously observed in patients with cirrhosis. In terminal cirrhosis the mortality rate was 88% in the presence of renal failure, 71% in its absence (p greater than 0.05), while the same figures in fulminant hepatic failure were 100% and 67% (p less than 0.05). The incidence, relative frequency, and prognosis of renal failure were not different in the two conditions, indicating identical pathophysiological circumstances. PMID:7262632
Labadarios, D; Rossouw, J E; McConnell, J B; Davis, M; Williams, R
Nine out of 24 patients with acute hepatocellular necrosis leading to fulminant hepatic failure showed biochemical evidence of thiamine deficiency early in the course of their illness, probably as a result of inadequate intake of the vitamin. This was corrected by twice daily administration of intravenous vitamin supplements containing thiamine hydrochloride (100 mg b.d.). These studies indicate that conversion of thiamine hydrochloride to its biologically active co-enzyme form, thiamine pyrophosphate, is possible even in the presence of severe acute hepatocellular necrosis, and it is suggested that supplements of the vitamin should be included in the routine management of patients with acute hepatic failure.
Tagle, Martin; Barriga, Jose A; Gutierrez, Sussy; Valdez, Luis Manuel; Castle, James; Antunez De Mayolo, Antonio; Scavino Levy, Yolanda; León Barúa, Raúl; Mendoza, Carlos; Cajas, Lucy; Santibáñez, Vilma
We report the case of a 42-year old male with an episode of relapsing hepatitis A of cholestatic pattern, which clinic course was complicated by fever, anemia and renal failure, requiring hemodialysis. The occurrence of cryglobulins and diminished complement levels was detected. A kidney biopsy was performed showing evidence of thrombotic microangiopathy. The patient had a good therapeutic response to corticosteroids, although he developed recurrence of fever and a palpable purpuric rush over his lower extremities when dose was reduced. A skin biopsy found leukocytoclastic vasculitis. Symptoms and physical findings improved when therapy with cycloposphamide was started and the dose of corticosteroids was increased. Hepatitis A virus infection usually has a benign course, although complications may occasionally develop. The relapsing form can be seen in 3-20% of the case; it can appear with a cholestatic pattern and most of the time it has a mild clinic development. Unlike hepatitis B, extra-hepatic manifestations are unusual in hepatitis A, and renal manifestations are even more infrequent. Acute renal failure (ARF) in non-fulminating hepatitis A has been reported only occasionally and its etiology remains unclear. Several hypotheses have been proposed, including renal toxicity due to hyperuricemia or increased bilirrubin, cryoglobulinemia, alterations in the renal blood flow due to endotoxemia or peripheral immune complex-mediated damage when hypocomplementemia is found. Kidney biopsy showed evidence of thrombotic microangiopathy, which raised the hypothesis of a Hemolytic Uremic Syndrome (HUS). An association with HUS has been described in a patient with surface antigen for hepatitis B (HBsAg) and anomalies in the hepatic biochemical tests, but as far as we know this is the first case of relapsing hepatitis A associated with a confirmed microangiopathic renal involvement.
Karki, Pragya; Malik, Sarthak; Mallick, Bipadabhanjan; Sharma, Vishal; Rana, Surinder S
Abstract Acute viral hepatitis is usually a self-limiting illness. However, it can lead to complications that can be life-threatening, such as acute liver failure. Glucose 6 phosphate dehydrogenase (G6PD) deficiency in the setting of acute viral hepatitis can lead to a massive hemolysis, manifesting as acute kidney injury and markedly raised bilirubin levels; although cases are rare. Here, we report such a case. The patient had a viral hepatitis E infection and presented with kidney injury requiring dialysis. Examination showed very high mixed hyperbilirubinemia due to massive intravascular hemolysis. The patient experienced a long, protracted course of illness, requiring renal replacement therapy with other supportive management, which led to improvement over a period of four weeks. This case highlights the importance of recognizing associated hemolysis in a patient with viral hepatitis who presents with very high bilirubin levels or associated kidney injury. Such patients will require aggressive supportive care with prompt fluid and electrolyte management. PMID:28097104
Davison, Beth A.; Filippatos, Gerasimos S.; Radovanovic, Slavica; Beleslin, Branko; Merkely, Bela; Musialek, Piotr; Wojakowski, Wojciech; Andreka, Peter; Horvath, Ivan G.; Katz, Amos; Dolatabadi, Dariouch; El Nakadi, Badih; Arandjelovic, Aleksandra; Edes, Istvan; Seferovic, Petar M.; Obradovic, Slobodan; Vanderheyden, Marc; Jagic, Nikola; Petrov, Ivo; Atar, Shaul; Halabi, Majdi; Gelev, Valeri L.; Shochat, Michael K.; Kasprzak, Jaroslaw D.; Sanz-Ruiz, Ricardo; Heyndrickx, Guy R.; Nyolczas, Noémi; Legrand, Victor; Guédès, Antoine; Heyse, Alex; Moccetti, Tiziano; Fernandez-Aviles, Francisco; Jimenez-Quevedo, Pilar; Bayes-Genis, Antoni; Hernandez-Garcia, Jose Maria; Ribichini, Flavio; Gruchala, Marcin; Waldman, Scott A.; Teerlink, John R.; Gersh, Bernard J.; Povsic, Thomas J.; Henry, Timothy D.; Metra, Marco; Hajjar, Roger J.; Tendera, Michal; Behfar, Atta; Alexandre, Bertrand; Seron, Aymeric; Stough, Wendy Gattis; Sherman, Warren; Cotter, Gad; Wijns, William
Aims Cardiopoietic cells, produced through cardiogenic conditioning of patients’ mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. Methods and results This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. Conclusion The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted. PMID:28025189
The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.
Baudouin, S. V.; Howdle, P.; O'Grady, J. G.; Webster, N. R.
BACKGROUND--There is little information on the incidence of acute lung injury or changes in the pulmonary circulation in acute liver failure. The aim of this study was to record the incidence of acute lung injury in fulminant hepatic failure caused by paracetamol poisoning, to document the associated pulmonary circulatory changes, and to assess the impact of lung injury on patient outcome. METHODS--The degree of lung injury was retrospectively assessed by a standard scoring system (modified from Murray) in all patients with fulminant hepatic failure caused by paracetamol poisoning, admitted to the intensive care unit over a one year period. The severity of liver failure and illness, other organ system failure, and patient outcome were also analysed. RESULTS--Twenty four patients with paracetamol-induced liver failure were admitted and nine developed lung injury of whom eight (33%) had severe injury (Murray score > 2.5). In two patients hypoxaemia contributed to death. Patients with lung injury had higher median encephalopathy grades (4 v 2 in the non-injured group) and APACHE II scores (29 v 16). Circulatory failure, requiring vasoconstrictor support, occurred in all patients with lung injury but in only 40% of those without. Cerebral oedema, as detected by abnormal rises in intracranial pressure, also occurred in all patients with lung injury but in only 27% of the non-injured patients. The incidence of renal failure requiring renal replacement therapy was similar in both groups (67% and 47%). Pulmonary artery occlusion pressures were normal in the lung injury group. Cardiac output was high (median 11.2 1/min), systemic vascular resistance low (median 503 dynes/s/cm-5), and pulmonary vascular resistance low (median 70 dynes/s/cm-5), but not significantly different from the group without lung injury. Mortality was much higher in the lung injury group than in the non-injured group (89% v 13%). CONCLUSIONS--Acute lung injury was common in patients with paracetamol
Patel, Harish; Tariq, Hassan; Gaduputi, Vinaya; Vakde, Trupti; Makker, Jasbir; Daniel, Myrta
Herpes hepatitis is a rare cause of fulminant hepatic failure contributing to less than 1% of all cases. It is most often seen in persons who are immunosuppressed and in pregnant women. The presentation is usually non-specific and rapidly progressive, thus making antemortem diagnosis of this condition rare. We present a patient who was on chronic immunosuppressive therapy for systemic lupus erythematosus and subsequently developed multi-organ failure with anicteric transaminitis as a result of disseminated herpes infection. The diagnosis was only made post-mortem. A confounding factor in this case was the fact that the patient underwent plasmapheresis, which skewed the interpretation of liver function tests in the setting of acute liver failure. PMID:27829961
Patel, Harish; Tariq, Hassan; Gaduputi, Vinaya; Vakde, Trupti; Makker, Jasbir; Daniel, Myrta
Herpes hepatitis is a rare cause of fulminant hepatic failure contributing to less than 1% of all cases. It is most often seen in persons who are immunosuppressed and in pregnant women. The presentation is usually non-specific and rapidly progressive, thus making antemortem diagnosis of this condition rare. We present a patient who was on chronic immunosuppressive therapy for systemic lupus erythematosus and subsequently developed multi-organ failure with anicteric transaminitis as a result of disseminated herpes infection. The diagnosis was only made post-mortem. A confounding factor in this case was the fact that the patient underwent plasmapheresis, which skewed the interpretation of liver function tests in the setting of acute liver failure.
Cameron, Andrew M; Truty, Jadwiga; Truell, Jeff; Lassman, Charles; Zimmerman, Michael A; Kelly, Burnett S; Farmer, Douglas G; Hiatt, Jonathan R; Ghobrial, Rafik; Busuttil, Ronald W
Systemic lymphomas may involve the liver but rarely cause fulminant hepatic failure (FHF). Acute liver failure from primary hepatic lymphoma (PHL) is even less common with most patients succumbing to the sequelae of FHF before the correct diagnosis is made. We report a patient who underwent successful orthotopic liver transplant (OLT) and chemotherapy for FHF secondary to PHL. This previously-well male developed profound coagulopathy and encephalopathy 6 weeks after the onset of jaundice and fatigue. Workup failed to reveal the underlying cause of his liver failure and the patient soon required urgent OLT. Pathologic evaluation of his explanted liver revealed a malignant T-cell rich, large B-cell non-Hodgkin's lymphoma with widespread hepatocellular necrosis. The patient made an excellent clinical recovery and is undergoing CHOP-Rituxan chemotherapy. This scenario demonstrates that lymphoma should be considered in the differential diagnosis of FHF without clear etiology because of the potential for intervention with transplant and chemotherapy.
Chi, Heng; Haagsma, Elizabeth B; Riezebos-Brilman, Annelies; van den Berg, Arie P; Metselaar, Herold J; de Knegt, Robert J
We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the King's College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and recovered. Careful investigation identified imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010 affecting 13 patients. Virus sequence analysis of our patient's virus showed a strain commonly found in Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute liver failure, and hepatitis A vaccine.
Zhou, Ping; Xia, Jie; Guo, Gang; Huang, Zi-Xing; Lu, Qiang; Li, Li; Li, Hong-Xia; Shi, Yu-Jun; Bu, Hong
AIM: To establish an appropriate primate model of fulminant hepatic failure (FHF). METHODS: We have, for the first time, established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin. Clinical features, biochemical indexes, histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model. RESULTS: Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration. Coagulation activity was significantly decreased. Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h. The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h, respectively. The autopsy showed typical yellow atrophy of the liver. Hepatic encephalopathy of the models was also confirmed by hepatic coma, MRI and pathological changes of cerebral edema. The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices, imaging and histopathology. CONCLUSION: We have established an appropriate large primate model of FHF, which is closely similar to clinic cases, and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies. PMID:22346249
Automatic identification of type 2 diabetes, hypertension, ischaemic heart disease, heart failure and their levels of severity from Italian General Practitioners' electronic medical records: a validation study
Schuemie, Martijn J; Mazzaglia, Giampiero; Lapi, Francesco; Francesconi, Paolo; Pasqua, Alessandro; Bianchini, Elisa; Montalbano, Carmelo; Roberto, Giuseppe; Barletta, Valentina; Cricelli, Iacopo; Cricelli, Claudio; Dal Co, Giulia; Bellentani, Mariadonata; Sturkenboom, Miriam; Klazinga, Niek
Objectives The Italian project MATRICE aimed to assess how well cases of type 2 diabetes (T2DM), hypertension, ischaemic heart disease (IHD) and heart failure (HF) and their levels of severity can be automatically extracted from the Health Search/CSD Longitudinal Patient Database (HSD). From the medical records of the general practitioners (GP) who volunteered to participate, cases were extracted by algorithms based on diagnosis codes, keywords, drug prescriptions and results of diagnostic tests. A random sample of identified cases was validated by interviewing their GPs. Setting HSD is a database of primary care medical records. A panel of 12 GPs participated in this validation study. Participants 300 patients were sampled for each disease, except for HF, where 243 patients were assessed. Outcome measures The positive predictive value (PPV) was assessed for the presence/absence of each condition against the GP's response to the questionnaire, and Cohen's κ was calculated for agreement on the severity level. Results The PPV was 100% (99% to 100%) for T2DM and hypertension, 98% (96% to 100%) for IHD and 55% (49% to 61%) for HF. Cohen's kappa for agreement on the severity level was 0.70 for T2DM and 0.69 for hypertension and IHD. Conclusions This study shows that individuals with T2DM, hypertension or IHD can be validly identified in HSD by automated identification algorithms. Automatic queries for levels of severity of the same diseases compare well with the corresponding clinical definitions, but some misclassification occurs. For HF, further research is needed to refine the current algorithm. PMID:27940627
Hwang, Youn-Hwan; Yun, Hyo-In
The aim of this study was to investigate the effects of hepatic and renal failure on the pharmacokinetics of flunixin in carbon tetrachloride (CCl(4))- and glycerol-treated rats. After intravenous administration of flunixin (2 mg/kg), the plasma concentration of flunixin was measured by high-performance liquid chromatography. Both acute hepatic and renal failure resulted in significantly increased area under the curve (AUC), prolonged elimination half-life (t(1/2β)), and reduced total body clearance (Cl(tot)) compared with respective controls (P<0.05). In conclusion, hepatic failure as well as renal failure modified the pharmacokinetics of flunixin.
French, Samuel W; Masouminia, Maryam; Samadzadeh, Sara; Tillman, Brittany C; Mendoza, Alejandro; French, Barbara A
The mechanisms of protein quality control in hepatocytes in cases of alcoholic hepatitis (AH) including ufmylation, FAT10ylation, metacaspase 1 (Mca1), ERAD (endoplasmic reticulum-associated degradation), JUNQ (juxta nuclear quality control), IPOD (insoluble protein deposit) autophagocytosis, and ER stress are reviewed. The Mallory-Denk body (MDB) formation develops in the hepatocytes in alcoholic hepatitis as a consequence of the failure of these protein quality control mechanisms to remove misfolded and damaged proteins and to prevent MDB aggresome formation within the cytoplasm of hepatocytes. The proteins involved in the quality control pathways are identified, quantitated, and visualized by immunofluorescent antibody staining of liver biopsies from patients with AH. Quantification of the proteins are achieved by measuring the fluorescent intensity using a morphometric system. Ufmylation and FAT10ylation pathways were downregulated, Mca1 pathways were upregulated, autophagocytosis was upregulated, and ER stress PERK (protein kinase RNA-like endoplasmic reticulum kinase) and CHOP (CCAAT/enhancer-binding protein homologous protein) mechanisms were upregulated.
Chen, Paul; Marentis, Theodore; Brown, Richard K J
Hepatic uptake on an MDP bone scan is a non-specific finding. When present, the etiology needs to be determined. The differential diagnosis depends on the pattern of uptake. Metastatic breast and colon cancer are frequent causes of focal faint uptake. Diffuse uptake is rare, but can be seen with hepatitis, amyloid, and IV gadolinium administration. In addition, aluminum breakthrough from the molybdenum generator can cause colloid formation and subsequent diffuse hepatic uptake. We present a case of diffuse uptake in a patient with acute hepatic failure. The etiology of the failure was extensive thrombosis of the inferior vena cava (IVC).
Poddar, U; Thapa, B; Prasad, A; Sharma, A; Singh, K
Background: The natural history of fulminant hepatic failure (FHF) without liver transplantation is not well known. Aims: To study the natural history and prognostic factors, especially the presence of ascites and spontaneous bacterial peritonitis (SBP), in children with FHF. Methods: FHF was defined by the onset of encephalopathy within 12 weeks of onset of jaundice. From August 1997 to December 2000, 67 children (≤12 years) were diagnosed with FHF. Their clinical features, investigations and outcome were noted. Viral markers A to E (IgM, anti-HAV; IgM, anti-HEV, HBsAg, and anti-HCV) were determined by ELISA. SBP was defined by the presence of ≥250 neutrophils with or without a positive culture in ascitic fluid. Results: Mean age of the children was 5.8 years with an almost equal sex distribution. Viral markers were positive in 63 (94%) cases: hepatitis A in 34 (54%), E in 17 (27%), A+E in seven (11%), and B in five (8%). Thirty one children presented with grade I or II encephalopathy and all recovered, whereas 17 of 36 children who had grade III or IV encephalopathy died. Ascites was detected (both clinically and ultrasonically) in 34 (51%) cases, nine (26%) of which had SBP. Overall mortality was 25%. Mortality was higher in those who had ascites than in those who did not (32% v 18%); among those with ascites it was maximum in those who had SBP (78% v 16%). Total serum bilirubin and grade of encephalopathy were significantly higher, serum albumin was significantly lower, and prothrombin time was significantly prolonged in those who died than in those who recovered. Conclusion: The natural history of FHF in Indian children depends on age, grade of encephalopathy, ascites, and SBP. SBP depicts worse outcome. In all cases of FHF with ascites, the presence of SBP should be investigated. PMID:12089125
Latt, N L; Araz, F; Alachkar, N; Durand, C M; Gurakar, A
Hepatitis C virus (HCV) infection is a rising global public health burden with an estimated 130-150 million infected people worldwide and 350,000 to 500,000 HCV-related deaths each year. Chronic kidney disease (CKD) is also a highly prevalent public health issue as the escalating numbers of patients worldwide are developing type 2 diabetes mellitus and hypertension due to high fat diets and a growing obesity epidemic. The high incidence and prevalence of HCV infection leads to substantial morbidity and mortality among renal dialysis patients. Recommendations are to screen for HCV infection among all patients with renal failure especially prior to initiation of hemodialysis and renal transplant evaluation. HCV-antibody enzyme immunoassay (EIA) followed by confirmation with HCV RNA nucleic acid test (NAT) is recommended for low prevalence regions, but in dialysis centers with a high prevalence of HCV, initial testing with NAT is recommended due to higher false positive EIA rates. Liver biopsy is used to assess of liver disease severity. Transjugular liver biopsy, as an effective and safe technique in patients with ESRD can be considered instead of percutaneous approach. Non-invasive approaches to staging fibrosis, including liver stiffness measurement by transient elastography and panels of serum fibrosis biomarkers, are also widely used. Although difficult to manage, combined pegylated- interferon (PEG IFN) and ribavirin therapy was the only treatment modality available for HCV-positive patients until the recently introduced new direct-acting antiviral agents. However, except boceprevir, there are no currently available data to suggest that these new anti-viral drugs are safe and effective among end-stage renal failure patients. IFN-containing regimens were also associated with high rates of renal graft loss in post-renal transplant patients. Therefore, management of HCV infection in renal failure patients is unique and should be tailored individually with
Pestalozza, Isabella F; Di Legge, Silvia; Calabresi, Marco; Lenzi, Gian Luigi
The ischaemic penumbra was described for the first time in the late 1970s as a ring of hypoperfused zone surrounding the region of complete infarction. The penumbral zone is a functionally silent tissue which is able to regain its function if promptly reperfused. This implies that the ischaemic penumbra is not a static but a "dynamic" and "time-dependent" concept. In this paper we describe the role of neuroimmaging tecniques such as single photon emission tomography (SPET), positron emission tomography (PET), and diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI and PWI) in the study of ischaemic penumbra. These functional imaging techniques have the advantage of giving "in vivo" quantitative estimate of cerebral blood flow (CBF) as well as information on how the ischaemic tissue metabolic changes develop. It follows that, as therapeutic options for treating acute stroke evolve, neuroimaging strategies are assuming an increasingly important role in the initial evaluation and management of the acute ischaemic patient. In this regard, a wide range of therapeutic approaches have been investigated for either ameliorating the perfusion, or interfering with the pathobiochemical cascade leading to ischaemic neuronal damage, or improving endogenous neuroprotection pathways. The "time windows" required for these treatments to be effective varies being rather short for reperfusion and longer for neuroprotection. Salvaging more penumbra would enhance recovery and thereby allow the most appropriate candidate for therapeutic trials to be selected.
Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM
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
Voiculescu, Mihai; Ionescu, Camelia; Ismail, Gener; Mandache, Eugen; Hortopan, Monica; Constantinescu, Ileana; Iliescu, Olguta
Renal transplantation is often associated with severe complications. Except for acute rejection, infections and toxicity of immunosuppressive treatment are the most frequent problems observed after transplantation. Infections with hepatic viruses (HBV, HDV, HCV, HGV) and cytomegalic virus (CMV) are the main infectious complications after renal transplantation. Cyclosporine toxicity is not unusual for a patient with renal transplantation and is even more frequent for patients with hepatic impairment due to viral infections. The subjects of this report are two renal transplant recipients with acute pancreatitis, severe hepatitis and acute renal failure on graft, receiving immunosuppressive therapy for maintaining renal graft function
Cao, Xu; Liu, Mei; Wang, Peng; Liu, Dong-Yan
AIM: To investigate the change in intestinal dendritic cell (DC) number in fulminant hepatic failure (FHF). METHODS: An animal model of FHF was created. Intestinal CD11b/c was detected by immunohistochemistry and Western blot. Quantitative real-time polymerase chain reaction (PCR) was used to detect intestinal integrin-α mRNA expression. Intestinal CD83, CD86, CD74, CD3 and AKT were detected by immunohistochemistry, Western blot and PCR. Phosphorylated-AKT (p-AKT) was detected by immunohistochemistry and Western blot. RESULTS: In the FHF group [D-galactosamine (D-Galn) + lipopolysaccharide (LPS) group], the mice began to die after 6 h; conversely, in the D-Galn and LPS groups, the activity of mice was poor, but there were no deaths. Immunohistochemistry results showed that in FHF, the expression of CD11b/c (7988400 ± 385941 vs 1102400 ± 132273, P < 0.05), CD83 (13875000 ± 467493 vs 9257600 ± 400364, P < 0.05), CD86 (7988400 ± 385941 vs 1102400 ± 13227, P < 0.05) and CD74 (11056000 ± 431427 vs 4633400 ± 267903, P < 0.05) was significantly increased compared with the normal saline (NS) group. Compared with the NS group, the protein expression of CD11b/c (5.4817 ± 0.77 vs 1.4073 ± 0.37, P < 0.05) and CD86 (4.2673 ± 0.69 vs 1.1379 ± 0.42, P < 0.05) was significantly increased. Itg-α (1.1224 ± 0.3 vs 0.4907 ± 0.19, P < 0.05), CD83 (3.6986 ± 0.40 vs 1.0762 ± 0.22, P < 0.05) and CD86 (1.5801 ± 0.32 vs 0.8846 ± 0.10, P < 0.05) mRNA expression was increased significantly in the FHF group. At the protein level, expression of CD74 in the FHF group (2.3513 ± 0.52) was significantly increased compared with the NS group (1.1298 ± 0.33), whereas in the LPS group (2.3891 ± 0.47), the level of CD74 was the highest (P < 0.05). At the gene level, the relative expression of CD74 mRNA in the FHF group (1.5383 ± 0.26) was also significantly increased in comparison to the NS group (0.7648 ± 0.22; P < 0.05). CD3 expression was the highest in the FHF group (P < 0
Curran, B J; Havill, J H
Hereditary fructose intolerance is a rare inherited metabolic disorder. Although fructose intolerance usually presents in the paediatric age group, individuals can survive into adulthood by self.manipulation of diet. Hospitalisation can become a high.risk environment for these individuals because of loss of control of their strict dietary constraints and the added danger of administration of medications containing fructose, sucrose and sorbitol. We report a case of hereditary fructose intolerance in an adult presenting with hepatic and renal failure associated with an amiodarone infusion and explore the possibility of polysorbate 80 as a cause of this patient's hepatic and renal failure.
Tschiedel, E; Gierenz, N; Wieland, R; Wulff, B; Ballauff, A
Aplastic anaemia can coincide with non-A-E hepatitis. Treatment follows a standardised study protocol of the German Society of Paediatric Oncology and Haematology (GPOH). Patients receive immunosuppression and/or bone marrow transplantation. We present six cases of aplastic anaemia after non-A-E hepatitis with different courses. In four of these children illness first presented with acute gastroenteritis. Five out of six children fully recovered, two of these with immunosuppression alone, three after bone marrow transplantation. One patient died due to complications of the bone marrow transplantation. In two patients steroid therapy was carried out to treat the hepatitis. This did not have any effect on the course of their aplastic anemia. We emphasise this common combination of aplastic anemia following non-A-E hepatitis. This overview underlines the necessity of regular blood testing after non-A-E hepatitis. Often gastroenteritis seems to precede illness thus perhaps indicating an infectious trigger.
Ben Ari, Ziv; Avlas, Orna; Pappo, Orit; Zilbermints, Veacheslav; Cheporko, Yelena; Bachmetov, Larissa; Zemel, Romy; Shainberg, Asher; Sharon, Eran; Grief, Franklin; Hochhauser, Edith
Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), D-galactosamine (GalN)-induced FHF is a well established model of liver injury in mice. Toll-Like Receptor 4 (TLR4) has been identified as a receptor for LPS. The aim of this study was to investigate the role of TLR4 in FHF induced by D-GalN/LPS administration in mice. Wild type (WT) and TLR4 deficient (TLR4ko) mice were studied in vivo in a fulminant model induced by GalN/LPS. Hepatic TLR4 expression, serum liver enzymes, hepatic and serum TNF-α and interleukin-1β levels were determined. Apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor-kappaβ (NF-κ β) and phosphorylated c-Jun hepatic expression were studied using Western blot analysis. All WT mice died within 24 hours after administration of GalN/LPS while all TLR4ko mice survived. Serum liver enzymes, interleukin-1β, TNF-α level, TLR4 mRNA expression, hepatic injury and hepatocyte apoptosis all significantly decreased in TLR4ko mice compared with WT mice. A significant decrease in hepatic c-Jun and IκB signaling pathway was noted in TLR4ko mice compared with WT mice. In conclusion, following induction of FHF, the inflammatory response and the liver injury in TLR4ko mice was significantly attenuated through decreased hepatic c-Jun and NF-κB expression and thus decreased TNF-α level. Down-regulation of TLR4 expression plays a pivotal role in GalN/LPS induced FHF. These findings might have important implications for the use of the anti TLR4 protein signaling as a potential target for therapeutic intervention in FHF.
Denis, J; Opolon, P; Nusinovici, V; Granger, A; Darnis, F
Forty-one patients with fulminant hepatic failure and coma underwent 180 periods of haemodialysis with polyacrylonitrile membrane (AN 69 HD). Hepatic failure was due to viral hepatitis in 40 and drugs in one. Total recovery of consciousness occurred in 17 patients (43.6%), and partial in seven (17.9%)--that is, an overall figure of 61.5%. Regain of consciousness was not related to liver regeneration as assessed by levels of factor V and hepatocyte volume fraction. At the time of the first haemodialysis, neurological status was significantly impaired in the patients who could not be aroused. Mean duration of coma grade IV averaged 6.1 +/- 4.3 days and mean duration of illness until death or decerebration 8.6 +/- 8.3 days. Of the 17 patients who totally regained consciousness, nine recovered and eight died (three from intercurrent complications and five with no liver regeneration). PMID:710967
Liver failure is a frequent and serious complication that causes morbidity and mortality in haematopoietic stem cell transplantation (HCT) recipients. Liver dysfunction in these patients can be related to infectious causes, most common viral hepatitis. We report a case of disseminated acyclovir-resistant herpes simplex virus (HSV) infection following HCT that led to acute liver failure and death. Although rare, HSV hepatitis leads to high morbidity and mortality and should be considered in the differential diagnosis of HCT recipients with marked elevation of hepatic transaminase. Acyclovir is a first-line therapy for HSV infection; however, acyclovir-resistant viral strains should be considered and alternative HSV therapies given in HCT recipients whose HSV infection does not improve on acyclovir therapy.
Avraham, Y; Grigoriadis, NC; Magen, I; Poutahidis, T; Vorobiav, L; Zolotarev, O; Ilan, Y; Mechoulam, R; Berry, EM
Background and purpose: Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. In view of the effects of cannabinoids in a thioacetamide-induced model of hepatic encephalopathy and liver disease and the beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed that capsaicin may also affect hepatic encephalopathy. Experimental approach: Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later, the animals were injected with one of the following compound(s): 2-arachidonoylglycerol (CB1, CB2 and TRPV1 receptor agonist); HU308 (CB2 receptor agonist), SR141716A (CB1 receptor antagonist); SR141716A+2-arachidonoylglycerol; SR144528 (CB2 receptor antagonist); capsaicin; and capsazepine (TRPV1 receptor agonist and antagonist respectively). Their neurological effects were evaluated on the basis of activity in the open field, cognitive function in an eight-arm maze and a neurological severity score. The mice were killed 3 or 14 days after thioacetamide administration. 2-arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection, respectively. Results: Capsaicin had a neuroprotective effect in this animal model as shown by the neurological score, activity and cognitive function. The effect of capsaicin was blocked by capsazepine. Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin, SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels, an effect reversed by capsaicin. Conclusions: Capsaicin improved both liver and brain dysfunction caused by thioacetamide, suggesting that both the endocannabinoid and the vanilloid systems play important roles in hepatic encephalopathy. Modulation of these systems may have therapeutic value. PMID:19764982
Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro
Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians
Colpitts, Che C; Baumert, Thomas F
Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs) revolutionized hepatitis C virus (HCV) treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.
Frass, Michael; Zagorchev, Petko; Yurukova, Vasilka; Wulkersdorfer, Beatrix; Thieves, Karin; Zedtwitz-Liebenstein, Konstantin; Bursch, Willfried; Kaye, Alan David
Background Intoxication with Amanita phalloides is associated with high morbidity and mortality. Treatment therapies include general support, toxin elimination, pharmacotherapy with agents such as the hepatoprotective agent silibinin, and, in extreme states, liver transplantation. Despite these therapeutic interventions, mortality remains relatively high. Case Reports We present reports of 2 patients with severe hepatic failure following intoxication with Amanita phalloides. Both patients were admitted to the intensive care unit; 1 patient suffered from hepatic failure solely, and the second patient experienced severe 5-organ failure. In addition to conventional intensive care treatment, both patients were treated additively with classical homeopathy. The 2 patients survived without any residual pathological sequelae. Conclusion Based on the 2 cases, including 1 extreme situation, we suggest that adjunctive homeopathic treatment has a role in the treatment of acute Amanita phalloides–induced toxicity following mushroom poisoning. Additional studies may clarify a more precise dosing regimen, standardization, and better acceptance of homeopathic medicine in the intensive care setting. PMID:24940137
Malla, Ivone; Fauda, Martín; Casanueva, Enrique; Fernández, María Isabel; Amante, Marcelo; Cheang, Yu; Giacove, Gisela; Pedreira, Alejandra; Petracca, Pablo; González Campaña, Ariel; Silva, Marcelo; Podestá, Gustavo
Hepatoxicity of isoniazid, mainly in association with rifampin, is a rare secondary effect of tuberculostatic treatment. In the United States, it accounts for 0.2% of all pediatric orthotropic liver transplant, and 14% of transplants for drug hepatotoxicity. We report the case of a 10 year-old patient who presented with acute liver failure requiring orthotropic liver transplant after forty days of tuberculostatic treatment with isoniazid, rifampin and pyrazinamide.
Fagugli, R M; Gentile, G; Ferrara, G; Brugnano, R
Hyperuricemia is present in about 5% of the population, and allopurinol is frequently used to treat it. The use of this drug can be associated with a number of side effects, indicating allergic reactions, such as skin rash, reversible after its withdrawal. In some cases more severe hypersensitivity reactions may be seen, such as erythema multiforme exudativum, or Steven-Johnson Syndrome (SJS). Reversible clinical hepatotoxicity, as well as acute renal failure, may also develop after allopurinol therapy. We describe here the case of a 74-year-old woman with chronic renal failure who was admitted to hospital after 1 week of sore throat and fever, presenting mucous membrane lesions, widespread blistering of the skin, evolving to flaccid vesicles and bullae, and extensive epidermal detachment associated with acute renal failure and cholestatic jaundice. A diagnosis of allopurinol-induced toxic epidermal necrolysis (TEN) was established. Allopurinol was discontinued, and intensive care management was required: the patient was successfully treated by using intravenous immunoglobulin (IVIg), standard hemodialysis, and albumin dialysis (Molecular Adsorbents Recirculating System - MARS, Teraklin AG, Rostock, Germany). Allopurinol-induced TEN is extremely rare, however, the survival rate is extremely low. Clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of an aggressive pharmacological and dialysis treatment in the case of TEN.
Brotons, Carlos; Cuende, José I; Fernández Pardo, Jacinto; Plana, Nuria; Moral, Irene
In the year 2011, cardiovascular diseases were responsible of 31.2% of total deaths in Spain. The absolute number of cases of acute coronary syndrome in this year will be approximately 115,752 cases (95%CI: 114,822-116,687). The prevalence of stable angina in the population aged 25-74 years is 2.6% in men and 3.5% in women. Cardiovascular diseases were in the year 2011 the first cause of hospitalizations representing 14.1% of the total hospitalizations. Diagnose of ischaemic heart disease and acute myocardial infarction were responsible of 110,950 and 50,064 hospitalizations, respectively. In the year 2003, the hospitalization rate was 314 while in the year 2011 was 237 per 100,000, a reduction of 24.4%. The average cost of hospitalization due to ischaemic heart disease in 1997 was 3,093.7euros while in the year 2011 was 7,028.71euros. Cardiovascular mortality rates have decreased from 2007 to 2011, showing a relative reduction of 7% in women and 8% in men. With regard to myocardial infarction, it was observed a relative reduction of 17% in men and 20% in women. According to EUROASPIREIII survey done in 8,966 patients with ischaemic heart disease in Europe, 17% of patients were still smokers, 35% were obese, 56% has uncontrolled blood pressure, 51% has raised blood cholesterol and 25% were diabetics. With regard to drugs utilisation, 91% were treated with antiplatelets agents, 80% with beta blockers, 71% with ACE inhibitors/ARBs.
Lunsford, Keri E; Bodzin, Adam S; Reino, Diego C; Wang, Hanlin L; Busuttil, Ronald W
Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.
Lunsford, Keri E; Bodzin, Adam S; Reino, Diego C; Wang, Hanlin L; Busuttil, Ronald W
Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients. PMID:28018115
Mhanni, A A; Chan, A; Collison, M; Seifert, B; Lehotay, D C; Sokoro, Ah; Huynh, H Q; Greenberg, C R
We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving.
Olivier, François; Wieckowska, Anna; Piedboeuf, Bruno; Alvarez, Fernando
Unexpected severe cholestasis is part of the presentation in some neonates with hemolytic anemia but is usually self-resolving. Here we report the case of a neonate with pyruvate kinase deficiency (PKD) who presented severe hemolytic anemia at birth, characterized by a rapidly progressive and severe cholestasis with normal γ-glutamyl transpeptidase level associated with hepatic failure. After an extensive investigation to rule out contributing conditions explaining the severity of this patient's clinical presentation, PKD has remained the sole identified etiology. The patient abruptly died of sepsis at 3 months of age before a planned splenectomy and ongoing evaluation for liver transplantation. To the best of our knowledge, only a few similar cases of severe neonatal presentation of PKD complicated with severe hepatic failure and cholestasis have been reported.
Step, D L; Blue, J T; Dill, S G
Acute, severe hemolytic anemia occurred in a horse being treated for tetanus with intravenous penicillin and tetanus antitoxin. During treatment, the horse developed a positive direct antiglobulin test and a high titer (maximum 1:1024) of IgG anti-penicillin antibody. The horse recovered from the tetanus and penicillin induced hemolytic anemia, but later developed acute hepatic failure, probably resulting from the administration of equine origin tetanus antitoxin.
Hori, Tomohide; Chen, Feng; Baine, Ann-Marie T.; Gardner, Lindsay B.; Nguyen, Justin H.
Aim To develop a reliable murine model for fulminant liver failure (FLF). Material and Methods We treated three groups of male C57BL/6 mice:as controls, with azoxymethane (AOM), and with galactosamine (Gal) and tumor necrosis factor-alpha (TNFα). Effects of body temperature (BT) control on survival, in all three groups were investigated. Using BT control, survival, histopathological findings and biochemical/coagulation profiles were compared between the experimental groups. Effects of hydration on international normalized ratios of prothrombin time (PT-INR) were also checked. Dose-dependent survival curves were made for both experimental groups. Neurological behaviors were assessed using a coma scale. Results No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. Between the experimental groups, there were significant differences in aspartate aminotransferase levels and PT-INR; and significant differences in PT-INRs between sufficiently- and insufficiently-hydrated groups. There were significant differences between FLF models, in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the diseased state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study. Conclusion Azoxymethane can provide a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models. PMID:24713795
Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M
MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed.
Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H
Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.
Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru
A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.
Yamanishi, A; Ishibashi, Y; Kuriyama, K; Tachiiri, T; Kusajima, H; Kojima, E; Momo, K
To predict the potential utility of calcitriol in human osteoporosis with hepatic dysfunction, we examined the effects of calcitriol and alfacalcidol in ovariectomized (OVX) aged-rats with CCl4-induced hepatic failure. In OVX+CCl4 rats, GOT, GTP, alkaline phosphatase and total bilirubin increased and hepatic enzyme activity (cytochrome b5 and P450) decreased. Repeated oral doses of calcitriol (0.1 and 0.2 microgram/kg) for 51 days inhibited a decrease in serum calcium concentration. This effect was more potent than that of alfacalcidol at the same dose. Both drugs tended to inhibit a decrease in femoral calcium contents. Calcitriol (0.2 microgram/kg) prevented a decrease in femoral bone density (dry and ash weight per volume), unlike alfacalcidol. Soft X-ray imaging analysis revealed that both drugs tended to inhibit the decrease in femoral bone density. There were no differences in the femoral bone strength between OVX+CCl4 and sham-operated rats. The serum calcitriol concentrations increased after the last doses of calcitriol, while they did not increase after the last dose of alfacalcidol. All these effects of calcitriol were related to the serum calcitriol levels. These results suggest that calcitriol, unlike alfacalcidol, may have a clinical therapeutic effect in osteoporosis with hepatic dysfunction.
Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling
Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687
Tokarz, D; Poppenga, R; Kaae, J; Filigenzi, M; Lowenstine, L J; Pesavento, P
Amanitin is a toxic cyclopeptide present in several species of poisonous mushrooms. Amanitin toxicosis was diagnosed in 2 cats from separate premises. Both cats initially had lethargy and vomiting, and they rapidly developed depression and neurological signs over 24-48 hours. Marked elevation of alanine aminotransferase was the primary finding, with subsequent serum chemistry values compatible with hepatic and renal failure. Histopathological findings consisted of submassive to massive acute hepatic necrosis, renal proximal tubular epithelial necrosis, and foci of necrosis and inflammation in the gastrointestinal tract. Amanitin exposure was confirmed postmortem by detection of α-amanitin in the kidney by liquid chromatography-mass spectrometry. A similar clinical course and pathological changes are reported in human and canine amanitin intoxication; however, gastrointestinal lesions are not typically described.
Haas, Christopher; Ziccardi, Mary Rodriguez; Borgman, Jody
Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen.
Dostovic, Zikrija; Dostovic, Ernestina; Smajlovic, Dzevdet; Ibrahimagic, Omer C.; Avdic, Leila
Objectives: To determine the incidence of brain edema after ischaemic stroke and its impact on the outcome of patients in the acute phase of ischaemic stroke. Patients and Methods: We retrospectively analyzed 114 patients. Ischaemic stroke and brain edema are verified by computed tomography. The severity of stroke was determined by National Institutes of Health Stroke Scale. Laboratory findings were made during the first four days of hospitalization, and complications were verified by clinical examination and additional tests. Results: In 9 (7.9%) patients developed brain edema. Pneumonia was the most common complication (12.3%). Brain edema had a higher incidence in women, patients with hypertension and elevated serum creatinine values, and patients who are suffering from diabetes. There was no significant correlation between brain edema and survival in patients after acute ischaemic stroke. Patients with brain edema had a significantly higher degree of neurological deficit as at admission, and at discharge (p = 0.04, p = 0.004). Conclusion: The cerebral edema is common after acute ischaemic stroke and no effect on survival in the acute phase. The existence of brain edema in acute ischaemic stroke significantly influence the degree of neurological deficit. PMID:27994292
Gulia, Seema; Khurana, Sachin; Shet, Tanuja; Gupta, Sudeep
The liver is one of the commonest sites of metastatic involvement in breast cancer, usually evident as focal lesions on imaging tests. Rarely, the pattern of metastatic spread is so diffuse that it remains radiologically occult. Such patients usually present with signs of hepatic insufficiency without any focal lesions on liver imaging. In such cases, liver biopsy is required to make a definitive diagnosis. We report a case of a 56-year-old postmenopausal woman with metastatic breast cancer who presented with subacute progressive liver failure. Repeated imaging of the liver was normal or non-descript. Liver biopsy finally established the diagnosis of intrasinusoidal metastases from breast cancer.
Liang, Wei-Cheng; Liang, Pu-Ping; Wong, Cheuk-Wa; Ng, Tzi-Bun; Huang, Jun-Jiu; Zhang, Jin-Fang; Waye, Mary Miu-Yee; Fu, Wei-Ming
Fulminant hepatic failure is a life-threatening disease which occurs in patients without preexisting liver disease. Nowadays, there is no ideal therapeutic tool in the treatment of fulminant hepatic failure. Recent studies suggested that a novel technology termed CRISPR/Cas9 may be a promising approach for the treatment of fulminant hepatic failure. In this project, we have designed single chimeric guide RNAs specifically targeting the genomic regions of mouse Fas gene. The in vitro and in vivo effects of sgRNAs on the production of Fas protein were examined in cultured mouse cells and in a hydrodynamic injection-based mouse model, respectively. The in vivo delivery of CRISPR/Cas9 could maintain liver homeostasis and protect hepatocytes from Fas-mediated cell apoptosis in the fulminant hepatic failure model. Our study indicates the clinical potential of developing the CRISPR/Cas9 system as a novel therapeutic strategy to rescue Concanavalin-A-induced fulminant hepatic failure in the mouse model. J. Cell. Biochem. 118: 530-536, 2017. © 2016 Wiley Periodicals, Inc.
Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized Phase II trial
Chung, Eugene S.; Miller, Leslie; Patel, Amit N.; Anderson, Russell David; Mendelsohn, Farrell O.; Traverse, Jay; Silver, Kevin H.; Shin, Julia; Ewald, Gregory; Farr, Mary Jane; Anwaruddin, Saif; Plat, Francis; Fisher, Scott J.; AuWerter, Alexander T.; Pastore, Joseph M.; Aras, Rahul; Penn, Marc S.
Background Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF). Methods Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections. Safety and efficacy parameters were assessed at 4 and 12 months after injection. Left ventricular functional and structural measures were assessed by contrast echocardiography and quantified by a blinded independent core laboratory. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure was powered based on change in 6 MWD and MLWHFQ at 4 months. Results Subject profiles at baseline were (mean ± SD): age 65 ± 9 years, LVEF 28 ± 7%, left ventricular end-systolic volume (LVESV) 167 ± 66 mL, N-terminal pro brain natriuretic peptide (BNP) (NTproBNP) 1120 ± 1084 pg/mL, MLWHFQ 50 ± 20 points, and 6 MWD 289 ± 99 m. Patients were 11 ± 9 years post most recent myocardial infarction. Study injections were delivered without serious adverse events in all subjects. Sixty-two patients received drug with no unanticipated serious product-related adverse events. The primary endpoint was a composite of change in 6 MWD and MLWHFQ from baseline to 4 months follow-up. The primary endpoint was not met (P = 0.89). For the patients treated with pSDF-1, there was a trend toward an
Wilkinson, S P; Arroyo, V A; Moodie, H; Blendis, L M; Williams, R
Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis). PMID:964682
... Loss Surgery? A Week of Healthy Breakfasts Shyness Hepatitis KidsHealth > For Teens > Hepatitis Print A A A ... to a liver condition called hepatitis . What Is Hepatitis? The liver is one of the body's powerhouses. ...
... de los dientes Video: Getting an X-ray Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...
Zhang, Peng; Zhang, Meisheng; Wan, Mengqi; Huang, Xiaoliu; Jiang, Yan; Xu, Siying; Luo, Mansheng
Bacterial lipopolysaccharide (LPS)-induced acute liver failure (ALF) is a common severe clinical syndrome in intensive care unit. No other methods are available for its prevention apart from supportive treatment and liver transplantation. Tamoxifen (TAM) was reported to attenuate ALF induced by excessive acetaminophen, while its effect on LPS-induced ALF remained unknown. For this, in the present study, we comprehensively assessed whether TAM can attenuate ALF induced by LPS/galactosamine (GaIN). Mice were given TAM once a day for three times. Twelve hours after the last treatment, mice were given LPS/GaIN (intraperitoneally [i.p.]). Survival, plasma transaminases, and histopathology were examined. Serum TNF-α and IL-1β were analyzed by ELISA. Hepatic apoptosis was analyzed by TUNEL and caspase-3 Western blotting, respectively. Compared to the model group, ALF induced by LPS/GaIN was alleviated remarkably following TAM administration, as evidenced by the improvement of survival (87.5% vs. 37.5%), hepatic swell, moderate transaminases, slightly increased serum TNF-α, IL-1β (P < 0.05), and moderate histopathology. In respect of apoptosis, severe hepatocellular apoptosis was reduced notably by TAM treatment confirmed by less TUNEL-positive hepatocytes and decreased caspase-3 cleavage. The results demonstrated that TAM could attenuate LPS/GaIN-induced ALF effectively, probably due to hepatic inflammation and apoptosis antagonism. Furthermore, it was the first report about the effect of TAM on LPS/GaIN-induced ALF.
Ataergin, Selmin; Tasar, Mustafa; Solchaga, Luis; Ozet, Ahmet; Arpaci, Fikret
We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.
Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria
In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney. The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure
Tuñón, María Jesús; Alvarez, Marcelino; Culebras, Jesús M; González-Gallego, Javier
Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed. PMID:19575487
Agarwal, R. K.; Moudgil, A.; Kishore, K.; Srivastava, R. N.; Tandon, R. K.
Five patients with acute viral hepatitis developed severe intrasvascular haemolysis and unusually high levels of serum bilirubin (427 to 1368 mumol/l). All 5 had high fever, marked anaemia, reticulocytosis and neutrophilic leucocytosis. Three of them developed acute renal failure, which was of non-oliguric type in 2. The clinical course was protracted, but complete recovery occurred in 4 patients between 4 to 10 weeks. One patient with hepatic coma and oliguric renal failure died. Deficiency of the enzyme G-6-PD was confirmed in 4 cases. Massive haemolysis in the patients was probably induced by the administration of chloroquine and other drugs. Intravascular haemolysis should be suspected in patients with acute viral hepatitis, if they show unexplained anaemia and very high serum bilirubin levels, and measures to prevent renal failure should be instituted in such cases. PMID:4070114
Zhang, Li-Mei; Liu, Dian-Wu; Liu, Jian-Bo; Zhang, Xiao-Lin; Wang, Xiao-Bo; Tang, Long-Mei; Wang, Li-Qin
AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intraven-ously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals. RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the
Lim, Jong-Hwan; Kim, Tae-Won; Park, Sang-Jin; Song, In-Bae; Kim, Myoung-Seok; Kwon, Hyo-Jung; Cho, Eun-Sang; Son, Hwa-Young; Lee, Sang-Wook; Suh, Joo-Won; Kim, Jong-Woo; Yun, Hyo-In
The aim of the present study was to evaluate the protective activity of aqueous extract from Platycodon grandiflorum (BC703) on thioacetamide (TA)-induced hepatotoxicity in mice. We found that BC703 significantly decreased mortality and the change in serum transaminase following TA administration. The group treated with BC703 at doses of 1, 5, and 10 mg/kg produced significant hepatoprotective effects against TA-induced liver damage by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation in dose-dependent manners. Histopathological studies further substantiated the protective effect of BC703. These results show the hepatoprotective activity of aqueous extract from Platycodon grandiflorum on thioacetamide-induced fulminant hepatic failure. PMID:22319234
Pawa, Sonica; Ali, Shakir
Boron has well-defined biological effects and may be of therapeutic benefit. In the current paper, the effect of boron in the form of borax was tested in experimental animal model of fulminant hepatic failure (FHF). The syndrome was induced in female Wistar rats by three consecutive daily intraperitoneal injections of thioacetamide (400 mg/kg). In the treatment groups, rats received borax (4.0 mg/kg) orally for three consecutive days followed by thioacetamide. The group administered with thioacetamide plus vehicle, and the borax alone treated rats served as controls. In all groups, rats were terminated 4 h after administering the last dose of thioacetamide, and the tissue/serum was used to measure hepatic levels of thiobarbituric acid reactive substances, reduced glutathione, and various enzymes associated with oxidative stress including peroxide metabolizing enzymes and xanthine oxidase. In thioacetamide treated group, many fold increase in the activity level of serum marker enzymes suggesting FHF was observed that could be brought down significantly in rats receiving boron. Modulation and a correlation in the activity level of oxidant generating enzyme and lipid peroxidation as well as hepatic glutathione level was also observed in rats receiving thioacetamide. In the group receiving boron followed by thioacetamide, these changes could be minimized moderately. The activity level of the peroxide metabolizing enzymes and the tripeptide glutathione, which decreased following thioacetamide treatment were moderately elevated in the group receiving boron followed by thioacetamide. The data clearly shows that borax partly normalizes the liver and offsets the deleterious effects observed in FHF by modulating the oxidative stress parameters.
Tinti, F; Umbro, I; Meçule, A; Rossi, M; Merli, M; Nofroni, I; Corradini, S Ginanni; Poli, L; Pugliese, F; Ruberto, F; Berloco, P B; Mitterhofer, A P
Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.
... clotting problems or chronic liver disease. previous continue Hepatitis B and Hepatitis C Although hep A is a ... does — through direct contact with infected body fluids. Hepatitis B and C are even more easily passed in ...
... A if they've been vaccinated against it. Hepatitis B Hepatitis B is a more serious infection. It may lead ... of which cause severe illness and even death. Hepatitis B virus (HBV) is transmitted from person to person ...
... Issues Listen Español Text Size Email Print Share Hepatitis Page Content Article Body Hepatitis means “inflammation of ... it has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool ...
Kasmi, Irena; Sallabanda, Sashenka; Kasmi, Gentian
BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses. CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day. The blood level of acetaminophen after 10 hours of the last administered dose was 32 mg/l. The patient presented with high fever, jaundice, lethargic, agitating with abdominal pain accompanied by encephalopathy. The liver function test revealed with high level of alanine aminotransferase 5794 UI/l and aspartate aminotransferase 6000 UI/l. Early initiation of oral N-acetylcysteine (NAC) after biochemical evidence of liver toxicity was beneficial with rapid improvement of liver enzymes, hepatic function and encephalopathy. During the course of the illness the child developed acute pancreatitis with hyperamylasemia 255 UI/L and hyperlypasemia 514 UI/L. Patient totally recovered within 29 days. CONCLUSION: Healthcare providers should considered probable acetaminophen toxicity in any child who has received the drug and presented with liver failure. When there is a high index of suspicion of acetaminophen toxicity NAC should be initiated and continued until there are no signs of hepatic dysfunction. PMID:27275268
Majmudar, Maulik D.; Murthy, Venkatesh L.; Shah, Ravi V.; Kolli, Swathy; Mousavi, Negareh; Foster, Courtney R.; Hainer, Jon; Blankstein, Ron; Dorbala, Sharmila; Sitek, Arkadiusz; Stevenson, Lynne W.; Mehra, Mandeep R.; Di Carli, Marcelo F.
Aims Patients with left ventricular systolic dysfunction frequently show abnormal coronary vascular function, even in the absence of overt coronary artery disease. Moreover, the severity of vascular dysfunction might be related to the aetiology of cardiomyopathy. We sought to determine the incremental value of assessing coronary vascular dysfunction among patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy at risk for adverse cardiovascular outcomes. Methods and results Coronary flow reserve (CFR, stress/rest myocardial blood flow) was quantified in 510 consecutive patients with rest left ventricular ejection fraction (LVEF) ≤45% referred for rest/stress myocardial perfusion PET imaging. The primary end point was a composite of major adverse cardiovascular events (MACE) including cardiac death, heart failure hospitalization, late revascularization, and aborted sudden cardiac death. Median follow-up was 8.2 months. Cox proportional hazards model was used to adjust for clinical variables. The annualized MACE rate was 26.3%. Patients in the lowest two tertiles of CFR (CFR ≤ 1.65) experienced higher MACE rates than those in the highest tertile (32.6 vs. 15.5% per year, respectively, P = 0.004), irrespective of aetiology of cardiomyopathy. Conclusion Impaired coronary vascular function, as assessed by reduced CFR by PET imaging, is common in patients with both ischaemic and non-ischaemic cardiomyopathy and is associated with MACE. PMID:25719181
Shao, Zhexin; Zhao, Ying; Feng, Limin; Feng, Guofang; Zhang, Juanwen; Zhang, Jie
Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672-0.820, P < 0.001), and the fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094-0.983; P = 0.047). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients.
Neumann-Haefelin, Christoph; Thimme, Robert
Hepatitis C virus (HCV) infection is only cleared in a minority of infected individuals, the majority of patients develop chronic infection. Chronic HCV infection potentially leads to liver fibrosis, cirrhosis and finally hepatocellular carcinoma. The host immune response is an important determinant in the outcome of HCV infection. Innate as well as adaptive cellular and humoral immune responses mediate important antiviral actions; however, virus-specific T cell responses appear to be most critical. Indeed, strong and multispecific CD4+ as well as CD8+ T cell responses are required for viral clearance. Interestingly, individuals who express certain HLA alleles (which are important for antigen presentation to CD4+ and CD8+ T cells) have a higher chance to clear the virus. The mechanisms of protection by HLA class I alleles such as HLA-B27 have been characterized recently. In most individuals, however, the HCV-specific immune response fails to clear the virus. Several mechanisms underlying this HCV-specific T cell failure have been identified. These include viral factors such as viral escape mutations and immunological factors such as the expression of inhibitory receptors, which lead to CD8+ T cell dysfunction. An in-depth understanding of the determinants of success or failure of the HCV-specific T cell response is critical for the development of prophylactic as well as therapeutic vaccination regimes against HCV. Here, we will discuss the virological and immunological determinants of HCV clearance and persistence.
Vaboe, A L; Leh, S; Forslund, T
This is the first report from Norway of a patient with interstitial nephritis and renal failure due to non-fulminant hepatitis A virus (HAV) infection. HAV infection was confirmed by positive anti-HAV IgM serology. All tests for other virus infections were negative. At admittance serum creatinine (s-Creat) and blood urea nitrogen (BUN) concentration were 539 microlmol/l and 32.6 mmol/l increasing the following days to 890 micromol/l and 39.9 mmol/l, respectively. Nine courses of hemodialysis had to be given. Kidney biopsy specimen showed interstitial edema, lymphocytic cell infiltration and acute tubular injury with normal glomeruli. Examination with immunohistochemistry was negative. In contrast to the findings associated with HBV and HCV infection in which glomerular disease is predominantly found, the HAV infection in our patient was associated with interstitial nephritis and acute tubular necrosis. The prognosis of the renal failure due to HAV infection was good although the recovery was substantially delayed.
de Andrade Júnior, D R; Fujita Neto, F G; Vieira, G S; Tibério, I F; Warth, M P; Calich, I
We describe in this work a clinical case of a female patient aged 21 years, bearer of Wilson's disease, a first clinical manifestation of the disease occurred as an acute hemolytic crisis followed by fulminant hepatic failure evolving to death after 26 days' internment. The definitive diagnosis was obtained only as a quantitative measurement of hepatic copper from the necropsy material. The search for Kayser-Fleischer ring was negative and the serum ceruloplasmin level was 9 mg/dl (15 to 60). No involvement of the central nervous system was noted from the pathologic analysis. The patient presented two Coombs negative hemolytic crises during the internment; the first on being admitted to hospital and the second after a transjugular hepatic biopsy carried out on the 16th day after internment. The last hemolytic crisis was accompanied by an increase of serum and urinary copper levels. On this occasion the patient evolved to a progressive hepatic failure with severe jaundice and hepatic encephalopathy. We are presenting the clinical-biochemical evolution of the patient and we shall discuss the existent hypotheses to the pathophysiology of this rare form for manifestation of the Wilson's disease as well the diagnostic difficulties.
Miyakoshi, Shigesaburo; Kami, Masahiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Kusumi, Eiji; Matsumura, Tomoko; Onishi, Yasushi; Kobayashi, Kazuhiko; Kim, Sung-Won; Hamaki, Tamae; Takaue, Yoichi; Taniguchi, Shuichi
A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.
Background Hepatitis G virus (HGV) is an RNA virus. It is mainly transmitted through exposure to contaminated blood although other routes may also exist. Patients with chronic renal failure (CRF) are at high risk of acquiring HGV because they require frequent blood transfusions. Ongoing HGV infection can be only diagnosed by demonstrating viremia in patient sample by reverse transcriptase (RT) PCR. Antibodies to the envelop protein E2 (anti E2) of HGV is an indicator of virus clearance and testify past HGV contact. This cross sectional study was done to assess the frequency of HGV exposure (ongoing and past infection) in Egyptian children with CRF and to study the possible risk factors of infection. Methods This study included 100 children with CRF [34 on regular haemodialysis (HD) and 66 before the start of dialysis (predialysis)]. All patients sera were tested for HGV RNA by RT-PCR, anti E2, hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAB). Twenty five healthy children of matched age & sex were used as controls. Results HGV RNA was positive in 9 (26.5%) of HD and 9 (13.6%) of predialysis children. Anti E2 was positive in 14 (41.2%) of HD and 19 (28.8%) of predialysis children. In comparison to controls; CRF (n = 100); HD and predialysis children had significantly higher prevalence of anti E2 [4% VS 33% for all CRF cases; (p = 0.002)& 41.2% (p = 0.002) and 28.8% (p = 0.01); for HD and predialysis groups; respectively]. HGV RNA was significantly more prevalent only in HD children in comparison to controls (p = 0.03). HD and predialysis children did not have significant difference in the prevalence of HGV RNA (p = 0.16) or anti E2 (p = 0.26). HGV exposure was not correlated with positivity of anti HCV (p = 0.32), HCV RNA (0.09), HBsAg/HBcAB (p = 1), age (p = 0.06), or gender (p = 0.83). It was significantly correlated with duration of the disease (p < 0.001). Ongoing HGV infection was significantly more
Chang, Timothy S; Jensen, Matthew B
Background Ischaemic stroke interrupts the flow of blood to part of the brain. Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infarct size. Objectives To assess the effects of haemodilution in acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (Issue 1, 2014), MEDLINE (January 2008 to October 2013) and EMBASE (January 2008 to October 2013). We also searched trials registers, scanned reference lists and contacted authors. For the previous version of the review, the authors contacted manufacturers and investigators in the field. Selection criteria Randomised trials of haemodilution treatment in people with acute ischaemic stroke. We included only trials in which treatment was started within 72 hours of stroke onset. Data collection and analysis Two review authors assessed trial quality and one review author extracted the data. Main results We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No
Cooper, Sheldon C; Aldridge, Roland C; Shah, Tahir; Webb, Kerry; Nightingale, Peter; Paris, Sue; Gunson, Bridget K; Mutimer, David J; Neuberger, James M
Paracetamol (acetaminophen) hepatotoxicity, whether due to intentional overdose or therapeutic misadventure, is an indication for liver transplantation in selected cases. However, there is a concern that long-term outcomes may be compromised by associated psychopathology that may predispose patients to further episodes of self-harm or poor treatment adherence. We therefore undertook a retrospective analysis of patients transplanted for paracetamol-induced fulminant hepatic failure (FHF) to determine their long-term outcomes, psychiatric problems, and compliance and whether these issues could be predicted from pretransplant information. Records from patients undergoing liver transplantation for paracetamol-associated liver failure in this unit and 2 comparison groups (patients undergoing liver replacement for FHF from other causes and for chronic liver diseases) were examined. Of 60 patients transplanted for paracetamol-induced FHF between 1989 and 2007, 44 (73%) survived to discharge. Currently, 35 patients (58%) are surviving at an average of 9 years post-transplantation. The incidence of psychiatric disease (principally depression) and 30-day mortality were greatest in the paracetamol group, but for those who survived 30 days, there was no difference in long-term survival rates between the groups. Adherence to follow-up appointments and compliance with immunosuppression were lowest in the paracetamol overdose group. Poor adherence was not predicted by any identifiable premorbid psychiatric conditions. Two patients grafted for paracetamol FHF died from self-harm (1 from suicide and 1 from alcoholic liver disease after 5 years). This study suggests that, notwithstanding the shortage of donor liver grafts, transplantation is an appropriate therapy in selected patients, although close follow-up is indicated.
Sathyasaikumar, K V; Swapna, I; Reddy, P V B; Murthy, Ch R K; Dutta Gupta, A; Senthilkumaran, B; Reddanna, P
Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.
HSV hepatitis is a rare but often fatal cause of liver failure which tends to affect immunocompromised individuals. Early treatment with Acyclovir has been shown to reduce mortality in HSV hepatitis making recognition of the condition critically important. Here, we present a case of HSV hepatitis in a young woman with Crohn's disease on Prednisone, Azathioprine, and Infliximab. We discuss the clinical presentation of HSV hepatitis as well as the possible causes of hepatitis in a patient on these medications. This case helps demonstrate the importance of early clinical suspicion for HSV in undifferentiated fulminate liver failure. It is also the first reported case of HSV hepatitis in a patient on Infliximab, raising the possibility of HSV reactivation in patients on Infliximab. PMID:27818806
Weiner, Joshua; Griesemer, Adam; Island, Eddie; Lobritto, Steven; Martinez, Mercedes; Selvaggi, Gennaro; Lefkowitch, Jay; Velasco, Monica; Tryphonopoulos, Panagiotis; Emond, Jean; Tzakis, Andreas; Kato, Tomoaki
By preserving part of the native liver, auxiliary partial orthotopic liver transplantation (APOLT) provides the advantage of potential immunosuppression (ISP) withdrawal if the native liver recovers but has had limited acceptance, especially in the United States, due to technical complications and low rates of native liver regeneration. No previous study has evaluated APOLT specifically for preadolescent children with fulminant hepatic failure (FHF). This population might benefit especially based on greater capacity for liver regeneration. Data from 13 preadolescent children who underwent APOLT were compared to 13 matched controls who underwent orthotopic liver transplantation (OLT) for FHF from 1996 to 2013. There were no significant differences in patient demographics or survival between the 2 groups. However, all surviving OLT recipients (10/13) remain on ISP, while all but 1 surviving APOLT recipient (12/13) showed native liver regeneration, and the first 10 recipients (76.9%) are currently off ISP with 2 additional patients currently weaning. In our experience, APOLT produced excellent survival and high rates of native liver regeneration in preadolescent children with FHF. This represents the largest series to date to report such outcomes. Liberating these children from lifelong ISP without the downside of increased surgical morbidity makes APOLT an attractive alternative. In conclusion, we therefore propose that, with the availability of technical expertise and with the technical modifications above, APOLT for FHF should be strongly considered for preteenage children with FHF.
de Amorim, Regina Maria Santos; Coelho, Alexandre; Lampe, Elisabeth; Raiol, Tainá; Martins, Regina Maria Bringel
Hepatitis C virus (HCV) quasispecies constitute a dynamic population in a continuous process of variation and selection. To investigate effect of the immune system on the genetic variability of HCV, we compared the hypervariable region 1 (HVR1) of immunosuppressed patients with chronic renal failure (CRF group) to immunocompetent patients with HCV chronic infection (control group). The HVR1 from ten samples of each group was amplified, cloned and sequenced. The HCV quasispecies from the control group had a higher frequency of variable sites in HVR1 (83.9 % vs 59.3 %, p < 0.05), as well as a greater diversity within (intra-patient) and between samples, compared to the CRF group. The clustering of the majority of the quasispecies of the CRF group in the phylogenetic tree also showed the limited diversity of the quasispecies in immunosuppressed patients. Moreover, a higher variability of amino acids at positions 384, 386, 391, 394, 397, 398, 400, 405 and 410 was observed in the control group than in the CRF group, which showed a greater variability only at position 388 (p < 0.05). These data corroborates the hypothesis that the major selective pressure factor is the immune system, which promotes a high degree of diversity in the viral progeny and contributes to a constant evolution of HCV.
Wollersheim, Susan K; Humphries, Romney M; Cherry, James D; Krogstad, Paul
We describe a case of acute liver failure caused by echovirus 25 (E25) in a previously healthy 2-year-old boy. Initial serological studies were consistent with hepatitis A virus (HAV), with prozone phenomenon. The similarity of E25 to HAV may obscure accurate diagnosis in some cases of hepatitis.
Background Although patients with liver failure exhibit a generalized inflammatory-imbalance status, substantial evidence indicates that this immunosuppressive or anti-inflammatory state may be deleterious. Increased expression of CD163 (known to be involved in several anti-inflammatory functions of the immune system) in patients with liver failure is significantly correlated with a fatal outcome. However, little is known of the regulatory mechanisms that influence the expression of CD163. Methods We assessed the expression of CD163 on monocytes from both circulating cells and the liver tissues of patients with hepatitis B induced liver failure using flow cytometry and isolated the myofibroblasts from diseased livers. The ability of human liver myofibroblasts to regulate CD163 expression on monocytes was studied in vitro. Results We showed that CD163+ monocytes were enriched primarily in diseased livers and that they were associated with liver myofibroblasts in the same area. Accordingly, liver myofibroblasts were significantly superior to normal skin fibroblasts in inducing the expression of CD163 on monocytes in vitro. Moreover, we found that liver myofibroblasts triggered the activation of monocytes by secreting PGE2. Inhibition of PGE2 production in liver myofibroblasts using NS-398 markedly reduced CD163 expression in vitro. Conclusion These results suggest that liver myofibroblasts play a direct role in regulating the expression of CD163 on monocytes in human liver tissues and thereby may regulate monocyte function during hepatitis B induced liver failure. PMID:24597777
Yang, Xue-Fei; He, Yi; Li, Hai-Yuan; Liu, Xin; Chen, Huan; Liu, Jian-Bang; Ji, Wen-Jun; Wang, Bing; Chen, Li-Na
Fulminant hepatic failure is a severe clinical syndrome associated with a high rate of patient mortality. Recent studies have shown that in addition to its hematopoietic effect, erythropoietin (EPO) has multiple protective effects and exhibits antiapoptotic, antioxidant and anti-inflammatory activities. The present study aimed to determine the hepatoprotective effect of EPO and to elucidate the underlying mechanisms using a D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced model of acute liver injury. Experimental groups of mice were administered with various doses of EPO (1,000, 3,000 or 10,000 U/kg, intraperitoneal) once per day for 3 days, prior to injection with D-GalN (700 mg/kg)/LPS (10 µg/kg). Mice were sacrificed 8 h after treatment with D‑GalN/LPS. Liver function and histopathology, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH‑Px) activities and EPO receptor (EPOR) and phosphatidylinositol 3-kinase (PI3K) mRNA expression were evaluated. D-GalN/LPS administration markedly induced liver injury, as evidenced by elevated levels of serum aminotransferases, as well as histopathological changes. Compared with the D-GalN/LPS group, pretreatment with EPO significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase and MDA, and increased the activities of SOD and GSH-Px. Furthermore, the protective effects of EPO were paralleled by an upregulation in the mRNA expression of EPOR and PI3K. These data suggest that EPO can ameliorate D-GalN/LPS-induced acute liver injury by reducing oxidative stress and upregulating the mRNA expression of EPOR and PI3K.
PATRONO, D.; PARALUPPI, G.; PERINO, M.; PALISI, M.; MIGLIARETTI, G.; BERCHIALLA, P.; ROMAGNOLI, R.; SALIZZONI, M.
Background Posthepatectomy liver failure (PHLF) is the third most frequent complication and the major cause of postoperative mortality after resection of colorectal cancer liver metastases (CRLM). In case of synchronous resectable CRLM, it is still unclear if surgical strategy (simultaneous versus staged resection of colorectal cancer and hepatic metastases) influences the incidence and severity of PHLF. The aim of this study was to evaluate the impact of surgical strategy on PHLF and on the early and long-term outcome. Patients and Methods Retrospective study on 106 consecutive patients undergoing hepatectomy for synchronous CRLM between 1997 and 2012. Results Of 106 patients, 46 underwent simultaneous resection and 60 had staged hepatectomy. The rate of PHLF was similar between groups (16.7% vs 15.2%; p=1) and subgroup analysis restricted to patients undergoing major hepatectomy confirmed this observation (31.8% vs 23.8%; p=0.56). Propensity-score analysis showed that pre-operative total bilirubin level and the amount of intra-operative blood transfusion were independently associated with an increased risk of PHLF. Nevertheless, the risk of severe PHLF (grade B – C) was increased in patients who underwent simultaneous resection and major hepatectomy (OR: 4.82; p=0.035). No significant differences were observed in severe (Dindo – Clavien 3 – 4) postoperative morbidity (23.9% vs 20.0%; p=0.64) and survival (3 and 5-year survival: 55% and 34% vs 56% and 33%; p=0.83). Conclusions The risk of PHLF is not associated with surgical strategy in the treatment of synchronous CRLM. Nevertheless, the risk of severe PHLF is increased in patients undergoing simultaneous resection and major hepatectomy. PMID:24841686
Overton, E. Turner; Tamhane, Ashutosh R.; Forsythe, Jordan M.; Rodgers, Joel B.; Schexnayder, Julie K.; Guthrie, Deanne; Thogaripally, Suneetha; Zinski, Anne; Saag, Michael S.; Mugavero, Michael J.; Wang, Henry E.; Galbraith, James W.
Background. Emergency departments (EDs) are high-yield sites for hepatitis C virus (HCV) screening, but data regarding linkage to care (LTC) determinants are limited. Methods. Between September 2013 and June 2014, 4371 baby boomers unaware of their HCV status presented to the University of Alabama at Birmingham ED and underwent opt-out screening. A linkage coordinator facilitated referrals for positive cases. Demographic data, International Classification of Diseases, Ninth Revision codes, and clinic visits were collected, and patients were (retrospectively) followed up until February 2015. Linkage to care was defined as an HCV clinic visit within the hospital system. Results. Overall, 332 baby boomers had reactive HCV antibody and detectable plasma ribonucleic acid. The mean age was 57.3 years (standard deviation = 4.8); 70% were male and 61% were African Americans. Substance abuse (37%) and psychiatric diagnoses (30%) were prevalent; 9% were identified with cirrhosis. During a median follow-up of 433 days (interquartile range, 354–500), 117 (35%) linked to care and 48% needed inpatient care. In multivariable analysis, the odds of LTC failure were significantly higher for white males (adjusted odds ratio [aOR], 2.57; 95% confidence interval [CI], 1.03–6.38) and uninsured individuals (aOR, 5.16; 95% CI, 1.43–18.63) and lower for patients with cirrhosis (aOR, 0.36; 95% CI, 0.14–0.92) and access to primary care (aOR, 0.20; 95% CI, 0.10–0.41). Conclusions. In this cohort of baby boomers with newly diagnosed HCV in the ED, only 1 in 3 were linked to HCV care. Although awareness of HCV diagnosis remains important, intensive strategies to improve LTC and access to curative therapy for diagnosed individuals are needed. PMID:28066793
Michelena, Javier; Altamirano, José; Abraldes, Juan G.; Affò, Silvia; Morales-Ibanez, Oriol; Sancho-Bru, Pau; Dominguez, Marlene; García-Pagán, Juan Carlos; Fernández, Javier; Arroyo, Vicente; Ginès, Pere; Louvet, Alexandre; Mathurin, Philippe; Mehal, Wajahat Z.; Caballería, Juan; Bataller, Ramón
Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P <0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P=0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone. Conclusion In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids. PMID:25761863
Stott, D J; Spilg, E; Campbell, A M; Rumley, A; Mansoor, M A; Lowe, G D
Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.
Eguchi, S; Lilja, H; Hewitt, W R; Middleton, Y; Demetriou, A A; Rozga, J
We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased
Liu, Mei; Wang, Peng; Zhao, Min; Liu, DY
Fulminant hepatic failure (FHF) is defined as rapid acute liver injury, often complicated with spontaneous bacterial peritonitis (SBP). The precise onset of FHF with SBP is still unknown, but it is thought that SBP closely correlates with a weakened intestinal barrier. Dendritic cells (DCs) play a crucial role in forming the intestinal immune barrier, therefore the number, maturity and chemotactic ability of intestinal DCs were studied in FHF. Mouse intestinal and spleen DCs were isolated by magnetic-activated cell sorting (MACS) and surface markers of DCs, namely CD11c, CD74, CD83 and CD86, were identified using flow cytometry. Immunohistochemistry and Western blotting were performed to detect the distribution and expression of CC-chemokine receptor 7 (CCR7) and CC-chemokine receptor 9 (CCR9), as well as their ligands-CC-chemokine ligand 21 (CCL21) and CC-chemokine ligand 25 (CCL25). Real-time PCR was used to detect CCR7 and CCR9 mRNA, along with their ligands-CCL21 and CCL25 mRNA. Flow cytometry analysis showed that the markers CD74, CD83 and CD86 of CD11c+DCs were lower in the D-galactosamine (D-GalN) group and were significantly decreased in the FHF group, while there were no significant changes in the expression of these markers in the lipopolysaccharide (LPS) group. Immunohistochemistry results showed that staining for CCR7 and CCR9, as well as their ligands CCL21 and CCL25, was significantly weaker in the D-GalN and FHF groups compared with the normal saline (NS) group or the LPS group; the FHF group even showed completely unstained parts. Protein expression of CCR7 and CCR9, as well as their ligands- CCL21 and CCL25, was also lower in the D-GalN group and decreased even more significantly in the FHF group. At the gene level, CCR7 and CCR9, along with CCL21 and CCL25 mRNA expression, was lower in the D-GalN group and significantly decreased in the FHF group compared to the NS and LPS groups, consisting with the protein expression. Our study indicated that
Lakhin, R E; Belozerova, L A; Maksimets, V A; Romanov, D M
Effects of hyperbaric oxygenation, bemitil, and solcoseryl used in preoperative treatment of patients with hepatic failure on the oxidant-antioxidant system are studied. Lipid peroxidation (LPO) was assessed from changes in the levels of malonic dialdehyde and diene conjugate and the antioxidant system from the number of SH-groups. Hyperbaric oxygenation led to activation of LPO processes. Bemitil decreased the intensity of LPO by extending the potentialities of the antioxidant system. Antioxidant properties of solcoseryl were not realized through the thiol buffer of the antioxidant system. Only a course of treatment with this drug brings about a stable effect.
Kobashi-Margáin, Ramón A; Gavilanes-Espinar, Juan G; Gutiérrez-Grobe, Ylse; Gutiérrez-Jiménez, Angel A; Chávez-Tapia, Norberto; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez Sánchez, Nahum
Acute, acute-on-chronic and chronic liver diseases are major health issues worldwide, and most cases end with the need for liver transplantation. Up to 90% of the patients die waiting for an organ to be transplanted. Hepatic encephalopathy is a common neuropsychiatric syndrome that usually accompanies liver failure and impacts greatly on the quality of life. The molecular adsorbent recirculating system (MARS) is a recently developed form of artificial liver support that functions on a base of albumin dialysis. It facilitates the dialysis of albumin-bound and water-soluble toxins, allowing the patient to survive and even improving some clinical features of liver failure. The following manuscript reviews the technical features of MARS operation and some of the clinical trials that analyze the efficacy of the system in the therapy of liver diseases.
Abdel-Rahman, Islam; Murphy, Christie
Polycythaemia vera is a recognised cause of ischaemic stroke. If not treated, this condition may result in recurrent strokes. This is a case of a 61-year-old Caucasian man presenting with the inability to ambulate for 3 days. Brain imaging revealed acute and chronic infarctions in the brain stem and the cerebrum. Polycythaemia vera was diagnosed and treated during the admission. The unique mechanisms and management issues of ischaemic stroke associated with polycythaemia vera are discussed. PMID:25754163
Wang, Jia M.; Ma, Cheng J.; Li, Guang Y.; Wu, Xiao Y.; Thayer, Penny; Greer, Pamela; Smith, Ashley M.; High, Kevin P.; Moorman, Jonathan P; Yao, Zhi Q.
Hepatitis B virus (HBV) vaccination is recommended for individuals with hepatitis C virus (HCV) infection given their shared risk factors and increased liver-related morbidity and mortality upon super-infection. Vaccine responses in this setting are often blunted, with poor response rates to HBV vaccinations in chronically HCV-infected individuals compared to healthy subjects. In this study, we investigated the role of T cell immunoglobulin mucin domain-3 (Tim-3)-mediated immune regulation in HBV vaccine responses during HCV infection. We found that Tim-3, a marker for T cell exhaustion, was over-expressed on monocytes, leading to a differential regulation of IL-12/IL-23 production with in turn TH17 cell accumulation, in HCV-infected HBV vaccine non-responders compared to HCV-infected HBV vaccine responders or healthy subjects (HS). Importantly, ex vivo blockade of Tim-3 signaling corrected the imbalance of IL-12/IL-23 as well as the IL-17 bias observed in HBV vaccine non-responders during HCV infection. These results suggest that Tim-3-mediated dysregulation of innate to adaptive immune responses is involved in HBV vaccine failure in individuals with chronic HCV infection, raising the possibility that blocking this negative signaling pathway might improve the success rate of HBV immunization in the setting of chronic viral infection. PMID:23499521
Philips, Cyriac Abby; Sarin, Shiv Kumar
Acute on chronic liver failure (ACLF) is a disease entity with a high mortality rate. The acute event arises from drugs and toxins, viral infections, bacterial sepsis, interventions (both surgical and non-surgical) and vascular events on top of a known or occult chronic liver disease. ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition; the high mortality of which can be managed in the wake of new potent antiviral therapy. For example, lamivudine and entecavir use has shown definite short-term survival benefits, even though drug resistance is a concern in the former. The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction. Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients. This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B, thereby providing an algorithm in management of such patients.
Jamshidzadeh, Akram; Heidari, Reza; Abasvali, Mozhgan; Zarei, Mehdi; Ommati, Mohammad Mehdi; Abdoli, Narges; Khodaei, Forouzan; Yeganeh, Yasaman; Jafari, Faezeh; Zarei, Azita; Latifpour, Zahra; Mardani, Elnaz; Azarpira, Negar; Asadi, Behnam; Najibi, Asma
Ammonia-induced mitochondrial dysfunction and energy crisis is known as a critical consequence of hepatic encephalopathy (HE). Hence, mitochondria are potential targets of therapy in HE. The current investigation was designed to evaluate the role of taurine treatment on the brain and liver mitochondrial function in a rat model of hepatic encephalopathy and hyperammonemia. The animals received thioacetamide (400mg/kg, i.p, for three consecutive days at 24-h intervals) as a model of acute liver failure and hyperammonemia. Several biochemical parameters were investigated in the serum, while the animals' cognitive function and locomotor activity were monitored. Mitochondria was isolated from the rats' brain and liver and several indices were assessed in isolated mitochondria. Liver failure led to cognitive dysfunction and impairment in locomotor activity in the rats. Plasma and brain ammonia was high and serum markers of liver injury were drastically elevated in the thioacetamide-treated group. An assessment of brain and liver mitochondrial function in the thioacetamide-treated animals revealed an inhibition of succinate dehydrogenase activity (SDA), collapsed mitochondrial membrane potential, mitochondrial swelling, and increased reactive oxygen species (ROS). Furthermore, a significant decrease in mitochondrial ATP was detected in the brain and liver mitochondria isolated from thioacetamide-treated animals. Taurine treatment (250, 500, and 1000mg/kg) decreased mitochondrial swelling, ROS, and LPO. Moreover, the administration of this amino acid restored brain and liver mitochondrial ATP. These data suggest taurine to be a potential protective agent with therapeutic capability against hepatic encephalopathy and hyperammonemia-induced mitochondrial dysfunction and energy crisis.
Ficko, C; Conan, P L; Bigaillon, C; Duron, S; Rapp, C
In stays in tropical countries, the French military, and travelers in general, are exposed to diseases transmitted by the fecal-oral route, some of which are vaccine-preventable. Here we report a 42-yer-old soldier with hepatitis A, which first appeared on his return from a military operation in the Central African Republic. Despite its excellent immunogenicity and a duration of seroprotection extending beyond 20 years in the vast majority of cases, the hepatitis A vaccine can fail. This reminds us of the importance of combining vaccine and non-vaccine prevention in tropical countries, especially in precarious living conditions.
Santos, Wilson JQ; Zanetta, Dirce MT; Pires, Antonio C; Lobo, Suzana MA; Lima, Emerson Q; Burdmann, Emmanuel A
Introduction Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group. Method We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000. Results Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64–5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04–3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60–3.76 [P < 0.001] for all patients combined]). Conclusion The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The
Chang, Hua-Ming; Liao, Yi-Wen; Chiang, Chih-Hung; Chen, Yi-Jen; Lai, Ying-Hsiu; Chang, Yuh-Lih; Chen, Hen-Li; Jeng, Shaw-Yeu; Hsieh, Jung-Hung; Peng, Chi-Hsien; Li, Hsin-Yang; Chien, Yueh; Chen, Szu-Yu; Chen, Liang-Kung; Huo, Teh-Ia
The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases. PMID:22489170
Maznyczka, Annette; Sen, Sayan; Cook, Christopher; Francis, Darrel P
The ischaemic cascade is the concept that progressive myocardial oxygen supply-demand mismatch causes a consistent sequence of events, starting with metabolic alterations and followed sequentially by myocardial perfusion abnormalities, wall motion abnormalities, ECG changes, and angina. This concept would suggest that investigations that detect expressions of ischaemia earlier in the cascade should be more sensitive tests of ischaemia than those that detect expressions appearing later in the cascade. However, careful review of the studies on which the ischaemic cascade is based suggests that the ischaemic cascade concept may be less well supported by the literature than assumed. In this review we explore this, discuss an alternative method for conceptualising ischaemia, and discuss the potential implications of this new approach to clinical studies and clinical practice.
Li, Hai; Chen, Liu-Ying; Zhang, Nan-nan; Li, Shu-Ting; Zeng, Bo; Pavesi, Marco; Amorós, Àlex; Mookerjee, Rajeshwar P; Xia, Qian; Xue, Feng; Ma, Xiong; Hua, Jing; Sheng, Li; Qiu, De-kai; Xie, Qing; Foster, Graham R; Dusheiko, Geoffrey; Moreau, Richard; Gines, Pere; Arroyo, Vicente; Jalan, Rajiv
The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles. PMID:27146801
Beinhardt, Sandra; Tomasits, Josef; Dienes, Hans Peter
We present a case of severe fatal hepatitis in a young patient presumably triggered by two ubiquitous viral diseases which occurred in close succession. This case is unusual because of the exceptional chronological sequence of primary Epstein–Barr virus and herpes simplex virus type 1 infection causing systemic immune dysregulation associated with rapidly developing liver failure and consecutive multiorgan failure. Clinical, laboratory and histopathological findings indicated the development of secondary haemophagocytic lymphohistiocytosis triggered by these closely succeeding viral primary infections. PMID:28356254
Ridgley, Joanne; Raison, Nicholas; Sheikh, M. Iqbal; Dasgupta, Prokar; Khan, M. Shamim; Ahmed, Kamran
Objective Ischaemic priapism is a rare condition characterised by little or no cavernosal blood flow, pain and rigidity of the penis. Immediate intervention is required to restore blood flow, prevent necrosis and erectile dysfunction. This review was conducted to determine the best course of treatment and identify areas in current guidelines to which improvements could be made. Material and methods PubMed, Ovid, MEDLINE (1946–December 2016) and the Cochrane Library were searched as sources for literature. Key studies in each of the areas of management were identified and analysed. Results A total of 45 articles were reviewed. The first step in treatment should be aspiration of corporeal blood. Further studies are needed to make firm recommendations as to whether irrigation should follow, as currently literature is inconclusive. If this fails to cause detumescence, sympathomimetics should be injected. The sympathomimetic of choice is phenylephrine as it is effective, specific and causes minimal cardiovascular side effects. It should be injected at a concentration of 100–500 μg/mL, with 1 mL being injected every 3–5 minutes for up to an hour (maximum 1mg in an hour). Surgical shunting is the next step, except in the cases of delayed priapism (48–72 hours duration) where immediate penile prosthesis insertion may be considered more appropriate. Distal shunts should be performed first, followed by proximal ones to minimise damage leading to erectile dysfunction. There exists little evidence recommending one shunting procedure over another. The final intervention is insertion of a penile prosthesis. Literature suggests that an inflatable prosthesis inserted immediately will yield the greatest patient satisfaction. Conclusion A review of the literature has highlighted areas in which further research needs to be done to make conclusive recommendations, including whether irrigation should accompany aspiration and efficacy of shunting procedures. Further studies are
Wardlaw, Joanna M; Murray, Veronica; Berge, Eivind; del Zoppo, Gregory J
Background Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Thrombolytic drugs, however, can also cause serious bleeding in the brain, which can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is licensed for use in selected patients within 4.5 hours of stroke in Europe and within three hours in the USA. There is an upper age limit of 80 years in some countries, and a limitation to mainly non-severe stroke in others. Forty per cent more data are available since this review was last updated in 2009. Objectives To determine whether, and in what circumstances, thrombolytic therapy might be an effective and safe treatment for acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (last searched November 2013), MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013).We also handsearched conference proceedings and journals, searched reference lists and contacted pharmaceutical companies and trialists. Selection criteria Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke. Data collection and analysis Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We verified the extracted data with investigators of all major trials, obtaining additional unpublished data if available. Main results We included 27 trials, involving 10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial administration, while the rest used the intravenous route. Most data come from trials that started treatment up to six hours after stroke. About 44% of the trials (about 70% of the participants) were testing intravenous rt-PA. In earlier studies very few of the participants (0
Zhong, Yaogang; Guo, Yonghong; Liu, Xiawei; Zhang, Jiaxu; Ma, Tianran; Shu, Jian; Yang, Jiajun; Zhang, Jing; Jia, Zhansheng; Li, Zheng
Acute-on-chronic hepatitis B liver failure (ACHBLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with cirrhosis, so little is known about the alterations of protein glycopatterns in serum with its development. We aimed to identify the alterations of serum glycopatterns in ACHBLF and probe the possibility of them as novel potential biomarkers for diagnosis of ACHBLF. As a result, there were 18 lectins (e.g., WFA, GSL-II, and PNA) to give significantly alterations of serum glycopatterns in ACHBLF compared with healthy controls (HC) (all p ≤ 0.0386). Meanwhile, among these lectins, there were 12 lectins (e.g., WFA, GAL-II, and EEL) also exhibited significantly alterations of serum glycopatterns in ACHBLF compared with HBV-infected chronic hepatitis (cHB) (all p ≤ 0.0252). The receiver-operating characteristic (ROC) curve analysis indicated there were 5 lectins (PHA-E + L, BS-I, ECA, ACA, and BPL) had the greatest discriminatory power for distinguishing ACHBLF and HC or cHB, respectively (all p ≤ 0.00136). We provided a new basic insight into serum glycopatterns in ACHBLF and investigated the correlation of alterations in serum glycopatterns as novel potential biomarkers for diagnosis of ACHBLF. PMID:28383031
Zhao, Guangyu; Zhou, Xiaojun; Li, Junfeng; Hu, Jingya; Yu, Hong; Chen, Yu; Song, Hongbin; Qiao, Fei; Xu, Guilian; Yang, Fei; Wu, Yuzhang; Tomlinson, Stephen; Duan, Zhongping; Zhou, Yusen
Fulminant hepatic failure (FHF) is a clinically severe type of liver injury with an extremely high mortality rate. Although the pathological mechanisms of FHF are not well understood, evidence suggests that the complement system is involved in the pathogenesis of a variety of liver disorders. In the present study, to investigate the role of complement in FHF, we examined groups of mice following intraperitoneal injection of LPS/D-GalN: wild-type C57BL/6 mice, wild-type mice treated with a C3aR antagonist, C5aR monoclonal antibody (C5aRmAb) or CR2-Factor H (CR2-fH, an inhibitor of the alternative pathway), and C3 deficient mice (C3−/− mice). The animals were euthanized and samples analyzed at specific times after LPS/D-GalN injection. The results show that intraperitoneal administration of LPS/D-GalN activated the complement pathway, as evidenced by the hepatic deposition of C3 and C5b-9 and elevated serum levels of the complement activation product C3a, the level of which was associated with the severity of the liver damage. C3a receptor (C3aR) and C5a receptor (C5aR) expression was also upregulated. Compared with wild-type mice, C3−/− mice survived significantly longer and displayed reduced liver inflammation and attenuated pathological damage following LPS/D-GalN injection. Similar levels of protection were seen in mice treated with C3aR antagonist,C5aRmAb or CR2-fH. These data indicate an important role for the C3a and C5a generated by the alternative pathway in LPS/D-GalN-induced FHF. The data further suggest that complement inhibition may be an effective strategy for the adjunctive treatment of fulminant hepatic failure. PMID:22069473
Rangegowda, Devaraja; Vyas, Tanmay; Kulkarni, Anand; Grover, Shrruti; Mahiwall, Rakhi; Sarin, Shiv Kumar
Systemic amyloidosis of amyloid light chain associated protein (AL), also called primary amyloidosis, frequently involves the liver, but rarely causes clinically apparent liver disease. The more common presentation is with acute renal failure. Hepatomegaly and mild elevation of alkaline phosphatase are the most common clinical and biochemical findings, respectively. We report a case of systemic amyloidosis of AL that clinically presented as acute-on-chronic liver failure and resulted in a fatal clinical course in a 56-year-old man. PMID:28286788
Bose, Somnath; Sonny, Abraham; Rahman, Nadeem
A teenager was admitted to an outside hospital ED following an episode of melena. He had been complaining of intermittent abdominal pain, nausea, malaise, and easy fatigability for 2 months, with significant worsening of symptoms 2 weeks prior to this episode. He had no significant medical, surgical, or family history. On presentation at the outside ED, he was found to be profoundly icteric and encephalopathic. Initial laboratories suggested anemia, acute kidney injury, and acute liver failure, leading to a presumptive diagnosis of acute fulminant liver failure necessitating transfer to our institution.
Borrego, F J; Viedma, G; Pérez del Barrio, P; Gil, J M; de Santis-Scoccia, C; Ramírez Huerta, J M; Alcalá, A; Pérez Bañasco, V
Acute renal failure following bone marrow transplantation is a frequent complication with an incidence ranging 15-30% and with high rates of morbidity and mortality. Numerous potential etiologies can be implicated as chemotherapy regimen, use of nephrotoxic antibiotics, sepsis-induced damage, cyclosporine toxicity and other especific pathologies as graft-v-host disease or veno-occlusive disease of the liver. We report the case of a 41-year-old man who underwent autologous peripheral blood stem cell transplantation and developed and acute renal failure secondary to a fatal veno-occlusive disease of the liver. Incidence, potential predisposing factors, outcome and possibilities of treatment are reviewed.
Viertmann, Anne-Odette; Janßen, Claudia; Birklein, Frank; Thüroff, Joachim W.; Stein, Raimund
Intermittent hyperammonemic encephalopathy after ureterosigmoidostomy is a rare, but if unrecognized, potentially lethal condition. Ureterosigmoidostomy was performed in a male patient with bladder extrophy. After 35 years, he developed hyperammonemic encephalopathy. Diagnostic procedures did not reveal hepatic nor metabolic disorders. Despite administration of preventive medical treatment, several episodes recurred. A durable prevention was finally achieved by conversion into an ileal conduit. Intermittent hyperammonemic encephalopathy can occur decades after ureterosigmoidostomy. In the case of absence of metabolic disorders and resistance to medical treatment, conversion into a urinary diversion using an ileal segment constitutes an effective ultima ratio. PMID:25914851
Masoud, Waleed G.T.; Abo Al-Rob, Osama; Yang, Yang; Lopaschuk, Gary D.; Clanachan, Alexander S.
Aims Post-infarction remodelled failing hearts have reduced metabolic efficiency. Paradoxically, they have increased tolerance to further ischaemic injury. This study was designed to investigate the metabolic mechanisms that may contribute to this phenomenon and to examine the relationship between ischaemic tolerance and metabolic efficiency during post-ischaemic reperfusion. Methods and results Male C57BL/6 mice were subjected to coronary artery ligation (CAL) or SHAM surgery. After 4 weeks, in vivo mechanical function was assessed by echocardiography, and then isolated working hearts were perfused in this sequence: 45 min aerobic, 15 min global no-flow ischaemia, and 30 min aerobic reperfusion. Left ventricular (LV) function, metabolic rates, and metabolic efficiency were measured. Relative to SHAM, both in vivo and in vitro CAL hearts had depressed cardiac function under aerobic conditions (45 and 36%, respectively), but they had a greater recovery of LV function during post-ischaemic reperfusion (67 vs. 49%, P < 0.05). While metabolic efficiency (LV work per ATP produced) was 50% lower during reperfusion of SHAM hearts, metabolic efficiency in CAL hearts did not decrease. During ischaemia, glycogenolysis was 28% lower in CAL hearts, indicative of lower ischaemic proton production. There were no differences in mitochondrial abundance, calcium handling proteins, or key metabolic enzymes. Conclusion Compared with SHAM, remodelled CAL hearts are more tolerant to ischaemic injury and undergo no further deterioration of metabolic efficiency during reperfusion. Less glycogen utilization in CAL hearts during ischaemia may contribute to increased ischaemic tolerance by limiting ischaemic proton production that may improve ion homeostasis during early reperfusion. PMID:26150203
Hasebe, Chitomi; Osaki, Yukio; Joko, Kouji; Yagisawa, Hitoshi; Sakita, Shinya; Okushin, Hiroaki; Satou, Takashi; Hisai, Hiroyuki; Abe, Takehiko; Tsuji, Keiji; Tamada, Takashi; Kobashi, Haruhiko; Mitsuda, Akeri; Ide, Yasushi; Ogawa, Chikara; Tsuruta, Syotaro; Takaguchi, Kouichi; Murakawa, Miyako; Asahina, Yasuhiro; Enomoto, Nobuyuki; Izumi, Namiki
Backgrounds & Aims We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. Methods This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment. RASs in NS5A and NS3 were determined by population sequencing. Results The frequency of signature RASs at position D168 of NS3 was 68%, and at positions L31 and Y93 of NS5A was 79 and 76%, respectively. The frequency of dual signature RASs in NS5A (L31-RAS and Y93-RAS) was 63%. RASs at L28, R30, P32, Q54, P58, and A92 in addition to dual signature RAS were detected in 5, 5, 1, 22, 2, and 0 patients, respectively. In total, triple, quadruple, and quintuple RASs in combination with dual signature RAS were detected in 35, 10, and 1.5% patients, respectively. These RASs were detected in patients without baseline RASs or who prematurely discontinued therapy. Co-existence of D168 RAS in NS3 and L31 and/or Y93 RAS in NS5A was observed in 62% of patients. Conclusion Treatment-emergent RASs after failure with DCV/ASV combination therapy are highly complex in more than 50% of the patients. The identification of complex RAS patterns, which may indicate high levels of resistance to NS5A inhibitors, highlights the need for RAS sequencing when considering re-treatment with regimens including NS5A inhibitors. PMID:27776192
Roberts, Lara N.; Patel, Raj; Pathansali, Rohan; Kalra, Lalit; Arya, Roopen
Introduction. Stroke remains a global leading cause of death and disability. Traditional description of plasma biology in the aftermath of acute ischaemic stroke favours development of hypercoagulability, resulting from complex interplay between plasma and endothelial factors. However, no single assay measures the overall global coagulation process. We postulate that thrombin generation would assist in identifying coagulation abnormalities after acute stroke. Aim. To investigate the coagulation abnormalities after acute ischaemic stroke using thrombin generation. Methods. We evaluated thrombin generation, measured with calibrated automated thrombography in stroke of different aetiological types (n = 170) within 48 hours of symptoms onset (baseline) and in the second week (time 2) and in normal healthy volunteers (n = 71). Results. Two-point thrombin generation assays showed prolonged lag time and time to peak at baseline (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7); p = 0.005) and (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7); p = 0.002), respectively, and at time 2 (3.5 (2.9, 4.2) versus 4.0 (3.1, 4.9); p = 0.004) and (5.9 (5.3, 6.6) versus 6.8 (5.8, 7.7) p = 0.05), respectively, in cardioembolic stroke (n = 39), when compared to noncardioembolic stroke (n = 117). The result was reproduced in multiple comparisons between acute ischaemic stroke subgroups and normal healthy volunteers. Endogenous thrombin potential and peak thrombin did not indicate hypercoagulability after acute ischaemic stroke, and thrombolytic therapy did not affect thrombin generation assays. Conclusion. Our findings suggest that thrombin generation in platelet poor plasma is not useful in defining hypercoagulability in acute ischaemic stroke. This is similar to observed trend in coronary artery disease and contrary to other hypercoagulable states. PMID:28116215
Fontenele, Andrea Martins Melo; Gainer, Juliana Braga Furtado; da Silva E Silva, Daniel Viana; Cruz Santos, Max Diego; Salgado, João Victor; Salgado Filho, Natalino; Ferreira, Adalgisa Sousa Paiva
Occult hepatitis B (OHB) is characterized by the presence of HBV-DNA in the absence of HBsAg in the serum of patients. Hemodialysis patients are at high risk for hepatitis B virus and there are few data on the prevalence of OHB in this population, mainly in Brazil. Thus, the aim of this study was to determine the prevalence of OHB in patients undergoing hemodialysis. A cross-sectional study was performed, including 301 patients on chronic hemodialysis at two dialysis centers in São Luís (Maranhão), northeast Brazil. Serological tests were performed for HBsAg, anti-HBc, anti-HBs, and anti-HCV using enzyme immunoassays (ELISA); HBV-DNA and HCV-RNA were studied by real-time PCR. The mean age was 49 ± 15 years, and 128 (42%) were female. Serological tests confirmed that all samples were HBsAg negative. Anti-HBc was positive in 114 (38%) patients, anti-HBc and anti-HBs were simultaneously positive in 104 (35%), and anti-HBc alone was positive in 10 (3%). Tests were negative for anti-HBc and anti-HBs in 55 patients (18%). Anti-HBs was the only positive marker in 132 (44%) patients. Anti-HCV was positive in 15 (5%) patients with HCV-RNA present in 14 of them (93%). HBV-DNA was positive in seven cases (2.3%). There was no association of HBV-DNA with age, gender, time on dialysis, previous kidney transplant, or HBV serological pattern, but there was a positive correlation with the presence of anti-HCV (P < 0.001). OHB in chronic renal failure patients on hemodialysis appears to be a relevant finding, suggesting that studying HBV-DNA in this population using sensitive molecular tests should be a recommended course of action, especially in candidates for renal transplant.
Schneider, Jaime L; Villarroya, Joan; Diaz-Carretero, Antonio; Patel, Bindi; Urbanska, Aleksandra M; Thi, Mia M; Villarroya, Francesc; Santambrogio, Laura; Cuervo, Ana Maria
Chaperone-mediated autophagy (CMA), a cellular process that contributes to protein quality control through targeting of a subset of cytosolic proteins to lysosomes for degradation, undergoes a functional decline with age. We have used a mouse model with liver-specific defective CMA to identify changes in proteostasis attributable to reduced CMA activity in this organ with age. We have found that other proteolytic systems compensate for CMA loss in young mice which helps to preserve proteostasis. However, these compensatory responses are not sufficient for protection against proteotoxicity induced by stress (oxidative stress, lipid challenges) or associated with aging. Livers from old mice with CMA blockage exhibit altered protein homeostasis, enhanced susceptibility to oxidative stress and hepatic dysfunction manifested by a diminished ability to metabolize drugs, and a worsening of the metabolic dysregulation identified in young mice. Our study reveals that while the regulatory function of CMA cannot be compensated for in young organisms, its contribution to protein homeostasis can be handled by other proteolytic systems. However, the decline in the compensatory ability identified with age explains the more severe consequences of CMA impairment in older organisms and the contribution of CMA malfunction to the gradual decline in proteostasis and stress resistance observed during aging. PMID:25620427
Maitta, Robert W; Choate, Jacquelyn; Emre, Sukru H; Luczycki, Stephen M; Wu, Yanyun
The increasing demand for solid organ transplants has brought to light the need to utilize organs in critical situations despite ABO-incompatibility. However, these transplantations are complicated by pre-existing ABO antibodies which may be potentially dangerous and makes the transplantation prone to failure due to rejection with resulting necrosis or intrahepatic biliary complications. We report the clinical outcome of an emergency ABO-incompatible liver transplant (due to fulminant hepatic failure with sudden and rapidly deteriorating mental status) using a modified therapeutic plasma exchange (TPE) protocol. The recipient was O-positive with an initial anti-B titer of 64 and the cadaveric organ was from a B-positive donor. The patient underwent initial TPE during the peri-operative period, followed by a series of postoperative daily TPE, and later a third series of TPE for presumptive antibody-mediated rejection. The latter two were performed in conjunction with the use of IVIg and rituximab. The recipient's anti-B titer was reduced and maintained at 8 or less 8 months post-op. However, an elevation of transaminases 3 months post-transplant triggered a biopsy which was consistent with cellular rejection and with weak C4d positive staining suggestive of antibody mediated rejection. Additional plasma exchange procedures were performed. The patient improved rapidly after modification of her immunosuppression regimen and treatment with plasma exchange. This case illustrates that prompt and aggressive plasma exchange, in conjunction with immunosuppression, is a viable approach to prevent and treat antibody mediated transplant rejection in emergency ABO-incompatible liver transplant.
Pereira, L M; Langley, P G; Hayllar, K M; Tredger, J M; Williams, R
The value of coagulation factor V and VIII/V levels as prognostic indicators was assessed in 27 patients with fulminant hepatic failure and compared with other predictive indices. Admission factor V levels were significantly reduced in 22 patients with paracetamol induced hepatic failure compared with a healthy control group (median 9.5% v 103%, respectively; p less than 0.001) and with lower values in non-A non-B hepatitis (median 2.7%). Values in the seven patients who died after paracetamol overdose, considered together with the four who underwent liver transplantation (group median 5.1%), were significantly lower than in the 11 who survived (median 11.8%; p less than 0.01). Median admission factor VIII was higher in those who died or received a transplant than in those who survived (298% v 162%; p less than 0.05), with both results higher than in healthy volunteers (median 104%; p less than 0.01) but lower than in non-A non-B hepatitis (median 340%). The ratio of factor VIII/V on admission was less than 30 in all patients who survived paracetamol overdose (median 17) with corresponding values greater than 30 in 10 of 11 of those who died (median 39). A factor V result less than or equal to 10% on admission predicted an adverse outcome in 10 of 11 fatal cases, a 91% sensitivity which was greater than for the previously defined indicator of an arterial blood pH less than 7.30 on admission (sensitivity 82%). Prothrombin time at admission or on day 4 did not usefully predict outcome in our series. Predictive accuracy was 73% and 82% for factor V and admission acidosis respectively and 95% for factor V in conjunction with admission coma grade III or IV and factor VIII (ratio > 30). These criteria may be useful in selecting patients with paracetamol induced fulminant hepatic failure for transplantation. PMID:1740285
Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Martinez-Perez, Yoalli; Lezama-Palacios, Ruth; Franco-Colin, Margarita; Ortiz-Butron, Rocio
The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment.
Wu, Weimin; Chen, Zhaochun; Cheng, Naiqian; Watts, Norman R; Stahl, Stephen J; Farci, Patrizia; Purcell, Robert H; Wingfield, Paul T; Steven, Alasdair C
Previously, the livers of patients suffering from acute liver failure (ALF), a potentially fatal syndrome arising from infection by Hepatitis B Virus (HBV), were found to contain massive amounts of an antibody specific for the core antigen (HBcAg) capsid. We have used cryo-electron microscopy and molecular modeling to define its epitope. HBV capsids are icosahedral shells with 25Å-long dimeric spikes, each a 4-helix bundle, protruding from the contiguous "floor". Of the anti-HBcAg antibodies previously characterized, most bind around the spike tip while one binds to the floor. The ALF-associated antibody binds tangentially to a novel site on the side of the spike. This epitope is conformational. The Fab binds with high affinity to its principal determinants but has lower affinities for quasi-equivalent variants. The highest occupancy site is on one side of a spike, with no detectable binding to the corresponding site on the other side. Binding of one Fab per dimer was also observed by analytical ultracentrifugation. The Fab did not bind to the e-antigen dimer, a non-assembling variant of capsid protein. These findings support the propositions that antibodies with particular specificities may correlate with different clinical expressions of HBV infection and that antibodies directed to particular HBcAg epitopes may be involved in ALF pathogenesis.
Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa
It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging.
Martínez-Sellés, M; Gómez Huelgas, R; Abu-Assi, E; Calderón, A; Vidán, M T
It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging.
Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa
It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging.
Gleadle, Jonathan M.; Mazzone, Annette
Brief periods of ischaemia followed by reperfusion of one tissue such as skeletal muscle can confer subsequent protection against ischaemia-induced injury in other organs such as the heart. Substantial evidence of this effect has been accrued in experimental animal models. However, the translation of this phenomenon to its use as a therapy in ischaemic disease has been largely disappointing without clear evidence of benefit in humans. Recently, innovative experimental observations have suggested that remote ischaemic preconditioning (RIPC) may be largely mediated through hypoxic inhibition of the oxygen-sensing enzyme PHD2, leading to enhanced levels of alpha-ketoglutarate and subsequent increases in circulating kynurenic acid (KYNA). These observations provide vital insights into the likely mechanisms of RIPC and a route to manipulating this mechanism towards therapeutic benefit by direct alteration of KYNA, alpha-ketoglutarate levels, PHD inhibition, or pharmacological targeting of the incompletely understood cardioprotective mechanism activated by KYNA. PMID:28163901
Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P
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.
Kim, Sung-Hwa; Heo, Jeong-Haing; Kim, Yeong Shik; Kang, Sam Sik; Choi, Jae Sue; Lee, Sun-Mee
This study examined the effects of daidzin, a major isoflavone from Puerariae Radix, on D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced liver failure. Mice were given an intraperitoneal injection of daidzin (25, 50, 100 and 200 mg/kg) 1 h before receiving an injection of D-GalN (700 mg/kg)/LPS (10 microg/kg). Daidzin markedly reduced the elevated serum aminotransferase activity and the levels of lipid peroxidation and tumor necrosis factor-alpha. The glutathione content was lower in the D-GalN/LPS group, which was attenuated by daidzin. The daidzin pretreatment attenuated the swollen mitochondria observed in the d-GalN/LPS group. Daidzin attenuated the apoptosis of hepatocytes, which was confirmed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and a caspase-3 assay. Overall, these results suggest that the liver protection of daidzin is due to reduced oxidative stress and its antiapoptotic activity.
Zielińska, Magdalena; Obara-Michlewska, Marta; Hilgier, Wojciech; Albrecht, Jan
L-citrulline (Cit) is a co-product of NO synthesis and a direct L-arginine (Arg) precursor for de novo NO synthesis. Acute liver failure (ALF) is associated with increased nitric oxide (NO) and cyclic GMP (cGMP) synthesis in the brain, indirectly implicating a role for active transport of Cit. In the present study we characterized [(3)H]Cit uptake to the cortical brain slices obtained from control rats and rats with thioacetamide (TAA)-induced ALF ("TAA slices"). In both control and TAA slices the uptake was partially Na(+)-dependent and markedly inhibited by substrates of systems L and N, including L-glutamine (Gln), which accumulates in excess in brain during ALF. Cit uptake was not affected by Arg, the y(+)/y(+)L transport system substrate, nor by amino acids taken up by systems A, xc (-)or XAG. The Vmax of the uptake in TAA slices was ~60 % higher than in control slices. Chromatographic (HPLC) analysis revealed a ~30 % increase of Cit concentration in the cerebral cortical homogenates of TAA rats. The activity of argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL), the two enzymes of Cit-NO cycle catalyzing synthesis of Arg, showed an increase in TAA rats, consistent with increased ASS and ASL protein expression, by ~30 and ~20 %, respectively. The increased Cit-NO cycle activity was paralleled by increased expression of mRNA coding for inducible nitric oxide synthase (iNOS). Taken together, the results suggest a role for Cit in the activation of cerebral NO synthesis during ALF.
Shi, K-Q; Zhou, Y-Y; Yan, H-D; Li, H; Wu, F-L; Xie, Y-Y; Braddock, M; Lin, X-Y; Zheng, M-H
At present, there is no ideal model for predicting the short-term outcome of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). This study aimed to establish and validate a prognostic model by using the classification and regression tree (CART) analysis. A total of 1047 patients from two separate medical centres with suspected ACHBLF were screened in the study, which were recognized as derivation cohort and validation cohort, respectively. CART analysis was applied to predict the 3-month mortality of patients with ACHBLF. The accuracy of the CART model was tested using the area under the receiver operating characteristic curve, which was compared with the model for end-stage liver disease (MELD) score and a new logistic regression model. CART analysis identified four variables as prognostic factors of ACHBLF: total bilirubin, age, serum sodium and INR, and three distinct risk groups: low risk (4.2%), intermediate risk (30.2%-53.2%) and high risk (81.4%-96.9%). The new logistic regression model was constructed with four independent factors, including age, total bilirubin, serum sodium and prothrombin activity by multivariate logistic regression analysis. The performances of the CART model (0.896), similar to the logistic regression model (0.914, P=.382), exceeded that of MELD score (0.667, P<.001). The results were confirmed in the validation cohort. We have developed and validated a novel CART model superior to MELD for predicting three-month mortality of patients with ACHBLF. Thus, the CART model could facilitate medical decision-making and provide clinicians with a validated practical bedside tool for ACHBLF risk stratification.
Vaughan, Gilberto; Forbi, Joseph C; Xia, Guo-Liang; Fonseca-Ford, Maureen; Vazquez, Roberto; Khudyakov, Yury E; Montiel, Sonia; Waterman, Steve; Alpuche, Celia; Gonçalves Rossi, Livia Maria; Luna, Norma
Clinical infection by hepatitis A virus (HAV) is generally self-limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full-genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common-source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes.
Ward, Paul W; Shaneyfelt, Terrence M; Roan, Ronald M
In this case, the authors have presented for the first time that ischaemic colitis may be associated with phenylephrine use. Since phenylephrine is the more common active ingredient in over-the-counter (OTC) cold medications, other presentations may follow this case. A MEDLINE search was performed for all case reports or case series of ischaemic colitis secondary to pseudoephedrine or phenylephrine use published between 1966 and 2013. The search resulted in four case reports and one case series describing patients with acute onset ischaemic colitis with exposure to pseudoephedrine immediately prior to onset. However, we found no case reports of ischaemic colitis associated with phenylephrine use. We present this case as an unexpected clinical outcome of phenylephrine, which has not been associated with ischaemic colitis in the literature. Also, this case serves as a reminder of the important clinical lesson to question all patients' use of OTC and prescribed medications.
Nieswandt, Bernhard; Kleinschnitz, Christoph; Stoll, Guido
Abstract Ischaemic stroke is a leading cause of death and disability worldwide. The complex cellular interactions leading from thromboembolic vessel occlusion to infarct development within the brain parenchyma in acute stroke are poorly understood, which translates into only one approved effective treatment, thrombolysis. Importantly, however, patients can develop progressive stroke despite reperfusion of previously occluded major intracranial arteries, a process referred to as ‘reperfusion injury’ which can be reproduced in the mouse model of transient middle cerebral artery occlusion (tMCAO). Although pathological platelet and coagulant activity have long been recognized to be involved in the initiation of ischaemic stroke, their contribution to infarct maturation remained elusive. Experimental evidence now suggests that early platelet adhesion/activation mechanisms involving the von Willebrand factor (vWF) receptor glycoprotein (GP) Ib, its ligand vWF, and the collagen receptor GPVI are critical pathogenic factors in infarct development following tMCAO, whereas platelet aggregation through GPIIb/IIIa is not. Further experimental work indicates that these pathways in conjunction with coagulation factor XII (FXII)-driven processes orchestrate a ‘thrombo-inflammatory’ cascade in acute stroke that results in infarct growth. This review summarizes these recent developments and briefly discusses their potential clinical impact. PMID:21768262
Singri, Naveen; Gleason, Briana; Flamm, Steve L; Kanwar, Yashpal S; Ghossein, Cybele
Patients with end-stage liver disease are prone to hemodynamic and immunologic renal injury, the latter at times manifesting as glomerulonephritis. Elevated serum immunoglobulin A (IgA) levels and mesangial IgG-IgA deposits are common in these patients, but are often clinically silent. We report a patient with autoimmune hepatitis and secondary IgA nephropathy (IgAN) who presented with nephrotic syndrome, acute renal failure (ARF), with 30% of the renal glomeruli having undergone crescentic change, and with IgA2 deposits in the glomerular mesangium. This article discusses secondary IgAN pathogenesis and its therapeutic management.
Andalib, Sasan; Divani, Afshin A; Michel, Tanja M; Høilund-Carlsen, Poul F; Vafaee, Manouchehr S; Gjedde, Albert
Ischaemic heart disease and stroke are vascular events with serious health consequences worldwide. Recent genetic and epigenetic techniques have revealed many genetic determinants of these vascular events and simplified the approaches to research focused on ischaemic heart disease and stroke. The pathogenetic mechanisms of ischaemic heart disease and stroke are complex, with mitochondrial involvement (partially or entirely) recently gaining substantial support. Not only can mitochondrial reactive oxygen species give rise to ischaemic heart disease and stroke by production of oxidised low-density lipoprotein and induction of apoptosis, but the impact on pericytes contributes directly to the pathogenesis. Over the past two decades, publications implicate the causative role of nuclear genes in the development of ischaemic heart disease and stroke, in contrast to the potential role of mitochondrial DNA (mtDNA) in the pathophysiology of the disorders, which is much less understood, although recent studies do demonstrate that the involvement of mitochondria and mtDNA in the development of ischaemic heart disease and stroke is likely to be larger than originally thought, with the novel discovery of links among mitochondria, mtDNA and vascular events. Here we explore the molecular events and mtDNA alterations in relation to the role of mitochondria in ischaemic heart disease and stroke.
Mendizabal, Manuel; Rowe, Carlos; Piñero, Federico; Gonzalez-Campaña, Ariel; Fauda, Martín; Tomás Arufe, Diego; Pía Raffa, María; Barreiro, Mariano; Keller, Rodolfo; Cacheiro, Fernando; Beruti, Ernesto; Andriani, Oscar; Oscar Silva, Marcelo; Podestá, Luis Gustavo
Severe liver dysfunction during pregnancy implies a serious risk for both mother and fetus, and represents a technical and ethical challenge for treating physicians. We report a case of a previously healthy 32-year old woman who was admitted to our hospital with idiopathic fulminant hepatic failure and underwent successful orthotopic liver transplantation (OLT) at gestation week 21. Patient's and fetus' immediate postoperative course were relatively uneventful until week six after OLT, when the mother developed oligohydramnios and preeclampsia. At pregnancy week 27, after inducing baby's lung maturation, a cesarean section was performed with the delivery of an otherwise healthy girl. After 3 years of follow-up, mother and child are leading normal lives with no complications related either to pregnancy or to OLT. We describe the case of a successful emergency liver transplant in a woman during the second trimester of pregnancy, demonstrating that OLT can be a viable option to preserve the life of the mother and an otherwise unviable fetus. Intrauterine baby's growths until the attainment of a viable gestational age was feasible despite the mother's fulminant hepatic failure and liver transplant surgery.
Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells
Kim, Yu Ri; Ban, Jung Ok; Yoo, Hwan Soo; Lee, Yong Moon; Yoon, Yeo Pyo; Eum, So Young; Jeong, Heon Sang; Yoon, Do-young; Han, Sang Bae; Hong, Jin Tae
High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity. PMID:23935693
Park, Eun-Jeon; Nan, Ji-Xing; Zhao, Yu-Zhe; Lee, Sung Hee; Kim, Young Ho; Nam, Jeong Bum; Lee, Jung Joon; Sohn, Dong Hwan
The aim of this study was to investigate whether Eleutherococcus senticosus stems could attenuate D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. E. senticosus, known as Siberian ginseng, is a popular folk medicine used as a tonic in Asia. Preparations of E. senticosus used in this study were as follows; (i) 70% ethanol extract (ii) water extract (iii) ethanol-soluble part of the water extract (iv) polysaccharide obtained as an 80% ethanol insoluble of the water extract. Preparations were given by intraperitoneal (300 mg/kg and 50 mg/kg) or oral (300 mg/kg) injection at 12 hr and 1 hr before a D-galactosamine/lipopolysaccharide injection. The intraperitoneal injection of water extract and polysaccharide significantly lowered serum levels of tumour necrosis factor-alpha, aspartate transaminase and alanine transaminase, improved the histologic changes in liver, inhibited hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay, and suppressed the lethality induced by D-galactosamine/lipopolysaccharide. The oral administration of water extract and polysaccharide also reduced serum aspartate transaminase, alanine transaminase and tumour necrosis factor-alpha levels. In contrast 70% ethanol extract and ethanol-soluble part of the water extract had no protective effect when treated intraperitoneally or orally. These results indicate E. senticosus stems attenuate fulminant hepatic failure induced by D-galactosamine/lipopolysaccharide in mice and the protective effect is due to water-soluble polysaccharides in E. senticosus stems.
Gallagher, Kara Lee
An 81-year-old man with a medical history significant for diverticulosis and irritable bowel syndrome presented to the emergency department with a 1-day history of periumbilical pain that woke him from sleep and ultimately localised to his right lower quadrant. He reported nausea, anorexia and chills but denied vomiting, diarrhoea, melena, hematochezia or fever. His physical exam was notable for focal tenderness at McBurney's point. Diagnostic information included a normal white blood cell count and an abdominal CT scan that demonstrated a normal appendix with no other pathology noted. The patient opted to proceed with laparoscopy where a normal appendix was found. The caecum, however, contained a large ischaemic diverticulum not noted on CT scan. Following laparoscopic ileocecectomy, pathology demonstrated haemorrhage, inflammation, oedema and full thickness necrosis of the caecal wall. Recovery was uneventful; the patient was discharged from the hospital 3 days following surgery. PMID:23893271
Chiang, Chih-Hung; Wu, Wai-Wah; Li, Hsin-Yang; Chien, Yueh; Sun, Cho-Chin; Peng, Chi-Hsien; Lin, Alex Tong-Long; Huang, Chi-Shuan; Lai, Ying-Hsiu; Chiou, Shih-Hwa; Hung, Shuen-Iu; Chang, Yuh-Lih; Lan, Yuan-Tzu; Liu, Dean-Mo; Chien, Chian-Shiu; Huo, Teh-Ia; Lee, Shou-Dong; Wang, Chien-Ying
Acute hepatic failure (AHF) is a severe liver injury leading to sustained damage and complications. Induced pluripotent stem cells (iPSCs) may be an alternative option for the treatment of AHF. In this study, we reprogrammed human dental pulp-derived fibroblasts into iPSCs, which exhibited pluripotency and the capacity to differentiate into tridermal lineages, including hepatocyte-like cells (iPSC-Heps). These iPSC-Heps resembled human embryonic stem cell-derived hepatocyte-like cells in gene signature and hepatic markers/functions. To improve iPSC-Heps engraftment, we next developed an injectable carboxymethyl-hexanoyl chitosan hydrogel (CHC) with sustained hepatocyte growth factor (HGF) release (HGF-CHC) and investigated the hepatoprotective activity of HGF-CHC-delivered iPSC-Heps in vitro and in an immunocompromised AHF mouse model induced by thioacetamide (TAA). Intrahepatic delivery of HGF-CHC-iPSC-Heps reduced the TAA-induced hepatic necrotic area and rescued liver function and recipient viability. Compared with PBS-delivered iPSC-Heps, the HGF-CHC-delivered iPSC-Heps exhibited higher antioxidant and antiapoptotic activities that reduced hepatic necrotic area. Importantly, these HGF-CHC-mediated responses could be abolished by administering anti-HGF neutralizing antibodies. In conclusion, our findings demonstrated that HGF mediated the enhancement of iPSC-Hep antioxidant/antiapoptotic capacities and hepatoprotection and that HGF-CHC is as an excellent vehicle for iPSC-Hep engraftment in iPSC-based therapy against AHF.
Di, L; Restuccia, D; Oliviero, A; Profice, P; Nardone, R; Valeriani, M; Colosimo, C; Tartaglione, T; Della, C; Pennisi, M; Tonali, P
Two patients with spinal infarction and one patient with the previously unreported complication of spinal transient ischaemic attack associated with cocaine misuse are reported. Spinal MRI documented an infarction in the territory of the anterior spinal artery in the first two patients and was completely normal in the patient with a transient ischaemic attack. Motor evoked potentials were abnormal in all three patients. PMID:9343140
Remme, W J
In addition to being accepted therapy in hypertension and heart failure, ACE inhibitors may well offer a new dimension in anti-ischaemic therapy. Currently, anti-ischaemic properties have been demonstrated by ACE inhibitors in selected patient groups, including patients with left ventricular dysfunction with or without a direct temporal relationship with myocardial infarction. Anti-ischaemic effects of ACE inhibitors become apparent late after initiation of treatment and suggest a structural rather than a functional effect. Underlying mechanisms may include a reduction in ventricular dilatation and (abnormal) cardiac hypertrophy, leading to less myocardial oxygen demand and, possibly, improved subendocardial blood supply, and vasculoprotective effects, i.e. anti-atherosclerotic and antiremodelling properties, a beneficial effect on the fibrinolytic system and an improvement in abnormal endothelial vasodilator function. The latter aspect is most probably the pivotal mode of action where the anti-ischaemic profile of ACE inhibition is concerned. An improvement in endothelial dysfunction has been shown in patients with mild to moderate coronary artery disease [Trial on Reversing ENdothelial Dysfunction (TREND)]. It is of importance that, in both clinical experiments and human studies, the role of bradykinin appears central in the structural and functional cardiovascular effects of ACE inhibition. This is particularly true for the improvement of impaired endothelial function. Myocardial ischaemia evokes vasoconstrictor neurohormonal activation, which may lead to coronary vasoconstriction in diseased coronary segments. The subsequent abnormal endothelial function leads to diminished coronary flow and also increases systemic vasotone and afterload, thus unfavourably altering the myocardial oxygen supply/demand ratio. Under laboratory conditions, acute ACE inhibition counteracts this activation in humans. However, it is speculated that this anti-ischaemic mechanism may
Examples of single gene disorders have been described for all major subtypes of ischaemic stroke: accelerated atherosclerosis and subsequent thrombo-embolism (e.g. homocysteinuria), weakening of connective tissue resulting in arterial dissections (e.g. Ehler-Danlos type IV), disorders of cerebral small vessels (e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the collagen COL4A1 mutation), disorders increasing the thrombogenic potential of the heart through affecting the myocardium or the heart valves or through disturbance of the heart rhythm (e.g. hypertrophic cardiomyopathy), mitochondrial cytopathies increasing cerebral tissue susceptibility to insults (e.g. mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and finally disorders of coagulation that can either directly cause stroke or act synergistically with the aforementioned abnormalities (e.g. sickle cell disease). Most of these disorders are rare but they are important to consider particularly in young patients with stroke, those with a family history or those who have other characteristics of a particular syndrome.
Xu, Ruonan; Bao, Chunmei; Huang, Huihuang; Lin, Fang; Yuan, Yue; Wang, Siyu; Jin, Lei; Yang, Tao; Shi, Ming; Zhang, Zheng; Wang, Fu-Sheng
Polymorphonuclear neutrophils (PMNs) and proinflammatory cytokines have been implicated in the pathogenesis of acute-on-chronic liver failure (ACLF). But the utility of CXC chemokine receptor expression on PMNs as a biomarker for prediction of disease severity is still uncertain. In this study, we investigated the dynamic expression of CXCR1 and CXCR2 on neutrophils, and found that patients with hepatitis B virus-related ACLF displayed low expression of CXCR1 and CXCR2 on peripheral neutrophils compared with healthy subjects and patients with chronic hepatitis B. This expression pattern was correlated with disease severity. Additionally, increased production of IL-8 in peripheral blood was significantly associated with reduced CXCR1 and CXCR2 expression, as shown by the decreased CXCR1 and CXCR2 expression on neutrophils after treating neutrophils with plasma from ACLF patients. This effect could be overcomed through IL-8 blockage with an anti-IL-8 antibody. We also found that IL-8 production and neutrophil infiltration were coordinately increased in the liver tissue of HBV-ACLF patients, and this increase was associated with liver inflammation. Overall, increased production of IL-8 associated with neutrophils infiltration into the liver and decreased CXCR1/2 expression on peripheral neutrophils. CXCR1 and CXCR2 expression levels could be served as early markers to predict the severity of ACLF. PMID:27974825
Unzu, Carmen; Sampedro, Ana; Sardh, Eliane; Mauleón, Itsaso; Enríquez de Salamanca, Rafael; Prieto, Jesús
Chronic kidney disease is a long-term complication in acute intermittent porphyria (AIP). The pathophysiological significance of hepatic overproduction of the porphyrin precursors aminolevulinate acid (ALA) and porphobilinogen (PBG) in chronic kidney disease is unclear. We have investigated the effect of repetitive acute attacks on renal function and the effect of total or five-sixth nephrectomy causing renal insufficiency on hepatic heme synthesis in the porphobilinogen deaminase (PBGD)-deficient (AIP) mouse. Phenobarbital challenge in the AIP-mice increased urinary porphyrin precursor excretion. Successive attacks throughout 14 weeks led to minor renal lesions with no impact on renal function. In the liver of wild type and AIP mice, 5/6 nephrectomy enhanced transcription of the first and rate-limiting ALA synthase. As a consequence, urinary PBG excretion increased in AIP mice. The PBG/ALA ratio increased from 1 in sham operated AIP animals to over 5 (males) and over 13 (females) in the 5/6 nephrectomized mice. Total nephrectomy caused a rapid decrease in PBGD activity without changes in enzyme protein level in the AIP mice but not in the wild type animals. In conclusion, high concentration of porphyrin precursors had little impact on renal function. However, progressive renal insufficiency aggravates porphyria attacks and increases the PBG/ALA ratio, which should be considered a warning sign for potentially life-threatening impairment in AIP patients with signs of renal failure. PMID:22412963
Thölen, H; Bianchi, L; Ulrich, J; Heierli, C; Ritz, R
The clinical course of a 26 year old female patient with acute liver necrosis and coma due to hepatitis B is reported. The disturbances of conciousness had improved. The patient survived 41 days after the beginning of the coma and developed liver cell regeneration and an acute post-hepatitic liver cirrhosis. As a grave complication a septicemia with aspergillus was observed. The patient died because of gastro-intestinal hemorrhage. At autopsy there were no signs of brain edema. The treatment consisted in: daily infusions with coenzyme A, nicotinamid-adenin-dinucleotide, alpha lipoic acid and cocarboxylase to improve the metabolic disorders and the clinical picture; mannitol intravenously to prevent and to treat cerebral edema; 33 charcoal-hemoperfusions to remove toxic substances of acute liver failure. Treatment of the aspergillus infection with 5-fluorocytosine and amphotericine B and infusion of concentrated ascites led to a decompensation of liver functions. From this observation the following conclusions can be drawn: after an acute viral hepatic necrosis, new synthetic functions and improvements of the disturbed intermediary metabolism in regenerated liver-cells can eventually be seen only after twenty-four to thirty days. With systematically applicated mannitol infusions it is possible to treat cerebral edema effectively.
Schmedt Auf der Günne, Wenke; Zhao, Yi; Hedderich, Jürgen; Gohlke, Peter; Culman, Juraj
Omapatrilat (OMA), which simultaneously inhibits the angiotensin-converting enzyme (ACE) and the neutral endopeptidase (neprilysin (NEP)), is widely used in experimental protocols related to hypertension and heart failure. The penetration of OMA across the blood-brain barrier (BBB) and the effects of ACE/NEP inhibition on the recovery from ischaemic stroke have not yet been investigated. Angiotensin (Ang) I injected intracerebroventricularly (ICV) or intravenously (IV) is converted to Ang II by ACE and induces an immediate increase in blood pressure. The pressor responses to OMA administered ICV, orally or IV were studied in male Wistar rats instrumented with an ICV and arterial and venous catheters. OMA infused ICV rapidly appeared in the systemic circulation and more effectively attenuated the systemic than the central pressor responses to Ang I. OMA administered orally (5, 25, 100 μmol/kg body weight) or IV (0.5, 1, 5, 25 μmol/kg body weight) completely abolished increases in blood pressure to IV Ang I up to 2 h after treatment. The pressor responses to ICV Ang I were not altered, indicating that systemically administered OMA does not cross the BBB. To study the effects of ACE and NEP inhibition in the brain on the recovery from ischaemic stroke, OMA was infused ICV over a 5-day period before and 24 h after the occlusion of the middle cerebral artery (MCAO) for 90 min. ICV application of OMA had no effect on infarction volume and marginally improved neurological outcome. We demonstrate for the first time that simultaneous inhibition of ACE and NEP in the brain tissue does not alter the recovery from ischaemic stroke.
Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena
Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.
Shi, Dan; Xie, Duanyang; Zhang, Hong; Zhao, Hong; Huang, Jian; Li, Changming; Liu, Yi; Lv, Fei; The, Erlinda; Liu, Yuan; Yuan, Tianyou; Wang, Shiyi; Chen, Jinjin; Pan, Lei; Yu, Zuoren; Liang, Dandan; Zhu, Weidong; Zhang, Yuzhen; Li, Li; Peng, Luying; Li, Jun; Chen, Yi-Han
Ischaemic cardiac arrhythmias cause a large proportion of sudden cardiac deaths worldwide. The ischaemic arrhythmogenesis is primarily because of the dysfunction and adverse remodelling of sarcolemma ion channels. However, the potential regulators of sarcolemma ion channel turnover and function in ischaemic cardiac arrhythmias remains unknown. Our previous studies indicate that dynamin-2 (DNM2), a cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes. Here, we have found that DNM2 plays an important role in acute ischaemic arrhythmias. In rat ventricular tissues and primary cardiomyocytes subjected to acute ischaemic stress, the DNM2 protein and transcription levels were markedly down-regulated. This DNM2 reduction was coupled with severe ventricular arrhythmias. Moreover, we identified that the down-regulation of DNM2 within cardiomyocytes increases the action potential amplitude and prolongs the re-polarization duration by depressing the retrograde trafficking of Nav1.5 and Kir2.1 channels. These effects are likely to account for the DNM2 defect-induced arrhythmogenic potentials. These results suggest that DNM2, with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies.
Slivka, A; Levy, D E; Lapinski, R H
Intravenous heparin is frequently used to treat thromboembolic disease, but the consequences of stopping heparin have not been studied systematically. To determine whether discontinuing heparin poses a clinical risk, we examined the charts of 378 patients treated with heparin for transient ischaemic attack (TIA), reversible ischaemic neurological deficit, or ischaemic stroke from October 1979 to June 1985. Clinical deterioration, or a new TIA or stroke was more likely (p = 0.01) during the 24 hours after heparin was stopped in patients not already on aspirin or warfarin (10/143, 7%) than in patients receiving aspirin or warfarin before heparin withdrawal (3/215, 1%). Stopping heparin in patients not receiving aspirin or warfarin appears to expose them to an increased risk for TIA, stroke, or clinical deterioration. PMID:2614427
Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S
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.
Wader, Jyotsna; Gajbi, Neha; Kumbhar, Sujata
We are reporting a case of ischaemic fasciitis which occurred in a 55-year-old female with no debilitating or long bed ridden history. She presented with a large swelling over left gluteal region. On evaluation, swelling was found to be of size, 5x5 cm, slightly tender and with induration. The operative findings led to a probable diagnosis of a calcified lesion, due to its hard consistency. However, the microscopic picture was typical of ischaemic fasciitis, because of its characteristic central necrosis, vascular and atypical fibroblastic proliferations. Also seen was presence of foreign body giant cell reactions, inflammatory cells and extravasated RBCs. Ischaemic fasciitis is a very rare pseudo sarcomatous proliferation of atypical fibroblasts, which has been described to be located over bony protuberances and said to develop most often in immobile elderly or debilitated patients. Recognition of this distinct entity as a reactive process, mostly associated with debilitation is rare in occurrence.
Labal, S.E.; Pola, J.L.; Seeber, A. Martinez; Taquini, A.C.
The re-establishment of blood flow to an ischaemic kidney produced an elevation of blood pressure in the rat. This response did not occur in animals with a pithed spinal cord or in rats with low blood pressure produced by haemorrhage. When the blood pressure was raised in rats with pithed spinal cords, by the intravenous infusion of noradrenaline, the response was restored. Occlusion of the subclavian arteries did not prevent the response. It is considered that the increase in blood pressure, produced by renin release, after re-establishment of the blood flow in an ischaemic kidney is a 'washout' phenomenon independent of the integrity of the nervous system. PMID:4447861
Power, Albert; Moser, Steven; Duncan, Neill
Stroke is a leading cause of death worldwide and is associated with significant morbidity in survivors. Early thrombolytic therapy in acute ischaemic stroke has been shown to dramatically improve patient outcomes. Although the age-adjusted incidence of stroke is 5-10 times greater in haemodialysis patients, the use of thrombolysis for this indication in this group of patients has not been described to date. We present a case where alteplase was used successfully for acute ischaemic stroke in a patient established on maintenance haemodialysis in the setting of an international randomized controlled trial and advocate caution with the use of systemic thrombolytics despite the favourable outcome seen with this case.
Zheng, Zhen; Li, Xu; Li, Zhiliang; Ma, Xiaochun
Artificial and bioartificial liver support systems (LSSs) appear to be safe and effective in the treatment of acute and acute-on-chronic hepatic failure (AHF and AOCHF); however, individually published studies and previous meta-analyses have revealed inconclusive results. The aim of the present meta-analysis was to derive a more precise estimation of the benefits and disadvantages of artificial and bioartificial LSSs for patients with AHF and AOCHF. A literature search was conducted in the PubMed, Embase, Web of Science and Chinese Biomedical (CBM) databases for publications prior to March 1, 2013. Crude relative risks (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (95% CI) were calculated using either the fixed effects or random effects models. Nineteen randomized controlled trials (RCTs) were included, which comprised a total of 566 patients with AHF and 371 patients with AOCHF. The meta-analysis showed that artificial LSS therapy significantly reduced mortality in patients with AOCHF; however, it had no apparent effect on total mortality in patients with AHF. The results also indicated that the use of bioartificial LSSs was correlated with decreased mortality in patients with AHF. A significant reduction in the bridging to liver transplantation was observed in patients with AOCHF following artificial LSS therapy; however, similar results were not observed in patients with AHF. Patients with AHF and those with AOCHF showed significant reductions in total bilirubin levels following artificial LSS therapy. There were no significantly increased risks of hepatic encephalopathy or bleeding in either the patients with AHF or AOCHF following artificial or bioartificial LSS therapies. Univariate and multivariate meta-regression analyses confirmed that none of the factors explained the heterogeneity. The present meta-analysis indicated that artificial LSSs reduce mortality in patients with AOCHF, while the use of bioartificial LSSs was
ZHENG, ZHEN; LI, XU; LI, ZHILIANG; MA, XIAOCHUN
Artificial and bioartificial liver support systems (LSSs) appear to be safe and effective in the treatment of acute and acute-on-chronic hepatic failure (AHF and AOCHF); however, individually published studies and previous meta-analyses have revealed inconclusive results. The aim of the present meta-analysis was to derive a more precise estimation of the benefits and disadvantages of artificial and bioartificial LSSs for patients with AHF and AOCHF. A literature search was conducted in the PubMed, Embase, Web of Science and Chinese Biomedical (CBM) databases for publications prior to March 1, 2013. Crude relative risks (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (95% CI) were calculated using either the fixed effects or random effects models. Nineteen randomized controlled trials (RCTs) were included, which comprised a total of 566 patients with AHF and 371 patients with AOCHF. The meta-analysis showed that artificial LSS therapy significantly reduced mortality in patients with AOCHF; however, it had no apparent effect on total mortality in patients with AHF. The results also indicated that the use of bioartificial LSSs was correlated with decreased mortality in patients with AHF. A significant reduction in the bridging to liver transplantation was observed in patients with AOCHF following artificial LSS therapy; however, similar results were not observed in patients with AHF. Patients with AHF and those with AOCHF showed significant reductions in total bilirubin levels following artificial LSS therapy. There were no significantly increased risks of hepatic encephalopathy or bleeding in either the patients with AHF or AOCHF following artificial or bioartificial LSS therapies. Univariate and multivariate meta-regression analyses confirmed that none of the factors explained the heterogeneity. The present meta-analysis indicated that artificial LSSs reduce mortality in patients with AOCHF, while the use of bioartificial LSSs was
Hansen, Gorm Mørk; Holmstrup, Palle; Tolker-Nielsen, Tim; Køllgaard, Tania; Nielsen, Claus Henrik; Givskov, Michael; Hansen, Peter Riis
Periodontitis is a prevalent chronic inflammatory disease induced by bacterial biofilm in the dental pocket resulting in destruction of the periodontal tissues. Periodontitis is associated with ischaemic heart disease and we here provide a summary of the current evidence linking these two disorders.
Mauri-Capdevila, Gerard; Jove, Mariona; Suarez-Luis, Idalmis; Portero-Otin, Manuel; Purroy, Francisco
The study of biomarkers related with ischaemic stroke is becoming increasingly more important as a way to further our knowledge of the pathophysiological changes that occur in cerebrovascular disease and to make it easier to reach an early diagnosis. Within this field, metabolomics offers a novel approach. The field is defined as the study of the small-molecule metabolites derived from cell metabolism. Its interest lies in the fact that, using a biological sample, it offers a snapshot of the cellular changes that are taking place. Today, the application of metabolomics requires a complex methodology that includes the application of laboratory separation techniques, multivariant statistical analyses and the use of bioinformatic tools. A number of studies conducted within the field of cardiovascular disease have focused on the application of this approach. In recent years there has been a steady growth in the number of publications referring to the metabolic changes related with ischaemic stroke, both in animal models and in patients. Metabolomics makes it possible to obtain the profiles of metabolites that identify patients who have suffered an ischaemic stroke. Furthermore, since studies have been carried out that relate certain metabolites with the most common causations of ischaemic stroke, metabolomics may eventually play a significant role in the study of cryptogenic stroke. The most exhaustive knowledge of the changes in the metabolic pathways involved in cerebrovascular disease could lay the foundations for the development of new neuroprotector strategies.
Martínez-Jardón, C S; Meza-de Regil, A; Dalma-Weiszhausz, J; Leizaola-Fernández, C; Morales-Cantón, V; Guerrero-Naranjo, J L; Quiroz-Mercado, H
Background/aims: Ischaemic central retinal vein occlusion (CRVO) accounts for 20–50% of all CRVO. No treatment has been proved to be effective. The efficacy of radial optic neurotomy (RON) was evaluated in eyes with ischaemic CRVO. Methods: 10 patients with ischaemic CRVO underwent RON. After pars plana vitrectomy, a microvitreoretinal blade was used to incise the scleral ring, cribriform plate, and adjacent sclera at the nasal edge of the optic disc. Best corrected visual acuity (BCVA), intraocular pressure (IOP), fluorescein angiography (FA), multifocal electroretinography (mfERG), and optical coherence tomography (OCT) were measured preoperatively and at 1, 3, and 6 months postoperatively. Results: No visual improvement was noted in the eyes that underwent RON. FA and mfERG showed no increase in retinal perfusion or retinal function postoperatively. Mean macular central thickness changed from 841 (SD 170) μm preoperatively to 162 (SD 34) μm at the sixth postoperative month. One patient had retinal central artery perforation intraoperatively. One patient developed neovascular glaucoma. Conclusion: RON in ischaemic CRVO did not improve visual function (by mfERG) or visual acuity although macular thickness did improve. This technique may be associated with potential risks. Randomised studies are needed to corroborate these results. PMID:15834084
Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad
We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.
... Home » Hepatitis B » Hepatitis B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis B Entire Lesson for Veterans and the Public ...
Guo, Yutao; Wang, Hao; Tian, Yingchun; Wang, Yutang; Lip, Gregory Y H
Ischaemic stroke risk rises with the increasing cardiovascular risk factors. How atrial fibrillation (AF) incrementally contributes to the risk for ischaemic stroke with increasing age and multiple cardiovascular risk factors is unclear. In an individual patient with AF the mechanism of ischaemic stroke may be related directly to AF itself or to risk factors associated with AF. It was this study's objective to investigate incident ischaemic stroke in relation to age and increasing cardiovascular risk factor(s), and the incremental impact of AF on stroke rates. We studied a 5% random sampling from Chinese medical insurance data covering more than 10 million individuals, for the years 2001 to 2012. The rate of ischaemic stroke was calculated amongst the individuals with no prior history of ischaemic stroke, in relation to age groups (aged < 65, 65-74, ≥ 75 years old; n = 348,431, n = 56,952, n = 20,217, respectively), and increasing risk factors using the CHA2DS2-VASc score. Among the randomly sampled 425,600 individuals with total follow-up of 1,864,232 patient-years [63.8% male, mean age 60 years; 880 with AF, vs 424,720 non-AF], there were 13,242 (3.1%) ischaemic strokes after 64,834 person-years follow-up. Overall, ischaemic stroke incidence (per 100 person-years) was 0.35 (95%CI 0.34-0.35) in the non-AF population and 1.11 (0.84-1.45) with AF. The AF population age < 65 and 65-74 had higher CHA2DS2-VASc scores than the non-AF population (p< 0.001), but this was non-significant between the non-AF and AF population age ≥ 75 (p=0.086). For the population age ≥ 75 years, incident stroke rates were 2.07 (0.86-4.76) and 4.29 (4.08-4.51) in non-AF and AF populations, respectively. The non-AF population age ≥ 65 years with ≥ 2 additional comorbidities (hypertension, vascular disease, diabetic, or heart failure) had ischaemic stroke rates similar to an AF population with CHA2DS2-VASc ≥ 4. In both non-AF and AF populations, those with CHA2DS2
Ryti, Niilo R. I.; Mäkikyrö, Elina M. S.; Antikainen, Harri; Junttila, M. Juhani; Hookana, Eeva; Ikäheimo, Tiina M.; Kortelainen, Marja-Leena; Huikuri, Heikki V.; Jaakkola, Jouni J. K.
Sudden cardiac death (SCD) is the leading cause of death. The current paradigm in SCD requires the presence of an abnormal myocardial substrate and an internal or external transient factor that triggers cardiac arrest. Based on prior mechanistic evidence, we hypothesized that an unusually cold weather event (a cold spell) could act as an external factor triggering SCD. We tested potential effect modification of prior diagnoses and select pharmacological agents disrupting pathological pathways between cold exposure and death. The home coordinates of 2572 autopsy-verified cases of ischaemic SCD aged ≥35 in the Province of Oulu, Finland, were linked to 51 years of home-specific weather data. Based on conditional logistic regression, an increased risk of ischaemic SCD associated with a cold spell preceding death (OR 1.49; 95% CI: 1.06–2.09). Cases without a prior diagnosis of ischaemic heart disease seemed more susceptible to the effects of cold spells (OR 1.70; 95% CI: 1.13–2.56) than cases who had been diagnosed during lifetime (OR 1.14; 95% CI: 0.61–2.10). The use of aspirin, β-blockers, and/or nitrates, independently and in combinations decreased the risk of ischaemic SCD during cold spells. The findings open up new lines of research in mitigating the adverse health effects of weather. PMID:28106161
Ma, Li; Gong, Xia; Kuang, Ge; Jiang, Rong; Chen, Rongchun; Wan, Jingyuan
Sesamin has been described to exert anti-oxidant and anti-inflammatory properties. In present study, we investigated the potential effects and mechanisms of sesamin on lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in d-galactosamine (D-GalN)-sensitized mice. Our results showed that pretreatment with sesamin dose-dependently improved LPS/D-GalN-induced mortality and liver injury as indicated by reduced serum levels of aminotransferases and alleviated pathological damage as well as hepatocyte apoptosis in mice. Additionally, sesamin markedly attenuated LPS/D-GalN-induced adhesion molecules expression, and decreased neutrophils recruitment. Furthermore, sesamin inhibited LPS-induced tumor necrosis factor-alpha (TNF-α) production, p38 mitogen-activated protein kinases (MAPK) and NF-κB activation, and Toll like receptor (TLR) 4 expression in mice and in RAW264.7 macrophage cells. In summary, these results demonstrate that sesamin protects mice from LPS-induced FHF and the molecular mechanisms may down-regulate the expression of TLR4, block MAPK and NF-κB activation, decrease the production of TNF-α.
Kim, Sung-Hwa; Kim, Yeong Shik; Kang, Sam Sik; Bae, Kihwan; Hung, Tran Manh; Lee, Sun-Mee
This study examined the effects of gomisin A, a lignan compound from Schisandra fructus, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic apoptosis and liver failure. Mice were given an intraperitoneal injection of GalN (700 mg/kg) / LPS (10 microg/kg). Gomisin A (25, 50, 100, and 200 mg/kg) was administered intraperitoneally 1 h before the GalN/LPS injection. The liver injury was assessed biochemically and histologically. GalN/LPS increased the serum aminotransferase levels and lipid peroxidation but decreased the reduced glutathione level. The pretreatment with gomisin A attenuated these changes in a dose-dependent manner. The survival rate of the gomisin A group was significantly higher than that of the control. The mitochondria isolated after the mice had been injected with GalN/LPS were swollen, which was attenuated by the gomisin A pretreatment. The elevation of serum tumor necrosis factor-alpha and activation of caspase-3 were observed in the GalN/LPS group, which was attenuated by gomisin A. The gomisin A-pretreated groups showed significantly fewer apoptotic (TUNEL-positive) cells and DNA fragmentation as compared with the GalN/LPS mice. The liver protection afforded by gomisin A is the result of the reduced oxidative stress and its anti-apoptotic activity.
Muir, Keith W; Ford, Gary A; Messow, Claudia-Martina; Ford, Ian; Murray, Alicia; Clifton, Andrew; Brown, Martin M; Madigan, Jeremy; Lenthall, Rob; Robertson, Fergus; Dixit, Anand; Cloud, Geoffrey C; Wardlaw, Joanna; Freeman, Janet; White, Philip
Objective The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0–2 at day 90. Results Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13–21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0–1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0–2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021). Conclusions The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability
Chronic active hepatitis is a liver disease caused by infection, drug ingestion, metabolic or autoimmune disorders. Necrosis (death) of liver cells, inflammation and fibrosis may lead to liver failure. Death within 5 years of onset occurs in ...
Díaz, Juan J; Gura, Kathleen M.; Roda, Juliamna; Perez-Atayde, Antonio R.; Duggan, Christopher; Jaksic, Tom; Lo, Clifford W.
Patients with Intestinal failure (IF) require parenteral nutrition (PN) support to obtain enough nutrients to sustain growth. long-term PN use is associated with significant liver damage. Objective To analyze the utility of a non-invasive test, the aspartate aminotransferase (AST) to platelet ratio index (APRI), in the diagnosis of liver disease in pediatric patients with IF. Methods Medical records of all Boston Children’s Hospital patients who received PN and underwent a liver biopsy from January 2006 until November 2010 were reviewed. Patients with a clinical diagnosis with IF were selected. APRI was calculated as follows (AST (U/L)/ upper normal limit) × 100/ platelets (109/L). Presence of fibrosis and cirrhosis was estimated using the METAVIR score in liver biopsies. Results 62 liver biopsies from 48 patients (22 female) were studied. Mean APRI values in the different METAVIR categories (0-1; 2-3; 4) were: 1.80, 1.17, and 4.24 respectively (ANOVA; P=0.053; Bonferroni test for cirrhosis versus fibrosis P=0.048). APRI could significantly predict cirrhosis (OR 1.2.; 95% CI 1.001-1.43) but not significant fibrosis (METAVIR 2-3, OR 1.00; 95% CI =0.86-1.18). Area under the receiver operating characteristic curve for cirrhosis was 0.67 (95% CI= 0.45-0.89; p=0.13). Conclusion APRI, a non invasive, easy to obtain bedside test significantly predicts cirrhosis but not fibrosis in pediatric patients with IFALD. As the clinicians need a non invasive test to differentiate among different stages of liver fibrosis rather than differentiating cirrhosis from normal, we cannot recommend the use of this test in pediatric patients with IFALD for this purpose. PMID:23666459
Kappelle, L J; van Latum, J C; van Swieten, J C; Algra, A; Koudstaal, P J; van Gijn, J
The incidence and vascular type of recurrent ischaemic stroke was studied in patients with supratentorial transient ischaemic attacks or non-disabling ischaemic strokes, who were treated with aspirin (30 or 283 mg). Patients were divided into groups with small vessel disease (SVD) (n = 1216) or large vessel disease (LVD) (n = 1221) on the grounds of their clinical features and CT at baseline. Patients with evidence of both SVD and LVD (n = 180) were excluded from further analyses. During follow up (mean 2.6 years) annual stroke rate was 3.6% in both groups. Of the 107 patients with SVD at baseline who had recurrent strokes, 83 proved to have an identifiable infarct: 30 (28%) again had a small vessel infarct, 39 (36%) had a large vessel ischaemic stroke and in 14 (13%) the recurrent ischaemic stroke was in the posterior fossa. Of the 110 patients with LVD at baseline and recurrent stroke, 91 had an identifiable infarct: 67 (61%) again had a large vessel ischaemic stroke, 16 (15%) had a small vessel ischaemic stroke, and eight (7%) had the recurrent ischaemic stroke in the posterior fossa. Thus patients with a transient ischaemic attack or non-disabling ischaemic stroke caused by LVD were more likely to have an ischaemic stroke of the same vessel type during follow up than patients with SVD (relative risk 2.2; 95% confidence interval 1.5-3.4). Possible explanations for this difference are: (1) patients with a small vessel ischaemic stroke at baseline had both SVD and LVD or were misdiagnosed; (2) recurrent small vessel ischaemic stroke may have occurred more often than reported, because they were silent or only minimally disabling; (3) recurring large vessel ischaemic strokes occurring in patients initially diagnosed as having SVD might have been related to potential cardiac sources of emboli that had not been previously recognized; (4) the antiplatelet drug aspirin (30 or 283 mg) prescribed in this patient group may have prevented thrombosis in small vessels better
Wu, Sheng-Jie; Yan, Hua-Dong; Zheng, Zai-Xing; Shi, Ke-Qing; Wu, Fa-Ling; Xie, Yao-Yao; Fan, Yu-Chen; Ye, Bo-Zhi; Huang, Wei-Jian; Chen, Yong-Ping; Zheng, Ming-Hua
Abstract Currently, there are no robust models for predicting the outcome of acute-on-chronic hepatitis B liver failure (ACHBLF). We aimed to establish and validate a new prognostic scoring system, named ALPH-Q, that integrates electrocardiography parameters that may be used to predict short-term mortality of patients with ACHBLF. Two hundred fourteen patients were included in this study. The APLH-Q score was constructed by Cox proportional hazard regression analysis and was validated in an independent patient cohort. The area under the receiver-operating characteristic curve was used to compare the performance of different models, including APLH-Q, Child–Pugh score (CPS), model of end-stage liver disease (MELD), and a previously reported logistic regression model (LRM). The APLH-Q score was constructed with 5 independent risk factors, including age (HR = 1.034, 95% CI: 1.007–1.061), liver cirrhosis (HR = 2.753, 95% CI: 1.366–5.548), prothrombin time (HR = 1.031, 95% CI: 1.002–1.062), hepatic encephalopathy (HR = 2.703, 95% CI: 1.630–4.480), and QTc (HR = 1.008, 95% CI: 1.001–1.016). The performance of the ALPH-Q score was significantly better than that of MELD and CPS in both the training (0.896 vs 0.712, 0.896 vs 0.738, respectively, both P < 0.05) and validation cohorts (0.837 vs 0.689, 0.837 vs 0.585, respectively, both P < 0.05). Compared with LRM, APLH-Q also showed a better performance (0.896 vs 0.825, 0.837 vs 0.818, respectively). We have developed a novel APLH-Q score with greater performance than CPS, MELD, and LRM for predicting short-term mortality of patients with ACHBLF. PMID:25590846
Amin, Osama S M
Bilateral internal carotid artery occlusion (BICAO) is a rare disease that carries a gloomy prognosis. We report a case of a 52-year-old man who developed ischaemic infarction at the region of the right middle cerebral artery; he was found to have atherosclerotic occlusion of both internal carotid arteries on Doppler-duplex examination. He received medical treatment only. After 1 year, he developed a new infarction at the region of the left middle cerebral artery. Conventional angiography revealed bilateral occlusion of internal carotid arteries at their origin, approximately 50% stenosis of the common carotid bulbs and mild stenosis of the origin of external carotid arteries. The patient did not undergo any form of surgical revascularisation procedures and died of severe aspiration pneumonia approximately 2 months after the second stroke. BICAO portends a poor outcome and carries a risk of recurrent ischaemic events. The best management strategy for this vascular occlusion remains unclear.
Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S.H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P.
Ischaemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses through generation of mitochondrial reactive oxygen species (ROS)1-5. Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion1,3. Here, we developed a comparative in vivo metabolomic analysis and unexpectedly identified widely conserved metabolic pathways responsible for mitochondrial ROS production during IR. We showed that selective accumulation of the citric acid cycle (CAC) intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase (SDH), which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. Upon reperfusion, the accumulated succinate is rapidly re-oxidised by SDH, driving extensive ROS generation by reverse electron transport (RET) at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo IR injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of IR injury. Furthermore, these findings reveal a novel pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation upon subsequent reperfusion is a potential therapeutic target to decrease IR injury in a range of pathologies. PMID:25383517
Iadecola, Costantino; Kahles, Timo; Gallo, Eduardo F; Anrather, Josef
Abstract Nitric oxide (NO) has emerged as a key mediator in the mechanisms of ischaemic tolerance induced by a wide variety of preconditioning stimuli. NO is involved in the brain protection that develops either early (minutes–hours) or late (days–weeks) after the preconditioning stimulus. However, the sources of NO and the mechanisms underlying the protective effects differ substantially. While in early preconditioning NO is produced by the endothelial and neuronal isoform of NO synthase, in delayed preconditioning NO is synthesized by the inducible or ‘immunological’ isoform of NO synthase. Furthermore, in early preconditioning, NO acts through the canonical cGMP pathway, possibly through protein kinase G and opening of mitochondrial KATP channels. In late preconditioning, the protection is mediated by peroxynitrite formed by the reaction of NO with superoxide derived from the enzyme NADPH oxidase. The mechanisms by which peroxynitrite exerts its protective effect may include improvement of post-ischaemic cerebrovascular function, leading to enhancement of blood flow to the ischaemic territory, and expression of prosurvival genes resulting in cytoprotection. The evidence suggests that NO can engage highly effective and multifunctional prosurvival pathways, which could be exploited for the prevention and treatment of cerebrovascular pathologies. PMID:21746790
Elevated serum cholesterol concentrations are known to be predictive of ischaemic heart disease. It remained to be proven, however, whether reduction of clinically manifest ischaemic heart disease could be achieved by the lowering of elevated serum-cholesterol levels. In order to create a clear and simple unifactorial study design, a lipid-lowering substance (clofibrate) was administered to this effect in a double-blind trial to middle-aged male volunteers whose serum cholesterol levels were within the upper third of the distribution in their respective populations (Budapest, Edinburgh, Prague). After an average of 5.3 years of observation, and with a reduction of some 9% of the initial serum cholesterol levels, the incidence of ischaemic heart disease was reduced by 20% in the intervention group as compared with the placebo group, thus demonstrating the preventive value of lowering this plasma lipid. There was, however, a significant increase in total mortality and in non-cardiovascular mortality in the clofibrate group, precluding the community-wide use of this drug for reduction of serum cholesterol. The explanation of this is not clear, but possible mechanisms are discussed. PMID:317255
Munuera, Josep; Blasco, Gerard; Hernández-Pérez, María; Daunis-I-Estadella, Pepus; Dávalos, Antoni; Liebeskind, David S; Wintermark, Max; Demchuk, Andrew; Menon, Bijoy K; Thomalla, Götz; Nael, Kambiz; Pedraza, Salvador; Puig, Josep
Vascular neuroimaging plays a decisive role in selecting the best therapy in patients with acute ischaemic stroke. However, compared with the arterial system, the role of veins has not been thoroughly studied. In this review, we present the major venous imaging-based biomarkers in ischaemic stroke. First, the presence of hypodense veins in the monophasic CT angiography ipsilateral to the arterial occlusion. Second, the asymmetry of venous drainage in the pathological cerebral hemisphere on CT and MRI dynamic angiography. Finally, the presence of hypodense veins on T2* -based MRI. From the physiological point of view, the venous imaging-based biomarkers would detect the alteration of brain perfusion (flow), as well as the optimisation of extraction oxygen mechanisms (misery perfusion). Several studies have correlated the venous imaging-based biomarkers with grade of collateral circulation, the ischaemic penumbra and clinical functional outcome. Although venous imaging-based biomarkers still have to be validated, growing evidence highlights a potential complementary role in the acute stroke clinical decision-making process.
Faganeli Pucer, Jana; Demšar, Janez; Kukar, Matjaž
Coronary artery disease is the developed world's premier cause of mortality and the most probable cause of myocardial ischaemia. More advanced diagnostic tests aside, in electrocardiogram (ECG) analysis it manifests itself as a ST segment deviation, targeted by both exercise ECG and ambulatory ECG. In ambulatory ECG, besides ischaemic ST segment deviation episodes there are also non-ischaemic heart rate related episodes which aggravate real ischaemia detection. We present methods to transform the features developed for the heart rate adjustment of ST segment depression in exercise ECG for use in ambulatory ECG. We use annotations provided by the Long-Term ST Database to plot the ST/HR diagrams and then estimate the overall and maximal slopes of the diagrams in the exercise and recovery phase for each ST segment deviation episode. We also estimate the angle at the extrema of the ST/HR diagrams. Statistical analysis shows that ischaemic ST segment deviation episodes have significantly steeper overall and maximal slopes than heart rate related episodes, which indicates the explored features' utility for distinguishing between the two types of episodes. This makes the proposed features very useful in automated ECG analysis.
Keynes, Robert G; Garthwaite, John
The role of the neural messenger nitric oxide (NO) in cerebral ischaemia has been investigated extensively in the past decade. NO may play either a protective or destructive role in ischaemia and the literature is plagued with contradictory findings. Working with NO presents many unique difficulties and here we review the potential artifacts that may have contributed to discrepancies and cause future problems for the unwary investigator. Recent evidence challenges the idea that NO from neurones builds up to levels (micromolar) sufficient to directly elicit cell death during the post-ischaemic period. Concomitantly, the case is strengthened for a role of NO in delayed death mediated post-ischaemia by the inducible NO synthase. Mechanistically it seems unlikely that NO is released in high enough quantities to inhibit respiration in vivo; the formation of reactive nitrogen species, such as peroxynitrite, represents the more likely pathway to cell death. The protective and restorative properties of NO have become of increasing interest. NO from endothelial cells may, via stimulating cGMP production, protect the ischaemic brain by acutely augmenting blood flow, and by helping to form new blood vessels in the longer term (angiogenesis). Elevated cGMP production may also stop cells dying by inhibiting apoptosis and help repair damage by stimulating neurogenesis. In addition NO may act as a direct antioxidant and participate in the triggering of protective gene expression programmes that underlie cerebral ischaemic preconditioning. Better understanding of the molecular mechanisms by which NO is protective may ultimately identify new potential therapeutic targets.
Chen, En-Qiang; Wang, Meng-Lan; Zhang, Dong-Mei; Shi, Ying; Wu, Do-Bo; Yan, Li-Bo; Du, Ling-Yao; Zhou, Ling-Yun; Tang, Hong
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition, and the lipid metabolism disorder is common in the development of this disease. This prospective observational study aimed to define the characteristics of plasma apolipoprotein A-V (apoA-V) in long-term outcome prediction of HBV-ACLF, and a total of 330 HBV-ACLF patients were included and followed for more than 12 months. In this cohort, the 4-week, 12-week, 24-week and 48-week cumulative mortality of HBV-ACLF was 18.2%(60/330), 50.9%(168/330), 59.7%(197/330) and 63.3%(209/330), respectively. As compared to survivors, the non-survivors had significantly lower concentrations of plasma apoA-V on admission. Plasma apoA-V concentrations were positively correlated with prothrombin time activity (PTA), and negatively correlated with interleukin-10, tumor necrosis factor-α, and iMELD scores. Though plasma apoA-V, PTA, total bilirubin(TBil) and blood urea nitrogen(BUN) were all independent factors to predict one-year outcomes of HBV-ACLF, plasma apoA-V had the highest prediction accuracy. And its optimal cutoff value for one-year survival prediction was 480.00 ng/mL, which had a positive predictive value of 84.68% and a negative predictive value of 92.23%. In summary, plasma apoA-V decreases significantly in non-survivors of HBV-ACLF, and it may be regarded as a new predictive marker for the prognosis of patients with HBV-ACLF. PMID:28358016
Ren, F; Shi, H; Zhang, L; Zhang, X; Wen, T; Xie, B; Zheng, S; Chen, Y; Li, L; Chen, D; Duan, Z
Although endoplasmic reticulum (ER) stress is critical in various liver diseases, its role in acute-on-chronic liver failure (AoCLF) caused by acute exacerbation of chronic hepatitis B (CHB) is still elusive. This study aimed to analyse ER stress responses in the progression of HBV-related AoCLF. Normal liver tissues (n = 10), liver tissues of CHB (n = 12) and HBV-related patients with AoCLF (n = 19) were used. Electron microscopy of the ultrastructure of the ER was carried out on liver specimens. The gene and protein expression levels of ER stress-related genes were measured. We further analysed the correlation between the expression levels of ER stress-related molecules and liver injury. Electron microscopy identified typical features of the ER microstructure in AoCLF subjects. Among the three pathways of unfolded protein responses, the PKR-like ER kinase and inositol-requiring enzyme 1 signalling pathway were activated in CHB subjects and inactivated in AoCLF subjects, while the activating transcription factor 6 signalling pathway was sustained in the activated form during the progression of AoCLF; the expression of glucose-regulated protein (Grp)78 and Grp94 was gradually decreased in AoCLF subjects compared to healthy individuals and CHB subjects, showing a negative correlation with serum ALT, AST and TBIL; moreover, the ER stress-related apoptosis molecules were activated in the progression of acute exacerbation of CHB. The dysregulated ER stress response may play a complicated role in the pathogenesis of AoCLF, and a severe ER stress response may predict the occurrence of AoCLF caused by acute exacerbation of CHB.
Hepatitis A Hepatitis A Hepatitis A is a contagious viral infection that can easily affect children and adults. It is one of the most common types of hepatitis virus. Often when you hear about hepatitis A ...
Jürgensen, Jan Steffen; Kettritz, Ralf; Schneider, Wolfgang; Koop, Herbert; Hildebrand, Thorsten Sven; Frei, Ulrich; Eckardt, Kai-Uwe
We describe a young woman whose initial presentation was dominated by acute diarrhoea. Life-threatening multiorgan failure rapidly ensued and necessitated mechanical ventilation and dialysis treatment. An initially elongated activated partial thromboplastin time prompted further coagulation tests that led to the detection of positive lupus anticoagulant, a highly elevated IgG-anticardiolipin (aCL) antibody titre, and prolonged dilute Russell's viper venom time. Histological examination of samples obtained during endoscopy revealed widespread intestinal thrombotic microangiopathy. In view of these serologic and histologic features, a diagnosis of the malignant variant of the antiphospholipid syndrome (APS), also termed 'catastrophic APS', was established. In spite of this syndrome's grim prognosis, the patient recovered following intensive anticoagulation and adjunct treatment with steroids and immunoglobulins.
... Châu và vùng Thái Bình Dương Hepatitis C Hepatitis C What is hepatitis C? Hepatitis C is a viral infection that ... can cure most cases of hepatitis C. Acute hepatitis C Acute hepatitis C is a short-term ...
... Châu và vùng Thái Bình Dương Hepatitis C Hepatitis A What is hepatitis A? Hepatitis A is a viral infection that ... spreading hepatitis A to others . How common is hepatitis A? In the United States, hepatitis A has ...
... Châu và vùng Thái Bình Dương Hepatitis C Hepatitis B What is hepatitis B? Hepatitis B is a viral infection that ... to prevent spreading hepatitis B to others . Acute hepatitis B Acute hepatitis B is a short-term ...
Tandon, B. N.; Gandhi, B. M.; Joshi, Y. K.
The etiological spectrum of viral hepatitis and the prevalence of serological markers of hepatitis A and B virus infection in healthy persons in north India were studied. Hepatitis A virus was found to be the most common cause of acute hepatitis in children (67%). It was a less frequent cause of this disease in adults (14%). Hepatitis A virus was only rarely the cause of acute (12%) and subacute (4%) liver failure. It was recorded as the etiological agent in an epidemic among schoolchildren. Exposure to hepatitis A virus occurs in early childhood, and by the age of 10 years, 90% of healthy persons have serological evidence of hepatitis A virus infection. Hepatitis non-A non-B virus was the cause of acute hepatitis in 44% of adults and 24% of children with this disease. This virus was also the most important etiological agent in acute liver failure (55%) and subacute hepatic failure (51%). It was the cause of all the hepatitis epidemics in the general population. Only 9% of hepatitis cases in children were due to hepatitis B virus whereas 42% of cases in adults were attributable to this virus. Hepatitis B virus was the causative agent in 33% of cases of acute hepatic failure and 45% of cases of subacute hepatic failure. The carrier rate for hepatitis B virus was 5% and antibody to hepatitis B surface antigen was found in up to 38% of specific population groups. PMID:6424958
Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob
The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO2 ) were associated with present as well as increasing levels of DR. Four of six studies also found increased retinal arterial oxygen saturation (raSatO2 ) in patients with DR. In patients with central retinal vein occlusion (CRVO), all studies found that rvSatO2 was reduced, but raSatO2 remained unchanged. Branch retinal vein occlusion was not associated with changes in retinal oxygen saturation, but this was based on a single study. In conclusion, DR is associated with increased rvSatO2 and might also be related to increased raSatO2 . Central retinal vein occlusion (CRVO) is correlated with increased rvSatO2 but unrelated to raSatO2 . Prospective studies are needed to expand these findings. These would tell whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases.
Verma, Rajesh; Praharaj, Heramba Narayan
Reflex or stimulus-sensitive epilepsies are uncommon epileptic syndromes triggered by exogenous-specific sensory stimulus or endogenous various mental activities. Gelastic-dacrystic seizures are rare epileptic manifestations characterised by ictal laughter and crying. Gelastic-dacrystic seizures are commonly caused by hypothalamic hamartoma but rarely described due to cortical dysplasia, lesions of frontal and temporal lobes, tumours and vascular malformations. We report a young woman who presented with somatosensory-evoked gelastic-dacrystic seizures. This patient had a positive history of perinatal insult substantiated by MRI findings. Hypoxic-ischaemic encephalopathy as the cause of gelastic-dacrystic seizures has not been reported so far in the literature.
Steventon, D M; John, P R
Following neonatal ischaemic brain injury, irregular vessels increase in size owing to luxury perfusion. These may be demonstrated by conventional colour flow Doppler (CFD) imaging at the periphery of the infarcted area. We present a case in which power Doppler imaging (PDI) was performed in addition to CFD in a neonate with unexplained seizures and which proved more sensitive than CFD in demonstrating luxury perfusion. Ultrasound appearances were compared with those seen on cranial CT. PDI can be a useful adjunct to conventional CFD examination of the neonatal brain in cerebral infarction.
... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...
... Cholangitis Wilson Disease Liver Disease A-Z Autoimmune Hepatitis What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ... bacteria, viruses, toxins, and medications. What causes autoimmune hepatitis? A combination of autoimmunity, environmental triggers, and a ...
Arroja, Mariana Moreira Coutinho; Reid, Emma; McCabe, Christopher
The renin angiotensin system (RAS) consists of the systemic hormone system, critically involved in regulation and homeostasis of normal physiological functions [i.e. blood pressure (BP), blood volume regulation], and an independent brain RAS, which is involved in the regulation of many functions such as memory, central control of BP and metabolic functions. In general terms, the RAS consists of two opposing axes; the 'classical axis' mediated primarily by Angiotensin II (Ang II), and the 'alternative axis' mediated mainly by Angiotensin-(1-7) (Ang-(1-7)). An imbalance of these two opposing axes is thought to exist between genders and is thought to contribute to the pathology of cardiovascular conditions such as hypertension, a stroke co-morbidity. Ischaemic stroke pathophysiology has been shown to be influenced by components of the RAS with specific RAS receptor antagonists and agonists improving outcome in experimental models of stroke. Manipulation of the two opposing axes following acute ischaemic stroke may provide an opportunity for protection of the neurovascular unit, particularly in the presence of pre-existing co-morbidities where the balance may be shifted. In the present review we will give an overview of the experimental stroke studies that have investigated pharmacological interventions of the RAS.
Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI) of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity. PMID:27047695
... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...
Torok, Natalie J
Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%-50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies.
Lopez, Annette M; Hendrickson, Robert G
Toxins such as pharmaceuticals, herbals, foods, and supplements may lead to hepatic damage. This damage may range from nonspecific symptoms in the setting of liver test abnormalities to acute hepatic failure. The majority of severe cases of toxin-induced hepatic injury are caused by acetaminophen and ethanol. The most important step in the patient evaluation is to gather an extensive history that includes toxin exposure and exclude common causes of liver dysfunction. Patients whose hepatic dysfunction progresses to acute liver failure may benefit from transfer to a transplant service for further management. Currently, the mainstay in management for most exposures is discontinuing the offending agent. This manuscript will review the incidence, pathophysiology, diagnosis and management of the different forms of toxin-induced hepatic injury and exam in-depth the most common hepatic toxins.
Szolnoki, Z; Somogyvari, F; Kondacs, A; Szabo, M; Fodor, L; Bene, J; Melegh, B
Objectives: Ischaemic stroke is a frequent heterogeneous multifactorial disease that is affected by a number of genetic mutations and environmental factors. We hypothesised the clinical importance of the interactions between common, unfavourable genetic mutations and clinical risk factors in the development of ischaemic stroke. Methods: The Factor V Leiden G1691A (Leiden V), the prothrombin G20210A, the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations, the angiotensin converting enzyme I/D (ACE I/D), and apolipoprotein allele e4 (APO e4) genotypes were examined by the polymerase chain reaction (PCR) technique in 867 ischaemic stroke patients and 743 healthy controls. Logistic regression models were used to estimate the roles of the co-occurrences of the clinical risk factors and common genetic mutations in ischaemic stroke. Results: The Leiden V mutation in combination with hypertension or diabetes mellitus increased the risk of ischaemic stroke. We found synergistic effects between the ACE D/D and MTHFR 677TT genotypes and drinking or smoking. The presence of the APO e4 greatly facilitated the unfavourable effects of hypertension, diabetes mellitus, smoking, or drinking on the incidence of ischaemic stroke. Conclusion: In certain combinations, pairing of common unfavourable genetic factors, which alone confer only minor or non-significant risk, with clinical risk factors can greatly increase the susceptibility to ischaemic stroke. PMID:14638877
Gimson, A E; Tedder, R S; White, Y S; Eddleston, A L; Williams, R
Serological markers for hepatitis B virus infection have been examined in 34 patients with acute hepatitis B, 17 of whom developed fulminant hepatic failure. Hepatitis B surface antigen concentrations were significantly lower and hepatitis Be antigen was less frequently detectable in patients with fulminant hepatic failure compared with those with acute hepatitis (median 0.64 micrograms, range 16-0 and median 32 micrograms and range 100-4 micrograms respectively, p less than 0.001; HBeAg detected in 12% and 88% respectively, p less than 0.001). The IgM component of hepatitis B core antibody was significantly higher in the patients with fulminant hepatic failure with median values of 500 IU/ml compared with those with uncomplicated hepatitis (median 202 IU/ml, p less than 0.05 Wilcoxon's rank test). Three patients who developed a fulminant course had detectable levels of either anti-HBs or anti-HBe. These results are consistent with enhanced antibody responses to all three hepatitis B virus antigens and more rapid clearance of the latter during fulminant hepatic failure. PMID:6862284
Rothwell, Peter M; Algra, Ale; Chen, Zhengming; Diener, Hans-Christoph; Norrving, Bo; Mehta, Ziyah
Background Aspirin is recommended for secondary prevention after transient ischaemic attack (TIA) and ischaemic stroke based on trials showing about a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke and observational studies show substantially greater benefits of early medical treatment in the acute phase. We hypothesised that the short-term benefits of early aspirin have been underestimated. Methods Using individual patient data from all randomised trials of aspirin vs placebo in secondary prevention after TIA or ischaemic stroke, we studied the time-course of effects on risk and severity (modified Rankin score - mRS) of recurrent stroke and myocardial infarction. To more reliably determine the very early time-course of effect of aspirin on risk of recurrent ischaemic stroke, we also studied trials in treatment of acute stroke stratified by severity of baseline neurological deficit. To understand possible mechanisms of action, we also studied the time-course of the interaction between effects of aspirin and dipyridamole in secondary prevention of stroke. Results Among 15,778 patients in 12 trials of aspirin vs. control in secondary prevention, aspirin reduced the 6-week risk of major ischaemic vascular events by 70-80% (disabling or fatal ischaemic stroke - HR=0.29,0.20-0.43, p<0.0001; acute myocardial infarction - HR=0.22, 0.09-0.53, p=0.0008), with greatest benefit in patients with TIA or minor stroke (disabling or fatal ischaemic stroke: 0-2 weeks-HR=0.07,0.02-0.31,p=0.0004; 0-6 weeks-HR=0.19,0.11-0.34,p<0.0001). The effect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis: OR=0.43,0.26-0.72,p=0.001). These effects were independent of dose, patient characteristics or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke on aspirin only vs control
Verma, Rajesh; Praharaj, Heramba Narayan
Reflex or stimulus-sensitive epilepsies are uncommon epileptic syndromes triggered by exogenous-specific sensory stimulus or endogenous various mental activities. Gelastic–dacrystic seizures are rare epileptic manifestations characterised by ictal laughter and crying. Gelastic–dacrystic seizures are commonly caused by hypothalamic hamartoma but rarely described due to cortical dysplasia, lesions of frontal and temporal lobes, tumours and vascular malformations. We report a young woman who presented with somatosensory-evoked gelastic–dacrystic seizures. This patient had a positive history of perinatal insult substantiated by MRI findings. Hypoxic–ischaemic encephalopathy as the cause of gelastic–dacrystic seizures has not been reported so far in the literature. PMID:23853086
Bertram, Kelly L; Madan, Anoop; Frayne, Judith
Young onset stroke is uncommon, and may be due to conditions other than traditional vascular risk factors. A 42-year-old woman with an ischaemic stroke was found to have left atrial bubble study positivity on transthoracic echocardiogram (TTE) suggestive of patent foramen ovale, however she also had low peripheral oxygen saturation. Investigation revealed an isolated pulmonary arteriovenous malformation (PAVM), visible on admission chest radiograph. This can cause embolic stroke and is an alternate cause of the TTE findings. The PAVM was able to be closed via endovascular intervention, removing the shunt and therefore removing her risk of recurrent stroke events. This is a rare cause of embolic stroke in young people which can be easily missed on investigation yet is amenable to treatment.
Franco, Daniela; Alves, Daniela; Almeida, Ana Cristina; Almeida, Carlos Costa; Moreno, Cecília; Freixo, Joâo
The spontaneous non-ischaemic blue finger is a rare and benign disorder, characterized by purple discoloration of a finger, with complete resolution. This article reports the case of a woman of 88 years, which after a few hours of stay in the emergency department developed without associated trauma, a purplish color of the 3rd finger of the right hand, with a palpable pulse and without temperature changes or pain. The etiological investigation was negative. The patient was assessed one week after the event and showed completeresolution. There are several diseases that share the same signs and symptoms, as such the diagnosis is based on the spontaneous violaceous color sparing the finger tip, and fast resolution without treatment. Though being a harmless phenomenon, it requires early assessment for timely differential diagnosis with severe pathologies.
Afzal, Hasnain; Umair, Syed Farrukh
Haemoglobin-D, Los Angeles or Haemoglobin D-Punjab is not a rare variant of haemoglobin worldwide especially in Punjab, North western India, and South Asian continent. It can be inherited rarely as homozygous causing no symptoms or heterozygous with Haemoglobin A, commonly not related to clinical symptomatology. However, these variants can co-exist rarely with other haemoglobinopathies such as thalassemia or haemoglobin-S. We describe the case of doubly heterozygous Hb-SD Punjab in a 8 year old girl who presented with ischaemic stroke. Before this case, only one case has been reported but it was with reversible hyperbilirubinaemia in Hb-SD from Rawalpindi, Pakistan. This case images the propensity for occurrence of rare phenotype within our population and underlines the importance of genotyping to avoid erroneous management and poor counseling hence preventing life altering complications which our case developed.
... your doctor may want you to get the hepatitis B vaccine (and maybe the hepatitis A vaccine, too), if you don't already have these viruses. If you have hepatitis C, you are more likely to catch hepatitis A or hepatitis B, which would cause more damage to your liver. ...
van Wijk, I; Lindeman, E; Kappelle, L J; van Gijn, J; Koudstaal, P J; Gorter, J W; Algra, A
Background Stroke may have a major effect on survivors and on the healthcare system. Aims To study the functional status and use of healthcare facilities in long‐term survivors of a transient ischaemic attack (TIA) or minor ischaemic stroke (MIS) and evaluate associations with baseline and follow‐up characteristics. Methods Follow‐up of patients who had participated in the Dutch TIA Trial or the European Atrial Fibrillation Trial was extended to a mean period of 15.6 years. Patients were interviewed through a postal questionnaire (n = 468) and a sample of this group was also interviewed at home (n = 198). Demographic data, information on comorbidity, functional status (Barthel Index, Frenchay Activities Index and modified Rankin Scale) and use of healthcare facilities were recorded. Results About one third of the survivors interviewed at home experienced any residual disability and 26% were moderately to severely handicapped. Factors associated with poor functional status were advanced age and the presence of any infarct on a baseline computed tomography scan, the recurrence of a new major stroke or the presence of comorbidity of locomotion. One third of survivors used any kind of professional care, which was predominantly related to the functional status at follow‐up. Conclusions Recurrent stroke and the presence of comorbidity of locomotion are important determinants of long‐term disability of survivors of a TIA or an MIS, which, in turn, is strongly associated with the long‐term use of professional care. The need for measuring comorbidity with regard to functional status is recommended in research on stroke outcome. PMID:16735396
Yin, Xinru; Gong, Xia; Zhang, Li; Jiang, Rong; Kuang, Ge; Wang, Bin; Chen, Xinyu; Wan, Jingyuan
Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100mg/kg) 1h before lipopolysaccharide (LPS)/d-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production.
Hepatitis C Overview By Mayo Clinic Staff Hepatitis C is a viral infection that causes liver inflammation, sometimes leading to serious liver damage. The hepatitis C virus (HCV) spreads through contaminated ...
Toxic hepatitis Overview By Mayo Clinic Staff Toxic hepatitis is an inflammation of your liver in reaction to certain substances to which you're exposed. Toxic hepatitis can be caused by alcohol, chemicals, drugs or ...
Pais, Christopher C.
Introduction Cardiovascular and cerebrovascular diseases are leading causes of morbidity and mortality worldwide. Stroke accounts for the second leading cause of death, about 11.13% of total deaths worldwide. Microalbuminuria is known to be associated with increased risk of mortality in ischaemic stroke patients. But there have been no studies to assess whether microalbuminuria affects the early clinical outcome of patients with acute ischaemic stroke. Aim This study aims to investigate whether microalbuminuria affects the early clinical outcome of patients with acute ischaemic stroke. Materials and Methods This is a prospective study of patients with ischaemic stroke (who presented within 24 hours of symptom onset) who were consecutively admitted in three tertiary care centres during the time period from November 2013 to June 2015. Early clinical outcomes in patients were assessed by investigating the presence of Early Neurological Deterioration (END) using the National Institute of Health Stroke Scale. Urine albumin creatinine ratio was divided into two categories – Normal (less than 30mg/g of creatinine) or Urine Microalbuminuria (30-300 mg/g of creatinine). Results Total 42 out of 70 patients (60%) were found to have microalbuminuria. In multivariate logistic regression analysis, microalbuminuria was found to be independently associated with END in patients with acute ischaemic stroke (p=0.044). Conclusion In the early periods following acute ischaemic stroke, patients with microalbuminuria have worse clinical outcome. PMID:27790489
Morrison, B F; Thompson, E B; Shah, S D; Wharfe, G H
Ischaemic priapism is a devastating urological condition that has the potential to cause permanent erectile dysfunction. The disorder has been associated with numerous medical conditions and the use of pharmacotherapeutic agents. The aetiology is idiopathic in a number of cases. There are two prior case reports of the association of ischaemic priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report on a third case of priapism associated with G6PD deficiency and review recently described molecular mechanisms of increased oxidative stress in the pathophysiology of ischaemic priapism. The case report of a 32-year old Afro-Caribbean male with his first episode of major ischaemic priapism is described. Screening for common causes of ischaemic priapism, including sickle cell disease was negative. Glucose-6-phosphate dehydrogenase deficiency was discovered on evaluation for priapism. Penile aspiration was performed and erectile function was good post treatment.Glucose-6-phosphate dehydrogenase deficiency is a cause for ischaemic priapism and should be a part of the screening process in idiopathic causes of the disorder. Increased oxidative stress occurs in G6PD deficiency and may lead to priapism.
Abdurrachim, Desiree; Luiken, Joost J F P; Nicolay, Klaas; Glatz, Jan F C; Prompers, Jeanine J; Nabben, Miranda
The shift in substrate preference away from fatty acid oxidation (FAO) towards increased glucose utilization in heart failure has long been interpreted as an oxygen-sparing mechanism. Inhibition of FAO has therefore evolved as an accepted approach to treat heart failure. However, recent data indicate that increased reliance on glucose might be detrimental rather than beneficial for the failing heart. This review discusses new insights into metabolic adaptations in heart failure. A particular focus lies on data obtained from mouse models with modulations of cardiac FA metabolism at different levels of the FA metabolic pathway and how these differently affect cardiac function. Based on studies in which these mouse models were exposed to ischaemic and non-ischaemic heart failure, we discuss whether and when modulations in FA metabolism are protective against heart failure.
Hepatitis E is a form of acute hepatitis, which is caused by infection with hepatitis E virus. The infection is transmitted primarily through fecal-oral route and the disease is highly endemic in several developing countries with opportunities for contamination of drinking water. In these areas with high endemicity, it occurs as outbreaks and as sporadic cases of acute hepatitis. The illness often resembles that associated with other hepatotropic viruses and is usually self-limiting; in some cases, the disease progresses to acute liver failure. The infection is particularly severe in pregnant women. Patients with chronic liver disease and superimposed HEV infection can present with severe liver injury, the so-called acute-on-chronic liver failure. In recent years, occasional sporadic cases with locally acquired hepatitis E have been reported from several developed countries in Europe, United States, and Asia. In these areas, in addition to acute hepatitis similar to that seen in highly endemic areas, chronic hepatitis E has been reported among immunosuppressed persons, in particular solid organ transplant recipients. HEV-infected mothers can transmit the infection to foetus, leading to premature birth, increased fetal loss and hypoglycaemia, hypothermia, and anicteric or icteric acute hepatitis in the newborns. Occasional cases with atypical non-hepatic manifestations, such as acute pancreatitis, hematological abnormalities, autoimmune phenomena, and neurological syndromes have been reported from both hyperendemic and non-endemic regions. The pathogenesis of these manifestations remains unclear.
... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...
Law, M. R.; Morris, J. K.; Wald, N. J.
OBJECTIVES: To estimate the risk of ischaemic heart disease caused by exposure to environmental tobacco smoke and to explain why the associated excess risk is almost half that of smoking 20 cigarettes per day when the exposure is only about 1% that of smoking. DESIGN: Meta-analysis of all 19 acceptable published studies of risk of ischaemic heart disease in lifelong non-smokers who live with a smoker and in those who live with a non-smoker, five large prospective studies of smoking and ischaemic heart disease, and studies of platelet aggregation and studies of diet according to exposure to tobacco smoke. RESULTS: The relative risk of ischaemic heart disease associated with exposure to environmental tobacco smoke was 1.30 (95% confidence interval 1.22 to 1.38) at age 65. At the same age the estimated relative risk associated with smoking one cigarette per day was similar (1.39 (1.18 to 1.64)), while for 20 per day it was 1.78 (1.31 to 2.44). Two separate analyses indicated that non-smokers who live with smokers eat a diet that places them at a 6% higher risk of ischaemic heart disease, so the direct effect of environmental tobacco smoke is to increase risk by 23% (14% to 33%), since 1.30/1.06 = 1.23. Platelet aggregation provides a plausible and quantitatively consistent mechanism for the low dose effect. The increase in platelet aggregation produced experimentally by exposure to environmental tobacco smoke would be expected to have acute effects increasing the risk of ischaemic heart disease by 34%. CONCLUSION: Breathing other people's smoke is an important and avoidable cause of ischaemic heart disease, increasing a person's risk by a quarter. PMID:9365294
Thijssen, Dick H J; Maxwell, Joseph; Green, Daniel J; Cable, N Timothy; Jones, Helen
What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact
... transaminase enzyme levels Treatment There is no specific treatment for hepatitis A. You should rest when the symptoms are ... and have not had hepatitis A or the hepatitis A vaccine. Common reasons for getting one or both of these treatments include: You live with someone who has hepatitis ...
Di Piero, V; Chollet, F M; MacCarthy, P; Lenzi, G L; Frackowiak, R S
The metabolic changes occurring after ischaemic stroke were measured to investigate the functional anatomy of clinical motor recovery. Positron emission tomography (PET) and the steady-state 15O technique was used to compare resting relative metabolic distributions at the onset of functional deficit with those following recovery. Ten patients were studied with repeat scans. Motor recovery was associated in some patients with an increase of relative oxygen metabolism in anatomical structures normally involved in motor function in the affected hemisphere, particularly in the cortical motor areas. In those patients without such metabolic changes in the cortex of the diseased hemisphere, relative increases in cortical metabolism in the contralateral hemisphere were associated with better motor recovery than in patients with no relative cortical metabolic increase in either hemisphere. There was no correlation between the degree of improvement in motor function and the severity of motor deficit at onset, the size and site of the lesion and the metabolic changes in the infarcted zone. No particular pattern of global metabolic changes was observed after recovery. Thus different relative patterns of metabolic recovery were seen in patients with different lesions and evidence was found for the participation of contralateral structures in the recovery process in some patients. Images PMID:1469418
Medcalf, Robert L
Nature has provided a vast array of bioactive compounds that have been exploited for either diagnostic or therapeutic use. The field of thrombosis and haemostasis in particular has enjoyed much benefit from compounds derived from nature, notably from snakes and blood-feeding animals. Indeed, the likelihood that blood-feeding animals would harbour reagents with relevant pharmacology and with potential pharmaceutical benefit in haemostasis was not too far-fetched. Blood-feeding animals including leeches and ticks have evolved a means to keep blood from clotting or to at least maintain the liquid state, and some of these have been the subject of clinical development. A more recent example of this has been the saliva of the common vampire bat Desmodus rotundus, which has proven to harbour a veritable treasure trove of novel regulatory molecules. Among the bioactive compounds present is a fibrinolytic compound that was shown over 40 years ago to be a potent plasminogen activator. Studies of this vampire bat-derived plasminogen activator, more recently referred to as desmoteplase, revealed that this protease shared a number of structural and functional similarities to the human fibrinolytic protease, tissue-type plasminogen activator (t-PA) yet harboured critically important differences that have rendered this molecule attractive for clinical development for patients with ischaemic stroke.
Sjogren, B; Weiner, J; Larsson, K
Aims: To compare the occurrence of ischaemic heart disease (IHD) among male and female livestock and agricultural workers with gainfully employed men and women in Sweden. Methods: Male and female livestock and agricultural workers were identified in the Swedish National Censuses of 1970 and 1990 and were followed until the end of 1995. The IHD mortality among the livestock and agricultural workers was compared with that of gainfully employed men and women. Information of smoking habits was gathered from a previous national survey. Results: Male as well as female livestock workers had slightly higher standardised mortality ratios (SMR) regarding IHD compared with all gainfully employed men and women in Sweden. The SMR for male workers was 1.06 (95% CI 0.95 to 1.18). The SMR for female workers was 1.10 (95% CI 0.98 to 1.23). Agricultural workers had lower SMRs. Adjustments for smoking habits would further increase the SMRs by about 9% in male workers and about 5% in female workers. Conclusion: The present data suggest a slightly increased risk for IHD among both male and female livestock workers, which may be the result of organic dust exposure. PMID:12883028
Morrow, David A.; Sabatine, Marc S.; Brennan, Marie-Luise; de Lemos, James A.; Murphy, Sabina A.; Ruff, Christian T.; Rifai, Nader; Cannon, Christopher P.; Hazen, Stanley L.
Aims We investigated the prognostic performance of myeloperoxidase (MPO), and soluble CD40 ligand (sCD40L) along with B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and cardiac troponin I (cTnI) for non-fatal recurrent ischaemic events in non-ST elevation acute coronary syndrome (ACS). Methods and results We measured plasma MPO and sCD40L in 1524 patients with ACS treated with tirofiban and randomized to early invasive vs. conservative management in the TACTICS-TIMI 18 trial who survived to 180 days. Patients with elevated baseline MPO (>884 pM) were at higher risk of non-fatal myocardial infarction or rehospitalization for ACS at 30 days (9.3 vs. 4.6%, P < 0.001). In contrast, no difference was observed with higher sCD40L (>989 pg/mL, 7.6 vs. 6.3%, P = 0.31). MPO remained associated with recurrent ischaemic events after adjustment for age, ST-deviation, diabetes, prior coronary artery disease, heart failure, cTnI, hsCRP, and sCD40L (OR 2.10; 95% CI 1.36–3.23, P = 0.001). This association was attenuated by 180 days (OR 1.26; 0.95–1.68). Stratification using baseline MPO, BNP, and cTnI identified a >3-fold gradient of risk. Conclusion MPO adds to BNP and cTnI for short-term risk assessment for recurrent ischaemic events in non-ST elevation ACS. sCD40L was not associated with risk in this population treated with a platelet GPIIb/IIIa receptor antagonist. PMID:18339606
Harston, George W. J.; Tee, Yee Kai; Blockley, Nicholas; Okell, Thomas W.; Thandeswaran, Sivarajan; Shaya, Gabriel; Sheerin, Fintan; Cellerini, Martino; Payne, Stephen; Jezzard, Peter; Chappell, Michael
The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke. PMID:25564491
Harston, George W J; Tee, Yee Kai; Blockley, Nicholas; Okell, Thomas W; Thandeswaran, Sivarajan; Shaya, Gabriel; Sheerin, Fintan; Cellerini, Martino; Payne, Stephen; Jezzard, Peter; Chappell, Michael; Kennedy, James
The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.
Cucchiara, B; Kasner, S; Wolk, D; Lyden, P; Knappertz, V; Ashwood, T; Odergren, T; Nordlund, A
Background: Previous reports have suggested left hemispheric dominance for maintaining consciousness, although there is controversy over this claim. Objective: To compare early impairment of level of consciousness between patients with right and left hemispheric stroke. Methods: Data from 564 patients with ischaemic stroke enrolled in the placebo arm of a trial of a putative neuroprotectant were analysed. All patients had major hemispheric stroke with cortical dysfunction, visual field deficit, and limb weakness, with symptom onset within 12 hours of enrolment. Patients were prospectively evaluated on a predefined scale (1–6; 1 = fully awake, higher scores representing greater impairment) to measure level of consciousness at multiple time points over the initial 24 hours after presentation. The National Institutes of Health (NIH) stroke scale score at presentation and infarct volume at 30 days were determined. Results: Some degree of impairment in level of consciousness was observed in 409 of the 564 patients (73%). Median maximum sedation score was 2 for both right and left hemispheric stroke (p = 0.91). Mean sedation score over 24 hours was 1.5 for both right and left stroke (p = 0.75). There was no difference between level of consciousness scores in right and left stroke at any individual time point during the 24 hour monitoring period. No association between side and impairment in level of consciousness was seen after adjustment for stroke severity and infarct volume. Conclusions: In contrast to previous reports, there was no evidence for hemispheric dominance for consciousness in the setting of a major hemispheric stroke. PMID:12810773
Riggio, Oliviero; Marzano, Chiara; Papa, Alessia; Pasquale, Chiara; Gasperini, Maria Ludovica; Gigante, Antonietta; Valla, Dominique Charles; Plessier, Aurélie; Amoroso, Antonio
Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction at any level from the small hepatic veins to the atrio-caval junction, in the absence of heart failure or constrictive pericarditis. Various imaging modalities are available for investigating the gross hepatic vascular anatomy but there are rare forms of this disease where the obstruction is limited to the small intrahepatic veins, with normal appearance of the large hepatic veins at imaging. In this cases only a liver biopsy can demonstrate the presence of a small vessels outflow block. We report two cases of small hepatic veins Budd-Chiari syndrome.
Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves
This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255
Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves
This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.
Emdin, M; Taddei, A; Varanini, M; Raciti, M; Pola, S; Marchesi, C; L'Abbate, A
The current role of ECG and signal monitoring in the diagnosis of Ischaemic Heart Disease is outlined in relation to imaging techniques giving accurate information on myocardial anatomy and function. ECG monitoring during stress testing remains the first step non-invasive method providing pathophysiological information. Long term continuous monitoring of the ECG and of other signals (e.g. arterial blood pressure and respiration) is commonly used to control patients with suspected or ascertained IHD. Progress of technology and of signal processing methods are driving the exploitation of signal information for diagnosis, prognosis and therapy control of ischaemic patients.
Guo, Yutao; Wang, Hao; Tao, Tao; Tian, Yingchun; Wang, Yutang; Chen, Yundai; Lip, Gregory Y. H.
Background The clinical epidemiology of stroke has been widely investigated in Caucasian populations, but the changes over time in the proportion of ischaemic to haemorrhagic strokes is less clear, especially in the Chinese population. Aims Our objective was to study the determinants and time trends for ischaemic and haemorrhagic stroke, in relation to age, in a large Chinese population cohort. Methods Using a medical insurance database in the southwest of China from 2001 to 2012, time trends in age-adjusted ischaemic and haemorrhagic stroke incidence and the contributing risk factors associated with age were investigated. Results Among 425,901 individuals without prior stroke (52.4% male, median age 54), the rate of ischaemic stroke (per 1000 patient-years) decreased between 2002–2007, then remained broadly similar between 2008–2012. The rate of haemorrhagic stroke showed a similar trend, being approximately 1.3–1.9 from 2008–2012. Compared to patients age<65, ischaemic and haemorrhagic stroke incidences (rate, 95% confidential interval, CI) were higher in the elderly population (age <65 versus age ≥65: ischaemic: 3.64, 3.33–4.00, vs 14.33, 14.01–14.60; haemorrhagic: 1.09, 1.00–1.10 vs 2.52,2.40–2.70, respectively, both p<0.001). There were no significant differences in haemorrhagic stroke rates between the elderly and the very elderly population. Ischaemic and haemorrhagic stroke shared similar risk factors (age, hypertension, coronary artery disease (CAD), vascular disease, and diabetes mellitus) (all p<0.05). In subjects age<75 years, CAD (7.17, 4.14–12.37) and diabetes mellitus (3.27, 2.42–4.42) contributed most to the developing of haemorrhagic stroke (all p<0.001). Amongst the very elderly, vascular disease (2.24, 1.49–3.37) was an additional major risk factor for haemorrhagic stroke, together with CAD and diabetes mellitus (all p<0.001). Conclusion In this large Chinese cohort, there was an increased risk of ischaemic stroke compared
... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...
... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...
... commonly used with viral hepatitis and related conditions. Web Resources American Liver Foundation A national nonprofit organization ... other liver diseases through research, education, and advocacy. Web site features a database directory of hepatitis clinical ...
Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...
... times more infectious than HIV. Which adults need hepatitis B vaccine? Any sexually active adult who is not in ... share needles, syringes, or other drug-injection equipment. Hepatitis B vaccine is available alone or in a combination with ...
Hepatitis C virus (HCV) is a leading cause of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. HCV nearly always recurs in liver-transplanted patients, and 10 to 25% of them develop cirrhosis within 5 to 10 years. One of the strategies suggested to limit virological HCV recurrence is pretransplant antiviral treatment, but studies are warranted on the pharmacokinetics of antiviral drugs in cirrhotic patients, the benefits of fixed or escalating antiviral drug dosage schedules, the duration of the treatment, and the indications for using growth factors. Several risk factors are associated with a more aggressive recurrent HCV and early allograft failure, such as an older donor age. The relationship between immunosuppression and fibrosis progression in HCV recurrence remains uncertain. Concerning the antiviral treatment, treating established recurrent disease with a combination of interferon and ribavirin has been the mainstay of management to date, but when it is best to start and how to manage the side effects are still controversial issues. Antiviral treatment should be started once the disease has been confirmed by a biopsy when the fibrosis develops, providing that ongoing acute or chronic rejection, biliary obstruction, vascular damage, autoimmune diseases and sepsis, and any other standard contraindications for antiviral therapy, have been excluded. HCV recurrence after liver transplantation may well lead to graft failure and become an indication for retransplantation, but this is done in a relatively small number of cases, accounting for only 3 to 5% of retransplanted patients, since retransplantation is associated with much worse results than primary liver transplant procedures. We must be prepared for the fact that increasing numbers of HCV-positive recipients with allografts failing due to recurrent HCV will be asking to be retransplanted-and we do not know yet how to respond to this
Ferramosca, Emiliana; Serra, Carla; Di Felice, Antonio; Mandreoli, Marcora; Brunocilla, Eugenio; Santoro, Antonio
A patient with a pseudoaneurysm of the right renal artery underwent treatment with percutaneous approach. No complications were observed. Based on the experience described in this report, a percutaneous ultrasound guided approach can be proposed in selected patients. Renal insufficiency and allergic reactions are potential contraindications to angiography with conventional ionic iodinated contrast dye in patients who need endovascular stent-graft placement. Real-time contrast-enhanced ultrasound (CEUS) guided endovascular procedures may provide an alternative to overcome these limitations. We report an endovascular renal artery repair in a solitary kidney patient with an asymptomatic infrarenal aortic aneurysm and renal insufficiency due to phenacetin abuse. The precise placement of the stent-graft was performed with CEUS and intraprocedural angiographic fluoroscopy without the use of any nephrotoxic contrast dye. During follow-up, CEUS was used to exclude endoleaks, stent-graft failure or malposition.
Cornberg, M; Manns, M P
Infection with hepatitis viruses can lead to acute hepatitis with the risk of developing liver failure. Chronic viral hepatitis may evolve into liver cirrhosis and hepatocellular carcinoma. Thus, prevention of viral hepatitis and its sequels is essential. Vaccination against hepatitis A is successful in almost all individuals. Protective antibodies maintain for at least 20 years. Booster vaccinations are not necessary. Since the introduction of hepatitis A vaccines, the incidence of new HAV-infections has declined significantly. Hepatitis B vaccines are safe and highly effective. Special populations such as dialysis patients or immunocompromised patients require special vaccine schedules. New vaccines with improved adjuvants are currently being tested in clinical trials. So far there is no hepatitis C vaccine on the horizon. Prophylaxis of HCV-infections relies primarily on hygiene measures. Early therapy of acute hepatitis C can prevent chronic hepatitis C. HDV-infection can only be established if HBsAg is present. Thus, prevention of hepatitis B or elimination of HBsAg means prevention of hepatitis delta. Hepatitis E vaccines have been evaluated in phase III studies. The development of HEV vaccines becomes more relevant since chronic HEV infections have been reported in immunosuppressed individuals.
... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...
Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.
This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.
Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok
The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.
Heloury, Y; Valayer, J; Hay, J M; Gauthier, F; Alagille, D
88 porto systemic shunts were performed between 1977-1985; 14 failures were observed. These failures occurred in ten children with extra-hepatic portal obstruction and in four with intra-hepatic obstruction. The treatment of these failures was different in these two groups: 7 reoperations in the extra-hepatic obstruction, none in the intra-hepatic. That reoperation is often not suitable in the intrahepatic obstruction because of the hepatic failure. The use of sclerotherapy or the beta receptor blocking agents is discussed in this group.
Braun, K. P. J.; Bulder, M. M. M.; Chabrier, S.; Kirkham, F. J.; Uiterwaal, C. S. P.; Tardieu, M.; Sebire, G.
Arteriopathies are the commonest cause of arterial ischaemic stroke (AIS) in children. Repeated vascular imaging in children with AIS demonstrated the existence of a "transient cerebral arteriopathy" (TCA), characterized by lenticulostriate infarction due to non-progressive unilateral arterial disease affecting the supraclinoid internal…
Akahori, Hirokuni; Karmali, Vinit; Polavarapu, Rohini; Lyle, Alicia N.; Weiss, Daiana; Shin, Eric; Husain, Ahsan; Naqvi, Nawazish; Van Dam, Richard; Habib, Anwer; Choi, Cheol Ung; King, Adrienne L.; Pachura, Kimberly; Taylor, W. Robert; Lefer, David J.; Finn, Aloke V.
Macrophages are an essential component of the immune response to ischaemic injury and play an important role in promoting inflammation and its resolution, which is necessary for tissue repair. The type I transmembrane glycoprotein CD163 is exclusively expressed on macrophages, where it acts as a receptor for haemoglobin:haptoglobin complexes. An extracellular portion of CD163 circulates in the blood as a soluble protein, for which no physiological function has so far been described. Here we show that during ischaemia, soluble CD163 functions as a decoy receptor for TWEAK, a secreted pro-inflammatory cytokine of the tumour necrosis factor family, to regulate TWEAK-induced activation of canonical nuclear factor-κB (NF-κB) and Notch signalling necessary for myogenic progenitor cell proliferation. Mice with deletion of CD163 have transiently elevated levels of TWEAK, which stimulate muscle satellite cell proliferation and tissue regeneration in their ischaemic and non-ischaemic limbs. These results reveal a role for soluble CD163 in regulating muscle regeneration after ischaemic injury. PMID:26242746
Wanigasinghe, Jithangi; Reid, Susan M.; Mackay, Mark T.; Reddihough, Dinah S.; Harvey, A. Simon; Freeman, Jeremy L.
Aim: The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS). Method: The study group comprised 63 participants (41 males, 22 females) from a population-based CP register whose brain imaging showed…
Albucher, J; Ferrieres, J; Ruidavets, J; Guiraud-Chaumeil, B; Perret, B; Chollet, F
OBJECTIVES—The relation betweem serum lipids and ischaemic stroke remains controversial. Studies of lipid related risk factors in cerebrovascular disease have varied greatly in their findings and also in their definition of the cerebrovascular end points. Serum lipids are thought to interact with the pathogenesis of stroke through an atherosclerosis mechanism. Stroke in young patients have been shown to be related to non-atherosclerotic causes most of the time. The aim was to determine the serum lipid profile and the vascular risk factors for ischaemic stroke in a series of patients under 45 with an ischaemic stroke and to compare them with a series of controls of the same age. METHODS—Ninety four consecutive patients with ischaemic stroke were compared with 111 controls of the same age recruited from a regional electoral list. Vascular risk factors were recorded and serum lipid profile was determined in all of them. RESULTS—Multivariate analyses showed that low HDL cholesterol, male sex, smoking, hypertension, and oral contraceptives were risk factors for intracerebral arterial occlusion. CONCLUSION—Low HDL cholesterol was the only serum lipid index to be associated to an increased risk of stroke in this population. Low HDL cholesterol must be considered in the care management of young patients regardless of the detectable presence of atherosclerosis. PMID:10864600
Gill, Sudeep S; Rochon, Paula A; Herrmann, Nathan; Lee, Philip E; Sykora, Kathy; Gunraj, Nadia; Normand, Sharon-Lise T; Gurwitz, Jerry H; Marras, Connie; Wodchis, Walter P; Mamdani, Muhammad
Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics. Design Population based retrospective cohort study. Setting Ontario, Canada. Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an atypical antipsychotic and 14 865 dispensed a typical antipsychotic). Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended. Results After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. Conclusion Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics. PMID:15668211
Milocco, I; Schlossman, D; William-Olsson, G; Appelgren, L K
Haemodynamic stability and left ventricular function (LVF) during induction of anaesthesia and sternotomy were compared in three groups of patients with ischaemic heart disease, angiographically classified as having good, poor and depressed LVF. Anaesthesia was given with fentanyl-droperidol and nitrous oxide. The group with good LVF showed large variations in arterial pressure and heart rate between stimulated and unstimulated states with a reasonable preservation of LVF, expressed as stroke volume, through the whole observation period. The group with poor LVF showed monotonously falling arterial pressure, and no heart rate response to tracheal intubation. These patients maintained remarkably stable stroke volumes in connection with low afterloads. After nitrous oxide, additional volume loading was required because of profound hypotension. The majority of the patients in the intermediate group, labelled "depressed LVF", reacted to intubation and sternotomy with signs of left ventricular failure in connection with tachycardia and increased afterloads. The individual variations between patients with different degrees of left ventricular impairment were considerable, and these haemodynamic patterns need to be confirmed with a larger material.
Ganai, Ajaz A. Khan, Athar A. Malik, Zainul A. Farooqi, Humaira
Genistein is an isoflavanoid abundantly found in soy. It has been found to play an important role in the prevention of various chronic diseases including cancer. In this study, we evaluated potential therapeutic properties of Genistein against D-Galactosamine (D-GalN) induced inflammation and hepatotoxicity in male Wistar rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal injection of D-GalN (700 mg/kgBW). Genistein (5 mg/kgBW/day) was given as pre-treatment for 30 days via intra-gastric route followed by D-GalN (700 mg/kgBW) injection. The hepatoprotective and curative effects of Genistein were evident from a significant decrease in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as prevention of histological damage by pre-treatment of Genistein. Genistein pre-treatment significantly inhibited the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly suppressed the production of D-GalN-induced proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. These inhibitory effects were associated with the suppression of nuclear factor-kappa B (NF-ĸB) activation, IKKα/β and Mitogen activated protein kinase (MAPK) phosphorylation by Genistein in D-GalN-treated animals. In conclusion, our results suggest that Genistein may serve as a potential supplement in the prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to maintain the redox potential and strengthens the antioxidant defense system of a cell. - Highlights: • First study to evaluate hepatoprotective effect of Genistein against D-GalN • Genistein prevents oxidative damage induced by D-GalN. • Genistein blunts iNOS, COX-2, NF-ĸB, IKKα/β and MAPK expression. • Genistein prevents D-GalN induced apoptosis and
Ignat'ev, I M
The present study was aimed at specifying the indications for operations performed on carotid arteries in an acute period of ischaemic stroke and assessing the results thus obtained. Between January 2008 and July 2010, we carried out a total of 372 operations on carotid arteries in three hundred and sixty patients. Of these, thirty-two subjects were operated on in an acute period of stroke. Neurovisualization was performed by means of magnetic resonance imaging (MRI) and computed tomography (CT). The condition of the carotid arteries was assessed by means of duplex scanning (DS). The operations performed on the carotid arteries were as follows: thrombembolectomy (n=4), carotid thrombendarterectomy (n 5), carotid endarterectomy (CEAE, n=21), and stent grafting of the internal carotid arteries (1СA, n 2). Five CEAE operations were carried out after thrombolysis. The interventions on the carotid arteries were performed within 6 hours to 12 days from the onset of the first symptoms of ischaemic stroke. Neurologists were actively engaged in both determining the indications for the operations and monitoring of neurological functions. There were no perioperative complications encountered. Regression of the neurological deficit during 7 days of in-hospital follow up occurred in sixteen patients (50%) (neurological deficit scoring 1-2 by the Rankin scale). One patient (3%) developed ischaemic stroke on postoperative day 3 after CEAE. Two patients were diagnosed as having transitory ischaemic attacks. Stenting turned out successful in the both patients. The remote results at terms ranging from 12 months to 2 years were followed up in fifteen patients. Of these, twelve patients (80%) showed complete restoration of neurological functions (Rankin scale scoring 0). Neither lethal outcomes nor relapsing strokes were observed over the follow-up period. The obtained outcomes strongly suggest certain advantages and advisability of active surgical policy of treating patients
Censori, B.; Colombo, F.; Valsecchi, M. G.; Clivati, L.; Zonca, A.; Camerlingo, M.; Casto, L.; De Tommasi, M. S.; Mamoli, A.
OBJECTIVES—To test the hypothesis that transoesophageal echocardiography (TOE) carried out within three days of a first stroke or transient ischaemic attack of cryptogenic or lacunar type may disclose more thrombi or spontaneous echo contrast (SEC) than previously reported. This finding may help early treatment decisions. METHODS—Patients aged between 40 and 80 years, admitted for transient ischaemic attack or ischaemic stroke during a 40 month period, were prospectively considered. TOE was carried out within 72 hours of symptom onset with a 5 MHz biplanar transducer. Subjects with recurring events, very severe strokes, large artery obstructions, or obvious cardiac sources of embolism were excluded. RESULTS—Sixty five patients were studied, 43 with a cryptogenic stroke or transient ischaemic attack (66.2%), and 22 with a lacunar stroke (33.8%). The mean (SD) interval between symptom onset and TOE was 43.4 (17.2) hours for cryptogenic, and 48.5 (19.5) hours for lacunar patients. Atrial thrombi were found in one patient with a cryptogenic stroke (2.32% of cryptogenic events; 95% confidence interval 0.06-12.29), whereas SEC was found in five patients (7.7% overall), two with a lacunar and three with a cryptogenic stroke. CONCLUSIONS—An early TOE does not seem to increase substantially the detection of atrial thrombi or SEC in patients with a first stroke or transient ischaemic attack of cryptogenic or lacunar nature. Therefore, this examination can be carried out when the patients' conditions are stable, and without overloading the cardiovascular laboratory daily schedule. PMID:9598678
Antunes-Correa, Ligia M; Ueno-Pardi, Linda M; Trevizan, Patricia F; Santos, Marcelo R; da Silva, Carlos Henrique P; Franco, Fábio Gm; Alves, Maria Janieire Nn; Rondon, Maria Urbana Pb; Negrao, Carlos E
Background Exercise training improves neurovascular control and functional capacity in heart failure (HF) patients. However, the influence of the aetiology on these benefits is unknown. We compared the effects of exercise training on neurovascular control and functional capacity in idiopathic, ischaemic and hypertensive HF patients. Design Subjects consisted of 45 exercise-trained HF patients from our database (2000-2015), aged 40-70 years old, functional class II/III and ejection fraction ≤40%, and they were divided into three groups: idiopathic ( n = 11), ischaemic ( n = 18) and hypertensive ( n = 16). Methods Functional capacity was determined by cardiopulmonary exercise testing. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Results Four months of exercise training significantly reduced MSNA and significantly increased FBF in all groups. However, the relative reduction in MSNA was greater in hypertensive patients compared with that in idiopathic patients (frequency: -34% vs . -15%, p = 0.01; incidence: -31% vs . -12%, p = 0.02). No differences were found between hypertensive patients and ischaemic patients. The relative increase in FBF was greater in hypertensive patients than in ischaemic and idiopathic patients (42% vs. 15% and 17%, respectively, p = 0.02). The relative increase in forearm vascular conductance was greater in hypertensive patients compared with those in ischaemic and idiopathic patients (57% vs . 13% and 26%, respectively, p = 0.001). Exercise training significantly and similarly increased peak oxygen consumption in all groups. Conclusion The exercise-induced improvement in neurovascular control is more pronounced in hypertensive HF patients than in idiopathic and ischaemic HF patients. The increase in functional capacity is independent of aetiology.
Ogholikhan, Sina; Schwarz, Kathleen B.
Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406
Obara-Michlewska, Marta; Pannicke, Thomas; Karl, Anett; Bringmann, Andreas; Reichenbach, Andreas; Szeliga, Monika; Hilgier, Wojciech; Wrzosek, Antoni; Szewczyk, Adam; Albrecht, Jan
Brain edema in acute hepatic encephalopathy (HE) is due mainly to swelling of astrocytes. Efflux of potassium is implicated in the prevention of glial swelling under hypoosmotic conditions. We investigated whether pathogenic factors of HE, glutamine (Gln) and/or ammonia, induce alterations in the expression of glial potassium channels (Kir4.1, Kir2.1) and Na(+) -K(+) -2Cl(-) cotransporter-1 (NKCC1) in rat cerebral cortex and cultured rat cortical astrocytes and whether these alterations have consequences for potassium efflux and astrocytic swelling. Thioacetamide-induced acute liver failure in rats resulted in significant decreases in the Kir4.1 mRNA and protein contents of cerebral cortex, whereas expression of Kir2.1 and NKCC1 remained unaltered. Incubation of primary cortical astrocytes for 72 hr in the presence of Gln (5 mM), but not of ammonia (5 mM or 10 mM), induced a decrease in the levels of Kir4.1 mRNA and protein. Similarly to incubation with Gln, reduction of Kir4.1 mRNA expression by RNA interference caused swelling of astrocytes as shown by confocal imaging followed by 3D computational analysis. Gln reduced the astrocytic uptake of D-[(3) H]aspartate, but, in contrast to the earlier reported effect of ammonia, this reduction was not accompanied by decreased expression of the astrocytic glutamate transporter GLT-1 mRNA. Both Gln and ammonia decreased hypoosmolarity-induced (86) Rb efflux from the cells, but the effect was more pronounced with Gln. The results indicate that down-regulation of Kir4.1 may mediate distinct aspects of Gln-induced astrocytic dysfunction in HE.
... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...
... travelers How can hepatitis B be prevented? The hepatitis B vaccine offers the best protection. All infants and unvaccinated ... should receive hepatitis B immune globulin and the hepatitis B vaccine within 12 hours of birth to help prevent ...
... Hepatitis C Antibody; Anti-HCV; HCV-PCR; HCV-RNA; Hepatitis C Viral Load Formal name: Viral Hepatitis C Antibody Screen; Viral Hepatitis C RNA by PCR; Hepatitis C Virus Genotype Related tests: ...
... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one of the ...
... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...
... Old Feeding Your 1- to 2-Year-Old Hepatitis KidsHealth > For Parents > Hepatitis Print A A A ... to Call the Doctor en español Hepatitis About Hepatitis The word hepatitis simply means an inflammation of ...
... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B is ... their exposures. Map 3-04. Prevalence of chronic hepatitis B virus infection among adults PDF Version (printable) ...
Kahn, S Lowell; McClain, Jonathan; Kaufman, Jeffrey L
A 66-year-old man, with an abnormal porta hepatis, consistent with tumor or inflammation, developed massive bleeding from one of numerous hepatic artery aneurysms, and coil embolization achieved control of bleeding. He died of subsequent multisystem organ failure, and the most likely diagnosis was either polyarteritis nodosa or segmental arterial mediolysis. Although the dual hepatic blood supply allows a degree of arterial embolization, this case demonstrates the risks associated with large territory hepatic arterial embolization in the presence of hemodynamic instability. We discuss the management issues related to massive hepatic bleeding when no surgical approach is possible.
Neri, S; Pulvirenti, D; Patamia, I; Zoccolo, A; Castellino, P
We report an unusual case of transfusion-transmitted malaria which remained undiagnosed for several months in an Italian woman splenectomised and polytransfused for thalassaemia major. The infecting species was Plasmodium malariae, and the patient developed acute renal failure, severe thrombocytopenia, and hepatic failure. Treatment with chlorochine was followed by a slow, but complete recovery of renal function.
Gove, C D; Wardle, E N; Williams, R
The activities of the lysosomal enzymes acid and neutral protease, N-acetylglucosaminidase, and acid phosphatase were measured in the serum of patients with fulminant hepatic failure. Acid protease (cathepsin D) activity was increased about tenfold in patients who died and nearly fourfold in those who survived fulminant hepatic failure after paracetamol overdose, whereas activities were increased equally in patients with fulminant hepatic failure due to viral hepatitis whether or not they survived. A correlation was found between serum acid protease activity and prothrombin time, and the increase in cathepsin D activity was sustained over several days compared with aspartate aminotransferase, which showed a sharp early peak and then a fall. Circulating lysosomal proteases can damage other organs, and measurement of their activity may therefore be of added value in assessing prognosis in this condition. PMID:7007443
Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco
Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.
... inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There are at least 5 hepatitis viruses. Hepatitis A is contracted when a child eats food or drinks water that is contaminated with the virus or has ...
... B to come back?Should I get the hepatitis B vaccine?What are the side effects of antiviral medicines?Will my liver ever be normal again? Last Updated: October 1996 This article ... B, hepatitis virus, Interferon alpha-2b, jaundice, Lamivudine, liver ...
Bolger, Aidan P; Gatzoulis, Michael A
Injury to the myocardium disrupts geometric integrity and results in changes to intracardiac pressure, wall stress and tension, and the pattern of blood flow through the heart. Significant disruption to pump function results in heart failure which is defined in terms of symptoms: breathlessness and fatigue, signs of salt and water retention, and neurohormonal activation. This syndrome most commonly occurs in the context of injury due to ischaemic heart disease and dilated cardiomyopathy but because patients with congenital heart disease (CHD) are born with sometimes gross distortions of cardiac anatomy they too are subject to the forces that drive heart failure. This paper explores the available data relating to the clinical and neurohormonal manifestations of heart failure in patients with congenital heart disease and describes how, by additionally exploring events at a cellular level, we may be able to arrive at a definition of heart failure relevant to this population.
Matthews, J G; Parks, T G
Hypovolaemia alone did not lead to ischaemic colitis but when venesection was induced immediately after the acute ligation of the common colic artery large bowel ischaemia ensued. Similarly, hypovolaemia induced one month after two major blood vessels had been occluded led to ischaemic colitis. These findings suggest that states of low blood flow in the presence of previous arterial constriction or blockage may lead to enough reduction in mesenteric perfusion for intestinal ischaemia to develop. Using an electromagnetic flowmeter placed in the cranial mesenteric artery of the dog, it was shown that hypovolaemia may lead to 50-75% reduction in mesenteric blood flow without producing any significant change in the systemic blood pressure. Images Fig. 5 Fig. 6 Fig. 7 Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:976807
Krause, B L; Hassan, M A; McMilan, A B; Brown, A H
Intracardiac surgical procedures are best carried out when the heart is still and bloodless. This condition, however, produces myocardial cellular damage with loss of contractility and compliance unless some protection can be provided. Myocardial contractility and compliance is best studied by isovolumic ventricular function tests, which were used to evaluate the protective effect of methylprednisolone on the isolated cross-perfused canine heart made ischaemic for 2 hours. Control experiments included 2 hours of ischaemia without methylprednisolone, and 2 hours of continuous normothermic cross-perfusion. The methylprednisolone-treated hearts had probably significantly better ventricular function after 2 hours of ischaemia than did hearts without the methylprednisolone, while the cross-perfused hearts were best overall. This work suggests that methylprednisolone may have a protective effect on the ischaemic myocardium of the intact canine heart. PMID:867332
Cardiovascular Magnetic Resonance (CMR) is recognised as a valuable clinical tool which in a single scan setting can assess ventricular volumes and function, myocardial fibrosis, iron loading, flow quantification, tissue characterisation and myocardial perfusion imaging. The advent of CMR using extrinsic and intrinsic contrast-enhanced protocols for tissue characterisation have dramatically changed the non-invasive work-up of patients with suspected or known cardiomyopathy. Although the technique initially focused on the in vivo identification of myocardial necrosis through the late gadolinium enhancement (LGE) technique, recent work highlighted the ability of CMR to provide more detailed in vivo tissue characterisation to help establish a differential diagnosis of the underlying aetiology, to exclude an ischaemic substrate and to provide important prognostic markers. The potential application of CMR in the clinical approach of a patient with suspected non-ischaemic cardiomyopathy is discussed in this review. PMID:22857649
Ho, Phoebe Wing-Lam; Pang, Wing-Fai; Szeto, Cheuk-Chun
Acute kidney injury (AKI) is a common complication associated with high morbidity and mortality in hospitalized patients. One potential mechanism underlying renal injury is ischaemia/reperfusion injury (IRI), which attributed the organ damage to the inflammatory and oxidative stress responses induced by a period of renal ischaemia and subsequent reperfusion. Therapeutic strategies that aim at minimizing the effect of IRI on the kidneys may prevent AKI and improve clinical outcomes significantly. In this review, we examine the technique of remote ischaemic preconditioning (rIPC), which has been shown by several trials to confer organ protection by applying transient, brief episodes of ischaemia at a distant site before a larger ischaemic insult. We provide an overview of the current clinical evidence regarding the renoprotective effect of rIPC in the key clinical settings of cardiac or vascular surgery, contrast-induced AKI, pre-existing chronic kidney disease (CKD) and renal transplantation, and discuss key areas for future research.
Villani, F; Misrachi, D; Galimberti, M
The aim of the present investigation was to evaluate the type and the incidence of cardiac arrhythmias and ischaemic events in patients suffering from testicular cancer and submitted to combination chemotherapy with cisplatin, bleomycin and vinblastine (PVB) or etoposide (PEB). Forty-seven patients took part in the study; 23 were treated with PVB and 24 with PEB. Holter monitoring was performed in each patient before chemotherapy and on the 1st, 2nd and 5th day of the first cycle of drug administration. The results showed that combination chemotherapy with PVB or PEB was accompanied by the appearance of, or an increase in, the incidence of supraventricular ectopic beats. No significant difference was found between the two groups. No significant conduction disturbances were recorded. These results show that combination chemotherapy with PVB or PEB, at least during the first cycle, has no significant ventricular arrhythmogenic or ischaemic potency in young people with no history of cardiac disease.
Riviello, J J; Halligan, G E; Dunn, S P; Widzer, S J; Foley, C M; Breningstall, G N; Grover, W D
Plasmapheresis is used for treating the complications of liver failure. We performed plasmapheresis on 6 children with hepatic encephalopathy resulting from acute hepatic failure and prospectively assessed its effects on neurologic and electrophysiologic (electroencephalography and evoked potentials) function. Clinical improvement was observed in 3 of 6 patients; changes in the serum ammonia value or the results of initial electrophysiologic tests did not predict the patient response. Two patients underwent transplantation after neurologic improvement was produced by plasmapheresis; however, despite plasmapheresis, 4 patients progressed to brain death. Our data demonstrate that plasmapheresis may transiently improve the encephalopathy of acute hepatic failure but is not curative alone. Therefore, plasmapheresis may be a useful adjunct in the treatment of liver failure, potentially improving the pretransplantation status of the patient.
Chang, Mei-Hwei; Chen, Ding-Shinn
Hepatitis B virus (HBV) causes life-threatening liver disease. It is transmitted through a horizontal route or a mother-to-infant route, and the latter is the major route in endemic areas. Prevention of HBV infection by immunization is the best way to eliminate HBV-related diseases. The HBV vaccine is the first human vaccine using a viral antigen from infected persons, which is safe and effective. Either passive immunization by hepatitis B immunoglobulin (HBIG) or active immunization by HBV vaccine is effective, and a combination of both yields the best efficacy in preventing HBV infection. The impact of universal HBV immunization is huge, with 90%–95% effectiveness in preventing chronic HBV infection. It is the first cancer preventive vaccine with a protective efficacy against hepatocellular carcinoma (HCC) of ∼70%. Nevertheless, further effort is still needed to avoid vaccine failure and to increase the global coverage rate. PMID:25732034
Alozie, Anthony; Westphal, Bernd; Yerebakan, Can; Steinhoff, Gustav
A frequently underdiagnosed complication of pacemaker and implantable cardioverter defibrillator lead implantation is the unintentional advancement of the leads into the systemic circulation. We report a case encountered in our clinic in a 70-year old man evaluated in a neighbouring clinic with symptoms of transient ischaemic attack with initially unclear aetiology. Posterior–anterior chest X-rays suggested that the lead was in the left heart. This finding was confirmed by transthoracic and transoesophageal echocardiography. PMID:22108939
Bhatt, Alok; Menon, Aravind Ajakumar; Bhat, Rama; Ramamoorthi, Kusugodlu
Cerebrovascular complications are rare following viper bites. A 65-year-old man presented with loss of consciousness and developed haemiparesis following a viper bite. Coagulation parameters were severely deranged. MRI showed acute ischaemic infarction on the left side in the precentral and postcentral gyrus, hemipons and cerebellum. Troponin T was elevated and transient left bundle branch block was seen. The patient had a good outcome following treatment with Anti Snake Venom and supportive therapy. Possible mechanisms of infarction are discussed.
Miguéns Blanco, I; Bravo Amaro, M
Ischaemic heart disease is the leading cause of mortality and morbidity and one of the primary causes of morbidity in Spain. The variability in the clinical presentation of this condition at both primary care and emergency services level requires a careful history and a thorough physical examination. In the case presented, the main symptoms of angina and dyspnea reported in the anamnesis, and the obvious pallor in the physical examination, were the key data to identify anaemia as a cause of angina.
Lamar, Melissa; Price, Cate C; Giovannetti, Tania; Swenson, Rod; Libon, David J
The introduction of diagnostic criteria for vascular dementia has helped to re-define the impact of various subcortical neuropathologies on aging; however, state-of-the-art neuroimaging techniques and autopsy studies suggest that not all structural brain alterations associated with vascular dementia are exclusive to this neurodegenerative process alone. Thus, a detailed analysis of the cognitive phenotype associated with ischaemic vascular disease is key to our understanding of subcortical neuropathology and its associated behaviors. Over the past twenty years, we have operationally defined this cognitive phenotype using the Boston Process Approach to neuropsychological assessment. This has led to both an empirical, as well as a theoretical understanding of three core constructs related to the dysexecutive syndrome associated with ischaemic vascular disease affecting periventricular and deep white matter as well as subcortical structures connecting these regions with the prefrontal cortex. Thus, difficulties with mental set, cognitive control and mental manipulation negatively impact executive functioning. This review will outline the subtle markers underlying this prefrontal dysfunction, i.e., the dysexecutive phenotype, associated with ischaemic vascular disease and relate it to fundamental impairments of gating subserved by basal ganglia-thalamic pathways within and across various dementia syndromes.
Mercuri, E.; Cowan, F.; Rutherford, M.; Acolet, D.; Pennock, J.; Dubowitz, L.
Serial ultrasound scans and conventional and diffusion weighted magnetic resonance imaging (MRI) were performed on 16 neonates who presented with seizures. The Apgar scores were normal and subsequently no metabolic or infective cause could be found. The aim of the study was to evaluate the extent to which early sequential imaging can elucidate the cause of seizures in apparently neurologically normal infants. Fourteen of the infants had haemorrhagic or ischaemic lesions on MRI and these were detected by ultrasound scanning in 11. Early ultrasound scanning detected the haemorrhagic lesions but the ischaemic lesions were often not seen until the end of the first week of life. Early MRI, however, was able to detect all the ischaemic lesions. The evolution of the insult could be timed by using serial ultrasound scans and a combination of diffusion weighted and conventional MRI during the first week of life, confirming a perinatal insult even in the absence of fetal distress. Although the aetiology of these lesions remains obscure, serial ultrasound scans will detect the presence of cerebral lesions in neonates presenting with isolated seizures but additional MRI sequences will give better definition on type, site, and extent of the pathology. Images Figures 5 and 6 Figure 2 Figures 3 and 4 Figure 1 PMID:7583609
Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...
Strubelt, O; Younes, M; Li, Y
In previous studies using isolated perfused rat livers, we have shown that reactive oxygen species are involved in hypoxic and ischaemic liver damage. Since albumin was shown to possess strong antioxidant properties we now investigated the capacity of albumin to prevent ischaemic and hypoxic damage in isolated perfused rat livers. Both, partial ischaemia and hypoxia/reoxygenation, resulted in marked hepatic injury as evidenced by an increased release of hepatic enzymes (GPT, LDH), by a strong decline of bile flow and by a decrease in hepatic GSH levels. With partial ischaemia, hepatic ATP depletion and calcium accumulation were also observed. Bovine serum albumin, added to the perfusate at concentrations of 0.1 or 1%, provided nearly complete protection against both types of liver injury. The same level of protection was also afforded by sulfhydryl-blocked and fatty acid-free bovine albumin preparations and by human albumin. In conclusion, the protective effect of albumin in our models of oxidative liver injury is neither due to the thiol moiety nor to the presence of oxidizable fatty acids in the albumin fraction. More likely, albumin provides protection by an unspecific binding of redox-active transition metal ions capable of catalyzing reactions which yield hydroxyl or hydroxyl-like radicals. Besides, unspecific sacrifice reactions of albumin with highly reactive oxygen species or other endogenous compounds may also be implicated.
Aronoff, Alex; Gault, Mathew H.; Huang, Shao-Nan; Lal, Stephan; Wu, Kwang-Tzen; Moinuddin, M.D.; Spence, Leslie; MacLean, Lloyd D.
Over a seven-year period 18 of 125 patients who underwent renal transplantation developed hepatitis. Acute hepatic necrosis occurred in two, chronic aggressive hepatitis progressing to posthepatitic cirrhosis in eight, chronic persistent hepatitis in five, acute hepatitis with recovery in two and cholestatic hepatitis in one. Hepatic failure was the cause of death in four and a major contributing factor in three. Fifteen of the 18 were of blood Group A. After renal transplantation Australia antigen (Au) was present in the blood of 12 of the 15 patients with hepatitis who were tested and in one of 38 patients without clinical evidence of liver disease. Once present, Au persisted in all patients but one. Particles measuring 210 to 250 Å, characteristic of Au, were seen in liver cells by electronmicroscopy in nine of the 10 patients examined who had hepatitis with Australia antigenemia, but they were not seen in the two patients studied with Au-negative hepatitis. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:4566289
Bouchard, Jean-François; Chouinard, Jérôme; Lamontagne, Daniel
The aim of this study was to assess whether the protective effect of ischaemic preconditioning on endothelial function in coronary arteries of the rat involves kinins. Isolated hearts of the rat were exposed to a 30-min low-flow ischaemia (flow rate of 1 ml min−1) followed by 20-min reperfusion, after which coronaries were precontracted with 0.1 μM U-46619, and the response to the endothelium-dependent vasodilator, 5-hydroxytryptamine (5-HT, 10 μM), compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 μM). In untreated hearts, ischaemia-reperfusion diminished selectively 5-HT-induced vasodilatation, compared with time-matched sham hearts. The vasodilatation to SNP was unaffected after ischaemia-reperfusion. Preconditioning (5 min of zero-flow ischaemia followed by 10 min reperfusion) in untreated hearts preserved the vasodilatation produced by 5-HT. Blockade of B1 and B2 receptors with either 3 nM [Lys0, Leu8, des-Arg9]-bradykinin (LLDBK) or 10 nM Hoe 140 (icatibant), respectively, (started 15 min before ischaemic preconditioning or a corresponding sham period and stopped just before the 20-min reperfusion period) had no effect on the vasodilatation produced by either 5-HT or SNP in sham hearts. Pretreatment with Hoe 140 did not block the protective effect of ischaemic preconditioning on the 5-HT vasodilatation. In contrast, LLDBK halved the protective effect of ischaemic preconditioning on endothelium-dependent vasodilatation. Perfusion with either bradykinin or des-Arg9-bradykinin (1 nM) 30 min before and lasting throughout the ischaemia protected the endothelium. In conclusion, ischaemic preconditioning affords protection to the endothelial function in coronary resistance arteries of the rat partly by activation of B1 receptors. Although exogenous BK perfusion can protect the endothelium, B2 receptors do not play an important role in this protection in the rat isolated heart. PMID:9504381
Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... Tiredness and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...
Brown, Robert S.
Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.
Carrion, Andres F; Czul, Frank; Arosemena, Leopoldo R; Selvaggi, Gennaro; Garcia, Monica T; Tekin, Akin; Tzakis, Andreas G; Martin, Paul; Ghanta, Ravi K
Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.
... bowel movements Loss of appetite Low-grade fever Dark urine Joint pain Yellowing of the skin and ... person ingests even tiny amounts of contaminated fecal matter. The hepatitis A virus infects liver cells and ...
... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ... travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic ...
... with a positive-sense, single-stranded ribonucleic acid (RNA) genome. The virus has at least 4 different ... RT-PCR) to detect the hepatitis E virus RNA in blood and/or stool; this assay requires ...
Shimokawa, Hiroaki; Miura, Masanobu; Nochioka, Kotaro; Sakata, Yasuhiko
Heart failure (HF) is an epidemic in healthcare worldwide, including Asia. It appears that HF will become more serious in the near future, with the epidemiological transition and ageing of the population. However, in contrast to Western countries, information on HF epidemiology is still limited in Asia, particularly in South Asia. In this review, we will briefly summarize available information regarding the current and future burden of HF in Asia, which indicates the importance of both primary prevention of underlying diseases of HF and secondary prevention, including management of ischaemic HF, HF with preserved EF, and HF in the elderly.
Krawczynski, K; Aggarwal, R; Kamili, S
Hepatitis E, previously known as enterically transmitted non-A, non-B hepatitis, is an infectious viral disease with clinical and morphologic features of acute hepatitis. Its causative agent, hepatitis E virus, consists of small, 32- to 34-nm diameter, icosahedral, nonenveloped particles with a single-stranded, positive-sense, 7.5-kb RNA. The virus has two main geographically distinct strains, Asian and Mexican; recently, novel isolates from nonendemic areas and a genetically related swine HEV have been described. HEV is responsible for large epidemics of acute hepatitis and a proportion of sporadic hepatitis cases in the Indian subcontinent, southeast and central Asia, the Middle East, parts of Africa, and Mexico. The virus is excreted in feces and is transmitted predominantly by fecal-oral route, usually through contaminated water. Person-to-person transmission is uncommon. Clinical attack rates are the highest among young adults. Recent evidence suggests that humans with subclinical HEV infection and animals may represent reservoirs of HEV; however, further data are needed. Diagnosis of hepatitis E is usually made by detection of specific IgM antibody, which disappears rapidly over a few months; IgG anti-HEV persists for at least a few years. Clinical illness is similar to other forms of acute viral hepatitis except in pregnant women, in whom illness is particularly severe with a high mortality rate. Subclinical and unapparent infections may occur; however, chronic infection is unknown. No specific treatment is yet available. Use of clean drinking water and proper sanitation is currently the most effective method of prevention. Passive immunization has not been proved to be effective, and recombinant vaccines for travelers to disease-endemic areas and for pregnant women currently are being developed.
... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Hepatitis A Testing Share this page: Was this page ... HAV-Ab total; Anti-HAV Formal name: Viral Hepatitis A Antibody Related tests: Hepatitis B Testing ; Hepatitis ...
... 3 - Helminths, Soil-Transmitted Chapter 3 - Hepatitis B Hepatitis A Noele P. Nelson, Trudy V. Murphy INFECTIOUS ... hepatitis/HAV Table 3-02. Vaccines to prevent hepatitis A VACCINE TRADE NAME (MANUFACTURER) AGE (Y) DOSE ...
... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 11 Other Languages . Resource Video See ...
... Professional Resources Patient Education Resources Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Grantees Policy and Programs Resource Center Viral Hepatitis Hepatitis A Questions and Answers for the Public Recommend ...
... people at risk for contracting hepatitis. But frequent hand washing and good hygiene practices can reduce this risk. ... After Having Hepatitis B? Hepatitis B (HBV) Hepatitis Hand Washing Blood Transfusions Body Piercing Tattoos Contact Us Print ...
... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...
Chavez-Tapia, Norberto C; Martinez-Salgado, Julio; Granados, Julio; Uribe, Misael; Tellez-Avila, Felix I
AIM: To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation. METHODS: A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran. Demographic, biochemical and severity indexes, and treatment and outcome were assessed. RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids. The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids. CONCLUSION: We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids. PMID:17465474
Mascarenhas, Maria Inês; Moniz, Marta; Ferreira, Sofia; Goulão, Augusto; Barroso, Rosalina
High-output cardiac failure is rare in newborns. Emergent diagnosis and management of this pathology is crucial. We report the case of a child, currently 12-months old; obstetric background is non-contributory. Clinic observation on D1 was normal except for the presence of a systolic cardiac murmur; cardiological evaluation revealed mild ventricular dysfunction of the right ventricle. On the third day of life, she developed cardiac failure with gallop rhythm, hepatomegaly and a murmur in the anterior fontanel; an echocardiogram confirmed clinic aggravation with biventricular dysfunction and right cavities and superior vena cava dilatation. The cranial MRI confirmed the presence of a pial arteriovenous malformation (AVM) involving the anterior and middle cerebral arteries with an associated fronto-parietal ischaemic lesion. The infant underwent embolisations of AVM with successful flow reduction and cardiac failure improvement. The multidisciplinary follow-up showed no cardiac dysfunction or permanent lesions but confirmed a severe psycho-motor delay and left hemiparesia.
van Gerven, Nicole Mf; de Boer, Ynto S; Mulder, Chris Jj; van Nieuwkerk, Carin Mj; Bouma, Gerd
To provide an update of the latest trends in epidemiology, clinical course, diagnostics, complications and treatment of auto immune hepatitis (AIH). A search of the MEDLINE database was performed using the search terms: "auto immune hepatitis", "clinical presentation", "symptoms", "signs", "diagnosis", "auto antibodies", "laboratory values", "serology", "histopathology", "histology", "genetics", "HLA genes", "non-HLA genes", "environment", "epidemiology", "prevalence", "incidence", "demographics", "complications", "HCC", "PBC", "PSC", "corticosteroid", "therapy", "treatment", "alternative treatment". English-language full-text articles and abstracts were considered. Articles included reviews, meta-analysis, prospective retrospective studies. No publication date restrictions were applied. AIH is an immune meditated progressive inflammatory liver disease that predominantly affects middle-aged females but may affect people of all ages. The clinical spectrum of AIH is wide, ranging from absent or mild symptoms to fulminant hepatic failure. The aetiology of AIH is still unknown, but is believed to occur as the consequence of an aberrant immune response towards an un-known trigger in a genetically susceptible host. In the absence of a gold standard, diagnosis is based on the combination of clinical, biochemical and histopathological criteria. Immunosuppressive treatment has been the cornerstone of treatment since the earliest description of the disease in 1950 by Waldenström. Such treatment is often successful at inducing remission and generally leads to normal life expectancy. Nevertheless, there remain significant areas of unmet aetiological a clinical needs including fundamental insight in disease pathogenesis, optimal therapy, duration of treatment and treatment alternatives in those patients unresponsive to standard treatment regimens.
Giles, Michelle; Hellard, Margaret; Sasadeusz, Joe
Hepatitis C is a slowly progressive disease with significant long-term sequelae including cirrhosis, liver failure and hepatocellular carcinoma. Many women of childbearing years are infected with this virus and are at risk of transmitting it to their offspring. Despite this, there are many unanswered questions about hepatitis C and pregnancy including who to screen, the risk factors associated with infection, how these women should be managed during pregnancy and the options available to them after delivery.
Pérez-Gracia, María Teresa; Suay-García, Beatriz; Mateos-Lindemann, María Luisa
Hepatitis E virus (HEV) is responsible for more than 50% of acute viral hepatitis cases in endemic countries. Approximately 2 billion individuals live in hepatitis E-endemic areas and, therefore, are at risk of infection. According to World Health Organization, HEV causes about 20.1 million infections and 70 000 deaths every year. In developing countries with poor sanitation, this disease is transmitted through contaminated water and is associated with large outbreaks, affecting hundreds or thousands of people. In developed countries, autochthonous cases of HEV have been increasingly recognized in the past several years. Hepatitis E virus typically causes an acute, self-limiting illness similar to other acute viral hepatitis, such as hepatitis A or B, with about 0.2% to 1% mortality rate in the general population. However, the course of hepatitis E in pregnancy is different than the mild self-constraining infection described in other populations. During pregnancy, HEV infection can take a fulminant course, resulting in fulminant hepatic failure, membrane rupture, spontaneous abortions, and stillbirths. Studies from various developing countries have shown a high incidence of HEV infection in pregnancy with a significant proportion of pregnant women progressing to fulminant hepatitis with a fatality rate of up to 30%. The present review will highlight new aspects of the HEV infection and pregnancy.
Design, methodology and baseline characteristics of Tai Chi and its protective effect against ischaemic stroke risk in an elderly community population with risk factors for ischaemic stroke: a randomised controlled trial
Zheng, Guohua; Zheng, Xin; Li, Junzhe; Duan, Tingjin; Qi, Dalu; Ling, Kun; He, Jian; Chen, Lidian
Introduction Controlling risk factors with regular exercise is effective and cost-effective for the primary prevention of ischaemic stroke. As a traditional Chinese form of exercise, Tai Chi might be beneficial in decreasing ischaemic stroke, but the evidence remains insufficient. We hypothesise that elderly community adults with risk factors for ischaemic stroke will decrease their ischaemic stroke risk by improving cerebral haemodynamic parameters, cardiopulmonary function, motor function, plasma risk indices, physical parameters or psychological outcomes after receiving 12 weeks of regular Tai Chi training compared with those who maintained their original physical activities. Therefore, we designed a randomised controlled trial that will systematically evaluate the protective effects of Tai Chi exercise on ischaemic stroke risk in an elderly community population with risk factors for ischaemic stroke. Methods and analysis A total of 170 eligible participants were randomly allocated into either the Tai Chi training group or the usual physical activity group. This paper reports on the design, intervention development and baseline characteristics of the participants. There were no significant differences between comparison groups in demographic characteristics or the baseline data of primary or secondary outcomes. Participants in the Tai Chi training group will receive 12 weeks of Tai Chi training with a frequency of 5 days/week and 60 min/day, while those in the usual physical activities group will maintain their original activities. Primary and secondary outcomes will be measured at the 12-week and 24-week follow-ups. Ethics and dissemination Ethical approval has been obtained from the Medical Ethics Committee of The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine (number 2013-020-02). The findings of this study will be communicated to healthcare professionals, participants and the public through peer
... Our Accomplishments Annual Reports Our Videos What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...
... with Hepatitis » Sex and Sexuality: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... hepatitis C virus through sex. Can you pass hepatitis C to a sex partner? Yes, but it ...
Lai, Leon Tat; Morgan, Michael Kerin
Microscope-integrated near-infrared indocyanine green videoangiography (ICGVA) has been shown to be a useful adjunct for intracranial aneurysm surgery. That the routine application of this technique reduces the risk of postoperative ischaemic complication, however, has not been reported. We present a retrospective matched-pair comparison of ICGVA guided aneurysm surgery versus historic control surgical cohort treated by the same author. Index patients and controls were matched for aneurysm size, location, patient demographics, risk factors, comorbidities, and surgical treatments. Ninety-one eligible patients with 100 intracranial aneurysms were treated using ICGVA assistance. There were no statistically significant differences between the two groups in terms of patient age, sex, risk factors, comorbidities and aneurysm characteristics. Of the 100 aneurysms in the ICGVA group, 107 investigations of ICGVA were performed. In 79 aneurysms (79.0%), ICGVA was considered useful but did not affect surgical management. In six patients (6.0%), ICGVA led to a crucial change of intraoperative strategies. In nine patients (9.0%), it was considered critical in assuring patency of small perforators. ICGVA was of no benefit in four patients (4.0%) and was misleading in two (2.0%). Postoperative ischaemic complications occurred in three patients (3.3%) in the ICGVA group compared with seven patients (7.7%) in the control group (p<0.001). Our study supports the use of ICGVA in aneurysm surgery as a safe and effective modality of intraoperative blood flow assessment. With all limitations of a retrospective matched-pair comparison, the use of ICGVA during routine aneurysm surgery reduces the incidence of postoperative ischaemic complications.
Basalay, Marina V.; Mastitskaya, Svetlana; Mrochek, Aleksander; Ackland, Gareth L.; del Arroyo, Ana Gutierrez; Sanchez, Jenifer; Sjoquist, Per-Ove; Pernow, John; Gourine, Alexander V.; Gourine, Andrey
Aims Although the nature of the humoral factor which mediates cardioprotection established by remote ischaemic conditioning (RIc) remains unknown, parasympathetic (vagal) mechanisms appear to play a critical role. As the production and release of many gut hormones is modulated by the vagus nerve, here we tested the hypothesis that RIc cardioprotection is mediated by the actions of glucagon-like peptide-1 (GLP-1). Methods and results A rat model of myocardial infarction (coronary artery occlusion followed by reperfusion) was used. Remote ischaemic pre- (RIPre) or perconditioning (RIPer) was induced by 15 min occlusion of femoral arteries applied prior to or during the myocardial ischaemia. The degree of RIPre and RIPer cardioprotection was determined in conditions of cervical or subdiaphragmatic vagotomy, or following blockade of GLP-1 receptors (GLP-1R) using specific antagonist Exendin(9–39). Phosphorylation of PI3K/AKT and STAT3 was assessed. RIPre and RIPer reduced infarct size by ∼50%. In conditions of bilateral cervical or subdiaphragmatic vagotomy RIPer failed to establish cardioprotection. GLP-1R blockade abolished cardioprotection induced by either RIPre or RIPer. Exendin(9–39) also prevented RIPre-induced AKT phosphorylation. Cardioprotection induced by GLP-1R agonist Exendin-4 was preserved following cervical vagotomy, but was abolished in conditions of M3 muscarinic receptor blockade. Conclusions These data strongly suggest that GLP-1 functions as a humoral factor of remote ischaemic conditioning cardioprotection. This phenomenon requires intact vagal innervation of the visceral organs and recruitment of GLP-1R-mediated signalling. Cardioprotection induced by GLP-1R activation is mediated by a mechanism involving M3 muscarinic receptors. PMID:27702763
Sawai, Takeshi; Imano, Hironori; Muraki, Isao; Hayama-Terada, Mina; Shimizu, Yuji; Cui, Renzhe; Kitamura, Akihiko; Kiyama, Masahiko; Okada, Takeo; Ohira, Tetsuya; Yamagishi, Kazumasa; Umesawa, Mitsumasa; Sankai, Tomoko; Iso, Hiroyasu
Objective The prognostic importance of changes in ischaemic ECG abnormalities over time (especially ST-T abnormalities) among Asians has not been fully investigated. We examined the associations between changes in ischaemic abnormalities upon serial ECG (improvement, persistence, deterioration) and cardiovascular disease (CVD) risk. Methods A prospective study cohort was conducted with 9374 men and women aged 40–69 years in four communities. Participants had multiple ECGs at study entry and during the next 10 years, and were followed up for a median period of 23.0 years. Total CVD (stroke and coronary heart disease) was ascertained under systematic surveillance. ECG abnormalities were defined by the Minnesota Code, ST depression (Code4), abnormal T wave (Code5) and categorised into nine groups (no–no, no–minor, no–major, minor–no, minor–minor, minor–major, major–no, major–minor, major–major) by comparison with the point of entrance and maximum change. Results We documented 1196 CVD events. Compared with no–no abnormality, no–minor, minor–major and major–major in Code4, HRs (95% CI) adjusted for cardiovascular risk factors were 1.19 (1.00–1.42), 1.57 (1.15–2.12) and 1.87 (1.42–2.47). Similar results were observed in Code5. Conclusions Changes in ischaemic ECG abnormalities from none to minor, and minor to major, as well as persistent major abnormalities, were associated with an increased risk of CVD. PMID:28176973
Torén, Kjell; Bergdahl, Ingvar A; Nilsson, Tohr; Järvholm, Bengt
Objectives A growing number of epidemiological studies are showing that ambient exposure to particulate matter air pollution is a risk factor for cardiovascular disease; however, whether occupational exposure increases this risk is not clear. The aim of the present study was to examine whether occupational exposure to particulate air pollution increases the risk for ischaemic heart disease and cerebrovascular disease. Methods The study population was a cohort of 176 309 occupationally exposed Swedish male construction workers and 71 778 unexposed male construction workers. The definition of exposure to inorganic dust (asbestos, man‐made mineral fibres, dust from cement, concrete and quartz), wood dust, fumes (metal fumes, asphalt fumes and diesel exhaust) and gases and irritants (organic solvents and reactive chemicals) was based on a job‐exposure matrix with focus on exposure in the mid‐1970s. The cohort was followed from 1971 to 2002 with regard to mortality to ischaemic heart disease and cerebrovascular disease. Relative risks (RR) were obtained by the person‐years method and from Poisson regression models adjusting for baseline values of blood pressure, body mass index, age and smoking habits. Results Any occupational particulate air pollution was associated with an increased risk for ischemic heart disease (RR 1.13, 95% CI 1.07 to 1.19), but there was no increased risk for cerebrovascular disease (RR 0.97, 95% CI 0.88 to 1.07). There was an increased risk for ischaemic heart disease and exposure to inorganic dust (RR 1.07, 95% CI 1.03 to 1.12) and exposure to fumes (RR 1.05, 95% CI 1.00 to 1.10), especially diesel exhaust (RR 1.18, 95% CI 1.13 to 1.24). There was no significantly increased risk for cerebrovascular disease and exposure to inorganic dust, fumes or wood dust. Conclusions Occupational exposure to particulate air pollution, especially diesel exhaust, among construction workers increases the risk for ischaemic heart disease. PMID
Carrion, Diego M; Carrion, Andres F
Here we describe a patient with a rare movement disorder, hemichorea-hemiballismus, which is described as a complication of non-ketotic hyperglycaemia. This complication may be seen in individuals with poorly controlled long-standing diabetes mellitus. Proper diagnosis is established with CT and MRI of the brain, which typically show classic findings in the basal ganglia. Treatment focuses on improvement of glycaemic control and usually results in rapid resolution of the movement disorder. Nevertheless, recurrent episodes of hemichorea-hemiballismus, and even more ominous complications such as ischaemic stroke may occur.
Carrion, Diego M; Carrion, Andres F
Here we describe a patient with a rare movement disorder, hemichorea–hemiballismus, which is described as a complication of non-ketotic hyperglycaemia. This complication may be seen in individuals with poorly controlled long-standing diabetes mellitus. Proper diagnosis is established with CT and MRI of the brain, which typically show classic findings in the basal ganglia. Treatment focuses on improvement of glycaemic control and usually results in rapid resolution of the movement disorder. Nevertheless, recurrent episodes of hemichorea–hemiballismus, and even more ominous complications such as ischaemic stroke may occur. PMID:23470671
Hulstaert, E; Roggeman, E; Beeckman, A-S; Moerman, M; Vanderstraeten, E; Rasquin, K; Monsaert, E; Baert, D; Dewint, P; Burvenich, P; Van Steenkiste, C
Ischaemic necrosis of the tongue is an unusual clinical finding. In most cases it is associated with vasculitis, particularly giant cell arteritis (GCA). Other causes include profound cardiogenic shock. We report a case of tongue necrosis in an 81-year-old Caucasian woman. The patient was admitted to the intensive care unit (ICU) for cardiogenic shock. Swelling of the tongue was reported before intubation and evolved into tongue ischaemia and necrosis of the tip of the tongue. After surgical debridement the patient recovered. To our knowledge, this is the second report of a patient surviving tongue necrosis resulting from cardiogenic shock.
Licata, Giuseppe; Tuttolomondo, Antonino; Di Raimondo, Domenico; Corrao, Salvatore; Di Sciacca, Riccardo; Pinto, Antonio
Few studies have examined the relationship between inflammatory biomarker blood levels, cardioembolic stroke subtype and neurological deficit. So the aim of our study is to evaluate plasma levels of immuno-inflammatory variables in patients with cardio-embolic acute ischaemic stroke compared to other diagnostic subtypes and to evaluate the relationship between immuno-inflammatory variables, acute neurological deficit and brain infarct volume. One hundred twenty patients with acute ischaemic stroke and 123 controls without a diagnosis of acute ischaemic stroke were evaluated. The type of acute ischaemic stroke was classified according to the TOAST classification. We evaluated plasma levels of IL-1beta, TNF-alpha, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1,sVCAM-1, vWF, TPA and PAI-1. Patients with ischaemic stroke classified as cardio-embolic (CEI) showed, compared to other subtypes, significantly higher median plasma levels of TNF-alpha , IL-6 and IL-1beta. Furthermore stroke patients classified as lacunar showed, compared to other subtypes, significantly lower median plasma levels of TNF-alpha, IL-6 and IL-1beta. Multiple linear regression showed a significant association between the Scandinavian Stroke Scale (SSS) score at admission and diagnostic subtype, infarct volume of cardio-embolic strokes and some inflammatory variables. Our findings confirm that cardio-embolic strokes have a worse clinical presentation and produce larger and more disabling strokes than other ischaemic stroke subtypes reporting a possible explanation of higher immuno-inflammatory activation of the acute phase.
Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina
Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and N(G) -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease.
Mizock, B A
Hepatic encephalopathy (HE) is a syndrome of global cerebral dysfunction resulting from underlying liver disease or portal-systemic shunting. HE can present as one of four syndromes, depending on the rapidity of onset of hepatic failure and the presence or absence of preexisting liver disease. The precise pathogenesis is unknown but likely involves impaired hepatic detoxification of ammonia as well as alterations in brain transport and metabolism of amino acids and amines. The etiology of malnutrition in hepatic failure is multifactorial. Nutritional deficits may be clinically manifest as marasmus or kwashiorkor, or both. Nutritional support in HE is directed toward reducing morbidity related to underlying malnutrition and concurrent disease. However, reaching nutritional goals is often complicated by protein and carbohydrate intolerance. The use of protein restriction in HE is controversial. Modified formulas that are supplemented in branched chain amino acids may be of value in patients who exhibit protein intolerance with standard feeding solutions or in patients who present with advanced degrees of encephalopathy.
In computed tomography (CT) of the head of the femur, a star-shaped structure can be seen which we refer to as the asterisk or asterisk sign. The asterisk is formed by thickened weight-bearing bone trabeculae. It can be shown by CT that the asterisk exhibits a characteristic change in ischaemic bone necrosis of the femoral head, even when the disease is in an early stage. CT of the hip joint is therefore an important examination for early diagnosis of ischaemic disease of the femoral head.
Rongen, G A; van Dijk, J P; van Ginneken, E E; Stegeman, D F; Smits, P; Zwarts, M J
This study was performed to test two hypotheses: (1) ischaemic preconditioning (development of tolerance to ischaemia) influences muscle fibre conduction velocity (MFCV) during repeated ischaemic isometric exercise and (2) the increase in MFCV to supranormal levels during recovery from ischaemic exercise is caused by activation of Na+−K+-ATPase. For this purpose, MFCV was measured with surface electromyography (sEMG) during repeated ischaemic isometric exercise of the brachioradial muscle (2 min at 30 % of maximal voluntary contraction). The involvement of ischaemic preconditioning was tested by changing the duration of ischaemia and by intra-arterial infusion of adenosine (brachial artery, 50 μg min−1 dl−1). The role of Na+−K+-ATPase was explored using ouabain (0.2 μg min−1 dl−1). During the exercise, MFCV decreased from 4.4 ± 0.2 m s−1 to 3.7 ± 0.2 m s−1 (P < 0.01, n = 13). Similar reductions in MFCV were observed during repeated exercise, irrespective of the reperfusion time (10 min vs. 18 min) or duration of the ischaemia (2 vs. 10 min). However, initial MFCV gradually increased for each subsequent contraction when contractions were repeated at 10 min intervals (4.4 ± 0.2 m s−1vs. 4.9 ± 0.2 m s−1 for the first and fourth contraction respectively; P < 0.01; n = 13). This increase was not observed when contractions were performed at 18 min intervals, nor when additional ischaemia was applied. Intra-arterial adenosine did not affect MFCV. Intra-arterial ouabain did not affect the reduction in MFCV during exercise but completely prevented the increase in MFCV during recovery: from 4.7 ± 0.2 m s−1 to 5.2 ± 0.2 m s−1vs. 4.5 ± 0.1 m s−1 to 4.5 ± 0.1 m s−1 in the absence and presence of ouabain respectively (P < 0.05 for ouabain effect; n = 6). In conclusion, ischaemic preconditioning is not involved in changes in MFCV during repeated ischaemic isometric exercise. The increase in MFCV during recovery from repeated ischaemic
Law, M. R.; Wald, N. J.; Thompson, S. G.
OBJECTIVE--To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. DESIGN--Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). MAIN OUTCOME MEASURE--Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. RESULTS--For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being close to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. CONCLUSIONS--The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18,000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change, lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45,000 men and 4000
An experimental model was used to study the revascularization of an ischaemic skin lesion and the effect on this process of the blood extract Solcoseryl. Under the conditions given in the experiment, restoration of the circulation was by 2 modes--re-flow in the original vessels, and neovascularization. Solcoseryl given daily i.p. encouraged the re-flow phenomenon and therefore, by improving the microcirculation and nutrition, the healing of the ischaemic lesions. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:6176254
... dân Á Châu và vùng Thái Bình Dương Hepatitis B: Tips for Asian & Pacific Islander Americans Did ... to liver failure and liver cancer? What is hepatitis B? Hepatitis B is a liver disease spread ...
... that has been linked to high rates of heart failure and death in infants. Infants are most often diagnosed by the time ... Tying off (ligation) a liver artery Medicines for heart failure Surgery to remove the tumor Outlook (Prognosis) Surgery can cure a tumor in an infant if it is only in one lobe of ...
Sarin, Shiv K; Choudhury, Ashok
Acute-on-chronic liver failure (ACLF) is a distinct clinical entity and differs from acute liver failure and decompensated cirrhosis in timing, presence of acute precipitant, course of disease and potential for unaided recovery. The definition involves outlining the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific timeframe. The pathophysiology of ACLF relates to persistent inflammation, immune dysregulation with initial wide-spread immune activation, a state of systematic inflammatory response syndrome and subsequent sepsis due to immune paresis. The disease severity and outcome can be predicted by both hepatic and extrahepatic organ failure(s). Clinical recovery is expected with the use of nucleoside analogues for hepatitis B, and steroids for severe alcoholic hepatitis and, possibly, severe autoimmune hepatitis. Artificial liver support systems help remove toxins and metabolites and serve as a bridge therapy before liver transplantation. Hepatic regeneration during ongoing liver failure, although challenging, is possible through the use of growth factors. Liver transplantation remains the definitive treatment with a good outcome. Pre-emptive antiviral agents for hepatitis B before chemotherapy to prevent viral reactivation and caution in using potentially hepatotoxic drugs can prevent the development of ACLF.
Badin, Romina A; Modo, Michael; Cheetham, Mike; Thomas, David L; Gadian, David G; Latchman, David S; Lythgoe, Mark F
Heat shock proteins (HSPs) function as molecular chaperones involved in protein folding, transport and degradation and, in addition, they can promote cell survival both in vitro and in vivo after a range of stresses. Although some in vivo studies have suggested that HSP27 and HSP70 can be neuroprotective, current evidence is limited, particularly when HSPs have been delivered after an insult. The effect of overexpressing HSPs after transient occlusion of the middle cerebral artery in rats was investigated by delivering an attenuated herpes simplex viral vector (HSV-1) engineered to express HSP27 or HSP70 30 mins after tissue reperfusion. Magnetic resonance imaging scans were used to determine lesion size and cerebral blood flow at six different time points up to 1 month after stroke. Animals underwent two sensorimotor tests at the same time points to assess the relationship between lesion size and function. Results indicate that post-ischaemic viral delivery of HSP27, but not of HSP70, caused a statistically significant reduction in lesion size and induced a significant behavioural improvement compared with controls. This is the first evidence of effective post-ischaemic gene therapy with a viral vector expressing HSP27 in an experimental model of stroke. PMID:18781161
Gavin, J B; Maxwell, L; Sage, M D
This paper reviews various methods involving electron microscopy that have been used to investigate the ultrastructure of the vasculature of the normal and diseased heart. Whereas scanning electron microscopy is more commonly employed to record surface topography, it can be used to examine freeze-fracture planes within the myocardium and, using heavy-metal staining and back-scattered electron imaging, to examine large 2-mu-thick resin-embedded sections through the heart. The latter technique allows the comparison of structural alterations across the wall of the heart and thus accurate definition of the transmural progression of pathological processes. Transmission electron microscopy can then be used to provide more detailed information from precisely localised regions. Human myocardium can be usefully studied up to 12 hours post-mortem provided that suitable control material is included. Intravascular tracers including low-viscosity resin and nuclear track emulsion can be used to determine whether or not particular vessels allow flow at the time of fixation, and thus changes in the pattern of flow through the microvasculature due to ischaemia and reperfusion can be quantified and defined. Particular care is required in the fixation of ischaemic tissues because oxygen dissolved in the fixative can lead to the rapid formation of oxygen-free radicals on contact with the tissue. This produces artefactual reoxygenation damage characterised by membrane disruption and cell and organelle swelling, which has previously been attributed to ischaemic injury per se. Bubbling glutaraldehyde with nitrogen substantially reduces this artefact.
De Maria, Giovanni Luigi; Kassimis, George; Raina, Tushar; Banning, Adrian P
Coronary sinus interventions (CSI) are a class of invasive techniques (surgical and percutaneous) originally proposed in the first half of the 20th century, aiming to treat ischaemic heart disease by acting on the venous coronary system. Three main classes of CSI have been proposed and tested: (1) retroperfusion technique, (2) retroinfusion technique and (3) coronary sinus occlusion techniques. They all share the principle that a controlled increased pressure within the coronary sinus may promote a retrograde perfusion of the ischaemic myocardium with consequent cardioprotection. Development of arterial treatments including coronary aortic bypass grafting and then percutaneous coronary intervention deflected interest from interventions on the coronary venous system. However, CSI may still have a possible niche role today in specific and selected clinical contexts in which existing therapies are insufficient. In this review paper, we aim to revise the rationale for CSI, describing the details and the evidence collected so far about these techniques and to provide insights about the main clinical scenarios in which these strategies may find a contemporary application in combination or as an alternative to existing approaches.
Oh, Chung-Sik; Kim, Seong-Hyop; Lee, Jaemoon; Rhee, Ka Young
Background: Ischaemic reperfusion injury (IRI) after tourniquet release during total knee arthroplasty (TKR) is related to postoperative cerebral complications. Remote ischaemic preconditioning (RIPC) is known to minimise IRI in previous studies. Thus, we evaluated the effect of RIPC on regional cerebral oxygenation after tourniquet release during TKR. Methods: Patients undergoing TKR were randomly allocated to not receive RIPC (control group) and to receive RIPC (RIPC group). Regional cerebral oxygenation and pulmonary oxygenation were assessed up to 24 h postoperatively. The changes in serum cytokine and lactate dehydrogenase (LDH) levels were assessed and arterial blood gas analysis was performed. Total transfusion amounts and postoperative bleeding were also examined. Results: In total, 72 patients were included in the final analysis. Regional cerebral oxygenation (P < 0.001 in the left side, P = 0.003 in the right side) with pulmonary oxygenation (P = 0.001) was significantly higher in the RIPC group. The serum LDH was significantly lower in the RIPC group at 1 h and 24 h postoperatively (P < 0.001). The 24 h postoperative transfusion (P = 0.002) and bleeding amount (P < 0.001) were significantly lower in the RIPC group. Conclusions: RIPC increased cerebral oxygenation after tourniquet release during TKR by improving pulmonary oxygenation. Additionally, RIPC decreased the transfusion and bleeding amount with the serum LDH level. PMID:28260986
Sandercock, Peter; Lindley, Richard; Wardlaw, Joanna; Dennis, Martin; Lewis, Steff; Venables, Graham; Kobayashi, Adam; Czlonkowska, Anna; Berge, Eivind; Slot, Karsten Bruins; Murray, Veronica; Peeters, Andre; Hankey, Graeme; Matz, Karl; Brainin, Michael; Ricci, Stefano; Celani, Maria Grazia; Righetti, Enrico; Cantisani, Teresa; Gubitz, Gord; Phillips, Steve; Arauz, Antonio; Prasad, Kameshwar; Correia, Manuel; Lyrer, Phillippe
Background Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit. Design International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit. Trial procedures Patients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24–48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol). Trial registration ISRCTN25765518 PMID:18559104
O'Brien, T D; Raffe, M R; Cox, V S; Stevens, D L; O'Leary, T P
One goat anesthetized with thiamylal sodium, xylazine, and halothane for repair of an abominal hernia, and 7 of 29 goats similarly anesthetized for an experiment unrelated to considerations of anesthesia, developed signs of hepatic failure within 24 hours of anesthesia. Affected goats had high values for serum aspartate transaminase and serum total bilirubin by 12 to 24 hours after induction of anesthesia. Necropsy of the 8 affected goats revealed centrilobular to massive hepatic necrosis (8 of 8), brain lesions consistent with hepatic encephalopathy (3 of 4), and acute renal tubular necrosis (6 of 6). Two unaffected goats had no hepatic necrosis. Causes of hepatic necrosis other than those related to anesthesia (eg, infectious agents, toxins) were ruled out by lack of supporting necropsy findings or were considered unlikely because of lack of opportunity for exposure. Hepatic lesions in these goats closely resembled those described in human beings with halothane-associated hepatic injury, although in both species these lesions are nonspecific at the gross and light microscopic levels. The pathogenesis of halothane-associated hepatic injury in goats, as in human beings, remains to be determined.
... Dialysis or Transplant Paying for Kidney Failure Treatment Contact Us Health Information Center Phone: 1-800-860- ... to share this content freely. October 2, 2013 Contact Us Health Information Center Phone: 1-800-860- ...
... for people who can't tolerate ACE inhibitors. Beta blockers. This class of drugs not only slows your ... rhythms and lessen your chance of dying unexpectedly. Beta blockers may reduce signs and symptoms of heart failure, ...
Van Leer-Greenberg, Brett; Kole, Abhisake; Chawla, Saurabh
Kaposi sarcoma (KS) is an aggressive cancer caused by human herpesvirus-8, primarily seen in immunocompromised patients. As opposed to the well-described cutaneous manifestations and pulmonary complications of KS, hepatic KS is rarely reported before death as most patients with hepatic KS do not manifest symptoms or evidence of liver injury. In patients with acquired immune deficiency syndrome, hepatic involvement of KS is present in 12%-24% of the population on incidental imaging and in approximately 35% of patients with cutaneous KS if an autopsy was completed after their death. Patients with clinically significant hepatic injury due to hepatic KS usually have an aggressive course of disease with hepatic failure often progressing to multi-organ failure and death. Here we report an unusual presentation of acute liver injury due to hepatic KS and briefly review the published literature on hepatic KS. PMID:28217255
Salmasi, Mohammad Yousuf; Acharya, Metesh; Humayun, Nada; Baskaran, Dinnish; Hubbard, Stephanie; Vohra, Hunaid
Ischaemic mitral regurgitation (MR) is associated with poor survival. The favoured surgical option remains debatable. Our aim was to perform a meta-analysis to compare the outcomes of mitral valve repair (MVRp) with replacement (MVR). A literature search was conducted in PubMed, Medline and Ovid using the terms 'ischaemic mitral regurgitation', 'repair' and 'replacement'. The primary outcome measure was 30-day survival. The secondary outcome measures were MR recurrence and reoperation. Out of 310 articles, 18 fulfilled the inclusion criteria. A total of 3978 patients were included: 2563 (64%) MVRp cases and 1415 (36%) MVR cases. Operative techniques included annuloplasty for MVRp and subvalvular apparatus-sparing MVR techniques. Thirty-day mortality was lower after MVRp compared with MVR [OR 0.42; (95% CI 0.33-0.54; P = 0.0001)]. There was no difference in long-term survival ranging 1-5 years (HR 0.85, 95% CI 0.65-1.12). Recurrence of MR was significantly higher in the MVRp group (OR 4.26, 95% CI 2.52-7.22), as was the rate of reoperation (OR 2.03, 95% CI 1.49-2.77). Although MVR for ischaemic MR has a higher 30-day mortality rate compared with MVRp, MVRp is associated with the higher rate of MR recurrence and the need for reoperation. MVR remains an attractive option for ischaemic MR.
Ricci, S; Celani, M G; Righetti, E; Caruso, A; De Medio, G; Trovarelli, G; Romoli, S; Stragliotto, E; Spizzichino, L
A low dietary intake of unsaturated fatty acids has been found in male patients with stroke as compared with controls in Italy, and a high consumption of meat has been associated with an increased risk of stroke in Australia. We present a case-control study, comparing the unsaturated and saturated fatty acids content of red cell membranes (which reflects the dietary intake of saturated and unsaturated fats) in 89 patients with ischaemic stroke and 89 controls matched for age and sex. In univariate analysis, besides hypertension, atrial fibrillation, ischaemic changes in ECG and hypercholesterolaemia, stroke patients showed a lower level of oleic acid (P = 0.000), but a higher level of eicosatrienoic acid (P = 0.009). Conditional logistic regression (dependent variable; being a case) showed that the best model included atrial fibrillation, hypertension, oleic acid and eicosatrienoic acids. These results confirm a possible protective role of unsaturated fatty acids against vascular diseases; however, we did not find any difference in the content of omega3 acids, which have been considered in the past to protect against coronary heart disease. We conclude that the preceding diet of patients with ischaemic stroke may be poor in unsaturated fatty acids (namely, oleic acid), and this defect is independent of other vascular risk factors. Only further studies will show whether changes in diet and/or supplement of unsaturated fatty acids might reduce the incidence of ischaemic stroke.
Tsuji, Naoko; Yamashita, Shuji; Sugawara, Yasushi; Kobayashi, Eiji
Our aim was to test the influence of cold ischaemia on replanted limbs, focusing on muscular atrophy and neurological recovery. Inbred wild-type and green fluorescent protein (GFP) transgenic (Tg) Lewis rats aged 8-10 weeks were used. The amputated limbs were transplanted at several cold ischaemic times (0, 1, 8, 12, 24, 48, and 72 hours). An arterial ischaemic model and a denervation model were used as controls. To study nerve regeneration, a GFP limb was transplanted on to the syngenic wild Lewis rat. These animals were evaluated histologically, electrophysiologically, and immunohistochemically. The longer the ischaemic time, the more evident was atrophy of the muscles. Electrophysiological investigation showed that the latency at 3 weeks was longer in the transplantation models than in the normal controls, particularly in the longer ischaemia group. Larger numbers of migrating Schwann cells were seen in the group with no delay than in the group that had been preserved for 12 hours. Ischaemia after amputation of a limb causes muscle cells to necrose and atrophy, and these changes worsen in proportion to the ischaemic preservation time. A delay in nerve regeneration and incomplete paralysis caused by malregeneration also affect muscular atrophy.
Sandén, A; Järvholm, B; Larsson, S
The mortality from ischaemic heart disease was studied in a prospective cohort of 1725 shipyard workers exposed to asbestos. The analyses were stratified for age and smoking habits and restricted to men. In agreement with other findings, men with impaired lung function had a significantly higher risk (relative risk (RR) = 3.5) of dying from ischaemic heart disease than men with normal lung function. Men with asbestosis or suspected asbestosis had a significantly higher risk (RR = 3.1) of dying from ischaemic heart disease than men without asbestosis. Thus asbestosis or suspected asbestosis also seemed to be a risk factor for ischaemic heart disease. This finding was independent of respiratory function. There was no increased risk for ischaemic heart disease in men with compared with men without pleural plaques. Men with production of phlegm or sputum and wheezing or whistling had no increased risk for ischaemic heart disease compared with men without these symptoms. In the group with normal lung function men with dyspnoea had a significantly higher risk of dying from ischaemic heart disease than men without dyspnoea. The findings for men with asbestosis or suspected asbestosis indicated a further risk factor besides impaired lung function, in persons exposed to asbestos. Perhaps this risk factor is due to lesions of the pericardium with consequences for heart function. PMID:8398871
Nishimoto, Soh; Kawai, Kenichiro; Tsumano, Tomoko; Fukuda, Kenji; Fujiwara, Toshihiro; Kakibuchi, Masao
Platelet rich plasma (PRP) has attracted attention as a safe and cost-effective source of growth factors that stimulate cells to regenerate tissue. Bone marrow cells are also estimated as an effective material for treating chronic ulcers. With the same technique to concentrate PRP from peripheral blood, bone marrow aspirate was processed and marrow cells were concentrated as well as platelets. Impact of PRP derived from bone marrow aspirate (bm-PRP) and that from peripheral blood (pb-PRP) on wound healing of persistent ischaemic rabbits' limbs were observed. Full thickness skin defects were made on the thighs, which had been treated to be persistent ischaemic status 3 weeks previously. Saline, pb-PRP, and bm-PRP were injected into the wound floor, respectively. Skin defected areas on ischaemic limbs were significantly wider than those on non-ischaemic limbs. bm-PRP injected wounds showed a significantly smaller skin defect area compared with pb-PRP and ischaemic-saline wounds at all time points. Fluorescently dyed cells of bm-PRP, injected into the wounds, could be traced 4 weeks after, whereas those of pb-PRP could be traced no more than 2 weeks. Wound healing on an ischaemic limb was accelerated with bm-PRP, whereas pb-PRP could not show any significance from saline. This difference can be attributed to the kind of cells contained in the PRPs. Injection of bm-PRP is a good candidate for treating wounds on ischaemic limbs.
Mihăilă, Romeo-Gabriel; Cipăian, Remus-Călin
Chronic hepatitis C is a public health problem worldwide. Unfortunately, not all patients may benefit from antiviral therapy due to thrombocytopenia. Its causes are represented by portal hypertension and platelet sequestration in the spleen, decreased serum levels or activity of thrombopoietin, the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon. Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients. Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner. Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia. Its indication for other hemopathies or situations (like thrombocytopenia secondary to chemo- or radiotherapy, acute leukemia, myelodysplastic syndroms, acquired and hereditary bone marrow failure, and platelet donors) is under study. Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment. We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus, highlighting the benefits and mentioning possible adverse effects. In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery. Eltrombopag is a solution for many of these patients, which allows them receiving antiviral therapy and sometimes getting a sustained virological response, but they must be well monitored to prevent possible thromboembolic or bone marrow complications or liver failure occurrence. PMID:25253952
Introduction Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of multidisciplinary interventions for heart failure? What are the effects of exercise in people with heart failure? What are the effects of drug treatments for heart failure? What are the effects of devices for treatment of heart failure? What are the effects of coronary revascularisation for treatment of heart failure? What are the effects of drug treatments in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 80 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists, amiodarone, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation, antiplatelet agents, beta-blockers, calcium
Davidson, Colin; Coomber, Ben; Gibson, Claire L; Young, Andrew M J
Fast cyclic voltammetry can be used to measure dopamine release after oxygen and glucose deprivation (OGD) induced anoxic depolarization in vitro. Here we measure dopamine efflux with 1s time resolution, which is appropriate to measure OGD-evoked dopamine efflux accurately. In the present study, we examined whether OGD-evoked dopamine efflux could be used to show pre-ischaemic conditioning in the rat caudate brain slice. Caudate slices were exposed to 0, 2, or 10 min OGD pre-ischaemic conditioning, then 60 min later exposed to a second OGD event of 15 min duration. We measured the OGD-evoked dopamine efflux using fast cyclic voltammetry and in some experiments caudate dopamine and DOPAC tissue levels were measured using HPLC and 20 μm cryostat sections were Nissl stained to indicate neuronal loss. We found that 10 but not 2 min OGD pre-ischaemic conditioning resulted in a longer time to onset of OGD-evoked dopamine efflux on the main OGD event (475 ± 31 and 287 ± 30 s for 10 Vs 0 min pre-ischaemic conditioning respectively). Further, 10 min OGD pre-ischaemic conditioning resulted in less dopamine efflux on the second OGD event (4.23 ± 1.12 and 8.14 ± 0.82 μM for 10 Vs 0 min pre-ischaemic conditioning respectively), despite these slices having similar tissue dopamine content and DOPAC/DA ratio, and the rate of dopamine release was slower in the main OGD event (21 ± 5 and 74 ± 8 nM/s for 10 Vs 0 min pre-ischaemic conditioning respectively). These data suggest that 10 min OGD pre-ischaemic conditioning can evoke tolerance to a second OGD event and that voltammetric recording of OGD-evoked dopamine efflux is a useful model of pre-ischaemic conditioning in neuronal tissue.
Gredal, Hanne; Thomsen, Barbara B.; Boza-Serrano, Antonio; Garosi, Laurent; Rusbridge, Clare; Anthony, Daniel; Møller, Arne; Finsen, Bente; Deierborg, Tomas; Lambertsen, Kate L.
Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P=0.04) and CSF (P=0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines, such as tumour necrosis factor and IL-2, were unchanged. Plasma IL-8 levels correlated significantly with infarct volume (Spearman’s r=0.8, P=0.013). The findings showed increased concentrations of IL-6 in the plasma and CSF of dogs with acute ischaemic stroke comparable to humans. We believe that dogs with spontaneous stroke offer a unique, noninvasive means of studying the inflammatory processes that accompany stroke while reducing confounds that are unavoidable in experimental models. PMID:28079628
Gredal, Hanne; Thomsen, Barbara B; Boza-Serrano, Antonio; Garosi, Laurent; Rusbridge, Clare; Anthony, Daniel; Møller, Arne; Finsen, Bente; Deierborg, Tomas; Lambertsen, Kate L; Berendt, Mette
Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P=0.04) and CSF (P=0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines, such as tumour necrosis factor and IL-2, were unchanged. Plasma IL-8 levels correlated significantly with infarct volume (Spearman's r=0.8, P=0.013). The findings showed increased concentrations of IL-6 in the plasma and CSF of dogs with acute ischaemic stroke comparable to humans. We believe that dogs with spontaneous stroke offer a unique, noninvasive means of studying the inflammatory processes that accompany stroke while reducing confounds that are unavoidable in experimental models.
Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...
... please visit this page: About CDC.gov . Hepatitis Risk Assessment Recommend on Facebook Tweet Share Compartir Viral Hepatitis. ... you at risk? Take this 5 minute Hepatitis Risk Assessment developed by the CDC and get a personalized ...
Hepatitis A is inflammation (irritation and swelling) of the liver caused by the hepatitis A virus. You can take several steps to ... reduce your risk of spreading or catching the hepatitis A virus: Always wash your hands thoroughly after ...
... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Hepatitis B Testing Share this page: Was this page ... known as: HBV Tests; Hep B; anti-HBs; Hepatitis B Surface Antibody; HBsAg; Hepatitis B Surface Antigen; ...
... AIDS-Related Opportunistic Infections and Coinfections HIV and Hepatitis C (Last updated 8/31/2016; last reviewed ... the medicines for any side effects. What is hepatitis C? Hepatitis C is a liver disease caused ...
... AIDS-Related Opportunistic Infections and Coinfections HIV and Hepatitis B (Last updated 8/31/2016; last reviewed ... should be treated for both diseases. What is hepatitis B? Hepatitis B is a liver disease caused ...
Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...
Ballantyne, Angela O; Spilkin, Amy M; Hesselink, John; Trauner, Doris A
The developing brain has the capacity for a great deal of plasticity. A number of investigators have demonstrated that intellectual and language skills may be in the normal range in children following unilateral perinatal stroke. Questions have been raised, however, about whether these skills can be maintained at the same level as the brain matures. This study aimed to examine the stability of intellectual, academic and language functioning during development in children with perinatal stroke, and to resolve the inconsistencies raised in previous studies. Participants were 29 pre-school to school-age children with documented unilateral ischaemic perinatal stroke and 24 controls. Longitudinal testing of intellectual and cognitive abilities was conducted at two time points. Study 1 examined IQ, academic skills and language functions using the same test version over the test-retest interval. Study 2 examined IQ over a longer test-retest interval (pre-school to school-age), and utilized different test versions. This study has resulted in important new findings. There is no evidence of decline in cognitive function over time in children with perinatal unilateral brain damage. These results indicate that there is sufficient ongoing plasticity in the developing brain following early focal damage to result in the stability of cognitive functions over time. Also, the presence of seizures limits plasticity such that there is not only significantly lower performance on intellectual and language measures in the seizure group (Study 1), but the course of cognitive development is significantly altered (as shown in Study 2). This study provides information to support the notion of functional plasticity in the developing brain; yields much-needed clarification in the literature of prognosis in children with early ischaemic perinatal stroke; provides evidence that seizures limit plasticity during development; and avoids many of the confounds in prior studies. A greater
... Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection Prevention & ... Institute Education & Training Hep B United Coalition Hepatitis Delta Connect 2017 International HBV Meeting National Patient Advocacy ...
Seeger, Christoph; Mason, William S.
Hepadnaviruses (hepatitis B viruses) cause transient and chronic infections of the liver. Transient infections run a course of several months, and chronic infections are often lifelong. Chronic infections can lead to liver failure with cirrhosis and hepatocellular carcinoma. The replication strategy of these viruses has been described in great detail, but virus-host interactions leading to acute and chronic disease are still poorly understood. Studies on how the virus evades the immune response to cause prolonged transient infections with high-titer viremia and lifelong infections with an ongoing inflammation of the liver are still at an early stage, and the role of the virus in liver cancer is still elusive. The state of knowledge in this very active field is therefore reviewed with an emphasis on past accomplishments as well as goals for the future. PMID:10704474
Waseem, Najeff; Chen, Po-Hung
Abstract Hypoxic hepatitis (HH), also known as ischemic hepatitis or shock liver, is characterized by a massive, rapid rise in serum aminotransferases resulting from reduced oxygen delivery to the liver. The most common predisposing condition is cardiac failure, followed by circulatory failure as occurs in septic shock and respiratory failure. HH does, however, occur in the absence of a documented hypotensive event or shock state in 50% of patients. In intensive care units, the incidence of HH is near 2.5%, but has been reported as high as 10% in some studies. The pathophysiology is multifactorial, but often involves hepatic congestion from right heart failure along with reduced hepatic blood flow, total body hypoxemia, reduced oxygen uptake by hepatocytes or reperfusion injury following ischemia. The diagnosis is primarily clinical, and typically does not require liver biopsy. The definitive treatment of HH involves correction of the underlying disease state, but successful management includes monitoring for the potential complications such as hypoglycemia, hyperglycemia, hyperammonemia and hepatopulmonary syndrome. Prognosis of HH remains poor, especially for cases in which there was a delay in diagnosis. The in-hospital mortality rate is >50%, and the most frequent cause of death is the predisposing condition and not the liver injury itself. PMID:27777895
Pello Lázaro, Ana María; Cristóbal, Carmen; Franco-Peláez, Juan Antonio; Tarín, Nieves; Aceña, Álvaro; Carda, Rocío; Huelmos, Ana; Martín-Mariscal, María Luisa; Fuentes-Antras, Jesús; Martínez-Millá, Juan; Alonso, Joaquín; Lorenzo, Óscar; Egido, Jesús; López-Bescós, Lorenzo; Tuñón, José
Objectives Proton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD. Methods We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death. Results Patients on PPIs were older [62.0 (53.0–73.0) vs. 58.0 (50.0–70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244–4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628–20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results. Conclusions In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings. PMID:28103324
Pérez-Gracia, María Teresa; García, Mario; Suay, Beatriz; Mateos-Lindemann, María Luisa
Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin®. PMID:26355220
Pérez-Gracia, María Teresa; García, Mario; Suay, Beatriz; Mateos-Lindemann, María Luisa
Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin(®).
... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)
Zhang, Jian; Yang, Shi-Wei; Wang, Zheng; Wei, Guang-Ru; Zhou, Yu-Jie
A 58-year-old female with no history of heart disease was admitted to our hospital for abnormal ECG mimicking myocardial ischaemia. The ECG revealed persistent T-wave inversion in almost all leads, especially in precordial leads V2–V6. The patient had no complaints of chest pain, chest distress, short of breath or other atypical myocardial ischaemia symptoms. She had a history of amyotrophic lateral sclerosis (ALS) with a disease course more than 20 years. Examinations help rule out other diseases causing persistent T-wave inversion. Importantly, cardiac catheterisation showed nearly normal coronary arteries that could rule out myocardial ischaemia. Accordingly, the authors presumed that the pseudo-ischaemic ECG was associated with ALS in this patient. The findings of the present case provide new evidence that autonomic nervous system may involve in the pathophysiological progress of ALS. PMID:22665549
Matura-Bedouhene, M; Maatouk, A; Moulin, F; Welter, E; Morel, O; Perdriolle-Galet, E
Heart diseases complicate 1 to 3% of pregnancies and are the leading cause of indirect maternal deaths. Prior ischaemic heart event in pregnant patients is increasing. Most knowledge is based on few reports and there are no French nor international recommendations about the specific management of these patients. The specificity of the management of these patients during pregnancy, delivery and post-partum depends on the severity of the prior cardiac event and its consequences. This will be illustrated by the report of four recent cases managed in our hospital. First patient had myocardial infarction with normal left ventricular ejection fraction (LVEF). Second patient had a Tako-Tsubo syndrome with LVEF 45%. Third patient had ischemic cardiopathy with LVEF 30%. Fourth patient had myocardial infarction with LVEF 20%. A multidisciplinary follow-up should be required, especially in patients with severe ventricular dysfunction. The risk of fetal growth restriction appears to be increased, suggesting that closer ultrasound monitoring is necessary.
Bulens, C; Meerwaldt, J D; van der Wildt, G J; Keemink, C J
Contrast sensitivity function was studied in 16 patients with unilateral ischaemic lesions involving the posterior visual pathway. Sixty-two percent of the patients showed contrast sensitivity loss in at least one eye for horizontal or vertical stimulus orientation. Visual perception was distorted in a qualitatively different way according to the anteroposterior site of the lesion. Patients with occipital or occipitotemporal lesions showed high spatial frequency selective losses and patients with temporal or parietal lesions low frequency selective losses. Stimulus orientation selectivity was observed in patients with lesions of the primary visual cortex as well as in patients with lesions anterior to the striate cortex. Contrast sensitivity orientation-selective losses were demonstrated in 14 of the 17 'affected' eyes.
Lewis, B.; Chait, A.; Oakley, C. M. O.; Wootton, I. D. P.; Krikler, D. M.; Onitiri, A.; Sigurdsson, G.; February, A.
The frequency and nature of abnormalities of serum lipoproteins have been studied, using quantitative techniques, in 143 patients with ischaemic heart disease (I.H.D.). Rigorous selection criteria were used. The findings were related to the distribution of lipoprotein concentrations in a carefully screened control population. Hyperlipoproteinaemia occurred in 55% of patients and in 11 out of 15 patients aged less than 40 years. Raised triglyceride and cholesterol concentrations in very low density lipoprotein were the most frequent abnormalities followed by raised cholesterol content of low density lipoprotein. In young patients high density lipoprotein levels were subnormal. Hyperlipoproteinaemia of W.H.O. types IIa, IIb, III, IV, and V all seemed to be over-represented in I.H.D. I.H.D. patients with type IIa, IIb, and IV abnormalities were all significantly younger than I.H.D. patients with normal lipoprotein levels. PMID:4370367
Gutiérrez-Fernández, María; Fuentes, Blanca; Rodríguez-Frutos, Berta; Ramos-Cejudo, Jaime; Vallejo-Cremades, María Teresa; Díez-Tejedor, Exuperio
Brain repair involves a compendium of natural mechanisms that are activated following stroke. From a therapeutic viewpoint, reparative therapies that encourage cerebral plasticity are needed. In the last years, it has been demonstrated that modulatory treatments for brain repair such as trophic factor- and stem cell-based therapies can promote neurogenesis, gliogenesis, oligodendrogenesis, synaptogenesis and angiogenesis, all of which having a beneficial impact on infarct volume, cell death and, finally, and most importantly, on the functional recovery. However, even when promising results have been obtained in a wide range of experimental animal models and conditions these preliminary results have not yet demonstrated their clinical efficacy. Here, we focus on brain repair modulatory treatments for ischaemic stroke, that use trophic factors, drugs with trophic effects and stem cell therapy. Important and still unanswered questions for translational research ranging from experimental animal models to recent and ongoing clinical trials are reviewed here. PMID:22452968
Kim, Dae Hyun; Shin, Gwang Rae; Choi, Young Je
To determine the risk factors for non-arteritic anterior ischaemic optic neuropathy (NAION) in Korean patients, medical records from 45 Korean patients group and 45 healthy controls group were retrospectively reviewed. 10 NAION risk factors, including age, sex, associated systemic disease, past medical/social history, and fundus findings were analyzed. Significant risk factors for NAION in Korean patients were diabetes mellitus (odds ratio (OR) = 3.613, p = 0.020), hypercholesterolaemia (OR = 5.200, p = 0.001), smoking (OR = 3.58, p = 0.014), microaneurysm/haemorrhage (OR = 5.375, p = 0.024), and crowded small cup (OR = 17.200, p < 0.001).
Brown, A H; Krause, B L; Morritt, G M
Global myocardial ischaemia improves intracardiac operating conditions but damages the myocardium. Propranolol should reduce this damage but may impair postoperative myocardial contractility. An assessment of its protective effect during 90 minutes of normothermic ischaemia in canine hearts has been made. The early and late changes of contractility caused by low-dose propranolol were also recorded. A comparison of cardiac isovolumic contractile force, velocity, and compliance was made in three groups of dogs given 30 microgram/kg of propranolol with or without 90 minutes of cardiac ischaemia, or cardiac ischaemia without propranolol. Contractile force and velocity were significantly reduced by the propranolol, but recovered fully after 90 minutes. Ischaemia without propranolol reduced force and velocity of contraction significantly more than ischaemia with propranolol. Propranolol thus reduces operative ischaemic damage without itself impairing postoperative function. PMID:7330803
Nuttall, T J; Burrow, R; Fraser, I; Kipar, A
An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.
Sandercock, P A; van den Belt, A G; Lindley, R I; Slattery, J
A formal statistical overview of all truly randomised trials was undertaken to determine whether antithrombotic therapy is effective and safe in the early treatment of patients with acute stroke. There were 15 completed randomised controlled trials of the value of early antithrombotic treatment in patients with acute stroke. The regimes tested in acute presumed or confirmed ischaemic stroke were: heparin, 10 trials with 1047 patients: oral anticoagulants, one trial with 51 patients: antiplatelet therapy, three trials with 103 patients. Heparin was tested in one trial with 46 patients with acute haemorrhagic stroke. Outcome measures were deep venous thrombosis (confirmed by I125 scanning or venography), pulmonary embolism, death from all causes, haemorrhagic transformation of cerebral infarction, level of disability in survivors. In patients with acute ischaemic stroke, allocation to heparin was associated with a highly significant 81% (SD 8, 2p < 0.00001) reduction in deep venous thrombosis detected by I125 fibrinogen scanning or venogram. Only three trials systematically identified pulmonary emboli, which occurred in 6/106 (5.7%) allocated control vs 3/132 (2.3%) allocated heparin, a non-significant 58% reduction (SD 45.7, 2p > 0.1). There were relatively few deaths in the trials in patients with presumed ischaemic stroke: 94/485 (19.4%) among patients allocated to the control group vs 79/497 (15.9%) among patients who were allocated heparin. The observed 18% (SD 16) reduction in the odds of death was not statistically significant. The least biased estimated of the effect of treatment on haemorrhagic transformation of the cerebral infarct (HTI) comes from trials where all patients were scanned at the end of treatment, irrespective of clinical deterioration; using this analysis, haemorrhagic transformation occurred in 7/102 (6.9%) control vs 8/106 (7.5%) treated, a non-significant 12% increase (SD 56, 2p > 0.1). These data cannot exclude the possibility that
Introduction Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments, and of drug and invasive treatments, for heart failure? What are the effects of angiotensin-converting enzyme inhibitors in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 85 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists, amiodarone, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation, antiplatelet agents, beta-blockers, calcium channel blockers, cardiac resynchronisation therapy, digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors), exercise, hydralazine plus isosorbide dinitrate, implantable cardiac
Carboni, Gian Piero
Background Fifteen patients with ischaemic cardiomyopathy and inducible ischaemia were studied to determine the mechanisms of mortality. Failure of the contractile reserve during daily life activities may reflect a prognostic index. Methods Single photon emission cardiac tomography and radionuclide ambulatory monitoring (Vest) data were analysed in all patients with a 7-year follow-up. Results At peak exercise on Vest, the 7 non-survivors (N-SURV) showed worse peak ejection rates (PERs) and ejection fractions (EFs) compared with the 8 survivors (SURV), (2 ± 0.6 vs. 3.3 ± 0.7; end-diastolic volumes (EDVs), P < 0.003), and (34 ± 10% vs. 50 ± 13%; P < 0.02), respectively. However, exercise peak filling rates (PFRs) (1.9 ± 0.6 vs. 2.7 ± 0.9; EDVs/s) and exercise heart rates (HRs), (97 ± 17 vs. 106 ± 10), did not differ between the two groups (P > 0.05). In SURV, exercise PERs, which represented rapid left ventricular (LV) emptying, were significantly correlated with exercise PFRs, representing rapid LV filling, (r = 0.71, P < 0.04) but not in N-SURV (r = 0.66, P > 0.05). Among SURV, the Frank-Starling mechanism was thus preserved but not in N-SURV. Upon Cox analysis, overall LV function parameters, exercise PER was the only predictive measure associated with mortality (b = - 0.018, relative hazard ratio = 0.98, P = 0.02). Conclusions Exercise PER reduced values reflected failure of the Frank-Starling mechanism, the incapacity of the heart to perform rapid contractile adaptations to daily life activities and a poor prognosis.
Eames, P; Blake, M; Dawson, S; Panerai, R; Potter, J
Objectives: Hypertension and chronic cerebrovascular disease are known to alter static cerebral autoregulation (CA) but the effects of acute stroke on dynamic CA (dCA) have not been studied in detail. Those studies to date measuring dCA have used sympathetically induced blood pressure (BP) changes, which may themselves directly affect dCA. This study assessed whether dCA is compromised after acute stroke using spontaneous blood pressure (BP) changes as the stimulus for the dCA response. Methods: 56 patients with ischaemic stroke (aged 70 (SD 9) years), studied within 72 hours of ictus were compared with 56 age, sex, and BP matched normal controls. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound (TCD) with non-invasive beat to beat arterial BP levels, surface ECG, and transcutaneous CO2 levels and a dynamic autoregulatory index (dARI) calculated. Results: Beat to beat BP, but not pulse interval variability was significantly increased and cardiac baroreceptor sensitivity (BRS) decreased in the patients with stroke. Dynamic CA was significantly reduced in patients with stroke compared with controls (strokes: ARI 3.8 (SD 2.2) and 3.2 (SD 2.0) for pressor and depressor stimuli respectively v controls: ARI 4.7 (SD 2.2) and 4.5 (SD 2.0) respectively (p<0.05 in all cases)). There was no difference between stroke and non-stroke hemispheres in ARI, which was also independent of severity of stroke, BP, BP variability, BRS, sex, and age. Conclusion: Dynamic cerebral autoregulation, as assessed using spontaneous transient pressor and depressor BP stimuli, is globally impaired after acute ischaemic stroke and may prove to be an important factor in predicting outcome. PMID:11909905
Kuraitis, D; Ebadi, D; Zhang, P; Rizzuto, E; Vulesevic, B; Padavan, D T; Al Madhoun, A; McEwan, K A; Sofrenovic, T; Nicholson, K; Whitman, S C; Mesana, T G; Skerjanc, I S; Musarò, A; Ruel, M; Suuronen, E J
Biomaterial-guided regeneration represents a novel approach for the treatment of myopathies. Revascularisation and the intramuscular extracellular matrix are important factors in stimulating myogenesis and regenerating muscle damaged by ischaemia. In this study, we used an injectable collagen matrix, enhanced with sialyl LewisX (sLeX), to guide skeletal muscle differentiation and regeneration. The elastic properties of collagen and sLeX-collagen matrices were similar to those of skeletal muscle, and culture of pluripotent mESCs on the matrices promoted their differentiation into myocyte-like cells expressing Pax3, MHC3, myogenin and Myf5. The regenerative properties of matrices were evaluated in ischaemic mouse hind-limbs. Treatment with the sLeX-matrix augmented the production of myogenic-mediated factors insulin-like growth factor (IGF)-1, and IGF binding protein-2 and -5 after 3 days. This was followed by muscle regeneration, including a greater number of regenerating myofibres and increased transcription of Six1, M-cadherin, myogenin and Myf5 after 10 days. Simultaneously, the sLeX-matrix promoted increased mobilisation and engraftment of bone marrow-derived progenitor cells, the development of larger arterioles and the restoration of tissue perfusion. Both matrix treatments tended to reduce maximal forces of ischaemic solei muscles, but sLeX-matrix lessened this loss of force and also prevented muscle fatigue. Only sLeX-matrix treatment improved mobility of mice on a treadmill. Together, these results suggest a novel approach for regenerative myogenesis, whereby treatment only with a matrix, which possesses an inherent ability to guide myogenic differentiation of pluripotent stem cells, can enhance the endogenous vascular and myogenic regeneration of skeletal muscle, thus holding promise for future clinical use.
Fischer-Betz, R; Specker, C; Brinks, R; Schneider, M
Among the most prominent features associated with antiphospholipid syndrome (APS) are cerebral ischaemic events (CVE). Pregnancy with APS increases the risk of thrombosis, including CVE. This study was undertaken to assess the risk of obstetric complications and recurrence of CVE during pregnancy in women with APS and previous CVE. We prospectively observed 23 pregnancies in 20 women (median age 31 years) with primary (n = 8) or secondary APS (n = 12). Eight patients had transient ischaemic attacks (TIA) and 12 had stroke before pregnancy. All patients received aspirin 100 mg daily in combination with low molecular weight heparin (LMWH) during their pregnancies. The live birth rate was 91.3% (n = 21). Obstetrical complications consisted mainly of preeclampsia (n = 8, 34.8%) and preterm delivery (n = 9, 42.9%). The risk for preeclampsia increased in patients who were positive for multiple antiphospholipid antibodies (aPL) (odds ratio (OR) 3.06 (95% confidence interval (CI) 1.01-9.32)) per positive aPL test (i.e anticardiolipin antibody, anti-ß2-glycoprotein I antibody, lupus anticoagulant) (p 0.049). Three patients experienced recurrent CVE in the context of pregnancy (one during pregnancy, two in the postpartum period). We found an increased, but not significant, risk of a new episode of cerebral ischaemia in patients with pregnancies complicated by preeclampsia (two out of the eight preeclampsia (p 0.15). Despite treatment, there is a significant risk for pregnancy complications in APS patients with previous CVE. Especially in the context of preeclampsia, anticoagulation should be given rigorously to prevent recurrence of CVE.
Mangiafico, Salvatore; Saia, Valentina; Nencini, Patrizia; Romani, Ilaria; Palumbo, Vanessa; Pracucci, Giovanni; Consoli, Arturo; Rosi, Andrea; Renieri, Leonardo; Nappini, Sergio; Limbucci, Nicola; Inzitari, Domenico; Gensini, Gian Franco
Summary Identification of patients with acute ischaemic stroke who could most benefit from arterial recanalization after endovascular treatment remains an unsettled issue. Although several classifications of collateral circulation have been proposed, the clinical role of collaterals is still debated. We evaluated the effect of the collateral circulation in relation to recanalization as a predictor of clinical outcome. Data were prospectively collected from 102 patients consecutively treated for proximal middle cerebral or internal carotid artery occlusion. The collateral circulation was evaluated with a novel semiquantitative-qualitative score, the Careggi collateral score (CCS), in six grades. Both CCS and recanalization grades (TICI) were analysed in relation to clinical outcome. A statistical analysis was performed to evaluate the effect of interaction between recanalization and collateral circulation on clinical outcome. Out of the 102 patients, 37 (36.3%) had poor collaterals, and 65 (63.7%) had good collaterals. Patients with good collaterals had lower basal National Institute of Health Stroke Scale (NIHSS), more distal occlusion, smaller lesions at 24h CT scan and better functional outcome. After multivariate analysis, the interaction between recanalization and collateral grades was significantly stronger as a predictor of good outcome (OR 6.87, 95% CI 2.11 – 22.31) or death (OR 4.66, 95%CI 1.48 – 14.73) compared to the effect of the single variables. Collaterals showed an effect of interaction with the recanalization grade in determining a favourable clinical outcome. Assessment of the collateral circulation might help predict clinical results after recanalization in patients undergoing endovascular treatment for acute ischaemic stroke. PMID:25496680
Inui, N; Walsh, L D; Taylor, J L; Gandevia, S C
Contorted 'phantom' limbs often form when sensory inputs are removed, but the neural mechanisms underlying their formation are poorly understood. We tracked the evolution of an experimental phantom hand during ischaemic anaesthesia of the arm. In the first study subjects showed the perceived posture of their hand and fingers using a model hand. Surprisingly, if the wrist and fingers were held straight before and during anaesthesia, the final phantom hand was bent at the wrist and fingers, but if the wrist and fingers were flexed before and during anaesthesia, the final phantom was extended at wrist and fingers. Hence, no 'default' posture existed for the phantom hand. The final perceived posture may depend on the initial and evolving sensory input during the block rather than the final sensory input (which should not differ for the two postures). In the second study subjects selected templates to indicate the perceived size of their hand. Perceived hand size increased by 34 ± 4% (mean ± 95% CI) during the block. Sensory changes were monitored. In all subjects, impairment of large-fibre cutaneous sensation began distally with von Frey thresholds increasing before cold detection thresholds (Aδ fibres) increased. Some C fibres subserving heat pain still conducted at the end of cuff inflation. These data suggest that changes in both perceived hand size and perceived position of the finger joints develop early when large-fibre cutaneous sensation is beginning to degrade. Hence it is unlikely that block of small-fibre afferents is critical for phantom formation in an ischaemic block.
Akbulut, Sami; Yilmaz, Mehmet; Eris, Cengiz; Kutlu, Ramazan; Yilmaz, Sezai
Although rare, major congenital defects of the hepatic veins are detectable at autopsy, advanced, noninvasive imaging techniques such as Doppler ultrasonography and multislice computed tomography can accurately define these anomalies. One of these anomalies is congenital absence of the main right hepatic vein. We present a 21-year-old woman living-liver donor candidate with congenital absence of the right hepatic vein who underwent an extended right donor hepatectomy. She was tested for transplant compatibility with her 45-year-old brother, who had chronic liver failure secondary to hepatitis B. Multislice computed tomography revealed an absence of the right hepatic vein, and the right hepatic lobe was drained by 4 inferior hepatic veins with diameters ranging from 4 to 8.4 mm. An extended right-donor hepatectomy was performed. A common-large opening drainage reconstruction model that included all of the inferior hepatic veins and middle hepatic vein was created using the saphenous vein and an aortic homograft. There were no postoperative complications related to hepatic venous drainage thanks to the common-large opening model. We demonstrate that a right donor hepatectomy is feasible in congenital absence of the right hepatic vein solving the drainage problem using common-large opening reconstruction technique.
Diaz, Geraldine C; O'Connor, Michael F; Renz, John F
Hepatic function and pulmonary function are interrelated with failure of one organ system affecting the other. With improved therapies, patients with concomitant hepatic and pulmonary failure increasingly enjoy a good quality of life and life expectancy. Therefore, the prevalence of such patients is increasing with more presenting for both emergent and elective surgical procedures. Hypoxemia requires a thorough evaluation in patients with end-stage liver disease. The most common etiologies respond to appropriate therapy. Portopulmonary hypertension and hepatopulmonary syndrome are associated with increased perioperative morbidity and mortality. It is incumbent on the anesthesiologist to understand the physiology of liver failure and its early effect on pulmonary function to ensure a successful outcome.
... News Physician Resources Professions Site Index A-Z Kidney Failure Kidney failure, also known as renal failure, ... evaluated? How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain ...
Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade
Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties.
Masood, Irfan; Rafiq, Ali; Majid, Zain
We hereby present the case of a 25-year-old man who presented at the emergency department of Civil Hospital Karachi, Pakistan with signs and symptoms of acute viral hepatitis. Serology tests revealed that the patient was suffering from hepatitis E viral (HEV) infection. Concurrently, the patient was also found to have thrombocytopaenia (TCP). His TCP became better after the resolution of his jaundice, with the patient requiring a transfusion of one mega unit of platelets. After ruling out other common causes of TCP and after a thorough literature search, we concluded that an immune-mediated mechanism secondary to HEV infection might have been the cause behind his low platelet counts. Hence, we propose considering the possibility of HEV infection in patients presenting with acute liver failure and TCP, irrespective of age, gender, and geographical location of the patient.
[A case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after standard chemotherapy failure].
Osawa, Gakuji; Yoshimatsu, Kazuhiko; Yokomizo, Hajime; Otani, Taisuke; Yano, Yuki; Itagaki, Hiroko; Matsumoto, Atsuo; Fujimoto, Takashi; Umehara, Arihiro; Ogawa, Kenji
We report a case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after a standard chemotherapy was failed. A 61-year-old female who had sigmoid colon cancer with unresectable multiple lung and liver metastases underwent sigmoidectomy. Bevacizumab plus mFOLFOX6 was performed as first-line therapy. Partial response was obtained temporarily. After the first-line therapy failed, bevacizumab plus FOLFIRI as second-line, and cetuximab plus CPT-11 as third-line therapy were performed. Since these regimens did not work, her performance status got worse by cholangitis due to progressive liver metastases and anemia. Hepatic arterial infusion chemotherapy for liver metastases and cetuximab for lung metastases as fourth therapy were chosen because we thought her liver metastases should be critical for the maintenance of her QOL and diagnosis. After that, serum CEA was reduced from 14,715 to 6,940 ng/mL during the 3 month period. And her performance status got better as cholongitis and anemia were improved. Additionally, lung metastases were controlled by cetuximab.
Wardlaw, Joanna M.; von Kummer, Rüdiger; Farrall, Andrew J.; Chappell, Francesca M.; Hill, Michael; Perry, David
Background Early signs of ischaemic stroke on computerised tomography (CT) scanning are subtle but CT is the most widely available diagnostic test for stroke. Scoring methods that code for the extent of brain ischaemia may improve stroke diagnosis and quantification of the impact of ischaemia. Methodology and Principal Findings We showed CT scans from patients with acute ischaemic stroke (n = 32, with different patient characteristics and ischaemia signs) to doctors in stroke-related specialties world-wide over the web. CT scans were shown twice, randomly and blindly. Observers entered their scan readings, including early ischaemic signs by three scoring methods, into the web database. We compared observers' scorings to a reference standard neuroradiologist using area under receiver operator characteristic curve (AUC) analysis, Cronbach's alpha and logistic regression to determine the effect of scales, patient, scan and observer variables on detection of early ischaemic changes. Amongst 258 readers representing 33 nationalities and six specialties, the AUCs comparing readers with the reference standard detection of ischaemic signs were similar for all scales and both occasions. Being a neuroradiologist, slower scan reading, more pronounced ischaemic signs and later time to CT all improved detection of early ischaemic signs and agreement on the rating scales. Scan quality, stroke severity and number of years of training did not affect agreement. Conclusions Large-scale observer reliability studies are possible using web-based tools and inform routine practice. Slower scan reading and use of CT infarct rating scales improve detection of acute ischaemic signs and should be encouraged to improve stroke diagnosis. PMID:21209901
... cirrhosis (scarring of the liver), liver failure, or liver cancer. There is a vaccine for HBV. It requires three shots. All babies should get the vaccine, but older children and adults can get ... National Institute of Diabetes and Digestive and Kidney Diseases
... Loss Surgery? A Week of Healthy Breakfasts Shyness Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) A A A What's in this article? ... poisons). There are several different types of hepatitis . Hepatitis B is a type that can move from one ...
Cuthbert, Jennifer A.
The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis worldwide. Spread of infection is generally person to person or by oral intake after fecal contamination of skin or mucous membranes; less commonly, there is fecal contamination of food or water. Hepatitis A is endemic in developing countries, and most residents are exposed in childhood. In contrast, the adult population in developed countries demonstrates falling rates of exposure with improvements in hygiene and sanitation. The export of food that cannot be sterilized, from countries of high endemicity to areas with low rates of infection, is a potentially important source of infection. After ingestion and uptake from the gastrointestinal tract, the virus replicates in the liver and is excreted into the bile. Cellular immune responses to the virus lead to destruction of infected hepatocytes with consequent development of symptoms and signs of disease. Humoral immune responses are the basis for diagnostic serologic assays. Acute HAV infection is clinically indistinguishable from other causes of acute viral hepatitis. In young children the disease is often asymptomatic, whereas in older children and adults there may be a range of clinical manifestations from mild, anicteric infection to fulminant hepatic failure. Clinical variants include prolonged, relapsing, and cholestatic forms. Management of the acute illness is supportive, and complete recovery without sequelae is the usual outcome. Research efforts during World War II led to the development of passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the prevention and attenuation of disease in exposed individuals. More recently, active immunoprophylaxis by vaccination has been accomplished. Future eradication of this disease can now be contemplated. PMID:11148002
Téllez Villajos, L; Martínez González, J; Moreira Vicente, V; Albillos Martínez, A
Pulmonary hypertension is a relatively common phenomenon in patients with hepatic cirrhosis and can appear through various mechanisms. The most characteristic scenario that binds portal and pulmonary hypertension is portopulmonary syndrome. However, hyperdynamic circulation, TIPS placement and heart failure can raise the mean pulmonary artery pressure without increasing the resistances. These conditions are not candidates for treatment with pulmonary vasodilators and require a specific therapy. A correct assessment of hemodynamic, ultrasound and clinical variables enables the differential diagnosis of each situation that produces pulmonary hypertension in patients with cirrhosis.
Sandoval-Ramírez, Eunice; Camacho-Meza, Ignacio; Eduardo-Solís, Nery; Plascencia-Tabares, Oswaldo; Navarro-Olivos, Efraín; Ortiz-Aldana, Francisco Ignacio
Hemophagocytic syndrome is characterized by increased proliferation and activation of antigen presenting cells (histiocytes) in bone marrow and other organs of the reticuloendothelial system as well as CD8+ T cells that threatens life of patients. The predominant clinical manifestations such as fever, cytopenia, hepatitis, coagulopathy, neurological symptoms and multiple organ failure are related to systemic inflammation. We report the case of an infant who started with jaundice, abdominal pain, vomiting and malaise, at admission, hepatomegaly, splenomegaly and biochemically with features suggestive of hepatocellular inflammation and progressive cholestasis with poor outcome, it was added persistent fever, seizures, anemia, thrombocytopenia, leukopenia, elevated ferritin and hypertriglyceridemia integrating hemophagocytic syndrome with fatal outcome despite immunosuppressive therapy.
Li, Ting-Ting; Fan, Man-Li; Hou, Shi-Xiang; Li, Xiao-Yi; Barry, Devin M; Jin, Hui; Luo, Sheng-Yong; Kong, Feng; Lau, Lit-Fui; Dai, Xiang-Rong; Zhang, Guo-Hui; Zhou, Lan-Lan
Background and Purpose Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice. Experimental Approach Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 μg·kg−1), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control. Key Results Twenty-four hours after MCAO, anfibatide-treated mice showed significantly improved ischaemic lesions in a dose-dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide-treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban-treated mice. Conclusions and Implications Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke. PMID:25917571
Lee, Sam Man; Hutchinson, Mark; Saint, David A
Cardiac ischaemic-reperfusion injury (IRI) remains the primary cause of mortality throughout the developed world. Molecular mechanisms underlying IRI are complex and are often interlinked with each other driving a synergistic response. Toll-like receptor 4 (TLR4), an immunosurveillance receptor, is known to enhance tissue injury during IRI by enhancing the inflammatory response. The release of endogenous components during IRI bind onto TLR4 leading to the activation of multiple signalling kinases. Once this event occurs these proteins are defined as danger associated molecular patterns molecules (DAMPs) or alarmins. Examples include heat shock proteins, high mobility group box one (HMGB1) and extracellular matrix proteins, all of which are involved in IRI. However, literature in the last two decades suggests that transient stimulation of TLR4 may suppress IRI and thus improve cardiac recovery. Furthermore, it remains to be seen what role TLR4 plays during ischaemic-preconditioning where acute bouts of ischaemia, preceding a harmful bout of ischaemic-reperfusion, is cardioprotective. The other question which also needs to be considered is that if transient TLR4 signalling drives a preconditioning response then what are the ligands which drive this? Hence the second part of this review explores the possible TLR4 ligands which may promote cardioprotection against IRI.
Burnley, I H
This paper examines changes in ischaemic heart disease mortality in New South Wales between 1969 and 1994, with particular reference to the 1969-1973, 1979-1983, 1985-1989 and 1990-1994 periods. Using death certificate data and unit list mortality files, and considering occupational differentials among males, and marital status and regional and intra-metropolitan variations among males and females, the question whether changes in differentials in mortality from heart disease occurred during this mortality transition is asked. Mortality from ischaemic heart disease declined in all marital status and occupational status groups, and in all geographical areas, but it declined more slowly among never married and divorced males, among manual workers, and in lower income areas. Whereas ischaemic heart disease mortality was lower in most rural areas than in metropolitan Sydney at the beginning of the period, in the 1990s it was significantly more elevated in inland small towns and rural areas than in the metropolis. Differentials increased over time, more especially with males.
Bernal, William; Jalan, Rajiv; Quaglia, Alberto; Simpson, Kenneth; Wendon, Julia; Burroughs, Andrew
Acute-on-chronic liver failure combines an acute deterioration in liver function in an individual with pre-existing chronic liver disease and hepatic and extrahepatic organ failures, and is associated with substantial short-term mortality. Common precipitants include bacterial and viral infections, alcoholic hepatitis, and surgery, but in more than 40% of patients, no precipitating event is identified. Systemic inflammation and susceptibility to infection are characteristic pathophysiological features. A new diagnostic score, the Chronic Liver Failure Consortium (CLIF-C) organ failure score, has been developed for classification and prognostic assessment of patients with acute-on-chronic liver failure. Disease can be reversed in many patients, and thus clinical management focuses upon the identification and treatment of the precipitant while providing multiorgan-supportive care that addresses the complex pattern of physiological disturbance in critically ill patients with liver disease. Liver transplantation is a highly effective intervention in some specific cases, but recipient identification, organ availability, timing of transplantation, and high resource use are barriers to more widespread application. Recognition of acute-on-chronic liver failure as a clinically and pathophysiologically distinct syndrome with defined diagnostic and prognostic criteria will help to encourage the development of new management pathways and interventions to address the unacceptably high mortality.
... of Viral Hepatitis Contact Us Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Local Partners & Grantees Policy and Programs Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...
Frijns, C J M; Fijnheer, R; Algra, A; van Mourik, J A; van Gijn, J; Rinkel, G J E
Objective To investigate the relation of endothelial cell activation with delayed cerebral ischaemia (DCI) and outcome after subarachnoid haemorrhage (SAH). Methods Concentrations of soluble (s) intercellular adhesion molecule‐1, sE‐selectin, sP‐selectin, ED1‐fibronectin, von Willebrand Factor (vWf), and vWf propeptide were measured within three days of SAH onset. The associations with poor outcome were investigated at three months in 106 patients. In 90 patients in whom the occurrence of cerebral ischaemia could be dated accurately, two analyses were undertaken: one for all ischaemic events (n = 32), including those related to treatment, and another for spontaneous DCI (n = 11). Concentrations of markers were dichotomised at their medians. The associations of endothelial cell activation markers with outcome were expressed as odds ratios (OR) from logistic regression and those with ischaemic events as hazard ratios (HR) derived from Cox regression. Results Early vWf concentrations were associated with poor outcome (crude OR = 4.6 (95% CI, 2.0 to 10.9; adjusted OR = 3.3 (1.1 to 9.8). Early levels of vWf were also positively related to occurrence of all ischaemic events (crude HR = 2.3 (1.1 to 4.9); adjusted HR = 1.8 (0.8 to 3.9) and with occurrence of spontaneous DCI (crude HR = 3.5 (0.9 to 13.1); adjusted HR = 2.2 (0.5 to 9.8). None of the other markers showed any associations. Conclusions Concentrations of sICAM‐1, sP‐selectin, sE‐selectin, and ED1‐fibronectin do not predict the occurrence of DCI or outcome. The positive associations of raised early vWf concentrations with ischaemic events and poor outcome after SAH may reflect a predisposition to further ischaemic injury through formation of microthrombi in the cerebral circulation. PMID:16361599
Despite major improvements in the treatment of virtually all cardiac disorders, heart failure (HF) is an exception, in that its prevalence is rising, and only small prolongations in survival are occurring. An increasing fraction, especially older women with diabetes, obesity, and atrial fibrillation exhibit HF with preserved systolic function. Several pathogenetic mechanisms appear to be operative in HF. These include increased hemodynamic overload, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Biomarkers released as a consequence of myocardial stretch, imbalance between formation and breakdown of extracellular matrix, inflammation, and renal failure are useful in the identification of the pathogenetic mechanism and, when used in combination, may become helpful in estimating prognosis and selecting appropriate therapy. Promising new therapies that are now undergoing intensive investigation include an angiotensin receptor neprilysin inhibitor, a naturally-occurring vasodilator peptide, a myofilament sensitizer and several drugs that enhance Ca++ uptake by the sarcoplasmic reticulum. Cell therapy, using autologous bone marrow and cardiac progenitor cells, appears to be promising, as does gene therapy. Chronic left ventricular assistance with continuous flow pumps is being applied more frequently and successfully as destination therapy, as a bridge to transplantation, and even as a bridge to recovery and explantation. While many of these therapies will improve the care of patients with HF, significant reductions in prevalence will require vigorous, multifaceted, preventive approaches.
Background We assessed the prevalence, and potential impact of, trials of pharmacological agents for acute stroke that were completed but not published in full. Failure to publish trial data is to be deprecated as it sets aside the altruism of participants' consent to be exposed to the risks of experimental interventions, potentially biases the assessment of the effects of therapies, and may lead to premature discontinuation of research into promising treatments. Methods We searched the Cochrane Stroke Group's Specialised Register of Trials in June 2008 for completed trials of pharmacological interventions for acute ischaemic stroke, and searched MEDLINE and EMBASE (January 2007 - March 2009) for references to recent full publications. We assessed trial completion status from trial reports, online trials registers and correspondence with experts. Results We identified 940 trials. Of these, 125 (19.6%, 95% confidence interval 16.5-22.6) were completed but not published in full by the point prevalence date. They included 16,058 participants (16 trials had over 300 participants each) and tested 89 different interventions. Twenty-two trials with a total of 4,251 participants reported the number of deaths. In these trials, 636/4251 (15.0%) died. Conclusions Our data suggest that, at the point prevalence date, a substantial body of evidence that was of relevance both to clinical practice in acute stroke and future research in the field was not published in full. Over 16,000 patients had given informed consent and were exposed to the risks of therapy. Responsibility for non-publication lies with investigators, but pharmaceutical companies, research ethics committees, journals and governments can all encourage the timely publication of trial data. PMID:20412562
Lim, Chong Teik
Hepatic steatosis is becoming more common in Asia with prevalence becoming as common as Western countries. Concomitant Hepatitis B and hepatic steatosis is increasingly encountered in clinical practice. The interaction between the two concomitant conditions at both molecular level and clinical outcome remains to be explored. The present review is aimed at summarizing the existing literature on the complex interaction of the two-concomitant disease. PMID:28251117
Yan, Haijing; Zhang, Xiangnan; Hu, Weiwei; Ma, Jing; Hou, Weiwei; Zhang, Xingzhou; Wang, Xiaofen; Gao, Jieqiong; Shen, Yao; Lv, Jianxin; Ohtsu, Hiroshi; Han, Feng; Wang, Guanghui; Chen, Zhong
The role of the histamine H3 receptor (H3R) in cerebral ischaemia/reperfusion (I/R) injury remains unknown. Here we show that H3R expression is upregulated after I/R in two mouse models. H3R antagonists and H3R knockout attenuate I/R injury, which is reversed by an H3R-selective agonist. Interestingly, H1R and H2R antagonists, a histidine decarboxylase (HDC) inhibitor and HDC knockout all fail to compromise the protection by H3R blockade. H3R blockade inhibits mTOR phosphorylation and reinforces autophagy. The neuroprotection by H3R antagonism is reversed by 3-methyladenine and siRNA for Atg7, and is diminished in Atg5−/− mouse embryonic fibroblasts. Furthermore, the peptide Tat-H3RCT414-436, which blocks CLIC4 binding with H3Rs, or siRNA for CLIC4, further increases I/R-induced autophagy and protects against I/R injury. Therefore, H3R promotes I/R injury while its antagonism protects against ischaemic injury via histamine-independent mechanisms that involve suppressing H3R/CLIC4 binding-activated autophagy, suggesting that H3R inhibition is a therapeutic target for cerebral ischaemia. PMID:24566390
Miller, N R; Arnold, A C
Nonarteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Patients typically present with acute, painless, unilateral loss of vision associated with a variable visual field defect, a relative afferent pupillary defect, a swollen, hyperaemic optic disc, and one or more flame-shaped peripapillary retinal haemorrhages. The pathogenesis of this condition is unknown, but it occurs primarily in patients with structurally small optic discs that have little or no cup and a variety of underlying vascular disorders that may or may not be known at the time of visual loss. There is no consistently beneficial medical or surgical treatment for the condition, but there are now animal models that allow testing of various potential therapies. About 40% of patients experience spontaneous improvement in visual acuity. Patients in whom NAION occurs in one eye have a 15-19% risk of developing a similar event in the opposite eye over the subsequent 5 years.
Yasaka, M; Read, S J; O'Keefe, G J; Egan, G F; Pointon, O; McKay, W J; Donnan, G A
PET studies were performed in 37 patients up to 1 month after ischaemic stroke to observe the relationships between cerebral blood flow (CBF), rate of cerebral oxygen metabolism (CMRO(2)) and oxygen extraction fraction (OEF) with time. PET findings were classified as misery perfusion (two patients), luxury perfusion (15 patients), matched hypoperfusion-hypometabolism (17 patients) or normal (nine patients). Misery perfusion was seen up to 3 days post-stroke, suggesting an extended time window during which at least some tissue may be salvageable. Luxury perfusion, an indication of non-nutritional flow, was seen as early as 30 h and as late as 23 days, but more commonly between 3 and 7 days. A matched reduction of CBF and CMRO(2) was seen during all time periods, but as early as 27 hours. Since this was associated with severely impaired CBF, presumably from the onset of stroke, it can be assumed that the duration of cerebral tissue survival is less than 27 h under these conditions. We inferred that, for maximal tissue recovery, therapy will need to be introduced within 27 h after stroke, but that at least some potential for recovery exists up to 3 days.
Ebireri, Jennifer; Aderemi, Adewale V; Omoregbe, Nicholas; Adeloye, Davies
Background Ischaemic heart disease (IHD) is currently ranked eighth among the leading causes of deaths in sub-Saharan Africa (sSA). Yet, effective population-wide preventive measures targeting risks in the region are still largely unavailable. We aimed to review population-wide and individual-level interventions addressing risk factors of IHD among adults in sSA. Methods A systematic search of MEDLINE, EMBASE, Global Health and AJOL was conducted to identify studies focusing on population-wide and individual-level interventions targeting risks of IHD among adults in sSA. We conducted a detailed synthesis of basic findings of selected studies. Results A total of 2311 studies were identified, with only 9 studies meeting our selection criteria. 3 broad interventions were identified: dietary modifications, physical activity and community-based health promotion measures on tobacco and alcohol cessation. 3 studies reported significant reduction in blood pressure (BP), and another study reported statistically significant reduction in mean total cholesterol. Other outcome measures observed ranged from mild to no reduction in BP, blood glucose, body mass index and total cholesterol, respectively. Conclusions We cannot specify with all certainty contextually feasible interventions that can be effective in modifying IHD risk factors in population groups across sSA. We recommend more research on IHD, particularly on the understanding of the burden, geared towards developing and/or strengthening preventive and treatment interventions for the disease in sSA. PMID:27381212
Al-Kaabi, Abdullah; Haider, Agha S.; Shafeeq, Mohammed O.; El-Naggari, Mohammed A.; El-Nour, Ibtisam; Ganesh, Anuradha
Non-arteritic anterior ischaemic optic neuropathy (NAION) is a serious complication of continuous peritoneal dialysis (CPD) which can lead to poor vision and blindness. We report a five-year-old girl who had undergone a bilateral nephrectomy at the age of one year and was on home CPD. She was referred to the Paediatric Ophthalmology Unit of Sultan Qaboos University Hospital, Muscat, Oman, in 2013 with acute bilateral vision loss, preceded by a three-day history of poor oral intake. At presentation, the patient had severe systemic hypotension. An ophthalmological examination revealed severe bilateral visual impairment and NAION. She was treated with intravenous methylprednisolone and normal saline boluses. At a five-month follow-up, the visual acuity of the right eye had improved but vision in the left eye remained the same. Acute bilateral blindness due to NAION while on CPD is a rare condition in childhood. Paediatricians should be aware of this complication in order to ensure prompt management. PMID:28003901
Vaccarino, Viola; Badimon, Lina; Corti, Roberto; de Wit, Cor; Dorobantu, Maria; Hall, Alistair; Koller, Akos; Marzilli, Mario; Pries, Axel; Bugiardini, Raffaele
Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in women. PMID:21159671
Stevenson, N J; Korotchikova, I; Temko, A; Lightbody, G; Marnane, W P; Boylan, G B
Automated analysis of the neonatal EEG has the potential to assist clinical decision making for neonates with hypoxic-ischaemic encephalopathy. This paper proposes a method of automatically grading the degree of abnormality in an hour long epoch of neonatal EEG. The automated grading system (AGS) was based on a multi-class linear classifier grading of short-term epochs of EEG which were converted into a long-term grading of EEG using a majority vote operation. The features used in the AGS were summary measurements of two sub-signals extracted from a quadratic time-frequency distribution: the amplitude modulation and instantaneous frequency. These sub-signals were based on a model of EEG as a multiplication of a coloured random process with a slowly varying pseudo-periodic waveform and may be related to macroscopic neurophysiological function. The 4 grade AGS had a classification accuracy of 83% compared to human annotation of the EEG (level of agreement, κ = 0.76). Features estimated on the developed sub-signals proved more effective at grading the EEG than measures based solely on the EEG and the incorporation of additional sub-grades based on EEG states into the AGS also improved performance.
Tsang, G M; Green, M A; Crow, A J; Smith, F C; Beck, S; Hudlicka, O; Shearman, C P
There is currently no established treatment for intermittent claudication with proven long term benefit. Exercise classes have been shown to improve walking distance. Chronic electromyostimulation (CEMS) a method of stimulating skeletal muscle has effects on normal muscle which may also benefit claudicants. We investigated the effects of one month of CEMS on claudicants in a single blind placebo controlled study. Patients were randomised to either CEMS (treatment) or transcutaneous nerve stimulation (TENS) placebo. The effects of the two modalities were assessed using the conventional measures of claudicating distance (CD), maximum walking distance (MWD), ankle-brachial pressure index (ABPI) and pressure recovery time (PRT). Muscle performance was assessed by the fatigue index (FI) a technique determining the decrease in ischaemic muscle response to repeated contraction. After 4 weeks treatment the CEMS group showed significant improvements in their median CD (88 to 111) and MWD (118 to 158); this was not seen in the control group. Muscle performance also increased significantly during the 4 weeks of treatment in the CEMS group but not in the control group. These changes were not maintained after CEMS was stopped. This pilot study suggests that CEMS may well have a role to play in the treatment of intermittent claudication though a number of further studies need to be undertaken.
Siponen, Taina; Yli-Tuomi, Tarja; Aurela, Minna; Dufva, Hilkka; Hillamo, Risto; Hirvonen, Maija-Riitta; Huttunen, Kati; Pekkanen, Juha; Pennanen, Arto; Salonen, Iiris; Tiittanen, Pekka; Salonen, Raimo O; Lanki, Timo
Objective To compare short-term effects of fine particles (PM2.5; aerodynamic diameter <2.5 µm) from different sources on the blood levels of markers of systemic inflammation. Methods We followed a panel of 52 ischaemic heart disease patients from 15 November 2005 to 21 April 2006 with clinic visits in every second week in the city of Kotka, Finland, and determined nine inflammatory markers from blood samples. In addition, we monitored outdoor air pollution at a fixed site during the study period and conducted a source apportionment of PM2.5 using the Environmental Protection Agency's model EPA PMF 3.0. We then analysed associations between levels of source-specific PM2.5 and markers of systemic inflammation using linear mixed models. Results We identified five source categories: regional and long-range transport (LRT), traffic, biomass combustion, sea salt, and pulp industry. We found most evidence for the relation of air pollution and inflammation in LRT, traffic and biomass combustion; the most relevant inflammation markers were C-reactive protein, interleukin-12 and myeloperoxidase. Sea salt was not positively associated with any of the inflammatory markers. Conclusions Results suggest that PM2.5 from several sources, such as biomass combustion and traffic, are promoters of systemic inflammation, a risk factor for cardiovascular diseases. PMID:25479755
García-Esperón, Carlos; Hervás-García, José Vicente; Jiménez-González, Marta; Pérez de la Ossa-Herrero, Natalia; Gomis-Cortina, Meritxell; Dorado-Bouix, Laura; López-Cancio Martinez, Elena; Castaño-Duque, Carlos H; Millán-Torné, Mónica; Dávalos, Antonio
INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers.
Evans, A E; Ruidavets, J B; McCrum, E E; Cambou, J P; McClean, R; Douste-Blazy, P; McMaster, D; Bingham, A; Patterson, C C; Richard, J L
The WHO MONICA project monitors trends and determinants in cardiovascular disease to relate classical risk factor changes to trends in incidence rates. The Belfast and Toulouse MONICA centres have also collaborated in dietary studies. Both centres have validated incidence and attack rates for ischaemic heart disease using coronary event registration. These data confirm that the disease in middle-aged men is between three and four times as common in Belfast as in Toulouse. Risk factor surveys show some differences between the centres, but the overall risks assessed by two multiple logistic function scoring systems were identical. A weighed dietary survey revealed no important difference in macronutrient intake, although carbohydrate and saturated fat intake in Belfast was significantly higher. Protein, dietary cholesterol and polyunsaturated fat, particularly linoleic acid intake, was significantly higher in Toulouse, as was consumption of wine, cheese, fruit and vegetables, but not potatoes. The Northern Irish diet is typically Northern European, but although the diet in Toulouse has some features of the Mediterranean diet, it is not appreciably different from that in Belfast in terms of total fat intake. Major differences are present for several food items, and in general these differences add support to the antioxidant hypothesis.
Danesh‐Meyer, Helen V; Levin, Leonard A
Phosphodiesterase type 5 (PDE5) inhibitor drugs for erectile dysfunction have revolutionised the treatment of male sexual dysfunction and are among the best selling drugs worldwide. Several cases of non‐arteritic anterior ischaemic optic neuropathy (NAION) have been reported since 2005 in users of these agents. NAION is a sudden irreversible cause of visual loss with a poorly understood aetiology that affects up to 10 adults per 100 000 each year. Following a series of such case reports, WHO and FDA have labelled the association between use of PDE5 inhibitors and risk of NAION as “possibly” causal. There have been several recent studies of this association, including a rechallenge case report and a large managed care database study. However, the inability to confirm or refute claims of an association between NAION and EDD is generating clinical and regulatory uncertainty. Questions surrounding use of PDE5 inhibitors and risk of NAION highlight weaknesses in current systems used to identify and evaluate uncommon adverse effects of medication use. This paper reviews all the recent evidence on PDE5 inhibitors and the risk of NAION. PMID:17947271
Simpson, Katherine M; De Risio, Luisa; Theobald, Anita; Garosi, Laurent; Lowrie, Mark
All previous studies on feline ischaemic myelopathy (IM) have reported an acute onset of a single event with no recurrence of clinical signs. This study aimed to evaluate clinical and long-term follow-up data in cats presumptively diagnosed with cervical IM in the territory of the ventral spinal artery (VSA). Eight cats (four females and four males) were included with a mean age of 14 years and 2 months. Neurological status at the time of presentation ranged from ambulatory tetraparesis to tetraplegia with nociception present. Six cats had marked cervical ventroflexion. All eight cats were diagnosed with one or more concurrent medical conditions, including chronic kidney disease (n = 2), hypertrophic cardiomyopathy (n = 2) and hypertension (n = 6). Median time to ambulation was 5.7 days (range 2-14 days). Long-term follow-up ranged from 7 months to 3 years and 3 months (median 1 year and 2 months). Five cats had no reported recurrence of clinical signs and 3/8 had a chronic relapsing disease course. One cat had an acute recurrence of clinical signs 4 months after the first event and was euthanased. Two cats had acute onsets of suspected intracranial infarctions, one of which had further suspected intracranial infarcts every 3 months and was euthanased after one of these. This study highlights the importance of performing ancillary diagnostic tests in older cats presenting with IM, particularly when VSA embolisation is suspected.
Sarin, Shiv Kumar; Choudhury, Ashok
Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.
Kim, Seungtaek; Han, Kwang-Hyub; Ahn, Sang Hoon
Since its discovery in 1989, hepatitis C virus (HCV) has been intensively investigated to understand its biology and develop effective antiviral therapies. The efforts of the previous 25 years have resulted in a better understanding of the virus, and this was facilitated by the development of in vitro cell culture systems for HCV replication. Antiviral treatments and sustained virological responses have also improved from the early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C, similar to other chronic viral infections, and retreatment options following treatment failure have become important questions. Despite the clinical challenges in the management of chronic hepatitis C, substantial progress has been made in understanding HCV, which may facilitate the investigation of other closely related flaviviruses and lead to the development of antiviral agents against these human pathogens. PMID:27784846
... Our Accomplishments Annual Reports Our Videos What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...
Eeson, Gareth; Karanicolas, Paul J
Operative blood loss is a major source of morbidity and even mortality for patients undergoing hepatic resection. This review discusses strategies to minimize blood loss and the utilization of allogeneic blood transfusion pertaining to oncologic hepatic surgery.
... Boomers Hepatitis Risk Assessment Campaign Materials Fact Sheets Posters Infographics Videos Buttons & Badges Email Signatures Radio Ads and Scripts Know More Hepatitis Logos Presentation Templates Guidelines for using materials and logos About ...
... hepatitis A. Children can get hepatitis A at day care center from other children or from child care ... treatment with immunoglobulin therapy. If your child attends day care: Make sure the children and staff at the ...
... related side effects. The hepatic function panel evaluates: Alanine aminotransferase (ALT). This enzyme, found in the liver, ... MORE ON THIS TOPIC Mononucleosis Hepatitis Blood Test: Alanine Aminotransferase (ALT, or SGPT) Blood Test: Aspartate Aminotransferase ( ...
... million people globally. admin / 03/17/2015 Viral Hepatitis An estimated 4.4 million Americans from all ... Events section below. EVENTS FULL CALENDAR Loading… VIRAL HEPATITIS DISPARITIES HARD TO REACH, HARD TO TREAT™ AFRICAN ...
... at birth: Newborn babies should receive their first hepatitis B vaccine and one dose of immunoglobulins (IG) within 12 hours. The baby should complete all hepatitis B vaccines as recommended during the first six months. Some ...
... special immune injection and the first dose of hepatitis B vaccine at birth. How Is It Prevented? Because people ... B virus. Doctors recommend that teens get a hepatitis B immunization (vaccine). It's a series of three shots over a ...
Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs ...
Ciocca, Mirta; Álvarez, Fernando
Neonatal acute liver failure is a rare, very severe disease with a high rate of mortality. It is clinically and etiologically different from acute liver failure seen in older children and adults. Coagulopathy with an international normalized ratio ≥ 3 is the critical parameter that defines it. The most common causes are fetal alloimmune hepatitis, previously called neonatal hemochromatosis, viral infections, metabolic disorders, and hemophagocytic lymphohistiocytosis. There is a group of treatable diseases that require a very early diagnosis for the prescription of an adequate treatment. Patients should be immediately referred to a specialized facility where pediatric liver transplantation is available to implement such therapeutic alternative, if indicated.
Mihalčin, M; Polák, P; Husa, P
Hepatitis E (HE) is a ubiquitous infection, occurring both in developing and in developed countries. It is caused by the hepatitis E virus (HEV), a small, non-enveloped RNA virus. The reported incidence in the Czech Republic in 2013 was 2 cases per 100,000 inhabitants and the number of HE cases has been growing over the past years. Besides the long known fecal-oral transmission, zoonotic and blood product transmission of HEV has recently been observed in industrialized countries. Most infections are asymptomatic. Symptomatic infection may present as acute hepatitis with nonspecific flu-like symptoms and liver enzymes elevation. In immunocompromised patients, HEV can lead to chronic hepatitis E and can even cause acute liver failure in pregnant women. Several extrahepatic manifestations have also been reported. Antiviral therapy has been successfully used in chronic hepatitis E. The first vaccine available for clinical use is licensed in China so far.
Moreno Arroyo, M Carmen; Puig Llobet, Montserrat; Cuervo Lavado, Luis
Fulminant hepatic failure (FHF), also known as fulminant hepatitis, is a rare and extremely serious condition with a high mortality rate. Its rapid evolution and complexity in managing the treatment, creates the need to provide some immediate care by a team that specialises in intensive care. This acute decompensation is usually associated with other disorders, such as coagulopathy and hepatic encephalopathy, being responsible for major complications that can lead to organ failure. In our region the most common origin is unknown, followed by acute infection with hepatitis B. The treatment of this syndrome is based on the general measures applicable to any critically ill patient: treat the cause and early detection of extrahepatic complications, urgent liver transplantation being one of the alternatives with a better prognosis. This article presents a case report describing the monitoring of an Irish woman of 20 years who was transferred from a hospital in Ibiza to a hospital in Barcelona, with a suspected diagnosis of FHF. Following the conceptual model of Virginia Henderson, the collaborative problems and nursing diagnoses are described, presenting a care plan according to NANDA (North American Nursing Association), NIC (Nursing Intervention Classification), NOC (Nursing Outcomes Classification). This case helps to establish an individualised care plan that provides guidance to nurse professionals in critical patient care by increasing the knowledge of FHF.
Arain, Shafique Rehman; Umer, Tahira Perveen
Pegylated interferon remains the first line treatment for patients with hepatitis D virus and more than one year therapy may be necessary. Interferon a has the most extensive clinical application and is used for the treatment of chronic hepatitis B and D virus as well as HCV infections. The attachment of polyethylene glycol to interferon increases its half-life. Treatment with peg interferon is associated with many troublesome and occasionally with serious or even life-threatening side effects. In this case report, we have described a patient with chronic hepatitis B and D, who developed Raynaud's phenomenon, ischaemic digital necrosis and bilateral olecranon bursitis during Pegylated interferon therapy. The patient underwent a very extensive workup in order to determine the underlying cause of his digital ischaemia and olecranon bursitis, which was finally determined to be secondary to the use of Pegylated interferon.
Mitchell, Emma J.; Dewar, Deborah; Maxwell, David J
Following large strokes that encompass the cerebral cortex, it has been suggested that the corticospinal tract originating from the non-ischaemic hemisphere reorganises its pattern of terminal arborisation within the spinal cord to compensate for loss of function. However many strokes in humans predominantly affect subcortical structures with minimal involvement of the cerebral cortex. The aim of the present study was to determine whether remodelling of corticospinal terminals arising from the non-ischaemic hemisphere was associated with spontaneous recovery in rats with subcortical infarcts. Rats were subjected to transient middle cerebral artery occlusion or sham surgery and 28 days later, when animals exhibited functional recovery, cholera toxin b subunit was injected into the contralesional, intact forelimb motor cortex in order to anterogradely label terminals within cervical spinal cord segments. Infarcts were limited to subcortical structures and resulted in partial loss of corticospinal tract axons from the ischaemic hemisphere. Quantitative analysis revealed there was no significant difference in the numbers of terminals on the contralesional side of the spinal grey matter between ischaemic and sham rats. The results indicate that significant remodelling of the corticospinal tract from the non-ischaemic hemisphere is not associated with functional recovery in animals with subcortical infarcts. PMID:27014870
Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques
Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210
... عربي 中文 English Français Русский Español What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Know hepatitis - Act now Event notice Key ...
Shamma'a, M H
Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (less than 1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (greater than 14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.
Kaić, Bernard; Vilibić-Cavlek, Tatjana; Filipović, Sanja Kurecić; Nemeth-Blazić, Tatjana; Pem-Novosel, Iva; Vucina, Vesna Visekruna; Simunović, Aleksandar; Zajec, Martina; Radić, Ivan; Pavlić, Jasmina; Glamocanin, Marica; Gjenero-Margan, Ira
Understanding the country-specific epidemiology of disease, which may vary greatly among countries, is crucial for identifying the most appropriate preventive and control measures. An overview of the local epidemiology of viral hepatitis in Croatia is given in this paper. The overall prevalence of hepatitis B in Croatia is low (less than 2% HBsAg carriers in the general population). Hepatitis B incidence and prevalence began to decline significantly following the introduction of universal hepatitis B vaccination in 1999. Information on HBsAg seroprevalence is derived from routine testing of certain subpopulations (pregnant women, blood donors) and seroprevalence studies mostly targeted at high-risk populations. Universal childhood vaccination against hepatitis B remains the main preventive measure. We recommend testing for immunity one to two months after the third dose of hepatitis B vaccine for health-care workers. The incidence and prevalence of hepatitis C have also been declining in the general population. The main preventive measures are ensuring safety of blood products, prevention of drug abuse, and harm reduction programs for intravenous drug users. Hepatitis A incidence has declined dramatically since fifty years ago, when thousands of cases were reported annually. In the last five years, an average of twenty cases have been reported per year. The reduction of hepatitis A is a consequence of improved personal and community hygiene and sanitation. Hepatitis D has not been reported in Croatia. The risk of hepatitis D will get to be even smaller as the proportion of population vaccinated against hepatitis B builds up. Hepatitis E is reported only sporadically in Croatia, mostly in persons occupationally in contact with pigs and in travelers to endemic countries. In conclusion, Croatia is a low prevalence country for hepatitides A, B and C. Hepatitis D has not been reported to occur in Croatia and there are only sporadic cases of hepatitis E. Since hepatitis
Pellegrini, L; Belcaro, G; Dugall, M; Hu, S; Gizzi, G; Corsi, M; Hosoi, M; Luzzi, R; Feragalli, B; Cotellese, R
Mild, temporary hepatic failure (MTHF) is a common clinical problem; in case of repeated episodes MTHF may cause chronic liver impairment. This registry has evaluated MTHF in subjects using Liverubin (standardized Silymarin) for 8 weeks.
Chatmethakul, Trassanee; Bhat, Ramachandra; Alkaabi, Maryam; Siddiqui, Abdul; Peevy, Keith; Zayek, Michael
Multifocal and diffuse infantile hepatic hemangioendotheliomas commonly present with signs of high-output congestive heart failure. In addition, prolonged persistent pulmonary overcirculation eventually leads to the development of pulmonary hypertension at a later age. We report a 2-day old, full-term infant with multifocal, large infantile hepatic hemangioendothelioma, who presented with an early onset of pulmonary hypertension, managed successfully with supportive care and systemic therapy directed toward the involution of infantile hepatic hemangioendothelioma. PMID:27468364
Gomez, Alexandra; Dholaria, Kevin; Arosemena, Leopoldo R.; Ladino-Avellaneda, Marco A.; Barisoni, Laura; Bhamidimarri, Kalyan R.
Intestinal involvement of cryoglobulinemia is an uncommon manifestation and marker of severe vasculitis. We describe the case of a woman admitted to our service for management of acute renal failure and progressive gastrointestinal symptoms after initiating hepatitis C virus treatment with ribavirin and sofosbuvir 4 weeks prior. With an undetectable hepatitis C viral load and persistent symptoms despite hepatitis C virus therapy cessation, an upper endoscopy revealed duodenal sloughing, erythema, and bleeding, sparking suspicion for recurrence of cryoglobulinemic vasculitis. PMID:27807586
Chatmethakul, Trassanee; Bhat, Ramachandra; Alkaabi, Maryam; Siddiqui, Abdul; Peevy, Keith; Zayek, Michael
Multifocal and diffuse infantile hepatic hemangioendotheliomas commonly present with signs of high-output congestive heart failure. In addition, prolonged persistent pulmonary overcirculation eventually leads to the development of pulmonary hypertension at a later age. We report a 2-day old, full-term infant with multifocal, large infantile hepatic hemangioendothelioma, who presented with an early onset of pulmonary hypertension, managed successfully with supportive care and systemic therapy directed toward the involution of infantile hepatic hemangioendothelioma.
Colletti, L M; Green, M
Hepatic ischemia/reperfusion (I/R) results in tumor necrosis factor (TNF) release. Kupffer cells (KC) are one source of this TNF. This study investigates the effects of hepatic I/R combined with lipopolysaccharide (LPS) on the lung and liver injury that follow hepatic I/R and on hepatic release of TNF, epithelial neutrophil activating protein (ENA-78), and macrophage inflammatory protein-2 (MIP-2). The effects of these experimental conditions on TNF production by primary rat KC in vitro were also investigated. Rats were subjected to hepatic I/R alone, hepatic I/R + LPS, sham laparotomy alone, or sham laparotomy + LPS and pulmonary MPO, pulmonary microvascular permeability, hepatic neutrophil influx, hepatic injury, and hepatic TNF, ENA-78, and MIP-2 production were measured. These experiments demonstrated that hepatic I/R in conjunction with LPS results in a more severe lung and liver injury and increased hepatic TNF, ENA-78, and MIP-2 release. The effects of these experimental conditions on rat KC TNF production demonstrated that hepatic I/R + LPS results in a more significant release of TNF as compared to LPS alone or I/R alone. Hepatic I/R plus LPS results in a more severe lung and liver injury and is likely secondary to a more significant and prolonged release of TNF by KC. This may provide a mechanism for development of multiple organ system failure in some patients undergoing hepatic resection, hepatic transplantation, complex vascular operations, or in the setting of hypovolemic shock. Portal endotoxemia related to mesenteric venous congestion or other systemic insults may have a significant impact on post-operative complications and recovery in the setting of a local or global hepatic I/R injury.
Dehnadi, Abbas; Benedict Cosimi, A.; Neal Smith, Rex; Li, Xiangen; Alonso, José L.; Means, Terry K.; Arnaout, M. Amin
Ischaemic acute kidney injury (AKI), an inflammatory disease process, often progresses to chronic kidney disease (CKD), with no available effective prophylaxis. This is in part due to lack of clinically relevant CKD models in non-human primates. Here we demonstrate that inhibition of the archetypal innate immune receptor CD11b/CD18 prevents progression of AKI to CKD in cynomolgus monkeys. Severe ischaemia-reperfusion injury of the right kidney, with subsequent periods of the left ureter ligation, causes irreversible right kidney failure 3, 6 or 9 months after AKI. Moreover, prophylactic inactivation of CD11b/CD18, using the orthosteric CD11b/CD18 inhibitor mAb107, improves microvascular perfusion and histopathology, reduces intrarenal pro-inflammatory mediators and salvages kidney function long term. These studies reveal an important early role of CD11b+ leukocytes in post-ischaemic kidney fibrosis and failure, and suggest a potential early therapeutic intervention to mitigate progression of ischaemic AKI to CKD in humans. PMID:28071653
John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita
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.
John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita
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
Purrucker, Jan C.; Haas, Kirsten; Wolf, Marcel; Rizos, Timolaos; Khan, Shujah; Kraft, Peter; Poli, Sven; Dziewas, Rainer; Meyne, Johannes; Palm, Frederick; Jander, Sebastian; Möhlenbruch, Markus; Heuschmann, Peter U.; Veltkamp, Roland
Background and Purpose To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months. Results 231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5–26] vs. 1 d [0–4], P<0.001). Conclusions The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation. PMID:28178406
Mentias, Amgad; Raza, Mohammad Q; Barakat, Amr F; Hill, Elizabeth; Youssef, Dalia; Krishnaswamy, Amar; Desai, Milind Y; Griffin, Brian; Ellis, Stephen; Menon, Venu; Tuzcu, E Murat; Kapadia, Samir R
Background Ischaemic mitral regurgitation (IMR) is a detrimental complication of ST elevation myocardial infarction (STEMI). Objective We sought to determine patient characteristics and outcomes of patients with IMR with focus on anterior or inferior location of STEMI. Methods All patients presenting with STEMI complicated by IMR to our centre who underwent primary percutaneous coronary intervention within the first 12 hours of presentation from 1995 to 2014 were included. IMR was graded from 1+ to 4+ within 3 days of index myocardial infarction by echocardiography, divided into 2 groups based on infarct location and outcomes were compared. Results Overall, 805 patients were included. There were 302 (17.8%) patients with mitral regurgitation (MR) out of the 1700 patients with anterior STEMI while 503 (21.8%) had MR out of the 2305 patients with inferior STEMI. There was no significant difference between both groups in comorbidities, clinical presentation or door-to-balloon time (DBT; median 104 vs 106 min, p=0.5). 30-day and 1-year mortality were higher in anterior STEMI compared with inferior STEMI (14.9% vs 6.8% and 26.4% vs 14.3%, respectively, p<0.001 both), as well as 5-year mortality (39.7% vs 24.8%, p<0.01). When analysis was performed for each grade of IMR, anterior was associated with worse outcomes in every grade. On multivariate cox survival analysis, after adjustment for age, gender, comorbidities, grade of IMR, ejection fraction and DBT, anterior STEMI was still associated with worse outcomes (HR 1.62 (95% CI 1.23 to 2.12), p<0.001). Conclusions Although IMR occurs more frequently with inferior infarction, outcomes are worse following anterior infarction. PMID:27933193
Kumar, A; Prasad, M; Jali, V P; Pandit, A K; Misra, S; Kumar, P; Chakravarty, K; Kathuria, P; Gulati, A
Bone marrow mononuclear cell (BM-MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM-MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM-MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta-analysis. We included non-randomized open-label, single-arm and non-randomized comparative studies or randomized controlled trials (RCTs) if BM-MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non-randomized comparative trials and four single-arm open-label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta-analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16-0.43) who were exposed to BM-MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM-MNCs was 20% (95% CI 0.12-0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM-MNC therapy is safe up to 1 year post-intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well-designed randomized controlled trials are required to provide more information on the efficacy of BM-MNC transplantation in patients with IS.
Kharbanda, R K; Li, J; Konstantinov, I E; Cheung, M M H; White, P A; Frndova, H; Stokoe, J; Cox, P; Vogel, M; Van Arsdell, G; MacAllister, R; Redington, A N
Objectives To test the hypothesis that remote ischaemic preconditioning (rIPC) reduces injury after cardiopulmonary bypass (CPB). Design Randomised study with an experimental model of CPB (3 h CPB with 2 h of cardioplegic arrest). Twelve 15 kg pigs were randomly assigned to control or rIPC before CPB and followed up for 6 h. Intervention rIPC was induced by four 5 min cycles of lower limb ischaemia before CPB. Main outcome measures Troponin I, glial protein S‐100B, lactate concentrations, load‐independent indices (conductance catheter) of systolic and diastolic function, and pulmonary resistance and compliance were measured before and for 6 h after CPB. Results Troponin I increased after CPB in both groups but during reperfusion the rIPC group had lower concentrations than controls (mean area under the curve −57.3 (SEM 7.3) v 89.0 (11.6) ng·h/ml, p = 0.02). Lactate increased after CPB in both groups but during reperfusion the control group had significantly more prolonged hyperlactataemia (p = 0.04). S‐100B did not differ between groups. Indices of ventricular function did not differ. There was a tendency to improved lung compliance (p = 0.07), and pulmonary resistance changed less in the rIPC than in the control group during reperfusion (p = 0.02). Subsequently, peak inspiratory pressure was lower (p = 0.001). Conclusion rIPC significantly attenuated clinically relevant markers of myocardial and pulmonary injury after CPB. Transient limb ischaemia as an rIPC stimulus has potentially important clinical applications. PMID:16818489
Weir, C J; Bolster, A A; Tytler, S; Murray, G D; Corrigall, R S; Adams, F G; Lees, K R
Single-photon emission tomography (SPET) is widely used in the investigation of acute stroke. We investigated the relationship between SPET data and functional outcome in a large group of acute stroke patients. One hundred and eight patients underwent cerebral computed tomography (CT) and technetium-99m hexamethylpropylene amine oxime SPET after acute ischaemic stroke. We categorised the clinical presentation according to the Oxford classification of acute stroke. Outcome was measured 1 year after stroke using mortality and the Barthel Index for survivors. SPET scans were interpreted without reference to the clinical data using a semi-automatic technique. Three experienced observers determined the presence of luxury perfusion using suitably scaled SPET images in conjunction with the CT scan. Both SPET volume and severity of deficit were significantly negatively correlated with Barthel Index at 1 year (rs=-0.310, P<0.0001, and rs=-0.316, P<0.0001 respectively). In patients scanned with SPET within 16 h of stroke onset, the correlations were more strongly negative (rs=-0.606, P<0. 001, and rs=-0.492, P<0.005 respectively). Luxury perfusion was not associated (chi2=0.073, df=1, P=0.79) with good functional outcome (Barthel score >/=60). Stepwise logistic regression identified Oxford classification, total deficit volume and patient's age as significant predictors of functional outcome. Overall predictive accuracy was 72%. Predictive accuracy was better in patients who received SPET within 16 h of stroke onset. SPET provides useful information about the functional outcome of acute stroke at 1 year. However, the accuracy of prediction decreases the longer SPET is delayed. Prognostication using SPET in combination with clinical assessment and other investigations may also be considered.
Sun, Junhui; Nguyen, Tiffany; Aponte, Angel M.; Menazza, Sara; Kohr, Mark J.; Roth, David M.; Patel, Hemal H.; Murphy, Elizabeth; Steenbergen, Charles
Nitric oxide (NO) and protein S-nitrosylation (SNO) have been shown to play important roles in ischaemic preconditioning (IPC)-induced acute cardioprotection. The majority of proteins that show increased SNO following IPC are localized to the mitochondria, and our recent studies suggest that caveolae transduce acute NO/SNO cardioprotective signalling in IPC hearts. Due to the close association between subsarcolemmal mitochondria (SSM) and the sarcolemma/caveolae, we tested the hypothesis that SSM, rather than the interfibrillar mitochondria (IFM), are major targets for NO/SNO signalling derived from caveolae-associated eNOS. Following either control perfusion or IPC, SSM and IFM were isolated from Langendorff perfused mouse hearts, and SNO was analysed using a modified biotin switch method with fluorescent maleimide fluors. In perfusion control hearts, the SNO content was higher in SSM compared with IFM (1.33 ± 0.19, ratio of SNO content Perf-SSM vs. Perf-IFM), and following IPC SNO content significantly increased preferentially in SSM, but not in IFM (1.72 ± 0.17 and 1.07 ± 0.04, ratio of SNO content IPC-SSM vs. Perf-IFM, and IPC-IFM vs. Perf-IFM, respectively). Consistent with these findings, eNOS, caveolin-3, and connexin-43 were detected in SSM, but not in IFM, and IPC resulted in a further significant increase in eNOS/caveolin-3 levels in SSM. Interestingly, we did not observe an IPC-induced increase in SNO or eNOS/caveolin-3 in SSM isolated from caveolin-3−/− mouse hearts, which could not be protected with IPC. In conclusion, these results suggest that SSM may be the preferential target of sarcolemmal signalling-derived post-translational protein modification (caveolae-derived eNOS/NO/SNO), thus providing an important role in IPC-induced cardioprotection. PMID:25694588
Moran, G M; Fletcher, B; Feltham, M G; Calvert, M; Sackley, C; Marshall, T
Transient ischaemic attack (TIA) and minor stroke are characterized by short-lasting symptoms; however, anecdotal and empirical evidence suggests that these patients experience ongoing cognitive/psychological impairment for which they are not routinely treated. The aims were (i) to investigate the prevalence and time course of fatigue, anxiety, depression, post-traumatic stress disorder(PTSD) and cognitive impairment following TIA/minor stroke; (ii) to explore the impact on quality of life (QoL), change in emotions and return to work; and (iii) to identify where further research is required and potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PSYCINFO, CINAHL, the Cochrane libraries and the grey literature between January 1993 and April 2013 was undertaken. Literature was screened and data were extracted by two independent reviewers. Studies were included of adult TIA/minor stroke participants with any of the outcomes of interest: fatigue, anxiety, depression, PTSD, cognitive impairment, QoL, change in emotions and return to work. Random-effects meta-analysis pooled outcomes by measurement tool. Searches identified 5976 records, 289 were assessed for eligibility and 31 studies were included. Results suggest high levels of cognitive impairment and depression post-TIA/minor stroke which decreased over time. However, frequencies varied between studies. Limited information was available on anxiety, PTSD and fatigue. Meta-analysis revealed that the measurement tool administered influenced the prevalence of cognitive impairment: Mini-Mental State Examination 17% [95% confidence interval (CI) 7, 26]; neuropsychological test battery 39% (95% CI 28, 50); Montreal Cognitive Assessment 54% (95% CI 43, 66). There is evidence to suggest that TIA/minor stroke patients may experience residual impairments; however, results should be interpreted with caution because of the few high quality studies. Notwithstanding, it is important to raise awareness
Francesconi, M; Koizar, C; Wascher, T C
Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post-ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous-occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5.0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40.5 +/- 15.3; males 51.8 +/- 17.7 ml min-1 100 ml-1, P < 0.01). In diabetic patients, in addition to gender, actual blood glucose (r = 0.377, P < 0.05) and meal intake (non-fasting 42.8 +/- 19.2; fasting 51.2 +/- 19.5 ml min-1 100 ml-1, P < 0.05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P < 0.001) in non-fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.
Shankaran, Seetha; Barnes, Patrick D; Hintz, Susan R; Laptook, Abbott R; Zaterka-Baxter, Kristin M; McDonald, Scott A; Ehrenkranz, Richard A; Walsh, Michele C; Tyson, Jon E; Donovan, Edward F; Goldberg, Ronald N; Bara, Rebecca; Das, Abhik; Finer, Neil N; Sanchez, Pablo J; Poindexter, Brenda B; Van Meurs, Krisa P; Carlo, Waldemar A; Stoll, Barbara J; Duara, Shahnaz; Guillet, Ronnie; Higgins, Rosemary D
Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy. PMID:23080477
Mattey, D; Dawes, P; Nixon, N; Goh, L; Banks, M; Kitas, G
Objective: To determine whether raised levels of antibodies to CK18 in patients with RA are associated with ischaemic heart disease (IHD). Methods: IgA, IgG, and IgM antibodies to CK18 were measured by enzyme linked immunosorbent assay (ELISA) in patients with RA with (n = 34) or without (n = 28) IHD. The relationship between CK18 antibody levels and markers of inflammatory and/or cardiovascular disease was examined. Results: Initial analysis showed that IgG antibody levels to CK18 were higher in patients with RA with IHD than in those without (50.1 v 34.5 AU, p = 0.047), although significance was lost after correction for multiple comparisons. Further analysis showed a significant difference (p = 0.015) between patients with IHD and a positive family history, and patients without IHD and a negative family history (53.7 v 29.0 AU, Kruskal-Wallis multiple comparison Z value test). There was also a significant trend of increasing 10 year cardiovascular risk with increasing CK18 IgG antibody levels (p = 0.01). No association was found between CK18 antibody levels and conventional markers of inflammation or cardiovascular disease, but an association was found between levels of CK18 IgG and IgG antibodies to cytomegalovirus (CMV) (Spearman's rs = 0.379, pcorr = 0.04). No evidence for cross reactivity of CK18 antibodies with CMV antigens was found. Conclusion: Levels of IgG antibodies to CK18 are raised in patients with RA with IHD, particularly if they also have a positive family history. This may reflect damage to CK18 containing cells in the cardiac vasculature and/or in atherosclerotic plaques, and may be a useful additional marker for the identification of patients with, or likely to develop, IHD. PMID:15020337
Muir, A R; McMullin, M F; Patterson, C; McKeown, P P
Objective: Laboratory tests including optical platelet aggregometry (OPA), platelet function analyser (PFA-100), and thromboxane B2 (TXB2) metabolite levels have been used to define aspirin resistance. This study characterised the prevalence of aspirin resistance in patients with ischaemic heart disease (IHD) and investigated the concordance and repeatability of these tests. Design, setting and patients: Consecutive outpatients with stable IHD were enrolled. They were commenced on 150 mg aspirin daily (day 0) and had platelet function assessment (OPA and PFA-100) and quantitative analysis of serum/urine TXB2 at day ⩾7 and then at a second visit approximately 2 weeks later. Main outcome measures: We assessed the prevalence of aspirin resistance by each method, concordance between methods of measuring response to aspirin and association between time points to assess the predictability of response over time. Results: 172 patients (62.7 (SD 8.7) years, 83.1% male) were recruited. At visits 1 and 2, respectively, 1.7% and 4.7% were aspirin resistant by OPA, whereas 22.1% and 20.3% were aspirin resistant by PFA-100. There were poor associations between PFA-100 and OPA, and between TXB2 metabolites and platelet function tests. OPA and PFA-100 results were poorly associated between visits (κ = 0.16 and κ = 0.42, respectively) as were TXB2 metabolites, suggesting that aspirin resistance is not predictable over time. Conclusions: The prevalence of aspirin resistance is dependent on the method of testing. Response varies on a temporal basis, indicating that testing on a single occasion is inadequate to diagnose resistance or guide therapy in a clinical setting. PMID:18697805
Boo, Nem-Yun; Cheah, Irene Guat-Sim
INTRODUCTION This study aimed to determine the incidence of hypoxic-ischaemic encephalopathy (HIE) and predictors of HIE mortality in Malaysian neonatal intensive care units (NICUs). METHODS This was a retrospective study of data from 37 NICUs in the Malaysian National Neonatal Registry in 2012. All newborns with gestational age ≥ 36 weeks, without major congenital malformations and fulfilling the criteria of HIE were included. RESULTS There were 285,454 live births in these hospitals. HIE was reported in 919 newborns and 768 of them were inborn, with a HIE incidence of 2.59 per 1,000 live births/hospital (95% confidence interval [CI] 2.03, 3.14). A total of 144 (15.7%) affected newborns died. Logistic regression analysis showed that the significant predictors of death were: chest compression at birth (adjusted odds ratio [OR] 2.27, 95% CI 1.27, 4.05; p = 0.003), being outborn (adjusted OR 2.65, 95% CI 1.36, 5.13; p = 0.004), meconium aspiration syndrome (MAS) (adjusted OR 2.16, 95% CI 1.05, 4.47; p = 0.038), persistent pulmonary hypertension of the newborn (PPHN) (adjusted OR 4.39, 95% CI 1.85, 10.43; p = 0.001), sepsis (adjusted OR 4.46, 95% CI 1.38, 14.40; p = 0.013), pneumothorax (adjusted OR 4.77, 95% CI 1.76, 12.95; p = 0.002) and severe HIE (adjusted OR 42.41, 95% CI 18.55, 96.96; p < 0.0001). CONCLUSION The incidence of HIE in Malaysian NICUs was similar to that reported in developed countries. Affected newborns with severe grade of HIE, chest compression at birth, MAS, PPHN, sepsis or pneumothorax, and those who were outborn were more likely to die before discharge. PMID:27549510
Sweetnam, P M; Taylor, S W; Elwood, P C
The cohort of viscose rayon workers previously described by Tiller et al has been reconstructed and followed up to the end of 1982. The pattern of mortality at ages 45 to 64 for the extended period 1950-82 is similar to that described by Tiller et al for 1950-64. The spinners, the workers most heavily exposed to carbon disulphide, have a significantly higher mortality from all causes than the least exposed group. The excess mortality is largely accounted for by ischaemic heart disease (IHD) for which the spinners have an SMR of 172. When mortality is related to an exposure score in the same group, both all cause (p less than 0.01) and IHD (p less than 0.001) mortality increase with increasing exposure level. When this analysis is repeated covering all ages these trends become much less strong and only that for IHD remains significant (p less than 0.05). Over the age of 65 there is a tendency for mortality to decline with increasing exposure. This is contrary to expectation under the usual hypothesis that carbon disulphide promotes atherosclerosis. Instead it suggests that carbon disulphide has some type of reversible, direct cardiotoxic or thrombotic effect. This is supported by the findings that there is a strong trend (p less than 0.01) for IHD mortality to increase with increasing exposure in the previous two years. Further, both IHD (p less than 0.001) and total (p less than 0.01) mortality show highly significant trends with exposure among current workers but no such trends among workers who have left the industry. PMID:3567096
Dowrick, T; Blochet, C; Holder, D
Electrical impedance tomography (EIT) could be used as a portable non-invasive means to image the development of ischaemic stroke or haemorrhage. The purpose of this study was to examine if this was possible using time difference imaging, in the anesthetised rat using 40 spring-loaded scalp electrodes with applied constant currents of 50-150 μA at 2 kHz. Impedance changes in the largest 10% of electrode combinations were -12.8% ± 12.0% over the first 10 min for haemorrhage and +46.1% ± 37.2% over one hour for ischaemic stroke (mean ± SD, n = 7 in each group). The volume of the pathologies, assessed by tissue section and histology post-mortem, was 12.6 μl ± 17.6 μl and 12.6 μl ± 17.6 μl for haemorrhage and ischaemia respectively. In time difference EIT images, there was a correspondence with the pathology in 3/7 cases of haemorrhage and none of the ischaemic strokes. Although the net impedance changes were physiologically reasonable and consistent with expectations from the literature, it was disappointing that it was not possible to obtain reliable EIT images. The reason for this are not clear, but probably include confounding effects of secondary ischaemia for haemorrhage and tissue and cerebrospinal fluid shifts for the stroke model. With this method, it does not appear that EIT with scalp electrodes is yet ready for clinical use.
Waldenström, Anders; Ronquist, Gunnar; Aberg, Anna-Maja; Ahlström, Katarina; Hauck, Philip; Abrahamsson, Pernilla; Johansson, Göran; Biber, Björn; Haney, Michael F
During ischaemia, ATP depletion leads to insufficient fuelling for Na(+) /K(+) ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca(2+) pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. (45) Ca(2+) was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by (45) Ca(2+) recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca(2+) ionophore and tested for (45) Ca(2+) uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate (45) Ca(2+) recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca(2+) ionophore to increase the intracellular calcium ion pool and subsequently incubated with (45) Ca(2+) , displayed lower (45) Ca(2+) uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate (45) Ca(2+) recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and (45) Ca(2+) inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.
Schooling, C Mary; Zhong, Yi
Protein C is an environmentally modifiable anticoagulant, which protects against venous thrombosis, whether it also protects against ischaemic heart disease is unclear, based on observational studies and relatively small genetic studies. It was our study aim to clarify the role of protein C in ischaemic heart disease. The risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically predicted protein C in very large studies. Associations with lipids and diabetes were similarly assessed to rule out effects via traditional cardiovascular disease risk factors. Separate sample instrumental variable analysis with genetic instruments (Mendelian randomisation) was used to obtain an unconfounded estimate of the association of protein C (based on (rs867186 (PROCR), rs3746429 (EDEM2), rs7580658 (inter/PROC)) with CAD/MI in an extensively genotyped case (n=64374)-control (n=130681) study, CARDIoGRAMplusC4D. Associations with lipids and diabetes were similarly assessed using the Global Lipids Genetics Consortium Results (n=196,475) and the DIAbetes Genetics Replication And Meta-analysis case (n=34,380)-control (n=114,981) study. Genetically predicted protein C was negatively associated with CAD/MI, odds ratio (OR) 0.85 µg/ml, 95 % confidence interval 0.80 to 0.90, but had no such negative association with lipids or diabetes. Results were similar for the SNP rs867186 functionally relevant to protein C, and including additional potentially pleiotropic SNPs (rs1260326 (GCKR), rs17145713 (BAZ1B) and rs4321325 (CYP27C1)). In conclusion, protein C may protect against CAD/MI. Whether environmental or dietary items that raise protein C protect against ischaemic cardiovascular disease by that mechanism should be investigated.
Roldan-Valadez, Ernesto; Lopez-Mejia, Mariana
Recently, several medical societies published joint statements about imaging recommendations for acute stroke and transient ischaemic attack patients. In following with these published guidelines, we considered it appropriate to present a brief, practical and updated review of the most relevant concepts on the MRI assessment of acute stroke. Basic principles of the clinical interpretation of diffusion, perfusion, and MRI angiography (as part of a global MRI protocol) are discussed with accompanying images for each sequence. Brief comments on incidence and differential diagnosis are also included, together with limitations of the techniques and levels of evidence. The purpose of this article is to present knowledge that can be applied in day-to-day clinical practice in specialized stroke units or emergency rooms to attend patients with acute ischaemic stroke or transient ischaemic attack according to international standards. PMID:25758570
Ferrarese, Alberto; Zanetto, Alberto; Gambato, Martina; Bortoluzzi, Ilaria; Nadal, Elena; Germani, Giacomo; Senzolo, Marco; Burra, Patrizia; Russo, Francesco Paolo
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release. PMID:26819523
Mehta, Amit; Salama, Gayle; Hissong, Erika; Rosenblatt, Russell; Cantor, Michael; Helfgott, David; Marks, Kristen
Herpes simplex virus (HSV) hepatitis represents a rare complication of HSV infection, which can progress to acute liver failure and, in some cases, death. We describe an immunocompetent 67-year-old male who presented with one week of fever and abdominal pain. Computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen showed multiple bilobar hepatic lesions, some with rim enhancement, compatible with liver abscesses. Subsequent liver biopsy, however, revealed hepatocellular necrosis, HSV-type intranuclear inclusions, and immunostaining positive for herpes virus type 2 (HSV-2). Though initially treated with broad-spectrum antibiotics, following histologic diagnosis of HSV hepatitis, the patient was transitioned to intravenous acyclovir for four weeks and he achieved full clinical recovery. Given its high mortality and nonspecific presentation, one should consider HSV hepatitis in all patients with acute hepatitis with multifocal hepatic lesions of unknown etiology. Of special note, this is only the second reported case of HSV liver lesions mimicking pyogenic abscesses on CT and MRI. PMID:27872770
Nyolczas, Noémi; Heltai, Krisztina; Borbély, Attila; Habon, Tamás; Járai, Zoltán; Sziliczei, Erzsébet; Stadler, Péter; Faludi, Réka; Herczeg, Béla; Papp, Előd; Lakatos, Ferenc; Nagy, Katalin; Katona, András; Kovács, Imre; Tomcsányi, János; Nagy, András; Sepp, Róbert
Heart failure is associated with a poor prognosis despite significant advances in the pharmacological and device therapy and incurs very high cost because of frequent hospitalizations. Therefore, professional high-quality care is essential for both patients and the healthcare system. The best way to evaluate the quality of care for a particular disease is the use of disease-specific registries. Until now, there has not been a registry evaluating characteristics and management of heart failure patients in Hungary. For that reason, the Hungarian Society of Cardiology initiated the set-up of the Hungarian Heart Failure Registry. The Aim of this paper is to present the goals, methods and first year results of the Hungarian Heart Failure Registry. The goal of the Registry is to create a modern, web-based database that summarizes the data of large number of patients who are currently or were previously admitted to hospital or who are currently or were previously patients in an outpatient department due to severe heart failure (NYHA III-IV). Currently 17 cardiology departments participate in the development of the Registry. The planned number of patients is 2000. Initially follow-up was planned for one year (pilot study). After the evaluation of the relevant experiences of the pilot study, long-term follow-up is planned. The Registry collects information about the type of heart failure (heart failure with reduced - LVEF≤45% - vs. preserved - LVEF>45% - ejection fraction), etiology, co-morbidities, diagnostic methods, treatment as well as morbidity and mortality. After the first year, assessing the baseline parameters of 698 patients enrolled in the Registry we found that the majority of patients (87.8%) has heart failure with reduced ejection fraction and in 39.8% of the patients heart failure has an ischaemic origin. The most frequent co-morbidity was hypertension followed by diabetes, renal insufficiency and COPD. The patients were treated with ACE inhibitors or ARBs
Gerth, Hans Ulrich; Pohlen, Michele; Pavenstädt, Hermann; Schmidt, Hartmut
Extracorporeal liver support can be classified into cell-free, artificial methods (artificial liver support, ALS) and cell-based bioartificial methods (bioartificial liver support, BLS). ALS improves biochemical parameters of liver failure by the simultaneous removal of protein-bound and water-soluble substances. Here, the MARS therapy belongs to the most studied methods with a proved beneficial effect on hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or hyperbilirubinemia. However, a general survival advantage of any liver support for liver failure has not been shown yet and is restricted to meta-analyses or patient subgroups. There are no prospective randomized studies on the treatment of liver failure by intoxication. However, several case series report positive treatment effects using the MARS system, particularly in mushroom poisoning or acetaminophen intoxication. In acute liver failure (ALF) studies, the usage of BLS showed no survival advantage. Using ALS systems, a positive effect on mortality could be demonstrated in patient subgroups after several consecutive MARS therapies. The first randomized controlled trial demonstrating a survival benefit used large-volume plasmapheresis. Apparently, immunomodulatory and hemodynamic effects of the treatment play a crucial role in this context. In patients with acute-on-chronic liver failure (ACLF) accompanied by hyperbilirubinemia without any further organ failure (singular hepatic dysfunction), prognostic favorable effects by using a BLS system have been shown. However, once other extrahepatic organ systems are affected, indicating a progressive transition to multi-organ failure, a survival advantage could be achieved with the MARS and Prometheus system. Decisive for a successful therapy is the exact indication of the respective liver dialysis procedure for this very heterogeneous disease. Future studies are needed to define more accurate patient selection criteria for each liver support.
Maiwall, Rakhi; Kumar, Manoj
Chronic hepatitis B is a global health problem that leads to development of various complications, such as cirrhosis, liver cancer, and liver failure requiring liver transplantation. The recurrence of hepatitis B virus (HBV) post-liver transplantation is a major cause of allograft dysfunction, cirrhosis of the allograft, and graft failure. Patients with high viral load at the time of transplantation, hepatitis B e antigen (HBeAg) positivity, or those with a history of anti-viral drug resistance are considered as high-risk for recurrent HBV post-liver transplantation, while patients with low viral load, including HBeAg negative status, acute liver failure, and hepatitis D virus (HDV) co-infection are considered to be at low-risk for recurrent HBV post-liver transplantation. Antivirals for patients awaiting liver transplantation(LT) cause suppression of HBV replication and reduce the risk of recurrent HBV infection of the allograft and, therefore, all HBV patients with decompensated cirrhosis should be treated with potent antivirals with high genetic barrier to resistance (entecavir or tenofovir) prior to liver transplantation. Prevention of post-liver transplantation recurrence should be done using a combination of hepatitis B immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence. Low dose HBIG, HBIG-free protocols, and monoprophylaxis with high potency antivirals can still be considered in patients at low risk of recurrence. Even, marginal grafts from anti-HBc positive donors can be safely used in hepatitis B surface antigen (HBsAg) negative, preferably in anti-hepatitis B core (HBc)/anti-hepatitis B surface (HBs) positive recipients. In this article, we aim to review the mechanisms and risk factors of HBV recurrence post-LT in addition to the various treatment strategies proposed for the prevention of recurrent HBV infection PMID:27047773
Miura, Yoshifumi; Kanda, Tatsuo; Yasui, Shin; Takahashi, Koji; Haga, Yuki; Sasaki, Reina; Nakamura, Masato; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Nishizawa, Tsutomu; Okamoto, Hiroaki; Yokosuka, Osamu
We describe a case of acute liver failure (ALF) without hepatic encephalopathy with marked elevation of aminotransferase due to hepatitis A, according to the revised Japanese criteria of ALF. This liver biopsy of the patient showed compatible to acute viral hepatitis and she immediately recovered without intensive care. She had no comorbid disorders. Of interest, phylogenetic tree analysis using almost complete genomes of hepatitis A virus (HAV) demonstrated that the HAV isolate from her belonged to the HAV subgenotype IA strain and was similar to the HAJFF-Kan12 strain (99% nucleotide identity) or FH1 strain (98% nucleotide identity), which is associated with severe or fulminant hepatitis A. Careful interpretation of the association between HAV genome variations and severity of hepatitis A is needed and the mechanism of the severe hepatitis should be explored.
Natural Killer Group 2A Expressed on Both Peripheral CD3(-)CD56(+)NK Cells and CD3(+)CD8(+)T Cells Plays a Pivotal Negative Regulatory Role in the Progression of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.
Yi, Rui-Tian; Niu, Ying-Hua; Liu, Hong-Li; Zhang, Tie-Ying; Yang, Yu-Cong; Zhang, Yu; Yin, Dong-Lin; Chen, Tian-Yan; Zhao, Ying-Ren
To explore the role of surface receptors natural killer group 2A (NKG2A) and natural killer group 2D (NKG2D) on CD3(+)CD8(+)T cells and CD3(-)CD56(+)NK cells in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), we measured the expression of NKG2A and NKG2D on the surface of these 2 types of circulating cells by flow cytometry in 3 groups. One group consists of 36 patients with chronic hepatitis B (CHB), another one consists of 22 patients with HBV-related ACLF, and the last one has 12 normal controls (NC). The experimental result indicated that there was no significant difference in the proportion of CD3(+)CD8(+)T cells in total lymphocytes between the 3 groups. However, the percentage of CD3(-)CD56(+)NK cells in ACLF group was evidently higher than that in the CHB group (P < 0.05). In addition, the expression of NKG2D on CD3(+)CD8(+)T cells in the ACLF group was significantly lower than that in the CHB group (P < 0.05), but there were no statistically significant differences in its percentages on CD3(-)CD56(+)NK cells between the 3 groups. The expression of NKG2A on CD3(+)CD8(+)T cells in the ACLF group was significantly higher than that in the NC group (P < 0.05), and on NK cells was significantly higher than that in the CHB group (P < 0.05) and NC group (P < 0.01). The increase in ratios of NKG2A to NKG2D on CD3(+)CD8(+)T cells and CD3(-)CD56(+)NK cells in the ACLF group was significantly more than that in the CHB group and NC group. The results indicate that the imbalance between NKG2A and NKG2D may contribute to the progression of HBV-related ACLF mediated by CD3(-)CD56(+)NK cells and CD3(+)CD8(+)T cells. Compared with NKG2D, NKG2A expressed on both peripheral CD3(-)CD56(+)NK cells and CD3(+)CD8(+)T cells plays a more pivotal negative regulatory role in the progression of HBV-related ACLF.
Nascimento, A. C. M.; Maia, D. R.; Neto, S. M.; Lima, E. M.; Twycross, M.; Baquette, R. F.; Lobato, C. M. O.
Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of histological conditions, extending from simple steatosis to end-stage liver failure. The aim of this study was to examine the prevalence of NAFLD and its associations in chronic hepatitis B and C patients. Methods. We included all patients diagnosed with chronic hepatitis B and C who underwent a liver biopsy between January 2010 and October 2011 (n = 104). Parameters studied included hepatitis type, anthropometric data, histologic, hepatic, metabolic and lipid assessments, presence of hypertension and viral load. Results. Hepatitis B was presented in 28.8% (n = 30) of patients, while hepatitis C was presented in 71.2% (n = 74). In addition, hepatic steatosis was present in 25% (n = 26) of the patients. Steatosis was frequently found in hepatitis C patients (31.1%; 25% n = 23), but infrequently in hepatitis B patients (10%; n = 3) (P = 0.024). It was also found that steatosis was frequently present in hepatitis C patients with intense fibrosis (52.94%) (P = 0.025). Discussion. Our results suggest that steatosis is a common feature in patients with viral chronic hepatitis, and that it plays a different role in each type of hepatitis. PMID:22934189
Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...
... page from the NHLBI on Twitter. What Is Heart Failure? Heart failure is a condition in which the heart can' ... force. Some people have both problems. The term "heart failure" doesn't mean that your heart has stopped ...
Sato, Akira; Ishii, Toshiya; Adachi, Kayo; Takahashi, Hideaki; Sano, Fumiaki; Matsumoto, Nobuyuki
Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy. Spontaneous clearance of hepatitis C virus RNA can occur following antiviral failure in patients with persistently low viral loads, and virological follow-up is therefore necessary in chronic hepatitis C virus infection, even after antiviral failure. PMID:27721727
Mascarenhas, Maria Inês; Moniz, Marta; Ferreira, Sofia; Goulão, Augusto; Barroso, Rosalina
High-output cardiac failure is rare in newborns. Emergent diagnosis and management of this pathology is crucial. We report the case of a child, currently 12-months old; obstetric background is non-contributory. Clinic observation on D1 was normal except for the presence of a systolic cardiac murmur; cardiological evaluation revealed mild ventricular dysfunction of the right ventricle. On the third day of life, she developed cardiac failure with gallop rhythm, hepatomegaly and a murmur in the anterior fontanel; an echocardiogram confirmed clinic aggravation with biventricular dysfunction and right cavities and superior vena cava dilatation. The cranial MRI confirmed the presence of a pial arteriovenous malformation (AVM) involving the anterior and middle cerebral arteries with an associated fronto-parietal ischaemic lesion. The infant underwent embolisations of AVM with successful flow reduction and cardiac failure improvement. The multidisciplinary follow-up showed no cardiac dysfunction or permanent lesions but confirmed a severe psycho-motor delay and left hemiparesia. PMID:22783011
Poo, Jorge Luis; Góngora, Julieta
Hepatic perforation is an unusual complication of woman pregnancy associated with a poor outcome. A comprehensive review of epidemiology, clinical spectrum, diagnostic methods and therapeutic options is presented in this short paper.
CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...
Objective To determine whether therapeutic hypothermia after hypoxic ischaemic encephalopathy (HIE) in neonates increases the risk of cardiac arrhythmia during intervention. Design A meta-analysis was conducted using a fixed-effect model. Risk ratios, risk differences, and 95% confidence intervals, were measured. Data sources Studies identified from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Google Scholar, previous reviews, and abstracts from onset to August, 2016. Review methods Reports that compared therapeutic hypothermia with normal care for neonates with HIE and that included data on safety or cardiac arrhythmia, which is of interest to patients and clinicians, were selected. Results We found seven trials, encompassing 1322 infants that included information on safety or cardiac arrhythmia during intervention. Therapeutic hypothermia considerably increased the combined rate of cardiac arrhythmia in the seven trials (risk ratio 2.42, 95% confidence interval 1.23 to 4.76. p = 0.01; risk difference 0.02, 95% CI 0.01 to 0.04) during intervention. Conclusions In infants with hypoxic ischaemic encephalopathy, therapeutic hypothermia is associated with a consistent increase in cardiac arrhythmia during intervention. PMID:28273115
Shokeir, Ahmed A.; Hussein, Abdelaziz M.; Awadalla, Amira; Samy, Ahmed; Abdelaziz, Azza; Khater, Sheiri; Barakat, Nashwa
Objective To compare the effect of ischaemic preconditioning (Ipre) vs. ischaemic postconditioning (Ipost) on renal ischaemia/reperfusion (I/R) injury in rats. Materials and methods In all, 120 male Sprague–Dawley rats were classified into four groups of 30 rats each, designated sham, control, Ipre and Ipost. Renal function, including serum creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), fractional Na excretion (FENa) and renal histopathology were measured at 2, 24 and 48 h after ischaemia. Markers of lipid peroxidation (malondialdehyde, MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were measured in kidney tissues during the same intervals. Results Ipre caused a significant improvement in renal function, as indicated by a significant decrease in serum creatinine, BUN and FENa, with a significant increase in CrCl. However, Ipost caused no significant improvement in renal function. Morphologically Ipre caused a marked significant improvement in the renal tubular damage score compared to Ipost. Also, Ipre caused a significant decrease in MDA, and significant increase in GSH and SOD when compared to Ipost. Conclusion Ipre is more potent than Ipost for improving the renal injury induced by I/R. Ipre caused a marked improvement in renal function and morphology, while Ipost caused a minimal improvement in morphology only. Moreover, Ipre caused a marked and significant reduction in oxidative stress in kidney tissues, while Ipost caused a minimal reduction. PMID:26558061
Mercuri, E.; Haataja, L.; Guzzetta, A.; Anker, S.; Cowan, F.; Rutherford, M.; Andrew, R.; Braddick, O.; Cioni, G.; Dubowitz, L.; Atkinson, J.
AIMS—To determine if there is any association between the findings of visual assessment performed at the age of 5 months and neurodevelopmental outcome at the age of 2 years in children who have sustained hypoxic-ischaemic insults. METHODS—Twenty nine term infants with hypoxic-ischaemic encephalopathy and/or brain lesions on neonatal magnetic resonance imaging (MRI) were prospectively evaluated. At 5 months of age all the infants had their visual function assessed using the Atkinson Battery of Child Development for Examining Functional Vision, which includes the assessments of optokinetic nystagmus (OKN), acuity, visual fields, fixation shift and phase and orientation reversal visual evoked potentials. At 2 years of age the children had a structured neurological evaluation and a Griffiths developmental assessment. RESULTS—There was good correlation between the extent of the early detected visual impairment and both neuromotor and global development. Children with more than three out of five abnormal visual tests at 5 months of age tended to have abnormal neurological examination results and abnormal developmental quotients. Children with three or fewer abnormalities tended to have developmental quotients in the normal range; the level of their performance, however, was still related to the number of visual tests passed. CONCLUSIONS—Individual visual tests can provide important prognostic information. While abnormal OKN and acuity were always associated with abnormal outcome, normal results on visual evoked potentials and fixation shift tended to be associated with normal outcome. PMID:10325784
Calabresi, Paolo; Saulle, Emilia; Centonze, Diego; Pisani, Antonio; Marfia, Girolama A; Bernardi, Giorgio
In the present in vitro study of rat brain, we report that transient oxygen and glucose deprivation (in vitro ischaemia) induced a post-ischaemic long-term synaptic potentiation (i-LTP) at corticostriatal synapses. We compared the physiological and pharmacological characteristics of this pathological form of synaptic plasticity with those of LTP induced by tetanic stimulation of corticostriatal fibres (t-LTP), which is thought to represent a cellular substrate of learning and memory. Activation of N-methyl-D-aspartate (NMDA) receptors was required for the induction of both forms of synaptic plasticity. The intraneuronal injection of the calcium chelator BAPTA [bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate] and inhibitors of the mitogen-activated protein kinase pathway blocked both forms of synaptic plasticity. However, while t-LTP showed input specificity, i-LTP occurred also at synaptic pathways inactive during the ischaemic period. In addition, scopolamine, a muscarinic receptor antagonist, prevented the induction of t-LTP but not of i-LTP, indicating that endogenous acetylcholine is required for physiological but not for pathological synaptic potentiation. Finally, we found that striatal cholinergic interneurones, which are resistant to in vivo ischaemia, do not express i-LTP while they express t-LTP. We suggest that i-LTP represents a pathological form of synaptic plasticity that may account for the cell type-specific vulnerability observed in striatal spiny neurones following ischaemia and energy deprivation.
Geurts, Marjolein; van der Worp, H. Bart; Horsch, Alexander D.; Kappelle, L. Jaap; Biessels, Geert J.; Velthuis, Birgitta K.
Background Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. Methods We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days. Results Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94–1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Conclusions Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase. PMID:26473959
Blanco, D; García-Alix, A; Valverde, E; Tenorio, V; Vento, M; Cabañas, F
Standardisation of hypothermia as a treatment for perinatal hypoxic-ischaemic encephalopathy is supported by current scientific evidence. The following document was prepared by the authors on request of the Spanish Society of Neonatology and is intended to be a guide for the proper implementation of this therapy. We discuss the difficulties that may arise when moving from the strict framework of clinical trials to clinical daily care: early recognition of clinical encephalopathy, inclusion and exclusion criteria, hypothermia during transport, type of hypothermia (selective head or systemic cooling) and side effects of therapy. The availability of hypothermia therapy has changed the prognosis of children with hypoxic-ischaemic encephalopathy and our choices of therapeutic support. In this sense, it is especially important to be aware of the changes in the predictive value of the neurological examination and the electroencephalographic recording in cooled infants. In order to improve neuroprotection with hypothermia we need earlier recognition of to recognise earlier the infants that may benefit from cooling. Biomarkers of brain injury could help us in the selection of these patients. Every single infant treated with hypothermia must be included in a follow up program in order to assess neurodevelopmental outcome.
Gutierrez, J. Antonio; Harrington, Robert A.; Blankenship, James C.; Stone, Gregg W.; Steg, Ph. Gabriel; Gibson, C. Michael; Hamm, Christian W.; Price, Matthew J.; Généreux, Philippe; Prats, Jayne; Deliargyris, Efthymios N.; Mahaffey, Kenneth W.; White, Harvey D.; Bhatt, Deepak L.
Aims To assess whether the use of the femoral or radial approach for percutaneous coronary intervention (PCI) interacted with the efficacy and safety of cangrelor, an intravenous P2Y12 inhibitor, in CHAMPION PHOENIX. Methods and results A total of 11 145 patients were randomly assigned in a double-dummy, double-blind manner either to a cangrelor bolus and 2-h infusion or to clopidogrel at the time of PCI. The primary endpoint, a composite of death, myocardial infarction, ischaemia-driven revascularization, or stent thrombosis, and the primary safety endpoint, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) defined severe bleeding, were evaluated at 48 h. Of the patients undergoing PCI and receiving study drug treatment, a total of 8064 (74%) and 2855 (26%) patients underwent femoral or radial PCI, respectively. Among the femoral cohort, the primary endpoint rate was 4.8% with cangrelor vs. 6.0% with clopidogrel (odds ratio, OR [95% confidence interval, CI] = 0.79 [0.65–0.96]); among the radial cohort, the primary endpoint was 4.4% with cangrelor vs. 5.7% with clopidogrel (OR [95% CI] = 0.76 [0.54–1.06]), P-interaction 0.83. The rate of GUSTO severe bleeding in the femoral cohort was 0.2% with cangrelor vs. 0.1% with clopidogrel (OR [95% CI] = 1.73 [0.51–5.93]). Among the radial cohort, the rate of GUSTO severe bleeding was 0.1% with cangrelor vs. 0.1% with clopidogrel (OR [95% CI] = 1.02 [0.14–7.28]), P-interaction 0.65. The evaluation of safety endpoints with the more sensitive ACUITY-defined bleeding found major bleeding in the femoral cohort to be 5.2% with cangrelor vs. 3.1% with clopidogrel (OR [95% CI] = 1.69 [1.35–2.12]); among the radial cohort the rate of ACUITY major bleeding was 1.5% with cangrelor vs. 0.7% with clopidogrel (OR [95% CI] = 2.17 [1.02–4.62], P-interaction 0.54). Conclusion In CHAMPION PHOENIX, cangrelor reduced ischaemic events with no significant increase in GUSTO-defined severe bleeding. The absolute rates
Pakvasa, Mitali A; Winkler, Anne M; Hamrick, Shannon E; Josephson, Cassandra D
Objective Evaluate the relationship between initial haemostatic parameters and the frequency and severity of bleeding in neonates with hypoxic–ischaemic encephalopathy (HIE). Design Retrospective observational cohort study. Setting 2 academically affiliated level III neonatal intensive care units in Atlanta, Georgia. Participants 98 neonates with moderate-to-severe HIE who underwent haemostatic testing within 12 hours of birth and were born from 1 January 2008 to 31 December 2013. Primary and secondary outcome measures Initial haemostatic dysfunction was defined as one or more of the following: prothrombin time (PT) ≥18 s, platelet count <100×103/μL or fibrinogen <150 mg/dL. Bleeding assessed using the Neonatal Bleeding Assessment Tool and graded according to the WHO bleeding scale. The robust Poisson regression was used to evaluate the independent association between components of initial haemostatic dysfunction and bleeding. Results Among the 98 neonates evaluated, the prevalence of initial haemostatic dysfunction was 69% (95% CI 59% to 78%). 27 neonates (28%; 95% CI 19% to 38%) had abnormal bleeding events and 56 (57%) received at least 1 blood product transfusion. 3 neonates died from bleeding complications. The most common products transfused were fresh-frozen plasma (71%), followed by packed red blood cells (24%) and platelets (21%). In multivariable analysis, fibrinogen <150 mg/dL (adjusted relative risk 2.41, 95% CI 1.09 to 5.36) and platelet count <100×103/μL (adjusted relative risk 2.59, 95% CI 1.30 to 5.16), but not initial PT, were associated with an increased risk of bleeding. The most severe bleeding occurred in neonates with a fibrinogen <150 mg/dL. Conclusions Among neonates with moderate-to-severe HIE, haemostatic dysfunction is prevalent and associated with an increased risk of bleeding and high transfusion burden. Further studies are needed to determine the appropriate transfusion approaches in this population to prevent
Pickard, J M J; Burke, N; Davidson, S M; Yellon, D M
This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia-reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0.05 vs IPC). Moreover, the muscarinic antagonist, atropine (100 nM), also abrogated IPC-mediated protection (IS/AAR = 40 ± 3%, p < 0.05 vs IPC). This indicates that intrinsic cardiac ganglia remain intact in the Langendorff preparation and are important in the mechanism of IPC. In a second group of experiments, coronary effluent collected following IPC, from ex vivo perfused rat hearts, provided significant cardioprotection when perfused through a naïve isolated rat heart prior to induction of regional ischaemia-reperfusion injury (IRI) (IS/ARR = 19 ± 2, p < 0.05 vs control effluent). This protection was also abrogated by treating the naïve heart with hexamethonium, indicating the humoral trigger of IPC induces protection via an intrinsic neuronal mechanism (IS/AAR = 46 ± 5%, p < 0.05 vs IPC effluent). In addition, a large release in ACh was observed in coronary effluent was observed following IPC (IPCeff = 0.36 ± 0.03 μM vs C eff = 0.04 ± 0.04 μM, n = 4, p < 0.001). Interestingly, however, IPC effluent was not able to significantly protect isolated cardiomyocytes from simulated ischaemia-reperfusion injury (cell death = 45 ± 6%, p = 0.09 vs control effluent). In conclusion, IPC involves activation of the intrinsic cardiac nervous system, leading to release of ACh in the ventricles and induction of protection via activation of muscarinic receptors.
Pedersen, O D; Gram, J; Jespersen, J
The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008.(ABSTRACT TRUNCATED AT 250 WORDS)
Baxter, G. F.; Goodwin, R. W.; Wright, M. J.; Kerac, M.; Heads, R. J.; Yellon, D. M.
1. Monophosphoryl lipid A (MLA) is a non-pyrogenic derivative of Salmonella lipopolysaccharide. Administration of this agent at high doses to rats and at low doses to dogs was previously shown to confer marked protection against ischaemia-reperfusion 24 h later, although the cellular mechanisms of this delayed protection are obscure. We hypothesized that MLA pretreatment causes the induction of the 70 kDa cytoprotective stress protein HSP70i in the myocardium. If this were the case, protection against ischaemia-reperfusion injury would be observed both in vitro and in vivo. 2. Rabbits were pretreated with MLA 0.035 mg kg-1, i.v. or vehicle solution. For the in vitro study, hearts were isolated 24 h later and Langendorff-perfused with Krebs-Henseleit buffer at 37 degrees C. Global ischaemia was induced for 20 min followed by 120 min reperfusion. Recovery of post-ischaemic left ventricular function and lactate dehydrogenase efflux was similar in MLA and vehicle pretreated hearts and there was no significant difference in the percentage of infarction of the left ventricle determined by triphenyltetrazolium staining (MLA 22.4 +/- 5.2%, vehicle 24.8 +/- 5.1%). 3. When 30 min regional ischaemia and 120 min reperfusion was instituted in pentobarbitone-anaesthetized rabbits 24 h after pretreatment with MLA or vehicle, the percentage infarction within the risk zone was reduced from 42.6 +/- 5.7% in vehicle pretreated animals to 19.6 +/- 4.4% in MLA pretreated animals (P < 0.01). 4. Determination of myocardial HSP70i content by Western blot analysis showed that MLA treatment did not increase HSP70i immunoreactivity. 5. We conclude that MLA at this dose confers protection only against ischaemia-reperfusion injury in vivo and that this protection is not related to induction of HSP70i. Because protection was observed only in vivo it seems possible that the delayed protection conferred by MLA is mediated by effects on humoral or blood-borne factors. Images Figure 1 Figure 2
Song, Yang; Zhao, Yingying; Wang, Fei; Tao, Lichan; Xiao, Junjie; Yang, Changqing
Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future.
Drolet, Richard; D'Allaire, Sylvie; Chagnon, Madeleine
Data pertaining to factors associated with cardiac failure were collected as part of a study on sow mortality in which cardiac failure was the major cause of death. A total of 116 sows from 24 herds was used and divided into two groups: group 1 comprised sows dead of cardiac failure (n = 43), and group 2, sows dead of other causes (n = 73). Individual sow records, clinical history, backfat thickness, body weight, heart weight, selenium content in liver, and urea concentration in aqueous humor were obtained for each sow. Results from the groups were compared using Student's t-test. Maximum and minimum outside daily temperatures were obtained for the study period. A stressful or demanding event for the cardiovascular system of sows was identified in 84% of the cases of cardiac failure: nearly two-thirds of the cases occurred during the peripartum period, and other stressful events included heat, fighting, mating, and transport. More than 40% of the cardiac failures occurred during the months of July and August. Sows dead of cardiac failure were heavier and fatter than sows dead of other causes. The former group also had a significantly smaller heart weight to body weight ratio; this difference was attributed to a greater body weight since the heart weights were similar in the two groups. The hepatic selenium contents and urea concentrations in aqueous humor were not significantly different between the two groups. PMID:17424001
Alvarez, Alicia M.; Mukherjee, Debabrata
Heart failure (HF) is characterized by the inability of systemic perfusion to meet the body's metabolic demands and is usually caused by cardiac pump dysfunction and may occasionally present with symptoms of a noncardiac disorder such as hepatic dysfunction. The primary pathophysiology involved in hepatic dysfunction from HF is either passive congestion from increased filling pressures or low cardiac output and the consequences of impaired perfusion. Passive hepatic congestion due to increased central venous pressure may cause elevations of liver enzymes and both direct and indirect serum bilirubin. Impaired perfusion from decreased cardiac output may be associated with acute hepatocellular necrosis with marked elevations in serum aminotransferases. Cardiogenic ischemic hepatitis (“shock liver”) may ensue following an episode of profound hypotension in patients with acute HF. We discuss pathophysiology and identification of liver abnormalities that are commonly seen in patients with HF. PMID:22942628
Liberal, Rodrigo; Grant, Charlotte R; Mieli-Vergani, Giorgina; Vergani, Diego
Autoimmune hepatitis (AIH) is an immune-mediated liver disorder characterised by female preponderance, elevated transaminase and immunoglobulin G levels, seropositivity for autoantibodies and interface hepatitis. Presentation is highly variable, therefore AIH should be considered during the diagnostic workup of any increase in liver enzyme levels. Overlap/variant forms of the disease, presenting with concomitant features of primary biliary cirrhosis or primary sclerosing cholangitis are increasingly recognised. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. Difficult-to-treat or non-responsive patients should be treated with mycophenolate mofetil or, failing that, calcineurin inhibitors. Persistent failure to respond or lack of adherence to treatment result in end-stage liver disease. These patients, and those with fulminant liver failure (encephalopathy grade II-IV) at diagnosis, will require liver transplantation. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4(pos) T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. Animal models faithfully representing the human condition are needed to unravel the contribution of innate and adaptive, effector and regulatory immune responses. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigen-specific regulatory T-cells, which ultimately aim to restore tolerance to liver-derived antigens.
Epps, J A; Smart, N A
An emerging treatment modality for reducing damage caused by ischaemia-reperfusion injury is ischaemic conditioning. This technique induces short periods of ischaemia that have been found to protect against a more significant ischaemic insult. Remote ischaemic conditioning (RIC) can be administered more conveniently and safely, by inflation of a pneumatic blood pressure cuff to a suprasystolic pressure on a limb. Protection is then transferred to a remote organ via humoral and neural pathways. The diabetic state is particularly vulnerable to ischaemia-reperfusion injury, and ischaemia is a significant cause of many diabetic complications, including the diabetic foot. Despite this, studies utilising ischaemic conditioning and RIC in type 2 diabetes have often been disappointing. A newer strategy, repeat RIC, involves the repeated application of short periods of limb ischaemia over days or weeks. It has been demonstrated that this improves endothelial function, skin microcirculation, and modulates the systemic inflammatory response. Repeat RIC was recently shown to be beneficial for healing in lower extremity diabetic ulcers. This article summarises the mechanisms of RIC, and the impact that type 2 diabetes may have upon these, with the role of neural mechanisms in the context of diabetic neuropathy a focus. Repeat RIC may show more promise than RIC in type 2 diabetes, and its potential mechanisms and applications will also be explored. Considering the high costs, rates of chronicity and serious complications resulting from diabetic lower extremity ulceration, repeat RIC has the potential to be an effective novel advanced therapy for this condition.
Kuhlenbäumer, G; Berger, K; Huge, A; Lange, E; Kessler, C; John, U; Funke, H; Nabavi, D G; Stögbauer, F; Ringelstein, E B; Stoll, M
Genetic fine mapping of the first locus identified for genetically complex forms of stroke, STRK1 (which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (PDE4D) gene as a good candidate gene. Association analysis of single nucleotide polymorphisms (SNPs) in the PDE4D gene in an Icelandic stroke cohort demonstrated genetic association between six SNPs in the 5' region of PDE4D and ischaemic stroke. The present study aimed to test whether the same six SNPs in PDE4D were also associated with stroke in a large stroke cohort from northern Germany (stroke patients with acute completed ischaemic stroke: n = 1181; population based controls: n = 1569). None of the six SNPs showed significant association with ischaemic stroke in the whole stroke sample before and after adjustment for conventional stroke risk factors (age, sex, hypertension, diabetes, and hypercholesterolaemia). Haplotype analysis did also not reveal any significant association. Marginally positive statistical measures of association in the subgroup with cardioembolic stroke did not remain significant after correction for multiple testing. In conclusion, this study was unable to demonstrate an association between the six SNPs which had showed significant single marker association with stroke in the Icelandic stroke cohort and ischaemic stroke in a large German cohort.
van Schie, Petra Em; Becher, Jules G.; Dallmeijer, Annet J.; Barkhof, Frederik; van Weissenbruch, Mirjam M.; Vermeulen, R. Jeroen
Aim: To investigate the predictive value of motor testing at 1 year for motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy (HIE) in term neonates. Method: Motor and mental outcome at 2 years was assessed with the Bayley Scales of Infant Development, 2nd edition (BSID-II) in 32 surviving children (20 males, 12…
... Artery Disease Venous Thromboembolism Aortic Aneurysm More Advanced Heart Failure Updated:Feb 9,2017 When heart failure (HF) ... content was last reviewed on 04/06/2015. Heart Failure • Home • About Heart Failure • Causes and Risks for ...
Butterworth, Roger F
It is generally assumed that neuronal cell death is minimal in liver failure and is insufficient to account for the neuropsychiatric symptoms characteristic of hepatic encephalopathy. However, contrary to this assumption, neuronal cell damage and death are well documented in liver failure patients, taking the form of several distinct clinical entities namely acquired (non-Wilsonian) hepatocerebral degeneration, cirrhosis-related Parkinsonism, post-shunt myelopathy and cerebellar degeneration. In addition, there is evidence to suggest that liver failure contributes to the severity of neuronal loss in Wernicke's encephalopathy. The long-standing nature of the thalamic and cerebellar lesions, over 80% of which are missed by routine clinical evaluation, together with the probability that they are nutritional in origin, underscores the need for careful nutritional management (adequate dietary protein, Vitamin B(1)) in liver failure patients. Mechanisms identified with the potential to cause neuronal cell death in liver failure include NMDA receptor-mediated excitotoxicity, lactic acidosis, oxidative/nitrosative stress and the presence of pro-inflammatory cytokines. The extent of neuronal damage in liver failure may be attenuated by compensatory mechanisms that include down-regulation of NMDA receptors, hypothermia and the presence of neuroprotective steroids such as allopregnanolone. These findings suggest that some of the purported "sequelae" of liver transplantation (gait ataxia, memory loss, confusion) could reflect preexisting neuropathology.
Hori, T; Ogura, Y; Okamoto, S; Nakajima, A; Kami, K; Iwasaki, J; Yonekawa, Y; Ogawa, K; Oike, F; Takada, Y; Egawa, H; Nguyen, J H; Uemoto, S
Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.
Coppola, Nicola; Alessio, Loredana; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Zampino, Rosa; Sagnelli, Evangelista
Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention. PMID:26730274
Sinniah, M; Ooi, B G
We studied the presence of Hepatitis C Virus (HCV) antibodies in a defined Malaysian population and examined the association, if any, between HCV and the Hepatitis B Virus (HBV), using sensitive recombinant DNA second generation Enzyme Immunoassay (EIA) test kits. This sero-prevalence study comprised 1,434 sera from eleven distinct groups comprising intravenous drug users (IVDU), haemophiliacs, male homosexuals, female prostitutes, healthy blood donors, staff of dialysis unit and laboratory personnel, chronic renal failure patients undergoing dialysis (CRFD), patients with liver cirrhosis, chronic active hepatitis, chronic persistent hepatitis and primary liver cancer. Except in laboratory personnel and dialysis staff, HCV antibodies were detected in each group of patients ranging from 3% in blood donors to 85% in IVDU. The main modes of HCV transmission identified were parenteral drug use, transfusion and/or dialysis related. The HBV was found to be the major viral etiological agent in 75% of chronic liver disease (CLD); while in 10% of cases both HCV and HBV were detected. HCV was implicated as the sole viral agent in only a small proportion (1.5%) of patients with chronic liver disease.
Kantola, T; Ilmakunnas, M; Koivusalo, A-M; Isoniemi, H
Acute liver failure is a life-threatening condition in the absence of liver transplantation option. The aetiology of liver failure is the most important factor determining the probability of native liver recovery and prognosis of the patient. Extracorporeal liver assist devices like MARS (Molecular Adsorbent Recirculating System) may buy time for native liver recovery or serve as bridging therapy to liver transplantation, with reduced risk of cerebral complications. MARS treatment may alleviate hepatic encephalopathy even in patients with a completely necrotic liver. Taking this into account, better prognostic markers than hepatic encephalopathy should be used to assess the need for liver transplantation in acute liver failure.
Olson, Jody C
Chronic liver disease is the fifth leading cause of death worldwide and represents a major burden for the health care community. Cirrhosis is a progressive disease resulting in end-stage liver failure, which in the absence of liver transplantation is fatal. Acute-on-chronic liver failure carries high short-term mortality but is potentially reversible. Viral hepatitis, alcohol, and nonalcoholic fatty liver disease remain the principal causes of liver disease. Though treatments exist for hepatitis B and C, they remain unavailable to many with these diseases. This article reviews the epidemiology of advanced liver disease and the concept of acute-on-chronic liver failure.
Nouraei, Seyed Mahmoud; Baradari, Afshin Gholipour; Jazayeri, Asieh
Objective: To investigate efficacy of remote ischaemic preconditioning on reducing kidney injury and myocardial damage after coronary artery bypass grafting surgery (CABG). Background: Ischaemic preconditioning of a remote organ reduces ischaemia-reperfusion injury of kidney and myocardium after CABG. Method: To reduce myocardial damage and kidney injury by applying Remote Ischaemic Preconditioning we recruited 100 consecutive patients undergoing elective coronary artery bypass grafting surgery. We applied three cycles of lower limb tourniquet, inflated its cuff for 5 minutes in study group or left un-inflated (sham or control group) before the procedure. The primary outcome was serum creatinine, creatinine clearance and troponin-I Levels at time 0, 6, 12, 24 and 48 h. Secondary outcomes were serum C-reactive protein, inotrope score, ventilation time and ICU stay. Data’s were analyzed by MedCalc (MedCalc Software bvba, Acacialaan, Belgium). We compared the two group by student t test, chi-square and Mann-Whitney tests. Results: The two groups were not statistically different in terms of age, gender, smoking habits, drug use, hypertension, hyperlipidemia and diabetes mellitus. This study showed a higher CRP level in study group comparing with control group (P=0.003), creatinine clearance was slightly higher in study group specially 24 h after procedure but was not statistically significant (p=0.11). Troponin-I level was significantly lower in study group (p=0.001). Conclusion: This study showed a lower Troponin-I level in study group which suggest a cardio-myocyte protective function of RIPC. It also showed slightly lower Creatinine clearance in control group, gap between two group increases significantly 24 hours after procedure which may suggest a potential kidney protection by RIPC. Serum CRP level was higher in study group. A multi-center randomized controlled trial with a longer time for creatinine clearance measurement may show the potential effectiveness of
Choong, Y S; Gavin, J B
The duration of aortic clamping and the temperature of the arrested heart are two important factors in the overall strategy of myocardial protection with cardioplegic solutions. The isolated working rat heart was used to compare the cardioprotection effects (function, metabolism and ultrastructure) of the new "extracellular" crystalloid solution, MBS (containing glucose, aspartate and lactobionate) and St. Thomas' Hospital No. 2 (STH) during prolonged moderate hypothermic ischaemia (30 degrees C, 2 hours and 4 hours) with multidose reinfusion (2 min every 30 min interval). All MBS treated hearts (n = 9 per group) rapidly resumed spontaneous regular sinus rhythm (0.8 +/- 0.2 min) and had similar high degree of functional recovery (cardiac output: 90.2 +/- 4.5% & 80.9 +/- 3.5%, stroke volume: 89.1 +/- 4.7% & 81.9 +/- 3.4% and aortic pressure: 102.0 +/- 4.0% & 100.0 +/- 7.3% of pre-arrest values for 2 hours and 4 hours groups, respectively) during 30 min post-ischaemic reperfusion. In contrast, hearts protected with STH showed significantly (p<0.01) less recovery of left ventricular function (cardiac output: 64.3 +/- 2.9% & 5.5 +/- 3.9%, respectively) with two of the nine hearts failing to regain any cardiac pump function after 4 hours. MBS increased lactate efflux (glycolysis) and completely abolished the progressive increase in the coronary vascular resistance during 4 hours ischaemic arrest. These improvements were directly related to the significantly (p<0.01) reduced depletion of the myocardial adenosine triphosphate (13.32 +/- 1.65 vs 2.42 +/- 0.09 micromol/g dry wt) and guanosine triphosphate (1.56 +/- 0.08 vs 0.74 +/- 0.04 micromol/g dry wt) during arrest; to their enhanced repletion after reperfusion (ATP: 96% vs 36%, TAN: 90% vs 40% and GTP: 69% vs 48%); and to the absence of ultrastructural injury to cardiac myocytes and the microvasculature. We conclude that the new crystalloid cardioplegic solution MBS provides markedly improved myocardial protection
... children; HCV children; Pregnancy - hepatitis C - children; Maternal transmission - hepatitis C - children References Elisofon SA, Jonas MMF. ... Hospital, Hollywood, FL. Review provided by VeriMed Healthcare Network. Also reviewed by David ... this important distinction for online health information and services. Learn more about A.D.A. ...